WorldWideScience

Sample records for intranasal lectin-based amebiasis

  1. Amebiasis

    National Research Council Canada - National Science Library

    Alavi, Karim

    2007-01-01

    Amebiasis is an important cause of death from parasitic disease worldwide. The causative organism is ENTAMOEBA HISTOLYTICA, which has an infective cyst stage and a pathogenic and motile trophozoite stage...

  2. Cutaneous amebiasis.

    Science.gov (United States)

    Rimsza, M E; Berg, R A

    1983-04-01

    An infant with cutaneous amebiasis of the vulva and amebic liver abscess is described. Epidemiologic investigations and serologic studies were crucial in establishing the diagnosis. The vulvar amebic ulcers responded dramatically to metronidazole therapy. Cutaneous amebiasis is a rare complication of Entamoeba histolytica infection which should be considered in the differential diagnosis of perineovulvar or penile ulcers. Cutaneous amebiasis may also occur on the abdominal wall surrounding a draining hepatic abscess, colostomy site, or laparotomy incision.

  3. Amebiasis (For Parents)

    Science.gov (United States)

    ... Teaching Kids to Be Smart About Social Media Amebiasis KidsHealth > For Parents > Amebiasis Print A A A ... Prevention Treatment When to Call the Doctor About Amebiasis Amebiasis is an intestinal illness that's typically transmitted ...

  4. Pleuropulmonary amebiasis

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Dong Hoon; Suh, Soo Ji; Ra, Woo Youn; Woo, Won Hyung [Kyungpook National University, School of Medicine, Taegu (Korea, Republic of)

    1972-03-15

    Nineteen cases of pleuropulmonary amebiasis was proved by needle aspiration or surgery as complication of amebic liver abscess during the period from June, 1969 to August, 1971 at Kyungpook National University Hospital. The results obtained are as follows: 1. Male to female ratio was about 3:1 and most of cases belonged to the 4th through 6th decades. 2. The most frequent complaint was upper abdominal pain and the most frequent abnormal physical finding was hepatomegaly. 3. Abnormalities seen in the chest films were: (a) Elevation of right diaphragm: (b) Empyema and (c) Pulmonary consolidation. 4. The pleuropulmonary amebiasis was seen in 26% of amebic liver abscess.

  5. PLEUROPULMONARY AMEBIASIS

    Science.gov (United States)

    Daniels, Albert C.; Childress, Max E.

    1956-01-01

    Pleuropulmonary amebiasis may be manifest without diarrhea or dysentery. In obscure lesions of the right lower lung field, one should always consider pleuropulmonary amebiasis—especially with low grade fever and moderate leukocytosis. Abscess and empyema contents should be examined promptly microscopically or kept warm to preserve the motility of the trophozoites until satisfactory examination is possible. Conservative therapy will successfully manage most cases of pleuropulmonary amebiasis. If a thorough search fails to reveal Entameba histolytica, and the diagnosis is still entertained, a medical therapeutic trial is in order. ImagesFigure 3Figure 4Figure 5 PMID:13374556

  6. Hepatic amebiasis

    Directory of Open Access Journals (Sweden)

    José Maria Salles

    2003-04-01

    Full Text Available Amebiasis can be considered the most aggressive disease of the human intestine, responsible in its invasive form for clinical syndromes, ranging from the classic dysentery of acute colitis to extra-intestinal disease, with emphasis on hepatic amebiasis, unsuitably named amebic liver abscess. Found worldwide, with a high incidence in India, tropical regions of Africa, Mexico and other areas of Central America, it has been frequently reported in Amazonia. The trophozoite reaches the liver through the portal system, provoking enzymatic focal necrosis of hepatocytes and multiple micro-abscesses that coalesce to develop a single lesion whose central cavity contains a homogeneous thick liquid, with typically reddish brown and yellow color similar to "anchovy paste". Right upper quadrant pain, fever and hepatomegaly are the predominant symptoms of hepatic amebiasis. Jaundice is reported in cases with multiple lesions or a very large abscess, and it affects the prognosis adversely. Besides chest radiography, ultrasonography and computerized tomography have brought remarkable contributions to the diagnosis of hepatic abscesses. The conclusive diagnosis is made however by the finding of Entamoeba histolytica trophozoites in the pus and by the detection of serum antibodies to the amoeba. During the evolution of hepatic amebiasis, in spite of the availability of highly effective drugs, some important complications may occur with regularity and are a result of local perforation with extension into the pleural and pericardium cavities, causing pulmonary abscesses and purulent pericarditis, respectively The ruptures into the abdominal cavity may lead to subphrenic abscesses and peritonitis. The treatment of hepatic amebiasis is made by medical therapy, with metronidazole as the initial drug, followed by a luminal amebicide. In patients with large abscesses, showing signs of imminent rupture, and especially those who do not respond to medical treatment, a

  7. Radiologic analysis of amebiasis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, S. Y.; Lee, Y. H.; Park, C. Y. [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1980-06-15

    The amebiasis is a common diseases in Korea as well as worldwide especially frequent in tropical area such as India, Africa and South America. The diagnosis of amebiasis remain difficult and complex, despite of many diagnostic method, for example, direct stool test for ameba, many immunologic studies and biopsy. Authors analyzed radiologically the patient who have had confirmed as a amebiasis from June, 1976 to September, 1979 at Yonsei University, College of Medicine, Severance Hospital. The results as follows: 1. The amebic liver abscess was a most common from of the amebiasis in Korea, which were 40 cases among 56 cases. Plain abdomen showed huge hepatomegaly, compression and displacement in hepatic flexure of colon, and reflex gas distension in almost cases. Chest P-A showed nonspecific right lower lung findings from secondary to right upper abdominal pathology, such as elevated right diaphragm (61.3%), pleural effusion (60.0%), right lower lung consolidation (37.5%) and abscess cavities (5.0%). Liver scan showed large space occupying lesion, most commonly situated in right lobe of liver (68.6%). 2. Among total 15 cases of the amebic colitis, positive findings on barium enema were 80%. Barium enama showed spas and irritability (89.2%), narrowing of lumen and lack of distensibility (71.4%) and deformity of cecum (20.0%). Involved site was cecum, ascending colon, rectosigmoid, transeverse and descending colon in order of frequency. Unusual involvement of terminal ileum was 2 cases. 3. Combined cases of amebic liver abscess and colitis were 4 cases (27.7%)

  8. [An update on amebiasis].

    Science.gov (United States)

    Chacín-Bonilla, Leonor

    2013-05-01

    The description of Entamoeba dispar, and the recovery of Entamoeba moshkovskii from humans had a major impact in the epidemiology and clinical management of amebiasis. Infections range from asymptomatic colonization to hemorrhagic colitis and extra-intestinal diseases. Only a minority of amebiasis patients progress to the development of disease. Recent studies suggest that susceptibility to infection, and its outcome is influenced by the host, parasite genotype, and environment. The identification of Entamoeba histolytica is based on the detection of specific antigens by ELISA and DNA in stool and other clinical samples. Several diagnostic tests have been developed, including polymerase chain reaction, the technique of choice, for the detection and differentiation of E. histolytica, E. dispar, and E. moshkovskii. Combination of serologic tests with detection of the parasite DNA by PCR or antigen by ELISA offers the best approach to diagnosis. However, these techniques are impractical for clinical laboratories of developing countries. Clinicians must follow the guidelines of the World Health Organization to avoid unnecessary treatments. This review describes and discusses recent advances in amebiasis with emphasis in the clinical aspects and management of infection.

  9. Laboratory Diagnosis of Amebiasis

    Science.gov (United States)

    Tanyuksel, Mehmet; Petri, William A.

    2003-01-01

    The detection of Entamoeba histolytica, the causative agent of amebiasis, is an important goal of the clinical microbiology laboratory. To assess the scope of E. histolytica infection, it is necessary to utilize accurate diagnostic tools. As more is discovered about the molecular and cell biology of E. histolytica, there is great potential for further understanding the pathogenesis of amebiasis. Molecular biology-based diagnosis may become the technique of choice in the future because establishment of these protozoa in culture is still not a routine clinical laboratory process. In all cases, combination of serologic tests with detection of the parasite (by antigen detection or PCR) offers the best approach to diagnosis, while PCR techniques remain impractical in many developing country settings. The detection of amebic markers in serum in patients with amebic colitis and liver abscess appears promising but is still only a research tool. On the other hand, stool antigen detection tests offer a practical, sensitive, and specific way for the clinical laboratory to detect intestinal E. histolytica. All the current tests suffer from the fact that the antigens detected are denatured by fixation of the stool specimen, limiting testing to fresh or frozen samples. PMID:14557296

  10. Molecular Epidemiology of Amebiasis

    Science.gov (United States)

    Ali, Ibne Karim M.; Clark, C. Graham; Petri, William A.

    2008-01-01

    Entamoeba histolytica, the causative agent of human amebiasis, remains a significant cause of morbidity and mortality in developing countries and is responsible for up to 100,000 deaths worldwide each year. Entamoeba dispar, morphologically indistinguishable from E. histolytica, is more common in humans in many parts of the world. Similarly Entamoeba moshkovskii, which was long considered to be a free-living ameba, is also morphologically identical to E. histolytica and E. dispar, and is highly prevalent in some E. histolytica endemic countries. However, the only species to cause disease in humans is E. histolytica. Most old epidemiological data on E. histolytica are unusable as the techniques employed do not differentiate between the above three Entamoeba species. Molecular tools are now available not only to diagnose these species accurately but also to study intra-species genetic diversity. Recent studies suggest that only a minority of all E. histolytica infections progress to development of clinical symptoms in the host and there exist population level differences between the E. histolytica strains isolated from the asymptomatic and symptomatic individuals. Nevertheless the underlying factors responsible for variable clinical outcome of infection by E. histolytica remain largely unknown. We anticipate that the recently completed E. histolytica genome sequence and new molecular techniques will rapidly advance our understanding of the epidemiology and pathogenicity of amebiasis. PMID:18571478

  11. [The complicated intestinal amebiasis in emergency surgery].

    Science.gov (United States)

    Gostishev, V K; Khrupkin, V I; Afanas'ev, A N; Gorbacheva, I V; Bragin, M A

    2009-01-01

    18 patients with complicated forms of intestinal amebiasis were operated on acute appendicitis, liver abscess or total necrotic colitis. Appendectomy, abscess drainage and colon resection were performed respectively. There were no postoperative deaths. Features of amebic appendicitis and total necrotic amebic colitis are described using clinical cases demonstrations. Recommendations for the treatment of these forms of amebiasis are given.

  12. [Amebiasis. Surgical treatment in 1989].

    Science.gov (United States)

    Sigler Morales, L; Mier y Díaz, J; Melgoza Ortiz, C; Blanco Benavides, R; Medina González, E

    1989-01-01

    Even when the number of patients with invasive amebiasis has decreased, the internist and surgeon must be alert in case that the patient requires an operation. Amebic liver abscess is treated medically; percutaneous evacuation is rarely used and surgical drainage is made when there is not response to medical treatment or there is high risk of abscess rupture. Operation is mandatory when the abscess has ruptured to the abdominal cavity or through the pericardial sac. In fulminant colitis it is necessary to resect the diseased portion of the colon without primary anastomoses. Amebic apendicitis is difficult to diagnosis before an operation. It may be suspected in cases of apendicitis if the cecal wall is inflammed. Colon ameboma requires medical treatment except if it is associated with necrosis or perforation. In a four year period (1985-1988) 294 patients with diagnosis of invasive amebiasis were admitted to three hospitals of the Instituto Mexicano del Seguro Social in Mexico City. 218 had hepatic abscess, 45 required surgical drainage with four deaths (9%) and four not operated patients died. In this series only four patients had their abscess drained percutaneously. 31 patients with amebic colitis were treated; three required colonic resection with one death. Ameboma was seen in five patients and there were 11 cases of amebic apendicitis. No deaths occurred in these last two groups.

  13. Accurate diagnosis is essential for amebiasis

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    @@ Amebiasis is one of the three most common causes of death from parasitic disease, and Entamoeba histolytica is the most widely distributed parasites in the world. Particularly, Entamoeba histolytica infection in the developing countries is a significant health problem in amebiasis-endemic areas with a significant impact on infant mortality[1]. In recent years a world wide increase in the number of patients with amebiasis has refocused attention on this important infection. On the other hand, improving the quality of parasitological methods and widespread use of accurate tecniques have improved our knowledge about the disease.

  14. Primary cutaneous amebiasis with a fatal outcome.

    Science.gov (United States)

    Al-Daraji, Wael Ismail; Husain, Ehab A; Ilyas, Mohammed; Robson, Alistair

    2008-08-01

    We report a fatal case of disseminated amebiasis in a young African woman, which initially presented with an ulcerated cutaneous lesion on the left flank. The causative organism was confirmed by examination of a wet drop preparation from the ulcer discharge and by skin biopsy. The patient was not immunosuppressed and was treated unsuccessfully with metronidazole. Postmortem examination revealed the presence of intestinal amebiasis complicated by a liver abscess.

  15. Amebiasis

    Science.gov (United States)

    ... infection of the intestines caused by the parasite Entamoeba histolytica . Causes Entamoeba histolytica can live in the large intestine (colon) without ... have major health problems due to this disease. Entamoeba histolytica is spread through food or water contaminated with ...

  16. Amebiasis

    Science.gov (United States)

    2011-06-01

    ulcers, all covered with a heaped up gray exudates. Figure 8.24 A vertical section of the specimen shown in Figure 8.23. The ulcer on the left has...can extend through the muscularis mucosa into the submucosa (Figs 8.25 & 8.26).29 The ulcer crater is comprised of fibrin, cellular debris, and...edge of the ulcer retains a faint outline of pre- viously viable structures, suggesting that the necrosis may be partly ischemic (Fig 8.28). Early

  17. Human Amebiasis: Breaking the Paradigm?

    Directory of Open Access Journals (Sweden)

    Oswaldo Partida

    2010-03-01

    Full Text Available For over 30 years it has been established that the Entamoeba histolytica protozoan included two biologically and genetically different species, one with a pathogenic phenotype called E. histolytica and the other with a non-pathogenic phenotype called Entamoeba dispar. Both of these amoebae species can infect humans. E. histolytica has been considered as a potential pathogen that can cause serious damage to the large intestine (colitis, dysentery and other extraintestinal organs, mainly the liver (amebic liver abscess, whereas E. dispar is a species that interacts with humans in a commensal relationship, causing no symptoms or any tissue damage. This paradigm, however, should be reconsidered or re-evaluated. In the present work, we report the detection and genotyping of E. dispar sequences of DNA obtained from patients with amebic liver abscesses, including the genotyping of an isolate obtained from a Brazilian patient with a clinical diagnosis of intestinal amebiasis that was previously characterized as an E. dispar species. The genetic diversity and phylogenetic analysis performed by our group has shown the existence of several different genotypes of E. dispar that can be associated to, or be potentiality responsible for intestinal or liver tissue damage, similar to that observed with E. histolytica.

  18. The Intradermal Reaction in Amebiasis

    Science.gov (United States)

    Miller, Max J.; Scott, Frank

    1970-01-01

    Studies on the amebiasis skin test were carried out in Amerindians living on reserves of Northern Saskatchewan. Results indicate the skin test to be highly sensitive in patients with acute amebic dysentery and in individuals with a history of amebic disease. A high percentage of asymptomatic school children living on a reserve where amebic disease is of common occurrence were also skin reactors. In a similar group of school children living on a reserve where amebic disease had never been reported but where E. histolytica infection rates are high there were very few reactors. A control group of white adults living in a non-endemic area were uniformly negative to the skin test. A comparison with the indirect hemagglutination test showed a good general correlation, but the skin test proved to be more accurate in cases of acute amebic dysentery in children 5 years of age or under. The skin test appears to have potential as a diagnostic technique and may be of considerable value in defining endemic areas of amebic disease. ImagesFIG. 1 PMID:4317530

  19. Human Amebiasis: Breaking the Paradigm?

    Science.gov (United States)

    Ximénez, Cecilia; Cerritos, Rene; Rojas, Liliana; Dolabella, Silvio; Morán, Patricia; Shibayama, Mineko; González, Enrique; Valadez, Alicia; Hernández, Eric; Valenzuela, Olivia; Limón, Angélica; Partida, Oswaldo; Silva, Edwards F

    2010-01-01

    For over 30 years it has been established that the Entamoeba histolytica protozoan included two biologically and genetically different species, one with a pathogenic phenotype called E. histolytica and the other with a non-pathogenic phenotype called Entamoeba dispar. Both of these amoebae species can infect humans. E. histolytica has been considered as a potential pathogen that can cause serious damage to the large intestine (colitis, dysentery) and other extraintestinal organs, mainly the liver (amebic liver abscess), whereas E. dispar is a species that interacts with humans in a commensal relationship, causing no symptoms or any tissue damage. This paradigm, however, should be reconsidered or re-evaluated. In the present work, we report the detection and genotyping of E. dispar sequences of DNA obtained from patients with amebic liver abscesses, including the genotyping of an isolate obtained from a Brazilian patient with a clinical diagnosis of intestinal amebiasis that was previously characterized as an E. dispar species. The genetic diversity and phylogenetic analysis performed by our group has shown the existence of several different genotypes of E. dispar that can be associated to, or be potentiality responsible for intestinal or liver tissue damage, similar to that observed with E. histolytica. PMID:20617021

  20. Primary Pulmonary Amebiasis Complicated with Multicystic Empyema.

    Science.gov (United States)

    Zakaria, Ali; Al-Share, Bayan; Al Asad, Khaled

    2016-01-01

    Amebiasis is a parasitic infection caused by the protozoan Entamoeba histolytica. While most infections are asymptomatic, the disease could manifest clinically as amebic dysentery and/or extraintestinal invasion in the form of amebic liver abscess or other more rare manifestations such as pulmonary, cardiac, or brain involvement. Herein we are reporting a case of a 24-year-old male with history of Down syndrome who presented with severe right side pneumonia complicated with multicystic empyema resistant to regular medical therapy. Further investigation revealed a positive pleural fluid for E. histolytica cysts and trophozoites. The patient was diagnosed with primary pleuropulmonary amebiasis and he responded promptly to surgical drainage and metronidazole therapy. In patients from endemic areas all physicians should keep a high index of suspicion of amebiasis as a cause of pulmonary disease.

  1. Primary Pulmonary Amebiasis Complicated with Multicystic Empyema

    Directory of Open Access Journals (Sweden)

    Ali Zakaria

    2016-01-01

    Full Text Available Amebiasis is a parasitic infection caused by the protozoan Entamoeba histolytica. While most infections are asymptomatic, the disease could manifest clinically as amebic dysentery and/or extraintestinal invasion in the form of amebic liver abscess or other more rare manifestations such as pulmonary, cardiac, or brain involvement. Herein we are reporting a case of a 24-year-old male with history of Down syndrome who presented with severe right side pneumonia complicated with multicystic empyema resistant to regular medical therapy. Further investigation revealed a positive pleural fluid for E. histolytica cysts and trophozoites. The patient was diagnosed with primary pleuropulmonary amebiasis and he responded promptly to surgical drainage and metronidazole therapy. In patients from endemic areas all physicians should keep a high index of suspicion of amebiasis as a cause of pulmonary disease.

  2. Primary Pulmonary Amebiasis Complicated with Multicystic Empyema

    Science.gov (United States)

    Al-Share, Bayan; Al Asad, Khaled

    2016-01-01

    Amebiasis is a parasitic infection caused by the protozoan Entamoeba histolytica. While most infections are asymptomatic, the disease could manifest clinically as amebic dysentery and/or extraintestinal invasion in the form of amebic liver abscess or other more rare manifestations such as pulmonary, cardiac, or brain involvement. Herein we are reporting a case of a 24-year-old male with history of Down syndrome who presented with severe right side pneumonia complicated with multicystic empyema resistant to regular medical therapy. Further investigation revealed a positive pleural fluid for E. histolytica cysts and trophozoites. The patient was diagnosed with primary pleuropulmonary amebiasis and he responded promptly to surgical drainage and metronidazole therapy. In patients from endemic areas all physicians should keep a high index of suspicion of amebiasis as a cause of pulmonary disease. PMID:27478673

  3. Colitis amebiasis with symptom of occasional dripped anal bleeding.

    Science.gov (United States)

    Wandono, Hadi

    2007-01-01

    Colitis amebiasis is usually characterized by bloody and mucous diarrhea, abdominal pain and anal discomfort. However, there is unusual manifestation of colitis amebiasis, such as occasional dripped anal bleeding, which sometimes spouted. Therefore, we often do not suspect such symptoms for colitis amebiasis. Laboratory examination includes complete laboratory test, coagulation and hematologic test, ICT TBC and colonoscopy. The pathology anatomy examination reveals positive results of trophozoites. Treatment by using metronidazole tablet provides good result for this disease.

  4. Entamoeba Encystation: New Targets to Prevent the Transmission of Amebiasis

    OpenAIRE

    Mi-ichi, Fumika; Yoshida, Hiroki; Hamano, Shinjiro

    2016-01-01

    Amebiasis is caused by Entamoeba histolytica infection and can produce a broad range of clinical signs, from asymptomatic cases to patients with obvious symptoms. The current epidemiological and clinical statuses of amebiasis make it a serious public health problem worldwide. The Entamoeba life cycle consists of the trophozoite, the causative agent for amebiasis, and the cyst, the form responsible for transmission. These two stages are connected by “encystation” and “excystation.” Hence, deve...

  5. Primary Pulmonary Amebiasis Complicated with Multicystic Empyema

    OpenAIRE

    Ali Zakaria; Bayan Al-Share; Khaled Al Asad

    2016-01-01

    Amebiasis is a parasitic infection caused by the protozoan Entamoeba histolytica. While most infections are asymptomatic, the disease could manifest clinically as amebic dysentery and/or extraintestinal invasion in the form of amebic liver abscess or other more rare manifestations such as pulmonary, cardiac, or brain involvement. Herein we are reporting a case of a 24-year-old male with history of Down syndrome who presented with severe right side pneumonia complicated with multicystic empyem...

  6. Hepato-pulmonary amebiasis: a case report

    Directory of Open Access Journals (Sweden)

    Vishnu Prasad Shenoy

    Full Text Available Infections with Entamoeba histolytica are seen worldwide and are more prevalent in the tropics. About 90% of infections are asymptomatic, and the remaining 10% produce a spectrum of clinical syndromes, ranging from dysentery to abscesses of the liver or other organs. Extra-intestinal infection by E. histolytica most often involves liver. Pleuro-pulmonary involvement, seen as the second most common extra-intestinal pattern of infection, is frequently associated with amebic liver abscess. Pulmonary amebiasis occurs in about 2-3% of patients with invasive amebiasis. We report herein the case of a 45-year-old male presenting with hepato-pulmonary amebiasis. The diagnosis was established from direct examination of sputum, in which trophozoites of E. histolytica were detected, and by serology. Following treatment with metronidazole and chloroquine, the clinical evolution improved significantly. On regular follow-up visits, the patient was asymptomatic. This case report reiterates the need for collaboration between clinicians and microbiologists for timely diagnosis of such infections.

  7. Entamoeba Encystation: New Targets to Prevent the Transmission of Amebiasis

    Science.gov (United States)

    Mi-ichi, Fumika; Yoshida, Hiroki; Hamano, Shinjiro

    2016-01-01

    Amebiasis is caused by Entamoeba histolytica infection and can produce a broad range of clinical signs, from asymptomatic cases to patients with obvious symptoms. The current epidemiological and clinical statuses of amebiasis make it a serious public health problem worldwide. The Entamoeba life cycle consists of the trophozoite, the causative agent for amebiasis, and the cyst, the form responsible for transmission. These two stages are connected by “encystation” and “excystation.” Hence, developing novel strategies to control encystation and excystation will potentially lead to new measures to block the transmission of amebiasis by interrupting the life cycle of the causative agent. Here, we highlight studies investigating encystation using inhibitory chemicals and categorize them based on the molecules inhibited. We also present a perspective on new strategies to prevent the transmission of amebiasis. PMID:27764256

  8. Entamoeba Encystation: New Targets to Prevent the Transmission of Amebiasis.

    Science.gov (United States)

    Mi-Ichi, Fumika; Yoshida, Hiroki; Hamano, Shinjiro

    2016-10-01

    Amebiasis is caused by Entamoeba histolytica infection and can produce a broad range of clinical signs, from asymptomatic cases to patients with obvious symptoms. The current epidemiological and clinical statuses of amebiasis make it a serious public health problem worldwide. The Entamoeba life cycle consists of the trophozoite, the causative agent for amebiasis, and the cyst, the form responsible for transmission. These two stages are connected by "encystation" and "excystation." Hence, developing novel strategies to control encystation and excystation will potentially lead to new measures to block the transmission of amebiasis by interrupting the life cycle of the causative agent. Here, we highlight studies investigating encystation using inhibitory chemicals and categorize them based on the molecules inhibited. We also present a perspective on new strategies to prevent the transmission of amebiasis.

  9. Entamoeba Encystation: New Targets to Prevent the Transmission of Amebiasis.

    Directory of Open Access Journals (Sweden)

    Fumika Mi-Ichi

    2016-10-01

    Full Text Available Amebiasis is caused by Entamoeba histolytica infection and can produce a broad range of clinical signs, from asymptomatic cases to patients with obvious symptoms. The current epidemiological and clinical statuses of amebiasis make it a serious public health problem worldwide. The Entamoeba life cycle consists of the trophozoite, the causative agent for amebiasis, and the cyst, the form responsible for transmission. These two stages are connected by "encystation" and "excystation." Hence, developing novel strategies to control encystation and excystation will potentially lead to new measures to block the transmission of amebiasis by interrupting the life cycle of the causative agent. Here, we highlight studies investigating encystation using inhibitory chemicals and categorize them based on the molecules inhibited. We also present a perspective on new strategies to prevent the transmission of amebiasis.

  10. Amebiasis: Epidemiología y Tratamiento

    Directory of Open Access Journals (Sweden)

    Alberto Albornoz Plata

    1986-08-01

    Full Text Available

    Introducción

    El concepto que se tenía hace varios años de “Enfermedades Tropicales” (se pensaba en un tipo de medicina exótica, como se llamaban en Europa, la malaria y amebiasis ha cambiado totalmente en la actualidad y específicamente para la amebiasis en el sentido de considerarla como enfermedad universal a la que puede ser susceptible cualquier ser humano que viva en cualquier sitio del mundo. Actualmente esta parasitosis cobra especial interés por los estudios inmunológicos, enzimáticos, epidemiológicos, metabólicos y terapéuticos que se desarrollan en centros muy especializados y se supone, con fundamento lógico, que no estará lejos el día en que se disponga de una vacuna eficaz contra esta enfermedad que ataca a muchas gentes, es causa de ausentismo al trabajo, incapacita por períodos largos a muchos pacientes por la complicación hepática y muchas veces es causa de mortalidad en los llamados casos de amebiasis invasora-fulminante.

    En este escrito solo se explicará lo referen te al aspecto epidemiológico y preventivo y, además, se hará énfasis para combatir ideas diagnósticas equivocadas con la entidad colon irritable.

    Al final se explicará el tratamiento actual de la amebiasis.

    Prevalencia y Susceptibilidad
    La amebiasis se considera como una enfermedad mundial, pero la mayor frecuencia es en aquellos lugares en donde las condiciones higiénicas ambientales son defectuosas, en especial lo referente al correcto suministro de agua potable, al buen tratamiento de las excretas y al control sanitario de los alimentos; por este motivo, en los países sub-desarrollados, o mejor subprivilegiados, y en las clases socio-económicas débiles, es donde más se encunetra esta enfermedad.

    Se ha calculado que en el mundo, el 20%de la población alberga la Endamoeba histolytica (l pero la gran mayoría no se consideran enfermos ya que son simplemente

  11. Cutaneous Amebiasis: The Importance of Molecular Diagnosis of an Emerging Parasitic Disease

    OpenAIRE

    Morán, Patricia; Rojas, Liliana; Cerritos, René; Zermeño, Valeria; Valadez, Alicia; de Oca, Griselda Montes; Reyes, Miguel Ángel; González, Enrique; Partida, Oswaldo; Hernández, Eric; Nieves, Miriam; Portillo, Tobías; Gudiño, Marco; Ramiro, Manuel; Ximénez, Cecilia

    2013-01-01

    Cutaneous amebiasis is the least common clinical form of human amebiasis in Mexico, sexual amebiasis was only occasionally observed before the late 1980s. However, in the last few decades, most of the documented cases of cutaneous amebiasis from around the world are sexually transmitted. We present two cases of sexually transmitted genital amebiasis. The molecular characterization of the Entamoeba species in the affected tissues underlines the importance of an etiological diagnosis using spec...

  12. Intranasal insulin therapy

    DEFF Research Database (Denmark)

    Hilsted, J; Madsbad, S; Hvidberg, A;

    1995-01-01

    To evaluate metabolic control and safety parameters (hypoglycaemia frequency and nasal mucosa physiology), 31 insulin-dependent diabetic patients were treated with intranasal insulin at mealtimes for 1 month and with subcutaneous fast-acting insulin at meals for another month in an open, crossover...... randomized trial. During both treatment periods the patients were treated with intermediate-acting insulin at bedtime. Six of the patients were withdrawn from the study during intranasal insulin therapy due to metabolic dysregulation. Serum insulin concentrations increased more rapidly and decreased more...... quickly during intranasal as compared with subcutaneous insulin administration. Metabolic control deteriorated, as assessed by haemoglobin A1c concentrations, slightly but significantly after intranasal as compared with subcutaneous insulin therapy. The bioavailability of intranasally applied insulin...

  13. Increased serum nitric oxide and malondialdehyde levels in patients with acute intestinal amebiasis.

    Science.gov (United States)

    Namıduru, E S; Tarakçıoğlu, M; Namıduru, M; Kocabaş, R; Erbağcı, B; Meram, I; Karaoğlan, I; Yılmaz, N; Cekmen, M

    2011-12-01

    To determine the level of oxygen-nitrogen stress parameters in the pathogenesis of amebiasis. Twenty-four acute intestinal amebiasis patients and 20 healthy controls were enrolled in the present study. Serum malondialdehyde and nitric oxide levels were determined spectrophotometrically. Serum malondialdehyde and nitric oxide levels were significantly higher in acute intestinal amebiasis patients than healthy controls (Pamebiasis patients. Also these parameters can be used to supplement the conventional microscopic method for reliable diagnosis of intestinal amebiasis.

  14. Colonoscopic diagnosis of amebiasis: a case series and systematic review.

    Science.gov (United States)

    Lee, Ko-Chao; Lu, Chien-Chang; Hu, Wan-Hsiang; Lin, Shung-Eing; Chen, Hong-Hwa

    2015-01-01

    Nonspecific gastrointestinal symptoms make diagnosis of amebiasis difficult. Certain colonoscopic findings predict amebic colitis while others suggest different diagnoses. We aimed to evaluate the diagnostic capability of colonic evaluation of amebiasis. We retrospectively reviewed data of all amebiasis cases admitted to our institution between 2003 and 2012. Cases were diagnosed by clinical presentation, laboratory examinations, and colonoscopy with biopsy and microscopic examination. Patients were stratified as right-sided colitis and proctosigmoiditis. A systematic review was conducted by searching Medline, Cochrane, EMBASE, and Google Scholar using key words amebiasis, amebic colitis, amebic proctosigmoiditis, colonoscopy, and Entamoeba histolytica. Data were extracted from articles meeting the inclusion criteria. Colonoscopic findings were described and studies were assessed for quality. The current series included 20 patients (5 male, 15 female, median age 51), 7 with amebic liver abscess and 13 with amebic colitis. Colonoscopic findings of right-sided colitis included aphthae or erosions, ulcers, exudates, or edematous swollen mucosa in cecum, and findings for proctosigmoiditis were edematous swollen mucosa with bloody exudate. In 25 studies, colonoscopic findings of 41 patients (36 male, 5 female, median age 43.39 years) included mainly ulcers in the cecum and rectum, ulcerated mass, and edematous mucosa; and in fewer patients, submucosal invasion suggestive of colon cancer, bleeding ulcers, proctitis, and ulcers with aphthae in rectum. Colonic evaluation of suspected amebiasis is of diagnostic value when accompanied by biopsy and microscopic identification of Entamoeba species. Colonoscopic manifestations vary between right-sided colitis and proctosigmoiditis.

  15. Case report: Cutaneous amebiasis: the importance of molecular diagnosis of an emerging parasitic disease.

    Science.gov (United States)

    Morán, Patricia; Rojas, Liliana; Cerritos, René; Zermeño, Valeria; Valadez, Alicia; de Oca, Griselda Montes; Reyes, Miguel Ángel; González, Enrique; Partida, Oswaldo; Hernández, Eric; Nieves, Miriam; Portillo, Tobías; Gudiño, Marco; Ramiro, Manuel; Ximénez, Cecilia

    2013-01-01

    Cutaneous amebiasis is the least common clinical form of human amebiasis in Mexico, sexual amebiasis was only occasionally observed before the late 1980s. However, in the last few decades, most of the documented cases of cutaneous amebiasis from around the world are sexually transmitted. We present two cases of sexually transmitted genital amebiasis. The molecular characterization of the Entamoeba species in the affected tissues underlines the importance of an etiological diagnosis using specific and sensitive techniques that avoid the rapid destruction of tissues and the irreversible sequelae to the anatomy and function of the affected organs. In addition, for those interested in the study of the human-amoebic disease relationship and its epidemiology, the detection of a new, mixed infection in an invasive case of amebiasis reveals new perspectives in the study of the extraordinarily complex host-parasite relationship in amebiasis.

  16. Cutaneous Amebiasis: The Importance of Molecular Diagnosis of an Emerging Parasitic Disease

    Science.gov (United States)

    Morán, Patricia; Rojas, Liliana; Cerritos, René; Zermeño, Valeria; Valadez, Alicia; de Oca, Griselda Montes; Reyes, Miguel Ángel; González, Enrique; Partida, Oswaldo; Hernández, Eric; Nieves, Miriam; Portillo, Tobías; Gudiño, Marco; Ramiro, Manuel; Ximénez, Cecilia

    2013-01-01

    Cutaneous amebiasis is the least common clinical form of human amebiasis in Mexico, sexual amebiasis was only occasionally observed before the late 1980s. However, in the last few decades, most of the documented cases of cutaneous amebiasis from around the world are sexually transmitted. We present two cases of sexually transmitted genital amebiasis. The molecular characterization of the Entamoeba species in the affected tissues underlines the importance of an etiological diagnosis using specific and sensitive techniques that avoid the rapid destruction of tissues and the irreversible sequelae to the anatomy and function of the affected organs. In addition, for those interested in the study of the human-amoebic disease relationship and its epidemiology, the detection of a new, mixed infection in an invasive case of amebiasis reveals new perspectives in the study of the extraordinarily complex host-parasite relationship in amebiasis. PMID:23208883

  17. [Overdiagnosis of amebiasis in children with dysentery].

    Science.gov (United States)

    Beltramino, Juan Carlos; Sosa, Horacio; Gamba, Natalia; Busquets, Natalia; Navarro, Lucas; Virgolini, Stella; Ricardo, Omar

    2009-12-01

    There are morphologically identical amebaes, but with differences that can distinguish them; one as pathogenic: Entamoeba histolytica, and the other: Entamoeba dispar, as inoffensive. That brought the new hypothesis that many of the cases treated as amebiasis, weren't so. To identify E. hystolitica in patients with dysentery, supposed to be caused by amebae. Transversal and observational study performed between March 2005 and November 2007 in the city of Santa Fe, Argentina. Stools from children aged 2 months to 15 years-old with dysentery and direct exams with E. hystolitica/ dispar, were studied with ELISA to detect the adhesin of E. histolytica (adhesin Eh). Permanent stains for amebae were done as well as stool cultures. Clinical data were charted. 75 children were studied; 35 were male and 40, female, with a median age of 3 years-old. All of them presented diarrhea with leucocyte, 73% macroscopic blood on stool and 27% detectable on the microscope. Elisa Eh was positive in 21; 3 cases had hematophagous trophozoites. In 15 stool cultures were found: S. flexneri S2 type in 5 cases. Other parasites: 6 (Blastocystis homini 5). In 54 adhesin Eh was negative, 19% of the coulouring detected E. dispar. From 44 stool cultures: S. flexneri S2 type was detected in 13, Shigella sp in 1, C jejuni 5, other: 3. Other parasites: 12 (Blastocystis homini 9). In this group of children with "amebic dysentery", half of them developed invasive bacteriae and only 28% had E. histolytica on stools; that means that the prevalence of positive cases in the population could be 18% to 38% [CI 95% (0.179; 0.381)].

  18. Prevention of intestinal amebiasis by vaccination with the Entamoeba histolytica Gal/GalNac lectin.

    Science.gov (United States)

    Houpt, Eric; Barroso, Lisa; Lockhart, Lauren; Wright, Rhonda; Cramer, Carole; Lyerly, David; Petri, William A

    2004-01-26

    Prevention of intestinal infection by Entamoeba histolytica would block both invasive disease and parasite transmission. The amebic Gal/GalNAc lectin mediates parasite adherence to the colonic surface and fecal anti-lectin IgA is associated with protection from intestinal reinfection in children. We tested if vaccination with the E. histolytica Gal/GalNAc lectin could prevent cecal infection in a C3H mouse model of amebic colitis. Two trials using native lectin purified from the parasite and two trials using a 64 kDa recombinant fragment ("LecA") were performed with a combined intranasal and intraperitoneal immunization regimen using cholera toxin and Freund's adjuvants, respectively. Two weeks after immunization mice were challenged intracecally with trophozoites, and 4-12 weeks after challenge mice were sacrificed for histopathologic evaluation of infection. Vaccination prevented intestinal infection with efficacies of 84 and 100% in the two native lectin trials and 91 and 34% in the two LecA trials. Mice with detectable pre-challenge fecal anti-lectin IgA responses were significantly more resistant to infection than mice without fecal anti-lectin IgA responses. These results show for the first time that immunization with the Gal/GalNAc lectin can prevent intestinal amebiasis in mice and suggest a protective role for fecal anti-lectin IgA in vivo.

  19. [Ameboma: possible therapeutic decisions in an amebiasis-endemic region].

    Science.gov (United States)

    Villegas-Betanzo, Pavel; Martínez-Jiménez, Mario Aurelio; Guevara-Torres, Lorenzo; Quintero-Meza, Karla; Sánchez-Aguilar, Martín; Arriaga-Caballero, Jesús Emmanuel

    2015-01-01

    Amebiasis can mimic cecal tumors. Unless this infection is diagnosed in a timely manner, affected individuals may undergo extensive surgery. We carried out a retrospective analytical study of the therapeutic approach to amebiasis in a second-level hospital in an area of central Mexico with a high prevalence of this infection. Records from 2005-2011 were reviewed. There were 261 cases of amebiasis. Twenty cases were diagnosed by the histopathologist or on the basis of serological results. Sixteen patients underwent surgery due to acute abdomen, and four received medical treatment with metronidazole. Three treatment groups were analyzed: 1. hemicolectomy, 2. appendicectomy and antiamebic therapy, and 3. antiamoebic therapy alone. In the non-surgical group, imaging studies showed improvement with medical therapy. Length of hospital stay was higher in the group undergoing extensive surgery (p amebiasis or receive antiamebic therapy with monitoring of the mass to avoid extensive resective surgery. Copyright © 2014 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

  20. Epidemiology of Domestically Acquired Amebiasis in Japan, 2000-2013.

    Science.gov (United States)

    Ishikane, Masahiro; Arima, Yuzo; Kanayama, Atsuhiro; Takahashi, Takuri; Yamagishi, Takuya; Yahata, Yuichiro; Matsui, Tamano; Sunagawa, Tomimasa; Nozaki, Tomoyoshi; Oishi, Kazunori

    2016-05-04

    Notifications of amebiasis have been increasing in Japan. Using national surveillance data during 2000-2013, reported cases of amebiasis were analyzed. A case of amebiasis was defined as laboratory-confirmed Entamoeba histolytica infection, regardless of presence of symptoms. We described temporal trends and analyzed correlates of asymptomatic versus symptomatic cases based on odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression. Of 9,946 cases reported during 2000-2013, 7,403 were domestic cases. During this period, the proportion of domestic cases increased from 63% to 85%. Among male cases, majority were middle aged, and from 2008, the number of cases attributed to heterosexual contact surpassed that of homosexual contact. During 2010-2013, increase in notifications was associated with asymptomatic cases, colonoscopy diagnosis, and males with unknown or heterosexual route of infection. Among males, colonoscopy (OR = 31.5; 95% CI = 14.0-71.0) and cases with unknown route of infection, relative to homosexual contact (OR = 2.2; 95% CI = 1.3-3.9), were associated with asymptomatic infections in multivariate analysis. Although the recent rise may have been due to enhanced detection by colonoscopy or reporting, the large number of asymptomatic cases, with reportedly unknown or heterosexual route of infection, has led to a better understanding of amebiasis in Japan and highlights the potential public health concern. © The American Society of Tropical Medicine and Hygiene.

  1. Construction and immunogenicity of a codon-optimized Entamoeba histolytica Gal-lectin-based DNA vaccine.

    Science.gov (United States)

    Gaucher, Denis; Chadee, Kris

    2002-09-10

    Invasive amebiasis caused by Entamoeba histolytica is the third leading parasitic cause of mortality, and there are no vaccines available to help control the disease. The galactose-adherence lectin (Gal-lectin) is the parasite's major molecule allowing it to adhere to colonic mucin for colonization and to target cells for tissue destruction. It is immunodominant and is regarded as the most promising candidate molecule to be included in a subunit vaccine against amebiasis. In this study, we are reporting the construction of a codon-optimized DNA vaccine encoding a portion of the Gal-lectin heavy subunit that includes the carbohydrate recognition domain (CRD), and its in vivo testing in mice. The vaccine stimulated a Th1-type Gal-lectin-specific cellular immune response as well as the development of serum antibodies that recognized a recombinant portion of the heavy subunit, and that inhibited the adherence of trophozoites to target cells in vitro.

  2. [Amebiasis and amebic liver abscess in Mexico: a present-day public health problem].

    Science.gov (United States)

    Escandón Romero, C; García Manzo, N T; Escobedo de la Peña, J; Hernández Ramos, J M; Olvera Alvarez, J; Cabral Soto, J

    1996-01-01

    Amebiasis still remains as a major public health problem in the world. It is one of the most common reasons for medical consult. There are more than half a million cases of amebiasis just at the Mexican Institute of the Social Security. There is still a lack of epidemiologic information on amebiasis in Mexico. To describe the secular trend fro amebiasis and for amebic liver abscess in the Mexican population, as well as in those covered by IMSS Solidaridad. An ecologic trend study was carried on. Incidence rate of amebiasis in all of its forms of presentation, and of amebic liver abscess, were plotted against each year for the 1986-1994 period. Amebiasis incidence in all of its forms of presentation showed a stable trend in this period, as it was seen with amebic liver abscess. Amebiasis is more common in the first years of life. On the contrary, amebic liver abscess showed an inverted 'J' pattern; its occurrence is higher in the extreme years of life. Fatality rates have shown a descendent trend. Amebiasis reflects socioeconomic conditions in Mexico and the fact that Mexican is still an endless culture. There is a need to promote health education, better diagnostic procedures and detection of asymptomatic carriers. Health policies for mothers that are asymptomatic carriers should be reviewed, due to the high rates of amebiasis and amebic liver abscess in children under one year of age.

  3. The dynamic interdependence of amebiasis, innate immunity, and undernutrition.

    Science.gov (United States)

    Verkerke, Hans P; Petri, William A; Marie, Chelsea S

    2012-11-01

    Entamoeba histolytica, the protozoan parasite that causes amebic dysentery, greatly contributes to disease burden in the developing world. Efforts to exhaustively characterize the pathogenesis of amebiasis have increased our understanding of the dynamic host-parasite interaction and the process by which E. histolytica trophozoites transition from gut commensals to invaders of the intestinal epithelium. Mouse models of disease continue to be instrumental in this area. At the same time, large-scale studies in human populations have identified genetic and environmental factors that influence susceptibility to amebiasis. Nutritional status has long been known to globally influence immune function. So it is not surprising that undernutrition has emerged as a critical risk factor. A better understanding of how nutritional status affects immunity to E. histolytica will have dramatic implications in the development of novel treatments. Future work should continue to characterize the fascinating host-parasite arms race that occurs at each stage of infection.

  4. The Dynamic Interdependence of Amebiasis, Innate Immunity, and Undernutrition1

    Science.gov (United States)

    Verkerke, Hans P.; Petri, William A.; Marie, Chelsea S.

    2012-01-01

    Entamoeba histolytica, the protozoan parasite that causes amebic dysentery, greatly contributes to disease burden in the developing world. Efforts to exhaustively characterize the pathogenesis of amebiasis have increased our understanding of the dynamic host-parasite interaction and the process by which E. histolytica trophozoites transition from gut commensals to invaders of the intestinal epithelium. Mouse models of disease continue to be instrumental in this area. At the same time, large-scale studies in human populations have identified genetic and environmental factors that influence susceptibility to amebiasis. Nutritional status has long been known to globally influence immune function. So it is not surprising that undernutrition has emerged as a critical risk factor. A better understanding of how nutritional status affects immunity to E. histolytica will have dramatic implications in the development of novel treatments. Future work should continue to characterize the fascinating host-parasite arms race that occurs at each stage of infection. PMID:23114864

  5. Invasive amebiasis: an update on diagnosis and management.

    Science.gov (United States)

    Salles, José Maria; Salles, Mauro José; Moraes, Luiz Alberto; Silva, Mônica Cristina

    2007-10-01

    In its invasive form, the trophozoite is responsible for clinical syndromes, ranging from classical dysentery to extraintestinal disease with emphasis on hepatic amebiasis. Abdominal pain, tenderness and diarrhea of watery stool, sometimes with blood, are the predominant symptoms of amebic colitis. Besides the microscopic identification of Entamoeba histolytica, diagnosis should be based on the detection of specific antigens in the stool or PCR associated with the occult blood in the stool. Amebic dysentery is treated with metronidazole, followed by a luminal amebicide. The trophozoite reaches the liver causing hepatic amebiasis. Right upper quadrant pain, fever and hepatomegaly are the predominant symptoms. The diagnosis is made by the finding of E. histolytica in the hepatic fluid, or in the necrotic material at the edge of the lesion in a minority of patients, and by detection of antigens or DNA. Ultrasonography is the initial imaging procedure indicated. The local perforation of hepatic lesion leads to important and serious complications.

  6. The efficacy of plant extracts on cecal amebiasis in rats

    Directory of Open Access Journals (Sweden)

    Enerst C. Ohanu

    2015-02-01

    Full Text Available Amebiasis caused by Entamoeba histolytica is a major public health problem in tropical and subtropical countries. Treatment failure with specific chemotherapy has been reported suggesting the possibility of drug resistance. This study investigated the anti-amoebic effects of four plant extracts on cecal amebiasis in rats. The cecal amebiasis was induced by the injection of 3.0×105 troph/mL of E. histolytica parasite directly into the rat’s caecum. A total of 137 rats were used for these studies; five rats in each group for both positive and negative control, 15 rats in each group to test the four plant extracts and metronidazole. The infected rats were treated for cecal amebiasis using each of the four plant extracts at graded doses of 100 mg/kg, 200 mg/kg and 400 mg/kg and with metronidzole at a dose of 62.5 mg/kg,100 mg/kg and 125 mg/kg for five consecutive days. The efficacy of the four plant extracts were evaluated based on Neal’s, 1951 method. The plant extracts of Garlic, Guava, Pawpaw and Pumpkin at 400 mg/kg and 200 mg/kg body-weight gave a cure rate of 80%, 100%, 60%, 40% and 40%, 80%, 40%, 0%, respectively. The mean parasite count in the cecal contents of the treated rats at a dose 400 mg/kg were 18.5±1.6, 0.0±0.0, 33.3±1.8 and 49.5±4.0, respectively. The difference was statistically significant (P<0.05. This study has revealed that Guava at a high dosing level (400 mg/kg body weight is as good as the standard drug in reducing the both parasite load (probably with limited side effect.

  7. Impaired consciousness revealing a cerebral amebiasis in an immunocompetent adult

    Directory of Open Access Journals (Sweden)

    Hanane Ezzouine

    2012-01-01

    Full Text Available Amebiasis is a parasitic infection with manifestations, mainly digestives. It is rarely described extra-gastrointestinal locations including the brain. We report the case of a patient aged 42, made five months earlier for an appendectomy, and was admitted to the ICU after a convalescent stable uncomplicated. At admission, he was 12/15 in Glasgow and had a right hemiplegia. Brain CT revealed a discrete diffuse hypodensities perilesional edema. An abdominal ultrasound found an aspect for multiple hepatic abscesses. Abscess puncture was performed, which was not conclusive, and no seed could be identified. On Ultrasound, no cardiac abnormalities were found, and no endocarditis was present. And since the appearance macroscopic (chocolate-brown, amebic serology is performed and has been highly positive. The therapeutic management included an intubation and ventilation as well as a tri-antibiotic-based ceftriaxon, metronidazol and gentamycin. Confirmation of amebiasis required high doses of metronidazol for an extended period. The replay of the play was an appendectomy for an amebome. Evolution was favorable. Amebiasis can have extraintestinal locations, issues to think about including the cerebral forms.

  8. Entamoeba histolytica infection in children and protection from subsequent amebiasis.

    Science.gov (United States)

    Haque, Rashidul; Mondal, Dinesh; Duggal, Priya; Kabir, Mamun; Roy, Shantanu; Farr, Barry M; Sack, R Bradley; Petri, William A

    2006-02-01

    The contribution of amebiasis to the burden of diarrheal disease in children and the degree to which immunity is acquired from natural infection were assessed in a 4-year prospective observational study of 289 preschool children in an urban slum in Dhaka, Bangladesh. Entamoeba histolytica infection was detected at least once in 80%, and repeat infection in 53%, of the children who completed 4 years of observation. Annually there were 0.09 episodes/child of E. histolytica-associated diarrhea and 0.03 episodes/child of E. histolytica-associated dysentery. Fecal immunoglobulin A (IgA) anti-parasite Gal/GalNAc lectin carbohydrate recognition domain (anti-CRD) was detected in 91% (183/202) of the children at least once and was associated with a lower incidence of infection and disease. We concluded that amebiasis was a substantial burden on the overall health of the cohort children. Protection from amebiasis was associated with a stool anti-CRD IgA response. The challenge of producing an effective vaccine will be to improve upon naturally acquired immunity, which does not provide absolute protection from reinfection.

  9. Subjective adverse reactions to metronidazole in patients with amebiasis.

    Science.gov (United States)

    Ohnishi, Kenji; Sakamoto, Naoya; Kobayashi, Ken-Ichiro; Iwabuchi, Sentaro; Nakamura-Uchiyama, Fukumi; Ajisawa, Atsushi; Yamauchi, Yuko; Takeshita, Nozomi; Yamamoto, Yasuyuki; Tsunoda, Takafumi; Yoshimura, Yukihiro; Tachikawa, Natsuo; Uehira, Tomoko

    2014-10-01

    Subjective adverse reactions to metronidazole were analyzed in 111 patients with amebiasis. Metronidazole was administered to 36 patients at a daily dose of 2250 mg and 75 patients at daily doses lower than 2250 mg. The reactions reported included nausea without vomiting in 11 (9.9%) patients, nausea with vomiting in 2 (1.8%), dysgeusia in 2 (1.8%), diarrhea in 1 (0.9%), headache in 1 (0.9%), numbness in 1 (0.9%), dizziness in 1 (0.9%), urticaria in 1 (0.9%), exanthema in 1 (0.9%), and discomfort in 1 (0.9%). Nausea was reported by 28% (10/36) of the patients receiving metronidazole at a daily dose of 2250 mg and 4% (3/75) of the patients receiving lower daily doses. The duration of the metronidazole administration in days was not associated with the appearance of nausea. No life-threatening adverse reactions were identified, and good clinical therapeutic effects were observed in 96% (107/111) of the patients. While metronidazole appears to be a safe anti-protozoal agent for patients with amebiasis, our results indicate that a daily metronidazole dose of 2250 mg is excessive for amebiasis, as it often induces nausea. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  10. Extra-intestinal amebiasis: clinical presentation in a non-endemic setting

    DEFF Research Database (Denmark)

    Thorsen, S; Rønne-Rasmussen, J; Petersen, E;

    1993-01-01

    37/38 patients with reciprocal titers > or = 512 against Entamoeba histolytica in Denmark over a 5-year period were evaluated retrospectively in order to establish the clinical profile of extra-intestinal amebiasis in a non-endemic area. 24 of these had extra-intestinal amebiasis, all presenting 1...

  11. Evolution of surgical treatment of amebiasis-associated colon perforation.

    Science.gov (United States)

    Athié-Gutiérrez, César; Rodea-Rosas, Heriberto; Guízar-Bermúdez, Clemente; Alcántara, Avisaí; Montalvo-Javé, Eduardo E

    2010-01-01

    Amebiasis is a worldwide health problem that mainly affects developing countries. Invasive amebiasis tends to develop complications, and among these, perforation of the colon, although infrequent (1.9-9.1%), is the most lethal. Surgical treatment in these cases should be carried out in a timely fashion prior to the presentation of systemic repercussions or death. In the present study, we analyzed a total of 122 cases of invasive amebiasis-associated colon perforation. We conducted a clinical, retrospective, and observational study and presented cases of colonic perforation observed over the past 30 years at the Medical-Surgical Emergency Service of the Mexico City-based Hospital General de México OD during the 1970-1999 period. During this time, a total of 19,916 emergency abdominal surgeries were performed. One hundred twenty-two of these procedures corresponded to cases of colon perforation by ameba, which represents 0.6%; 80 patients were men (65.6%) and 42 were women (34.4%), with an average age of 48 years. Multiple colon perforation was 74%, with right colon the most affected (90.5%). Depending on the perforation's extension and localization, right hemicolectomy with ileostomy were performed in 53 patients (43.45%), subtotal colectomy with ileostomy in 43 (35.25%), left hemicolectomy with transverse colostomy in 12 (9.83%), exteriorization of perforated left colon (stoma) in 13 (10.65%), and primary closure with exteriorization in one patient (0.8%). Post-operative complications were present in 48 patients (39.3%), and 20 cases were related with the creation of a stoma. Eighteen of these cases were due to persistent abdominal sepsis and ten due to toxic colon; the latter correspond solely to patients with initial nonresective treatment. General mortality was 40%, with 32% (17 of 53 cases) of mortality in those submitted to right hemicolestomy, 16.7% (two of 12) of left hemicolestomy, 44.2% (19 of 43) in those in whom a subtotal colectomy was performed, with

  12. Dyspnea and dysentery: a case report of pleuropulmonary amebiasis.

    Science.gov (United States)

    Shrestha, Merica; Shah, Anita; Lettieri, Christopher

    2010-02-01

    Pleuropulmonary amebiasis is an uncommon complication of Entamoeba histolytica infection. It typically occurs in endemic regions including Central and South America, Africa and the Indian subcontinent. The case of a previously healthy US Army male stationed in Liberia with an acute onset of fevers, abdominal pain and bloody diarrhea is presented. He developed a productive cough with pleuritic chest pain and imaging revealed multiple liver abscesses, with rupture through the diaphragm causing a large right pleural empyema. A positive Entamoeba histolytica serum antibody and pleural fluid antigen confirmed the diagnosis. Surgical drainage of the pleural empyema and medical treatment with antiparasitics were necessary for symptom and disease resolution.

  13. Host-parasite interactions and mechanisms of infection in amebiasis

    Directory of Open Access Journals (Sweden)

    Suriptiastuti Suriptiastuti

    2016-02-01

    Full Text Available Amebiasis is caused by E. histolytica, which is the only species pathogenic in humans, while the pathogeneicity of E. dispar and E. moshkovskii is still unclear. The disease is endemic in the developing countries, mainly due to poor sanitation and lack of clean water supplies. Infection occurs by ingestion of E. histolytica cysts in fecally contaminated food or water. Excystation in the small intestine releases motile invasive trophozoites which migrate to the large intestine, adhere to the colonic epithelium by means of galactose and an amebic surface antigen, N-acetyl-D-galactosamine-specific lectin. This results in killing of epithelial cells, neutrophils, and lymphocytes by the trophozoites, presumably through secretion of the pore-forming proteins called amebapores and activation of caspase 3. The trophozoite virulence factor, cysteine proteinase, induces an inflammatory response, resulting in neutrophil-mediated damage. Hematogenous spread of trophozoites causes extraintestinal amebiasis, particularly amebic liver abscess (ALA, in the formation of which caspase 3 presumably also plays a role. The trophozoites in the liver induce tissue destruction, cellular necrosis and formation of microabcesses that coalesce into a large solitary abscess in 65-75% of cases. Results from pediatric studies reveal that partial immunity is acquired after infection with E.histolytica, the immunity however declining with age.

  14. Immune Response of Amebiasis and Immune Evasion by Entamoeba histolytica

    Science.gov (United States)

    Nakada-Tsukui, Kumiko; Nozaki, Tomoyoshi

    2016-01-01

    Entamoeba histolytica is a protozoan parasite and the causative agent of amebiasis. It is estimated approximately 1% of humans are infected with E. histolytica, resulting in an estimate of 100,000 deaths annually. Clinical manifestations of amebic infection range widely from asymptomatic to severe symptoms, including dysentery and extra-intestinal abscesses. Like other infectious diseases, it is assumed that only ~20% of infected individuals develop symptoms, and genetic factors of both the parasite and humans as well as the environmental factors, e.g., microbiota, determine outcome of infection. There are multiple essential steps in amebic infection: degradation of and invasion into the mucosal layer, adherence to the intestinal epithelium, invasion into the tissues, and dissemination to other organs. While the mechanisms of invasion and destruction of the host tissues by the amebae during infection have been elucidated at the molecular levels, it remains largely uncharacterized how the parasite survive in the host by evading and attacking host immune system. Recently, the strategies for immune evasion by the parasite have been unraveled, including immunomodulation to suppress IFN-γ production, elimination of immune cells and soluble immune mediators, and metabolic alterations against reactive oxygen and nitrogen species to fend off the attack from immune system. In this review, we summarized the latest knowledge on immune reaction and immune evasion during amebiasis. PMID:27242782

  15. Host-parasite interactions and mechanisms of infection in amebiasis

    Directory of Open Access Journals (Sweden)

    Suriptiastuti

    2010-08-01

    Full Text Available Amebiasis is caused by E. histolytica, which is the only species pathogenic in humans, while the pathogeneicity of E. dispar and E. moshkovskii is still unclear. The disease is endemic in the developing countries, mainly due to poor sanitation and lack of clean water supplies. Infection occurs by ingestion of E. histolytica cysts in fecally contaminated food or water. Excystation in the small intestine releases motile invasive trophozoites which migrate to the large intestine, adhere to the colonic epithelium by means of galactose and an amebic surface antigen, N-acetyl-D-galactosamine-specific lectin. This results in killing of epithelial cells, neutrophils, and lymphocytes by the trophozoites, presumably through secretion of the pore-forming proteins called amebapores and activation of caspase 3. The trophozoite virulence factor, cysteine proteinase, induces an inflammatory response, resulting in neutrophil-mediated damage. Hematogenous spread of trophozoites causes extraintestinal amebiasis, particularly amebic liver abscess (ALA, in the formation of which caspase 3 presumably also plays a role. The trophozoites in the liver induce tissue destruction, cellular necrosis and formation of microabcesses that coalesce into a large solitary abscess in 65-75% of cases. Results from pediatric studies reveal that partial immunity is acquired after infection with E.histolytica, the immunity however declining with age.

  16. Efficacy and safety of paromomycin for treating amebiasis in Japan.

    Science.gov (United States)

    Kikuchi, Tadashi; Koga, Michiko; Shimizu, Shoichi; Miura, Toshiyuki; Maruyama, Haruhiko; Kimura, Mikio

    2013-12-01

    The clinical management of amebiasis is a growing concern, particularly among human immunodeficiency virus (HIV)-infected individuals who are predisposed to severe illness. Treatment with a luminal amebicide is strongly recommended following acute-stage treatment with a nitroimidazole. In 2004, the Japanese Research Group on Chemotherapy of Tropical Diseases introduced paromomycin, which was not nationally licensed, and offered it to a number of patients. From 2004 to 2011, 143 case records of amebiasis (123 with amebic colitis, 16 with amebic liver abscess, and 4 with both) in which patients were treated with paromomycin, mainly 1,500 mg/day for 9 or 10 days following metronidazole treatment, were submitted. Among 123 evaluable cases, 23 (18.7%) experienced possible adverse effects, the most common being diarrhea (17/123, 13.8%) and other gastrointestinal problems that were resolved after the completion or discontinuation of treatment. In addition, single cases of bloody stools associated with Clostridium difficile colitis, skin rash, and the elevation of liver enzymes were also reported, although the causal relationship was not clear. HIV infection did not appear to increase the incidence of adverse drug effects. Each of the 11 asymptomatic or mildly symptomatic amebic colitis cases became negative for stool cysts after paromomycin treatment. Paromomycin was shown to be safe and well tolerated, as well as effective in a special subset of amebic colitis cases. © 2013.

  17. Progress towards development of a vaccine for amebiasis.

    Science.gov (United States)

    Stanley, S L

    1997-01-01

    The application of molecular biologic techniques over the past decade has seen a tremendous growth in our knowledge of the biology of Entamoeba histolytica, the causative agent of amebic dysentery and amebic liver abscess. This approach has also led to the identification and structural characterization of three amebic antigens, the serine-rich Entamoeba histolytica protein (SREHP), the 170-kDa subunit of the Gal/GalNAc binding lectin, and the 29-kDa cysteine-rich protein, which all show promise as recombinant antigen-based vaccines to prevent amebiasis. In recent studies, an immunogenic dodecapeptide derived from the SREHP molecule has been genetically fused to the B subunit of cholera toxin, to create a recombinant protein capable of inducing both antiamebic and anti-cholera toxin antibodies when administered by the oral route. Continued progress in this area will bring us closer to the goal of a cost-effective oral combination "enteric pathogen" vaccine, capable of inducing protective mucosal immune responses to several clinically important enteric diseases, including amebiasis. PMID:9336666

  18. Immune Response of Amebiasis and Immune Evasion by Entamoeba histolytica.

    Science.gov (United States)

    Nakada-Tsukui, Kumiko; Nozaki, Tomoyoshi

    2016-01-01

    Entamoeba histolytica is a protozoan parasite and the causative agent of amebiasis. It is estimated approximately 1% of humans are infected with E. histolytica, resulting in an estimate of 100,000 deaths annually. Clinical manifestations of amebic infection range widely from asymptomatic to severe symptoms, including dysentery and extra-intestinal abscesses. Like other infectious diseases, it is assumed that only ~20% of infected individuals develop symptoms, and genetic factors of both the parasite and humans as well as the environmental factors, e.g., microbiota, determine outcome of infection. There are multiple essential steps in amebic infection: degradation of and invasion into the mucosal layer, adherence to the intestinal epithelium, invasion into the tissues, and dissemination to other organs. While the mechanisms of invasion and destruction of the host tissues by the amebae during infection have been elucidated at the molecular levels, it remains largely uncharacterized how the parasite survive in the host by evading and attacking host immune system. Recently, the strategies for immune evasion by the parasite have been unraveled, including immunomodulation to suppress IFN-γ production, elimination of immune cells and soluble immune mediators, and metabolic alterations against reactive oxygen and nitrogen species to fend off the attack from immune system. In this review, we summarized the latest knowledge on immune reaction and immune evasion during amebiasis.

  19. Neurosurgical complications after intranasal ethmoidectomy.

    OpenAIRE

    Toselli, R M; dePapp, A; Harbaugh, R E; Saunders, R. L.

    1991-01-01

    Intranasal ethmoidectomy is a common otolaryngological procedure. Despite the potential for serious intracranial complications, there is a paucity of reports describing the neurosurgical complications of the procedure. Two patients with intracranial complications of intranasal ethmoidectomy, and the relevant medical literature, are reviewed. The anatomy of the ethmoid air cells and their relation to the intracranial cavity are described. The importance of definitive, emergent repair with atte...

  20. Diagnosis of colonic amebiasis and coexisting signet-ring cell carcinoma in intestinal biopsy.

    Science.gov (United States)

    Grosse, Alexandra

    2016-09-28

    Amebiasis is uncommon in developed countries. Several case reports in the literature emphasize that both the presenting symptoms and the radiological findings of colonic amebiasis closely resemble more common conditions, such as idiopathic inflammatory bowel disease and gastro-intestinal malignancy. We describe a unique case of colonic amebiasis (amebomas) coexisting with signet-ring cell carcinoma of the ileocecal valve, the cecum and the appendix. Endoscopically, the ulcerated tumor was indistinguishable from the ulcerations and pseudotumors (amebomas) detected in the ascending colon. Histological examination of biopsy specimens revealed the pathognomonic features of protozoa with ingested erythrocytes in combination with signet-ring cell infiltration. The author concludes that amebiasis may not only mimic carcinoma but, rarely, may coexist with carcinoma in the same patient. Clinicians and pathologists should be aware of this possibility in order not to delay diagnosis and treatment of malignant disease.

  1. An unusual cause of unilateral hydronephrosis: invasive colonic amebiasis.

    Science.gov (United States)

    Pirti, Okay; Koçak, Erdem; Güler, Osman; Koçak, Gülay; Altunkaya, Canan; Caydere, Muzaffer; Köklü, Seyfettin

    2012-01-01

    A 62-year-old man was admitted to our hospital with complaints of abdominal pain and rectal bleeding. Although the colonoscopic examination was highly suggestive of a carcinoma, the histopathological examinations were consistent with chronic inflammation. CT examination revealed a solid lesion from cecum to the ascending colon with right urethral invasion. Percutaneous right nephrostomy was performed for grade 2-3 hydronephrosis. Three days after hospitalization, ileus developed and right hemicolectomy was performed. During surgery we observed that the lesion had invaded the middle part of ureter. So the middle part of ureter was removed with side-to-side urethral anastomosis and 6F double-J catheter was placed. The histopathological findings of resected specimen were consistent with ameboma. Reviewing the literature unilateral hydronephrosis due to colonic amebiasis has not been reported.

  2. Inflammatory reaction in experimental hepatic amebiasis. An ultrastructural study.

    Science.gov (United States)

    Tsutsumi, V.; Martinez-Palomo, A.

    1988-01-01

    One of the hallmarks of tissue necrosis produced by the human protozoan parasite Entamoeba histolytica, the causative agent of human amebiasis, appeared to be the lack of inflammatory reaction to the invading trophozoites. Recent evidence suggests, however, that inflammatory cells do appear during early stages of amebic destructive lesions and that they contribute to the establishment of foci of tissue necrosis in intestinal and liver lesions. The present analysis of the fine-structural changes that take place during early stages of amebic liver abscesses induced in hamsters after the intraportal inoculation of axenic amebas has shown that large numbers of polymorphonuclear leukocytes (PMNs) are recruited around invading amebas. These leukocytes lyse as a consequence of contact-mediated damage induced by the trophozoites. Amebas were also capable of ingesting apparently intact PMNs. Macrophages and eosinophils were also recruited at the foci of inflammation. At all times examined, trophozoites of Entamoeba histolytica survived in spite of being in close contact with PMNs or degranulating eosinophils. The ultrastructural observations have also shown the lack of direct contact between amebas and liver parenchymal cells during the initial stages of the focal liver necrosis induced by the parasite, therefore supporting the view that hepatic damage may be effected indirectly through lysis of inflammatory cells. The results also provide a basis for the understanding of the induction of experimental protective immunity against invasive amebiasis, a process which seems to be mostly dependent on cellular mechanisms. Images Figure 1 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 PMID:3337207

  3. 21 CFR 874.4780 - Intranasal splint.

    Science.gov (United States)

    2010-04-01

    .... An intranasal splint is intended to minimize bleeding and edema and to prevent adhesions between the septum and the nasal cavity. It is placed in the nasal cavity after surgery or trauma. The intranasal...

  4. Lectin-based glycoproteomics to explore and analyze hepatocellular carcinoma-related glycoprotein markers.

    Science.gov (United States)

    Dai, Zhi; Zhou, Jian; Qiu, Shuang-Jian; Liu, Yin-Kun; Fan, Jia

    2009-09-01

    More and more new diagnostic biomarkers of hepatocellular carcinoma (HCC) have been found in association with advances in the standardization of 2-DE coupled with MS analysis. However, the diagnosis of HCC is still detected in the late stages of the disease, when treatment options are limited and prognosis is poor. The glycosylation of proteins is known to change in tumor cells during the development of HCC as the result of alterations in the levels of glycosyltransferases, such as increased fucosylation of Golgi Protein 73 and alpha-fetoprotein. These structural changes can influence the function or physiochemical properties of a protein, resulting in abnormal cancer cell behavior. Therefore, identification of HCC-related glycoprotein markers and analysis of glycan structural alterations might assist in the early detection of HCC. Here, we summarize lectin-based glycoproteomic strategies for the discovery of relevant biomarkers of HCC. The carbohydrate-binding specificities of different lectins offer a biological affinity approach that complements existing MS capabilities. These strategies involve the enrichment of glycoproteins or glycopeptides by lectins, followed by releasing carbohydrates with peptide-N-glycosidase F or reductive beta-elimination. The obtained glycopeptides are then identified by automated MS/MS and structural analysis of glycans is performed through modern methods such as quadrupole IT-TOF, MALDI-TOF/TOF and lectin microarray. These strategies will lead to faster and more clinically adaptable tests with greater sensitivity and specificity.

  5. Intranasal sedatives in pediatric dentistry

    Science.gov (United States)

    AlSarheed, Maha A.

    2016-01-01

    Objectives: To identify the intranasal (IN) sedatives used to achieve conscious sedation during dental procedures amongst children. Methods: A literature review was conducted by identifying relevant studies through searches on Medline. Search included IN of midazolam, ketamine, sufentanil, dexmedetomidine, clonidine, haloperidol and loranzepam. Studies included were conducted amongst individuals below 18 years, published in English, and were not restricted by year. Exclusion criteria were articles that did not focus on pediatric dentistry. Results: Twenty studies were included. The most commonly used sedatives were midazolam, followed by ketamine and sufentanil. Onset of action for IN midazolam was 5-15 minutes (min), however, IN ketamine was faster (mean 5.74 min), while both IN sufentanil (mean 20 min) and IN dexmedetomidine (mean 25 min) were slow in comparison. Midazolam was effective for modifying behavior in mild to moderately anxious children, however, for more invasive or prolonged procedures, stronger sedatives, such as IN ketamine, IN sufentanil were recommended. In addition, ketamine fared better in overall success rate (89%) when compared with IN midazolam (69%). Intranasal dexmedetomidine was only used as pre-medication amongst children. While its’ onset of action is longer when compared with IN midazolam, it produced deeper sedation at the time of separation from the parent and at the time of anesthesia induction. Conclusion: Intranasal midazolam, ketamine and sufentanil are effective and safe for conscious sedation, while intranasal midazolam, dexmedetomidine and sufentanil have proven to be effective premedications. PMID:27570849

  6. Intranasal sedatives in pediatric dentistry.

    Science.gov (United States)

    AlSarheed, Maha A

    2016-09-01

    To identify the intranasal (IN) sedatives used to achieve conscious sedation during dental procedures amongst children. A literature review was conducted by identifying relevant studies through searches on Medline. Search included IN of midazolam, ketamine, sufentanil, dexmedetomidine, clonidine, haloperidol, and loranzepam. Studies included were conducted amongst individuals below 18 years, published in English, and were not restricted by year. Exclusion criteria were articles that did not focus on pediatric dentistry.  Twenty studies were included. The most commonly used sedatives were midazolam, followed by ketamine and sufentanil. Onset of action for IN midazolam was 5-15 minutes (min), however, IN ketamine was faster (mean 5.74 min), while both IN sufentanil (mean 20 min) and IN dexmedetomidine (mean 25 min) were slow in comparison. Midazolam was effective for modifying behavior in mild to moderately anxious children, however, for more invasive or prolonged procedures, stronger sedatives, such as IN ketamine, IN sufentanil were recommended. In addition, ketamine fared better in overall success rate (89%) when compared with IN midazolam (69%). Intranasal dexmedetomidine was only used as pre-medication amongst children. While its' onset of action is longer when compared with IN midazolam, it produced deeper sedation at the time of separation from the parent and at the time of anesthesia induction. Intranasal midazolam, ketamine, and sufentanil are effective and safe for conscious sedation, while intranasal midazolam, dexmedetomidine, and sufentanil have proven to be effective premedications.

  7. Intranasal Oxytocin: Myths and Delusions.

    Science.gov (United States)

    Leng, Gareth; Ludwig, Mike

    2016-02-01

    Despite widespread reports that intranasal application of oxytocin has a variety of behavioral effects, very little of the huge amounts applied intranasally appears to reach the cerebrospinal fluid. However, peripheral concentrations are increased to supraphysiologic levels, with likely effects on diverse targets including the gastrointestinal tract, heart, and reproductive tract. The wish to believe in the effectiveness of intranasal oxytocin appears to be widespread and needs to be guarded against with scepticism and rigor. Preregistering trials, declaring primary and secondary outcomes in advance, specifying the statistical methods to be applied, and making all data openly available should minimize problems of publication bias and questionable post hoc analyses. Effects of intranasal oxytocin also need proper dose-response studies, and such studies need to include control subjects for peripheral effects, by administering oxytocin peripherally and by blocking peripheral actions with antagonists. Reports in the literature of oxytocin measurements include many that have been made with discredited methodology. Claims that peripheral measurements of oxytocin reflect central release are questionable at best.

  8. Does the eosinophil have a protective role in amebiasis?

    Directory of Open Access Journals (Sweden)

    López-Osuna Martha

    1997-01-01

    Full Text Available While normal human eosinophils are destroyed in vitro by virulent Entamoeba histolytica, notwhistanding the presence of antibodies and complement, activated eosinophils promptly destroy the parasite although dying also at the end of the process. To study the possible in vivo participation of eosinophils in invasive amebiasis, we compared the induction of experimental amebic abscess of the liver (AAL in gerbils (Meriones unguiculatus previously made eosinophilic through Toxocara canis antigen injection and in normal control gerbils. After intraportal inoculation of 10(5 ameba trophozoites (6 and 24 hr, the ratio of gerbils with AAL, as well as the number and size of the microabscesses was comparable in eosinophilic and control gerbils. However, at 96 hr the number and size of the microabscesses were significanly smaller (p<0.05 in eosinophilic gerbils. On the other hand the actuarial AAL survival curve up to 45 days post-amebic inoculation was signficantly (p<0.05 shifted to the right in controls. These results suggest that antigen-induced eosinophilia may exert a protective effect against AAL in gerbils.

  9. Pathogenesis of Intestinal Amebiasis: From Molecules to Disease

    Science.gov (United States)

    Espinosa-Cantellano, Martha; Martínez-Palomo, Adolfo

    2000-01-01

    In spite of a wealth of knowledge on the biochemistry and cellular and molecular biology of Entamoeba histolytica, little has been done to apply these advances to our understanding of the lesions observed in patients with intestinal amebiasis. In this review, the pathological and histological findings in acute amebic colitis are related to the molecular mechanisms of E. histolytica pathogenicity described to date. Infection of the human colon by E. histolytica produces focal ulceration of the intestinal mucosa, resulting in dysentery (diarrhea with blood and mucus). Although a complete picture has not yet been achieved, the basic mechanisms involved in the production of focal lytic lesions include complex multifactorial processes in which lectins facilitate adhesion, proteases degrade extracellular matrix components, porins help nourish the parasite and may also kill incoming polymorphonuclear leukocytes and macrophages, and motility is used by the parasite to invade deeper layers of the colon. In addition, E. histolytica has developed mechanisms to modulate the immune response during acute infection. Nevertheless, much still needs to be unraveled to understand how this microscopic parasite has earned its well-deserved histolytic name. PMID:10756002

  10. Amebic lung abscess with coexisting lung adenocarcinoma: a unusual case of amebiasis.

    Science.gov (United States)

    Zhu, Hailong; Min, Xiangyang; Li, Shuai; Feng, Meng; Zhang, Guofeng; Yi, Xianghua

    2014-01-01

    Amebic lung abscess with concurrent lung cancer, but without either a liver abscess or amebic colitis, is extremely uncommon. Here, we report a 70-year-old man presenting with pulmonary amebiasis and coexisting lung adenocarcinoma. During his first-time hospitalization, the diagnosis of lung amebiasis was confirmed by morphological observation and PCR in formalin-fixed and paraffin-embedded sediments of pleural effusion. Almost four months later, the patient was readmitted to hospital for similar complaints. On readmission, lung adenocarcinoma was diagnosed by liquid-based sputum cytology and thought to be delayed because coexisting amebic lung abscess. This case demonstrated that sediments of pleural effusion may be used for further pathological examination after routine cytology has shown negative results. At the same time, we concluded that lung cancer may easily go undetected in the patients with pulmonary amebiasis and repetitive evaluation by cytology and imaging follow-up are useful to find potential cancer.

  11. [Vulvar amebiasis. Report of a case and review of the literature].

    Science.gov (United States)

    Cornejo Juárez, Patricia; Avilés-Salas, A

    2003-02-01

    Genital amebiasis by Entamoeba histolytica is rare, even in Mexico where the disease is endemic. We report a case of genital amebiasis in a female patient with a recto-perineal fistula and two-week history of a profuse vaginal discharge, a painful and friable vulvar ulcer and induration in gluteal and inner side of thighs. The PAP smear and the biopsy showed trophozoites, no malignant cells were observed. The findings were compatible with genital amebiasis. The serology test for E. histolytica was positive (> 1: 512). The patient was treated with metronidazol 750 mg tid for 3 weeks. Complete resolution was achieved. The long term fistula, the low socioeconomic status, the poor hygiene and diabetes mellitus of a recent onset were probably the risk factors associated to this infection. We reviewed the literature.

  12. Amebiasis in HIV-1-Infected Japanese Men: Clinical Features and Response to Therapy

    Science.gov (United States)

    Watanabe, Koji; Gatanaga, Hiroyuki; Cadiz, Aleyla Escueta-de; Tanuma, Junko; Nozaki, Tomoyoshi; Oka, Shinichi

    2011-01-01

    Invasive amebic diseases caused by Entamoeba histolytica are increasing among men who have sex with men and co-infection of ameba and HIV-1 is an emerging problem in developed East Asian countries. To characterize the clinical and epidemiological features of invasive amebiasis in HIV-1 patients, the medical records of 170 co-infected cases were analyzed retrospectively, and E. histolytica genotype was assayed in 14 cases. In this series of HIV-1-infected patients, clinical presentation of invasive amebiasis was similar to that described in the normal host. High fever, leukocytosis and high CRP were associated with extraluminal amebic diseases. Two cases died from amebic colitis (resulting in intestinal perforation in one and gastrointestinal bleeding in one), and three cases died from causes unrelated to amebiasis. Treatment with metronidazole or tinidazole was successful in the other 165 cases. Luminal treatment was provided to 83 patients following metronidazole or tinidazole treatment. However, amebiasis recurred in 6 of these, a frequency similar to that seen in patients who did not receive luminal treatment. Recurrence was more frequent in HCV-antibody positive individuals and those who acquired syphilis during the follow-up period. Various genotypes of E. histolytica were identified in 14 patients but there was no correlation between genotype and clinical features. The outcome of metronidazole and tinidazole treatment of uncomplicated amebiasis was excellent even in HIV-1-infected individuals. Luminal treatment following metronidazole or tinidazole treatment does not reduce recurrence of amebiasis in high risk populations probably due to amebic re-infection. PMID:21931875

  13. Amebiasis in HIV-1-infected Japanese men: clinical features and response to therapy.

    Directory of Open Access Journals (Sweden)

    Koji Watanabe

    2011-09-01

    Full Text Available Invasive amebic diseases caused by Entamoeba histolytica are increasing among men who have sex with men and co-infection of ameba and HIV-1 is an emerging problem in developed East Asian countries. To characterize the clinical and epidemiological features of invasive amebiasis in HIV-1 patients, the medical records of 170 co-infected cases were analyzed retrospectively, and E. histolytica genotype was assayed in 14 cases. In this series of HIV-1-infected patients, clinical presentation of invasive amebiasis was similar to that described in the normal host. High fever, leukocytosis and high CRP were associated with extraluminal amebic diseases. Two cases died from amebic colitis (resulting in intestinal perforation in one and gastrointestinal bleeding in one, and three cases died from causes unrelated to amebiasis. Treatment with metronidazole or tinidazole was successful in the other 165 cases. Luminal treatment was provided to 83 patients following metronidazole or tinidazole treatment. However, amebiasis recurred in 6 of these, a frequency similar to that seen in patients who did not receive luminal treatment. Recurrence was more frequent in HCV-antibody positive individuals and those who acquired syphilis during the follow-up period. Various genotypes of E. histolytica were identified in 14 patients but there was no correlation between genotype and clinical features. The outcome of metronidazole and tinidazole treatment of uncomplicated amebiasis was excellent even in HIV-1-infected individuals. Luminal treatment following metronidazole or tinidazole treatment does not reduce recurrence of amebiasis in high risk populations probably due to amebic re-infection.

  14. Asymptomatic Intestinal Amebiasis in Japanese HIV-1–Infected Individuals

    Science.gov (United States)

    Watanabe, Koji; Nagata, Naoyoshi; Sekine, Katsunori; Watanabe, Kazuhiro; Igari, Toru; Tanuma, Junko; Kikuchi, Yoshimi; Oka, Shinichi; Gatanaga, Hiroyuki

    2014-01-01

    Seventy-one asymptomatic human immunodeficiency virus-1 (HIV-1) -infected individuals who underwent colonoscopy for detection of diseases other than amebiasis were included in this study. Ulcerative lesions caused by Entamoeba histolytica were identified by colonoscopy and biopsy in 11.3% (8 of 71) of individuals. Stool microscopic examination hardly identified Entamoeba, whereas serum antibody against E. histolytica was often elevated in patients with subclinical intestinal amebiasis. Human leukocyte antigen (HLA) class II allele against E. histolytica infection (DQB1*06:01) was frequently identified in these patients. This study emphasizes the endemic nature of E. histolytica infection in our cohort and the difficulties in epidemiological control. PMID:25048374

  15. Intranasal sedatives in pediatric dentistry

    OpenAIRE

    AlSarheed, Maha A

    2016-01-01

    Objectives: To identify the intranasal (IN) sedatives used to achieve conscious sedation during dental procedures amongst children. Methods: A literature review was conducted by identifying relevant studies through searches on Medline. Search included IN of midazolam, ketamine, sufentanil, dexmedetomidine, clonidine, haloperidol and loranzepam. Studies included were conducted amongst individuals below 18 years, published in English, and were not restricted by year. Exclusion criteria were art...

  16. Prevalence of amebiasis in inflammatory bowel disease in Turkey

    Institute of Scientific and Technical Information of China (English)

    Sebnem Ustun; Hande Dagci; Umit Aksoy; Yuksel Guruz; Galip Ersoz

    2003-01-01

    AIM: To explore the prevalence of amebiasis in inflammatory bowel disease (IBD) in Turkey.METHODS: In this study, amoeba prevalence in 160 cases of IBD, 130 of ulcerative colitis and 30 of Crohn′s disease were investigated in fresh faeces by means of wet mount+Lugol′s iodine staining, modified formol ethyl acetate and trichrome staining methods and to compare the diagnostic accuracy of wet mount+Lugol′s iodine staining,modified formol ethyl acetate and trichrome staining methods in the diagnosis of Entamoeba histolytica (E. histolytica)/Entamoeba dispar (E. dispar).RESULTS: E. histolytica/E. dispar cysts and trophozoites were found in 14 (8.75 %) of a total of 160 cases, 13 (10.0 %)of the 130 patients with ulcerative colitis and 1 (3.3 %) of the 30 patients with Crohn′s disease. As for the 105 patients in the control group who had not any gastrointestinal complaints, 2 (1.90 %) patients were found to have E.histolytica/E. dispar cysts in their faeces. Parasite prevalence in the patient group was determined to be significantly higher than that in the control group (Fischer′s Exact Test, P<0.05).When the three methods of determining parasites were compared with one another, the most effective one was found to be trichrome staining method (Kruskal-Wallis Test, P<0.01).CONCLUSION: Consequently, amoeba infections in IBD cases have a greater prevalence compared to the normal population. The trichrome staining method is more effective for the detection of E. histolytica/E. dispar than the wet mount+Lugol′s iodine staining, modified formol ethyl acetate methods.

  17. Intranasal insulin therapy: the clinical realities

    DEFF Research Database (Denmark)

    Hilsted, J; Madsbad, Sten; Hvidberg, A

    1995-01-01

    To evaluate metabolic control and safety parameters (hypoglycaemia frequency and nasal mucosa physiology), 31 insulin-dependent diabetic patients were treated with intranasal insulin at mealtimes for 1 month and with subcutaneous fast-acting insulin at meals for another month in an open, crossover...... was low, since intranasal insulin doses were approximately 20 times higher than subcutaneous doses. The frequency of hypoglycaemia was similar during intranasal and subcutaneous insulin therapy, and nasal mucosa physiology was unaffected after intranasal insulin. We conclude that due to low...

  18. [The current view of the diagnosis and management of amebiasis in the light of the authors own case reports].

    Science.gov (United States)

    Voldřich, M; Novotný, P; Tyll, T; Rudiš, J; Belšan, T; Hedlová, D; Stefanová, M

    2014-09-01

    This comprehensive review is focused on a serious protozoan disease, amebiasis. This disease is caused by the human parasite Entamoeba histolytica (E. histolytica), the second leading cause of mortality due to protozoan disease worldwide (the leading cause is malaria). The incidence of amebiasis in the Czech Republic is very low, but it may be underreported as the disease often escapes diagnosis. Intestinal colonisation by E. histolytica may be asymptomatic. The clinical picture ranges from diarrhea to colitis or fulminant colitis when the parasite progresses to the trophozoite stage. Secondary dissemination in the blood or lymph system may induce systemic signs of the disease. Liver abscess is the most common extraintestinal form of amebiasis. The diagnosis of intestinal amebiasis is based on the clinical picture and parasitological examination of the stool. To diagnose extraintestinal amebiasis, serology tests are used to detect antibodies in the blood. Recently, molecular methods have been increasingly used for the detection of the nucleic acids of the pathogen in biological specimens. The first line therapy for amebiasis are 5-nitroimidazole drugs, currently available in the Czech Republic. However, surgical intervention should also be considered in patients with a severe course of the disease. Included in the review are the case reports of patients with severe concomitant intestinal and extraintestinal amebiasis.

  19. Amebiasis presenting as acute appendicitis: Report of a case and review of Japanese literature

    Science.gov (United States)

    Ito, Daisuke; Hata, Shojirou; Seiichiro, Shimizu; Kobayashi, Kaoru; Teruya, Masanori; Kaminishi, Michio

    2014-01-01

    INTRODUCTION Outside of these high-risk regions, acute amebic appendicitis is considerably rarer and the mortality rate is much higher than with non-amebic appendicitis. PRESENTATION OF CASE A 31-year-old woman presented with fever and right lower abdominal pain with no history of traveling abroad or sexual infection. Computed tomography revealed a dilated appendix and thickened cecal and ascending colon walls. She underwent an appendectomy for appendicitis. Owing to a lack of symptom resolution, we performed a pathologic examination of the appendix again that revealed multiple Entamoeba histolytica trophozoites; the serum amebic antibody was positive. She was treated postoperatively with metronidazole for amebiasis and discharged on postoperative day 12. DISCUSSION The mortality rate and frequency of severe postoperative intraabdominal complications were higher in the Japanese literature (1995–2013) (25% and 33%, respectively) than in other developed countries (3.3% and 19.4%, respectively). Japan is a low-risk area for amebiasis; many physicians fail to consider amebiasis in the differential diagnosis of acute abdomen. It is important to conduct further examinations, including those for amebiasis, when appendectomy does not resolve acute appendicitis. CONCLUSION We report a case of acute amebic appendicitis in a 31-year-old woman and review the ages at presentation, causative factors, treatments, and outcomes of 11 cases reported in Japan between 1995 and 2013. PMID:25460473

  20. Case Report: Endemic Amebiasis in Australia: Implications for Residents, Travelers, and Clinicians.

    Science.gov (United States)

    Smith, Simon; Phillips, Gael E; McBride, William J H; Hanson, Josh

    2017-07-01

    Entamoeba histolytica is considered endemic in Australia; however, cases are rare, occurring almost exclusively in high-risk individuals. We describe a series of locally acquired, complicated cases in low-risk individuals from Far North Queensland in whom the diagnosis was delayed. Amebiasis may pose a greater local threat than is currently recognized.

  1. Amebiasis presenting as acute appendicitis: Report of a case and review of Japanese literature.

    Science.gov (United States)

    Ito, Daisuke; Hata, Shojirou; Seiichiro, Shimizu; Kobayashi, Kaoru; Teruya, Masanori; Kaminishi, Michio

    2014-01-01

    Outside of these high-risk regions, acute amebic appendicitis is considerably rarer and the mortality rate is much higher than with non-amebic appendicitis. A 31-year-old woman presented with fever and right lower abdominal pain with no history of traveling abroad or sexual infection. Computed tomography revealed a dilated appendix and thickened cecal and ascending colon walls. She underwent an appendectomy for appendicitis. Owing to a lack of symptom resolution, we performed a pathologic examination of the appendix again that revealed multiple Entamoeba histolytica trophozoites; the serum amebic antibody was positive. She was treated postoperatively with metronidazole for amebiasis and discharged on postoperative day 12. The mortality rate and frequency of severe postoperative intraabdominal complications were higher in the Japanese literature (1995-2013) (25% and 33%, respectively) than in other developed countries (3.3% and 19.4%, respectively). Japan is a low-risk area for amebiasis; many physicians fail to consider amebiasis in the differential diagnosis of acute abdomen. It is important to conduct further examinations, including those for amebiasis, when appendectomy does not resolve acute appendicitis. We report a case of acute amebic appendicitis in a 31-year-old woman and review the ages at presentation, causative factors, treatments, and outcomes of 11 cases reported in Japan between 1995 and 2013. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. Intranasal insulin therapy: the clinical realities

    DEFF Research Database (Denmark)

    Hilsted, J; Madsbad, Sten; Hvidberg, A

    1995-01-01

    To evaluate metabolic control and safety parameters (hypoglycaemia frequency and nasal mucosa physiology), 31 insulin-dependent diabetic patients were treated with intranasal insulin at mealtimes for 1 month and with subcutaneous fast-acting insulin at meals for another month in an open, crossover...... randomized trial. During both treatment periods the patients were treated with intermediate-acting insulin at bedtime. Six of the patients were withdrawn from the study during intranasal insulin therapy due to metabolic dysregulation. Serum insulin concentrations increased more rapidly and decreased more...... quickly during intranasal as compared with subcutaneous insulin administration. Metabolic control deteriorated, as assessed by haemoglobin A1c concentrations, slightly but significantly after intranasal as compared with subcutaneous insulin therapy. The bioavailability of intranasally applied insulin...

  3. Comparison of dexmedetomidine versus midazolam for intranasal ...

    African Journals Online (AJOL)

    in children posted for elective surgery: a double-blind, randomised study. Deepak Singlaa* , Gunjan ... Intranasal midazolam as premedication in preschool children was first studied by Wilton ... Material and methods. This double-blind equally ...

  4. Towards the establishment of a porcine model to study human amebiasis.

    Directory of Open Access Journals (Sweden)

    Fabienne Girard-Misguich

    Full Text Available BACKGROUND: Entamoeba histolytica is an important parasite of the human intestine. Its life cycle is monoxenous with two stages: (i the trophozoite, growing in the intestine and (ii the cyst corresponding to the dissemination stage. The trophozoite in the intestine can live as a commensal leading to asymptomatic infection or as a tissue invasive form producing mucosal ulcers and liver abscesses. There is no animal model mimicking the whole disease cycle. Most of the biological information on E. histolytica has been obtained from trophozoite adapted to axenic culture. The reproduction of intestinal amebiasis in an animal model is difficult while for liver amebiasis there are well-described rodent models. During this study, we worked on the assessment of pigs as a new potential model to study amebiasis. METHODOLOGY/PRINCIPAL FINDINGS: We first co-cultured trophozoites of E. histolytica with porcine colonic fragments and observed a disruption of the mucosal architecture. Then, we showed that outbred pigs can be used to reproduce some lesions associated with human amebiasis. A detailed analysis was performed using a washed closed-jejunal loops model. In loops inoculated with virulent amebas a severe acute ulcerative jejunitis was observed with large hemorrhagic lesions 14 days post-inoculation associated with the presence of the trophozoites in the depth of the mucosa in two out four animals. Furthermore, typical large sized hepatic abscesses were observed in the liver of one animal 7 days post-injection in the portal vein and the liver parenchyma. CONCLUSIONS: The pig model could help with simultaneously studying intestinal and extraintestinal lesion development.

  5. Towards the establishment of a porcine model to study human amebiasis.

    Science.gov (United States)

    Girard-Misguich, Fabienne; Cognie, Juliette; Delgado-Ortega, Mario; Berthon, Patricia; Rossignol, Christelle; Larcher, Thibaut; Melo, Sandrine; Bruel, Timothée; Guibon, Roseline; Chérel, Yan; Sarradin, Pierre; Salmon, Henri; Guillén, Nancy; Meurens, François

    2011-01-01

    Entamoeba histolytica is an important parasite of the human intestine. Its life cycle is monoxenous with two stages: (i) the trophozoite, growing in the intestine and (ii) the cyst corresponding to the dissemination stage. The trophozoite in the intestine can live as a commensal leading to asymptomatic infection or as a tissue invasive form producing mucosal ulcers and liver abscesses. There is no animal model mimicking the whole disease cycle. Most of the biological information on E. histolytica has been obtained from trophozoite adapted to axenic culture. The reproduction of intestinal amebiasis in an animal model is difficult while for liver amebiasis there are well-described rodent models. During this study, we worked on the assessment of pigs as a new potential model to study amebiasis. We first co-cultured trophozoites of E. histolytica with porcine colonic fragments and observed a disruption of the mucosal architecture. Then, we showed that outbred pigs can be used to reproduce some lesions associated with human amebiasis. A detailed analysis was performed using a washed closed-jejunal loops model. In loops inoculated with virulent amebas a severe acute ulcerative jejunitis was observed with large hemorrhagic lesions 14 days post-inoculation associated with the presence of the trophozoites in the depth of the mucosa in two out four animals. Furthermore, typical large sized hepatic abscesses were observed in the liver of one animal 7 days post-injection in the portal vein and the liver parenchyma. The pig model could help with simultaneously studying intestinal and extraintestinal lesion development.

  6. Towards the Establishment of a Porcine Model to Study Human Amebiasis

    Science.gov (United States)

    Girard-Misguich, Fabienne; Cognie, Juliette; Delgado-Ortega, Mario; Berthon, Patricia; Rossignol, Christelle; Larcher, Thibaut; Melo, Sandrine; Bruel, Timothée; Guibon, Roseline; Chérel, Yan; Sarradin, Pierre; Salmon, Henri; Guillén, Nancy; Meurens, François

    2011-01-01

    Background Entamoeba histolytica is an important parasite of the human intestine. Its life cycle is monoxenous with two stages: (i) the trophozoite, growing in the intestine and (ii) the cyst corresponding to the dissemination stage. The trophozoite in the intestine can live as a commensal leading to asymptomatic infection or as a tissue invasive form producing mucosal ulcers and liver abscesses. There is no animal model mimicking the whole disease cycle. Most of the biological information on E. histolytica has been obtained from trophozoite adapted to axenic culture. The reproduction of intestinal amebiasis in an animal model is difficult while for liver amebiasis there are well-described rodent models. During this study, we worked on the assessment of pigs as a new potential model to study amebiasis. Methodology/Principal Findings We first co-cultured trophozoites of E. histolytica with porcine colonic fragments and observed a disruption of the mucosal architecture. Then, we showed that outbred pigs can be used to reproduce some lesions associated with human amebiasis. A detailed analysis was performed using a washed closed-jejunal loops model. In loops inoculated with virulent amebas a severe acute ulcerative jejunitis was observed with large hemorrhagic lesions 14 days post-inoculation associated with the presence of the trophozoites in the depth of the mucosa in two out four animals. Furthermore, typical large sized hepatic abscesses were observed in the liver of one animal 7 days post-injection in the portal vein and the liver parenchyma. Conclusions The pig model could help with simultaneously studying intestinal and extraintestinal lesion development. PMID:22205970

  7. Polymerase chain reaction confirmation of diagnosis of intestinal amebiasis in Puducherry.

    Science.gov (United States)

    Parija, Subhash Chandra; Garg, Atul; Pushpa, K; Khairnar, Krishna; Priya, T

    2010-07-01

    Stool microscopy, the commonly used test for diagnosis of intestinal amebiasis, is unreliable as it does not differentiate Entamoeba histolytica, the causative agent for amebiasis, from non-pathogenic Entamoeba dispar and Entamoeba moshkovskii. Two hundred and forty-six stool samples collected between January to February 2009, were examined microscopically for E. histolytica/E. dispar/E. moshkovskii complex cysts and trophozoites. Nested multiplex PCR targeting a 16 S-like rRNA gene for differential detection of all the three morphologically similar forms of E. histolytica, E. moshkovskii and E. dispar simultaneously was done on all microscopy positive stool samples. Forty-nine stool samples were positive for Entamoeba spp. by microscopy. Nested multiplex PCR for E. histolytica, E. moshkovskii and E. dispar was positive in only 19 of these samples, and only 6 of the 19 samples were positive for E. histolytica. Stool microscopy grossly over-diagnosed intestinal amebiasis and is likely to result in unnecessary treatment with anti-protozoal drugs.

  8. Population Dependency of Measles, Syphilis, and Amebiasis in Japan and Community Evolution.

    Science.gov (United States)

    Yoshikura, Hiroshi; Takeuchi, Fumihiko

    2017-05-24

    The population dependency of measles, syphilis, and amebiasis was expressed as P = kN(m), where P, N, and m were number of patients, population size, and a constant (~2 for measles, and 1.3~1.4 for syphilis and amebiasis), respectively. The population size dependency emerged only when conditions other than population size, such as infant mortality, hygienic condition, vaccination practices, and others, improved to the same level in all the prefectures in Japan. The formation of prefectures and municipalities was well simulated by the random coin toss assuming that people are attracted to a community with a probability proportional to the number of the residents to the 1.3rd power. When the number of inflow population was plotted against the number of the resident population in a prefecture, or when the number of coins that were added in a round was plotted against the number of coins that were present before the coin toss, the plots fell on a straight line with the slope ~1.3, which was almost the same as the slope obtained when the number of cases of syphilis or amebiasis was plotted against the population size.

  9. Activity and safety of synthetic lectins based on benzoboroxole-functionalized polymers for inhibition of HIV entry.

    Science.gov (United States)

    Mahalingam, Alamelu; Geonnotti, Anthony R; Balzarini, Jan; Kiser, Patrick F

    2011-12-05

    Lectins derived from plant and microbial sources constitute a vital class of entry inhibitors that target the oligomannose residues on the HIV envelope gp120. Despite their potency and specificity, success of lectin-based entry inhibitors may be impeded by high manufacturing costs, formulation and potential mitogenicity. Therefore, there exists a gap in the HIV microbicides pipeline that underscores the need for mass producible, synthetic, broad-spectrum, and biocomptabile inhibitors of HIV entry. Here, we present the development of a polymeric synthetic lectin, based on benzoboroxole (BzB), which exhibits weak affinity (∼25 M(-1)) for nonreducing sugars, similar to those found on the HIV envelope. High molecular weight BzB-functionalized polymers demonstrated antiviral activity that increased with an increase in ligand density and molecular weight of the polymer construct, revealing that polyvalency improves activity. Polymers showed significant increase in activity from 25 to 75 mol % BzB functionalization with EC(50) of 15 μM and 15 nM, respectively. A further increase in mole functionalization to 90% resulted in an increase of the EC(50) (59 ± 5 nM). An increase in molecular weight of the polymer at 50 mol % BzB functionalization showed a gradual but significant increase in antiviral activity, with the highest activity seen with the 382 kDa polymer (EC(50) of 1.1 ± 0.5 nM in CEM cells and 11 ± 3 nM in TZM-bl cells). Supplementing the polymer backbone with 10 mol % sulfonic acid not only increased the aqueous solubility of the polymers by at least 50-fold but also demonstrated a synergistic increase in anti-HIV activity (4.0 ± 1.5 nM in TZM-bl cells), possibly due to electrostatic interactions between the negatively charged polymer backbone and the positively charged V3-loop in the gp120. The benzoboroxole-sulfonic acid copolymers showed no decrease in activity in the presence of a seminal concentration of fructose (p > 0.05). Additionally, the copolymers

  10. Live attenuated intranasal influenza vaccine.

    Science.gov (United States)

    Esposito, Susanna; Montinaro, Valentina; Groppali, Elena; Tenconi, Rossana; Semino, Margherita; Principi, Nicola

    2012-01-01

    Annual vaccination is the most effective means of preventing and controlling influenza epidemics, and the traditional trivalent inactivated vaccine (TIV) is by far the most widely used. Unfortunately, it has a number of limitations, the most important of which is its poor immunogenicity in younger children and the elderly, the populations at greatest risk of severe influenza. Live attenuated influenza vaccine (LAIV) has characteristics that can overcome some of these limitations. It does not have to be injected because it is administered intranasally. It is very effective in children and adolescents, among whom it prevents significantly more cases of influenza than the traditional TIV. However, its efficacy in adults has not been adequately documented, which is why it has not been licensed for use by adults by the European health authorities. LAIV is safe and well tolerated by children aged > 2 y and adults, but some concerns arisen regarding its safety in younger children and subjects with previous asthma or with recurrent wheezing. Further studies are needed to solve these problems and to evaluate the possible role of LAIV in the annual vaccination of the general population.

  11. Influenza (Flu) vaccine (Live, Intranasal): What you need to know

    Science.gov (United States)

    ... is taken in its entirety from the CDC Influenza Live, Intranasal Flu Vaccine Information Statement (VIS): www.cdc.gov/vaccines/ ... flulive.html . CDC review information for Live, Intranasal Influenza VIS: Vaccine Information Statement Influenza Page last reviewed: ...

  12. Population Pharmacokinetics of Intranasal Scopolamine

    Science.gov (United States)

    Wu, L.; Chow, D. S. L.; Putcha, L.

    2013-01-01

    Introduction: An intranasal gel dosage formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness (SMS).The bioavailability and pharmacokinetics (PK) was evaluated using data collected in Phase II IND protocols. We reported earlier statistically significant gender differences in PK parameters of INSCOP at a dose level of 0.4 mg. To identify covariates that influence PK parameters of INSCOP, we examined population covariates of INSCOP PK model for 0.4 mg dose. Methods: Plasma scopolamine concentrations versus time data were collected from 20 normal healthy human subjects (11 male/9 female) after a 0.4 mg dose. Phoenix NLME was employed for PK analysis of these data using gender, body weight and age as covariates for model selection. Model selection was based on a likelihood ratio test on the difference of criteria (-2LL). Statistical significance for base model building and individual covariate analysis was set at P less than 0.05{delta(-2LL)=3.84}. Results: A one-compartment pharmacokinetic model with first-order elimination best described INSCOP concentration ]time profiles. Inclusion of gender, body weight and age as covariates individually significantly reduced -2LL by the cut-off value of 3.84(P less than 0.05) when tested against the base model. After the forward stepwise selection and backward elimination steps, gender was selected to add to the final model which had significant influence on absorption rate constant (ka) and the volume of distribution (V) of INSCOP. Conclusion: A population pharmacokinetic model for INSCOP has been identified and gender was a significant contributing covariate for the final model. The volume of distribution and Ka were significantly higher in males than in females which confirm gender-dependent pharmacokinetics of scopolamine after administration of a 0.4 mg dose.

  13. INTRANASAL DEXMEDETOMIDINE VS. INTRANASAL MIDAZOLAM FOR PREMEDICATION OF PAEDIATRIC SURGERY PATIENTS

    Directory of Open Access Journals (Sweden)

    Revi N

    2016-06-01

    Full Text Available AIM Preoperative anxiety is one of the most common problems faced by anyone practising paediatric anaesthesia. Various drugs have been used in various routes to get a calm but cooperative child before induction of anaesthesia. Midazolam and dexmedetomidine have already proved their value in paediatric premedication. This study was conducted to compare the effects of these two drugs given intranasally. MATERIALS AND METHODS 100 children falling under the inclusion criteria were assigned to groups of 50 each. They received either intranasal midazolam 0.2 mg/kg (group M or intranasal dexmedetomidine 2 mcg/kg (Group D as premedication. They were compared with regards to the sedation status, anxiety levels and cardiovascular status every 10 minutes, at parental separation and at face mask application. RESULTS The mean sedation score obtained at all-time intervals, at parental separation and more importantly at mask induction were much lower for the midazolam group compared to the dexmedetomidine group. The mean anxiety levels, in general, were lower in the midazolam group, but they attained statistical significance only at 10 minutes and at mask induction. The heart rate measured up to 20 minutes after drug administration did not show much difference between both groups, but at 30 minutes, 40 minutes and at parental separation, heart rate was found to be lower in the dexmedetomidine group. CONCLUSION Intranasal dexmedetomidine and intranasal midazolam are equally effective in providing satisfactory parental separation, but intranasal midazolam produced superior conditions for mask acceptance than intranasal dexmedetomidine.

  14. Comparison of two methods (microscopy and enzyme-linked immunosorbent assay) for the diagnosis of amebiasis.

    Science.gov (United States)

    Tanyuksel, Mehmet; Yilmaz, Hasan; Ulukanligil, Mustafa; Araz, Engin; Cicek, Mutalip; Koru, Ozgur; Tas, Zeynep; Petri, William A

    2005-07-01

    Diagnosis of amebiasis is usually performed on a clinical basis alone in most endemic countries having limited economic resources. This epidemiological study was conducted using modern diagnostic tests for amebiasis in the southeastern region of Turkey, an endemic area for amebiasis. The population of this study included patients with symptomatic diarrhea/dysentery attending both Yuzuncu Yil University, Van and Harran University, Sanliurfa, Turkey. A total of 380 stool specimens were collected and examined for Entamoeba by light microscopy (fresh, lugol, and trichrome staining) and stool antigen detection based- enzyme-linked immunosorbent assay (EIA) test (TechLab Entamoeba histolytica II). 24% (91/380) of stool specimens were positive for E. histolytica/Entamoeba dispar trophozoites/cysts microscopically using trichrome staining. 13% (51/380) of the stool specimens were found to be positive for E. histolytica by the EIA test, including 15% (14/91) of microscopy (+) stool specimens and 13% (37/289) of microscopy (-) stool specimens. Enteric parasites were common in these populations with 66% (251/380) of the study population harboring more than one parasite. In addition to the 13% (51/380) of patients determined to have E. histolytica by EIA, eighty-six patients (22.6%) had Blastocystis hominis, 54 (14.2%) Entamoeba coli, 44 (11.5%) Giardia lamblia, 16 (4.2%) Chilomastix mesnili, 15 (3.9%) Iodamoeba bütschlii, 12 (3.1%) Hymenolepis nana, 9 (2.3%) Endolimax nana, 9 (2.3%) Dientamoeba fragilis, and 8 (2.1%) had Ascaris lumbricoides. We concluded that E. histolytica infection was found in 13% of the patients presenting with diarrhea in Van and Sanliurfa Turkey.

  15. A study with quinfamide in the treatment of chronic amebiasis in adults.

    Science.gov (United States)

    Guevara, L; Garcia Tsao, G; Uscanga, L F

    1983-01-01

    Quinfamide, a luminal amebicide, is a dichloroacetyl quinolol used to treat chronic and subacute intestinal amebiasis. Several previous dose-ranging studies have indicated that quinfamide is effective in a total dose of 300, 600, or 1,200 mg. The present study was undertaken to determine the efficacy of 100- and 200-mg doses, each given three times daily. A cure rate of 100% was found at a dosage of 100 mg/8 hr and of 93.3% at 200 mg/8 hr. These results indicate that quinfamide is an effective luminal amebicide at the doses studied.

  16. Intranasal H5N1 vaccines, adjuvanted with chitosan derivatives, protect ferrets against highly pathogenic influenza intranasal and intratracheal challenge

    NARCIS (Netherlands)

    A.J. Mann (Alex); N. Noulin (Nicolas); A. Catchpole (Andrew); K.J. Stittelaar (Koert); L. de Waal (Leon); E.J.B. Veldhuis Kroeze (Edwin); M. Hinchcliffe (Michael); A. Smith (Alan); E. Montomoli (Emanuele); S. Piccirella (Simona); A.D.M.E. Osterhaus (Albert); A. Knight (Alastair); J. Oxford; G. Lapini (Giulia); R. Cox (Ruben); R. Lambkin-Williams (Rob)

    2014-01-01

    textabstractWe investigated the protective efficacy of two intranasal chitosan (CSN and TM-CSN) adjuvanted H5N1 Influenza vaccines against highly pathogenic avian Influenza (HPAI) intratracheal and intranasal challenge in a ferret model. Six groups of 6 ferrets were intranasally vaccinated twice, 21

  17. Intranasal steroids for acute sinusitis.

    Science.gov (United States)

    Zalmanovici Trestioreanu, Anca; Yaphe, John

    2013-12-02

    Acute sinusitis is a common reason for primary care visits. It causes significant symptoms and often results in time off work and school. We examined whether intranasal corticosteroids (INCS) are effective in relieving symptoms of acute sinusitis in adults and children. We searched CENTRAL 2013, Issue 4, MEDLINE (January 1966 to May week 2, 2013), EMBASE (1990 to May 2013) and bibliographies of included studies. Randomised controlled trials (RCTs) comparing INCS treatment to placebo or no intervention in adults and children with acute sinusitis. Acute sinusitis was defined by clinical diagnosis and confirmed by radiological evidence or by nasal endoscopy. The primary outcome was the proportion of participants with either resolution or improvement of symptoms. Secondary outcomes were any adverse events that required discontinuation of treatment, drop-outs before the end of the study, rates of relapse, complications and return to school or work. Two review authors independently extracted data, assessed trial quality and resolved discrepancies by consensus. No new trials were found for inclusion in this update. Four studies involving 1943 participants with acute sinusitis met our inclusion criteria. The trials were well-designed and double-blind and studied INCS versus placebo or no intervention for 15 or 21 days. The rates of loss to follow-up were 7%, 11%, 41% and 10%. When we combined the results from the three trials included in the meta-analysis, participants receiving INCS were more likely to experience resolution or improvement in symptoms than those receiving placebo (73% versus 66.4%; risk ratio (RR) 1.11; 95% confidence interval (CI) 1.04 to 1.18). Higher doses of INCS had a stronger effect on improvement of symptoms or complete relief: for mometasone furoate 400 µg versus 200 µg (RR 1.10; 95% CI 1.02 to 1.18 versus RR 1.04; 95% CI 0.98 to 1.11). No significant adverse events were reported and there was no significant difference in the drop-out and

  18. Cilioretinal artery occlusion following intranasal cocaine insufflations

    Directory of Open Access Journals (Sweden)

    Balaji Kannan

    2011-01-01

    Full Text Available Cocaine is used to produce a euphoric effect by abusers, who may be unaware of the devastating systemic and ocular side effects of this drug. We describe the first known case of cilioretinal artery occlusion after intranasal cocaine abuse.

  19. Intestinal Amebiasis: A Concerning Cause of Acute Gastroenteritis Among Hospitalized Lebanese Children

    Science.gov (United States)

    Naous, Amal; Naja, Ziad; Zaatari, Nour; Kamel, Raymond; Rajab, Mariam

    2013-01-01

    Background: Intestinal amebiasis is an important public health problem worldwide. More severe disease is associated with young age, malnutrition and immunosuppression. Aim: The aim of this study is to evaluate the prevalence and characteristic nature of intestinal amebiasis among pediatric population, and compare it with other causes of gastroenteritis. Materials and Methods: This is a retrospective comparative study conducted at Makassed General Hospital between January 2008 and December 2012, including all pediatric patients between birth and 15 years of age, who presented with symptoms of acute gastroenteritis. Results: One thousand three hundred ninety-five patients were included in the study, and were divided into four groups: Group I (Entameba histolytica group = 311 cases, 22.3%), group II (Rotavirus group = 427 cases, 30.6%), group III (bacterial group = 107 cases, 7.7%), group IV (unidentified group = 550 cases, 39.4%). Significant leukocytosis, neutrophilia and positive C-reactive protein were found among more than 50% of admitted Entemaba histolytica cases with a picture of severe invasive disease in young infants. Conclusion: Entameba histolytica can be an emerging serious infection, especially when it finds suitable environmental conditions and host factors, so we should be ready to face it with effective preventive measures. PMID:24404551

  20. [Amebiasis: implications of the recognition of Entamoeba dispar and the identification of Entamoeba moshkovskii in humans].

    Science.gov (United States)

    Chacín-Bonilla, Leonor

    2010-06-01

    The history of Entamoeba histolytica is very confuse and shows several wrong concepts about the parasite and its relationship with the host. The poor correlation between the prevalence of asymptomatic and symptomatic amebiasis originated the proposal of three explicative hypothesis, among them was the concept of Brumpt that E. histolytica comprised two morphologically identical species, E. dysenteriae and E. dispar. The application of modern molecular techniques irrefutably proved that E. histolytica was really a complex of two species, confirming the concept of Brumpt almost 7 decades later. Recent studies have identified in humans E. moshkovskii, morphologically indistinguishable from E. histolytica and E. dispar, a great genetic diversity within each of these species, and heterogeneity in virulence among E. histolytica strains. The redescription of E. dispar, and the recovery of E. moshkovskii from humans have had a major impact in our understanding of E. histolytica and amebiasis with important clinical and epidemiologic implications. This has led to the need of a reevaluation of the infection in terms of prevalence and morbidity in the global population and to study the geographic distribution, prevalence, and transmission pattern of E. histolytica strains in order to detect those with epidemiologic relevance and predict the risk of amebic disease in a population.

  1. Intranasal formulations: promising strategy to deliver vaccines.

    Science.gov (United States)

    Riese, Peggy; Sakthivel, Priya; Trittel, Stephanie; Guzmán, Carlos A

    2014-10-01

    The emergence of new diseases and the lack of efficient vaccines against numerous non-treatable pathogens require the development of novel vaccination strategies. To date, only a few mucosal vaccines have been approved for humans. This was in part due to i) the use of live attenuated vaccines, which are not suitable for certain groups of individuals, ii) safety concerns derived from implementation in humans of some mucosal vaccines, iii) the poor stability, absorption and immunogenicity of antigens delivered by the mucosal route and iv) the limited number of available technologies to overcome the bottlenecks associated with mucosal antigen delivery. Recent advances make feasible the development of efficacious mucosal vaccines with adequate safety profile. Thus, currently intranasal vaccines represent an attractive and valid alternative to conventional vaccines. The present review is focused on the potentials and limitations of market-approved intranasal vaccines and promising candidates undergoing clinical investigations. Furthermore, emerging strategies to overcome main bottlenecks including efficient breaching of the mucosal barrier and safety concerns by implementation of new adjuvants and delivery systems are discussed. The rational design of intranasal vaccines requires an in-depth understanding of the anatomic, physicochemical and barrier properties of the nasal mucosa, as well as the molecular mechanisms governing the activation of the local innate and adaptive immune system. This would provide the critical knowledge to establish effective approaches to deliver vaccine antigens across the mucosal barrier, supporting the stimulation of a long-lasting protective response at both mucosal and systemic levels. Current developments in the area of adjuvants, nanotechnologies and mucosal immunology, together with the identification of surface receptors that can be exploited for cell targeting and manipulating their physiological properties, will become instrumental

  2. Use of intranasal corticosteroids in adenotonsillar hypertrophy.

    Science.gov (United States)

    Sakarya, E U; Bayar Muluk, N; Sakalar, E G; Senturk, M; Aricigil, M; Bafaqeeh, S A; Cingi, C

    2017-05-01

    This review examined the efficacy of intranasal corticosteroids for improving adenotonsillar hypertrophy. The related literature was searched using PubMed and Proquest Central databases. Adenotonsillar hypertrophy causes mouth breathing, nasal congestion, hyponasal speech, snoring, obstructive sleep apnoea, chronic sinusitis and recurrent otitis media. Adenoidal hypertrophy results in the obstruction of nasal passages and Eustachian tubes, and blocks the clearance of nasal mucus. Adenotonsillar hypertrophy and obstructive sleep apnoea are associated with increased expression of various mediators of inflammatory responses in the tonsils, and respond to anti-inflammatory agents such as corticosteroids. Topical nasal steroids most likely affect the anatomical component by decreasing inspiratory upper airway resistance at the nasal, adenoidal or tonsillar levels. Corticosteroids, by their lympholytic or anti-inflammatory effects, might reduce adenotonsillar hypertrophy. Intranasal corticosteroids reduce cellular proliferation and the production of pro-inflammatory cytokines in a tonsil and adenoid mixed-cell culture system. Intranasal corticosteroids have been used in adenoidal hypertrophy and adenotonsillar hypertrophy patients, decreasing rates of surgery for adenotonsillar hypertrophy.

  3. Treatment of chronic amebiasis in pediatric patients with a suspension of quinfamide.

    Science.gov (United States)

    Araujo Rojas, F; Benavides Ledezma, M; Vega Martinez, C; Gomez Garza, R

    1983-01-01

    Quinfamide, a dichloroacetyl quinolol synthesized and tested at Sterling Winthrop Research Institute, is a potent luminal amebicide with potential utility for a one-day treatment of chronic and subacute amebiasis caused by Entamoeba histolytica. Previous studies demonstrated that quinfamide is a safe and efficacious drug for adult patients when given as a one-day treatment regimen of 300 mg taken in tablet form at a dosage of 100 mg every eight hours. To test the drug in suspension form in pediatric patients, 46 children from newborn to 12 years old, assigned to groups according to age, were administered quinfamide in doses ranging from 50 to 300 mg/day as either single or divided doses. In all age groups quinfamide suspension, given as multiple doses in a single day, was shown to be highly effective in eliminating trophozoites from the stool. Cure rates ranged from 77.8% to 100%.

  4. Entamoeba moshkovskii perspectives of a new agent to be considered in the diagnosis of amebiasis.

    Science.gov (United States)

    Heredia, Rubén Darío; Fonseca, Jairo Andrés; López, Myriam Consuelo

    2012-09-01

    During the last decade Entamoeba moshkovskii has become relevant given its capacity to infect humans, especially when considering that it is morphologically indistinguishable from E. histolytica. For a long time, E. moshkovskii was considered as a free living amoeba, but in the last decade it has been demonstrated that E. moshkovskii can infect humans and can be found more frequently in regions where amebiasis shows high prevalence values, becoming a challenge to differentiate it from the E. histolytica/E. dispar complex. Recently there have been studies that raise the possibility that E. moshkovskii could be a pathogenic species, as there are reports in different countries that associated this infection with gastrointestinal symptoms even though others have described it as a non pathogenic species. For this reasons, both clinical and epidemiological studies are required.

  5. Intranasal glukagon til behandling af hypoglykaemi. En fremtidig behandlingsmulighed

    DEFF Research Database (Denmark)

    Carstens, S; Andersen, I; Gustafsson, Ida

    1994-01-01

    or glucose administered intravenously by a physician. These are however not optimal treatments. Obtaining intravenous access requires a medical doctor and glucagon injection is not always properly done by family members. Glucagon administered intranasally has been proven to raise blood glucose levels...... in volunteers. The effect of intranasal glucagon on blood glucose is similar to that seen after intramuscular administration for the first 15 minutes following administration. However, intranasal glucagon seems more physiological in that is stabilizes blood glucose concentrations at nearfasting levels, whereas...... glucagon given intramuscularly tends to give hyperglycaemia. Intranasal glucagon is easy to administer, and can thus prevent serious hypoglycaemic crises and thereby make diabetics and their families more secure....

  6. [Intestinal amebiasis].

    Science.gov (United States)

    Badell Urdaneta, A; Villasmil Morillo, A; Prieto Núnez, A; Bolaño Albarran, H

    1975-01-01

    Infection produced by Entamoeba histolytica constitutes a clinical problem of great importance due to its frequence and serious complications. Age, diagnosis and clinical manifestations, phisic exploration, lab. procedures, proctosigmoidoscopy, radiology, complications, pathologic anatomy, statistical reports from the Ministry of Health and Social Asistence in addition we emphasize on the importance of an accurate and precocious diagnosis. We expose an effective terapeutic regimen for the different amibiasis states.

  7. IL-17A contributes to reducing IFN-γ/IL-4 ratio and persistence of Entamoeba histolytica during intestinal amebiasis.

    Science.gov (United States)

    Deloer, Sharmina; Nakamura, Risa; Kikuchi, Mihoko; Moriyasu, Taeko; Kalenda, Yombo Dan Justin; Mohammed, Eman Sayed; Senba, Masachika; Iwakura, Yoichiro; Yoshida, Hiroki; Hamano, Shinjiro

    2017-09-16

    Amebiasis is an infectious disease caused by Entamoeba histolytica, an anaerobic protozoan parasite, and is a major public health problem worldwide, particularly in areas with inadequate sanitation and poor hygiene. Th1 responses, represented by interferon gamma (IFN-γ), play a protective role by clearing the amebae from the gut, whereas Th2 responses are responsible for chronic infection. Th17 responses preconditioned by vaccination or by modulating the intestinal microbiome protect mice from the settlement of E. histolytica. However, the role of interleukin-17A (IL-17A), which is upregulated during the natural course of intestinal amebiasis, has not been clarified. The aim of this study was to investigate the role of IL-17A during intestinal amebiasis in a mouse model. IL-17A knockout and wild-type CBA/J mice were challenged intracecally with 2×10(6)E. histolytica trophozoites, and their infection, pathology, and immune responses were monitored. Neither the initial settlement of E. histolytica nor the inflammation of the cecum was affected by the absence of IL-17A for week 1, but the infection rate and parasite burden declined in a late stage of infection, accompanied by an increased IFN-γ/IL-4 ratio. Therefore, IL-17A contributes to the persistence of E. histolytica and modulates the immune response, including the IFN-γ/IL-4 ratio, which may be responsible for the reduction of the parasite burden in the IL-17A knockout mice during the chronic phase of intestinal amebiasis. Copyright © 2017. Published by Elsevier B.V.

  8. Fluticasone furoate: A new intranasal corticosteroid

    Directory of Open Access Journals (Sweden)

    R Kumar

    2012-01-01

    Full Text Available Intranasal corticosteroids are recommended as one of the first-line therapies for the treatment of allergic rhinitis (AR, especially when associated with nasal congestion and recurrent symptoms. Fluticasone furoate is a novel enhanced-affinity glucocorticoid for the treatment of AR approved by the Food and Drug Administration in 2007 and recently introduced in India. Fluticasone furoate nasal spray is indicated for the treatment of the symptoms of seasonal and perennial AR in patients aged two years and older. This review summarizes the clinical data on fluticasone furoate nasal spray and discusses its role in the management of AR. Important attributes of fluticasone furoate include low systemic bioavailability (<0.5%, 24-h symptom relief with once-daily dosing, comprehensive coverage of both nasal and ocular symptoms, safety and tolerability with daily use, and availability in a side-actuated device that makes medication delivery simple and consistent. With these properties, fluticasone furoate nasal spray has the potential to enhance patient satisfaction and compliance, thus making it a good choice amongst available intranasal steroids.

  9. [Comparison of quinfamide vs etofamide in the Mexican population with intestinal amebiasis].

    Science.gov (United States)

    Olaeta Elizalde, R; Pérez Huacuja, R; Nájera Ruano, S

    1996-01-01

    An open comparative, prospective and randomized study was carried out to evaluate the efficacy and safety of quinfamide and etofamide in the treatment of intestinal amebiasis. This study evaluate two populations: children (1-16 years) and adults (17-80 years). The drugs used were quinfamide at doses of 4.3 mg/kg b.i.d. in children, and 100 mg t.i.d. adults both for one day; and etofamide at doses of 200 mg t.i.d. in children and 500 mg b.i.d. in adults both for three days. A total of 110 patients were included, 54 in the quinfamide group and 56 in the etofamide group. No significant difference between groups in baseline demographics characteristics were observed. Global healing rate for quinfamide group was 87% and for etofamife group was 76.8% (p = 0.0696). This difference was similar considering both group of populations. It is concluded that the therapeutical response was better for the quinfamide group than for the etofamide group. Both drugs have the same safety profile.

  10. Comparison of real-time PCR protocols for differential laboratory diagnosis of amebiasis.

    Science.gov (United States)

    Qvarnstrom, Yvonne; James, Cleve; Xayavong, Maniphet; Holloway, Brian P; Visvesvara, Govinda S; Sriram, Rama; da Silva, Alexandre J

    2005-11-01

    Specific identification of Entamoeba spp. in clinical specimens is an important confirmatory diagnostic step in the management of patients who may be infected with Entamoeba histolytica, the species that causes clinical amebiasis. Distinct real-time PCR protocols have recently been published for identification of E. histolytica and differentiation from the morphologically identical nonpathogenic Entamoeba dispar. In this study, we compared three E. histolytica real-time PCR techniques published by December 2004. The limits of detection and efficiency of each real-time PCR assay were determined using DNA extracted from stool samples spiked with serially diluted cultured E. histolytica trophozoites. The ability of each assay to correctly distinguish E. histolytica from E. dispar was evaluated with DNA extracted from patients' stools and liver aspirates submitted for confirmatory diagnosis. Real-time PCR allowed quantitative analysis of the spiked stool samples, but major differences in detection limits and assay performance were observed among the evaluated tests. These results illustrate the usefulness of comparative evaluations of diagnostic assays.

  11. Risk factors for intestinal invasive amebiasis in Japan, 2003-2009.

    Science.gov (United States)

    Nagata, Naoyoshi; Shimbo, Takuro; Akiyama, Junichi; Nakashima, Ryo; Nishimura, So; Yada, Tomoyuki; Watanabe, Koji; Oka, Shinichi; Uemura, Naomi

    2012-05-01

    We determined yearly change in prevalence and risk factors for amebic colitis caused by intestinal invasive amebiasis among persons who underwent endoscopy and assessed differences between HIV-positive and HIV-negative persons in Japan. A total of 10,930 patients were selected for analysis, of whom 54 had amebic colitis. Prevalence was in 2009 (0.88%, 12/1360) compared with 2003 (0.16%, 3/1904). Male sex (odds ratio [OR] 8.39, 95% CI 1.99-35.40), age <50 years (OR 4.73, 95% CI 2.43-9.20), history of syphilis (OR 2.90, 95% CI 1.40-5.99), and HIV infection (OR 15.85, 95% CI 7.93-31.70) were independent risk factors. No differences in risk factors were identified between HIV-positive and HIV-negative patients. Contact with commercial sex workers was a new risk factor among HIV-negative patients. Homosexual intercourse, rather than immunosuppressed status, appears to be a risk factor among HIV-positive patients.

  12. [Taeniasis, amebiasis and other intestinal parasitosis in school age children from Michoacan State, Mexico].

    Science.gov (United States)

    Lara-Aguilera, R; Aguilar-Bucio, M T; Martínez-Toledo, J L

    1990-03-01

    92.3% schoolchildren aged 6-13 years of a mexican rural village, suspected foci of Taenia solium cysticercosis were screened for intestinal parasites with the main purpose to know the infection rate by taeniasis. An stool sample was collected to schoolchildren of the village and 95.4% of a urban private school as comparative group. Laboratory examinations were performed with the most accurate technics, included microscopies with an ocular micrometer. The general parasitation rate was 4 times higher in the rural village, but the percentages of Taenia spp. infection were 0.6% both of them. Entamoeba histolytica was observed 1.8% and 7.2% in the city and rural village, respectively. All the cases with taeniasis passed T. saginata after treatment with niclosamide. Negative results were obtained with the same chemotherapy in a randomly selected group of 112 schoolchildren which previous stool examination was reported negative. Neither taeniasis were demonstrated in 94 adult persons. These data are suggestive of the great variability on the transmission rates of T. solium cysticercosis in endemic areas and illustrate the faced methodological problems to confirm the diagnosis of taeniasis. By other hand support the hypothesis that estimates of infection rates with E. histolytica have been overdiagnosed in the country. Taeniasis-cysticercosis; schoolchildren; Taenia saginata; amebiasis.

  13. Cost-effectiveness of detection of intestinal amebiasis by using serology and specific-amebic-antigen assays among persons with or without human immunodeficiency virus infection.

    Science.gov (United States)

    Chang, Sui-Yuan; Sun, Hsin-Yun; Ji, Dar-Der; Lo, Yi-Chun; Wu, Cheng-Hsin; Wu, Pei-Ying; Liu, Wen-Chun; Hung, Chien-Ching; Chang, Shan-Chwen

    2008-09-01

    Among 345 persons who underwent indirect hemagglutination (IHA) serological assays and assays of specific amebic antigens in their stool samples, 24 of 36 (66.7%) who were seropositive for Entamoeba histolytica had intestinal amebiasis as determined by antigen assays compared with 2 of 309 (0.2%) who were seronegative (odds ratio, 307; 95% confidence interval, 64.9 to 1,451). The estimated cost to detect a case of intestinal amebiasis by serology followed by antigen assays ($52) could be reduced by 74.3% and 69.9%, respectively, compared with the costs of the concurrent use of both assays ($202) and the antigen assays alone ($173). Our finding suggests that IHA assays followed by specific-amebic-antigen assays can be cost-effective in the diagnosis of intestinal amebiasis among persons with or without human immunodeficiency virus infection who are at risk for E. histolytica infection.

  14. Comparison between intranasal dexmedetomidine and intranasal midazolam as premedication for brain magnetic resonance imaging in pediatric patients: A prospective randomized double blind trial

    Directory of Open Access Journals (Sweden)

    Ayushi Gupta

    2017-01-01

    Conclusion: Intranasal dexmedetomidine results in more successful parental separation and yields a higher sedation level at the time of induction of anesthesia than intranasal midazolam as premedication, with negligible side effects. However, its onset of action is relatively prolonged.

  15. Non-clinical safety evaluation of intranasal iota-carrageenan.

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    Alexandra Hebar

    Full Text Available Carrageenan has been widely used as food additive for decades and therefore, an extended oral data set is available in the public domain. Less data are available for other routes of administration, especially intranasal administration. The current publication describes the non-clinical safety and toxicity of native (non-degraded iota-carrageenan when applied intranasally or via inhalation. Intranasally applied iota-carrageenan is a topically applied, locally acting compound with no need of systemic bioavailability for the drug's action. Animal experiments included repeated dose local tolerance and toxicity studies with intranasally applied 0.12% iota-carrageenan for 7 or 28 days in New Zealand White rabbits and nebulized 0.12% iota-carrageenan administered to F344 rats for 7 days. Permeation studies revealed no penetration of iota-carrageenan across nasal mucosa, demonstrating that iota-carrageenan does not reach the blood stream. Consistent with this, no relevant toxic or secondary pharmacological effects due to systemic exposure were observed in the rabbit or rat repeated dose toxicity studies. Data do not provide any evidence for local intolerance or toxicity, when carrageenan is applied intranasally or by inhalation. No signs for immunogenicity or immunotoxicity have been observed in the in vivo studies. This is substantiated by in vitro assays showing no stimulation of a panel of pro-inflammatory cytokines by iota-carrageenan. In conclusion, 0.12% iota-carrageenan is safe for clinical use via intranasal application.

  16. Cytotoxic Effects of Intranasal Midazolam on Nasal Mucosal Tissue.

    Science.gov (United States)

    Ozbay, I; Kucur, C; Değer, A; Ital, I; Kasim, Cayci M; Oghan, F

    2015-09-01

    The aim of this experimental study was to investigate the cytotoxic effects of intranasal midazolam on nasal mucosal tissue in rats. Forty healthy rats were randomly divided into 5 groups. Group 1 (n = 8) was the control group, group 2 (n = 8) received intranasal saline, group 3 (n = 8) received intranasal midazolam, group 4 (n = 8) received intraperitoneal saline, and group 5 received intraperitoneal midazolam (n = 8). Midazolam and saline were administered via intraperitoneal and intranasal routes at doses of 200 μg/kg. Nasal septal mucosal stripe tissues were removed at the 6th hour. All materials were evaluated according to Ki67 and p53 staining to evaluate proliferation and apoptosis, respectively, and hemotoxylin and eosin staining was performed for histopathology evaluation. Ki67 values and inflammation in group 3 were statistically higher compared to group 1, group 2, and group 4. P53 values in group 3 were statistically higher compared to group 1. Assessment of subepithelial edema between group 3 and the other groups revealed no statistically significant differences. Assessment of cilia loss between group 3 and group 1, group 2, and group 4 revealed no statistically significant difference. The evaluation of goblet cell loss between group 3 and group 1 revealed a statistically significant difference. Intranasal midazolam had adverse effects on nasal mucosa. However, intranasal midazolam is as safe as systemic midazolam administration with respect to nasal mucosa.

  17. Intranasal mucoadhesive microemulsion of mirtazapine: Pharmacokinetic and pharmacodynamic studies

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    Hetal P Thakkar

    2013-01-01

    Full Text Available The aim of this investigation was to prepare and characterize mirtazapine microemulsion for intranasal delivery, to determine its brain drug delivery using pharmacokinetic studies, and assess its performance pharmacodynamically for the antidepressant activity. Mirtazapine microemulsion of different compositions were prepared by water titration method and characterized for globule size and zeta potential. Microemulsion with maximum drug solubilization, lowest globule size and lowest zeta potential was considered optimal and taken for further studies with or without addition of chitosan, a mucoadhesive agent. Pharmacokinetics of optimized mirtazapine microemulsion, mucoadhesive microemulsion and mirtazapine solution were studied in brain and blood of male Wistar rats post intranasal and oral administration. Despair Swim test, locomotor activity and plus maze test were carried out in rats in order to compare therapeutic activity of the drug formulation for oral and intranasal route. Brain/blood uptake ratios were found to be highest for mirtazapine mucoadhesive microemulsion (MMME followed by mirtazapine microemulsion (MME post-intranasal administration compared to oral delivery of microemulsion. Significant ( P < 0.05 reduction in assessed pharmacodynamic parameters was observed after intranasal administration of MMME against control group. This investigation demonstrates a more rapid and larger extent of transport of mirtazapine into the brain with intranasal MMME, which may prove useful in treating depression.

  18. Modulation of innate immune response by the vagus nerve in experimental hepatic amebiasis in rats.

    Science.gov (United States)

    Martínez-Jaimes, Mercedes D; García-Lorenzana, Mario; Muñoz-Ortega, Martin H; Quintanar-Stephano, Andrés; Ávila-Blanco, Manuel E; García-Agueda, Carlos E; Ventura-Juárez, Javier

    2016-10-01

    The parasympathetic nervous system has a crucial role in immunomodulation of the vagus nerve, its structure provides a pathogen detection system, and a negative feedback to the immune system after the pathogenic agent has been eliminated. Amebiasis is a disease caused by the protozoan parasite Entamoeba histolytica, considered the third leading cause of death in the world. The rats are used as a natural resistance model to amoebic liver infection. The aim of this study is to analyze the interaction of Entamoeba histolytica with neutrophils, macrophages, and NK cells in livers of intact and vagotomized rats. Six groups were studied (n = 4): Intact (I), Intact + amoeba (IA), Sham (S), Sham + amoeba (SA), Vagotomized (V) and Vagotomized + amoeba (VA). Animals were sacrificed at 8 h post-inoculation of E. histolytica. Then, livers were obtained and fixed in 4% paraformaldehyde. Tissue liver slides were stained with H-E, PAS and Masson. The best development time for E. histolytica infection was at 8 h. Amoeba was identified with a monoclonal anti-220 kDa E. histolytica lectin. Neutrophils (N) were identified with rabbit anti-human neutrophil myeloperoxidase, macrophages (Mɸ) with anti-CD68 antibody and NK cells (NK) with anti-NK. Stomachs weight and liver glycogen were higher in V. Collagen increased in VA, whereas vascular and neutrophilic areas were decreased. There were fewer N, Mɸ, NK around the amoeba in the following order IA > SA > VA (p < 0.05 between IA and VA). In conclusion, these results suggest that the absence of parasympathetic innervation affects the participation of neutrophils, macrophages and NK cells in the innate immune response, apparently by parasympathetic inhibition on the cellular functions and probably for participation in sympathetic activity.

  19. [Seroepidemiology of amebiasis in the northern region of the Republic of Mexico].

    Science.gov (United States)

    Isibasi, A; González, C; Ortíz, V; Muy, M; Paniagua, J; Blanco, F; Pelayo, R; Magdaleno, V; Ramírez, A; Kumate, J

    1990-01-01

    The object of paper has been the study of amebic seroepidemiology in the northern region of Mexico, by means of an immunoenzymatic assay in solid phase (ELISA). The proteic antigen was obtained from axenic culture of E. histolytica's trophozoites of strain HM1:IMSS, by means of solubilization with phenoxy polyethoxyethanol (Triton X-100). Standardization of the method was obtained by analysis of 80 sera from patients with both a clinical and radiologic diagnosis of amebic hepatic abscess and 80 sera from healthy patients. The sensitivity reached 95% and the specificity was 90.7%. 15,457 sera from eight Mexican northern states were tested as part of the National Seroepidemiologic Survey. A semiautomatic BIOMEK 1,000 (Beckman Ins.) equipment was used. The positive ratio varied between 2.0% in Southern Baja California and 4.92% in Chihuahua, with an average ratio for the whole group of 3.34%. The first three places, in descending order, are Chihuahua (4.92%), Sinaloa (4.01%) and Northern Baja California (3.78%). The positive man: woman ratio was 0.87:1 and fluctuated between 0.38:1 in Coahuila and 1.76:1 in Nuevo Leon. In the whole sample the positive ratio of men was 3.00% and in women was 3.43%. The antibody profile related to age, is similar to diseases reported to be highly endemic; the percentage of positive sera rose progressively up to the age of 20 years (4.05%), at which a plateau occurred with a slight descending tendency up to 60 years of age (3.54%), after which a clear descent in the positive index is seen. No important variations were observed when comparing groups of ages and sexes. The antibody level seems to show an inverse relationship with the incidence rate of amebiasis.

  20. Proinflammatory responses in the murine brain after intranasal delivery of cholera toxin: implications for the use of AB toxins as adjuvants in intranasal vaccines.

    Science.gov (United States)

    Armstrong, Michelle E; Lavelle, Ed C; Loscher, Christine E; Lynch, Marina A; Mills, Kingston H G

    2005-11-01

    Intranasal delivery of vaccines provides an attractive alternative to parenteral delivery, but it requires appropriate mucosal adjuvants. Cholera toxin (CT) is a powerful mucosal adjuvant, but it can undergo retrograde transport to the brain via the olfactory system after intranasal delivery. We demonstrate that intranasal delivery of CT increases the expression of interleukin-1 beta , cyclooxygenase-2, and chemokine messenger RNA in the murine hypothalamus, whereas parenterally delivered CT has little effect. Our findings suggest that CT can induce proinflammatory mediators in the brain when it is administered intranasally but not parenterally, and they raise concerns about the use of AB toxins as adjuvants in intranasal vaccines.

  1. Prevalence of Entamoeba spp. in Stool Samples of Patients with Amebiasis Suspect by Native-Lugol and ELISA.

    Science.gov (United States)

    Beyhan, Yunus Emre; Yılmaz, Hasan; Taş Cengiz, Zeynep

    2016-06-01

    This study aimed to determine the prevalence of Entamoeba spp. in suspected stool samples submitted to our laboratory. In this retrospective study, stool samples of 998 patients with suspected amebiasis were sent from various clinics and services to our laboratory and were investigated by native-Lugol and enzyme-linked immunosorbent assay (ELISA) [for Entamoeba spp. antigen (Ridascreen® Entamoeba)] between January 2010 and December 2014. By the end of the study, it was shown that 8.5% (85) of 997 patients, 7.45% (39) of males and 9.8% (46) of females whom amoeba antigen inspected in their stool samples, were positive. No parasite was identified by the saline-Lugol method. The highest antigen positivity was detected in the 25-44-year-old group with 11% positivity, and a high positivity of 23.2% was seen in March. These results demonstrate that amebiasis is still a major health concern for our region. Although no parasite was detected during microscopic examinations, the detection of antigen positivity by ELISA reveals that microscopic examinations require experience and utilizing only microscopic examinations may lead to overlooks. To obtain more reliable results in diagnosis, ELISA analyses that use E. histolytica-specific monoclonal antibodies should be applied in addition to microscopic methods.

  2. The pathology of experimentally induced cecal amebiasis in gerbils (Meriones unguiculatus). Liver changes and amebic liver abscess formation.

    Science.gov (United States)

    Chadee, K.; Meerovitch, E.

    1985-01-01

    The pathogenesis of experimentally induced cecal amebiasis in gerbils (Meriones unguiculatus) was studied from 5 to 60 days after inoculation. Ulcerative lesions were noted 10 to 60 days after inoculation. The sequential development of lesions was asynchronous and progressed from destruction of the interglandular epithelium and of glandular crypt elements to loss of mucosa and formation of granulomatous lesions in the submucosa involving the muscularis mucosae. Pathologic changes in the liver correlated with the formation of ulcerative cecal lesions. Subacute hepatic changes showed lymphocytic portal infiltrate, Kupffer cell hyperplasia, multinucleated giant cells, granuloma formation, and sinusoidal mononuclear and granulocytic infiltrates. Metastatic amebic liver abscesses occurred as early as 10 days after inoculation, and small abscesses were found in the portal areas of the right liver lobe. The sequential development and pathologic manifestation of the infection and the usefulness of the gerbil for the study of human intestinal amebiasis are discussed. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 Figure 15 Figure 16 Figure 17 Figure 18 PMID:4014436

  3. Increased Risk for Entamoeba histolytica Infection and Invasive Amebiasis in HIV Seropositive Men Who Have Sex with Men in Taiwan

    Science.gov (United States)

    Hung, Chien-Ching; Ji, Dar-Der; Sun, Hsin-Yun; Lee, Ya-Tien; Hsu, Shui-Yuan; Chang, Sui-Yuan; Wu, Cheng-Hsin; Chan, Yun-Hsien; Hsiao, Chin-Fu; Liu, Wen-Chun; Colebunders, Robert

    2008-01-01

    Background Incidence of Entamoeba histolytica infection and clinical manifestations and treatment response of invasive amebiasis (IA) in HIV-infected patients have rarely been investigated before. Methodology/Principal Findings At the National Taiwan University Hospital, medical records of HIV-infected patients who received a diagnosis of IA between 1994 and 2005 were reviewed. The incidence of amebiasis was investigated in serial blood and stool samples from 670 and 264 HIV-infected patients, respectively, using serological and specific amebic antigen assays. DNA extracted from stool samples containing E. histolytica were analyzed by PCR, sequenced, and compared. Sixty-four (5.8%) of 1,109 HIV-infected patients had 67 episodes of IA, and 89.1% of them were men having sex with men (MSM). The CD4 count at diagnosis of IA was significantly higher than that of the whole cohort (215 cells/µL vs. 96 cells/µL). Forty episodes (59.7%) were liver abscesses, 52 (77.6%) colitis, and 25 (37.3%) both liver abscesses and colitis. Fever resolved after 3.5 days of metronidazole therapy (range, 1–11 days). None of the patients died. The incidence of E. histolytica infection in MSM was higher than that in other risk groups assessed by serological assays (1.99 per 100 person-years [PY] vs. 0 per 100 PY; pamebiasis than patients from other risk groups. Despite immunosuppression, amebic liver abscesses and colitis responded favorably to treatment. PMID:18301730

  4. The use of Midazolam as an Intranasal Sedative in Dentistry.

    Science.gov (United States)

    Greaves, Anwen

    2016-01-01

    The administration of midazolam intranasally exploits the unique structure of the nasopharynx thus ensuring rapid delivery to the systemic circulation (The Nose - Brain Pathway). The absorption of midazolam nasally is influenced by the volume and concentration of midazolam, its physicochemical properties and the characteristics of the nasal mucosa. Delivering midazolam intranasally is non-titratable. The level of conscious sedation may be equivalent to that achieved by intravenous routes but is approached in a less controlled manner. Randomised Control trials using intranasal sedation in children have shown the technique to be safe and effective in secondary care for dental procedures at concentrations varying from 0.2 mg/kg to 0.5 mg/kg. A combined technique of intranasal midazolam (to facilitate cannulation) and intravenous midazolam is used for adults with moderate to severe learning disabilities. This has revolutionised dental treatment for this group of patients as treatment under General Anaesthesia (GA) may be avoided. Intranasal delivery of midazolam is emerging as a significant tool in our dental armamentarium for the treatment of anxious children, phobic adult patients and patients with learning disabilities.

  5. Pharmacokinetics and pharmacodynamics of midazolam administered as a concentrated intranasal spray. A study in healthy volunteers.

    NARCIS (Netherlands)

    Knoester, P.D.; Jonker, D.M.; Hoeven, R.T. van der; Vermeij, T.A.; Edelbroek, P.M.; Brekelmans, G.J.; Haan, G.J. de

    2002-01-01

    AIMS: To investigate the pharmacokinetic and pharmacodynamic profile of midazolam administered as a concentrated intranasal spray, compared with intravenous midazolam, in healthy adult subjects. METHODS: Subjects were administered single doses of 5 mg midazolam intranasally and intravenously in a cr

  6. Pharmacokinetics of Intranasal Scopolamine Gel Formulation (Inscop)

    Science.gov (United States)

    Boyd, Jason L.; Du, Brian; Daniels, Vernie; Simmons, Rita; Buckey, Jay; Putcha, Lakshmi

    2009-01-01

    Space Motion Sickness (SMS) is commonly experienced by astronauts and often requires treatment with medications during early flight days of space missions. Orally administered scopolamine is commonly used by astronauts to prevent SMS. Bioavailability of oral (PO) SMS medications is often low and highly variable. Intranasal (IN) administration of medications achieves higher and more reliable bioavailability than from an equivalent PO dose. Methods: To test the safety and reliability of INSCOP, two clinical studies were performed, a dose escalation study and a comparison study administering INSCOP during normal ambulation and head down tilt bedrest. Efficacy was evaluated by testing INSCOP with two, different motion sickness inducing paradigms. Results: Preliminary results indicate that INSCOP demonstrates linear pharmacokinetics and a low side effect profile. In head down tilt bedrest, relative bioavailability of INSCOP was increased for females at both doses (0.2 and 0.4 mg) and for males at the higher dose (0.4 mg) but is reduced at the lower dose (0.2 mg) compared to normal ambulation. INSCOP displays gender specific differences during ABR. One of the treatment efficacy trials conducted at Dartmouth Hitchcock Medical Center demonstrated that INSCOP is efficacious at both doses (0.2 and 0.4 mg) in suppressing motion sickness symptoms as indicated by longer chair ride times with INSCOP administration than with placebo, and efficacy increases with dose. Similar results were seen using another motion sickness simulator, the motion simulator dome, at the Naval Aerospace Medical Research Laboratory, with significantly increased time in the dome in motion-susceptible subjects when using INSCOP compared to untreated controls. Conclusion: Higher bioavailability, linear pharmacokinetics, a low incidence of side effects, and a favorable efficacy profile make INSCOP a desirable formulation for prophylactic and rescue treatment of astronauts in space and military personnel on

  7. ENHANCED BIOAVAILABILITY OF DRUGS VIA INTRANASAL DRUG DELIVEY SYSTEM

    Directory of Open Access Journals (Sweden)

    kumar Brajesh

    2012-07-01

    Full Text Available The aim of present investigation is to explain the enhancement of bioavailability of drug through intranasal drug delivery system. Intranasal Therapy has been an accepted form of treatment in the Ayurvedic system of Indian Medicine. Recently, it has been shown that many drugs have better bioavailability by nasal route than the oral route. This has been attributed to rich vasculature and a highly permeable structure of the nasal mucosa coupled with avoidance of hepatic first-pass elimination, gut wall metabolism and/or destruction in the gastrointestinal tract. Intranasal microemulsion, gels, nanoparticles, liposome and microspheres have gained increased interest in recent years as a delivery system for protein and peptides through the nasal route. Thus this review focuses on nasal drug delivery, nasal drug absorption mechanisms, various mechanisms for increasing the bioavailability of drug, and their applications in drug delivery.

  8. The safety and tolerability of intranasal midazolam in epilepsy.

    Science.gov (United States)

    Mula, Marco

    2014-07-01

    Midazolam is a short-acting benzodiazepine that has clearly demonstrated to be an effective option for the acute management of epileptic seizures. It has the advantage of being water-soluble, with a rapid onset of action and it can be administered orally or intranasally, implementing an early intervention at the pre-hospital setting. This article aims to provide an overview of intranasal midazolam in the acute management of epileptic seizures. Available data suggest that midazolam 0.2 mg/kg is as effective as diazepam 0.5 mg/kg, especially in children with febrile or afebrile seizures. Local mucosal irritation seems to occur in less than one-third of cases while serious side effects such as respiratory depression in about 1%. Future studies need to be focused on adults and optimized technologies for intranasal delivery. Moreover, comparisons with buccal midazolam are warranted.

  9. Increased risk for Entamoeba histolytica infection and invasive amebiasis in HIV seropositive men who have sex with men in Taiwan.

    Directory of Open Access Journals (Sweden)

    Chien-Ching Hung

    Full Text Available BACKGROUND: Incidence of Entamoeba histolytica infection and clinical manifestations and treatment response of invasive amebiasis (IA in HIV-infected patients have rarely been investigated before. METHODOLOGY/PRINCIPAL FINDINGS: At the National Taiwan University Hospital, medical records of HIV-infected patients who received a diagnosis of IA between 1994 and 2005 were reviewed. The incidence of amebiasis was investigated in serial blood and stool samples from 670 and 264 HIV-infected patients, respectively, using serological and specific amebic antigen assays. DNA extracted from stool samples containing E. histolytica were analyzed by PCR, sequenced, and compared. Sixty-four (5.8% of 1,109 HIV-infected patients had 67 episodes of IA, and 89.1% of them were men having sex with men (MSM. The CD4 count at diagnosis of IA was significantly higher than that of the whole cohort (215 cells/microL vs. 96 cells/microL. Forty episodes (59.7% were liver abscesses, 52 (77.6% colitis, and 25 (37.3% both liver abscesses and colitis. Fever resolved after 3.5 days of metronidazole therapy (range, 1-11 days. None of the patients died. The incidence of E. histolytica infection in MSM was higher than that in other risk groups assessed by serological assays (1.99 per 100 person-years [PY] vs. 0 per 100 PY; p<0.0001 and amebic antigen assays (3.16 per 100 PY vs. 0.68 per 100 PY; p = 0.12. In multiple logistic regression analysis, only MSM was significantly associated with acquisition of E. histolytica infection (adjusted odds ratio, 14.809; p = 0.01. Clustering of E. histolytica isolates by sequencing analyses from geographically-unrelated patients suggested person-to-person transmission. CONCLUSIONS/SIGNIFICANCE: HIV-infected MSM were at significantly higher risk of amebiasis than patients from other risk groups. Despite immunosuppression, amebic liver abscesses and colitis responded favorably to treatment.

  10. Glucose recovery after intranasal glucagon during hypoglycaemia in man

    DEFF Research Database (Denmark)

    Hvidberg, A; Djurup, R; Hilsted, J

    1994-01-01

    concentrations 15 min after intranasal and i.m. administration of glucagon differed marginally. However, after 5 min the glucose appearance rate, as well as the incremental values for plasma glucose, were significantly higher for the i.m. glucagon treatment. The mean time taken for incremental plasma glucose...... to exceed 3 mmol.l-1 was significantly shorter for i.m. glucagon. The mean plasma glucagon level increased faster after i.m. glucagon than after intranasal glucagon, and the levels remained higher throughout the study period. We conclude that glucose recovery was significantly better after i...

  11. Intranasal H5N1 vaccines, adjuvanted with chitosan derivatives, protect ferrets against highly pathogenic influenza intranasal and intratracheal challenge.

    Directory of Open Access Journals (Sweden)

    Alex J Mann

    Full Text Available We investigated the protective efficacy of two intranasal chitosan (CSN and TM-CSN adjuvanted H5N1 Influenza vaccines against highly pathogenic avian Influenza (HPAI intratracheal and intranasal challenge in a ferret model. Six groups of 6 ferrets were intranasally vaccinated twice, 21 days apart, with either placebo, antigen alone, CSN adjuvanted antigen, or TM-CSN adjuvanted antigen. Homologous and intra-subtypic antibody cross-reacting responses were assessed. Ferrets were inoculated intratracheally (all treatments or intranasally (CSN adjuvanted and placebo treatments only with clade 1 HPAI A/Vietnam/1194/2004 (H5N1 virus 28 days after the second vaccination and subsequently monitored for morbidity and mortality outcomes. Clinical signs were assessed and nasal as well as throat swabs were taken daily for virology. Samples of lung tissue, nasal turbinates, brain, and olfactory bulb were analysed for the presence of virus and examined for histolopathological findings. In contrast to animals vaccinated with antigen alone, the CSN and TM-CSN adjuvanted vaccines induced high levels of antibodies, protected ferrets from death, reduced viral replication and abrogated disease after intratracheal challenge, and in the case of CSN after intranasal challenge. In particular, the TM-CSN adjuvanted vaccine was highly effective at eliciting protective immunity from intratracheal challenge; serologically, protective titres were demonstrable after one vaccination. The 2-dose schedule with TM-CSN vaccine also induced cross-reactive antibodies to clade 2.1 and 2.2 H5N1 viruses. Furthermore ferrets immunised with TM-CSN had no detectable virus in the respiratory tract or brain, whereas there were signs of virus in the throat and lungs, albeit at significantly reduced levels, in CSN vaccinated animals. This study demonstrated for the first time that CSN and in particular TM-CSN adjuvanted intranasal vaccines have the potential to protect against significant

  12. A novel Entamoeba histolytica cysteine proteinase, EhCP4, is key for invasive amebiasis and a therapeutic target.

    Science.gov (United States)

    He, Chen; Nora, George P; Schneider, Eric L; Kerr, Iain D; Hansell, Elizabeth; Hirata, Ken; Gonzalez, David; Sajid, Mohammed; Boyd, Sarah E; Hruz, Petr; Cobo, Eduardo R; Le, Christine; Liu, Wei-Ting; Eckmann, Lars; Dorrestein, Pieter C; Houpt, Eric R; Brinen, Linda S; Craik, Charles S; Roush, William R; McKerrow, James; Reed, Sharon L

    2010-06-11

    Entamoeba histolytica cysteine proteinases (EhCPs) play a key role in disrupting the colonic epithelial barrier and the innate host immune response during invasion of E. histolytica, the protozoan cause of human amebiasis. EhCPs are encoded by 50 genes, of which ehcp4 (ehcp-a4) is the most up-regulated during invasion and colonization in a mouse cecal model of amebiasis. Up-regulation of ehcp4 in vivo correlated with our finding that co-culture of E. histolytica trophozoites with mucin-producing T84 cells increased ehcp4 expression up to 6-fold. We have expressed recombinant EhCP4, which was autocatalytically activated at acidic pH but had highest proteolytic activity at neutral pH. In contrast to the other amebic cysteine proteinases characterized so far, which have a preference for arginine in the P2 position, EhCP4 displayed a unique preference for valine and isoleucine at P2. This preference was confirmed by homology modeling, which revealed a shallow, hydrophobic S2 pocket. Endogenous EhCP4 localized to cytoplasmic vesicles, the nuclear region, and perinuclear endoplasmic reticulum (ER). Following co-culture with colonic cells, EhCP4 appeared in acidic vesicles and was released extracellularly. A specific vinyl sulfone inhibitor, WRR605, synthesized based on the substrate specificity of EhCP4, inhibited the recombinant enzyme in vitro and significantly reduced parasite burden and inflammation in the mouse cecal model. The unique expression pattern, localization, and biochemical properties of EhCP4 could be exploited as a potential target for drug design.

  13. Intranasal corticosteroids compared with oral antihistamines in allergic rhinitis

    DEFF Research Database (Denmark)

    Juel-Berg, Nanna; Darling, Peter; Bolvig, Julie

    2017-01-01

    Background: Intranasal corticosteroids (INS) (corticosteroid nasal sprays) and oral antihistamines (OA) are two of the most common treatments for patients with allergic rhinitis (AR). To our knowledge, there are no systematic reviews on this topic including trials published after 2007. Objective...

  14. Intranasal Insulin: A Novel Treatment for Gulf War Multisymptom Illness

    Science.gov (United States)

    2013-10-01

    study pharmacist in an effort to finalize the logistics related to ordering and preparing study medication , and delivery of the intranasal device...completeness of the data and reduce human error . All study staff, including a new clinical psychologist and two recently hired research coordinators...Multisymptom Illness PRINCIPAL INVESTIGATOR: Dr. Julia Golier CONTRACTING ORGANIZATION: Bronx Veterans Medical Research

  15. Intranasal administration of oxytocin: Behavioral and clinical effects, a review

    NARCIS (Netherlands)

    Veening, J.G.; Olivier, B.

    2013-01-01

    The intranasal (IN-) administration of substances is attracting attention from scientists as well as pharmaceutical companies. The effects are surprisingly fast and specific. The present review explores our current knowledge about the routes of access to the cranial cavity. 'Direct-access-pathways'

  16. Kliniske konsekvenser af intranasal insulinbehandling ved insulinkraevende diabetes mellitus

    DEFF Research Database (Denmark)

    Hilsted, J C; Madsbad, S; Rasmussen, M H;

    1996-01-01

    Metabolic control, hypoglycaemia frequency and nasal mucosal physiology were evaluated in 31 insulin-dependent diabetics treated with intranasal insulin at mealtimes for one month and with subcutaneous fast-acting insulin for another month in a randomized crossover trial. During both periods...

  17. Intranasal clobazam delivery in the treatment of status epilepticus.

    Science.gov (United States)

    Florence, Kiruba; Manisha, Lalan; Kumar, Babbar Anil; Ankur, Kaul; Kumar, Mishra Anil; Ambikanandan, Misra

    2011-02-01

    The aim of the present investigation was to prepare and characterize clobazam mucoadhesive microemulsion (CZMME) to assess brain drug uptake and protection against pentylenetetrazole (PTZ)-induced convulsions in mice. Clobazam microemulsion (CZME) and CZMME were prepared by titration method and characterized. Brain uptake and pharmacokinetic parameters were calculated from drug concentration in mice brain versus time plots following intranasal administration of radiolabeled CZME and CZMME, intravenous and intranasal administration of radiolabeled clobazam solution. Gamma scintigraphy imaging of rabbit brain following intranasal administration was performed. Formulations were investigated for the onset of seizures in PTZ-challenged mice. Brain targeting efficiency and direct nose-to-brain transport percentage for mucoadhesive microemulsion suggested an improved brain uptake following intranasal administration. The findings were supported by gamma scintigraphy images. Delay in onset of PTZ-induced seizures with CZMME compared with positive control and placebo-treated groups confirmed the improved brain uptake. However, extensive animal studies followed by clinical trials are necessary to develop a product suitable for emergencies of acute seizures in status epilepticus and patients suffering from drug tolerance and hepatic impairment on long-term use in treatment of epilepsy, schizophrenia, and anxiety.

  18. Comparison of intranasal hypertonic dead sea saline spray and intranasal aqueous triamcinolone spray in seasonal allergic rhinitis.

    Science.gov (United States)

    Cordray, Scott; Harjo, Jim B; Miner, Linda

    2005-07-01

    Intranasal corticosteroids are well known to be efficacious in the treatment of allergic rhinitis. Nasal irrigation with saline, including hypertonic saline, has long been recommended for the treatment of sinonasal disease, and it has been shown to have a positive effect on the physiology of the nasal mucosa. Until now, no study of the clinical efficacy of intranasal hypertonic Dead Sea saline as a monotherapy for seasonal allergic rhinitis has been reported. We conducted a prospective, randomized, single-blind, placebo-controlled comparison of intranasal hypertonic Dead Sea saline spray and intranasal aqueous triamcinolone spray in 15 patients with seasonal allergic rhinitis. Results were based on a 7-day regimen. Based on Rhinoconjunctivitis Quality of Life Questionnaire scores, clinically and statistically significant (p Dead Sea saline solution can be an effective alternative in mild-to-moderate allergic rhinitis, particularly with respect to nasal and eye symptoms. The hypertonicity of the Dead Sea solution may have a positive effect on the physiology of the nasal mucosa by improving mucociliary clearance. In addition, the dominant cation in the Dead Sea solution--magnesium--probably exerts anti-inflammatory effects on the nasal mucosa and on the systemic immune response.

  19. A label-free fluorescence biosensor for highly sensitive detection of lectin based on carboxymethyl chitosan-quantum dots and gold nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Ziping; Liu, Hua; Wang, Lei; Su, Xingguang, E-mail: suxg@jlu.edu.cn

    2016-08-17

    In this work, we report a novel label-free fluorescence “turn off-on” biosensor for lectin detection. The highly sensitive and selective sensing system is based on the integration of carboxymethyl chitosan (CM-CHIT), CuInS{sub 2} quantum dots (QDs) and Au nanoparticles (NPs). Firstly, CuInS{sub 2} QDs featuring carboxyl groups were directly synthesized via a hydrothermal synthesis method. Then, the carboxyl groups on the CuInS{sub 2} QDs surface were interacted with the amino groups (−NH{sub 2}), carboxyl groups (−COOH) and hydroxyl groups (−OH) within CM-CHIT polymeric chains via electrostatic interactions and hydrogen bonding to form CM-CHIT-QDs assemblies. Introduction of Au NPs could quench the fluorescence of CM-CHIT-QDs through electron and energy transfer. In the presence of lectin, lectin could bind exclusively with CM-CHIT-QDs by means of specific multivalent carbohydrate-protein interaction. Thus, the electron and energy transfer process between CM-CHIT-QDs and Au NPs was inhibited, and as a result, the fluorescence of CM-CHIT-QDs was effectively “turned on”. Under the optimum conditions, there was a good linear relationship between the fluorescence intensity ratio I/I{sub 0} (I and I{sub 0} were the fluorescence intensity of CM-CHIT-QDs-Au NPs in the presence and absence of lectin, respectively) and lectin concentration in the range of 0.2–192.5 nmol L{sup −1}, And the detection limit could be down to 0.08 nmol L{sup −1}. Furthermore, the proposed biosensor was employed for the determination of lectin in fetal bovine serum samples with satisfactory results. - Graphical abstract: A label-free fluorescence biosensor for highly sensitive detection of lectin based on the integration of carboxymethyl chitosan, CuInS{sub 2} quantum dots and gold nanoparticles. - Highlights: • A label-free near-infrared fluorescence “turn off-on” biosensor for detection of lectin was established. • The highly sensitive biosensor was based on the

  20. Targeting glioblastoma via intranasal administration of Ff bacteriophages

    Science.gov (United States)

    Dor-On, Eyal; Solomon, Beka

    2015-01-01

    Bacteriophages (phages) are ubiquitous viruses that control the growth and diversity of bacteria. Although they have no tropism to mammalian cells, accumulated evidence suggests that phages are not neutral to the mammalian macro-host and can promote immunomodulatory and anti-tumorigenic activities. Here we demonstrate that Ff phages that do not display any proteins or peptides could inhibit the growth of subcutaneous glioblastoma tumors in mice and that this activity is mediated in part by lipopolysaccharide molecules attached to their virion. Using the intranasal route, a non-invasive approach to deliver therapeutics directly to the CNS, we further show that phages rapidly accumulate in the brains of mice and could attenuate progression of orthotopic glioblastoma. Taken together, this study provides new insight into phages non-bacterial activities and demonstrates the feasibility of delivering Ff phages intranasally to treat brain malignancies. PMID:26074908

  1. Targeting glioblastoma via intranasal administration of Ff bacteriophages

    Directory of Open Access Journals (Sweden)

    Eyal eDor-On

    2015-05-01

    Full Text Available Bacteriophages (phages are ubiquitous viruses that control the growth and diversity of bacteria. Although they have no tropism to mammalian cells, accumulated evidence suggests that phages are not neutral to the mammalian macro-host and can promote immunomodulatory and anti-tumorigenic activities. Here we demonstrate that Ff phages that do not display any proteins or peptides could inhibit the growth of subcutaneous glioblastoma tumors in mice and that this activity is mediated in part by lipopolysaccharide molecules attached to their virion. Using the intranasal route, a non-invasive approach to deliver therapeutics directly to the CNS, we further show that phages rapidly accumulate in the brains of mice and could attenuate progression of orthotopic glioblastoma. Taken together, this study provides new insight into phages non-bacterial activities and demonstrates the feasibility of delivering Ff phages intranasally to treat brain malignancies.

  2. Targeting glioblastoma via intranasal administration of Ff bacteriophages.

    Science.gov (United States)

    Dor-On, Eyal; Solomon, Beka

    2015-01-01

    Bacteriophages (phages) are ubiquitous viruses that control the growth and diversity of bacteria. Although they have no tropism to mammalian cells, accumulated evidence suggests that phages are not neutral to the mammalian macro-host and can promote immunomodulatory and anti-tumorigenic activities. Here we demonstrate that Ff phages that do not display any proteins or peptides could inhibit the growth of subcutaneous glioblastoma tumors in mice and that this activity is mediated in part by lipopolysaccharide molecules attached to their virion. Using the intranasal route, a non-invasive approach to deliver therapeutics directly to the CNS, we further show that phages rapidly accumulate in the brains of mice and could attenuate progression of orthotopic glioblastoma. Taken together, this study provides new insight into phages non-bacterial activities and demonstrates the feasibility of delivering Ff phages intranasally to treat brain malignancies.

  3. Assessment of the pharmacodynamics of intranasal, intravenous and oral scopolamine

    Science.gov (United States)

    Tietze, Karen J.

    1990-01-01

    Space motion sickness is an important issue in the space medical sciences program. One of the objectives of the ongoing clinical experimental protocol Pharmacokinetics of Intranasal Scopolamine in Normal Subjects is to evaluate the pharmacodynamics of scopolamine using salivary flow rate and pH profiles and cognitive performance tests as pharmacodynamic parameters. Normal volunteers collected saliva and performed the NTI Multiresource Performance Battery tests at designed time intervals to establish control saliva flow rates, salivary pH profiles, and the characteristics of the learning curve for the performance program under normal conditions. In the clinical part of the study, saliva samples and performance test scores are collected from healthy nonsmoking subjects after receiving a single 0.4 mg dose of either intranasal, intravenous, or oral scopolamine.

  4. Gene therapy prospects--intranasal delivery of therapeutic genes.

    Science.gov (United States)

    Podolska, Karolina; Stachurska, Anna; Hajdukiewicz, Karolina; Małecki, Maciej

    2012-01-01

    Gene therapy is recognized to be a novel method for the treatment of various disorders. Gene therapy strategies involve gene manipulation on broad biological processes responsible for the spreading of diseases. Cancer, monogenic diseases, vascular and infectious diseases are the main targets of gene therapy. In order to obtain valuable experimental and clinical results, sufficient gene transfer methods are required. Therapeutic genes can be administered into target tissues via gene carriers commonly defined as vectors. The retroviral, adenoviral and adeno-associated virus based vectors are most frequently used in the clinic. So far, gene preparations may be administered directly into target organs or by intravenous, intramuscular, intratumor or intranasal injections. It is common knowledge that the number of gene therapy clinical trials has rapidly increased. However, some limitations such as transfection efficiency and stable and long-term gene expression are still not resolved. Consequently, great effort is focused on the evaluation of new strategies of gene delivery. There are many expectations associated with intranasal delivery of gene preparations for the treatment of diseases. Intranasal delivery of therapeutic genes is regarded as one of the most promising forms of pulmonary gene therapy research. Gene therapy based on inhalation of gene preparations offers an alternative way for the treatment of patients suffering from such lung diseases as cystic fibrosis, alpha-1-antitrypsin defect, or cancer. Experimental and first clinical trials based on plasmid vectors or recombinant viruses have revealed that gene preparations can effectively deliver therapeutic or marker genes to the cells of the respiratory tract. The noninvasive intranasal delivery of gene preparations or conventional drugs seems to be very encouraging, although basic scientific research still has to continue.

  5. Pharmaceutical Product Development: Intranasal Scopolamine (INSCOP) Metered Dose Spray

    Science.gov (United States)

    Putcha, Lakshmi; Crady, Camille; Putcha, Lakshmi

    2012-01-01

    Motion sickness (MS) has been a problem associated with space flight, the modern military and commercial air and water transportation for many years. Clinical studies have shown that scopolamine is the most effective medication for the prevention of motion sickness (Dornhoffer et al, 2004); however, the two most common methods of administration (transdermal and oral) have performance limitations that compromise its utility. Intranasal administration offers a noninvasive treatment modality, and has been shown to counter many of the problems associated with oral and transdermal administration. With the elimination of the first pass effect by the liver, intranasal delivery achieves higher and more reliable bioavailability than an equivalent oral dose. This allows for the potential of enhanced efficacy at a reduced dose, thus minimizing the occurrence of untoward side effects. An Intranasal scopolamine (INSCOP) gel formulation was prepared and tested in four ground-based clinical trials under an active Investigational New Drug (IND) application with the Food and Drug Administration (FDA). Although there were early indicators that the intranasal gel formulation was effective, there were aspects of formulation viscosity and the delivery system that were less desirable. The INSCOP gel formulation has since been reformulated into an aqueous spray dosage form packaged in a precise, metered dose delivery system; thereby enhancing dose uniformity, increased user satisfaction and palatability, and a potentially more rapid onset of action. Recent reports of new therapeutic indications for scopolamine has prompted a wide spread interest in new scopolamine dosage forms. The novel dosage form and delivery system of INSCOP spray shows promise as an effective treatment for motion sickness targeted at the armed forces, spaceflight, and commercial sea, air, and space travel markets, as well as prospective psychotherapy for mental and emotional disorders.

  6. Intranasal delivery of antiepileptic medications for treatment of seizures.

    Science.gov (United States)

    Wermeling, Daniel P

    2009-04-01

    Acute isolated seizure, repetitive or recurrent seizures, and status epilepticus are all deemed medical emergencies. Mortality and worse neurologic outcome are directly associated with the duration of seizure activity. A number of recent reviews have described consensus statements regarding the pharmacologic treatment protocols for seizures when patients are in pre-hospital, institutional, and home-bound settings. Benzodiazepines, such as lorazepam, diazepam, midazolam, and clonazepam are considered to be medications of first choice. The rapidity by which a medication can be delivered to the systemic circulation and then to the brain plays a significant role in reducing the time needed to treat seizures and reduce opportunity for damage to the CNS. Speed of delivery, particularly outside of the hospital, is enhanced when transmucosal routes of delivery are used in place of an intravenous injection. Intranasal transmucosal delivery of benzodiazepines is useful in reducing time to drug administration and cessation of seizures in the pre-hospital setting, when actively seizing patients arrive in the emergency room, and at home where caregivers treat their dependents. This review summarizes factors to consider when choosing a benzodiazepine for intranasal administration, including formulation and device considerations, pharmacology and pharmacokinetic/pharmacodynamic profiles. A review of the most relevant clinical studies in epilepsy patients will provide context for the relative success of this technique with a number of benzodiazepines and relatively less sophisticated nasal preparations. Neuropeptides delivered intranasally, crossing the blood-brain barrier via the olfactory system, may increase the availability of medications for treatment of epilepsy. Consequently, there remains a significant unmet medical need to serve the pharamcotherapeutic requirements of epilepsy patients through commercial development and marketing of intranasal antiepileptic products.

  7. Delivery of cefotaxime to the brain via intranasal administration.

    Science.gov (United States)

    Manda, Prashanth; Hargett, Jamie K; Vaka, Siva Ram Kiran; Repka, Michael A; Murthy, S Narasimha

    2011-11-01

    The purpose of this study was to investigate the plausibility of delivery of cefotaxime to the brain via intranasal administration. In vitro permeation studies were carried out using Franz diffusion cells, and the effect of different concentrations of chitosan (0.1% w/v and 0.25% w/v) on drug permeation across the bovine olfactory mucosa was determined. Samples were collected from the receiver compartment at different time points and analyzed using HPLC. The amount of cefotaxime that permeated across the olfactory mucosa when 0.25% w/v of chitosan was used as a permeation enhancer was ~1.5- and ~2-fold higher at the end of the first hour and second hour, respectively, over control (29.56 ± 6.18 µg/cm(2)). There was no significant enhancement in drug permeation when 0.1% w/v chitosan was used as the permeation enhancer. Pharmacokinetic studies were carried out using Sprague-Dawley rats. Cefotaxime solution with 0.25% w/v chitosan (40 mg/kg) was administered intravenously (i.v.) to rats in groups 1 and 3 and intranasally to those in group 2 and 4. The time course of drug in the brain was investigated by performing microdialysis in rats of groups 1 and 2. Blood samples were withdrawn from rats in groups 3 and 4, and cefotaxime in plasma was analyzed using HPLC after extraction with a hydrochloric acid-chloroform:1-pentanol (3:1) and phosphate buffer solvent system. Pharmacokinetic parameters were calculated using the trapezoidal rule. The results imply that the drug levels attained in the brain following i.v. and intranasal administrations were comparable. These results suggest that intranasal administration of cefotaxime could be a potential method of delivering antibacterial agents because of it being noninvasive and patient compliant.

  8. Implementation of Intranasal Midazolam for Prolonged Seizures in a Child Neurology Practice.

    Science.gov (United States)

    Crawford, Daniel

    2016-12-01

    Currently, evidence supports the use of intranasal midazolam as an effective, and in many cases, preferable treatment option for prolonged seizures in children. Despite this knowledge, intranasal midazolam is not routinely found as a standard of care. The goal of this project was to implement the use of intranasal midazolam as a rescue medication for prolonged seizures within a child neurology practice and, in doing so, create a model for implementation that would be replicable for other practice sites. This project focused on the development of a process to make intranasal midazolam available as a treatment option and then the creation of an educational intervention for providers within a child neurology practice. Provider surveys analyzed provider attitudes toward intranasal midazolam and its frequency of use. Because of this project, a dramatic increase in the prescribing of intranasal midazolam was observed within a child neurology practice.

  9. Intranasal mesenchymal stem cell treatment for neonatal brain damage : long-term cognitive and sensorimotor improvement

    NARCIS (Netherlands)

    Donega, Vanessa; van Velthoven, Cindy T J; Nijboer, Cora H; van Bel, Frank; Kas, Martien J H; Kavelaars, Annemieke; Heijnen, Cobi J

    2013-01-01

    Mesenchymal stem cell (MSC) administration via the intranasal route could become an effective therapy to treat neonatal hypoxic-ischemic (HI) brain damage. We analyzed long-term effects of intranasal MSC treatment on lesion size, sensorimotor and cognitive behavior, and determined the therapeutic wi

  10. Intranasal Delivery of pGDNF Nanoparticles for Parkinson's Disease

    Science.gov (United States)

    Harmon, Brendan Trevor

    Parkinson's disease (PD) is a progressive neurodegenerative disorder that primarily affects the dopaminergic A9 nigrostriatal tract. For dopamine neurons specifically, glial cell-derived neurotrophic factor (GDNF) has been shown to promote their survival and proliferation both in culture and in vivo. GDNF has also proven to be neuroprotective and restorative in various animal models of PD and some human clinical trials. However, its delivery to the brain has required invasive surgical routes which are not clinically practical for many patients. The main objective of this project was to test intranasal delivery to the brain of a nanoparticle vector incorporating an expression plasmid for GDNF (pGDNF). The intranasal route circumvents the blood-brain barrier, allowing larger sized vectors into the central nervous system while avoiding peripheral distribution. This approach would provide a renewable source of GDNF within the target areas of the brain, the striatum and the substantia nigra (SN) without the need for surgical injections or frequent re-dosing. A PEGylated polylysine compacted plasmid nanoparticle vector (PEG-CK30), developed by Copernicus Therapeutics, Inc., has been shown to transfect neurons and glial cells in vivo while lacking the safety issues present with other vectors. The first goal of this work was to determine if these PEG-CK30 compacted plasmid nanoparticles can successfully transfect cells and express the reporter protein, enhanced green fluorescent protein (eGFP) in the rat brain after intranasal administration. Initial in vivo experiments utilized the expression plasmid pCG, expressing eGFP under the fast-acting cytomegalovirus (CMV) promoter. Intranasal administration of pCG nanoparticles resulted in evidence of transfection of brain cells, as shown both qualitatively, by GFP-immunohistochemistry, and quantitatively, by GFP-ELISA. Expression was detected throughout the rat brain two days post-administration. Following the proof

  11. Thermoreversible biogels for intranasal delivery of rizatriptan benzoate

    Directory of Open Access Journals (Sweden)

    Chand Renuka

    2009-01-01

    Full Text Available The objective of the present study was to formulate and evaluate a thermoreversible formulation containing rizatriptan benzoate for intranasal administration. Chitosan and aqueous β-glycerolphosphate were mixed in cold condition to obtain chitosan-β-glycerolphosphate mixtures, which served as the thermoreversible systems. Rizatriptan benzoate was incorporated at a final strength of 25 mg/ml. Both in vitro release and ex vivo permeation of rizatriptan from gels were measured at 37º using Franz diffusion cells Formulations were tested in vivo in mice for reduction in locomotor activity using digital actophotometer and nasal mucosal tissues were examined histopathologically.

  12. A new minimal-stress freely-moving rat model for preclinical studies on intranasal administration of CNS drugs

    NARCIS (Netherlands)

    Stevens, Jasper; Suidgeest, Ernst; van der Graaf, Piet Hein; Danhof, Meindert; de Lange, Elizabeth C M

    2009-01-01

    PURPOSE: To develop a new minimal-stress model for intranasal administration in freely moving rats and to evaluate in this model the brain distribution of acetaminophen following intranasal versus intravenous administration. METHODS: Male Wistar rats received one intranasal cannula, an intra-cerebra

  13. Intranasal sufentanil for cancer-associated breakthrough pain.

    Science.gov (United States)

    Good, P; Jackson, K; Brumley, D; Ashby, M

    2009-01-01

    The objective of this study was to demonstrate the efficacy, safety and patient acceptability of the use of intranasal sufentanil for cancer-associated breakthrough pain. This was a prospective, open label, observational study of patients in three inpatient palliative care units in Australia. Patients on opioids with cancer-associated breakthrough pain and clinical evidence of opioid responsiveness to their breakthrough pain were given intranasal (IN) Sufentanil via a GO Medical patient controlled IN analgesia device. The main outcome measures were pain scores, need to revert to previous breakthrough opioid after 30 min, number of patients who chose to continue using IN sufentanil, and adverse effects. There were 64 episodes of use of IN sufentanil for breakthrough pain in 30 patients. There was a significant reduction in pain scores at 15 (P < 0.0001) and 30 min (P < 0.0001). In only 4/64 (6%) episodes of breakthrough pain did the participants choose to revert to their prestudy breakthrough medication. Twenty-three patients (77%) rated IN sufentanil as better than their prestudy breakthrough medication. The incidence of adverse effects was low and most were mild. Our study showed that IN sufentanil can provide relatively rapid onset, intense but relatively short lasting analgesia and in the palliative care setting it is an effective, practical, and safe option for breakthrough pain.

  14. [Effectiveness of intranasal salmon calcitonin treatment in postmenopausal osteoporosis].

    Science.gov (United States)

    Kopaliani, M

    2005-04-01

    The aim of this study was to assess clinical efficacy of intranasal salmon calcitonin (Miacalcic, Novartis pharma) treatment in women with established postmenopausal osteoporosis. 30 women of the main group with established postmenopausal osteoporosis(T-score salmon calcitonin: 200 IU daily for 2 months with subsequent pause of 2 months (3 cycles), 12 months in total. Age matched control group was formed by 25 postmenopausal women with similar clinical status. SOS (speed of sound) of cortical bone was measured in the middle of the tibia by ultrasound densitometer--Sound Scan Compact (Myriad-Israel). Patients of both groups received 500 mg Ca and 200 IU vit.D3 (CaD3 Nycomed) two times daily in the same regimen (two months treatment--two months pause). Our results showed that intranasal treatment with 200 IU daily effectively influence the back pain, reduces bone turnover and significantly increases cortical BMD. Significant changes were not observed in patients of the control group, who received only CaD3 Nycomed, that showed that Calcium and vitamin D supplementation is more effective for prevention of bone lose in postmenopausal women, rather for treatment of established osteoporosis.

  15. Intranasal midazolam vs rectal diazepam in acute childhood seizures.

    Science.gov (United States)

    Bhattacharyya, Madhumita; Kalra, Veena; Gulati, Sheffali

    2006-05-01

    One hundred eighty-eight seizure episodes in 46 children were randomly assigned to receive treatment with rectal diazepam and intranasal midazolam with doses of 0.3 mg/kg body weight and 0.2 mg/kg body weight, respectively. Efficacy of the drugs was assessed by drug administration time and seizure cessation time. Heart rate, blood pressure, respiratory rate, and oxygen saturation were measured before and after 5, 10, and 30 minutes following administration of the drugs in both groups. Mean time from arrival of doctor to drug administration was 68.3 +/- 55.12 seconds in the diazepam group and 50.6 +/- 14.1 seconds in the midazolam group (P = 0.002). Mean time from drug administration to cessation of seizure was significantly less in the midazolam group than the diazepam group (P = 0.005). Mean heart rate and blood pressure did not vary significantly between the two drug groups. However, mean respiratory rate and oxygen saturation differed significantly between the two drug groups at 5, 10, and 30 minutes after drug administration. Intranasal midazolam is preferable to rectal diazepam in the treatment of acute seizures in children. Its administration is easy, it has rapid onset of action, has no significant effect on respiration and oxygen saturation, and is socially acceptable.

  16. Intranasal oxytocin administration is reflected in human saliva.

    Science.gov (United States)

    Weisman, Omri; Zagoory-Sharon, Orna; Feldman, Ruth

    2012-09-01

    Following the discovery that intranasal administration of neuropeptides can reach the central nervous system, a growing number of studies applied intranasal oxytocin (OT) paradigms to demonstrate the positive effects of OT on social and emotional processes. The three-step paradigm typically included: OT administration, a 45-min waiting period, and approximately 1-h period of active drug effects when experimental manipulations are applied. Yet, this schedule has not been put to systematic validation. Utilizing a double-blind placebo-control within-subject design, ten individuals were administered OT or placebo and salivary OT was measured ten times, at baseline and nine times over four consecutive hours. OT administration induced substantial increases in salivary OT across the entire period. OT rose dramatically 15 min after administration (from 6.9 pg/ml at baseline to 1265.4 pg/ml), reached plateau at 45-120 min (range=131.6 and 105.3 pg/ml), and did not return to baseline by 4h. Results contribute to discussion on brain-periphery coordination of OT and highlight the need for further research on the temporal dynamics and durations of OT administration effects.

  17. Entamoeba histolytica: Overexpression of the gal/galnac lectin, ehcp2 and ehcp5 genes in an in vivo model of amebiasis.

    Science.gov (United States)

    Sánchez, Virginia; Serrano-Luna, Jesús; Ramírez-Moreno, Esther; Tsutsumi, Víctor; Shibayama, Mineko

    2016-12-01

    The parasite Entamoeba histolytica causes intestinal amebiasis and amebic liver abscess as its main extraintestinal manifestation. To study the in vivo events related to inflammation and the interactions between hosts and parasites during amebiasis, we designed a novel model of host-parasite interactions using cellulose membrane dialysis bags containing E. histolytica trophozoites. A bag is placed into the hamster peritoneal cavity, as has been reported in previous studies of programmed cell death (PCD) in E. histolytica trophozoites. To determine if virulence factors such as cysteine proteinases (EhCP2 and EhCP5) and Gal/GalNAc lectin could be involved in the host-parasite interaction using this model, we examined the relative expression of the ehcp2 and ehcp5 genes and the carbohydrate recognition domain (crd) of Gal/GalNAc lectin using real-time quantitative PCR (qRT-PCR). All analyzed genes were over-expressed 0.5h after the initiation of the host-parasite interaction and were then progressively down-regulated. However, Gal/GalNAc lectin had the greatest increase in gene expression 1.5h after host-parasite interaction; Gal/GalNAc lectin had a 250-fold increase with respect to the axenically grown trophozoites, which over-express Gal/GalNAc lectin in in vivo models. These results support the important role of these molecules in the initiation of cell damage by E. histolytica. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Intranasal oxytocin increases social grooming and food sharing in the common vampire bat Desmodus rotundus.

    Science.gov (United States)

    Carter, Gerald G; Wilkinson, Gerald S

    2015-09-01

    Intranasal oxytocin (OT) delivery has been used to non-invasively manipulate mammalian cooperative behavior. Such manipulations can potentially provide insight into both shared and species-specific mechanisms underlying cooperation. Vampire bats are remarkable for their high rates of allogrooming and the presence of regurgitated food sharing among adults. We administered intranasal OT to highly familiar captive vampire bats of varying relatedness to test for an effect on allogrooming and food sharing. We found that intranasal OT did not have a detectable effect on food-sharing occurrence, but it did increase the size of regurgitated food donations when controlling for dyad and amount of allogrooming. Intranasal OT in females increased the amount of allogrooming per partner and across all partners per trial, but not the number of partners. We also found that the peak effect of OT treatments occurred 30-50min after administration, which is consistent with the reported latency for intranasal OT to affect relevant brain areas in rats and mice. Our results suggest that intranasal OT is a potential tool for influencing dyadic cooperative investments, but measuring prior social relationships may be necessary to interpret the results of hormonal manipulations of cooperative behavior and it may be difficult to alter partner choice in vampire bats using intranasal OT alone.

  19. Intranasal delivery of obidoxime to the brain prevents mortality and CNS damage from organophosphate poisoning.

    Science.gov (United States)

    Krishnan, Jishnu K S; Arun, Peethambaran; Appu, Abhilash P; Vijayakumar, Nivetha; Figueiredo, Taíza H; Braga, Maria F M; Baskota, Sudikshya; Olsen, Cara H; Farkas, Natalia; Dagata, John; Frey, William H; Moffett, John R; Namboodiri, Aryan M A

    2016-03-01

    Intranasal delivery is an emerging method for bypassing the blood brain barrier (BBB) and targeting therapeutics to the CNS. Oximes are used to counteract the effects of organophosphate poisoning, but they do not readily cross the BBB. Therefore, they cannot effectively counteract the central neuropathologies caused by cholinergic over-activation when administered peripherally. For these reasons we examined intranasal administration of oximes in an animal model of severe organophosphate poisoning to determine their effectiveness in reducing mortality and seizure-induced neuronal degeneration. Using the paraoxon model of organophosphate poisoning, we administered the standard treatment (intramuscular pralidoxime plus atropine sulphate) to all animals and then compared the effectiveness of intranasal application of obidoxime (OBD) to saline in the control groups. Intranasally administered OBD was effective in partially reducing paraoxon-induced acetylcholinesterase inhibition in the brain and substantially reduced seizure severity and duration. Further, intranasal OBD completely prevented mortality, which was 41% in the animals given standard treatment plus intranasal saline. Fluoro-Jade-B staining revealed extensive neuronal degeneration in the surviving saline-treated animals 24h after paraoxon administration, whereas no detectable degenerating neurons were observed in any of the animals given intranasal OBD 30min before or 5min after paraoxon administration. These findings demonstrate that intranasally administered oximes bypass the BBB more effectively than those administered peripherally and provide an effective method for protecting the brain from organophosphates. The addition of intranasally administered oximes to the current treatment regimen for organophosphate poisoning would improve efficacy, reducing both brain damage and mortality.

  20. Intranasal delivery of ciprofloxacin to rats: A topical approach using a thermoreversible in situ gel.

    Science.gov (United States)

    Sousa, Joana; Alves, Gilberto; Oliveira, Paula; Fortuna, Ana; Falcão, Amílcar

    2017-01-15

    Intranasal administration of antibiotics is an alternative and attractive delivery approach in the treatment of local infections such as chronic rhinosinusitis. This topical route has the advantage of delivering high drug concentrations directly to the site of infection when trying to eradicate the highly resistant bacterial biofilms. The purpose of this study was to assess and compare the pharmacokinetic parameters of ciprofloxacin following intranasal and intravenous administrations to rats in plasma, olfactory bulb and nasal mucosa of two different nasal regions. For intranasal administration a thermoreversible in situ gel was used to increase drug residence time in nasal cavity. Ciprofloxacin concentration time-profile in nasal mucosa of the studied anterior region (at naso- and maxilloturbinates level) was markedly higher after intranasal administration (0.24mg/kg) than that following intravenous administration (10mg/kg), while in nasal mucosa of the more posterior region (at ethmoidal turbinates level) ciprofloxacin concentrations were found to be higher after intranasal administration when the different dose administered by both routes is taken into account. A plateau in ciprofloxacin concentration was observed in nasal mucosa of both studied regions after intranasal administration, suggesting a slow delivery of the drug over a period of time using the nasal gel formulation. In plasma and olfactory bulb, concentration of ciprofloxacin was residual after intranasal administration, which demonstrates this is a safe administration route by preventing systemic and particularly central nervous system adverse effects. Dose-normalized pharmacokinetic parameters of ciprofloxacin exposure to nasal mucosa revealed higher values after intranasal delivery not only in the anterior region but also in the posterior nasal region. In conclusion, topical intranasal administration appears to be advantageous for delivering ciprofloxacin to the biophase, with negligible systemic

  1. Intranasal location and immunohistochemical characterization of the equine olfactory epithelium

    Directory of Open Access Journals (Sweden)

    Alexandra Kupke

    2016-10-01

    Full Text Available The olfactory epithelium (OE is the only body site where neurons contact directly the environment and are therefore exposed to a broad variation of substances and insults. It can serve as portal of entry for neurotropic viruses which spread via the olfactory pathway to the central nervous system (CNS. For horses, it has been proposed and concluded mainly from rodent studies that different viruses, e.g. Borna disease virus (BoDV, equine herpesvirus 1 (EHV-1, hendra virus, influenza virus, rabies virus, vesicular stomatitis virus (VSV can use this route. However, little is yet known about cytoarchitecture, protein expression and the intranasal location of the equine OE. Revealing differences in cytoarchitecture or protein expression pattern in comparison to rodents, canines or humans might help to explain varying susceptibility to certain intranasal virus infections. On the other hand, disclosing similarities especially between rodents and other species, e.g. horses would help to underscore transferability of rodent models. Analysis of the complete noses of 5 adult horses revealed that in the equine OE two epithelial subtypes with distinct marker expression exist, designated as types a and b which resemble those previously described in dogs. Detailed statistical analysis was carried out to confirm the results obtained on the descriptive level. The equine OE was predominantly located in caudodorsal areas of the nasal turbinates with a significant decline in rostroventral direction, especially for type a. Immunohistochemically, olfactory marker protein (OMP and doublecortin (DCX expression was found in more cells of OE type a, whereas expression of proliferating cell nuclear antigen (PCNA and tropomyosin receptor kinase A (TrkA was present in more cells of type b. Accordingly, type a resembles the mature epithelium, in contrast to the more juvenile type b. Protein expression profile was comparable to canine and rodent OE but equine type a and b were

  2. Intranasal Location and Immunohistochemical Characterization of the Equine Olfactory Epithelium

    Science.gov (United States)

    Kupke, Alexandra; Wenisch, Sabine; Failing, Klaus; Herden, Christiane

    2016-01-01

    The olfactory epithelium (OE) is the only body site where neurons contact directly the environment and are therefore exposed to a broad variation of substances and insults. It can serve as portal of entry for neurotropic viruses which spread via the olfactory pathway to the central nervous system. For horses, it has been proposed and concluded mainly from rodent studies that different viruses, e.g., Borna disease virus, equine herpesvirus 1 (EHV-1), hendra virus, influenza virus, rabies virus, vesicular stomatitis virus can use this route. However, little is yet known about cytoarchitecture, protein expression and the intranasal location of the equine OE. Revealing differences in cytoarchitecture or protein expression pattern in comparison to rodents, canines, or humans might help to explain varying susceptibility to certain intranasal virus infections. On the other hand, disclosing similarities especially between rodents and other species, e.g., horses would help to underscore transferability of rodent models. Analysis of the complete noses of five adult horses revealed that in the equine OE two epithelial subtypes with distinct marker expression exist, designated as types a and b which resemble those previously described in dogs. Detailed statistical analysis was carried out to confirm the results obtained on the descriptive level. The equine OE was predominantly located in caudodorsal areas of the nasal turbinates with a significant decline in rostroventral direction, especially for type a. Immunohistochemically, olfactory marker protein and doublecortin (DCX) expression was found in more cells of OE type a, whereas expression of proliferating cell nuclear antigen and tropomyosin receptor kinase A was present in more cells of type b. Accordingly, type a resembles the mature epithelium, in contrast to the more juvenile type b. Protein expression profile was comparable to canine and rodent OE but equine types a and b were located differently within the nose and

  3. Case presentation of an intranasal ectopic tooth in a pediatric patient.

    Science.gov (United States)

    Yu, Chao; Gu, Deying; An, Junnan; Tang, Yuedi

    2015-01-01

    An ectopic tooth in the nasal cavity is a rare phenomenon, especially on the inferior turbinate. In most of the reported cases, no etiological explanation of the intranasal teeth has been suggested or found. In children, intranasal ectopic teeth are usually associated with cleft lip and alveolus. Here, we report a rare case of a pediatric patient with unilateral nasal obstruction due to an intranasal ectopic tooth originating from the inferior turbinate without any facial and dental deformities. This case is unique due to the unusual location of the ectopic tooth and its presentation in a child without facial and dental deformities.

  4. Topical and Intranasal Analgesic Therapy in a Woman with Refractory Postherpetic Neuralgia

    Directory of Open Access Journals (Sweden)

    Kenneth C. Hohmeier

    2015-01-01

    Full Text Available A patient-specific, stepped approach to topical and intranasal analgesic pharmacotherapy was effective in reducing refractory postherpetic neuralgia (PHN not responding to the current standard of care for PHN. The use of topical analgesic therapy allowed for higher concentrations of medication locally while reducing the likelihood of systemic side effects common to the drugs used. No adverse effects were noted for either topical or intranasal drug therapy. The patient-specific, stepped approach resulted in clinically significant decreases in pain on visual analog scale (VAS, with the use of intranasal ketamine 10% solution and topical gabapentin 6%, ketoprofen 10%, lidocaine 5%, and ketamine 10% cream.

  5. Nanoemulsion based intranasal delivery of antimigraine drugs for nose to brain targeting

    Directory of Open Access Journals (Sweden)

    Bhanushali R

    2009-01-01

    Full Text Available The objective of this study was to develop intranasal nanoemulsion and gel formulations for rizatriptan benzoate for prolonged action. Nanoemulsion formulations were prepared by constructing pseudo-ternary phase diagrams using lipophilic and hydrophilic surfactants and water. Various mucoadhesive agents were tried out to form thermo-triggered mucoadhesive nanoemulsions. Mucoadhesive gel formulations of rizatriptan were prepared using different ratios of HPMC and Carbopol 980. Comparative evaluation of intranasal nanoemulsions and intranasal mucoadhesive gels indicated that greater brain-targeting could be achieved with nanoemulsions.

  6. Intranasal Tooth - An Ectopic Eruption of Mesiodens in Nasal Cavity: A Case Report and Review

    Directory of Open Access Journals (Sweden)

    R Guru Prasad

    2011-01-01

    Full Text Available An intranasal tooth (INT is an ectopic tooth erupting into the nasal cavity. It is a rare clinical entity. Ectopic and supernumerary teeth may be present in many regions of maxillofacial skeleton. Ectopic teeth maybe supernumerary, deciduous or permanent. The clinical manifestations of intranasal tooth are quite variable and they may cause a variety of symptoms and complications. Their clinical and radiographic presentations are classical, posing little challenge to the diagnostician. The identification of such teeth can be important since they have potential to cause considerable morbidity. Here, we describe a case of intranasal tooth along with possible etiopathogenesis, clinical and radiographic features, differential diagnosis, potential complications and treatment modalities.

  7. Formulation and kinetic modeling of curcumin loaded intranasal mucoadhesive microemulsion

    Directory of Open Access Journals (Sweden)

    B Mikesh Patel

    2012-01-01

    Full Text Available It is a challenge to develop the optimum dosage form of poorly water-soluble drugs and to target them due to limited bioavailability, intra and inter subject variability. In this investigation, mucoadhesive microemulsion of curcumin was developed by water titration method taking biocompatible components for intranasal delivery and was characterized. Nasal ciliotoxicity studies were carried out using excised sheep nasal mucosa. in vitro release studies of formulations and PDS were performed. Labrafil M 1944 CS based microemulsion was transparent, stable and nasal non-ciliotoxic having particle size 12.32±0.81nm (PdI=0.223 and from kinetic modeling, the release was found to be Fickian diffusion for mucoadhesive microemulsion.

  8. Formulation and characterization of nanoemulsion of olanzapine for intranasal delivery.

    Science.gov (United States)

    Kumar, Mukesh; Misra, Ambikanandan; Pathak, Kamla

    2009-01-01

    The objective was to formulate an olanzapine nanoemulsion that could potentially deliver the drug directly to the brain following intranasal administration. The nanoemulsions were prepared using the water titration method. The mucoadhesive character was imparted by the addition of 0.5%w/w chitosan and 0.5%w/w polycarbophil and was characterized for drug content, pH, percentage transmittance, globule size, zeta potential, and PDI. The composition (%w/w) of the optimized olanzapine nanoemulsion was capmul MCM, tween 80, and a mixture of 1:1 ratio of polyethylene glycol 400 and ethanol, and aqueous phase in a ratio of 15:35:17.5:32.5. The optimized olanzapine nanoemulsion exhibited a high diffusion coefficient and no nasal cilio-toxicity. The drug release followed the Higuchi model. The optimized nanoemulsions were found to be stable for 3 months.

  9. INTRANASAL LIPOSOMES : AN APPROACH FOR DRUG DELIVERY TO BRAIN

    Directory of Open Access Journals (Sweden)

    Mr. Jatin B. Trivedi

    2012-05-01

    Full Text Available Targeting drug molecules to brain is one of the most challenging research areas in pharmaceuticalsciences. Drugs that are effective against diseases in the CNS and reach the brain via the bloodcompartment must pass the BBB. The blood-brain barrier (BBB represents an insurmountable obstaclefor a large number of drugs, including antibiotics, anti-neoplastic agents, and a variety of central nervoussystem (CNS-active drugs. Therefore, various strategies have been proposed to improve the delivery ofdifferent drugs to this tissue which includes liposomes, colloidal drug carriers, micelles, chimericpeptide technology, intranasal and olfactory route of administration and nano technology. The discoveryof liposome or lipid vesicle emerged from self forming enclosed lipid bi-layer upon hydration; liposomedrug delivery systems have played a significant role in formulation of potent drug to improvetherapeutics Liposomes have been investigated as carriers of various pharmacologically active agentssuch as antineoplastic, antimicrobial drugs, chelating agents, steroids, vaccines, and genetic materials.Liposomes provide an efficient drug delivery system because they can alter the pharmacokinetics andpharmacodynamics of the entrapped drugs. Liposomes have been widely used for brain delivery in vivo.Nowadays, the nasal route for systemic drug delivery has gained great interest. It provides severaladvantages over other routes of drug administrations, which includes rapid absorption, avoids intestinaland hepatic presystemic disposition and high potential for drug transfer to the CSF. Moreover, the nasalroute is a potential alternative route for systemic availability of drugs restricted to intravenousadministration, viz. peptide and protein drugs and vaccines. As well, intranasal route has also beensuccessfully exploited for bypassing the blood brain barrier [BBB] and subsequently delivering drugmolecules to central nervous system [CNS].

  10. Plasma oxytocin concentrations following MDMA or intranasal oxytocin in humans.

    Science.gov (United States)

    Kirkpatrick, Matthew G; Francis, Sunday M; Lee, Royce; de Wit, Harriet; Jacob, Suma

    2014-08-01

    MDMA (±3,4-methylenedioxymethamphetamine, 'ecstasy') is reportedly used recreationally because it increases feelings of sociability and interpersonal closeness. Prior work suggests that the pro-social effects of MDMA may be mediated by release of oxytocin. A direct examination of plasma levels of oxytocin after acute doses of oxytocin and MDMA, in the same individuals, would provide further evidence for the idea that MDMA produces its pro-social effects by increasing oxytocin. Fourteen healthy MDMA users participated in a 4-session, double-blind study in which they received oral MDMA (0.75 and 1.5mg/kg), intranasal oxytocin (20IU or 40IU), and placebo. Plasma oxytocin concentrations, as well as cardiovascular and subjective effects were assessed before and at several time points after drug administration. MDMA (1.5mg/kg only) increased plasma oxytocin levels to a mean peak of 83.7pg/ml at approximately 90-120min, compared to 18.6pg/ml after placebo. Intranasal oxytocin (40IU, but not 20IU) increased plasma oxytocin levels to 48.0pg/ml, 30-60min after nasal spray administration. MDMA dose-dependently increased heart rate, blood pressure, feelings of euphoria (e.g., 'High' and 'Like Drug'), and feelings of sociability, whereas oxytocin had no cardiovascular or subjective effects. The subjective and cardiovascular responses to MDMA were not related to plasma oxytocin levels, although the N was small for this analysis. Future studies examining the effects of oxytocin antagonists on responses to MDMA will help to determine the mechanism by which MDMA produces pro-social effects.

  11. Thermoreversible nanoethosomal gel for the intranasal delivery of Eletriptan hydrobromide.

    Science.gov (United States)

    Shelke, Santosh; Shahi, Sadhana; Jadhav, Kiran; Dhamecha, Dinesh; Tiwari, Roshan; Patil, Hemlata

    2016-06-01

    The objective of the current study was to formulate and characterize thermoreversible gel of Eletriptan Hydrobromide for brain targeting via the intranasal route. Ethosomes were prepared by 3(2) factorial design with two independent variables (concentration of soya lecithin and ethanol) and two response variables [percent entrapment efficiency and vesicle size (nm)] using ethanol injection method. Formulated ethosomes were evaluated for preliminary microscopic examination followed by percent drug entrapment efficiency, vesicle size analysis, zeta potential, polydispersibility index and Transmission electron microscopy (TEM). TEM confirms spherical morphology of ethosomes, whereas Malvern zeta sizer confirms that the vesicle size was in the range of 191 ± 6.55-381.3 ± 61.0 nm. Ethosomes were incorporated in gel using poloxamer 407 and carbopol 934 as thermoreversible and mucoadhesive polymers, respectively. Ethosomal gels were evaluated for their pH, viscosity, mucoadhesive strength, in vitro drug release and ex vivo drug permeation through the sheep nasal mucosa. Mucoadhesive strength and pH was found to be 4400 ± 45 to 5500 ± 78.10 dynes/cm(2) and 6.0 ± 0.3 to 6.2 ± 0.1, respectively. In-vitro drug release from the optimized ethosomal gel formulation (G4) was found to be almost 100 % and ex vivo permeation of 4980 µg/ml with a permeability coefficient of 11.94 ± 0.04 × 10(-5) cm/s after 24 h. Histopathological study of the nasal mucosa confirmed non-toxic nature of ethosomal gels. Formulated EH loaded ethosomal thermoreversible gel could serve as the better alternative for the brain targeting via the intranasal route which in turn could subsequently improve its bioavailability.

  12. Buccal midazolam spray as an alternative to intranasal route for conscious sedation in pediatric dentistry.

    Science.gov (United States)

    Chopra, Radhika; Mittal, Meenu; Bansal, Kalpana; Chaudhuri, Payal

    2013-01-01

    To evaluate the acceptance of midazolam spray through buccal route as compared to intranasal route and compare the efficacy of the drug through both the routes. 30 patients aged 2-8 years with Grade I or II Frankl's Behaviour Rating Scale were selected who required similar treatment under local anesthesia on two teeth. Midazolam spray was administered randomly through buccal or intranasal routes for the two appointments. Scoring was done for the acceptance of drug and Houpt's score was recorded for the behaviour of patients during the treatment. Acceptance of drug through buccal route was significantly better than the intranasal route (p 0.05). Midazolam spray can be effectively used through the buccal mucosa in children who give poor compliance with the intranasal administration.

  13. Intranasal epidermoid cyst causing upper airway obstruction in three brachycephalic dogs.

    Science.gov (United States)

    Murgia, D; Pivetta, M; Bowlt, K; Volmer, C; Holloway, A; Dennis, R

    2014-08-01

    This case report describes three brachycephalic dogs with intranasal epidermoid cysts that were causing additional upper airway obstruction. Although epidermoid cysts have been described in several locations in dogs, to the authors' knowledge intranasal epidermoid cysts have not been previously reported. All dogs had mucopurulent to haemorrhagic nasal discharge. Magnetic resonance imaging of the head revealed the presence of unilateral or bilateral intranasal cystic lesions obstructing the nasal cavities partially or completely, with atrophy of the ipsilateral nasal turbinates. The cystic lesions were surgically excised in all dogs using a modified lateral alveolar mucosal approach to the affected nasal cavity. Aerobic, anaerobic and fungal culture of the cystic contents were negative and histology of the excised tissue was consistent with a benign intranasal epidermoid cyst in each dog. Upper airway obstruction was clinically improved in two dogs.

  14. Intravenous ketamine plus midazolam is superior to intranasal midazolam for emergency paediatric procedural sedation

    OpenAIRE

    Acworth, J; Purdie, D.; Clark, R

    2001-01-01

    Objectives—This study compared intranasal midazolam (INM) with a combination of intravenous ketamine and intravenous midazolam (IVKM) for sedation of children requiring minor procedures in the emergency department.

  15. Enhanced brain targeting efficiency of intranasally administered plasmid DNA: an alternative route for brain gene therapy.

    Science.gov (United States)

    Han, In-Kwon; Kim, Mi Young; Byun, Hyang-Min; Hwang, Tae Sun; Kim, Jung Mogg; Hwang, Kwang Woo; Park, Tae Gwan; Jung, Woon-Won; Chun, Taehoon; Jeong, Gil-Jae; Oh, Yu-Kyoung

    2007-01-01

    Recently, nasal administration has been studied as a noninvasive route for delivery of plasmid DNA encoding therapeutic or antigenic genes. Here, we examined the brain targeting efficiency and transport pathways of intranasally administered plasmid DNA. Quantitative polymerase chain reaction (PCR) measurements of plasmid DNA in blood and brain tissues revealed that intranasally administered pCMVbeta (7.2 kb) and pN2/CMVbeta (14.1 kb) showed systemic absorption and brain distribution. Following intranasal administration, the beta-galactosidase protein encoded by these plasmids was significantly expressed in brain tissues. Kinetic studies showed that intranasally administered plasmid DNA reached the brain with a 2,595-fold higher efficiency than intravenously administered plasmid DNA did, 10 min post-dose. Over 1 h post-dose, the brain targeting efficiencies were consistently higher for intranasally administered plasmid DNA than for intravenously administered DNA. To examine how plasmid DNA enters the brain and moves to the various regions, we examined tissues from nine brain regions, at 5 and 10 min after intranasal or intravenous administration of plasmid DNA. Intravenously administered plasmid DNA displayed similar levels of plasmid DNA in the nine different regions, whereas, intranasally administered plasmid DNA exhibited different levels of distribution among the regions, with the highest plasmid DNA levels in the olfactory bulb. Moreover, plasmid DNA was mainly detected in the endothelial cells, but not in glial cells. Our results suggest that intranasally applied plasmid DNA may reach the brain through a direct route, possibly via the olfactory bulb, and that the nasal route might be an alternative method for efficiently delivering plasmid DNA to the brain.

  16. Comparative pharmacokinetics of single doses of doxylamine succinate following intranasal, oral and intravenous administration in rats.

    Science.gov (United States)

    Pelser, Andries; Müller, Douw G; du Plessis, Jeanetta; du Preez, Jan L; Goosen, Colleen

    2002-09-01

    The intranasal route of administration provides a potential useful way of administering a range of systemic drugs. In order to assess the feasibility of this approach for the treatment of nausea and vomiting, doxylamine succinate was studied in rats for the pharmacokinetics (AUC, C(max), t(max)) following intranasal, oral and intravenous administrations. Subjects (six male Sprague-Dawley rats per time interval for each route of administration) received 2-mg doses of doxylamine succinate orally and I-mg doses intranasally and intravenously, respectively. The various formulations were formulated in isotonic saline (0.9% w/v) at 25 +/- 1 degrees C. Doxylamine succinate concentrations in plasma were determined with a high-performance liquid chromatographic assay and a liquid-liquid extraction procedure. Intranasal and oral bioavailabilities were determined from AUC values relative to those after intravenous dosing. Intranasal bioavailability was greater than that of oral doxylamine succinate (70.8 vs 24.7%). The intranasal and oral routes of administration differed significantly from the intravenous route of administration. Peak plasma concentration (C(max)) was 887.6 ng/ml (S.D. 74.4), 281.4 ng/ml (S.D. 24.6) and 1296.4 ng/ml (S.D. 388.9) for the intranasal, oral and intravenous routes, respectively. The time to achieve C(max) for the intranasal route (t(max)=0.5 h) was faster than for the oral route (t(max)=1.5 h), but no statistically significant differences between the C(max) values were found using 95% confidence intervals. The results of this study show that doxylamine succinate is rapidly and effectively absorbed from the nasal mucosa.

  17. The rostral migratory stream plays a key role in intranasal delivery of drugs into the CNS.

    Directory of Open Access Journals (Sweden)

    Robert A Scranton

    Full Text Available BACKGROUND: The blood brain barrier (BBB is impermeable to most drugs, impeding the establishment of novel neuroprotective therapies and strategies for many neurological diseases. Intranasal administration offers an alternative path for efficient drug delivery into the CNS. So far, the anatomical structures discussed to be involved in the transport of intranasally administered drugs into the CNS include the trigeminal nerve, olfactory nerve and the rostral migratory stream (RMS, but the relative contributions are debated. METHODS AND FINDINGS: In the present study we demonstrate that surgical transection, and the resulting structural disruption of the RMS, in mice effectively obstructs the uptake of intranasally administered radioligands into the CNS. Furthermore, using a fluorescent cell tracer, we demonstrate that intranasal administration in mice allows agents to be distributed throughout the entire brain, including olfactory bulb, hippocampus, cortex and cerebellum. CONCLUSIONS: This study provides evidence of the vital role the RMS has in the CNS delivery of intranasally administered agents. The identification of the RMS as the major access path for intranasally administered drugs into the CNS may contribute to the development of treatments that are tailored for efficient transport within this structure. Research into the RMS needs to continue to elucidate its limitations, capabilities, mechanisms of transport and potential hazards before we are able to advance this technique into human research.

  18. Local Th17/IgA immunity correlate with protection against intranasal infection with Streptococcus pyogenes.

    Science.gov (United States)

    Mortensen, Rasmus; Christensen, Dennis; Hansen, Lasse Bøllehuus; Christensen, Jan Pravsgaard; Andersen, Peter; Dietrich, Jes

    2017-01-01

    Streptococcus pyogenes (group A streptococcus, GAS) is responsible for a wide array of infections. Respiratory transmission via droplets is the most common mode of transmission but it may also infect the host via other routes such as lesions in the skin. To advance the development of a future vaccine against GAS, it is therefore important to investigate how protective immunity is related to the route of vaccine administration. To explore this, we examined whether a parenterally administered anti-GAS vaccine could protect against an intranasal GAS infection or if this would require locally primed immunity. We foundd that a parenteral CAF01 adjuvanted GAS vaccine offered no protection against intranasal infection despite inducing strong systemic Th1/Th17/IgG immunity that efficiently protected against an intraperitoneal GAS infection. However, the same vaccine administered via the intranasal route was able to induce protection against repeated intranasal GAS infections in a murine challenge model. The lack of intranasal protection induced by the parenteral vaccine correlated with a reduced mucosal recall response at the site of infection. Taken together, our results demonstrate that locally primed immunity is important for the defense against intranasal infection with Streptococcus pyogenes.

  19. [Pleuropulmonary manifestations of amebiasis].

    Science.gov (United States)

    Mbaye, P S; Koffi, N; Camara, P; Burgel, P R; Hovette, P; Klotz, F

    1998-12-01

    Amibiasis is the third leading cause of death due to parasitic infections in the world. Amibiasis is endemic in the warm regions of the world with deficient hygiene and socio-economic situations. Entamoeba histolytica is the causal agent of invasive amibiasis, unlike Entamoeba dispar which is not a pathogen for humans. Amibian colitis and amibian abscess of the liver are the most frequent intestinal and extra-intestinal manifestations. Pleuropulmonary complications almost always occur in patients with a liver abscess, the intrathoracic contamination via transphrenic dissemination predominating. Respiratory signs are inaugural in 80% of the cases. Pleuropulmonary ambiasis designates the localization of the amibian infestation, but the clinical expression may vary: pneumonia, lung abscess, pleurisy, hepatobronchial fistulization and more infrequently pulmonary embolism. The preferential localization is the right hemithorax related to abscess in the right lobe of the liver. Left lobe abscesses lead to left-sided pleuropulmonary complications with the risk of rupture into the pericardium. Chocolate-colored pus from a pleural or abscess puncture or vomitus strongly suggests the diagnosis, which is confirmed by highly-positive serology. Metronidazole is the treatment of choice, providing cure without sequellae. In Africa, mortality and morbidity due to ambiasis are high. In Abidjan, 92% of cured patients have sequella, and mortality reaches 15%, the consequence of late diagnosis.

  20. Intranasal epidermal growth factor treatment rescues neonatal brain injury

    Science.gov (United States)

    Scafidi, Joseph; Hammond, Timothy R.; Scafidi, Susanna; Ritter, Jonathan; Jablonska, Beata; Roncal, Maria; Szigeti-Buck, Klara; Coman, Daniel; Huang, Yuegao; McCarter, Robert J.; Hyder, Fahmeed; Horvath, Tamas L.; Gallo, Vittorio

    2014-02-01

    There are no clinically relevant treatments available that improve function in the growing population of very preterm infants (less than 32 weeks' gestation) with neonatal brain injury. Diffuse white matter injury (DWMI) is a common finding in these children and results in chronic neurodevelopmental impairments. As shown recently, failure in oligodendrocyte progenitor cell maturation contributes to DWMI. We demonstrated previously that the epidermal growth factor receptor (EGFR) has an important role in oligodendrocyte development. Here we examine whether enhanced EGFR signalling stimulates the endogenous response of EGFR-expressing progenitor cells during a critical period after brain injury, and promotes cellular and behavioural recovery in the developing brain. Using an established mouse model of very preterm brain injury, we demonstrate that selective overexpression of human EGFR in oligodendrocyte lineage cells or the administration of intranasal heparin-binding EGF immediately after injury decreases oligodendroglia death, enhances generation of new oligodendrocytes from progenitor cells and promotes functional recovery. Furthermore, these interventions diminish ultrastructural abnormalities and alleviate behavioural deficits on white-matter-specific paradigms. Inhibition of EGFR signalling with a molecularly targeted agent used for cancer therapy demonstrates that EGFR activation is an important contributor to oligodendrocyte regeneration and functional recovery after DWMI. Thus, our study provides direct evidence that targeting EGFR in oligodendrocyte progenitor cells at a specific time after injury is clinically feasible and potentially applicable to the treatment of premature children with white matter injury.

  1. Rapid widespread distribution of intranasal naloxone for overdose prevention.

    Science.gov (United States)

    Madah-Amiri, Desiree; Clausen, Thomas; Lobmaier, Philipp

    2017-04-01

    Take home naloxone programs have been successful internationally in training bystanders to reverse an opioid overdose with naloxone, an opioid antagonist. A multi-site naloxone distribution program began in Norway in 2014 as part of a national overdose prevention strategy. The aim of this study was to a) describe the program, and b) present findings from the government-supported intervention. From July 2014 to December 2015, staff from multiple low-threshold facilities trained clients on how to use intranasal naloxone. Distribution occurred without an individual prescription or physician present. Questionnaires from initial and refill trainings were obtained, and distribution rates were monitored. There were 2056 naloxone sprays distributed from one of the 20 participating facilities, with 277 reports of successful reversals. Participants exhibited known risks for overdosing, with injecting (p=0.02, OR=2.4, 95% CI=1.14, 5.00) and concomitant benzodiazepine use (p=0.01, OR=2.6, 95% CI=1.31, 5.23) being significant predictors for having had high rates of previous overdoses. Suggested target coverage for large-scale programs was met, with an annual naloxone distribution rate of 144 per 100,000 population, as well as 12 times the cities mean annual number of opioid-related deaths. A government-supported multisite naloxone initiative appears to achieve rapid, high volume distribution of naloxone to an at-risk population. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  2. Intranasal Midazolam Sedation in a Pediatric Emergency Dental Clinic.

    Science.gov (United States)

    Peerbhay, Fathima; Elsheikhomer, Ahmed Mahgoub

    2016-01-01

    The purpose of this study was to compare the effectiveness and recovery times of 0.3 and 0.5 mg/kg intranasal midazolam (INM) administered with a mucosal atomizer device (MAD) in a pediatric emergency dental hospital clinic. One hundred eighteen children aged from 4 to 6 years were randomly administered either 0.3 or 0.5 mg/kg INM via an MAD in a triple-blinded randomized controlled trial. Sedation was achieved to some degree in 100% of the sample. The pulse rate and oxygen saturation were within the normal range in 99% of the patients. A burning sensation was reported in 9% of children. The recovery time of the 0.5 mg/kg group was statistically longer than that of the 0.3 mg/kg group (16.5 vs 18.8 minutes) but the difference was not clinically significant. The findings of this study show that 0.3 or 0.5 mg/kg doses of INM resulted in safe and effective sedation. The 0.5 mg/kg dose was more effective than the 0.3 mg/kg dose in reducing anxiety.

  3. Distribution of nimodipine in brain following intranasal administration in rats

    Institute of Scientific and Technical Information of China (English)

    Qi-zhi ZHANG; Xin-guo JIANG; Chun-hua WU

    2004-01-01

    AIM: To determine whether nasally applied nimodipine (NM) could improve its systemic bioavailability and be transported directly from the nasal cavity to the brain. METHODS: NM was administered nasally, intravenously (iv), and orally to male Sprague-Dawley rats. At different times post dose, blood, cerebrospinal fluid (CSF), and brain tissue samples were collected, and the concentrations of NM in the samples were analyzed by HPLC. RESULTS:Oral systemic bioavailability of NM in rats was 1.17 %, nasal dosing improved bioavailibility to 67.4 %. Following intranasal administration, NM concentrations in olfactory bulb (OB) within 30 min post dose were found significant higher than in the other brain tissues. However, similar NM levels in different brain regions were observed after iv injection. AUC in CSF and OB from the nasal route was 1.26 and 1.39 fold compared with the iv route, respectively.The brain-to-plasma AUC ratios were significantly higher after nasal administration than after iv administration (P<0.01). CONCLUSION: Nasally administered NM could markedly improve the bioavailability and a fraction of the NM dose could be transported into brain via the olfactory pathway in rats.

  4. Pharmacokinetic Modeling of Intranasal Scopolamine in Plasma Saliva and Urine

    Science.gov (United States)

    Wu, L.; Tam, V. H.; Chow, D. S. L.; Putcha, L.

    2015-01-01

    An intranasal gel dosage formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness (SMS). The bioavailability and pharmacokinetics (PK) were evaluated under IND (Investigational New Drug) guidelines. The aim of the project was to develop a PK model that can predict the relationships among plasma, saliva and urinary scopolamine concentrations using data collected from the IND clinical trial protocol with INSCOP. Twelve healthy human subjects were administered at three dose levels (0.1, 0.2 and 0.4 mg) of INSCOP. Serial blood, saliva and urine samples were collected between 5 min to 24 h after dosing and scopolamine concentrations were measured by using a validated LC-MS-MS assay. PK compartmental models, using actual dosing and sampling time, were established using Phoenix (version 1.2). Model selection was based on a likelihood ratio test on the difference of criteria (-2LL (i.e. log-likelihood ratio test)) and comparison of the quality of fit plots. The results: Predictable correlations among scopolamine concentrations in compartments of plasma, saliva and urine were established, and for the first time the model satisfactorily predicted the population and individual PK of INSCOP in plasma, saliva and urine. The model can be utilized to predict the INSCOP plasma concentration by saliva and urine data, and it will be useful for monitoring the PK of scopolamine in space and other remote environments using non-invasive sampling of saliva and/or urine.

  5. Bioavailability enhancement of verapamil HCl via intranasal chitosan microspheres.

    Science.gov (United States)

    Abdel Mouez, Mamdouh; Zaki, Noha M; Mansour, Samar; Geneidi, Ahmed S

    2014-01-23

    Chitosan microspheres are potential drug carriers for maximizing nasal residence time, circumventing rapid mucociliary clearance and enhancing nasal absorption. The aim of the present study was to develop and characterize chitosan mucoadhesive microspheres of verapamil hydrochloride (VRP) for intranasal delivery as an alternative to oral VRP which suffers low bioavailability (20%) due to extensive first pass effect. The microspheres were produced using a spray-drying and precipitation techniques and characterized for morphology (scanning electron microscopy), particle size (laser diffraction method), drug entrapment efficiency, thermal behavior (differential scanning calorimetry) and crystallinity (X-ray diffractometric studies) as well as in vitro drug release. Bioavailability of nasal VRP microspheres was studied in rabbits and the results were compared to those obtained after nasal, oral and intravenous administration of VRP solution. Results demonstrated that the microspheres were spherical with size 21-53 μm suitable for nasal deposition. The spray-drying technique was superior over precipitation technique in providing higher VRP entrapment efficiency and smaller burst release followed by a more sustained one over 6h. The bioavailability study demonstrated that the nasal microspheres exhibited a significantly higher bioavailability (58.6%) than nasal solution of VRP (47.8%) and oral VRP solution (13%). In conclusion, the chitosan-based nasal VRP microspheres are promising for enhancing VRP bioavailability by increasing the nasal residence time and avoiding the first-pass metabolism of the drug substance. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Influence of intranasal and carotid cooling on cerebral temperature balance and oxygenation

    Directory of Open Access Journals (Sweden)

    Lars eNybo

    2014-02-01

    Full Text Available The present study evaluated the influence of intranasal cooling with balloon catheters, increased nasal ventilation, or percutaneous cooling of the carotid arteries on cerebral temperature balance and oxygenation in six healthy male subjects. Aortic arch and internal jugular venous blood temperatures were measured to assess the cerebral heat balance and corresponding paired blood samples were obtained to evaluate cerebral metabolism and oxygenation at rest, following 60 min of intranasal cooling, 5 min of nasal ventilation, and 15 min with carotid cooling. Intranasal cooling induced a parallel drop in jugular venous and arterial blood temperatures by 0.30 ± 0.08 ºC (mean ± SD, whereas nasal ventilation and carotid cooling failed to lower the jugular venous blood temperature. The magnitude of the arterio-venous temperature difference across the brain remained unchanged at - 0.33 ± 0.05 ºC following intranasal and carotid cooling, but increased to - 0.44 ± 0.11 ºC (P< 0.05 following nasal ventilation. Calculated cerebral capillary oxygen tension was 43 ± 3 mmHg at rest and remained unchanged during intranasal and carotid cooling, but decreased to 38 ± 2 mmHg (P< 0.05 following increased nasal ventilation. In conclusion, percutaneous cooling of the carotid arteries and intranasal cooling with balloon catheters are insufficient to influence cerebral oxygenation in normothermic subjects as the cooling rate is only 0.3 ºC per hour and neither intranasal nor carotid cooling is capable of inducing selective brain cooling.

  7. Suburban amoebiasis. CT and US findings and percutaneous treatment of amoebic liver abscess; Amebiasi sub-urbana: aspetti diagnostici con tomografia computerizzata ed ecografia e trattamento percutaneo degli ascessi amebici del fegato

    Energy Technology Data Exchange (ETDEWEB)

    Salzano, A.; De Rosa, A. [Ospedale Loreto Mare, Naples (Italy). Servizio di Radiologia; Rossi, E.; Carbone, M.; Mondillo, F. [Naples Univ. II, Naples (Italy).Dipt. di Scienze Biomorfologiche e Funzionali, Servizio di Diagnostica per Immagini; Tuccillo, M. [Azienda Ospedaliera di Rilievo Nazionale A. Cardarelli, Naples (Italy). Servizio di Radiologia; Capuano, N. [Ospedale Loreto Mare, Naples (Italy). Div. di Chirurgia; Nunziata, A. [Naples Univ. II, Naples (Italy). Ist. di Radiologia

    2000-03-01

    The study reports ultrasonography and computerise tomography findings in 16 patients with amoebic abscesses, 12 of whom lived in a temperate peripheral area north-east of Naples (Italy). All patients have a clinical-diagnostic condition called sub-urban amoebiasis. The personal experience with the US guided therapeutic drainage of amoebic abscess with repeated cavity washing, which is important for positive parasitology. Combined US and CT assessment facilitated the diagnosis of amoebiasis and its differentiation from pyogenic abscess and hepatoma. [Italian] La colonizzazione epatica rappresenta la localizzazione piu' comune dell'amebiasi extraintestinale e gli ascessi epatici ne costituiscono la manifestazione piu' frequente sviluppandosi nel 3-9 % dei pazienti affetti da infezione parassitaria. Diversi studi confermano che la terapia medica dell'amebiasi risulta piu' efficace quando viene associato il drenaggio percutaneo degli ascessi epatici con piu' rapida guarigione clinica e risposta favorevole dell'organismo. Scopo del presente lavoro e' di descrivere gli aspetti ecografici e di tomografia computerizzata degli ascessi amebici in un gruppo di 16 pazienti, 12 dei quali residenti in zona temperata e periferica di una vasta area a nord-est di Napoli presentandosi con caratteristico e raro quadro clinico-diagnostico definito amebiasi sub-urbana. Si discute infine l'esperienza personale del drenaggio terapeutico sotto guida ecografica dell'ascesso con tecnica del lavaggio ripetuto dalla cavita', importante ai fini della positivita' dell'esame. L'associazione dei reperti tipici ecografici e TC ha consentito la diagnosi agevole dell'amebiasi differenziandola dall'ascesso piogenico e dall'epatoma.

  8. Comparison of desmopressin (DDAVP tablet and intranasal spray in the treatment of central diabetes insipidus

    Directory of Open Access Journals (Sweden)

    "Bagher Larijani

    2005-07-01

    Full Text Available Desmoperssin is the drug of choice for treatment of central diabetes insipidus and most commonly it is used as intranasal spray. In this study, efficacy and side effects of oral desmopressin was compared with the intranasal spray. This study was before -after clinical trial on 14 outpatients (9 F, 5 M, age 14 -50 Y with central diabetes insipidus who had been treated with intranasal spray of desmopressin previously. Weight, pulse rate and blood pressure (sitting -standing, biochemical profile, serum electrolytes, 24h urine volume, specific gravity of urine and LFT was measured before and after 1 month study. Starting dose for each patient was one oral tablet of DDAVP (0.1 mg per 8 hours. Paired Samples T-Test was used for data analysis. No clinically significant changes were found as regard to weight, pulse rate, blood pressure, blood chemistry, electrolyte and urinalysis. Single reported adverse effect was headache (43% in tablet group and dyspnea (7% in spray group. Both dosage forms were able to control diurnal polyuria and nocturnal polyuria. The antidiuretic dose - equivalence ratio for intranasal to oral desmopressin was 1: 18. Spray was superior in terms of rapid onset of action and duration of antidiuretic action in 100% and 78% of cases (not significant, respectively. Tablets were more available and much more easily consumed as reported by patients, in 86% (P=0.0006. Treatment with tablets offers a good alternative to the intranasal route, especially in patients with chronic rhinitis or common cold and similar conditions.

  9. Intranasal Rapamycin Rescues Mice from Staphylococcal Enterotoxin B-Induced Shock

    Directory of Open Access Journals (Sweden)

    Teresa Krakauer

    2012-09-01

    Full Text Available Staphylococcal enterotoxin B (SEB and related exotoxins produced by Staphylococcus aureus are potent activators of the immune system and cause toxic shock in humans. Currently there is no effective treatment except for the use of intravenous immunoglobulins administered shortly after SEB exposure. Intranasal SEB induces long-lasting lung injury which requires prolonged drug treatment. We investigated the effects of rapamycin, an immunosuppressive drug used to prevent graft rejection, by intranasal administration in a lethal mouse model of SEB-induced shock. The results show that intranasal rapamycin alone delivered as late as 17 h after SEB protected 100% of mice from lethal shock. Additionally, rapamycin diminished the weight loss and temperature fluctuations elicited by SEB. Intranasal rapamycin attenuated lung MCP-1, IL-2, IL-6, and IFNγ by 70%, 30%, 64%, and 68% respectively. Furthermore, short courses (three doses of rapamycin were sufficient to block SEB-induced shock. Intranasal rapamycin represents a novel use of an immunosuppressant targeting directly to site of toxin exposure, reducing dosages needed and allowing a wider therapeutic window.

  10. Early influence of bilateral turbinoplasty combined with septoplasty on intranasal air conditioning.

    Science.gov (United States)

    Lindemann, Joerg; Keck, Tilman; Leiacker, Richard; Dzida, Rene; Wiesmiller, Kerstin

    2008-01-01

    Too extensive resection of the inferior turbinates (ITs) during nasal surgery leads to a severely disturbed intranasal air conditioning. Data comparing nasal air conditioning before and after turbinoplasty in nasal surgery are still lacking. The aim of this study was to determine the early effect of bilateral turbinoplasty combined with septoplasty on intranasal heating and humidification. Twelve patients were included into this prospective study. In one-half of the patients a bilateral turbinoplasty of the IT during nasal surgery was performed, in the other half no surgery on the IT was performed. Intranasal air temperature and humidity were measured before and after surgery. A combined miniaturized thermocouple and a humidity sensor were used for simultaneous in vivo intranasal measurements. There were no statistically significant differences in temperature and humidity values between the two study groups before surgery (p > 0.05). In both groups, the postoperative temperature and humidity values were statistically significantly higher compared with the preoperative ones (p air conditioning was improved after surgery. A carefully performed and conservative reduction of the IT in nasal surgery seems to even improve intranasal air conditioning.

  11. Evaluation of the effectiveness and safety of chitosan derivatives as adjuvants for intranasal vaccines.

    Science.gov (United States)

    Kobayashi, Takashi; Fukushima, Kenji; Sannan, Takanori; Saito, Noriko; Takiguchi, Yasuyuki; Sato, Yuko; Hasegawa, Hideki; Ishikawa, Koichi

    2013-04-01

    Intranasal immunization is currently used to deliver live virus vaccines such as influenza. However, to develop an intranasal vaccine to deliver inactivated virus, a safe and effective adjuvant is necessary to enhance the mucosal immune response. Here, we demonstrate the effectiveness of a chitosan microparticle (1-20 μm, 50 kDa, degree of deacetylation=85%) and a cationized chitosan (1000 kDa, degree of deacetylation=85%) derived from natural crab shells as adjuvants for an intranasal vaccine candidate. We examined the effectiveness of chitosan derivatives as an adjuvant by co-administering them with ovalbumin (OVA) intranasally in BALB/c mice, polymeric Ig receptor knockout (pIgR-KO) mice, and cynomolgus monkeys (Macaca fascicularis). pIgR-KO mice were used to evaluate S-IgA production on the mucosal surface without nasal swab collection. Administration of OVA with chitosan microparticles or cationized chitosan induced a high OVA-specific IgA response in the serum of pIgR-KO mice and a high IgG response in the serum of BALB/c mice and cynomolgus monkeys. We also found that administration of chitosan derivatives did not have a detrimental effect on cynomolgus monkeys as determined by complete blood count, blood chemistries, and gross pathology results. These results suggest that chitosan derivatives are safe and effective mucosal adjuvants for intranasal vaccination.

  12. ROLE OF INTRANASAL STEROIDAL SPRAY IN SEASONAL ALLERGIC RHINITIS WITH OCULAR SYMPTOMS

    Directory of Open Access Journals (Sweden)

    Vineel Muppidi

    2017-06-01

    Full Text Available BACKGROUND The eye is especially susceptible to the symptoms of allergic rhinitis, itching (pruritus, tearing (epiphora and redness (erythema because it lacks a mechanical barrier that could prevent the deposition of allergens, such as pollen on the conjunctival surface. These ocular symptoms have been described as examples of the type 1 immediate hypersensitivity reaction. A number of recently published clinical studies apparently support the positive effect of intranasal steroidal sprays on ocular allergy symptoms. The aim of the study is to evaluate the role of intranasal steroids in relieving ocular symptoms in allergic rhinitis. MATERIALS AND METHODS 60 subjects who had seasonal allergic rhinitis with ocular symptoms came to Outpatient Department of Chalmeda Anand Rao Hospital in the year 2015-2016. Randomly, each intranasal steroid is given to 12 patients to a total of 60 patients for 4 weeks 2 puffs in each nostril twice daily and the clinical response is observed. RESULTS A subjective improvement in ocular symptoms was observed in 11 of the 12 patients treated with fluticasone furoate, 8 of 12 patients with fluticasone propionate, 7 of the 12 patients with mometasone furoate, 6 of the 12 patients with beclomethasone and 6 of the 12 patients with budesonide. CONCLUSION Intranasal corticosteroids, which are used for seasonal allergic rhinitis with ocular symptoms are effective in controlling of ocular symptoms. Among these, intranasal corticosteroids, which are used for allergic rhinitis, fluticasone furoate is more effective in relieving ocular symptoms in our study.

  13. [Pre-anesthetic medication with intranasal dexmedetomidine and oral midazolam as an anxiolytic. A clinical trial].

    Science.gov (United States)

    Linares Segovia, B; García Cuevas, M A; Ramírez Casillas, I L; Guerrero Romero, J F; Botello Buenrostro, I; Monroy Torres, R; Ramírez Gómez, X S

    2014-10-01

    Dexmedetomidine is a pharmacological option for sedation in children. In this study, the efficacy of intranasal dexmedetomidine to reduce preoperative anxiety in pediatric patients is compared with that of oral midazolam. A prospective, randomized, double-blind, controlled trial was conducted on children 2-12 years of age, randomly assigned to one of the following two groups: group A received premedication with oral midazolam and intranasal placebo, group B received intranasal dexmedetomidine and oral placebo. Anxiety was assessed with the modified Yale scale, and a risk analysis and number needed to treat was performed. A total of 108 patients were included, 52 (48.1%) treated with dexmedetomidine, and 56 (51.9%) with midazolam. Anxiety was less frequent in the dexmedetomidine group at 60minutes (P=.001), induction (p=.04), and recovery (P=.0001). Risk analysis showed that dexmedetomidine reduced the risk of anxiety by 28% (RAR=0.28, 95% CI; 0.12 to 0.43) and to prevent one case of anxiety, four patients need to be treated with intranasal dexmedetomidine (NNT=4, 95% CI: 3-9).Changes in heart rate, mean arterial pressure, and oxygen saturation, were statistically significant in the dexmedetomidine group, with no clinical consequences. There were no cases of bradycardia, hypotension or oxygen desaturation. Intranasal dexmedetomidine premedication is more effective than oral midazolam to reduce preoperative anxiety in pediatric patients. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  14. Position on zinc delivery to olfactory nerves in intranasal insulin phase I-III clinical trials.

    Science.gov (United States)

    Hamidovic, A

    2015-11-01

    Zinc in pancreatic insulin is essential for processing and action of the peptide, while in commercial preparations zinc promotes hexameric structure and prevents aggregate formation. In 2002, for the first time, insulin was delivered to humans intranasally with resulting cerebrospinal fluid insulin increases, but steady peripheral insulin levels. The novel method of increasing brain insulin levels without changes in the periphery resulted in an expansion of brain insulin research in clinical trials. As pre-clinical research has shown that brain insulin modulates a number functions, including food cravings and eating behavior, learning and memory functions, stress and mood regulation; realization of beneficial effects of insulin in modulating these functions in clinical populations became a possibility with the new direct-to-brain insulin delivery methodology. However, zinc, being integral to insulin structure and function, is neurotoxic, and has resulted in adverse effects to human health. In the last century, intranasal zinc was given preventively during the time of polio outbreak, and in the 21st century intranasal zinc was widely used over the counter to prevent common cold. In both cases, patients experienced partial or complete loss of smell. This paper is the first one to analyze zinc salts and concentrations of those two epidemiological adversities and directly compare formulations distributed to the public with animal toxicity data. The information gained from animal and epidemiological data provides a foundation for the formation of opinion given in this paper regarding safety of intranasal zinc in emerging clinical trials with intranasal insulin.

  15. Intranasal insulin enhances brain functional connectivity mediating the relationship between adiposity and subjective feeling of hunger.

    Science.gov (United States)

    Kullmann, Stephanie; Heni, Martin; Veit, Ralf; Scheffler, Klaus; Machann, Jürgen; Häring, Hans-Ulrich; Fritsche, Andreas; Preissl, Hubert

    2017-05-09

    Brain insulin sensitivity is an important link between metabolism and cognitive dysfunction. Intranasal insulin is a promising tool to investigate central insulin action in humans. We evaluated the acute effects of 160 U intranasal insulin on resting-state brain functional connectivity in healthy young adults. Twenty-five lean and twenty-two overweight and obese participants underwent functional magnetic resonance imaging, on two separate days, before and after intranasal insulin or placebo application. Insulin compared to placebo administration resulted in increased functional connectivity between the prefrontal regions of the default-mode network and the hippocampus as well as the hypothalamus. The change in hippocampal functional connectivity significantly correlated with visceral adipose tissue and the change in subjective feeling of hunger after intranasal insulin. Mediation analysis revealed that the intranasal insulin induced hippocampal functional connectivity increase served as a mediator, suppressing the relationship between visceral adipose tissue and hunger. The insulin-induced hypothalamic functional connectivity change showed a significant interaction with peripheral insulin sensitivity. Only participants with high peripheral insulin sensitivity showed a boost in hypothalamic functional connectivity. Hence, brain insulin action may regulate eating behavior and facilitate weight loss by modifying brain functional connectivity within and between cognitive and homeostatic brain regions.

  16. Blockade of STAT3 in T Cells Inhibits Germinal Center Reactions against Intranasal Allergens.

    Science.gov (United States)

    Choi, Garam; Chung, Yeonseok

    2016-05-01

    Understanding the developmental mechanisms of humoral immunity against intranasal antigens is essential for the development of therapeutic approaches against air-borne pathogens as well as allergen-induced pulmonary inflammation. Follicular helper T (Tfh) cells expressing CXCR5 are required for humoral immunity by providing IL-21 and ICOS costimulation to activated B cells. However, the regulation of Tfh cell responses against intranasal antigens remains unclear. Here, we found that the generation of Tfh cells and germinal center B cells in the bronchial lymph node against intranasal proteinase antigens was independent of TGF-β. In contrast, administration of STAT3 inhibitor STA-21 suppressed the generation of Tfh cells and germinal center B cells. Compared with wild-type OT-II T cells, STAT3-deficient OT-II T cells transferred into recipients lacking T cells not only showed significantly reduced frequency Tfh cells, but also induced diminished IgG as well as IgE specific for the intranasal antigens. Cotransfer study of wild-type OT-II and STAT3-deficient OT-II T cells revealed that the latter failed to differentiate into Tfh cells. These findings demonstrate that T cell-intrinsic STAT3 is required for the generation of Tfh cells to intranasal antigens and that targeting STAT3 might be an effective approach to ameliorate antibody-mediated pathology in the lung.

  17. Intranasal oxytocin enhances socially-reinforced learning in rhesus monkeys

    Directory of Open Access Journals (Sweden)

    Lisa A Parr

    2014-09-01

    Full Text Available There are currently no drugs approved for the treatment of social deficits associated with autism spectrum disorders (ASD. One hypothesis for these deficits is that individuals with ASD lack the motivation to attend to social cues because those cues are not implicitly rewarding. Therefore, any drug that could enhance the rewarding quality of social stimuli could have a profound impact on the treatment of ASD, and other social disorders. Oxytocin (OT is a neuropeptide that has been effective in enhancing social cognition and social reward in humans. The present study examined the ability of OT to selectively enhance learning after social compared to nonsocial reward in rhesus monkeys, an important species for modeling the neurobiology of social behavior in humans. Monkeys were required to learn an implicit visual matching task after receiving either intranasal (IN OT or Placebo (saline. Correct trials were rewarded with the presentation of positive and negative social (play faces/threat faces or nonsocial (banana/cage locks stimuli, plus food. Incorrect trials were not rewarded. Results demonstrated a strong effect of socially-reinforced learning, monkeys’ performed significantly better when reinforced with social versus nonsocial stimuli. Additionally, socially-reinforced learning was significantly better and occurred faster after IN-OT compared to placebo treatment. Performance in the IN-OT, but not Placebo, condition was also significantly better when the reinforcement stimuli were emotionally positive compared to negative facial expressions. These data support the hypothesis that OT may function to enhance prosocial behavior in primates by increasing the rewarding quality of emotionally positive, social compared to emotionally negative or nonsocial images. These data also support the use of the rhesus monkey as a model for exploring the neurobiological basis of social behavior and its impairment.

  18. Intranasal inhalation of oxytocin improves face processing in developmental prosopagnosia.

    Science.gov (United States)

    Bate, Sarah; Cook, Sarah J; Duchaine, Bradley; Tree, Jeremy J; Burns, Edwin J; Hodgson, Timothy L

    2014-01-01

    Developmental prosopagnosia (DP) is characterised by a severe lifelong impairment in face recognition. In recent years it has become clear that DP affects a substantial number of people, yet little work has attempted to improve face processing in these individuals. Intriguingly, recent evidence suggests that intranasal inhalation of the hormone oxytocin can improve face processing in unimpaired participants, and we investigated whether similar findings might be noted in DP. Ten adults with DP and 10 matched controls were tested using a randomized placebo-controlled double-blind within-subject experimental design (AB-BA). Each participant took part in two testing sessions separated by a 14-25 day interval. In each session, participants inhaled 24 IU of oxytocin or placebo spray, followed by a 45 min resting period to allow central oxytocin levels to plateau. Participants then completed two face processing tests: one assessing memory for a set of newly encoded faces, and one measuring the ability to match simultaneously presented faces according to identity. Participants completed the Multidimensional Mood Questionnaire (MMQ) at three points in each testing session to assess the possible mood-altering effects of oxytocin and to control for attention and wakefulness. Statistical comparisons revealed an improvement for DP but not control participants on both tests in the oxytocin condition, and analysis of scores on the MMQ indicated that the effect cannot be attributed to changes in mood, attention or wakefulness. This investigation provides the first evidence that oxytocin can improve face processing in DP, and the potential neural underpinnings of the findings are discussed alongside their implications for the treatment of face processing disorders.

  19. Intranasal midazolam administration enhances amnesic effect in rats.

    Science.gov (United States)

    Kadono, Takao; Kawano, Takashi; Yamanaka, Daiki; Tateiwa, Hiroki; Urakawa, Manami; Locatelli, Fabricio M; Yokoyama, Masataka

    2016-06-01

    Intranasal (i.n.) administration of midazolam has been shown to be effective and safe for its sedative, anxiolytic, and anticonvulsant effects. However, there has been no investigation on the influence of i.n. administration on midazolam-induced anterograde amnesia. In addition, although the potential of direct drug delivery from the nose to the central nervous system (CNS) has recently become a topic of great interest, it remains unclear whether this pathway is also involved after i.n. midazolam. In this study, we examined the efficacy and the underlying mechanism of i.n. administration compared with intramuscular (i.m.) administration on midazolam-induced amnesia in rats. Equivalent doses of 0.6 mg/kg midazolam were administered via either the i.m or the i.n. route. Anterograde amnesia was assessed by a contextual/cued fear conditioning test. Each animal was conditioned 20 min after drug administration and then tested for a freezing response 24 h later. Midazolam administration by either route produced a similar level of light sedation (minimum spontaneous activity). However, i.n. administration of midazolam induced significantly less freezing behavior compared with i.m. midazolam. Furthermore, in rats with disrupted electrical input from the olfactory epithelium after an olfactotoxicant 3-methylindole administration, the i.n.-mediated enhanced amnesic effect of midazolam was not observed. Our findings indicate that i.n midazolam could probably generate olfactory signals to the brain via benzodiazepine receptors and, compared with i.m. administration, can produce a more significant amnesic effect without alteration in sedative levels. Further clinical studies are warranted.

  20. Buccal, intranasal or intravenous lorazepam for the treatment of acute convulsions in children in Malawi: An open randomized trial

    Directory of Open Access Journals (Sweden)

    Samantha Lissauer

    2015-09-01

    Conclusions: Intravenous lorazepam effectively treats most childhood seizures in this setting. Intranasal and buccal routes are less effective but may be useful in pre-hospital care or when intravenous access cannot be obtained. Further studies comparing intranasal lorazepam to other benzodiazepines, or alternative doses by a non-intravenous route are warranted.

  1. Intranasal Dexmedetomidine for Procedural Sedation in Children, a Suitable Alternative to Chloral Hydrate.

    Science.gov (United States)

    Cozzi, Giorgio; Norbedo, Stefania; Barbi, Egidio

    2017-04-01

    Sedation is often required for children undergoing diagnostic procedures. Chloral hydrate has been one of the sedative drugs most used in children over the last 3 decades, with supporting evidence for its efficacy and safety. Recently, chloral hydrate was banned in Italy and France, in consideration of evidence of its carcinogenicity and genotoxicity. Dexmedetomidine is a sedative with unique properties that has been increasingly used for procedural sedation in children. Several studies demonstrated its efficacy and safety for sedation in non-painful diagnostic procedures. Dexmedetomidine's impact on respiratory drive and airway patency and tone is much less when compared to the majority of other sedative agents. Administration via the intranasal route allows satisfactory procedural success rates. Studies that specifically compared intranasal dexmedetomidine and chloral hydrate for children undergoing non-painful procedures showed that dexmedetomidine was as effective as and safer than chloral hydrate. For these reasons, we suggest that intranasal dexmedetomidine could be a suitable alternative to chloral hydrate.

  2. Comparison of Nanoemulsion and Aqueous Micelle Systems of Paliperidone for Intranasal Delivery.

    Science.gov (United States)

    Pidaparthi, Kartika; Suares, Divya

    2016-10-06

    The objective of the study was to develop and compare the efficiency of nanoemulsion and aqueous micelle system of Paliperidone on intranasal administration. Both the formulations were evaluated for physical parameters such as globule size, pH, viscosity, conductivity and in vitro drug release studies. The reduction in spontaneous motor activity of L-dopa and Carbidopa-treated Swiss Albino mice on intranasal administration of nanoemulsion and micellar system of Paliperidone was compared with plain drug suspension. Histopathological evaluation of formulation treated nasal mucosal membrane was performed. Nasal spray device was evaluated for spray pattern and volume per actuation. Globule size of micellar system and nanoemulsion was found to be 16.14 & 38.25 nm, respectively. In vitro release of drug from micellar system was found to be 1.8-fold higher than nanoemulsion. The loading of drug in nanoemulsion was found to be superior (2.5 mg/mL) when compared to micellar system (0.41 mg/mL). The spray pattern of micellar system and nanoemulsion from the device was elliptical and circular, respectively. The locomotor activity of L-dopa and Carbidopa-treated Swiss albino mice was found to be 1096.5±78.49, 551.5±13.43 and 535.5±24.75 counts/min in case of plain drug suspension, micellar system and nanoemulsion, respectively. The intranasal administration of developed formulations showed significant difference (p<0.01) in the locomotor activity when compared to intranasal administration of plain drug. Thus it can be concluded that both the developed formulations have shown improved in vivo activity on intranasal administration and pose great potential for delivery of Paliperidone through intranasal route.

  3. Intranasal mesenchymal stem cell treatment for neonatal brain damage: long-term cognitive and sensorimotor improvement.

    Directory of Open Access Journals (Sweden)

    Vanessa Donega

    Full Text Available Mesenchymal stem cell (MSC administration via the intranasal route could become an effective therapy to treat neonatal hypoxic-ischemic (HI brain damage. We analyzed long-term effects of intranasal MSC treatment on lesion size, sensorimotor and cognitive behavior, and determined the therapeutic window and dose response relationships. Furthermore, the appearance of MSCs at the lesion site in relation to the therapeutic window was examined. Nine-day-old mice were subjected to unilateral carotid artery occlusion and hypoxia. MSCs were administered intranasally at 3, 10 or 17 days after hypoxia-ischemia (HI. Motor, cognitive and histological outcome was investigated. PKH-26 labeled cells were used to localize MSCs in the brain. We identified 0.5 × 10(6 MSCs as the minimal effective dose with a therapeutic window of at least 10 days but less than 17 days post-HI. A single dose was sufficient for a marked beneficial effect. MSCs reach the lesion site within 24 h when given 3 or 10 days after injury. However, no MSCs were detected in the lesion when administered 17 days following HI. We also show for the first time that intranasal MSC treatment after HI improves cognitive function. Improvement of sensorimotor function and histological outcome was maintained until at least 9 weeks post-HI. The capacity of MSCs to reach the lesion site within 24 h after intranasal administration at 10 days but not at 17 days post-HI indicates a therapeutic window of at least 10 days. Our data strongly indicate that intranasal MSC treatment may become a promising non-invasive therapeutic tool to effectively reduce neonatal encephalopathy.

  4. A randomized controlled trial of intranasal-midazolam versus intravenous-diazepam for acute childhood seizures.

    Science.gov (United States)

    Thakker, Arpita; Shanbag, Preeti

    2013-02-01

    The objective of this study is to compare the safety and efficacy of midazolam given intranasally with diazepam given intravenously in the treatment of acute childhood seizures. A randomized controlled study was conducted in a pediatric emergency department in a tertiary general hospital. Fifty children aged from 1 month to 12 years presenting with acute seizures of at least 10 min duration were enrolled during a 12 month period. Intranasal midazolam (0.2 mg/kg) and intravenous diazepam (0.3 mg/kg) were administered. The main outcome measures were interval between arrival at hospital and starting treatment and interval between arrival at hospital and cessation of seizures. Intranasal midazolam and intravenous diazepam were equally effective. Overall 18 of 27 seizures were controlled with midazolam and 15 of 23 with diazepam. The mean interval between arrival at hospital and starting treatment was significantly shorter in the midazolam group [3.37 min (SD 2.46)] as compared to the diazepam group [14.13 min (SD 3.39)]. The mean interval between cessation of seizures and arrival at hospital was significantly shorter in the midazolam group [6.67 min (SD 3.12)] as compared to the diazepam group [17.18 min (SD 5.09)]. The mean interval between control of seizures and administration of the drug was shorter in the diazepam group [2.67 min (SD 2.31)] as compared to the midazolam group [3.01 min (SD 2.79)]. No significant side effects were observed in either group. Seizures were controlled more quickly with intravenous diazepam than with intranasal midazolam. Midazolam was as safe and effective as diazepam. The overall interval between arrival at hospital and cessation of seizures was shorter with intranasal midazolam than with intravenous diazepam. The intranasal route can be possibly used not only in medical centres, but with appropriate instruction by the parents of children with acute seizures at home.

  5. IS ATOMIZED INTRANASAL MIDAZOLAM A NOVEL SEDATIVE PREMEDICATION IN PAEDIATRIC PATIENTS?

    Directory of Open Access Journals (Sweden)

    Savitri D. Kabade

    2017-06-01

    Full Text Available BACKGROUND The successful conduct of anaesthesia in children depends on adequate premedication, which not only comforts the anxious child but also comforts the parents or guardians. Atomized Intranasal Midazolam is quickly absorbed through the nasal mucosa, resulting in a rapid and reliable onset of action. Clonidine has several applications in paediatric anaesthesia as a premedication and as an adjuvant in general as well as regional anaesthesia. Thus, in search of a novel premedication technique, we conducted a study to compare the effectiveness of atomized intranasal midazolam with intranasal clonidine for preoperative sedation in paediatric patients undergoing elective surgery. MATERIALS AND METHODS After obtaining Institutional Ethical Committee clearance and parent’s consent, a prospective, randomised, double-blinded clinical study was conducted in 78 children of ASA I and II, belonging to 2 - 10 years age, posted for various elective surgery. Group M (n= 39 received atomized intranasal midazolam (0.3 mg/kg and Group C (n= 39 received clonidine (4 mcg/kg instilled into both the nostrils. Sedation score (Ramsay, separation score, mask acceptance, recovery and vital parameters were recorded. Statistical analysis of data was done using IBM-SPSS version 21.0. RESULTS Mean sedation scores (± SD were higher in Group M than in Group C (at 5th minute 1.58 ± 0.55 in Group M and 1.15 ± 0.36 in Group C with P= 0.002, at 10th minute 2.34 ± 0.97 in Group M and 1.75 ± 0.71 in Group C with P= 0.008. Separation scores and mask acceptance were better with Group M than Group C. Haemodynamic parameters were similar in both the groups and no major adverse effects were noted. CONCLUSION Atomized intranasal midazolam produces superior sedation levels, child-parent separation and mask acceptance compared to intranasal clonidine in children.

  6. Human intestinal epithelial cells produce proinflammatory cytokines in response to infection in a SCID mouse-human intestinal xenograft model of amebiasis.

    Science.gov (United States)

    Seydel, K B; Li, E; Swanson, P E; Stanley, S L

    1997-01-01

    The protozoan parasite Entamoeba histolytica causes amebic dysentery and amebic liver abscess, diseases associated with significant morbidity and mortality worldwide. E. histolytica infection appears to involve the initial attachment of amebic trophozoites to intestinal epithelial cells, followed by lysis of these cells and subsequent invasion into the submucosa. A recent in vitro study (L. Eckmann, S. L. Reed, J. R. Smith, and M. F. Kagnoff, J. Clin. Invest. 96:1269-1279, 1995) demonstrated that incubation of E. histolytica trophozoites with epithelial cell lines results in epithelial cell production of inflammatory cytokines, including interleukin-1 (IL-1) and IL-8, suggesting that intestinal epithelial cell production of cytokines might play a role in the inflammatory response and tissue damage seen in intestinal amebiasis. To determine whether intestinal epithelial cell production of IL-1 and IL-8 occurs in response to E. histolytica infection in vivo and as an approach to studying the specific interactions between amebic trophozoites and human intestine, we used a SCID mouse-human intestinal xenograft (SCID-HU-INT) model of disease, where human intestinal xenografts were infected with virulent E. histolytica trophozoites. Infection of xenografts with E. histolytica trophozoites resulted in extensive tissue damage, which was associated with the development of an early inflammatory response composed primarily of neutrophils. Using oligonucleotide primers that specifically amplify human IL-1beta and IL-8, we could demonstrate by reverse transcription PCR that mRNA for both IL-1beta and IL-8 is produced by human intestinal xenografts in response to amebic infection. The increase in human intestinal IL-1beta and IL-8 in response to invasive amebiasis was confirmed by enzyme-linked immunosorbent assays specific for human IL-1beta and IL-8. Using immunohistochemistry, we confirmed that human intestinal epithelial cells were the source of IL-8 in infected xenografts

  7. Reduction of smoking urges with intranasal insulin: a randomized, crossover, placebo-controlled clinical trial.

    Science.gov (United States)

    Hamidovic, A; Khafaja, M; Brandon, V; Anderson, J; Ray, G; Allan, A M; Burge, M R

    2017-02-28

    Many cigarette smokers express a desire to quit smoking, but ~85% of cessation attempts fail. In our attempt to delineate genetic modulators of smoking persistence, we have earlier shown that a locus within an ~250 kb haplotype block spanning the 5' untranslated region region of insulin-degrading enzyme is associated with serum cotinine levels; the study's measure of smoking quantity. Based on our findings, and coupled with recent preclinical studies showing the importance of multiple neuropeptides in reinstatement of drug use, we formulated intranasal insulin to evaluate its efficacy during acute abstinence from smoking. Our original study was a crossover trial including 19 otherwise healthy smokers who abstained from smoking for 36 h. The morning following their second night of abstinence, in random order, study participants received intranasal insulin (60 IU) or placebo (8.7% sodium chloride). The goal of our second study was to replicate the craving findings from the original trial and expand this research by including additional stress-related measures. Thirty-seven study participants abstained from smoking overnight. The next day, they were administered either intranasal insulin (60 IU) or placebo, following which they participated in the Trier Social Stress Test Task. This was a parallel design study focusing on the standard stress subjective, hormonal and cardiovascular measures. We also evaluated any changes in circulating glucose, insulin and c-peptide (a marker of endogenous insulin). In the original study, intranasal insulin significantly reduced morning nicotine craving (b=3.65, P⩽0.05). Similarly, in the second study, intranasal insulin reduced nicotine cravings over time (b=0.065, P⩽0.05) and the effect lasted through the psychosocial stress period. Intranasal insulin also increased circulating cortisol levels (F=12.78, P⩽0.001). No changes in insulin or c-peptide were detected. A significant treatment × time interaction (P⩽0.05) was

  8. Comparison of clinical and laboratory characteristics of intestinal amebiasis with shigellosis among patients visiting a large urban diarrheal disease hospital in Bangladesh.

    Science.gov (United States)

    Das, Sumon Kumar; Chisti, Mohammod Jobayer; Malek, Mohammad Abdul; Salam, Mohammed Abdus; Ahmed, Tahmeed; Faruque, Abu Syed Golam; Mondal, Dinesh

    2013-08-01

    Between 1993 and 2011, a total of 371 intestinal amebiasis (IA), caused by Entamoeba histolytica cases were compared with 1,113 shigellosis (randomly selected) patients of icddr,b, excluding co-infections (rotavirus and Vibrio cholerae) in two age stratums: 0-14 years of age and ≥ 15 years of age. The number of IA and shigellosis cases gradually reduced over the study period. In multivariate analysis, individuals 0-14 years of age, slum dwellers (odds ratio [OR] 3.51; 95% confidence interval [CI] 1.69-7.24; P < 0.001), red blood cell (0.44 [0.24-0.86] 0.016), fecal leukocytes (0.17 [0.07-0.33] < 0.001), and alkaline stool (0.16 [0.07-0.36] < 0.001) were independently associated with IA; and among individuals ≥ 15 years of age, living in the slum area (1.88 [1.12-3.14] 0.016), watery stool (2.21 [1.37-3.55] 0.001), use of antimicrobials before visiting hospital (0.67 [0.46-0.99] 0.047), red blood cell (0.45 [0.22-0.94] 0.036), and fecal leukocytes (0.21 [0.12-0.35] < 0.001) in stool were independently associated with IA. Socio-demographic and clinical characteristics of IA and shigellosis varied distantly from each other.

  9. Intranasal fentanyl for the management of acute pain in children.

    Science.gov (United States)

    Murphy, Adrian; O'Sullivan, Ronan; Wakai, Abel; Grant, Timothy S; Barrett, Michael J; Cronin, John; McCoy, Siobhan C; Hom, Jeffrey; Kandamany, Nandini

    2014-10-10

    Pain is the most common symptom in the emergency setting; however, timely management of acute pain in children continues to be suboptimal. Intranasal drug delivery has emerged as an alternative method of achieving quicker drug delivery without adding to the distress of a child by inserting an intravenous cannula. We identified and evaluated all randomized controlled trials (RCTs) and quasi-randomized trials to assess the effects of intranasal fentanyl (INF) versus alternative analgesic interventions in children with acute pain, with respect to reduction in pain score, occurrence of adverse events, patient tolerability, use of "rescue analgesia," patient/parental satisfaction and patient mortality. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 1); MEDLINE (Ovid SP, from 1995 to January 2014); EMBASE (Ovid SP, from 1995 to January 2014); the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (EBSCO Host, from 1995 to January 2014); the Latin American and Caribbean Health Science Information Database (LILACS) (BIREME, from 1995 to January 2014); Commonwealth Agricultural Bureaux (CAB) Abstracts (from 1995 to January 2014); the Institute for Scientific Information (ISI) Web of Science (from 1995 to January 2014); BIOSIS Previews (from 1995 to January 2014); the China National Knowledge Infrastructure (CNKI) (from 1995 to January 2014); International Standard Randomized Controlled Trial Number (ISRCTN) (from 1995 to January 2014); ClinicalTrials.gov (from 1995 to January 2014); and the International Clinical Trials Registry Platform (ICTRP) (to January 2014). We included RCTs comparing INF versus any other pharmacological/non-pharmacological intervention for the treatment of children in acute pain (aged < 18 years). Two independent review authors assessed each title and abstract for relevance. Full copies of all studies that met the inclusion criteria were retrieved for further assessment. Mean difference (MD), odds

  10. Intranasal LH-RH treatment of cryptorchidism. A clinical trial and 5 years follow-up

    DEFF Research Database (Denmark)

    Thorup, Jørgen Mogens; Mauritzen, K; Skakkebaek, N E

    1987-01-01

    The effect of intranasal LH-RH on cryptorchidism was investigated in 45 prepubertal boys with 68 undescended testes. A daily dose of 1.2 mg LH-RH was given for 4 weeks. A total of 16 testes (24%) descended. Follow-up examination 5 years later showed that relapse had occurred in two cases. Fifty-t...

  11. Simultaneous intramammary and intranasal inoculation of lactating cows with bovine herpesvirus 4 induce subclinical mastitis

    NARCIS (Netherlands)

    Wellenberg, G.J.; Bruschke, C.J.M.; Wisselink, H.J.; Barkema, H.W.; Oirschot, van J.T.

    2002-01-01

    In this study, we examined whether an experimental bovine herpesvirus 4 (BHV4) infection can induce bovine mastitis, or can enhance bovine mastitis induced by Streptococcus uberis (S. uberis). Four lactating cows were inoculated intramammarily and intranasally with BHV4, and four lactating control c

  12. Intranasal Rapamycin Rescues Mice from Staphylococcal Enterotoxin B-Induced Shock

    Science.gov (United States)

    2012-09-18

    Mice from Staphylococcal Enterotoxin B-Induced Shock Teresa Krakauer * and Marilyn Buckley Integrated Toxicology Division, U.S. Army Medical...2012 / Published: 18 September 2012 Abstract: Staphylococcal enterotoxin B (SEB) and related exotoxins produced by Staphylococcus aureus are...allowing a wider therapeutic window. Keywords: intranasal rapamycin; staphylococcal enterotoxin B; shock 1. Introduction Staphylococcal

  13. Safety of Intranasal Fentanyl in the Out-of-Hospital Setting

    DEFF Research Database (Denmark)

    Karlsen, Anders P H; Pedersen, Danny M B; Trautner, Sven

    2014-01-01

    : In this prospective observational study, we administered intranasal fentanyl in the out-of-hospital setting to adults and children older than 8 years with severe pain resulting from orthopedic conditions, abdominal pain, or acute coronary syndrome refractory to nitroglycerin spray. Patients received 1 to 3 doses...

  14. Limited evidence for effects of intranasal corticosteroids on symptom relief for recurrent acute rhinosinusitis

    NARCIS (Netherlands)

    van Loon, J.W.L.; van Harn, R.P.; Venekamp, R.P.; Kaper, N.M.; Sachs, A.P.E.; van der Heijden, G.J.M.G.

    2013-01-01

    Objective To systematically review the evidence base on the effectiveness of intranasal corticosteroids in adult patients with recurrent acute rhinosinusitis. Data Sources Pubmed, EMBASE, and the Cochrane Library. Review Methods A comprehensive search was performed up to March 20, 2013. Two reviewer

  15. CSF and blood oxytocin concentration changes following intranasal delivery in macaque.

    Directory of Open Access Journals (Sweden)

    Olga Dal Monte

    Full Text Available Oxytocin (OT in the central nervous system (CNS influences social cognition and behavior, making it a candidate for treating clinical disorders such as schizophrenia and autism. Intranasal administration has been proposed as a possible route of delivery to the CNS for molecules like OT. While intranasal administration of OT influences social cognition and behavior, it is not well established whether this is an effective means for delivering OT to CNS targets. We administered OT or its vehicle (saline to 15 primates (Macaca mulatta, using either intranasal spray or a nebulizer, and measured OT concentration changes in the cerebral spinal fluid (CSF and in blood. All subjects received both delivery methods and both drug conditions. Baseline samples of blood and CSF were taken immediately before drug administration. Blood was collected every 10 minutes after administration for 40 minutes and CSF was collected once post-delivery, at the 40 minutes time point. We found that intranasal administration of exogenous OT increased concentrations in both CSF and plasma compared to saline. Both delivery methods resulted in similar elevations of OT concentration in CSF, while the changes in plasma OT concentration were greater after nasal spray compared to nebulizer. In conclusion our study provides evidence that both nebulizer and nasal spray OT administration can elevate CSF OT levels.

  16. Prevention or early cure of type 1 diabetes by intranasal administration of gliadin in NOD mice

    DEFF Research Database (Denmark)

    Funda, David; Fundova, Petra; Hansen, Axel Kornerup

    2014-01-01

    gluten-free diets prevent T1D in animal models. Herewith we investigated whether intranasal (i.n.) administration of gliadin or gluten may arrest the diabetogenic process. I.n. administration of gliadin to 4-week-old NOD mice significantly reduced the diabetes incidence. Similarly, the insulitis...

  17. Abuse potential of intranasal buprenorphine versus buprenorphine/naloxone in buprenorphine-maintained heroin users.

    Science.gov (United States)

    Jones, Jermaine D; Sullivan, Maria A; Vosburg, Suzanne K; Manubay, Jeanne M; Mogali, Shanthi; Metz, Verena; Comer, Sandra D

    2015-07-01

    In spite of the clinical utility of buprenorphine, parenteral abuse of this medication has been reported in several laboratory investigations and in the real world. Studies have demonstrated lower abuse liability of the buprenorphine/naloxone combination relative to buprenorphine alone. However, clinical research has not yet examined the utility of the combined formulation to deter intranasal use in a buprenorphine-maintained population. Heroin-using volunteers (n = 12) lived in the hospital for 8-9 weeks and were maintained on each of three sublingual buprenorphine doses (2, 8, 24 mg). Under each maintenance dose, participants completed laboratory sessions during which the reinforcing and subjective effects of intranasal doses of buprenorphine (8, 16 mg), buprenorphine/naloxone (8/2, 8/8, 8/16, 16/4 mg) and controls (placebo, heroin 100 mg, naloxone 4 mg) were assessed. Intranasal buprenorphine alone typically produced increases in positive subjective effects and the 8 mg dose was self-administered above the level of placebo. The addition of naloxone dose dependently reduced positive subjective effects and increased aversive effects. No buprenorphine/naloxone combination dose was self-administered significantly more than placebo. These data suggest that within a buprenorphine-dependent population, intranasal buprenorphine/naloxone has reduced abuse potential in comparison to buprenorphine alone. These data strongly argue in favor of buprenorphine/naloxone rather than buprenorphine alone as the more reasonable option for managing the risk of buprenorphine misuse.

  18. Intranasal delivery of liposomal indole-3-carbinol improves its pulmonary bioavailability.

    Science.gov (United States)

    Song, Jung Min; Kirtane, Ameya R; Upadhyaya, Pramod; Qian, Xuemin; Balbo, Silvia; Teferi, Fitsum; Panyam, Jayanth; Kassie, Fekadu

    2014-12-30

    Indole-3-carbinol (I3C), a constituent of commonly consumed Brassica vegetables, has been shown to have anticancer effects in a variety of preclinical models of lung cancer. However, it has shown only limited efficacy in clinical trials, likely due to its poor oral bioavailability. Intranasal administration of I3C has the potential to enhance the pulmonary accumulation of the drug, thereby improving its availability at the target site of action. In this study, we developed a liposomal formulation of I3C and evaluated its lung delivery and chemopreventive potential in tobacco smoke carcinogen [4-(methylnitro-samino)-1-(3-pyridyl)-1-butanone (NNK)]-treated mice. Intranasal administration of I3C liposomes led to a ∼100-fold higher lung exposure of I3C than the oral route of administration. Further, intranasal delivery of liposomal I3C led to a significant reduction (37%; pLiposomal I3C also significantly increased (by 10-fold) the expression of CYP1A1, a cytochrome P450 enzyme known to increase the detoxification of chemical carcinogens by enhancing their metabolism. Overall, our findings demonstrate that intranasal administration of liposomal I3C has the potential to significantly improve the efficacy of I3C for lung cancer chemoprevention.

  19. Preparation of lorazepam-loaded microemulsions for intranasal delivery and its pharmacokinetics.

    Science.gov (United States)

    Yao, J; Hou, L; Zhou, J P; Zhang, Z Q; Sun, L

    2009-10-01

    The purpose of this study was to develop a microemulsion system for intranasal delivery of lorazepam. The phase behavior and properties of microemulsions were characterized in a pseudo-ternary system composed of Cremophor EL 35/Transcutol P/Lauroglycol FCC or Labrafil M 1944CS/water, and intranasal absorption of lorazepam from microemulsions was investigated in rabbit. The microemulsions, comprising of FCC, Cremophor EL 35/Transcutol P (1.5:1) and water, were optimal for intranasal delivery of lorazepam. These systems had a higher solubilization capacity with the particle size of lorazepam from microemulsions at 0.38 mg/kg had the larger AUC(0-t), the longer half-life and the prolonged circulation time with the mean bioavailability of 80.84% for ME2 and 63.48% for ME8 as compared to the intramuscular injection at 0.16 mg/kg. These results indicate that microemulsions may bea promising approach for the intranasal delivery of lorazepam.

  20. Early experience of radio frequency coblation in the management of intranasal and sinus tumors.

    Science.gov (United States)

    Syed, Mohammed Iqbal; Mennie, Joanna; Williams, Alun T

    2012-02-01

    The purpose of this study was to evaluate the safety and efficacy of the use of radiofrequency coblation for endoscopic resection of intranasal and sinus tumors. A review was conducted of 15 adult patients with intranasal and or sinus tumors endoscopically treated with radio frequency coblation between November 2008 and November 2010 at St. John's Hospital at Livingston, a tertiary referral center that covers otolaryngology services for the southeast of Scotland. Fifteen patients with intranasal and sinus tumors were treated with transnasal endoscopic resection using radiofrequency coblation. The tumors included inverted papilloma (seven), paraganglioma (one), glomangiopericytoma (one), capillary hemangioma (one), hemangiopericytoma (one), juvenile angiofibroma (one), juvenile ossifying fibroma (one), oncocytic adenoma (one), and transitional cell carcinoma (one). We found that radiofrequency coblation is a useful and safe tool associated with minimal blood loss (<200 mL to 600 mL) in the resection of these tumors, and the average operating time was 1.67 hours. Radio frequency is a rapidly evolving technique and in the future will have an increasing role to play in the endoscopic resection of intranasal and sinus tumors.

  1. Effect of intranasally administered insulin on cerebral blood flow and perfusion

    DEFF Research Database (Denmark)

    Akintola, Abimbola A.; van Opstal, Anna M.; Westendorp, Rudi G.

    2017-01-01

    Insulin, a vasoactive modulator regulating peripheral and cerebral blood flow, has been consistently linked to aging and longevity. In this proof of principle study, using a randomized, double-blinded, placebo-controlled crossover design, we explored the effects of intranasally administered insulin...

  2. Simultaneous intramammary and intranasal inoculation of lactating cows with bovine herpesvirus 4 induce subclinical mastitis

    NARCIS (Netherlands)

    Wellenberg, G.J.; Bruschke, C.J.M.; Wisselink, H.J.; Barkema, H.W.; Oirschot, van J.T.

    2002-01-01

    In this study, we examined whether an experimental bovine herpesvirus 4 (BHV4) infection can induce bovine mastitis, or can enhance bovine mastitis induced by Streptococcus uberis (S. uberis). Four lactating cows were inoculated intramammarily and intranasally with BHV4, and four lactating control

  3. Direct nose-to-brain delivery of lamotrigine following intranasal administration to mice.

    Science.gov (United States)

    Serralheiro, Ana; Alves, Gilberto; Fortuna, Ana; Falcão, Amílcar

    2015-07-25

    Pharmacoresistance is considered one of the major causes underlying the failure of the anticonvulsant therapy, demanding the development of alternative and more effective therapeutic approaches. Due to the particular anatomical features of the nasal cavity, intranasal administration has been explored as a means of preferential drug delivery to the brain. The purpose of the present study was to assess the pharmacokinetics of lamotrigine administered by the intranasal route to mice, and to investigate whether a direct transport of the drug from nose to brain could be involved. The high bioavailability achieved for intranasally administered lamotrigine (116.5%) underscored the fact that a substantial fraction of the drug has been absorbed to the systemic circulation. Nonetheless, the heterogeneous biodistribution of lamotrigine in different brain regions, with higher concentration levels attained in the olfactory bulb comparatively to the frontal cortex and the remaining portion of the brain, strongly suggest that lamotrigine was directly transferred to the brain via the olfactory neuronal pathway, circumventing the blood-brain barrier. Therefore, it seems that intranasal route can be assumed as a suitable and valuable drug delivery strategy for the chronic treatment of epilepsy, also providing a promising alternative approach for a prospective management of pharmacoresistance.

  4. Comparative Study of Intranasal Midazolam and Intravenous Benzodiazepines in Control of Seizures in Children

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    Janki Panchal

    2013-02-01

    Full Text Available Background: Seizures are very common in pediatric patients. As duration of seizures impacts morbidity and mortality to child’s life, control of seizures should be achieved as early as possible, preferably at home. Rectal diazepam and intranasal midazolam are available methods for control of seizures and can be learnt by parents. Methods: We assessed safety and efficacy of intranasal midazolam for control of seizures and also compared its effect with other benzodiazepines given by intravenous route. Results: Among 84 patients, success rate of treatment with Midazolam (intranasal was 45.5% and success rate with Benzodiazepines (intravenous was 90%. The difference is statistically significant. In present study, average time recorded to give drug after arrival at hospital in IN Midazolam group was 0.379 min, where as it was 1.598 min in IV Benzodiazepine group. Average time for cessation of seizures after giving drug was 3.001 min in IN Midazolam group, where as it was 1.009 min in IV Benzodiazepine group. Conclusion: Intra-venous route for control of seizures is most effective compare to Inta-nasal Midazolam. However intranasal Midazolam can be use full when IV access is not available at home or during transport of patient to health care centre. [Natl J of Med Res 2013; 3(1.000: 30-33

  5. Intranasal oxytocin administration in relationship to social behaviour in domestic pigs

    NARCIS (Netherlands)

    Camerlink, Irene; Reimert, Inonge; Bolhuis, Liesbeth

    2016-01-01

    Intranasal administration of oxytocin has been shown to alter positive and negative social behaviour. Positive social behaviour in pigs (Sus scrofa) may be expressed through gentle social nosing, and greater insight in the specific expression hereof might contribute to the current search for posi

  6. Assessment of pharmacokinetics and tolerability of intranasal diazepam relative to rectal gel in healthy adults.

    Science.gov (United States)

    Henney, Herbert R; Sperling, Michael R; Rabinowicz, Adrian L; Bream, Gary; Carrazana, Enrique J

    2014-09-01

    Diazepam rectal gel (RG) is currently the only approved rescue therapy for outpatient management of seizure clusters in the United States. There is an unmet medical need for an alternative rescue therapy for seizure clusters that is effective, and more convenient to administer with a socially acceptable method of delivery. An intranasal diazepam formulation has been developed, and this study evaluates the tolerability and bioavailability of diazepam nasal spray (NS) relative to an equivalent dose of diazepam-RG in healthy adults. Twenty-four healthy adults were enrolled in a phase 1, open-label, 3-period crossover study. Plasma diazepam and metabolite concentrations were measured by serial sampling. Dose proportionality for 5- and 20-mg intranasal doses and the bioavailability of 20mg diazepam-NS relative to 20mg diazepam-RG were assessed by maximum plasma concentration (Cmax) and systemic exposure parameters (AUC0-∞ and AUC0-24). The mean Cmax values for 20mg diazepam-NS and 20mg diazepam-RG were 378 ± 106 and 328 ± 152 ng/mL, achieved at 1.0 and 1.5h, respectively. Subjects administered intranasal and rectal gel formulations experienced nasal and rectal leakage, respectively. Diazepam absorption following intranasal administration was consistent but 3 subjects with diazepam-RG had low plasma drug levels at the earliest assessment of 5 min, due to poor retention, and were excluded from analysis. Excluding them, the treatment ratios (20mg diazepam-NS:20mg diazepam-RG) and 90% confidence intervals for diazepam Cmax and AUC0-24 were 0.98 (0.85-1.14) and 0.89 (0.80-0.98), respectively, suggesting that the bioavailability was comparable between the two formulations. Dose proportionality was observed between the lowest and highest dose-strengths of intranasal formulation. Both intranasal and rectal treatments were well tolerated with mild to moderate adverse events. Results suggest that a single-dose of 20mg diazepam-NS is tolerable and comparable in bioavailability

  7. Direct nose-brain transport of benzoylecgonine following intranasal administration in rats.

    Science.gov (United States)

    Chow, H H; Anavy, N; Villalobos, A

    2001-11-01

    In our previous research, cocaine applied intranasally in rats diffused or was transported directly from the nasal cavity to the brain. However, the direct nose-brain cocaine transport only contributes to an initial increase in the relative cocaine brain exposure. In this study, we have determined the nose-brain transport of a polar metabolite of cocaine, benzoylecgonine, to help understand factors affecting drug transport via this novel pathway. The nasal cavity of male Sprague-Dawley rats was isolated to prevent drainage of nasally applied dosing solution to non-nasal regions. Benzoylecgonine was then administered, either by intranasal administration or by intravenous (iv) injection. At different times postdose, blood and tissues from different regions of the brain were collected from groups of rats (n = 4 for each collection time) and benzoylecgonine concentrations in these samples were analyzed by high-performance liquid chromatography. Benzoylecgonine concentrations in plasma were at maximal levels immediately after iv dosing and declined as a function of time. Following intranasal administration, benzoylecgonine concentrations in plasma reached maximal levels between 15 and 30 min after dosing and declined as a function of time. To allow comparison of brain benzoylecgonine content after iv and intranasal administration, brain benzoylecgonine contents were normalized by plasma benzoylecgonine concentrations. The ratios of the area under the benzoylecgonine concentration-time curve (AUC) between the olfactory bulb and plasma following intranasal administration were 10-100 times higher than those obtained after iv dosing. The olfactory tract-to-plasma benzoylecgonine AUC ratios after intranasal administration were significantly higher than those after iv dosing up to 120 min following dosing. The brain tissue-to-plasma AUC ratios in cerebellum, brain stem, and cerebral cortex after intranasal administration were significantly higher than the corresponding ratios

  8. Effects of intranasal and peripheral oxytocin or gastrin-releasing peptide administration on social interaction and corticosterone levels in rats.

    Science.gov (United States)

    Kent, Pamela; Awadia, Alisha; Zhao, Leah; Ensan, Donna; Silva, Dinuka; Cayer, Christian; James, Jonathan S; Anisman, Hymie; Merali, Zul

    2016-02-01

    The intranasal route of drug administration has gained increased popularity as it is thought to allow large molecules, such as peptide hormones, more direct access to the brain, while limiting systemic exposure. Several studies have investigated the effects of intranasal oxytocin administration in humans as this peptide is associated with prosocial behavior. There are, however, few preclinical studies investigating the effects of intranasal oxytocin administration in rodents. Oxytocin modulates hypothalamic-pituitary-adrenal (HPA) axis functioning and it has been suggested that oxytocin's ability to increase sociability may occur through a reduction in stress reactivity. Another peptide that appears to influence both social behavior and HPA axis activity is gastrin-releasing peptide (GRP), but it is not known if these GRP-induced effects are related. With this in mind, in the present study, we assessed the effects of intranasal and intraperitoneal oxytocin and GRP administration on social interaction and release of corticosterone in rats. Intranasal and intraperitoneal administration of 20, but not 5 μg, of oxytocin significantly increased social interaction, whereas intranasal and peripheral administration of GRP (20 but not 5 μg) significantly decreased levels of social interaction. In addition, while intranasal oxytocin (20 μg) had no effect on blood corticosterone levels, a marked increase in blood corticosterone levels was observed following intraperitoneal oxytocin administration. With GRP, intranasal (20 μg) but not peripheral administration increased corticosterone levels. These findings provide further evidence that intranasal peptide delivery can induce behavioral alterations in rodents which is consistent with findings from human studies. In addition, the peptide-induced changes in social interaction were not linked to fluctuations in corticosterone levels.

  9. Intranasal insulin prevents anesthesia-induced hyperphosphorylation of tau in 3xTg-AD mice

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    Yanxing eChen

    2014-05-01

    Full Text Available Background: It is well documented that elderly individuals are at increased risk of cognitive decline after anesthesia. General anesthesia is believed to be a risk factor for Alzheimer’s disease (AD. Recent studies suggest that anesthesia may increase the risk for cognitive decline and AD through promoting abnormal hyperphosphorylation of tau, which is crucial to neurodegeneration seen in AD. Methods: We treated 3xTg-AD mice, a commonly used transgenic mouse model of AD, with daily intranasal administration of insulin (1.75U/day for one week. The insulin- and control-treated mice were then anesthetized with single intraperitoneal injection of propofol (250 mg/kg body weight. Tau phosphorylation and tau protein kinases and phosphatases in the brains of mice 30 min and two hours after propofol injection were then investigated by using Western blots and immunohistochemistry.Results: Propofol strongly promoted hyperphosphorylation of tau at several AD-related phosphorylation sites. Intranasal administration of insulin attenuated propofol-induced hyperphosphorylation of tau, promoted brain insulin signaling, and led to up-regulation of protein phosphatase 2A, a major tau phosphatase in the brain. Intranasal insulin also resulted in down-regulation of several tau protein kinases, including cyclin-dependent protein kinase 5, calcium/calmodulin-dependent protein kinase II, and c-Jun N-terminal kinase. Conclusion: Our results demonstrate that pretreatment with intranasal insulin prevents AD-like tau hyperphosphorylation. These findings provide the first evidence supporting that intranasal insulin administration might be used for the prevention of anesthesia-induced cognitive decline and increased risk for AD and dementia.

  10. Intranasal Corticosteroids in Management of Acute Sinusitis: A Systematic Review and Meta-Analysis

    Science.gov (United States)

    Hayward, Gail; Heneghan, Carl; Perera, Rafael; Thompson, Matthew

    2012-01-01

    PURPOSE Acute sinusitis is a common condition in ambulatory care, where it is frequently treated with antibiotics, despite little evidence of their benefit. Intranasal corticosteroids might relieve symptoms; however, evidence for this benefit is currently unclear. We performed a systematic review and meta-analysis of the effects of intranasal corticosteroids on the symptoms of acute sinusitis. METHODS We searched MEDLINE, EMBASE, the Cochrane Central register of Controlled Trials (CENTRAL), and Centre for Reviews and Dissemination databases until February 2011 for studies comparing intranasal corticosteroids with placebo in children or adults having clinical symptoms and signs of acute sinusitis or rhinosinusitis in ambulatory settings. We excluded chronic/allergic sinusitis. Two authors independently extracted data and assessed the studies’ methodologic quality. RESULTS We included 6 studies having a total of 2,495 patients. In 5 studies, antibiotics were prescribed in addition to corticosteroids or placebo. Intranasal corticosteroids resulted in a significant, small increase in resolution of or improvement in symptoms at days 14 to 21 (risk difference [RD] = 0.08; 95% CI, 0.03–0.13). Analysis of individual symptom scores revealed most consistently significant benefits for facial pain and congestion. Subgroup analysis by time of reported outcomes showed a significant beneficial effect at 21 days (RD = 0.11; 95% CI, 0.06–0.17), but not at 14 to 15 days (RD = 0.05; 95% CI, −0.01 to 0.11). Meta-regression analysis of trials using different doses of mometasone furoate showed a significant dose-response relationship (P=.02). CONCLUSIONS Intranasal corticosteroids offer a small therapeutic benefit in acute sinusitis, which may be greater with high doses and with courses of 21 days’ duration. Further trials are needed in antibiotic-naïve patients. PMID:22585889

  11. Drug brain distribution following intranasal administration of Huperzine A in situ gel in rats

    Institute of Scientific and Technical Information of China (English)

    Yan ZHAO; Peng YUE; Tao TAO; Qing-hua CHEN

    2007-01-01

    Aim: To determine the uptake extent of Huperzine A (Hup A) into the brain after intranasal administration of Hup A in situ gel to rats, and to compare the pharma-cokinetic parameters between intranasal administration and iv and po. Methods: Hup A was administered to male Sprague-Dawley rats via nasal, iv and oral routes at the dose of 166.7, 166.7, and 500μg/kg, respectively. Blood and brain tissue samples including the cerebrum, hippocampus, cerebellum and olfactory bulb were collected, and the concentrations of Hup A in the samples were assayed by HPLC. The area under the concentration-time curve (AUC,0→6h) and the ratio of the AUC,brain, to the AUC,plasma (drug targeting efficiency, DTE) were calculated toevaluate the brain targeting efficiency of the drug via 3 administration routes. Results: The AUC,0→6h of the drug in the cerebrum, hippocampus, cerebellum, left olfactory bulb and right olfactory bulb after intranasal administration of the Hup A in situ gel were 1.5, 1.3, 1.0, 1.2, and 1.0 times of those after iv administration of the injection, and 2.7, 2.2, 1.9, 3.1, and 2.6 times of those after administration of the oral formulation. The AUC,brain0→6h/AUC,plasma0→6h of Hup A in the cerebrum, hippocampus and left olfactory bulb following the intranasal administration dose were significantly higher (P0.05) than the iv dose. Conclusion: Intranasal delivery showed a viable, non-invasive strategy for delivering the drug into brain.

  12. Estudio seroepidemiologico de la amibiasis en una comunidad del estado Zulia, Venezuela A seroepidemiological study of amebiasis in a community of Zulia State, Venezuela

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    Leonor Chacin-Bonilla

    1990-12-01

    Full Text Available Se realizó un estudio seroepidemiologico de amibiasis en una comunidad de bajas condiciones socioeconómicas del Municipio Mara, Estado Zulia, Venezuela. Se estudiaron 283 individuos cuyas edades fluctuaron de 2 a 53 años. Se obtuvieron muestras de sueros, las cuales se examinaron con la prueba de hemaglutinación indirecta de KESSEL et al., según una modificación de MILGRAM et al. Se utilizó antígeno amibiano obtenido de cultivos axénicos de la raza HK9 de E. histolytica. La tasa de seropositividad obtenida fué de 46.6%; la mayoría de los reactores tenía títulos bajos y no presentaba signos de amibiasis. El porcentaje de seropositividad aumentó con la edad. Los resultados sugieren una alta endemicidad de la infección en esta comunidad, ocurriendo la transmisión con mucha mayor frecuencia que la amibiasis invasiva.In the present evaluation, a community of low socioeconomical conditions from Zulia State, Venezuela, was analyzed for the prevalence of antibodies to E. histolytica. Two hundred and eighty three serum samples were collected and examined by the indirect hemagglutination test according to a microtiter modification of the KESSEL and LEWIS method, as used by MILGRAM et al. Antigen prepared from axenically-grown. E. histolytica strain HK9 in Diamond's medium was used. The seropositivity rate obtained was 46.6% and the frequency of positive cases was dependent on age. The antibody profiles obtained suggest a high endemicity for this parasitic infection in the area studied, with a much higher level of transmission than invasive amebiasis.

  13. Intranasal insulin improves cerebral blood flow, Nrf-2 expression and BDNF in STZ (ICV)-induced memory impaired rats.

    Science.gov (United States)

    Rajasekar, N; Nath, Chandishwar; Hanif, Kashif; Shukla, Rakesh

    2017-03-15

    Insulin/insulin receptor signaling is involved in cognitive functions. Clinical studies have shown that intranasal insulin administration improves memory functions. However, the molecular mechanisms associated with improvement in memory functions are largely unexplored. Therefore, we investigated the protective effect of intranasal insulin in intracerebroventricular (ICV) streptozotocin (STZ) induced memory impairment in rats. Rats were injected with STZ (3mg/kg, ICV) bilaterally twice, on days 1 and 3 and intranasal insulin (2IU/rat/day) was given for 14days. Memory was assessed by Morris water maze test. Cerebral blood flow (CBF) was measured by laser-Doppler flowmetry. The biochemical and molecular studies were done in cortex and hippocampus of rat brain. STZ (ICV) administration caused memory impairment along with the reduction of CBF, ATP level, and Nrf-2 expression. Treatment with intranasal insulin significantly improved memory functions as well as restored CBF, ATP content and Nrf-2 expression in STZ injected rats. STZ administration stimulated oxidative-nitrosative stress as evidenced by a significant increase in ROS, malondialdehyde, NO level and inducible nitric oxide synthase expression and the decrease in glutathione level; which was normalized by intranasal insulin delivery. STZ-induced cholinergic dysfunction (AChE activity and α7-nAChR expression), and mitochondrial hypofunction was largely prevented by treatment with intranasal insulin. Intranasal insulin delivery successfully restored BDNF level and pCREB expression in STZ injected rats. The study shows the beneficial effects of intranasal insulin against STZ-induced memory impairment, which attributed to improved CBF, cholinergic function, brain energy metabolism, BDNF, Nrf-2 expression and antioxidative action. Copyright © 2016. Published by Elsevier Inc.

  14. The effect of intranasal oxytocin on perceiving and understanding emotion on the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT).

    Science.gov (United States)

    Cardoso, Christopher; Ellenbogen, Mark A; Linnen, Anne-Marie

    2014-02-01

    Evidence suggests that intranasal oxytocin enhances the perception of emotion in facial expressions during standard emotion identification tasks. However, it is not clear whether this effect is desirable in people who do not show deficits in emotion perception. That is, a heightened perception of emotion in faces could lead to "oversensitivity" to the emotions of others in nonclinical participants. The goal of this study was to assess the effects of intranasal oxytocin on emotion perception using ecologically valid social and nonsocial visual tasks. Eighty-two participants (42 women) self-administered a 24 IU dose of intranasal oxytocin or a placebo in a double-blind, randomized experiment and then completed the perceiving and understanding emotion components of the Mayer-Salovey-Caruso Emotional Intelligence Test. In this test, emotion identification accuracy is based on agreement with a normative sample. As expected, participants administered intranasal oxytocin rated emotion in facial stimuli as expressing greater emotional intensity than those given a placebo. Consequently, accurate identification of emotion in faces, based on agreement with a normative sample, was impaired in the oxytocin group relative to placebo. No such effect was observed for tests using nonsocial stimuli. The results are consistent with the hypothesis that intranasal oxytocin enhances the salience of social stimuli in the environment, but not nonsocial stimuli. The present findings support a growing literature showing that the effects of intranasal oxytocin on social cognition can be negative under certain circumstances, in this case promoting "oversensitivity" to emotion in faces in healthy people.

  15. Visualization of murine intranasal dosing efficiency using luminescent Francisella tularensis: effect of instillation volume and form of anesthesia.

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    Mark A Miller

    Full Text Available Intranasal instillation is a widely used procedure for pneumonic delivery of drugs, vaccine candidates, or infectious agents into the respiratory tract of research mice. However, there is a paucity of published literature describing the efficiency of this delivery technique. In this report we have used the murine model of tularemia, with Francisella tularensis live vaccine strain (FTLVS infection, to evaluate the efficiency of pneumonic delivery via intranasal dosing performed either with differing instillation volumes or different types of anesthesia. FTLVS was rendered luminescent via transformation with a reporter plasmid that constitutively expressed the Photorhabdus luminescens lux operon from a Francisella promoter. We then used an IVIS Spectrum whole animal imaging system to visualize FT dissemination at various time points following intranasal instillation. We found that instillation of FT in a dose volume of 10 µl routinely resulted in infection of the upper airways but failed to initiate infection of the pulmonary compartment. Efficient delivery of FT into the lungs via intranasal instillation required a dose volume of 50 µl or more. These studies also demonstrated that intranasal instillation was significantly more efficient for pneumonic delivery of FTLVS in mice that had been anesthetized with inhaled (isoflurane vs. parenteral (ketamine/xylazine anesthesia. The collective results underscore the need for researchers to consider both the dose volume and the anesthesia type when either performing pneumonic delivery via intranasal instillation, or when comparing studies that employed this technique.

  16. Intranasal siRNA administration reveals IGF2 deficiency contributes to impaired cognition in Fragile X syndrome mice

    Science.gov (United States)

    Pardo, Marta; Cheng, Yuyan; Velmeshev, Dmitry; Magistri, Marco; Martinez, Ana; Faghihi, Mohammad A.; Jope, Richard S.; Beurel, Eleonore

    2017-01-01

    Molecular mechanisms underlying learning and memory remain imprecisely understood, and restorative interventions are lacking. We report that intranasal administration of siRNAs can be used to identify targets important in cognitive processes and to improve genetically impaired learning and memory. In mice modeling the intellectual deficiency of Fragile X syndrome, intranasally administered siRNA targeting glycogen synthase kinase-3β (GSK3β), histone deacetylase-1 (HDAC1), HDAC2, or HDAC3 diminished cognitive impairments. In WT mice, intranasally administered brain-derived neurotrophic factor (BDNF) siRNA or HDAC4 siRNA impaired learning and memory, which was partially due to reduced insulin-like growth factor-2 (IGF2) levels because the BDNF siRNA– or HDAC4 siRNA–induced cognitive impairments were ameliorated by intranasal IGF2 administration. In Fmr1–/– mice, hippocampal IGF2 was deficient, and learning and memory impairments were ameliorated by IGF2 intranasal administration. Therefore intranasal siRNA administration is an effective means to identify mechanisms regulating cognition and to modulate therapeutic targets. PMID:28352664

  17. Intranasal administration of nanostructured lipid carriers containing CNS acting drug: pharmacodynamic studies and estimation in blood and brain.

    Science.gov (United States)

    Alam, M Intakhab; Baboota, Sanjula; Ahuja, Alka; Ali, Mushir; Ali, Javed; Sahni, Jasjeet K

    2012-09-01

    The present study was aimed to investigate and compare the efficacy of duloxetine (DLX) loaded nanostructured lipid carriers (NLC) with DLX solution pharmacodynamically following intranasal administration. The study was further conducted to estimate DLX concentration in brain and blood. DLX was administered to albino Wistar rats either intranasally or orally in solution form (DLX solution) or encapsulated in NLC (DLX-NLC). These were evaluated in-vivo for pharmacodynamic studies for depression by forced swimming test and locomotor activity test. Intranasal DLX-NLC treatment exhibited improved behavioural analysis results (swimming, climbing, and immobility) than the DLX solution after 24 h of study. Furthermore, DLX-NLC significantly increased the total swimming and climbing time when compared with control and significantly reduced the immobility period. The intranasal DLX-NLC demonstrated improved locomotor activity when compared with DLX solution. Amount of DLX was quantified in blood and brain after the forced swimming test. The intranasal DLX-NLC demonstrated higher concentration in brain compared with DLX solution. Thus, intranasal DLX-NLC was found to be a promising formulation for the treatment of depression.

  18. Study of embryotoxic effects of intranasally administred desloratadine on laboratory animals

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    Alekhina Т.А.

    2017-04-01

    Full Text Available The study was conducted to detect possible changes in embryogenesis and negative effects of third generation antihistamine – desloratadine – after intranasal administration of 1.3 mg/m3 and 13.0 mg/m3 of the substance to laboratory animals during their prenatal period. In these circumstances, desloratadine does not cause any significant changes of embryogenesis parameters. Macroscopic examination of the fetus and placenta in animals of experimental groups did not reveal any pathology or physiological deviations from the norm. 13.0 mg/m3 concentration of the drug caused a decrease in the weight of embryos in comparison with control group of animals and physiological data, despite a well developed, without visible pathology, placenta. This neces­sitates an in-depth study of possible teratogenic effects of intranasally administred desloratadine to laboratory animals.

  19. Prevention or early cure of type 1 diabetes by intranasal administration of gliadin in NOD mice

    DEFF Research Database (Denmark)

    Funda, David; Fundova, Petra; Hansen, Axel Kornerup;

    2014-01-01

    gluten-free diets prevent T1D in animal models. Herewith we investigated whether intranasal (i.n.) administration of gliadin or gluten may arrest the diabetogenic process. I.n. administration of gliadin to 4-week-old NOD mice significantly reduced the diabetes incidence. Similarly, the insulitis......Induction of long-term tolerance to β-cell autoantigens has been investigated both in animal models and in human type 1 diabetes (T1D) in order to prevent the disease. As regards external compounds, the dietary plant protein fraction has been associated with high penetrance of the disease, whereas...... was lowered. Intranasal gliadin also rescued a fraction of prediabetic 13-week-old NOD mice from progressing to clinical onset of diabetes compared to OVA-treated controls. Vaccination with i.n. gliadin led to an induction of CD4+Foxp3+ T cells and even more significant induction of γδ T cells in mucosal...

  20. PPS nanoparticles as versatile delivery system to induce systemic and broad mucosal immunity after intranasal administration.

    Science.gov (United States)

    Stano, Armando; van der Vlies, André J; Martino, Mikael M; Swartz, Melody A; Hubbell, Jeffrey A; Simeoni, Eleonora

    2011-01-17

    Degradable polymer nanoparticles (NPs, 50 nm) based on polypropylene sulfide (PPS) were conjugated to thiolated antigen and adjuvant proteins by reversible disulfide bonds and evaluated in mucosal vaccination. Ovalbumin was used as a model antigen, and antigen-conjugated NPs were administered intranasally in the mouse. We show penetration of nasal mucosae, transit via M cells, and uptake by antigen-presenting cells in the nasal-associated lymphoid tissue. Ovalbumin-conjugated NPs induced cytotoxic T lymphocytic responses in lung and spleen tissues, as well as humoral response in mucosal airways. Co-conjugation of the TLR5 ligand flagellin further enhanced humoral responses in the airways as well as in the distant vaginal and rectal mucosal compartments and induced cellular immune responses with a Th1 bias, in contrast with free flagellin. The PPS NP platform thus appears interesting as a platform for intranasally-administered mucosal vaccination for inducing broad mucosal immunity.

  1. Intranasal oxytocin attenuates the human acoustic startle response independent of emotional modulation.

    Science.gov (United States)

    Ellenbogen, Mark A; Linnen, Anne-Marie; Cardoso, Christopher; Joober, Ridha

    2014-11-01

    Oxytocin promotes social affiliation in humans. However, the mechanisms underlying this phenomenon require further elucidation. The present study investigated the influence of intranasal oxytocin on basic emotional processing in men and women, using an emotion-modulated startle response paradigm. Eighty-four participants self-administered 24 IU of intranasal oxytocin or saline and completed an assessment of the acoustic startle reflex, using electromyography (EMG), with varying emotional foregrounds. Oxytocin had no impact on the affective modulation of the startle eye blink response, but significantly diminished the acoustic startle reflex irrespective of the emotional foreground. The results suggest that oxytocin facilitates prosocial behavior, in part, by attenuating basic physiological arousal. The dampening effect of oxytocin on EMG startle could possibly be used as an inexpensive marker of oxytocin's effect on limbic brain circuits.

  2. Brain Targeting of a Water Insoluble Antipsychotic Drug Haloperidol via the Intranasal Route Using PAMAM Dendrimer.

    Science.gov (United States)

    Katare, Yogesh K; Daya, Ritesh P; Sookram Gray, Christal; Luckham, Roger E; Bhandari, Jayant; Chauhan, Abhay S; Mishra, Ram K

    2015-09-01

    Delivery of therapeutics to the brain is challenging because many organic molecules have inadequate aqueous solubility and limited bioavailability. We investigated the efficiency of a dendrimer-based formulation of a poorly aqueous soluble drug, haloperidol, in targeting the brain via intranasal and intraperitoneal administration. Aqueous solubility of haloperidol was increased by more than 100-fold in the developed formulation. Formulation was assessed via different routes of administration for behavioral (cataleptic and locomotor) responses, and for haloperidol distribution in plasma and brain tissues. Dendrimer-based formulation showed significantly higher distribution of haloperidol in the brain and plasma compared to a control formulation of haloperidol administered via intraperitoneal injection. Additionally, 6.7 times lower doses of the dendrimer-haloperidol formulation administered via the intranasal route produced behavioral responses that were comparable to those induced by haloperidol formulations administered via intraperitoneal injection. This study demonstrates the potential of dendrimer in improving the delivery of water insoluble drugs to brain.

  3. Intranasal oxytocin reduces psychotic symptoms and improves Theory of Mind and social perception in schizophrenia.

    Science.gov (United States)

    Pedersen, Cort A; Gibson, Clare M; Rau, Shane W; Salimi, Kayvon; Smedley, Kelly L; Casey, Robin L; Leserman, Jane; Jarskog, L Fredrik; Penn, David L

    2011-10-01

    Oxytocin has numerous prosocial and antipsychotic-like effects in animals. Prosocial effects of acute intranasal oxytocin administration have also been reported in human subjects. We conducted a randomized, placebo-controlled trial testing the effects of twice daily intranasal oxytocin treatment for 14 days on psychotic symptoms and social cognition in patients with schizophrenia. PANSS scores declined significantly and several social cognition measures improved significantly or nearly significantly in oxytocin (N=11) but not placebo (N=9) recipients. Our results suggest that, in addition to reducing classic psychotic symptoms, oxytocin may diminish certain social cognition deficits that are not improved by current antipsychotic medications. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Levamisole induced necrosis of the skin and neutropenia following intranasal cocaine use: a newly recognized syndrome.

    Science.gov (United States)

    Mouzakis, John; Somboonwit, Charurut; Lakshmi, Seetha; Rumbak, Mark; Sinnott, John; Cherpelis, Basil; Keshishian, Jonathan

    2011-10-01

    Levamisole is a veterinary anti-helminthic used to treat several autoimmune conditions but also commonly utilized as an additive in cocaine distribution. Toxicity resulting in agranulocytosis and cutaneous necrosis in association with cocaine use is an infrequently described phenomenon of an emerging problem. Although levamisole is found extensively in the cocaine supply of the United States, relatively few cases of necrotic skin lesions associated with intranasal use have been reported. The skin necrosis secondary to levamisole toxicity is characterized by variable findings on biopsy, ranging from leukocytoclastic vasculitis to occlusive vasculopathy. The following case describes a 54-year-old male who developed fever, agranulocytosis, p-ANCA autoantibodies and extensive skin necrosis following heavy intranasal cocaine use. Necrosis of greater than 50% of the patient's total body surface area resulted and was followed by thorough wound debridement.

  5. Synthetic polyacrylate polymers as particulate intranasal vaccine delivery systems for the induction of mucosal immune response.

    Science.gov (United States)

    Zaman, Mehfuz; Simerska, Pavla; Toth, Istvan

    2010-04-01

    The nasal route as a site of vaccine delivery for both local and systemic effect is currently of considerable interest. The administration of vaccines to mucosal surfaces such as the nasopharynx associated lymphoid tissues confers many advantages since the nasal mucosa is a primary site through which most inhaled antigens are encountered. However, the success of intranasally delivered mucosal vaccines is limited by lack of effective vaccine formulations or delivery systems suitable for use in humans. This review provides a brief overview of the mucosal immune system at the nasal surface, enhancement techniques for induction of mucosal immune response after intranasal administration of particulate systems and an explanation of the inherent properties of polyacrylate polymer-based particulate systems that may facilitate mucosal immune responses.

  6. Liposome-based intranasal delivery of lipopeptide vaccine candidates against group A streptococcus.

    Science.gov (United States)

    Ghaffar, Khairunnisa Abdul; Marasini, Nirmal; Giddam, Ashwini Kumar; Batzloff, Michael R; Good, Michael F; Skwarczynski, Mariusz; Toth, Istvan

    2016-09-01

    Group A streptococcus (GAS), an exclusively human pathogen, causes a wide range of diseases ranging from trivial to life threatening. Treatment of infection is often ineffective following entry of bacteria into the bloodstream. To date, there is no vaccine available against GAS. In this study, cationic liposomes encapsulating lipopeptide-based vaccine candidates against GAS have been employed for intranasal vaccine delivery. Cationic liposomes were prepared with dimethyldioctadecylammonium bromide (DDAB) using the film hydration method. Female Swiss mice were immunized intranasally with the liposomes. In contrast to unmodified peptides, lipopeptides entrapped by liposomes induced both mucosal and systemic immunity, IgA and IgG (IgG1 and IgG2a) production in mice, respectively. High levels of antibody (IgA and IgG) titres were detected even five months post immunization. Thus, the combination of lipopeptides and liposomes generates a very promising delivery system for intranasal vaccines. Group A streptococcus, causing rheumatic heart diseases, kills approximately half a million people annually. There is no vaccine available against the infection. Mucosal immunity is vital in ensuring an individual is protected as this gram positive bacteria initially colonizes at the throat. Herein, we demonstrated that lipopeptides entrapped by liposomes induced both mucosal and systemic immunity. High levels of antibody (IgA and IgG) titres were detected even five months post immunization and lead vaccine candidate was able to induce humoral immune responses even after single immunization. Thus, the combination of lipopeptides and liposomes generates a very promising delivery system for intranasal vaccines. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  7. Mouse Model of Cat Allergic Rhinitis and Intranasal Liposome-Adjuvanted Refined Fel d 1 Vaccine

    Science.gov (United States)

    Tasaniyananda, Natt; Chaisri, Urai; Tungtrongchitr, Anchalee; Chaicumpa, Wanpen; Sookrung, Nitat

    2016-01-01

    Cats (Felis domesticus) are rich source of airborne allergens that prevailed in the environment and sensitized a number of people to allergy. In this study, a mouse model of allergic rhinitis caused by the cat allergens was developed for the first time and the model was used for testing therapeutic efficacy of a novel intranasal liposome-entrapped vaccines made of native Fel d 1 (major cat allergen) in comparison with the vaccine made of crude cat hair extract (cCE). BALB/c mice were sensitized with cCE mixed with alum intraperitoneally and intranasally. The allergic mice were treated with eight doses of either liposome (L)-entrapped native Fel d 1 (L-nFD1), L-cCE), or placebo on every alternate day. Vaccine efficacy evaluation was performed one day after provoking the treated mice with aerosolic cCE. All allergenized mice developed histological features of allergic rhinitis with rises of serum specific-IgE and Th2 cytokine gene expression. Serum IgE and intranasal mucus production of allergic mice reduced significantly after vaccination in comparison with the placebo mice. The vaccines also caused a shift of the Th2 response (reduction of Th2 cytokine expressions) towards the non-pathogenic responses: Th1 (down-regulation of the Th1 suppressive cytokine gene, IL-35) and Treg (up-regulation of IL-10 and TGF-β). In conclusions, a mouse model of allergic rhinitis to cat allergens was successfully developed. The intranasal, liposome-adjuvanted vaccines, especially the refined single allergen formulation, assuaged the allergic manifestations in the modeled mice. The prototype vaccine is worthwhile testing further for clinical use in the pet allergic patients. PMID:26954254

  8. Abuse Potential of Intranasal Buprenorphine versus Buprenorphine/Naloxone in Buprenorphine-Maintained Heroin Users

    OpenAIRE

    2014-01-01

    In spite of the clinical utility of buprenorphine, parenteral abuse of this medication has been reported in several laboratory investigations and in the real world. Studies have demonstrated lower abuse liability of the buprenorphine/naloxone combination relative to buprenorphine alone. However, clinical research has not yet examined the utility of the combined formulation to deter intranasal use in a buprenorphine-maintained population. Heroin-using volunteers (n = 12) lived in the hospital ...

  9. Mouse Model of Cat Allergic Rhinitis and Intranasal Liposome-Adjuvanted Refined Fel d 1 Vaccine.

    Directory of Open Access Journals (Sweden)

    Natt Tasaniyananda

    Full Text Available Cats (Felis domesticus are rich source of airborne allergens that prevailed in the environment and sensitized a number of people to allergy. In this study, a mouse model of allergic rhinitis caused by the cat allergens was developed for the first time and the model was used for testing therapeutic efficacy of a novel intranasal liposome-entrapped vaccines made of native Fel d 1 (major cat allergen in comparison with the vaccine made of crude cat hair extract (cCE. BALB/c mice were sensitized with cCE mixed with alum intraperitoneally and intranasally. The allergic mice were treated with eight doses of either liposome (L-entrapped native Fel d 1 (L-nFD1, L-cCE, or placebo on every alternate day. Vaccine efficacy evaluation was performed one day after provoking the treated mice with aerosolic cCE. All allergenized mice developed histological features of allergic rhinitis with rises of serum specific-IgE and Th2 cytokine gene expression. Serum IgE and intranasal mucus production of allergic mice reduced significantly after vaccination in comparison with the placebo mice. The vaccines also caused a shift of the Th2 response (reduction of Th2 cytokine expressions towards the non-pathogenic responses: Th1 (down-regulation of the Th1 suppressive cytokine gene, IL-35 and Treg (up-regulation of IL-10 and TGF-β. In conclusions, a mouse model of allergic rhinitis to cat allergens was successfully developed. The intranasal, liposome-adjuvanted vaccines, especially the refined single allergen formulation, assuaged the allergic manifestations in the modeled mice. The prototype vaccine is worthwhile testing further for clinical use in the pet allergic patients.

  10. Recurrent epistaxis caused by an intranasal supernumerary tooth in a young adult

    OpenAIRE

    Al Dhafeeri, Hamed O.; Kavarodi, Abdulmajid; Shaikh, Khalil Al; Bukhari, Ahmed; Hussain, Omair Al; Baramawy, Ahmed El

    2014-01-01

    Patient: Male, 27 Final Diagnosis: Recurrent epistaxis Symptoms: Nasal bleeding Medication: — Clinical Procedure: — Specialty: Pediatrics and Neonatology Objective: Congenital defects/diseases Background: Recurrent epistaxis is a common disorder among children and young adults. We report an unusual cause, intranasal supernumerary tooth causing friction with Little’s area of the nasal septum. Case Report: A 22-year-old male presented with recurrent, mild, unilateral left-sided epistaxis once t...

  11. A Comparison of Intranasal and Oral Scopolamine for Motion Sickness Prevention in Military Personnel

    Science.gov (United States)

    2008-08-18

    were recruited and randomized to one of three treatment groups [intranasal scopolamine gel (IN SCOP ); oral scopolamine (PO SCOP ); or placebo] and...head movements tolerated among groups and pharmacotherapeutics for IN SCOP and PO SCOP were determined by salivary assay. Side-effect profiles for all...cognitive battery, VA, or KSS, p > 0.05. An ANOVA revealed a significant decrease in heart rate over time for IN SCOP and PO SCOP versus placebo at

  12. Intranasal telmisartan ameliorates brain pathology in five familial Alzheimer's disease mice.

    Science.gov (United States)

    Torika, Nofar; Asraf, Keren; Cohen, Hagit; Fleisher-Berkovich, Sigal

    2017-08-01

    The renin-angiotensin system (RAS) is a major circulative system engaged in homeostasis modulation. Angiotensin II (Ang II) serves as its main effector hormone upon binding to its primary receptor, Ang II receptor type 1 (AT1R). It is well established that an intrinsic independent brain RAS exists. Abnormal AT1R activation both in the periphery and in the brain probably contributes to the development of Alzheimer's disease (AD) pathology that is characterized, among others, by brain inflammation. Moreover, treatment with drugs that block AT1R (AT1R blockers, ARBs) ameliorates most of the clinical risk factors leading to AD. Previously we showed that short period of intranasal treatment with telmisartan (a brain penetrating ARB) reduced brain inflammation and ameliorated amyloid burden (a component of Alzheimer's plaques) in AD transgenic mouse model. In the present study, we aimed to examine the long-term effect of intranasally administrated telmisartan on brain inflammation features including microglial activation, astrogliosis, neuronal loss and hippocampus-dependent cognition in five-familial AD mouse model (5XFAD). Five month of intranasal treatment with telmisartan significantly reduced amyloid burden in the cortex and hippocampus of 5XFAD mice as compared with the vehicle-treated 5XFAD group. Similar effects were also observed for CD11b staining, which is a marker for microglial accumulation. Telmisartan also significantly reduced astrogliosis and neuronal loss in the cortex of 5XFAD mice compared with the vehicle-treated group. Improved spatial acquisition of the 5XFAD mice following long-term intranasal administration of telmisartan was also observed. Taken together, our data suggest a significant role for AT1R blockage in mediating neuronal loss and cognitive behavior, possibly through regulation of amyloid burden and glial inflammation. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Preparation, characterization, and in vivo evaluation of intranasally administered liposomal formulation of donepezil

    Directory of Open Access Journals (Sweden)

    Al Asmari AK

    2016-01-01

    Full Text Available Abdulrahman K Al Asmari,1 Zabih Ullah,1 Mohammad Tariq,1 Amal Fatani21Department of Research, Prince Sultan, Military Medical City, 2Department of Pharmacy, King Saud University, Riyadh, Saudi ArabiaAbstract: The adequate amount of drug delivery to the brain in neurological patients is a major problem faced by the physicians. Recent studies suggested that intranasal administration of liposomal formulation may improve the drug delivery to the brain. In the present study, an attempt was made to study the brain bioavailability of commonly used anti-Alzheimer drug donepezil (DNP liposomal formulation by intranasal route in rats. We adopted the thin layer hydration technique for the preparation of liposomes by using cholesterol, polyethylene glycol, and 1,2-distearyl-sn-glycero-3-phosphocholine (DSPC. The prepared liposomes were characterized by determining particle size, shape, surface morphology, zeta potential, encapsulation efficiency, and in vitro release of DNP. The pharmacokinetic parameters of liposomal DNP in plasma and brain of rats were determined following oral and nasal administration. The results of this study showed that the DNP liposomal formulation was stable with a consistent size (102±3.3 nm and shape. The prepared liposomes showed high encapsulation efficiency (84.91%±3.31% and sustained-release behavior. The bioavailability of DNP in plasma and brain increased significantly (P<0.05 after administration of liposomal formulation by the intranasal route. Histopathological examination showed that the formulation was safe and free from toxicity. It can be concluded that the nasal administration of liposomal preparation may provide an efficient and reliable mode of drug delivery to the central nervous system.Keywords: donepezil, intranasal, liposomes, bioavailability, blood–brain barrier

  14. Nanoemulsion-based intranasal drug delivery system of saquinavir mesylate for brain targeting.

    Science.gov (United States)

    Mahajan, Hitendra S; Mahajan, Milind S; Nerkar, Pankaj P; Agrawal, Anshuman

    2014-03-01

    The central nervous system (CNS) is an immunological privileged sanctuary site-providing reservoir for HIV-1 virus. Current anti-HIV drugs, although effective in reducing plasma viral levels, cannot eradicate the virus completely from the body. The low permeability of anti-HIV drugs across the blood-brain barrier (BBB) leads to insufficient delivery. Therefore, developing a novel approaches enhancing the CNS delivery of anti-HIV drugs are required for the treatment of neuro-AIDS. The aim of this study was to develop intranasal nanoemulsion (NE) for enhanced bioavailability and CNS targeting of saquinavir mesylate (SQVM). SQVM is a protease inhibitor which is a poorly soluble drug widely used as antiretroviral drug, with oral bioavailability is about 4%. The spontaneous emulsification method was used to prepare drug-loaded o/w nanoemulsion, which was characterized by droplet size, zeta potential, pH, drug content. Moreover, ex-vivo permeation studies were performed using sheep nasal mucosa. The optimized NE showed a significant increase in drug permeation rate compared to the plain drug suspension (PDS). Cilia toxicity study on sheep nasal mucosa showed no significant adverse effect of SQVM-loaded NE. Results of in vivo biodistribution studies show higher drug concentration in brain after intranasal administration of NE than intravenous delivered PDS. The higher percentage of drug targeting efficiency (% DTE) and nose-to-brain drug direct transport percentage (% DTP) for optimized NE indicated effective CNS targeting of SQVM via intranasal route. Gamma scintigraphy imaging of the rat brain conclusively demonstrated transport of drug in the CNS at larger extent after intranasal administration as NE.

  15. The Pharmacokinetics and Efficacy of a Low-dose, Aqueous, Intranasal Scopolamine Spray

    Science.gov (United States)

    2017-09-27

    21. Simmons, R. G., Phillips , J. B., Lojewski, R. A., Wang, Z., Boyd, J. L., & Putcha, L. (2010). The efficacy of low-dose intranasal scopolamine...for motion sickness. Aviation, Space, and Environmental Medicine, 81, 405-412. 22. Simmons, R. G., Phillips , J. B., & Lojewski, R. A. (2008...of Medicine and Surgery, Department of the Navy. 23. Simmons, R. G., Phillips , J. B., Lowjeski, R. A., & Lawson, B. D. (2008). A comparison of

  16. A Feasibility Trial of Home Administration of Intranasal Vaccine by Parents to Eligible Children.

    Science.gov (United States)

    Jhaveri, Ravi; Allyne, Kristin

    2017-01-01

    Intranasal vaccines are being developed for protection against many different infectious agents. The currently available intranasal live attenuated influenza vaccine (LAIV) is only approved for administration by medical personnel. We conducted a pilot study to investigate the feasibility of training parents to give LAIV to their own children. Subjects were recruited from several sources: a university-based outpatient clinic, university employee e-mail announcement, and direct referrals from study subjects. After confirming eligibility to receive LAIV, consented parents were trained by viewing a video with the study staff. LAIV was provided in a cooler with instructions to vaccinate within 24 hours. Telephone follow-up was conducted to confirm proper administration and to assess parental attitudes about home administration. At season's end, immunization registry and hospital records were reviewed to confirm no additional doses were given. Twenty-seven families with 41 children were enrolled. All participants successfully administered LAIV to their children, and all preferred or strongly preferred home administration to an office visit for getting vaccinated. Two families stated that without this option they would not have otherwise vaccinated their children. Adverse events were minor. All patients had their state vaccine registries accurately updated and none received duplicate doses. Upon review, no reimbursement was received for vaccination. Home administration of intranasal LAIV was successful and well received. This option could be used in the future for LAIV or other intranasal vaccines as a way to increase vaccination rates and convenience for parents. ClinicalTrials.gov identifier: NCT01938170. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  17. Intranasal delivery of Natesto® testosterone gel and its effects on doping markers.

    Science.gov (United States)

    Miller, Geoffrey D; Nair, Vinod; Morrison, M Scott; Summers, Maggie; Willick, Stuart E; Eichner, Daniel

    2016-11-01

    The laboratory profile of intranasal testosterone gel has not been previously reported from an anti-doping perspective. Because intranasal testosterone gel is newly available as a commercial product, we sought to examine the laboratory parameters following administration of this formulation, with particular attention to anti-doping guidelines. Five healthy and active male subjects were administered testosterone intranasal gel three times daily for four weeks, using a pattern of five consecutive days on, two days off. Urine was collected after each five-day round of drug administration and analyzed using a full steroid screen and isotope ratio mass spectrometry (IRMS). Windows of detection for elevated testosterone/epitestosterone (T/E) and other steroid ratios, World Anti-Doping Agency (WADA) athlete biological passport (ABP) findings, and IRMS results were analyzed in this study. In the 0-24 h window post-administration, 70% of samples were flagged with a suspicious steroid profile and 85% were flagged as atypical passport findings according to the WADA ABP steroid module. In the 24-48 h window, 0% of samples displayed suspicious steroid profiles while 40% resulted in atypical passport findings. IRMS testing confirmed the presence of exogenous testosterone in 90% and 40% of samples in the 0-24 h and 24-48 h windows post-administration, respectively. Additionally, IRMS data were analyzed to determine commonalities in the population changes in δ(13) C values of testosterone, androsterone, etiocholanolone, 5αAdiol, and 5βAdiol. Though no discernible metabolic trend of the route of administration was identified, we discovered that intranasal gel testosterone is detectable using conventional anti-doping tests. Copyright © 2016 John Wiley & Sons, Ltd.

  18. Intranasal midazolam compared with intravenous diazepam in patients suffering from acute seizure: a randomized clinical trial.

    Science.gov (United States)

    Javadzadeh, Mohsen; Sheibani, Kourosh; Hashemieh, Mozhgan; Saneifard, Hedyeh

    2012-03-01

    Acute seizure attack is a stressful experience both for health care personnel and parents. These attacks might cause morbidity and mortality among patients, so reliable methods to control the seizure preferably at home should be developed. This study was performed to measure the time needed to control seizure attacks using intranasal midazolam compared to the common treatment (intravenous diazepam) and to evaluate its probable side effects. This study was conducted as a not blind randomized clinical trial among 60 patients coming to Imam Ali Hospital, Zahedan, Iran. The patients were 2 months to 15 years old children coming to our emergency department suffering from an acute seizure episode. Intranasal midazolam was administered 0.2 mg/kg equally dropped in both nostrils for case group and intravenous diazepam was administered 0.3mg/kg via IV line for control group. After both treatments the time needed to control the seizure was registered by the practitioner. Pulse rate and O2 saturation were recorded at patients' entrance and in minutes 5 and 10 after drug administration. The time needed to control seizure using intranasal midazolam (3.16±1.24) was statistically shorter than intravenous diazepam (6.42±2.59) if the time needed to establish IV line in patients treated by intravenous diazepam is taken into account (P<0.001). The readings for O2 saturation or heart rate did not indicate a statistically significant difference between two groups of patients either at entrance or 5 and 10 minutes after drug administration. Considering the shorter time needed to control acute seizure episodes compared to intravenous diazepam and its safety record, intranasal midazolam seems to be a good candidate to replace diazepam, as the drug of choice, in controlling this condition.

  19. INTRANASAL DELIVERY OF NERVE GROWTH FACTOR TO PROTECT THE CENTRAL NERVOUS SYSTEM AGAINST ACUTE CEREBRAL INFARCTION

    Institute of Scientific and Technical Information of China (English)

    Hong-mei Zhao; Xin-feng Liu; Xiao-wei Mao; Chun-fu Chen

    2004-01-01

    Objective To confirmed reliability and feasibility of intranasal nerve growth factor (NGF) bypassing the blood-brain barrier and its potential neuroprotective effects on acute cerebral ischemia.Methods (1) To assay NGF concentrations in different brain regions after middle cerebral artery occlusion (MCAO).Rats were randomly divided into intranasal (IN) NGF, intravenous (Ⅳ) NGF, and untreated group (n =4). The concentrations of NGF of different brain regions in the three groups after MCAO were measured by ELISA. (2) To observe neuroprotective action of NGF on focal cerebral ischemic damage. Rats were randomly assigned to 4 groups: IN vehicle, IN NGF,Ⅳ vehicle, Ⅳ NGF (n = 8). Treatment was initiated 30 minutes after onset of MCAO and given again 24 hours later. Three neurologic behavioral tests were performed 24 and 48 hours following onset of MCAO. Corrected infarct volumes were determined 48 hours after onset of MCAO.Results The olfactory bulb in IN NGF group obtained the highest concentration (3252 pg/g) of NGF among all regions, followed by the hippocumpus. The NGF concentrations in the olfactory bulb and hippocampus in IN NGF group were markedly higher than that in Ⅳ NGF and control groups. The infarct volume in IN NGF group was markedly reduced by 38.8% compared with IN vehicle group. IN NGF group vestibulum function markedly improved compared with IN vehicle group at 24 and 48 hours after onset of MCAO (P24h = 0.02 and P48h = 0.04, respectively).Conclusion Intranasal NGF could pass through the blood-brain barrier, reach the central nervous system, reduce infarct volume, and improve neurologic function in rats following MCAO. Intranasal delivery of NGF may be a promising treatment for stroke.

  20. Dente intranasal em portador de fissura de lábio e palato: relato de caso Intranasal tooth in patient with cleft lip and palate: case report

    Directory of Open Access Journals (Sweden)

    Aline Rogéria F. de Castilho

    2004-12-01

    Full Text Available A presença de dentes na cavidade nasal é rara e inclui alguns sinais e sintomas característicos, como obstrução nasal, rinite casual e odor fétido, entre outros, que podem ser confundidos com outras patologias. Por esta razão, o diagnóstico diferencial deve ser bem executado, por meio dos exames clínico e radiográfico da região. O tratamento, geralmente, é cirúrgico e pode prevenir complicações secundárias. O presente trabalho apresenta um caso de dente intranasal e seu respectivo tratamento cirúrgico para remoção.The presence of teeth at the nasal cavity is rare and involves some characteristic signs and symptoms, such as nasal obstruction, eventual rhinitis and fetid smell, and also others that may be confused with other pathologies. Therefore, differential diagnosis should be carefully accomplished by means of clinical and radiographic examinations of the area. Treatment is usually surgical and may prevent secondary complications. The present paper presents a case of intranasal tooth and the respective surgical treatment for its removal.

  1. Laboratory diagnosis of amebiasis in a sample of students from southeastern Brazil and a comparison of microscopy with enzyme-linked immunosorbent assay for screening of infections with Entamoeba sp.

    Directory of Open Access Journals (Sweden)

    Valeriana Valadares Pereira

    2014-01-01

    Full Text Available Introduction: Epidemiological studies on amebiasis have been reassessed since Entamoeba histolytica and E. dispar were first recognized as distinct species. Because the morphological similarity of these species renders microscopic diagnosis unreliable, additional tools are required to discriminate between Entamoeba species. The objectives of our study were to compare microscopy with ELISA kit (IVD® results, to diagnose E. histolytica infection, and to determine the prevalence of amebiasis in a sample of students from southeastern Brazil. Methods: In this study, diagnosis was based on microscopy due to its capacity for revealing potential cysts/trophozoites and on two commercial kits for antigen detection in stool samples. Results: For 1,403 samples collected from students aged 6 to 14 years who were living in Divinópolis, Minas Gerais, Brazil, microscopy underestimated the number of individuals infected with E. histolytica/E. dispar (5.7% prevalence compared with the ELISA kit (IVD®-based diagnoses (15.7% for E. histolytica/E. dispar. A comparison of the ELISA (IVD® and light microscopy results returned a 20% sensitivity, 97% specificity, low positive predictive value, and high negative predictive value for microscopy. An ELISA kit (TechLab® that was specific for E. histolytica detected a 3.1% (43/1403 prevalence for E. histolytica infection. Conclusions: The ELISA kit (IVD® can be used as an alternative screening tool. The high prevalence of E. histolytica infection detected in this study warrants the implementation of actions directed toward health promotion and preventive measures.

  2. Comparison of Behavior and Dental Anxiety During Intranasal and Sublingual Midazolam Sedation - A Randomized Controlled Trial.

    Science.gov (United States)

    Shanmugaavel, A K; Asokan, Sharath; Baby, John J; Priya, Geetha; Gnana Devi, J

    2016-01-01

    The objective of the study was to assess the behavioral effects and the changes in the anxiety level of children after intranasal and sublingual midazolam sedation using Venham's clinical anxiety scale and salivary cortisol level. Twenty children aged 3 to 7 years were randomly assigned to Group A (n=10) intranasal or Group B (n=10) sublingual midazolam (0.2mg/kg) sedation. The anxiety levels at various time periods were assessed using Venham clinical anxiety scale and corresponding changes in salivary cortisol levels were assessed before and after the drug administration. The anxiety levels were assessed independently by two pediatric dentists from recorded videos. Wilcoxon signed rank test and Mann Whitney U test were used for statistical analysis using SPSS version 19.0. There was a significant decrease in anxiety level from baseline to 20 minutes after drug administration in group A (p=0.004) and group B (p=0.003). There was no significant change in salivary cortisol levels before and after the drug administration in group A (p=0.07) and group B (p=0.38). Both intranasal and sublingual administration of midazolam was equally effective in reducing the child's anxiety. However, there was no significant difference in the salivary cortisol levels in both groups.

  3. Midazolam premedication in children: a pilot study comparing intramuscular and intranasal administration.

    Science.gov (United States)

    Lam, Christy; Udin, Richard D; Malamed, Stanley F; Good, David L; Forrest, Jane L

    2005-01-01

    The purpose of this study was to compare the effectiveness of intramuscular and intranasal midazolam used as a premedication before intravenous conscious sedation. Twenty-three children who were scheduled to receive dental treatment under intravenous sedation participated. The patients ranged in age from 2 to 9 years (mean age, 5.13 years) and were randomly assigned to receive a dose of 0.2 mg/kg of midazolam premedication via either intramuscular or intranasal administration. All patients received 50% nitrous oxide and 50% oxygen inhalation sedation and local anesthetic (0.2 mL of 4% prilocaine hydrochloride) before venipuncture. The sedation level, movement, and crying were evaluated at the following time points: 10 minutes after drug administration and at the times of parental separation, passive papoose board restraint, nitrous oxide nasal hood placement, local anesthetic administration, and initial venipuncture attempt. Mean ratings for the behavioral parameters of sedation level, degree of movement, and degree of crying were consistently higher but not significant in the intramuscular midazolam group at all 6 assessment points. Intramuscular midazolam was found to be statistically more effective in providing a better sedation level and less movement at the time of venipuncture than intranasal administration. Our findings indicate a tendency for intramuscular midazolam to be more effective as a premedication before intravenous sedation.

  4. COMPARING EFFECTIVENESS OF ORAL AND INTRANASAL MIDAZOLAM FOR PREMEDITATION IN CHILDREN

    Directory of Open Access Journals (Sweden)

    P SAJEDI

    2000-03-01

    Full Text Available Background. Preoperative evaluation and psychological preparation is important before anesthesia. Children are very dependent to their parents, specially before 5 years. Anesthesiologist must administer anxiolytic and sedative drugs before separation from parents as premeditation. The aim of this study is comparison survey on effect of oral midazolam and intranasal midazolam in children 1 to 5 years as premeditation. Methods. In a clinical trial study performed through first half of 1377 at St. Alzahra Center (Isfahan University of Medicine, sixty healthy children in first class of ASA who had non gastrointestinal elective surgery were studied. Group one consisted of thirty children who received intravenous form midazolam (0.5 mg/kg with fruit juice orally 45 to 60 minutes before operation. Group 2 consisted of thirty children who received midazolam (IV form 0.2 mg/kg intranasally 15 minutes before operation. Findings. Anxiety was less in first group during administration of drug. Forty four percent were quiet in this group (P < 0.005. Seventy six percent of children who well accepted the drug, were in the first group (P < 0.005. There was no significant statistical difference between two groups in other aspects of study. Conclusion. Oral administration of midazolam has better acceptance in children than intranasal with less anxiety.

  5. Optimization of combinational intranasal drug delivery system for the management of migraine by using statistical design.

    Science.gov (United States)

    Kumar, Animesh; Garg, Tarun; Sarma, Ganti S; Rath, Goutam; Goyal, Amit Kumar

    2015-04-01

    Migraine is a chronic disorder characterized by significant headache and various associated symptoms which worsen with exertion. Zolmitriptan approved for use in the acute treatment of migraine and related vascular headaches but are limited by high pain recurrence due to rapid drug elimination. Combinationalformulationof triptans and a nonsteroidal anti-inflammatory drug may provide a quicker and longer duration of relief from the subsequent pain during the attack. In this study, we formulate a Zolmitriptan (ZT) & ketorolac tromethamine (KT) loaded thermo reversible in-situ mucoadhesive intranasal gel (TMISG) formulation which gels at the nasal mucosal temperature and contains a bioadhesive polymer (Xyloglucan) that lengthens the residence time will enhance the bioavailability of the combinational drugs. This study uses Box-Behnken design for the first time to develop, optimize the TMISG and assess factors affecting the critical quality attributes. Histopathological study of the nasal mucosa suggested that the formulation was safe for nasal administration. The statistical difference in absolute bioavailability between oral and intranasal route suggested that intranasal route had almost 21% increases in bioavailability for ZT and for KT there was 16% increase over oral formulations. Optimized formulation would help mitigate migraine associated symptoms much better over the currently available formulations.

  6. Thermo-sensitive gels containing lorazepam microspheres for intranasal brain targeting.

    Science.gov (United States)

    Jose, S; Ansa, C R; Cinu, T A; Chacko, A J; Aleykutty, N A; Ferreira, S V; Souto, E B

    2013-01-30

    Thermo-sensitive gels containing lorazepam microspheres were developed and characterized for intranasal brain targeting. Pluronics (PF-127 and PF-68) have been selected since they are thermo-reversible polymers with the property of forming a solution at low temperatures (4-5 °C), and a gel at body temperature (37 °C). This property makes them an interesting material to work with, especially in case of controlled release formulations. The present study focuses on the development of an intranasal formulation for lorazepam, as an alternative route of drug delivery to the brain. Direct transport of drugs to the brain circumventing the brain barrier, following intranasal administration, provides a unique feature and better option to target brain. The presence of mucoadhesive microspheres in the gel vehicle via nasal route can achieve a dual purpose of prolonged drug release and enhanced bioavailability. To optimise the microsphere formulation, Box Behnken design was employed by investigating the effect of three factors, polymer concentration (chitosan), emulsifier concentration (Span 80) and cross-linking agent (glutaraldehyde) on the response variable which is the mean particle size. The concentration of 21% PF-127 and 1% PF-68 were found to be promising gel vehicles. The results showed that the release rate followed a prolonged profile dispersion of the microspheres in the viscous media, in comparison to the microspheres alone. Histopathological studies proved that the optimised formulation does not produce any toxic effect on the microscopic structure of nasal mucosa.

  7. [Targeting the brain through the nose. Effects of intranasally administered insulin].

    Science.gov (United States)

    Brünner, Y F; Benedict, C; Freiherr, J

    2013-08-01

    The assumption that the human brain is an insulin-independent organ was disproved with the discovery of insulin receptors in the central nervous system in the year 1978. Evidence has been provided for a high density of insulin receptors in brain regions responsible for cognitive memory processes (hippocampus) and for the regulation of appetite (hypothalamus). Accordingly, in animal studies an increased insulin level in the central nervous system leads to an improvement of hippocampal memory function and a decrease of food intake. Similar results were obtained in humans using the method of intranasal administration of insulin. Intranasal insulin reaches the brain and the cerebrospinal fluid via the olfactory epithelium and olfactory nerve fiber bundles leading through the lamina cribrosa to the olfactory bulb. Thus, this method renders the investigation of specific insulin effects in humans possible. The therapeutic potential of an intranasal insulin administration for the treatment of diseases for which an imbalance of the central nervous insulin metabolism is discussed (e.g. Alzheimer's disease, diabetes mellitus and obesity) can only be estimated with the help of further clinical studies.

  8. Mexico City air pollution adversely affects olfactory function and intranasal trigeminal sensitivity.

    Science.gov (United States)

    Guarneros, Marco; Hummel, Thomas; Martínez-Gómez, Margaríta; Hudson, Robyn

    2009-11-01

    Surprisingly little is known about the effects of big-city air pollution on olfactory function and even less about its effects on the intranasal trigeminal system, which elicits sensations like burning, stinging, pungent, or fresh and contributes to the overall chemosensory experience. Using the Sniffin' Sticks olfactory test battery and an established test for intranasal trigeminal perception, we compared the olfactory performance and trigeminal sensitivity of residents of Mexico City, a region with high air pollution, with the performance of a control population from the Mexican state of Tlaxcala, a geographically comparable but less polluted region. We compared the ability of 30 young adults from each location to detect a rose-like odor (2-phenyl ethanol), to discriminate between different odorants, and to identify several other common odorants. The control subjects from Tlaxcala detected 2-phenyl ethanol at significantly lower concentrations than the Mexico City subjects, they could discriminate between odorants significantly better, and they performed significantly better in the test of trigeminal sensitivity. We conclude that Mexico City air pollution impairs olfactory function and intranasal trigeminal sensitivity, even in otherwise healthy young adults.

  9. Intranasal Delivery of Camptothecin-Loaded Tat-Modified Nanomicells for Treatment of Intracranial Brain Tumors

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    Yuuki Takashima

    2012-10-01

    Full Text Available The blood-brain barrier is a substantial obstacle for delivering anticancer agents to brain tumors, and new strategies for bypassing it are sorely needed for brain tumor therapy. Intranasal delivery provides a practical, noninvasive method for delivering therapeutic agents to the brain. Intranasal application of nano-sized micelles that have been modified with Tat peptide facilitates brain delivery of fluorescent model materials. In this study, we evaluated a nose-to-brain delivery system for brain tumor therapy. We nasally administered the anti-tumor drug camptothecin (CPT in solution and in methoxy poly(ethylene glycol (MPEG/poly(e-caprolactone (PCL amphiphilic block copolymers (MPEG-PCL and cell penetrating peptide, Tat analog-modified MPEG-PCL (MPEG-PCL-Tat MPEG-PCL-Tat to rats bearing intracranial glioma tumors and quantified the cytotoxicity against glioma cells, and the therapeutic effects. CPT-loaded MPEG-PCL-Tat micelles showed higher cytotoxicity than CPT-loaded MPEG-PCL. CPT-free MPEG-PCL-Tat didn’t show any cytotoxicity, even at high concentrations (2 mmol/mL. CPT-loaded MPEG-PCL-Tat micelles significantly prolonged the median survival of rats. These results indicate that intranasal delivery of anti-cancer drugs with cell penetrating peptide-modified nanomicelles might be an effective therapy for brain tumors.

  10. Intranasal, siRNA Delivery to the Brain by TAT/MGF Tagged PEGylated Chitosan Nanoparticles

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    Meenakshi Malhotra

    2013-01-01

    Full Text Available Neurodegeneration is characterized by progressive loss of structure and function of neurons. Several therapeutic methods and drugs are available to alleviate the symptoms of these diseases. The currently used delivery strategies such as implantation of catheters, intracarotid infusions, surgeries, and chemotherapies are invasive in nature and pose a greater risk of postsurgical complications, which can have fatal side effects. The current study utilizes a peptide (TAT and MGF tagged PEGylated chitosan nanoparticle formulation for siRNA delivery, administered intranasally, which can bypass the blood brain barrier. The study investigates the optimal dose, duration, biodistribution, and toxicity, of the nanoparticle-siRNA formulation, in-vivo. The results indicate that 0.5 mg/kg of siRNA is delivered successfully to the hippocampus, thalamus, hypothalamus, and Purkinje cells in the cerebellum after 4 hrs of post intranasal delivery. The results indicate maximum delivery to the brain in comparison to other tissues with no cellular toxic effects. This study shows the potential of peptide-tagged PEGylated chitosan nanoparticles to be delivered intranasally and target brain tissue for the treatment of neurological disorders.

  11. Intranasal Insulin Improves Age-Related Cognitive Deficits and Reverses Electrophysiological Correlates of Brain Aging.

    Science.gov (United States)

    Maimaiti, Shaniya; Anderson, Katie L; DeMoll, Chris; Brewer, Lawrence D; Rauh, Benjamin A; Gant, John C; Blalock, Eric M; Porter, Nada M; Thibault, Olivier

    2016-01-01

    Peripheral insulin resistance is a key component of metabolic syndrome associated with obesity, dyslipidemia, hypertension, and type 2 diabetes. While the impact of insulin resistance is well recognized in the periphery, it is also becoming apparent in the brain. Recent studies suggest that insulin resistance may be a factor in brain aging and Alzheimer's disease (AD) whereby intranasal insulin therapy, which delivers insulin to the brain, improves cognition and memory in AD patients. Here, we tested a clinically relevant delivery method to determine the impact of two forms of insulin, short-acting insulin lispro (Humalog) or long-acting insulin detemir (Levemir), on cognitive functions in aged F344 rats. We also explored insulin effects on the Ca(2+)-dependent hippocampal afterhyperpolarization (AHP), a well-characterized neurophysiological marker of aging which is increased in the aged, memory impaired animal. Low-dose intranasal insulin improved memory recall in aged animals such that their performance was similar to that seen in younger animals. Further, because ex vivo insulin also reduced the AHP, our results suggest that the AHP may be a novel cellular target of insulin in the brain, and improved cognitive performance following intranasal insulin therapy may be the result of insulin actions on the AHP.

  12. Cellular immune responses to nine Mycobacterium tuberculosis vaccine candidates following intranasal vaccination.

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    Suraj B Sable

    Full Text Available BACKGROUND: The identification of Mycobacterium tuberculosis vaccines that elicit a protective immune response in the lungs is important for the development of an effective vaccine against tuberculosis. METHODS AND PRINCIPAL FINDINGS: In this study, a comparison of intranasal (i.n. and subcutaneous (s.c. vaccination with the BCG vaccine demonstrated that a single moderate dose delivered intranasally induced a stronger and sustained M. tuberculosis-specific T-cell response in lung parenchyma and cervical lymph nodes of BALB/c mice than vaccine delivered subcutaneously. Both BCG and a multicomponent subunit vaccine composed of nine M. tuberculosis recombinant proteins induced strong antigen-specific T-cell responses in various local and peripheral immune compartments. Among the nine recombinant proteins evaluated, the alanine proline rich antigen (Apa, Rv1860 was highly antigenic following i.n. BCG and immunogenic after vaccination with a combination of the nine recombinant antigens. The Apa-induced responses included induction of both type 1 and type 2 cytokines in the lungs as evaluated by ELISPOT and a multiplexed microsphere-based cytokine immunoassay. Of importance, i.n. subunit vaccination with Apa imparted significant protection in the lungs and spleen of mice against M. tuberculosis challenge. Despite observed differences in the frequencies and location of specific cytokine secreting T cells both BCG vaccination routes afforded comparable levels of protection in our study. CONCLUSION AND SIGNIFICANCE: Overall, our findings support consideration and further evaluation of an intranasally targeted Apa-based vaccine to prevent tuberculosis.

  13. Midazolam Premedication in Children: A Pilot Study Comparing Intramuscular and Intranasal Administration

    Science.gov (United States)

    Lam, Christy; Udin, Richard D; Malamed, Stanley F; Good, David L; Forrest, Jane L

    2005-01-01

    The purpose of this study was to compare the effectiveness of intramuscular and intranasal midazolam used as a premedication before intravenous conscious sedation. Twenty-three children who were scheduled to receive dental treatment under intravenous sedation participated. The patients ranged in age from 2 to 9 years (mean age, 5.13 years) and were randomly assigned to receive a dose of 0.2 mg/kg of midazolam premedication via either intramuscular or intranasal administration. All patients received 50% nitrous oxide and 50% oxygen inhalation sedation and local anesthetic (0.2 mL of 4% prilocaine hydrochloride) before venipuncture. The sedation level, movement, and crying were evaluated at the following time points: 10 minutes after drug administration and at the times of parental separation, passive papoose board restraint, nitrous oxide nasal hood placement, local anesthetic administration, and initial venipuncture attempt. Mean ratings for the behavioral parameters of sedation level, degree of movement, and degree of crying were consistently higher but not significant in the intramuscular midazolam group at all 6 assessment points. Intramuscular midazolam was found to be statistically more effective in providing a better sedation level and less movement at the time of venipuncture than intranasal administration. Our findings indicate a tendency for intramuscular midazolam to be more effective as a premedication before intravenous sedation. PMID:16048152

  14. Intranasal vaccination with leishmanial antigens protects golden hamsters (Mesocricetus auratus against Leishmania (Viannia Braziliensis infection.

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    Luzinei da Silva-Couto

    2015-01-01

    Full Text Available Previous results have shown that oral and intranasal administration of particulate Leishmania (Leishmania amazonensis antigens (LaAg partially protects mice against L. amazonensis infection. However, vaccination studies on species of the subgenus Viannia, the main causative agent of cutaneous and mucosal leishmaniasis in the Americas, have been hampered by the lack of easy-to-handle bio-models that accurately mimic the human disease. Recently, we demonstrated that the golden hamster is an appropriate model for studying the immunopathogenesis of cutaneous leishmaniasis caused by L. (Viannia braziliensis. Using the golden hamster model, our current study investigated whether the protective effect of intranasal immunisation with LaAg can be extended to L. braziliensis infection.Golden hamsters vaccinated with either two intranasal (IN doses of LaAg (10 µg or two intramuscular doses of LaAg (20 µg were challenged 2 weeks post-vaccination with L. braziliensis. The results showed that IN immunisation with LaAg significantly reduced lesion growth and parasitic load as well as serum IgG and IgG2 levels. At the experimental endpoint on day 114 post-infection, IN-immunised hamsters that were considered protected expressed IFN-γ and IL10 mRNA levels that returned to uninfected skin levels. In contrast to the nasal route, intramuscular (IM immunisation failed to provide protection.These results demonstrate for the first time that the nasal route of immunisation can induce cross protection against L. braziliensis infection.

  15. Mucoadhesive microemulsion of ibuprofen: design and evaluation for brain targeting efficiency through intranasal route

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    Surjyanarayan Mandal

    2015-09-01

    Full Text Available This study aimed at designing mucoadhesive microemulsion gel to enhance the brain uptake of Ibuprofen through intranasal route. Ibuprofen loaded mucoadhesive microemulsion (MMEI was developed by incorporating polycarbophil as mucoadhesive polymer into Capmul MCM based optimal microemulsion (MEI and was subjected to characterization, stability, mucoadhesion and naso-ciliotoxicity study. Brain uptake of ibuprofen via nasal route was studied by performing biodistribution study in Swiss albino rats. MEI was found to be transparent, stable and non ciliotoxic with 66.29 ± 4.15 nm, -20.9 ± 3.98 mV and 98.66 ± 1.01% as average globule size, zeta potential and drug content respectively. Transmission Electron Microscopy (TEM study revealed the narrow globule size distribution of MEI. Following single intranasal administration of MMEI and MEI at a dose of 2.86 mg/kg, uptake of ibuprofen in the olfactory bulb was around 3.0 and 1.7 folds compared with intravenous injection of ibuprofen solution (IDS. The ratios of AUC in brain tissues to that in plasma obtained after nasal administration of MMEI were significantly higher than those after intravenous administration of IDS. Findings of the present investigation revealed that the developed mucoadhesive microemulsion gel could be a promising approach for brain targeting of ibuprofen through intranasal route.

  16. Analgesic activity of DaChuanXiongFang after intranasal administration and its potential active components in vivo.

    Science.gov (United States)

    Guo, Jianming; Pan, Weiwei; Qian, Dawei; Duan, Jin-ao; Shang, Erxin; Tang, Yuping

    2013-11-25

    DaChuanXiongFang was a well-known formula originated from Jin Dynasty, China. It has been used in both China and Japan to treat migraine. In the present study, the analgesic and sedative efficacy of DaChuanXiongFang ethanol extract (DCXFEE) after intranasal administration was tested and compared with that by intragastric route. Three mice experimental models: acetic acid-induced writhing response test, hot-plate latent pain response test and pentobarbital-induced sleep model were used to evaluate DCXFEE activity. To further explore the in vivo potential active components of DCXFEE that contribute to the difference of activity induced by different administration route, ultra performance liquid chromatography-mass spectrometer (UPLC-MS) was utilized to analyze components in rat brain after given DCXFEE (60 mg/kg). DCXFEE showed analgesic efficacy after intranasal administration (15, 30 and 60 mg/kg) in acetic acid-induced writhing response in mice. While after intragastric administration, DCXFEE only showed analgesic efficacy at high dose (60 mg/kg). Moreover, the analgesic potency was weaker after intragastric administration compared with that after intranasal administration at the same dose (60 mg/kg). Similar results were obtained in hot-plate latent pain response test in mice. DCXFEE (60 mg/kg) had no sedative effect after intranasal and intragastric administration. No components originated from DCXFEE were identified in rat brain 15 min after oral administration. One major parent component ligustilide was detected in rat brain after intranasal administration. These data demonstrate that DCXFEE had faster onset of action as well as better analgesic efficacy after intranasal administration than that after intragastric administration. DCXFEE has no sedative activity on potentiation of pentobarbital-induced sleep in mice given by both routes. Ligustilide might represents the potential major bioactive component of DCXFEE after intranasal administration and contribute

  17. Intranasal inoculation of white-tailed deer (Odocoileus virginianus with lyophilized chronic wasting disease prion particulate complexed to montmorillonite clay.

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    Tracy A Nichols

    Full Text Available Chronic wasting disease (CWD, the only known prion disease endemic in wildlife, is a persistent problem in both wild and captive North American cervid populations. This disease continues to spread and cases are found in new areas each year. Indirect transmission can occur via the environment and is thought to occur by the oral and/or intranasal route. Oral transmission has been experimentally demonstrated and although intranasal transmission has been postulated, it has not been tested in a natural host until recently. Prions have been shown to adsorb strongly to clay particles and upon oral inoculation the prion/clay combination exhibits increased infectivity in rodent models. Deer and elk undoubtedly and chronically inhale dust particles routinely while living in the landscape while foraging and rutting. We therefore hypothesized that dust represents a viable vehicle for intranasal CWD prion exposure. To test this hypothesis, CWD-positive brain homogenate was mixed with montmorillonite clay (Mte, lyophilized, pulverized and inoculated intranasally into white-tailed deer once a week for 6 weeks. Deer were euthanized at 95, 105, 120 and 175 days post final inoculation and tissues examined for CWD-associated prion proteins by immunohistochemistry. Our results demonstrate that CWD can be efficiently transmitted utilizing Mte particles as a prion carrier and intranasal exposure.

  18. Sedation and physiologic response to manual restraint after intranasal administration of midazolam in Hispaniolan Amazon parrots (Amazona ventralis).

    Science.gov (United States)

    Mans, Christoph; Guzman, David Sanchez-Migallon; Lahner, Lesanna L; Paul-Murphy, Joanne; Sladky, Kurt K

    2012-09-01

    Administration of intranasal midazolam (2 mg/kg) was evaluated for sedation and effects on cloacal temperature, respiratory rate, and heart rate in manually restrained Hispaniolan Amazon parrots (Amazona ventralis). Adult parrots (n=9) were administered either midazolam (2 mg/kg) or an equal volume of saline solution intranasally before a 15-minute manual restraint in a complete crossover study. Respiratory rate and sedation scores were recorded before and during capture and during and after 15 minutes of manual restraint. Heart rate and cloacal temperature were recorded during manual restraint. After restraint, the parrots received intranasal flumazenil (0.05 mg/kg) or an equal volume of saline solution, and the recovery time was recorded. In those birds that received midazolam, sedation was observed within 3 minutes of administration, and vocalization, flight, and defense responses were significantly reduced during capture. During manual restraint, the mean rate of cloacal temperature increase was significantly slower and remained significantly lower in birds that received midazolam compared with controls. Mean respiratory rates were significantly lower for up to 12 minutes in parrots that received midazolam compared with those receiving saline solution. Flumazenil antagonized the effects of midazolam within 10 minutes. No overt clinical adverse effects to intranasal midazolam and flumazenil administration were observed. Further studies on the safety of intranasal midazolam and flumazenil in this species are warranted.

  19. Intranasal nerve growth factor bypasses the blood-brain barrier and affects spinal cord neurons in spinal cord injur y

    Institute of Scientific and Technical Information of China (English)

    Luigi Aloe; Patrizia Bianchi; Alberto De Bellis; Marzia Soligo; Maria Luisa Rocco

    2014-01-01

    The purpose of this work was to investigate whether, by intranasal administration, the nerve growth factor bypasses the blood-brain barrier and turns over the spinal cord neurons and if such therapeutic approach could be of value in the treatment of spinal cord injury. Adult Sprague-Dawley rats with intact and injured spinal cord received daily intranasal nerve growth factor administration in both nostrils for 1 day or for 3 consecutive weeks. We found an in-creased content of nerve growth factor and enhanced expression of nerve growth factor receptor in the spinal cord 24 hours after a single intranasal administration of nerve growth factor in healthy rats, while daily treatment for 3 weeks in a model of spinal cord injury improved the deifcits in locomotor behaviour and increased spinal content of both nerve growth factor and nerve growth factor receptors. These outcomes suggest that the intranasal nerve growth factor bypasses blood-brain barrier and affects spinal cord neurons in spinal cord injury. They also suggest exploiting the possible therapeutic role of intranasally delivered nerve growth factor for the neuroprotection of damaged spinal nerve cells.

  20. Preparation of ESAT-6 Nanoparticles and Evaluation of Humoral Immunity after Intranasal Administration

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    H Najminezhad

    2013-01-01

    Full Text Available Introduction: Among several tuberculosis vaccine candidates for replacement of BCG, ESAT-6 protein has a special role. Since mycobacterium tuberculosis infection most often attacks the lungs, intranasal rout can be regarded as appropriate methods for tuberculosis vaccines and drug delivery. One of the appropriate systems for intranasal vaccine delivery is using biodegradable nanoparticles. Among biodegradable polymers, chitosan polymer has great features to increase the response of immunity system. This study aimed to investigate the specific humoral immune response of mice model after encapsulation of recombinant ESAT-6 antigen in chitosan nanoparticles. Methods: The chitosan nanoparticles containing ESAT-6 antigen were synthesized by ionic gelation. Nanoparticle properties including morphology, particle size, zeta potential, encapsulation rates, and protein release were measured in vitro. The immunization was performed through the nose for 3 times on days 0 and 14 and 28. 2 weeks after last administration, blood samples were collected and specific IgG titers were measured by indirect ELISA. Results: The nanoparticles synthesized had appropriate properties. The mean size of resulting nanoparticles was 242.8 nm by excellent antigen loading capacity (95.23 %. The vitro release of antigen from nanoparticles after 200 hours was detected as 67.5%. The Level of IgG antibody showed significant increase in the group that had received chitosan nanoparticles containing ESAT-6 compared with other groups. Conclusion: ESAT-6 protein was encapsulated in chitosan nanoparticles successfully. Administration of chitosan nanoparticles can be a suitable method for administration of humoral immunity antigens of Mycobacterium tuberculosis through intranasal rout.

  1. Effect of intranasal manganese administration on neurotransmission and spatial learning in rats

    Energy Technology Data Exchange (ETDEWEB)

    Blecharz-Klin, Kamilla; Piechal, Agnieszka; Joniec-Maciejak, Ilona; Pyrzanowska, Justyna; Widy-Tyszkiewicz, Ewa, E-mail: etyszkiewicz@wum.edu.pl

    2012-11-15

    The effect of intranasal manganese chloride (MnCl{sub 2}·4H{sub 2}O) exposure on spatial learning, memory and motor activity was estimated in Morris water maze task in adult rats. Three-month-old male Wistar rats received for 2 weeks MnCl{sub 2}·4H{sub 2}O at two doses the following: 0.2 mg/kg b.w. (Mn0.2) or 0.8 mg/kg b.w. (Mn0.8) per day. Control (Con) and manganese-exposed groups were observed for behavioral performance and learning in water maze. ANOVA for repeated measurements did not show any significant differences in acquisition in the water maze between the groups. However, the results of the probe trial on day 5, exhibited spatial memory deficits following manganese treatment. After completion of the behavioral experiment, the regional brain concentrations of neurotransmitters and their metabolites were determined via HPLC in selected brain regions, i.e. prefrontal cortex, hippocampus and striatum. ANOVA demonstrated significant differences in the content of monoamines and metabolites between the treatment groups compared to the controls. Negative correlations between platform crossings on the previous platform position in Southeast (SE) quadrant during the probe trial and neurotransmitter turnover suggest that impairment of spatial memory and cognitive performance after manganese (Mn) treatment is associated with modulation of the serotonergic, noradrenergic and dopaminergic neurotransmission in the brain. These findings show that intranasally applied Mn can impair spatial memory with significant changes in the tissue level and metabolism of monoamines in several brain regions. -- Highlights: ► Intranasal exposure to manganese in rats impairs spatial memory in the water maze. ► Regional changes in levels of neurotransmitters in the brain have been identified. ► Cognitive disorder correlates with modulation of 5-HT, NA and DA neurotransmission.

  2. Intranasal vaccination promotes detrimental Th17-mediated immunity against influenza infection.

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    Asher Maroof

    2014-01-01

    Full Text Available Influenza disease is a global health issue that causes significant morbidity and mortality through seasonal epidemics. Currently, inactivated influenza virus vaccines given intramuscularly or live attenuated influenza virus vaccines administered intranasally are the only approved options for vaccination against influenza virus in humans. We evaluated the efficacy of a synthetic toll-like receptor 4 agonist CRX-601 as an adjuvant for enhancing vaccine-induced protection against influenza infection. Intranasal administration of CRX-601 adjuvant combined with detergent split-influenza antigen (A/Uruguay/716/2007 (H3N2 generated strong local and systemic immunity against co-administered influenza antigens while exhibiting high efficacy against two heterotypic influenza challenges. Intranasal vaccination with CRX-601 adjuvanted vaccines promoted antigen-specific IgG and IgA antibody responses and the generation of polyfunctional antigen-specific Th17 cells (CD4(+IL-17A(+TNFα(+. Following challenge with influenza virus, vaccinated mice transiently exhibited increased weight loss and morbidity during early stages of disease but eventually controlled infection. This disease exacerbation following influenza infection in vaccinated mice was dependent on both the route of vaccination and the addition of the adjuvant. Neutralization of IL-17A confirmed a detrimental role for this cytokine during influenza infection. The expansion of vaccine-primed Th17 cells during influenza infection was also accompanied by an augmented lung neutrophilic response, which was partially responsible for mediating the increased morbidity. This discovery is of significance in the field of vaccinology, as it highlights the importance of both route of vaccination and adjuvant selection in vaccine development.

  3. Intranasal Vaccination Promotes Detrimental Th17-Mediated Immunity against Influenza Infection

    Science.gov (United States)

    Maroof, Asher; Yorgensen, Yvonne M.; Li, Yufeng; Evans, Jay T.

    2014-01-01

    Influenza disease is a global health issue that causes significant morbidity and mortality through seasonal epidemics. Currently, inactivated influenza virus vaccines given intramuscularly or live attenuated influenza virus vaccines administered intranasally are the only approved options for vaccination against influenza virus in humans. We evaluated the efficacy of a synthetic toll-like receptor 4 agonist CRX-601 as an adjuvant for enhancing vaccine-induced protection against influenza infection. Intranasal administration of CRX-601 adjuvant combined with detergent split-influenza antigen (A/Uruguay/716/2007 (H3N2)) generated strong local and systemic immunity against co-administered influenza antigens while exhibiting high efficacy against two heterotypic influenza challenges. Intranasal vaccination with CRX-601 adjuvanted vaccines promoted antigen-specific IgG and IgA antibody responses and the generation of polyfunctional antigen-specific Th17 cells (CD4+IL-17A+TNFα+). Following challenge with influenza virus, vaccinated mice transiently exhibited increased weight loss and morbidity during early stages of disease but eventually controlled infection. This disease exacerbation following influenza infection in vaccinated mice was dependent on both the route of vaccination and the addition of the adjuvant. Neutralization of IL-17A confirmed a detrimental role for this cytokine during influenza infection. The expansion of vaccine-primed Th17 cells during influenza infection was also accompanied by an augmented lung neutrophilic response, which was partially responsible for mediating the increased morbidity. This discovery is of significance in the field of vaccinology, as it highlights the importance of both route of vaccination and adjuvant selection in vaccine development PMID:24465206

  4. Repeated intranasal TLR7 stimulation reduces allergen responsiveness in allergic rhinitis

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    Greiff Lennart

    2012-06-01

    Full Text Available Abstract Background Interactions between Th1 and Th2 immune responses are of importance to the onset and development of allergic disorders. A Toll-like receptor 7 agonist such as AZD8848 may have potential as a treatment for allergic airway disease by skewing the immune system away from a Th2 profile. Objective To evaluate the efficacy and safety of intranasal AZD8848. Methods In a placebo-controlled single ascending dose study, AZD8848 (0.3-600 μg was given intranasally to 48 healthy subjects and 12 patients with allergic rhinitis (NCT00688779. In a placebo-controlled repeat challenge/treatment study, AZD8848 (30 and 60 μg was given once weekly for five weeks to 74 patients with allergic rhinitis out of season: starting 24 hours after the final dose, daily allergen challenges were given for seven days (NCT00770003. Safety, tolerability, pharmacokinetics, and biomarkers were monitored. During the allergen challenge series, nasal symptoms and lavage fluid levels of tryptase and α2-macroglobulin, reflecting mast cell activity and plasma exudation, were monitored. Results AZD8848 produced reversible blood lymphocyte reductions and dose-dependent flu-like symptoms: 30–100 μg produced consistent yet tolerable effects. Plasma interleukin-1 receptor antagonist was elevated after administration of AZD8848, reflecting interferon production secondary to TLR7 stimulation. At repeat challenge/treatment, AZD8848 reduced nasal symptoms recorded ten minutes after allergen challenge up to eight days after the final dose. Tryptase and α2-macroglobulin were also reduced by AZD8848. Conclusions Repeated intranasal stimulation of Toll-like receptor 7 by AZD8848 was safe and produced a sustained reduction in the responsiveness to allergen in allergic rhinitis. Trial registration NCT00688779 and NCT00770003 as indicated above.

  5. Comparison of the distribution of intranasal steroid spray using different application techniques.

    Science.gov (United States)

    Tay, Sok Yan; Chao, Siew Shuen; Mark, Kim Thye Thong; Wang, De Yun

    2016-11-01

    Optimizing the intranasal distribution of nasal steroid spray (NS) is important in managing patients with allergic rhinitis (AR). Using a 3-dimensional computational model of the human nose, we found that inspiratory airflow improved particle distribution by 86%. We hence designed a study to determine if the intranasal distribution of NS is improved by (1) simultaneous gentle inspiration or (2) nasal decongestion. Twenty patients with AR were recruited. Colored triamcinolone nasal spray Nasacort®, was applied to 1 side of the nasal cavity with simultaneous gentle inspiration (technique1) and the other side with no inhalation (technique 2). Flexible nasoendoscopy with video documentation was performed immediately after each application. The same procedures were repeated 30 minutes after nasal decongestion. The nasal cavity was divided into 10 different regions and presence of the colored medication in each region was given 1 point. Prior to decongestion, the mean total score was significantly higher using technique 1 (4.61 ± 0.25) compared to technique 2 (3.80 ± 0.24), (p = 0.03). Following decongestion, the mean total score for techniques 1 and 2 was (5.20 ± 0.40) and (4.30 ± 0.32), respectively. The differences in total score for both techniques before and after decongestant were not significant. The presence of inspiratory airflow, using the gentle inspiration technique, improves the intranasal distribution of NS in patients with AR. The use of correct technique is more important than nasal decongestion in the distribution of nasal spray particles. © 2016 ARS-AAOA, LLC.

  6. Intranasal immunization of lambs with serine/threonine phosphatase 2A against gastrointestinal nematodes.

    Science.gov (United States)

    Mohamed Fawzi, Elshaima; Cruz Bustos, Teresa; Gómez Samblas, Mercedes; González-González, Gloria; Solano, Jenifer; González-Sánchez, María Elena; De Pablos, Luis Miguel; Corral-Caridad, María Jesús; Cuquerella, Montserrat; Osuna, Antonio; Alunda, José María

    2013-09-01

    Seven 3-month-old, female, helminth-free lambs were immunized intranasally with three doses (1 mg total) of a recombinant part of the catalytic region of the serine/threonine phosphatase 2A (PP2Ar) (group 1 [G1]). In addition, four lambs were used as an adjuvant control group (G2), four as unimmunized, infected controls (G3), and four as unimmunized, uninfected controls (G4). Fifteen days after the last immunization, lambs from G1, G2, and G3 were challenged with 10,000 larval stage 3 (L3) organisms in a plurispecific nematode infection composed of ca. 40% Trichostrongylus colubriformis, 40% Haemonchus contortus, and 20% Teladorsagia circumcincta. All the lambs were clinically monitored throughout the experiment. Parasitological (fecal egg output and immunological response), biopathological (packed-cell volume and leukocyte and eosinophil counts), and zootechnical (live-weight gain) analyses were conducted. On day 105 of the experiment, all the animals were slaughtered and the adult worm population in their abomasa examined. Intranasal administration of PP2Ar with bacterial walls as an adjuvant elicited a strong immune response in the immunized lambs, as evidenced by their humoral immune response. Immunized animals and animals receiving the adjuvant shed significantly (P 68%), protection being provided against both Haemonchus and Teladorsagia. Live-weight gain in the immunized lambs was similar to that in the uninfected controls versus the infected or adjuvanted animal groups. Our results suggest that heterologous immunization of ruminants by intranasal administration may be efficacious in the struggle to control gastrointestinal helminths in these livestock.

  7. Overcoming barriers to intranasal corticosteroid use in patients with uncontrolled allergic rhinitis

    Directory of Open Access Journals (Sweden)

    Bridgeman MB

    2017-05-01

    Full Text Available Mary Barna Bridgeman1,2 1Department of Pharmacy Practice and Administration, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, USA; 2Department of Pharmacy, Robert Wood Johnson University Hospital, New Brunswick, NJ, USA Abstract: Patients suffering from allergic rhinitis often attempt to self-manage their ­symptoms and may seek advice from pharmacists about nonprescription product choices. Several drug classes, both prescription and over-the-counter (OTC, are available, including intranasal corticosteroids (INCSs; oral, intranasal, and ocular antihistamines; leukotriene antagonists; and topical and systemic decongestants, as well as immunotherapies. Selection of the optimal treatment approach depends on the temporal pattern, frequency, and severity of symptoms as well as the patient’s age. Nasal congestion is typically the most bothersome symptom, although rhinorrhea, postnasal drip, and ocular symptoms are also problematic. Together, these symptoms may adversely impact the quality of life, work productivity, sleep quality, and the ability to perform daily activities, particularly when uncontrolled. Practice guidelines recognize that INCSs are the most effective medications for controlling allergic rhinitis symptoms, including nasal congestion. Available INCS products have comparable safety and efficacy profiles, but they differ in formulation characteristics and sensory attributes. Several barriers can impede the use of INCSs, including concerns about safety, misperceptions regarding the loss of response from frequent use, and undesirable sensations associated with intranasal administration. Given the increasing number of INCSs available OTC, pharmacists can help allay these concerns by discussing treatment expectations, recommending INCS products with favorable formulation characteristics, and reviewing proper use and technique for the administration of the selected product. These steps can help

  8. Development and evaluation of brain targeted intranasal alginate nanoparticles for treatment of depression.

    Science.gov (United States)

    Haque, Shadabul; Md, Shadab; Sahni, Jasjeet Kaur; Ali, Javed; Baboota, Sanjula

    2014-01-01

    The purpose of the present study was to investigate the potential of Venlafaxine loaded alginate nanoparticles (VLF AG-NPs) for treatment of depression via intranasal (i.n.) nose to brain delivery route. The VLF AG-NPs were prepared and optimized on the basis of various physio-chemical characteristics. Pharmacodynamic studies of the VLF AG-NPs for antidepressant activity were carried in-vivo by forced swimming test and locomotor activity test on albino Wistar rats. VLF AG-NPsi.n. treatment significantly improved the behavioural analysis parameters i.e. swimming, climbing, and immobility in comparison to the VLF solutioni.n. and VLF tabletoral. The intranasal VLF AG-NPs also improved locomotor activity when compared with VLF solutioni.n. and VLF tabletoral. Confocal laser scanning fluorescence microscopy studies were performed on isolated organs of rats after intravenous and intranasal administrations of Rodamine-123 loaded alginate nanoparticles to determine its efficacy for nose to brain delivery and also for its qualitative distribution to other organs. Brain uptake and pharmacokinetic studies were performed by determination of VLF concentration in blood and brain respectively for VLF AG-NPsi.n., VLF solutioni.n. and VLF solutioni.v. The greater brain/blood ratios for VLF AG-NPsi.n. in comparison to VLF solutioni.n. and VLF solutioni.v. respectively at 30 min are indicative of superiority of alginate nanoparticles for direct nose to brain transport of VLF. Thus, VLF AG-NPsi.n. delivered greater VLF to the brain in comparison to VLF solution which indicates that VLF AG-NPs could be a promising approach for the treatment of depression.

  9. Intranasal oxytocin administration in relationship to social behaviour in domestic pigs.

    Science.gov (United States)

    Camerlink, Irene; Reimert, Inonge; Bolhuis, J Elizabeth

    2016-09-01

    Intranasal administration of oxytocin has been shown to alter positive and negative social behaviour. Positive social behaviour in pigs (Sus scrofa) may be expressed through gentle social nosing, and greater insight in the specific expression hereof might contribute to the current search for positive indicators of animal welfare. We investigated whether oxytocin alters social nosing and whether this is specific to nose-body or nose-nose contact. Sixty-four focal female pigs of 13weeks of age (out of 16 groups) were given oxytocin (24IU dose) and saline (placebo) intranasally once on two consecutive days. The frequency of nose-to-nose contact and nose-to-body contact was recorded upon pigs' return in the home pen after being for 10min located in a separate area near pen mates undergoing a positive or negative event or not. The effect of intranasal oxytocin depended on the social context in which pigs were studied. Control pigs, which were not exposed to positively or negatively aroused pen mates, gave and received less nose-nose contact after oxytocin administration than after saline administration. Pigs exposed to positively aroused pen mates also tended to give less nose contact when given oxytocin compared to saline, whereas pigs exposed to negatively aroused pen mates and administered oxytocin tended to receive more nose contact. Nose-body contact was lowest in groups of negative social context, suggesting an effect of emotional state on social nosing. In contrast to nose-nose contact, nose-body contact was unaffected by oxytocin treatment. The relationship between social nosing and oxytocin merits further research.

  10. Brief Report: Oxytocin Enhances Paternal Sensitivity to a Child with Autism--A Double-Blind Within-Subject Experiment with Intranasally Administered Oxytocin

    Science.gov (United States)

    Naber, Fabienne B. A.; Poslawsky, Irina E.; van Ijzendoorn, Marinus H.; van Engeland, Herman; Bakermans-Kranenburg, Marian J.

    2013-01-01

    Oxytocin seems associated with parenting style, and experimental work showed positive effects of intranasally administered oxytocin on parenting style of fathers. Here, the first double-blind, placebo-controlled, within-subject experiment with intranasal oxytocin administration to fathers of children with autism spectrum disorder (ASD) is…

  11. Brain delivery of intranasal in situ gel of nanoparticulated polymeric carriers containing antidepressant drug: behavioral and biochemical assessment.

    Science.gov (United States)

    Kaur, Prabhjot; Garg, Tarun; Vaidya, Bhuvaneshwar; Prakash, Atish; Rath, Goutam; Goyal, Amit K

    2015-04-01

    This study was aimed for brain delivery of Tramadol HCl (centrally acting synthetic opioid) following intranasal administration for treatment of depression. Chitosan nanoparticles (NPs) were prepared by ionic gelation method followed by the addition of developed NPs with in the Pluronic and HPMC-based mucoadhesive thermo-reversible gel. Developed formulation optimized based on the various parameters such as particle size, entrapment efficiency, in vitro release study. Depression induction was done by forced swim test and evaluated by various behavioral and biochemical parameters. Furthermore, results showed significantly increased in locomotors activity, body weight as compared to control group. It also showed alteration in biochemical parameters such glutathione level and catalase levels significantly increased other than lipid peroxidation and nitrite level was found to be decreased after intranasal administration of formulation. Thus, intranasal TRM HCl NP-loaded in situ gel was found to be a promising formulation for the treatment of depression.

  12. Locus coeruleus response to single-prolonged stress and early intervention with intranasal neuropeptide Y.

    Science.gov (United States)

    Sabban, Esther L; Laukova, Marcela; Alaluf, Lishay G; Olsson, Emelie; Serova, Lidia I

    2015-12-01

    Dysregulation of the central noradrenergic system is a core feature of post-traumatic stress disorder (PTSD). Here, we examined molecular changes in locus coeruleus (LC) triggered by single-prolonged stress (SPS) PTSD model at a time when behavioral symptoms are manifested, and the effect of early intervention with intranasal neuropeptide Y (NPY). Immediately following SPS stressors, male SD rats were administered intranasal NPY (SPS/NPY) or vehicle (SPS/V). Seven days later, TH protein, but not mRNA, was elevated in LC only of the SPS/V group. Although 90% of TH positive cells expressed GR, its levels were unaltered. Compared to unstressed controls, LC of SPS/V, but not SPS/NPY, expressed less Y2 receptor mRNA with more CRHR1 mRNA in subset of animals, and elevated corticotropin-releasing hormone (CRH) in central nucleus of amygdala. Following testing for anxiety on elevated plus maze (EPM), there were significantly increased TH, DBH and NPY mRNAs in LC of SPS-treated, but not previously unstressed animals. Their levels highly correlated with each other but not with behavioral features on EPM. Thus, SPS triggers long-term noradrenergic activation and higher sensitivity to mild stressors, perhaps mediated by the up-regulation influence of amygdalar CRH input and down-regulation of Y2R presynaptic inhibition in LC. Results also demonstrate the therapeutic potential of early intervention with intranasal NPY for traumatic stress-elicited noradrenergic impairments. Single-prolonged stress (SPS)-triggered long-term changes in the locus coeruleus/norepinephrine (LC/NE) system with increased tyrosine hydroxylase (TH) protein and CRH receptor 1(CRHR1) mRNA and lower neuropeptide Y receptor 2 (Y2R) mRNA levels as well as elevated corticotropin-releasing hormone (CRH) in the central nucleus of amygdala (CeA) that were prevented by early intervention with intranasal neuropeptide Y (NPY). SPS treatment led to increased sensitivity of LC to mild stress of elevated plus maze

  13. Use of intranasal fentanyl for the relief of pediatric orthopedic trauma pain.

    Science.gov (United States)

    Saunders, Mary; Adelgais, Kathleen; Nelson, Douglas

    2010-11-01

    The objective was to evaluate the use of a single 2 μg/kg dose of intranasal fentanyl as analgesia for painful orthopedic injuries in children presenting to a pediatric emergency department (ED). This was a prospective, nonblinded interventional trial, in a convenience sample of patients 3 to 18 years of age seen in a tertiary care pediatric ED. All had clinically suspected fractures and were treated between July and November 2006. Eligible patients had moderate to severe pain based on initial pain scores using the Wong Baker Faces Scale (WBS) for patients aged 3-8 years or the Visual Analog Scale (VAS) for patients aged 9-18 years. All enrolled patients received fentanyl via intranasal atomization. Pain scores were obtained at baseline and at 10, 20, and 30 minutes after intranasal fentanyl administration. Satisfaction scores were obtained using a 100-mm VAS. Vital signs and adverse events were recorded. Eighty-one patients were enrolled, 28 in the VAS group and 53 in the WBS group. The mean patient age was 8 years. Fracture locations included forearm, 38 (47%); supracondylar, 16 (20%); clavicle, 7 (9%); tibia/fibula, 5 (6%); and other, 15 (18%). In the WBS group, the median pain scores decreased from five faces (interquartile range [IQR] = 4-6) at baseline to three faces (IQR = 2-5) at 10 minutes, two faces (IQR = 1-4) at 20 minutes, and two faces (IQR = 1-3) at 30 minutes. The mean pain score in the VAS group at baseline was 70 mm (95% confidence interval [CI] = 63 to 77 mm). In this group, the pain scores decreased by a mean of 21 mm (95% CI = 14 to 28 mm) at 10 minutes, 25 mm (95% CI = 15 to 34 mm) at 20 minutes, and 27 mm (95% CI = 16 to 37 mm) at 30 minutes. Mean satisfaction scores were 79 mm for providers, 74 mm for parents, and 62 mm for patients. No adverse events were recorded.   Intranasal fentanyl at a dose of 2 μg/kg provides effective analgesia for pediatric ED patients with painful orthopedic trauma within 10 minutes of administration. © 2010

  14. Validation of a Best-Fit Pharmacokinetic Model for Scopolamine Disposition after Intranasal Administration

    Science.gov (United States)

    Wu, L.; Chow, D. S-L.; Tam, V.; Putcha, L.

    2015-01-01

    An intranasal gel formulation of scopolamine (INSCOP) was developed for the treatment of Motion Sickness. Bioavailability and pharmacokinetics (PK) were determined per Investigative New Drug (IND) evaluation guidance by the Food and Drug Administration. Earlier, we reported the development of a PK model that can predict the relationship between plasma, saliva and urinary scopolamine (SCOP) concentrations using data collected from an IND clinical trial with INSCOP. This data analysis project is designed to validate the reported best fit PK model for SCOP by comparing observed and model predicted SCOP concentration-time profiles after administration of INSCOP.

  15. Intranasal Dexmedetomidine Sedation as Adjuvant Therapy in Acute Asthma Exacerbation With Marked Anxiety and Agitation.

    Science.gov (United States)

    Cozzi, Giorgio; Lega, Sara; Giorgi, Rita; Barbi, Egidio

    2017-01-01

    We describe 2 patients with acute asthma exacerbation who were admitted to the emergency department (ED) with severe agitation and restlessness as a prominent finding, for which bedside asthma treatment sedation with intranasal dexmedetomidine was performed. In both cases, dexmedetomidine allowed the patients to rest and improved tolerance to treatment. Dexmedetomidine is a unique sedative with an excellent safety profile and minimal effect on respiratory function. These properties render it particularly promising for the management of severe agitation in children admitted to the ED with acute asthma exacerbation. Copyright © 2016 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

  16. Early intervention with intranasal NPY prevents single prolonged stress-triggered impairments in hypothalamus and ventral hippocampus in male rats.

    Science.gov (United States)

    Laukova, Marcela; Alaluf, Lishay G; Serova, Lidia I; Arango, Victoria; Sabban, Esther L

    2014-10-01

    Intranasal administration of neuropeptide Y (NPY) is a promising treatment strategy to reduce traumatic stress-induced neuropsychiatric symptoms of posttraumatic stress disorder (PTSD). We evaluated the potential of intranasal NPY to prevent dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis, a core neuroendocrine feature of PTSD. Rats were exposed to single prolonged stress (SPS), a PTSD animal model, and infused intranasally with vehicle or NPY immediately after SPS stressors. After 7 days undisturbed, hypothalamus and hippocampus, 2 structures regulating the HPA axis activity, were examined for changes in glucocorticoid receptor (GR) and CRH expression. Plasma ACTH and corticosterone, and hypothalamic CRH mRNA, were significantly higher in the vehicle but not NPY-treated group, compared with unstressed controls. Although total GR levels were not altered in hypothalamus, a significant decrease of GR phosphorylated on Ser232 and increased FK506-binding protein 5 mRNA were observed with the vehicle but not in animals infused with intranasal NPY. In contrast, in the ventral hippocampus, only vehicle-treated animals demonstrated elevated GR protein expression and increased GR phosphorylation on Ser232, specifically in the nuclear fraction. Additionally, SPS-induced increase of CRH mRNA in the ventral hippocampus was accompanied by apparent decrease of CRH peptide particularly in the CA3 subfield, both prevented by NPY. The results show that early intervention with intranasal NPY can prevent traumatic stress-triggered dysregulation of the HPA axis likely by restoring HPA axis proper negative feedback inhibition via GR. Thus, intranasal NPY has a potential as a noninvasive therapy to prevent negative effects of traumatic stress.

  17. Prevalence of sinusitis and efficacy of intranasal corticosteroid treatment on asthmatic symptoms in asthmatic patients with rhinosinusitis: a pilot study.

    Science.gov (United States)

    Yatera, Kazuhiro; Yamasaki, Kei; Noguchi, Shingo; Nishida, Chinatsu; Oda, Keishi; Akata, Kentarou; Kido, Takashi; Ishimoto, Hiroshi; Mukae, Hiroshi

    2016-04-01

    Prevalence of sinusitis on sinus computed tomography (CT) in asthmatic patients and efficacy of intranasal corticosteroid treatment on asthmatic symptoms in asthmatic patients with rhinosinusitis on sinus CT is unclear. Sinus CT of asthmatic patients were evaluated using the Lund-Mackay system (LMS). Intranasal corticosteroid treatment (mometasone furoate) was newly added to symptomatic asthmatic patients with rhinosinusitis treated without intranasal corticosteroids, and the findings of the Asthma Control Test (ACT), Asthma Control Questionnaire in 5 items (ACQ5), spirometry, and sinus CT were evaluated before and 3 months after additional intranasal corticosteroid treatment. In a total of 160 asthmatic patients, rhinosinusitis and maxillary, ethmoidal, sphenoidal, and frontal sinusitis were observed in 75.0%, 70.0%, 53.1%, 33.1%, and 28.8%, respectively. Nasal symptoms and rhinophonia were observed in 81.9% and 72.5%, respectively, and patients with nasal symptoms and those with rhinophonia both showed significantly higher LMS scores in each sinus. Chronic rhinosinusitis (CRS) was observed in 66.9%, and these patients had significantly more severe asthma than the patients without CRS. In patients with CRS, patients with rhinophonia showed significantly higher LMS scores than those without rhinophonia. ACT, ACQ5, and the value of the forced expiratory volume in 1 second (FEV1) all significantly improved 3 months after the additive intranasal corticosteroid treatment in 24 patients, despite the fact that their LMS scores remained unchanged. Additive intranasal corticosteroid treatment may be an effective treatment option for symptomatic asthmatic patients with rhinosinusitis. © 2015 ARS-AAOA, LLC.

  18. Use of intranasal corticosteroids in the management of congestion and sleep disturbance in pediatric patients with allergic rhinitis.

    Science.gov (United States)

    Lanier, Bob Q

    2008-06-01

    Allergic rhinitis affects a large number of children and exerts a considerable socioeconomic impact. It is underdiagnosed and inadequately treated, which predisposes children to potentially serious comorbidities. Allergic rhinitis symptoms may create nighttime breathing problems and sleep disturbances and have a negative effect on a child's ability to learn in the classroom. Although antihistamines have shown efficacy in relieving many symptoms, they have little effect on nasal congestion. This article summarizes the advantages of intranasal corticosteroids, including their effectiveness against congestion and excellent safety profile. Intranasal corticosteroids with minimal systemic bioavailability provide topical drug delivery that minimizes the potential for systemic side-effects.

  19. The Clinical Study of Ulcerative Colitis Complicated with Intestinal Amebiasis%溃疡性结肠炎合并阿米巴肠病临床特点探讨

    Institute of Scientific and Technical Information of China (English)

    徐柳; 李胜保; 童强; 王小虎

    2012-01-01

    目的 探讨溃疡性结肠炎合并阿米巴肠病的临床特点.方法 回顾性分析2003~2010年共104例溃疡性结肠炎患者诊治资料,其中15例确诊合并阿米巴肠病(A组),单纯性溃疡性结肠炎患者89例(B组),统计各患者的腹泻次数、贫血程度、低白蛋白血症程度及结肠病变范围.结果 A、B组患者中腹泻>6次/d者分别为13例、40例,血红蛋白<90 g/L患者分别为8例、16例,血清蛋白<30 g/L患者分别为10例、23例,结肠病变范围超过1/2的患者分别为12例、31例,两组存在统计学差异;15例溃疡性结肠炎合并阿米巴肠病患者中7例为先确诊溃疡性结肠炎,后获得阿米巴感染并致病,其余8例患者无法判断两种疾病的发病先后顺序.所统计病例中溃疡性结肠炎并发阿米巴肠病发病率为14.4%(15/104),高于阿米巴肠病在普通人群中发病率(同地区平均为0.44%,最高2.43%).结论 溃疡性结肠炎合并阿米巴肠病病情较单纯性溃疡性结肠炎患者严重;溃疡性结肠炎患者较普通人群更容易获得溶组织内阿米巴感染并致病.%Objective To investigate the clinical characteristics of ulcerative colitis complicated with intestinal amebiasis. Methods There were 104 case of patients diagnosed as ulcerative colitis from 2003 to 2010,of which 15 cases were diagnosed complicated with intestinal amebiasis(group A) ,the other ulcerative colitis not complicated with intestinal amebiasis in 89 cases (greup B). Retrospective analysis the treatment process of patients and record the frequency of diarrhea, degree of anemia, low albumin levels and colonic lesions. Results In group A and B the number of patients with diarrhea more than 6 times everyday respectively for the 13 cases,40 cases, patients with hemoglobin <90 g/L were 8 cases,16 cases. Patients whih serum albumin <30 g/L were 10 cases,23 cases,the patients with colonic lesions over half of the colon were 12 cases,31 cases

  20. The effect of topical sodium cromoglycate on intranasal histamine challenge in allergic rhinitis.

    Science.gov (United States)

    Birchall, M A; Henderson, J C; Studham, J M; Pride, N B; Fuller, R W

    1994-12-01

    Topical sodium cromoglycate is used to treat allergic diseases of the upper and lower airways. To investigate its mechanisms of action, intranasal histamine challenge was used in nine subjects with perennial allergic rhinitis. After a preliminary day where subjects' reactivity thresholds (D100) for histamine were determined, intranasal sodium cromoglycate was administered in a double-blind, placebo-controlled fashion. Graded (D100/3, D100, D100X3), sequential challenges were performed on days 1 and 21 of each course, and responses measured by changes in nasal airway resistance, sneezes, secretion volume and secretion content: total protein, lysozyme and mucin. After a single dose of sodium cromoglycate, there was no change in resistance, but secretion volumes fell significantly (3.12 ml/5 min c.i. 2.83-3.4; placebo 3.61, c.i. 3.32-3.90: P = 0.026). After a 3-week-course, there was a significant fall in resistance (4.29 cm H2O/l/s, c.i. 3.85-4.72; placebo 5.45, c.i. 5.01-5.88: P sodium cromoglycate has both short- and long-term effects on nasal reactivity to histamine challenge. Acutely, there is a reduction in nasal lavage fluid volume which may be the result of reduced irritant receptor activity. After a 3-week course, there is a reduction in nasal resistance responses, a possible anti-inflammatory effect.

  1. Prevention or early cure of type 1 diabetes by intranasal administration of gliadin in NOD mice.

    Directory of Open Access Journals (Sweden)

    David P Funda

    Full Text Available Induction of long-term tolerance to β-cell autoantigens has been investigated both in animal models and in human type 1 diabetes (T1D in order to prevent the disease. As regards external compounds, the dietary plant protein fraction has been associated with high penetrance of the disease, whereas gluten-free diets prevent T1D in animal models. Herewith we investigated whether intranasal (i.n. administration of gliadin or gluten may arrest the diabetogenic process. I.n. administration of gliadin to 4-week-old NOD mice significantly reduced the diabetes incidence. Similarly, the insulitis was lowered. Intranasal gliadin also rescued a fraction of prediabetic 13-week-old NOD mice from progressing to clinical onset of diabetes compared to OVA-treated controls. Vaccination with i.n. gliadin led to an induction of CD4(+Foxp3(+ T cells and even more significant induction of γδ T cells in mucosal, but not in non-mucosal lymphoid compartments. This prevention strategy was characterized by an increased proportion of IL-10 and a decreased proportion of IL-2, IL-4 and IFN-γ-positive CD4(+Foxp3(+ T cells, and IFN-γ-positive γδ T cells, preferentially in mucosal lymphoid organs. In conclusion, i.n. vaccination with gliadin, an environmental antigen with possible etiological influence in T1D, may represent a novel, safer strategy for prevention or even early cure of T1D.

  2. Intranasal administration of one alpha gliadin can downregulate the immune response to whole gliadin in mice.

    Science.gov (United States)

    Maurano, F; Siciliano, R A; De Giulio, B; Luongo, D; Mazzeo, M F; Troncone, R; Auricchio, S; Rossi, M

    2001-03-01

    The mucosal lesion present in coeliac disease is an immune-mediated injury triggered by gliadin and restricted by a particular assortment of major histocompatibility complex genes. In view of this, an immunomodulatory approach that induces tolerance to this antigen appears to be a possible alternative to a strict gluten-free diet in treating coeliac disease. We have shown that intranasal administration of multiple doses of whole gliadin is required to specifically inhibit T helper 1-like T-cell reactivity in BALB/c mice immunized parenterally with whole gliadin. However, T-cell activation to multiple antigens, as a consequence of the chemical complexity shown by the antigen gliadin, could hamper efforts to identify single component(s) useful for tolerance induction. In this study, gliadin fractions were purified and administered intranasally to study their ability to induce tolerance to whole gliadin in our animal model. We found that the alpha fraction was particularly effective in downregulating both the in vitro gliadin-specific T-cell proliferation and interferon-gamma production to whole gliadin. In particular, a purified alpha-gliadin was able to suppress the immune response to the entire gliadin mixture. These results demonstrate how an immune response to a complex antigen may be controlled by treatment with a purified component and specifically indicate alpha-gliadin to be a good candidate for further identification of short peptides to be used as tolerogens in this model.

  3. Pharmacokinetics of Intranasal Scopolamine Gel Formation During Antiorthostatic Bedrest - A Microgravity Analog

    Science.gov (United States)

    Lakshmi, Putcha; Singh, R. P.; Crady, V. A.; Derendorf, H.

    2011-01-01

    Space Motion sickness (SMS) is an age old problem for astronauts on both short and long duration space flights. Scopolamine (SCOP) is the most frequently used drug for the treatment of motion sickness (MS) which is currently available in transdermal patch and tablet dosage forms. These formulations of SCOP are ineffective for the treatment of SMS. Intranasal dosage forms are noninvasive with rapid absorption and enhanced bioavailability thus allowing precise and reduced dosing options in addition to offering rescue and treatment options. As such, an intranasal gel dosage formulation of scopolamine (INSCOP) was developed and Pharmacokinetics (PK) and bioavailability were determined under IND guidelines. The present clinical trial compares PK and bioavailability of INSCOP in 12 normal, healthy subjects (6 male/ 6 female) during ambulation (AMB) and antiorthostatic bedrest (ABR) used as a ground-based microgravity analog. Subjects received 0.2 and 0.4 mg doses of INSCOP during AMB and ABR in a four-way crossover design. Results indicated no difference between AMB and ABR in PK parameters after 0.2 mg dose. Clearance (Cls) decreased with a concomitant increase in maximum concentration and area under concentration versus time curve (AUC) during ABR after the 0.4 mg dose. This difference in AUC and Cls at the higher but not the lower dose during ABR may suggest that ABR may affect metabolism and/or clearance at higher doses of INSCOP. These results indicate that dosing adjustment may be required for treatment of SMS with INSCOP in space.

  4. Intranasal oxytocin and salivary cortisol concentrations during social rejection in university students.

    Science.gov (United States)

    Linnen, Anne-Marie; Ellenbogen, Mark A; Cardoso, Christopher; Joober, Ridha

    2012-07-01

    Oxytocin facilitates pro-social behaviour and is proposed as a regulatory factor controlling stress reactivity. Previous research on oxytocin and stress has focused on achievement-related stressors among male participants. The aims of the study were to (1) examine the influence of oxytocin on the affective and cortisol response to the Yale Interpersonal Stressor (YIPS), a live social rejection paradigm, and (2) to replicate the finding that women exhibit a greater cortisol response to interpersonal stress than men (Stroud et al. 2002). Sex differences in stress responses: Social rejection versus achievement stress. Biol Psychiat 53:318-327. Ninety-six undergraduate students underwent the YIPS, where participants were excluded from two separate conversations by two same-sex confederates. Salivary cortisol concentrations and mood were repeatedly measured throughout the study. Participants were administered, in a double-blind design, a single dose of intranasal oxytocin (24 IU) or placebo prior to beginning the YIPS. The YIPS elicited a significant negative mood response that was more pronounced in females than in males. However, no significant cortisol response to the stressor and no sex difference in cortisol reactivity were observed. A significant effect of drug condition on cortisol levels was observed. Participants who were administered oxytocin exhibited a decrease in cortisol levels, relative to placebo, during the YIPS, F (4, 184)=4.50, pstress reported by Stroud et al. (2002). Intranasal oxytocin, however, appeared to reduce cortisol concentrations during an interpersonal challenge.

  5. Formulation and optimization of mucoadhesive microemulsion containing mirtazapine for intranasal delivery

    Directory of Open Access Journals (Sweden)

    Hetal P Thakkar

    2014-01-01

    Full Text Available Background: Mirtazapine, an antidepressant drug, has absolute bioavailability of only 50% due to high first pass metabolism. Aim: The purpose of this study was to develop and optimize mucoadhesive microemulsion containing mirtazapine for intranasal delivery. Materials and Methods: Based on solubility study, Capmul Medium chain Monoglyceride, Tween 80 and polyethylene glycol (PEG 400 were selected as oil, surfactant and co surfactant respectively. Microemulsions were prepared using water titration method. 3:1% w/w ratio (Tween 80: PEG 400 was selected for formulation development. The prepared microemulsions were optimized for globule size, zeta potential, % transmittance and polydispersity index. The optimized batch was further characterized for % drug content, conductivity and transmission electron microscopy. Results and Conclusion: All the parameters showed the suitability of microemulsion of mirtazapine for intranasal delivery. Chitosan (0.5% w/w was used as a polymer for the preparation of mucoadhesive microemulsion to enhance the retention time in the nasal mucosa. Results of nasal toxicity study using excised sheep nasal mucosa showed comparatively no damage to epithelium and so formulation was considered safe for nasal administration. mirtazapine mucoadhesive microemulsion showed the highest percentage of diffusion (57.11 ± 0.710% after 210 min during in-vitro drug diffusion study through sheep nasal mucosa, followed by mirtazapine microemulsion (46.08 ± 0.674% and finally by mirtazapine solution (17.63 ± 0.612%.

  6. Prehospital Medication Administration: A Randomised Study Comparing Intranasal and Intravenous Routes

    Directory of Open Access Journals (Sweden)

    Cian McDermott

    2012-01-01

    Full Text Available Introduction. Opioid overdose is an ever-increasing problem globally. Recent studies have demonstrated that intranasal (IN naloxone is a safe and effective alternative to traditional routes of naloxone administration for reversal of opioid overdose. Aims. This randomised controlled trial aimed to compare the time taken to deliver intranasal medication with that of intravenous (IV medication by advanced paramedic trainees. Methods. 18 advanced paramedic trainees administered either an IN or IV medication to a mannequin model in a classroom-based setting. The time taken for medication delivery was compared. End-user satisfaction was assessed using a 5-point questionnaire regarding ease of use and safety for both routes. Results. The mean time taken for the IN and IV group was 87.1 seconds and 178.2 seconds respectively. The difference in mean time taken was 91.1 seconds (95% confidence interval 55.2 seconds to 126.9 seconds, P≤0.0001. 89% of advanced paramedic trainees reported that the IN route was easier and safer to use than the IV route. Conclusion. This study demonstrates that, amongst advanced paramedic trainees, the IN route of medication administration is significantly faster, better accepted and perceived to be safer than using the IV route. Thus, IN medication administration could be considered more frequently when administering emergency medications in a pre-hospital setting.

  7. Effects of single dose intranasal oxytocin on social cognition in schizophrenia.

    Science.gov (United States)

    Davis, Michael C; Lee, Junghee; Horan, William P; Clarke, Angelika D; McGee, Mark R; Green, Michael F; Marder, Stephen R

    2013-07-01

    Deficits in social cognition are common in schizophrenia and predict poor community functioning. Given the current limitations of psychosocial treatments and the lack of pharmacological treatments for social cognitive deficits, the development of novel therapeutic agents could greatly enhance functional recovery in schizophrenia. This study evaluated whether a single dose of intranasal oxytocin acutely improves social cognitive functioning in schizophrenia. Twenty-three male veterans with schizophrenia completed baseline assessments of social cognition that were divided into lower-level (facial affect perception, social perception, detection of lies) and higher-level (detection of sarcasm and deception, empathy) processes. One week later, patients received the same battery after being randomized to a single dose of 40 IU intranasal oxytocin or placebo. Though the groups did not differ significantly on the social cognition composite score, oxytocin improved performance for the higher-level social cognitive tasks (Cohen's d=1.0, p=0.045). Subjects were unable to accurately guess which treatment they had received. The improvements found in higher-level social cognition encourage further studies into the therapeutic potential of oxytocin in schizophrenia.

  8. Induction of cytokines in different organs after intranasal inoculation of Campylobacter jejuni in mice

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    Al-Banna Nadia A

    2012-12-01

    Full Text Available Abstract Background Cytokine production and histopathological changes occur in the lungs of mice after intranasal inoculation with Campylobacter jejuni, but the levels of cytokines in different organs to which C. jejuni disseminates have not been studied. Findings Adult BALB/c mice were intranasally inoculated with C. jejuni 81–176 (test or phosphate-buffered saline (control (n=16 per group. The levels of cytokines in the organs (spleen, liver, and small and large intestines to which C. jejuni disseminated were measured by ELISA. Two cytokine patterns were observed. First, increased proinflammatory cytokines, TNF-α, IL-1, and IL-2, were followed by anti-inflammatory cytokines, IL-4 and IL-10 in the spleen and large intestine. Second, in the liver and small intestine, there was a predominant production of anti-inflammatory cytokines, IL-4 and IL-10, with some increase in IL-2 levels. In the spleen and intestines, the levels of pro- and anti-inflammatory cytokines were concurrently increased. Conclusion Dissemination of C. jejuni is associated with the production of different cytokine profiles in different tissues, with the proinflammatory response appearing in the spleen and large intestine at an earlier time point than in the liver and small intestine. The organs produce different cytokine profiles in response to C. jejuni dissemination. These preliminary findings should be confirmed with a study involving a larger group of animals.

  9. Cluster headache with ptosis responsive to intranasal lidocaine application: a case report

    Directory of Open Access Journals (Sweden)

    Bakbak Berker

    2012-02-01

    Full Text Available Abstract Introduction The application of lidocaine to the nasal mucosal area corresponding to the sphenopalatine fossa has been shown to be effective at extinguishing pain attacks in patients with a cluster headache. In this report, the effectiveness of local administration of lidocaine on cluster headache attacks as a symptomatic treatment of this disorder is discussed. Cases presentation A 22-year-old Turkish man presented with a five-year history of severe, repeated, unilateral periorbital pain and headache, diagnosed as a typical cluster headache. He suffered from rhinorrhea, lacrimation and ptosis during headaches. He had tried several unsuccessful daily medications. We applied a cotton tip with lidocaine hydrochloride into his left nostril for 10 minutes. The ptosis responded to the treatment and the intensity of his headache decreased. Conclusion Intranasal lidocaine is a useful treatment for the acute management of a cluster headache. Intranasal lidocaine blocks the neural transmission of the sphenopalatine ganglion, which contributes to the trigeminal nerve as well as containing both parasympathetic and sympathetic fibers.

  10. Naloxone therapy in opioid overdose patients: intranasal or intravenous? A randomized clinical trial.

    Science.gov (United States)

    Sabzghabaee, Ali Mohammad; Eizadi-Mood, Nastaran; Yaraghi, Ahmad; Zandifar, Samaneh

    2014-05-12

    This study was designed to compare the effects of intranasal (IN) and intravenous (IV) administration of naloxone in patients who had overdosed on opioids. This randomized clinical trial study was conducted in the Department of Poisoning Emergencies at Noor and Ali Asghar (PBUH) University Hospital. One hundred opioid overdose patients were assigned by random allocation software into two study groups (n = 50). Both groups received 0.4 mg naloxone: one group IN and the other IV. Outcomes included change in the level of consciousness (measured using a descriptive scale and the Glasgow Coma Scale (GCS)), time to response, vital signs (blood pressure, heart rate and respiratory rate), arterial blood O2 saturation before and after naloxone administration, side-effects (agitation) and length of hospital stay. Patients who had been administered IN naloxone demonstrated significantly higher levels of consciousness than those in the IV group using both descriptive and GCS scales (p IV groups (p = 0.003). However, blood pressure, respiratory rate and arterial O2 saturation were not significantly different between the two groups after naloxone administration (p = 0.18, p = 0.17, p = 0.32). There was also no significant difference in the length of hospital stay between the two groups (p = 0.14). Intranasal naloxone is as effective as IV naloxone in reversing both respiratory depression and depressive effects on the central nervous system caused by opioid overdose.

  11. Study of sodium hyaluronate-based intranasal formulations containing micro- or nanosized meloxicam particles.

    Science.gov (United States)

    Bartos, Csilla; Ambrus, Rita; Sipos, Péter; Budai-Szűcs, Mária; Csányi, Erzsébet; Gáspár, Róbert; Márki, Árpád; Seres, Adrienn B; Sztojkov-Ivanov, Anita; Horváth, Tamás; Szabó-Révész, Piroska

    2015-08-01

    This article reports on the micro- and nanonization of meloxicam (MEL) with the aim of developing pre-dispersions as intermediates for the design of intranasal formulations. As a new approach, combined wet milling technology was developed in order to reduce the particle size of the MEL. Different milling times resulted in micro- or nanosized MEL in the pre-dispersions with polyvinyl alcohol as stabilizer agent, which were directly used for preparing intranasal liquid formulations with the addition of sodium hyaluronate as mucoadhesive agent. Reduction of the MEL particle size into the nano range led to increased saturation solubility and dissolution velocities, and increased adhesiveness to surfaces as compared with microsized MEL particles. A linear correlation was demonstrated between the specific surface area of MEL and the AUC. The in vitro and in vivo studies indicated that the longer residence time and the uniform distribution of nano MEL spray throughout an artificial membrane and the nasal mucosa resulted in better diffusion and a higher AUC. Nanosized MEL may be suggested for the development of an innovative dosage form with a different dose of the drug, as a possible administration route for pain management.

  12. Intranasal microemulsion for targeted nose to brain delivery in neurocysticercosis: Role of docosahexaenoic acid.

    Science.gov (United States)

    Shinde, Rajshree L; Bharkad, Gopal P; Devarajan, Padma V

    2015-10-01

    Intranasal Microemulsions (MEs) for nose to brain delivery of a novel combination of Albendazole sulfoxide (ABZ-SO) and Curcumin (CUR) for Neurocysticercosis (NCC), a brain infection are reported. MEs prepared by simple solution exhibited a globule size brain concentrations and 10.76 (ABZ-SO) and 3.24 (CUR) fold enhancement in brain area-under-the-curve (AUC) compared to intravenous DHA MEs at the same dose. Direct nose to brain transport (DTP) of >95% was seen for both drugs. High drug targeting efficiency (DTE) to the brain compared to Capmul ME and drug solution (Pnose to brain delivery. Histopathology study confirmed no significant changes. High efficacy of ABZ-SO: CUR (100:10ng/mL) DHA ME in vitro on Taenia solium cysts was confirmed by complete ALP inhibition and disintegration of cysts at 96h. Considering that the brain concentration at 24h was 1400±160.1ng/g (ABZ-SO) and 120±35.2ng/g (CUR), the in vitro efficacy seen at a 10 fold lower concentration of the drugs strongly supports the assumption of clinical efficacy. The intranasal DHA ME is a promising delivery system for targeted nose to brain delivery.

  13. Development, characterization and application of in situ gel systems for intranasal delivery of tacrine.

    Science.gov (United States)

    Qian, Shuai; Wong, Yin Cheong; Zuo, Zhong

    2014-07-01

    The present study aimed to develop an in situ gel formulation for intranasal delivery of tacrine (THA), an anti-Alzheimer's drug. Thermosensitive polymer Pluronic F-127 was used to prepare THA in situ gels. Sol-gel transition temperature (Tsol-gel), rheological properties, in vitro release, and in vivo nasal mucociliary transport time were optimized. The pharmacokinetics and brain dispositions of in situ gel were compared with that from THA oral solution in rats. The in situ gel demonstrated a liquid state with Newtonian fluid behavior under 20 °C, while it exhibited as non-flowing gel with pseudoplastic fluid behavior beyond its Tsol-gel of 28.5 °C. Based on nasal mucociliary transport time, the in situ gel significantly prolonged its retention in nasal cavity compared to solution form. Moreover, the in situ gel achieved 2-3 fold higher peak plasma concentration (Cmax) and area under the curve (AUC) of THA in plasma and brain tissue, but lowered Cmax and AUC of the THA metabolites compared to that of oral solution. The enhanced nasal residence time, improved bioavailability, increased brain uptake of parent drug and decreased exposure of metabolites suggested that the in situ gel could be an effective intranasal formulation for THA.

  14. Intranasal DNA Vaccine for Protection against Respiratory Infectious Diseases: The Delivery Perspectives

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    Yingying Xu

    2014-07-01

    Full Text Available Intranasal delivery of DNA vaccines has become a popular research area recently. It offers some distinguished advantages over parenteral and other routes of vaccine administration. Nasal mucosa as site of vaccine administration can stimulate respiratory mucosal immunity by interacting with the nasopharyngeal-associated lymphoid tissues (NALT. Different kinds of DNA vaccines are investigated to provide protection against respiratory infectious diseases including tuberculosis, coronavirus, influenza and respiratory syncytial virus (RSV etc. DNA vaccines have several attractive development potential, such as producing cross-protection towards different virus subtypes, enabling the possibility of mass manufacture in a relatively short time and a better safety profile. The biggest obstacle to DNA vaccines is low immunogenicity. One of the approaches to enhance the efficacy of DNA vaccine is to improve DNA delivery efficiency. This review provides insight on the development of intranasal DNA vaccine for respiratory infections, with special attention paid to the strategies to improve the delivery of DNA vaccines using non-viral delivery agents.

  15. Ribavirin Protects Syrian Hamsters against Lethal Hantavirus Pulmonary Syndrome — After Intranasal Exposure to Andes Virus

    Science.gov (United States)

    Ogg, Monica; Jonsson, Colleen B.; Camp, Jeremy V.; Hooper, Jay W.

    2013-01-01

    Andes virus, ANDV, harbored by wild rodents, causes the highly lethal hantavirus pulmonary syndrome (HPS) upon transmission to humans resulting in death in 30% to 50% of the cases. As there is no treatment for this disease, we systematically tested the efficacy of ribavirin in vitro and in an animal model. In vitro assays confirmed antiviral activity and determined that the most effective doses were 40 µg/mL and above. We tested three different concentrations of ribavirin for their capability to prevent HPS in the ANDV hamster model following an intranasal challenge. While the highest level of ribavirin (200 mg/kg) was toxic to the hamster, both the middle (100 mg/kg) and the lowest concentration (50 mg/kg) prevented HPS in hamsters without toxicity. Specifically, 8 of 8 hamsters survived intranasal challenge for both of those groups whereas 7 of 8 PBS control-treated animals developed lethal HPS. Further, we report that administration of ribavirin at 50 mg/kg/day starting on days 6, 8, 10, or 12 post-infection resulted in significant protection against HPS in all groups. Administration of ribavirin at 14 days post-infection also provided a significant level of protection against lethal HPS. These data provide in vivo evidence supporting the potential use of ribavirin as a post-exposure treatment to prevent HPS after exposure by the respiratory route. PMID:24217424

  16. Ribavirin Protects Syrian Hamsters against Lethal Hantavirus Pulmonary Syndrome — After Intranasal Exposure to Andes Virus

    Directory of Open Access Journals (Sweden)

    Jay W. Hooper

    2013-11-01

    Full Text Available Andes virus, ANDV, harbored by wild rodents, causes the highly lethal hantavirus pulmonary syndrome (HPS upon transmission to humans resulting in death in 30% to 50% of the cases. As there is no treatment for this disease, we systematically tested the efficacy of ribavirin in vitro and in an animal model. In vitro assays confirmed antiviral activity and determined that the most effective doses were 40 µg/mL and above. We tested three different concentrations of ribavirin for their capability to prevent HPS in the ANDV hamster model following an intranasal challenge. While the highest level of ribavirin (200 mg/kg was toxic to the hamster, both the middle (100 mg/kg and the lowest concentration (50 mg/kg prevented HPS in hamsters without toxicity. Specifically, 8 of 8 hamsters survived intranasal challenge for both of those groups whereas 7 of 8 PBS control-treated animals developed lethal HPS. Further, we report that administration of ribavirin at 50 mg/kg/day starting on days 6, 8, 10, or 12 post-infection resulted in significant protection against HPS in all groups. Administration of ribavirin at 14 days post-infection also provided a significant level of protection against lethal HPS. These data provide in vivo evidence supporting the potential use of ribavirin as a post-exposure treatment to prevent HPS after exposure by the respiratory route.

  17. Low-dose intranasal versus oral midazolam for routine body MRI of claustrophobic patients

    Energy Technology Data Exchange (ETDEWEB)

    Tschirch, Frank T.C.; Goepfert, Kerstin; Brunner, Genevieve; Weishaupt, Dominik [University Hospital Zuerich, Institute of Diagnostic Radiology, Zuerich (Switzerland); Froehlich, Johannes M. [Klus-Apotheke, Zuerich (Switzerland)

    2007-06-15

    The purpose of this study was to assess prospectively the potential of low-dose intranasal midazolam compared to oral midazolam in claustrophobic patients undergoing routine body magnetic resonance imaging (MRI). Seventy-two adult claustrophobic patients referred for body MRI were randomly assigned to one of two treatment groups (TG1 and TG2). The 36 patients of TG1 received 7.5 mg midazolam orally 15 min before MRI, whereas the 36 patients of TG2 received one (or, if necessary, two) pumps of a midazolam nasal spray into each nostril immediately prior to MRI (in total, 1 or 2 mg). Patients' tolerance, anxiety and sedation were assessed using a questionnaire and a visual analogue scale immediately before and after MRI. Image quality was evaluated using a five-point-scale. In TG1, 18/36 MRI examinations (50%) had to be cancelled, the reduction of anxiety was insufficient in 12/18 remaining patients (67%). In TG2, 35/36 MRI examinations (97%) were completed successfully, without relevant adverse effects. MRI image quality was rated higher among patients of TG2 compared to TG1 (p<0.001). Low-dose intranasal midazolam is an effective and patient-friendly solution to overcome anxiety in claustrophobic patients in a broad spectrum of body MRI. Its anxiolytic effect is superior to that of the orally administrated form. (orig.)

  18. Intranasal Immunization of Mice to Avoid Interference of Maternal Antibody against H5N1 Infection.

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    Fenghua Zhang

    Full Text Available Maternally-derived antibodies (MDAs can protect offspring against influenza virus infection but may also inhibit active immune responses. To overcome MDA- mediated inhibition, active immunization of offspring with an inactivated H5N1 whole-virion vaccine under the influence of MDAs was explored in mice. Female mice were vaccinated twice via the intraperitoneal (IP or intranasal (IN route with the vaccine prior to mating. One week after birth, the offspring were immunized twice via the IP or IN route with the same vaccine and then challenged with a lethal dose of a highly homologous virus strain. The results showed that, no matter which immunization route (IP or IN was used for mothers, the presence of MDAs severely interfered with the active immune response of the offspring when the offspring were immunized via the IP route. Only via the IN immunization route did the offspring overcome the MDA interference. These results suggest that intranasal immunization could be a suitable inoculation route for offspring to overcome MDA interference in the defense against highly pathogenic H5N1 virus infection. This study may provide references for human and animal vaccination to overcome MDA-induced inhibition.

  19. Formulation and evaluation of microemulsion-based in situ ion-sensitive gelling systems for intranasal administration of curcumin.

    Science.gov (United States)

    Wang, Shuang; Chen, Ping; Zhang, Lin; Yang, Chunfen; Zhai, Guangxi

    2012-12-01

    The purpose of our study was to develop a microemulsion-based in situ ion-sensitive gelling system for intranasal administration of curcumin. A new microemulsion composition for curcumin was optimized with the simple lattice design. And the microemulsion-based in situ ion-sensitive gelling system consisted of Capryol 90 as oil phase, Solutol HS15 as surfactant, Transcutol HP as cosurfactant and 0.3% DGG solution as water phase. The physicochemical properties such as morphology, droplet size distribution, zeta value and the in vitro release were investigated. In addition, the histological section studies on the reaction between the obtained formulation and nasal mucosa showed that the microemulsion-based in situ ion-sensitive gelling system could not produce obvious damage to nasal mucosa. The pharmacokinetics results showed that the absolute bioavailability of curcumin in the microemulsion-based in situ ion-sensitive gelling system was 55.82% by intranasal administration. And the brain targeting index (BTI) was 6.50, and in the tissue distribution experiment, the value of (AUC(brain)/AUC(blood)) following intranasal administration was higher than that following intravenous administration, suggesting that the obvious brain targeting property by nasal delivery be attributed to a direct nose-to-brain drug transport. It can be concluded that the microemulsion-based in situ gelling as an effective and safe vehicle could greatly enhance the in vivo absorption and facilitate the delivery of curcumin to brain by intranasal administration.

  20. Intranasal Immunization with Chitosan/pCAGGS-flaA Nanoparticles Inhibits Campylobacter jejuni in a White Leghorn Model

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    Jin-lin Huang

    2010-01-01

    Full Text Available Campylobacter jejuni is the most common zoonotic bacterium associated with human diarrhea, and chickens are considered to be one of the most important sources for human infection, with no effective prophylactic treatment available. We describe here a prophylactic strategy using chitosan-DNA intranasal immunization to induce specific immune responses. The chitosan used for intranasal administration is a natural mucus absorption enhancer, which results in transgenic DNA expression in chicken nasopharynx. Chickens immunized with chitosan-DNA nanoparticles, which carried a gene for the major structural protein FlaA, produced significantly increased levels of serum anti-Campylobacter jejuni IgG and intestinal mucosal antibody (IgA, compared to those treated with chitosan-DNA (pCAGGS. Chitosan-pCAGGS-flaA intranasal immunization induced reductions of bacterial expellation by 2-3 log10 and 2 log10 in large intestine and cecum of chickens, respectively, when administered with the isolated C. jejuni strain. This study demonstrated that intranasal delivery of chitosan-DNA vaccine successfully induced effective immune response and might be a promising vaccine candidate against C. jejuni infection.

  1. A prospective randomised double-blinded study of intranasal midazolam atomizer spray for procedural sedation in paediatric patients

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    Vijaykumara

    2016-09-01

    Conclusions: We can thereby say that administration of preservative free intranasal midazolam atomizer spray in dose of 0.2mg/kg as premedication in paediatric patients produces satisfactory level of sedation and anxiolysis with minimal adverse effects. [Int J Res Med Sci 2016; 4(9.000: 3850-3854

  2. Immune Responses of Dairy Cattle to Parainfluenza-3 Virus in Intranasal Infectious Bovine Rhinotracheitis-Parainfluenza-3 Virus Vaccines

    OpenAIRE

    Burroughs, A.L.; Morrill, J L; Bostwick, J.L.; Ridley, R K; Fryer, H. C.

    1982-01-01

    Two hundred and fifty dairy heifers were vaccinated at three to six months of age with an intranasal infectious bovine rhinotracheitis-parainfluenza-3 vaccine. Eighteen additional heifers were tested prior to vaccination and again three to four weeks after vaccination. Neither cell-mediated nor humoral immunity was significantly raised to parainfluenza-3 virus in either group of cattle.

  3. Intranasal Vaccination Affords Localization and Persistence of Antigen-Specific CD8+ T Lymphocytes in the Female Reproductive Tract

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    Shailbala Singh

    2016-03-01

    Full Text Available Immunization strategies generating large numbers of antigen-specific T cells in the female reproductive tract (FRT can provide barrier protection against sexually-transmitted pathogens, such as the human immunodeficiency virus (HIV and human papillomaviruses (HPV. The kinetics and mechanisms of regulation of vaccine-induced adaptive T cell-mediated immune responses in FRT are less well defined. We present here evidence for intranasal delivery of the model antigen ovalbumin (OVA along with alpha-galactosylceramide adjuvant as a protein vaccine to induce significantly higher levels of antigen-specific effector and memory CD8+ T cells in the FRT, relative to other systemic and mucosal tissues. Antibody blocking of the CXCR3 receptor significantly reduced antigen-specific CD8+ T cells subsequent to intranasal delivery of the protein vaccine suggesting an important role for the CXCR3 chemokine-receptor signaling for T cell trafficking. Further, intranasal vaccination with an adenoviral vector expressing OVA or HIV-1 envelope was as effective as intramuscular vaccination for generating OVA- or ENV-specific immunity in the FRT. These results support the application of the needle-free intranasal route as a practical approach to delivering protein as well as DNA/virus vector-based vaccines for efficient induction of effector and memory T cell immunity in the FRT.

  4. A common oxytocin receptor gene (OXTR) polymorphism modulates intranasal oxytocin effects on the neural response to social cooperation in humans.

    Science.gov (United States)

    Feng, C; Lori, A; Waldman, I D; Binder, E B; Haroon, E; Rilling, J K

    2015-09-01

    Intranasal oxytocin (OT) can modulate social-emotional functioning and related brain activity in humans. Consequently, OT has been discussed as a potential treatment for psychiatric disorders involving social behavioral deficits. However, OT effects are often heterogeneous across individuals. Here we explore individual differences in OT effects on the neural response to social cooperation as a function of the rs53576 polymorphism of the oxytocin receptor gene (OXTR). Previously, we conducted a double-blind, placebo-controlled study in which healthy men and women were randomized to treatment with intranasal OT or placebo. Afterwards, they were imaged with functional magnetic resonance imaging while playing an iterated Prisoner's Dilemma Game with same-sex partners. Within the left ventral caudate nucleus, intranasal OT treatment increased activation to reciprocated cooperation in men, but tended to decrease activation in women. Here, we show that these sex differences in OT effects are specific to individuals with the rs53576 GG genotype, and are not found for other genotypes (rs53576 AA/AG). Thus, OT may increase the reward or salience of positive social interactions for male GG homozygotes, while decreasing those processes for female GG homozygotes. These results suggest that rs53576 genotype is an important variable to consider in future investigations of the clinical efficacy of intranasal OT treatment.

  5. Intranasal pyrrolidine dithiocarbamate decreases brain inflammatory mediators and provides neuroprotection after brain hypoxia-ischemia in neonatal rats.

    Science.gov (United States)

    Wang, Zhi; Zhao, Huijuan; Peng, Shuling; Zuo, Zhiyi

    2013-11-01

    Brain injury due to birth asphyxia is the major cause of death and long-term disabilities in newborns. We determined whether intranasal pyrrolidine dithiocarbamate (PDTC) could provide neuroprotection in neonatal rats after brain hypoxia-ischemia (HI). Seven-day old male and female Sprague-Dawley rats were subjected to brain HI. They were then treated with intranasal PDTC. Neurological outcomes were evaluated 7 or 30 days after the brain HI. Brain tissues were harvested 6 or 24 h after the brain HI for biochemical analysis. Here, PDTC dose-dependently reduced brain HI-induced brain tissue loss with an effective dose (ED)50 at 27 mg/kg. PDTC needed to be applied within 45 min after the brain HI for this neuroprotection. This treatment reduced brain tissue loss and improved neurological and cognitive functions assessed 30 days after the HI. PDTC attenuated brain HI-induced lipid oxidative stress, nuclear translocation of nuclear factor κ-light-chain-enhancer of activated B cells, and various inflammatory mediators in the brain tissues. Inhibition of inducible nitric oxide synthase after brain HI reduced brain tissue loss. Our results suggest that intranasal PDTC provides neuroprotection possibly via reducing inflammation and oxidative stress. Intranasal PDTC may have a potential to provide neuroprotection to human neonates after birth asphyxia.

  6. Laksekalcitonin ved osteoporose. Effekten af intranasal applikation på knoglemineralindhold og frakturhyppighed hos postmenopausale kvinder med manifeste osteoporotiske forandringer

    DEFF Research Database (Denmark)

    Ravn, Pernille

    1993-01-01

    The objective was to study the dose-related response of intranasal salmon calcitonin (Salcatonin) on bone mass and bone turnover and the effect of salcatonin on rates of fracture in elderly women with moderate osteoporosis. A total of 208 healthy women aged 68-72 years, who had a bone mineral...

  7. Acute and repeated intranasal oxytocin administration exerts anti-aggressive and pro-affiliative effects in male rats

    NARCIS (Netherlands)

    Calcagnoli, Federica; Kreutzmann, Judith C.; de Boer, Sietse F.; Althaus, Monika; Koolhaas, Jaap M.

    2015-01-01

    Socio-emotional deficits and impulsive/aggressive outbursts are prevalent symptoms of many neuropsychiatric disorders, and intranasal administration of oxytocin (OXT) is emerging as a putative novel therapeutic approach to curb these problems. Recently, we demonstrated potent anti-aggressive and pro

  8. Systemic and direct nose-to-brain transport pharmacokinetic model for remoxipride after intravenous and intranasal administration

    NARCIS (Netherlands)

    Stevens, Jasper; Ploeger, Bart A; van der Graaf, Piet H; Danhof, Meindert; de Lange, Elizabeth C M

    2011-01-01

    Intranasal (IN) administration could be an attractive mode of delivery for drugs targeting the central nervous system, potentially providing a high bioavailability because of avoidance of a hepatic first-pass effect and rapid onset of action. However, controversy remains whether a direct transport r

  9. Intranasal BMP9 Ameliorates Alzheimer Disease-Like Pathology and Cognitive Deficits in APP/PS1 Transgenic Mice

    Science.gov (United States)

    Wang, Zigao; Xiong, Lu; Wan, Wenbin; Duan, Lijie; Bai, Xiaojing; Zu, Hengbing

    2017-01-01

    Alzheimer’s disease (AD) is the most common type of dementia and has no effective therapies. Previous studies showed that bone morphogenetic protein 9 (BMP9), an important factor in the differentiation and phenotype maintenance of cholinergic neurons, ameliorated the cholinergic defects resulting from amyloid deposition. These findings suggest that BMP9 has potential as a therapeutic agent for AD. However, the effects of BMP9 on cognitive function in AD and its underlying mechanisms remain elusive. In the present study, BMP9 was delivered intranasally to 7-month-old APP/PS1 mice for 4 weeks. Our data showed that intranasal BMP9 administration significantly improved the spatial and associative learning and memory of APP/PS1 mice. We also found that intranasal BMP9 administration significantly reduced the amyloid β (Aβ) plaques overall, inhibited tau hyperphosphorylation, and suppressed neuroinflammation in the transgenic mouse brain. Furthermore, intranasal BMP9 administration significantly promoted the expression of low-density lipoprotein receptor-related protein 1 (LRP1), an important membrane receptor involved in the clearance of amyloid β via the blood-brain barrier (BBB), and elevated the phosphorylation levels of glycogen synthase kinase-3β (Ser9), which is considered the main kinase involved in tau hyperphosphorylation. Our results suggest that BMP9 may be a promising candidate for treating AD by targeting multiple key pathways in the disease pathogenesis. PMID:28228716

  10. Brain delivery of valproic acid via intranasal administration of nanostructured lipid carriers: in vivo pharmacodynamic studies using rat electroshock model

    Directory of Open Access Journals (Sweden)

    Sharareh Eskandari

    2011-02-01

    Full Text Available Sharareh Eskandari1, Jaleh Varshosaz1, Mohsen Minaiyan2, Majid Tabbakhian11Department of Pharmaceutics, 2Department of Pharmacology, School of Pharmacy and Isfahan Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, IranAbstract: The treatment of brain disorders is one of the greatest challenges in drug delivery because of a variety of main barriers in effective drug transport and maintaining therapeutic concentrations in the brain for a prolonged period. The objective of this study was delivery of valproic acid (VPA to the brain by intranasal route. For this purpose, nanostructured lipid carriers (NLCs were prepared by solvent diffusion method followed by ultrasonication and characterized for size, zeta potential, drug-loading percentage, and release. Six groups of rats each containing six animals received drug-loaded NLCs intraperitoneally (IP or intranasally. Brain responses were then examined by using maximal electroshock (MES. The hind limb tonic extension:flexion inhibition ratio was measured at 15-, 30-, 60-, 90-, and 120-minute intervals. The drug concentration was also measured in plasma and brain at the most protective point using gas chromatography method. The particle size of NLCs was 154 ± 16 nm with drug-loading percentage of 47% ± 0.8% and drug release of 75% ± 1.9% after 21 days. In vivo results showed that there was a significant difference between protective effects of NLCs of VPA and control group 15, 30, 60, and 90 minutes after treatment via intranasal route (P < 0.05. Similar protective effect was observed in rats treated with NLCs of VPA in intranasal route and positive control in IP route (P > 0.05. Results of drug determination in brain and plasma showed that brain:plasma concentration ratio was much higher after intranasal administration of NLCs of VPA than the positive control group (IP route. In conclusion, intranasal administration of NLCs of VPA provided a better protection

  11. EVALUATION OF EFFICACY OF INTRANASAL MIDAZOLAM SPRA Y FOR PREANAESTHETIC MEDICATION IN PAEDIATRIC PATIENTS

    Directory of Open Access Journals (Sweden)

    Sneha P.

    2013-05-01

    Full Text Available ABSTRACT: BACKGROUND: Preoperative anxiety and long-term behavioural pro blems are inevitable consequences in absence of preoperative sedation in paediatric patients undergoing surgery. An ideal premedicant removes fear and anxi ety in tender minds of children and achieves a calm, sedated child for smooth induction of anaesth esia and rapid recovery in postoperative period. Midazolam is the most commonly used premedicant in children as it satisfies most of the criteria of ideal premedicant but its route of administration i s a debatable issue in anaesthesia practice. AIMS: This study evaluated the efficacy of atomized intra nasal midazolam spray as a painless, user- friendly, needleless system of drug administration for pre-anaesthetic medication in paediatric patients. SETTINGS AND DESIGN: Tertiary hospital, a prospective, randomized, cont rolled, clinical study. METHODS AND MATERIAL: 60 ASA physical status I children of 2-5 years age group, weighing 10-18 kg scheduled for routine surgeries p articipated in the study. Children were randomly assigned to Group M: Received intranasal m idazolam spray in doses of 0.2 mg/kg and Group N: Received normal saline drops (1-2 drops/no stril. Patients were observed in preoperative room for 20 min. Acceptance of drug, response to dr ug administration, sedation scale, separation score, acceptance to mask, recovery score and side effects of drug were noted. STATISTICAL ANALYSIS: Student ‘t’ test, standard error of difference bet ween two means and Chi-square test. p value0.05. 20 min after p remedication 76.66% in group M and 10.00% group N, children showed satisfactory sedation (p<0 .05. 73.33% in group M while 26.66% in group N, children showed acceptable parental separa tion and 86.66% in group M while 23.33% group N, children showed satisfactory acceptance to mask (p<0.05. Transient nasal irritation in the form of rubbing of nose, watering, sneezing and lac rimation was observed in 40% children of

  12. Foot-and-mouth disease: a review of intranasal infection of cattle, sheep and pigs.

    Science.gov (United States)

    Sellers, Robert; Gloster, John

    2008-08-01

    In an outbreak of foot-and-mouth disease (FMD) it is important to identify animals at risk from airborne virus. Investigations have been carried out over the years to determine the dose required to infect cattle, sheep and pigs by the intranasal route. This paper reviews the results of investigations for animals which have been infected by instillation or spraying a virus suspension into the nostrils or by exposure to affected animals through a mask or by indirect contact. The lowest doses were found by use of a mask. With virus from affected pigs given through a mask, doses of 18 infectious units (IU) in cattle and 8 IU in sheep were found to cause infection and give rise to lesions. Overall, cattle required the least amount of virus followed by sheep. Pigs required a dose of 22 IU to cause infection and a dose of 125 IU to give rise to lesions. In many experiments pigs failed to become infected. With all three species the dose varied with the individual animal and the virus strain. For modelling previous outbreaks and in real time, a dose of 8 IU or 10 and 50% infectious doses (ID50) could be used where cattle and sheep were involved. Experience in the field, combined with the results from experiments involving natural infection, indicate that pigs are not readily infected by the intranasal route. However, for modelling purposes a dose of about 25 IU should be used with care. Investigations are needed to determine doses for virus strains currently in circulation around the world. In addition, the nature of the aerosol droplets needs to be analysed to determine how the respective amounts of infective and non-infective virus particles, host components and, in later emissions, the presence of antibody affect the survival in air and ability to infect the respiratory tract. Further work is also required to correlate laboratory and field findings through incorporation of the doses into modelling the virus concentration downwind in order that those responsible for

  13. Comparison of Oral and Intranasal Midazolam/Ketamine Sedation in 3‒6-year-old Uncooperative Dental Patients

    Directory of Open Access Journals (Sweden)

    Masoud Fallahinejad Ghajari

    2015-07-01

    Full Text Available Background and aims. There are several known sedative drugs, with midazolam and ketamine being the most commonly used drugs in children. The aim of this study was to compare the effect of intranasal and oral midazolam plus ketamine in children with high levels of dental anxiety. Materials and methods. A crossover double-blind clinical trial was conducted on 23 uncooperative children aged 3‒6 (negative or definitely negative by Frankel scale, who required at least two similar dental treatment visits. Cases were ran-domly given ketamine (10 mg/kg and midazolam (0.5 mg/kg through oral or intranasal routes in each visit. The sedative efficacy of the agents was assessed by an overall success rate judged by two independent pediatric dentists based on Houpt’s scale for sedation. Data analysis was carried out using Wilcoxon test and paired t-test. Results. Intranasal administration was more effective in reduction of crying and movement during dental procedures com-pared to oral sedation (P<0.05. Overall behavior control was scored higher in nasal compared to oral routes at the time of LA injection and after 15 minutes (P<0.05. The difference was found to be statistically significant at the start and during treatment. However, the difference was no longer significant after 30 minutes, with the vital signs remaining within physio-logical limits. Recovery time was longer in the intranasal group (P<0.001 with a more sleepy face (P=0.004. Conclusion. Intranasal midazolam/ketamine combination was more satisfactory and effective than the oral route when sedating uncooperative children.

  14. [Preparation of huperzine A nasal in situ gel and evaluation of its brain targeting following intranasal administration].

    Science.gov (United States)

    Tao, Tao; Zhao, Yan; Yue, Peng; Dong, Wen-xin; Chen, Qing-hua

    2006-11-01

    The feasibility of intranasal brain targeting drug delivery system via the olfactory pathway from nose to brain was explored. Using gellan gum, a cation-sensitive gel forming excipient, huperzine A (Hup A) nasal in situ gel was prepared by pH gradient precipitation method. The pharmacokinetics of Hup A in blood and cerebrospinal fluid (CSF) after intranasal, intravenous and intragastric adminstration to rats was studied using cisternal cannulation for serial CSF sampling and femoral artery cannulation for serial blood sampling. The distributions of Hup A into rat brain tissues following intranasal dosing were compared with those after intravenous and intragastric dosing by tissue homogeneization. The therapeutics effects of Hup A nasal in situ gel on cognitive function were tested in mice and rats with Morris water maze, step down test and step through test. The AUC(0-->6 h) value in plasma obtained after nasal administration was 0.94 of that after intravenous administration, but the AUC(0-->6 h) of CSF after nasal administration was 1.3 and 2.3 times of that after intravenous and intragastric administration. The AUC(0-->6 h), of cerebrum, hippocampus, cerebellum, left olfactory bulb and right olfactory bulb after nasal administration were 1.5, 1.3, 1.0, 1.2 and 1.0 of that after intravenous administration, 2.7, 2.2, 1.9, 3.1 and 2.6 times of that after intragastric administration, respectively. Intranasal adminintration of 17.5-35 microg x kg(-1) showed equal effects after oral adminintration of 70 microg x kg(-1) commercial tablets, which was in good agreement with the results of pharmacokinetics. Intranasal administration of huperzine A nasal in situ gel significantly increased the distributions of Hup A into rat brain tissues, especially into cerebrum and hippocampus which should be the target areas of Hup A, and enhanced the brain targeting of Hup A.

  15. Influenza A Virus Challenge Models in Cynomolgus Macaques Using the Authentic Inhaled Aerosol and Intra-Nasal Routes of Infection.

    Directory of Open Access Journals (Sweden)

    Anthony C Marriott

    Full Text Available Non-human primates are the animals closest to humans for use in influenza A virus challenge studies, in terms of their phylogenetic relatedness, physiology and immune systems. Previous studies have shown that cynomolgus macaques (Macaca fascicularis are permissive for infection with H1N1pdm influenza virus. These studies have typically used combined challenge routes, with the majority being intra-tracheal delivery, and high doses of virus (> 107 infectious units. This paper describes the outcome of novel challenge routes (inhaled aerosol, intra-nasal instillation and low to moderate doses (103 to 106 plaque forming units of H1N1pdm virus in cynomolgus macaques. Evidence of virus replication and sero-conversion were detected in all four challenge groups, although the disease was sub-clinical. Intra-nasal challenge led to an infection confined to the nasal cavity. A low dose (103 plaque forming units did not lead to detectable infectious virus shedding, but a 1000-fold higher dose led to virus shedding in all intra-nasal challenged animals. In contrast, aerosol and intra-tracheal challenge routes led to infections throughout the respiratory tract, although shedding from the nasal cavity was less reproducible between animals compared to the high-dose intra-nasal challenge group. Intra-tracheal and aerosol challenges induced a transient lymphopaenia, similar to that observed in influenza-infected humans, and greater virus-specific cellular immune responses in the blood were observed in these groups in comparison to the intra-nasal challenge groups. Activation of lung macrophages and innate immune response genes was detected at days 5 to 7 post-challenge. The kinetics of infection, both virological and immunological, were broadly in line with human influenza A virus infections. These more authentic infection models will be valuable in the determination of anti-influenza efficacy of novel entities against less severe (and thus more common influenza

  16. A comparison of costs and efficacy of intranasal fluticasone propionate and terfenadine tablets for seasonal allergic rhinitis.

    Science.gov (United States)

    Kozma, C M; Schulz, R M; Sclar, D A; Kral, K M; Mackowiak, J I

    1996-01-01

    This paper compares cost-efficacy ratios for intranasal fluticasone propionate and terfenadine tablets within a sample of patients with seasonal allergic rhinitis symptoms due to mountain cedar allergy. Efficacy was assessed using secondary data analysis of patient ratings of symptoms and their overall assessment of response to treatment within a previously conducted clinical trial. Costs include direct costs of the drugs used for therapy. Patients with documented mountain cedar allergy who were 12 years of age or older (N = 232) had been randomized to either receive intranasal fluticasone propionate, terfenadine, or placebo. The cost-efficacy ratios for intranasal fluticasone propionate 200 micrograms once daily were more favorable than the ratios for terfenadine 60 mg twice daily. This relationship remained throughout the sensitivity analysis. Because intranasal fluticasone propionate is only available in a fixed package size, the number of efficacy-adjusted days of terfenadine therapy that could be purchased to reach break-even costs for a 30-day supply of fluticasone was calculated. Cost efficacy-adjusted days ranged from 11 to 18 days. If cost-efficacy adjustments are not conducted, the upper end of the range increases from 18 to 22 days, since 22 days of terfenadine could be purchased for the price of a 30-day supply of intranasal fluticasone propionate. Depending on which of the efficacy measures the reader believes, if patients use terfenadine for longer than 11 to 22 days, fluticasone propionate is the more cost-efficacious choice. Because most allergies are seasonal and allergy seasons typically last longer than 11 to 22 days, it is likely that fluticasone propionate will frequently be the more cost-efficacious choice in the patient population represented in this study.

  17. A pilot study assessing the bioavailability and pharmacokinetics of diazepam after intranasal and intravenous administration in healthy volunteers.

    Science.gov (United States)

    Agarwal, Suresh K; Kriel, Robert L; Brundage, Richard C; Ivaturi, Vijay D; Cloyd, James C

    2013-08-01

    Diazepam rectal gel (Diastat(®)) is the only FDA-approved product indicated for acute repetitive seizures. Despite its proven efficacy, most older children and adults object to this route of administration. As a result, many patients do not realize the benefit of a therapy that can improve outcomes and decrease healthcare costs. Intranasal administration of benzodiazepines offers a potential alternative. The primary objective of this study was to compare the bioavailability and pharmacokinetics of two novel intranasal (IN) diazepam (DZP) formulations versus intravenous (IV) administration in healthy volunteers. Twenty-four healthy volunteers were randomized into an open-label, three-way crossover study. 10mg doses of two investigational intranasal DZP formulations (solution, suspension) and a 5mg IV dose of commercially available DZP injectable, USP were given. A two-week washout period separated treatments. Plasma samples for DZP analysis were collected pre-dose and at regular intervals up to 240 h post-dose. DZP concentration-time data were analyzed using a non-compartmental pharmacokinetics approach. Exposure following administration of DZP IN solution (absolute bioavailability - 97%) was greater than the IN suspension (absolute bioavailability - 67%). Mean Cmaxvalues for the suspension and solution formulations were 221 ng/mL and 272 ng/mL, respectively. Median time to maximum concentration (Tmax) was 1h and 1.5h for suspension and solution formulation, respectively. Both investigational intranasal formulations were well tolerated. The results of this pilot study indicate that development of an intranasal diazepam formulation with high bioavailability, reasonable variability, and good tolerability is feasible.

  18. Best BETs from the Manchester Royal Infirmary. BET 1: intranasal lorazepam is an acceptable alternative to intravenous lorazepam in the control of acute seizures in children.

    Science.gov (United States)

    Allan, Anna; Cullen, Jayne

    2013-09-01

    A short-cut review was carried out to determine whether intranasal lorazepam was as effective as intravenous lorazepam in the control of seizures in children. Eighteen papers were found using the reported search, of which one was directly relevant and another compared intranasal lorazepam with intramuscular paraldehyde. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses are shown in table 1. It is concluded that intranasal lorazepam appears to be a safe and effective treatment for this condition.

  19. Intranasal delivery of nanoparticle-based vaccine increases protection against S. pneumoniae

    Energy Technology Data Exchange (ETDEWEB)

    Mott, Brittney [University of North Texas Health Science Center, Department of Molecular Biology and Immunology (United States); Thamake, Sanjay [Radio-Isotope Therapy of America Foundation (United States); Vishwanatha, Jamboor; Jones, Harlan P., E-mail: harlan.jones@unthsc.edu [University of North Texas Health Science Center, Department of Molecular Biology and Immunology (United States)

    2013-05-15

    Nanoparticle (NP) technologies are becoming commonplace in the development of vaccine delivery systems to protect against various diseases. The current study determined the efficacy of intranasal delivery of a 234 {+-} 87.5 nm poly lactic-co-glycolic acid nanoparticle vaccine construct in establishing protection against experimental respiratory pneumococcal infection. Nanoparticles encapsulating heat-killed Streptococcus pneumoniae (NP-HKSP) were retained in the lungs 11 days following nasal administration compared to empty NP. Immunization with NP-HKSP produced significant resistance against S. pneumoniae infection compared to administration of HKSP alone. Increased protection correlated with a significant increase in antigen-specific Th1-associated IFN-{gamma} cytokine response by pulmonary lymphocytes. This study establishes the efficacy of NP-based technology as a non-invasive and targeted approach for nasal-pulmonary immunization against pulmonary infections.

  20. The relationship between temporal discounting and the prisoner's dilemma game in intranasal abusers of prescription opioids.

    Science.gov (United States)

    Yi, Richard; Buchhalter, August R; Gatchalian, Kirstin M; Bickel, Warren K

    2007-02-23

    Previous research on college students has found that cooperation in iterated prisoner's dilemma game is correlated with preference for delayed rewards in studies of temporal discounting. The present study attempted to replicate this finding in a drug-dependent population. Thirty-one individuals who intranasally abuse prescription opioids participated in temporal discounting and iterated prisoner's dilemma game procedures during intake for a treatment study. Rate of temporal discounting was determined for each participant at two hypothetical reward magnitudes, as well as proportion of cooperation in a 60-trial iterated prisoner's dilemma game versus a tit-for-tat strategy. Cooperation in the prisoner's dilemma game and temporal discounting rates were significantly correlated in the predicted direction: individuals who preferred delayed rewards in the temporal discounting task were more likely to cooperate in the prisoner's dilemma game.

  1. Development of questionnaires to measure patient preferences for intranasal corticosteroids in patients with allergic rhinitis.

    Science.gov (United States)

    Meltzer, Eli O; Hadley, James; Blaiss, Michael; Benninger, Michael; Kimel, Miriam; Kleinman, Leah; Dupclay, Leon; Garcia, Jorge; Leahy, Michael; Georges, George

    2005-02-01

    To develop a questionnaire to evaluate preferences for attributes of intranasal corticosteroids (INSs) in clinical trials with allergic rhinitis (AR) patients. Established questionnaire development practices were used, including performance of a literature review and use of patient and physician focus groups, cognitive debriefing interviews, and pilot testing before validation. Findings from patient and physician focus groups suggest that sensory attributes are relevant to AR patients when choosing INSs. Physician focus groups identified the need for 2 distinct preference instruments, a clinical trial patient preference questionnaire (CTPPQ) and a clinical practice preference questionnaire (CPPPQ). A pilot study suggests that the CTPPQ is capable of discriminating between 2 INSs in the clinical trial setting. Initial findings suggest that items in the CTPPQ and CPPPQ are easy to understand and relevant to patients. Further validation studies with larger sample sizes are needed to assess the psychometric properties of both questionnaires. B-20.

  2. Intranasal fentanyl in the treatment of acute pain--a systematic review

    DEFF Research Database (Denmark)

    Hansen, M S; Mathiesen, O; Trautner, S

    2012-01-01

    demonstrated some analgesic effect of IN fentanyl following myringotomy, no analgesic effect following voiding cystourethrography, and finally, no significant analgesic difference after long bone fractures, in burns patients, and in post-operative pain relief when compared to IV morphine, oral morphine, or IV......Due to its non-invasive mode of administration, intranasal (IN) application of drugs may be a valuable alternative to non-invasive pain management. With characteristics that appear to be ideal for IN application, IN fentanyl may have a place in the out-of-hospital treatment and the paediatric....... No significant analgesic differences between IN fentanyl and intravenous (IV) fentanyl were demonstrated in treatment of acute and post-operative pain. Significant analgesic effect of IN fentanyl was demonstrated in the treatment of breakthrough pain in cancer patients. In the paediatric population, results...

  3. Intranasal delivery of nanoparticle-based vaccine increases protection against S. pneumoniae

    Science.gov (United States)

    Mott, Brittney; Thamake, Sanjay; Vishwanatha, Jamboor; Jones, Harlan P.

    2013-05-01

    Nanoparticle (NP) technologies are becoming commonplace in the development of vaccine delivery systems to protect against various diseases. The current study determined the efficacy of intranasal delivery of a 234 ± 87.5 nm poly lactic-co-glycolic acid nanoparticle vaccine construct in establishing protection against experimental respiratory pneumococcal infection. Nanoparticles encapsulating heat-killed Streptococcus pneumoniae (NP-HKSP) were retained in the lungs 11 days following nasal administration compared to empty NP. Immunization with NP-HKSP produced significant resistance against S. pneumoniae infection compared to administration of HKSP alone. Increased protection correlated with a significant increase in antigen-specific Th1-associated IFN-γ cytokine response by pulmonary lymphocytes. This study establishes the efficacy of NP-based technology as a non-invasive and targeted approach for nasal-pulmonary immunization against pulmonary infections.

  4. Experimentally induced nasal hypersecretion does not reduce the efficacy of intranasal levocabastine

    DEFF Research Database (Denmark)

    Borum, Stefan; Nielsen, K; Bisgaard, H;

    1998-01-01

    In allergic rhinitis, a nasal H1-antihistamine spray seems to be well suited for usage on an as-needed basis, because it has a quick onset of action, and many patients prefer to take medicine only when they have symptoms. It is a prerequisite, however, that nasal hypersecretion during a rhinitis...... episode does not significantly reduce the efficacy of intranasal treatment by washing away the drug before it reaches the H1-histamine receptors. In order to investigate this problem, we have induced nasal hypersecretion with a methacholine challenge in one experiment and in four experiments we have......% (p antihistamine spray. We conclude that experimentally induced nasal hypersecretion does not reduce the efficacy...

  5. Antiglomerular basement membrane antibody-mediated glomerulonephritis after intranasal cocaine use.

    Science.gov (United States)

    Peces, R; Navascués, R A; Baltar, J; Seco, M; Alvarez, J

    1999-01-01

    We report a case of rapidly progressive glomerulonephritis due to antiglomerular basement membrane (anti-GBM) antibodies that progressed to end-stage renal disease in a 35-year-old man who used intranasal cocaine on an occasional basis. In contrast to many prior reports of acute renal failure occurring with cocaine-associated rhabdomyolysis, this patient did not have any evidence of acute muscle damage and myoglobin release. Circulating anti-GBM antibodies and renal biopsy with linear IgG and C3 deposits confirmed the diagnosis of anti-GBM disease. The possibility of anti-GBM must be considered in the differential diagnosis of acute renal failure in cocaine addicts. This unusual combination raises complex questions regarding the pathogenesis of this type of renal injury.

  6. Intranasal LPS-mediated Parkinson's model challenges the pathogenesis of nasal cavity and environmental toxins.

    Directory of Open Access Journals (Sweden)

    Qing He

    Full Text Available Accumulating evidence implicates the relationship between neuroinflammation and pathogenesis in idiopathic Parkinson's disease (iPD. The nose has recently been considered a gate way to the brain which facilitates entry of environmental neurotoxin into the brain. Our study aims to build a PD model by a natural exposure route. In this report, we establish a new endotoxin-based PD model in mice by unilateral intranasal (i.n. instillation of the lipopolysaccharides (LPS every other day for 5 months. These mice display a progressive hypokinesia, selective loss of dopaminergic neurons, and reduction in striatal dopamine (DA content, as well as α-synuclein aggregation in the SN, without systemic inflammatory and immune responses. This new PD model provides a tool for studying the inflammation-mediated chronic pathogenesis and searching for therapeutic intervention in glia-neuron pathway that will slow or halt neurodegeneration in PD.

  7. Development of intranasal nanovehicles of itraconazole and their immunological activities for the therapy of rhinovirus infection.

    Science.gov (United States)

    Lee, Jeong-Jun; Shim, Aeri; Jeong, Jae Young; Lee, Song Yi; Ko, Hyun-Jeong; Cho, Hyun-Jong

    2016-07-01

    Itraconazole (ITZ)-loaded microemulsion (ME) systems for intranasal (IN) delivery were developed for the treatment of human rhinovirus serotype 1B (HRV1B) infection. ITZ was incorporated into the oil-in-water (o/w) ME formulation composed of benzyl alcohol (oil), Cremophor EL (surfactant), Solutol HS15 (cosurfactant), and water. The optimized composition of ME was determined by constructing pseudo-ternary phase diagram. ITZ ME formulation with about 150nm mean diameter and spherical shape was prepared and the solubility of ITZ in blank ME was markedly improved (up to 13.9mg/mL). The initial value of droplet size was maintained with four times dilution in the aqueous buffer and 72h incubation. Released amounts of drug from ME formulation were significantly enhanced compared to drug suspension group (prhinovirus infection.

  8. No laughing matter: intranasal oxytocin administration changes functional brain connectivity during exposure to infant laughter.

    Science.gov (United States)

    Riem, Madelon M E; van IJzendoorn, Marinus H; Tops, Mattie; Boksem, Maarten A S; Rombouts, Serge A R B; Bakermans-Kranenburg, Marian J

    2012-04-01

    Infant laughter is a rewarding experience. It activates neural reward circuits and promotes parental proximity and care, thus facilitating parent-infant attachment. The neuropeptide oxytocin might enhance the incentive salience of infant laughter by modulating neural circuits related to the perception of infant cues. In a randomized controlled trial with functional magnetic resonance imaging we investigated the influence of intranasally administered oxytocin on functional brain connectivity in response to infant laughter. Blood oxygenation level-dependent responses to infant laughter were measured in 22 nulliparous women who were administered oxytocin and 20 nulliparous women who were administered a placebo. Elevated oxytocin levels reduced activation in the amygdala during infant laughter and enhanced functional connectivity between the amygdala and the orbitofrontal cortex, the anterior cingulate, the hippocampus, the precuneus, the supramarginal gyri, and the middle temporal gyrus. Increased functional connectivity between the amygdala and regions involved in emotion regulation may reduce negative emotional arousal while enhancing the incentive salience of the infant laughter.

  9. Thermosensitive PLA based nanodispersion for targeting brain tumor via intranasal route

    Energy Technology Data Exchange (ETDEWEB)

    Jain, Darshana S., E-mail: darshanaj_cup@yahoo.com [C.U. Shah College of Pharmacy, S.N.D.T Women' s University, Juhu Tara Road, Santacruz (West), Mumbai 400 049 (India); Bajaj, Amrita N. [C.U. Shah College of Pharmacy, S.N.D.T Women' s University, Juhu Tara Road, Santacruz (West), Mumbai 400 049 (India); Athawale, Rajani B., E-mail: rajani.athawale@gmail.com [C.U. Shah College of Pharmacy, S.N.D.T Women' s University, Juhu Tara Road, Santacruz (West), Mumbai 400 049 (India); Shikhande, Shruti S. [C.U. Shah College of Pharmacy, S.N.D.T Women' s University, Juhu Tara Road, Santacruz (West), Mumbai 400 049 (India); Pandey, Abhijeet [H. R Patel Institute of Pharmaceutical Education and Research, Shirpur, Maharashtra (India); Goel, Peeyush N.; Gude, Rajiv P. [Gude Lab, Advanced Centre for Treatment, Research & Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai 410 210 (India); Patil, Satish; Raut, Preeti [Cipla Pvt. Ltd., Vikhroli (West), Mumbai (India)

    2016-06-01

    Delivery of drugs to the brain via nasal route has been studied by many researchers. However, low residence time, mucociliary clearance and enzymatically active environment of nasal cavity pose many challenges to successful nasal delivery of drugs. We aim to deliver methotrexate by designing thermosensitive nanodispersion exhibiting enhanced residence time in nasal cavity and bypassing the blood brain barrier (BBB). PLA nanoparticles were developed using solvent evaporation technique. The developed nanoparticles were further dispersed in prepared thermosensitive vehicle of poloxamer 188 and Carbopol 934 to impart the property of increased residence time. The formulated nanoparticles demonstrated no interaction with the simulated nasal fluids (SNF), mucin, serum proteins and erythrocytes which demonstrate the safety of developed formulation for nasal administration. The penetration property of nanoparticles though the nasal mucosa was higher than the pure drug due to low mucociliary clearance. The developed nanoparticles diffused though the membrane pores and rapidly distributed into the brain portions compared to the pure drug. There was detectable and quantifiable amount of drug seen in the brain as demonstrated by in vivo brain distribution studies with considerably low amount of drug deposition in the lungs. The pharmacokinetic parameters demonstrated the enhancement in circulation half life, area under curve (AUC) and Cmax of the drug when administered intranasal in encapsulated form. Thus, the thermosensitive nanodispersions are surely promising delivery systems for delivering anticancer agents though the nasal route for potential treatment of brain tumors. - Highlights: • The present investigation explores intra-nasal route as potential route for targeting brain tumor. • Thermosensitive nanodispersion has been formulated for enhancing nasal residence time. • PLA nanoparticles enhance penetration into the brain owing to hydrophobic nature and small size

  10. Intranasal Oxytocin Selectively Modulates Social Perception, Craving, and Approach Behavior in Subjects With Alcohol Use Disorder.

    Science.gov (United States)

    Mitchell, Jennifer M; Arcuni, Peter A; Weinstein, Dawn; Woolley, Josh D

    2016-01-01

    A pharmacotherapy that both improves social abilities and promotes abstinence may be particularly helpful for the treatment of alcohol use disorder. Recent clinical and preclinical evidence suggests that oxytocin has prosocial and antiaddiction effects. We performed a pilot, laboratory-based, preclinical trial of oxytocin in subjects with alcohol abuse (as per Diagnostic and Statistical Manual of Mental Disorders, 4 Edition criteria) to evaluate therapeutic potential and assess tolerability. Social perceptual ability, cue-induced craving, and approach bias for alcohol and appetitive imagery were quantified after intranasal oxytocin and placebo administration to 32 nontreatment-seeking individuals with alcohol abuse in a double-blind, crossover study. Because attachment style can moderate the effects of oxytocin, we also explored whether attachment style moderated oxytocin's effects on our behavioral measures. Oxytocin significantly improved recognition of easier items on a social perception task, but had no significant group-level effect on cue-induced craving. However, oxytocin effects on craving were moderated by attachment anxiety, with oxytocin reducing craving in more anxiously attached individuals and increasing craving in less anxiously attached individuals. Subjects did not display an approach bias to alcohol images on the placebo day, preventing meaningful analysis of this measure. Subjects did display an approach bias to appetitive images on the placebo day, which was significantly reduced by oxytocin administration. No adverse reactions were observed. Intranasal oxytocin has potential to improve social perception, reduce cue-induced alcohol cravings, and reduce appetitive approach bias in subjects with alcohol abuse, and can be safely tolerated in this population. The effects of oxytocin are complex, however, and require further investigation.

  11. Comparison of Preanesthetic Sedation after Intranasal Administration of Fentanyle, Ketamin and Midazolam

    Directory of Open Access Journals (Sweden)

    F Javaherforoosh

    2006-07-01

    Full Text Available Introduction & Objective: Induction of anesthesia in children can be a challenge for anesthetist. A stormy induction may increase the personality & behavioral changes. Therefore, it is desirable that they enter the operating room sedated. Many drugs are used for preanesthetic medication and there are many routes for administration. One route of administration is nasal mucous. In this study we compared the effect and side effect of three drugs (midazolam, ketamin and fentanyle after intra nasal administration. Materials & Methods: This is a double blind clinical trial. In this study we selected 60 patients (20 patients for every group A, B or C. We used 3 mg/kg ketamin or 3µg/kg fentanyle or 0.3 mg/kg midazolam by intranasal spray. After administration and in 5, 10 and 15 minutes, we observed the SPO2, PR and RR. After 15 min’s we separated children from parents and brought them to the operating room and controlled the acceptance of separation, depth of sedation with Ramsay score, acceptance of mask and tolerance of IV canulation. The data were then analyzed using K2 and kruskal-wallis test. Results: In our study we found that in SPO2 fentanyle had the highest rate of reduction even though none of the children had SPO2 lower than 90%. There were no differences between drugs in RR. In fentanyle group, we had the lowest rate and in ketamin group the highest rate. Midazolam had the medium rate. The rate of sedation for acceptance of separation from parents had no difference between the groups and all drugs with this dosage were effective for this aim. However, in Ramsay score, acceptance of mask and tolerance of IV canulation, the midazolam was more effective than the others. Conclusion: Intranasal administration of midazolam is a safe route for sedation in children in the pre-anesthetic time.

  12. A new brain drug delivery strategy: focused ultrasound-enhanced intranasal drug delivery.

    Directory of Open Access Journals (Sweden)

    Hong Chen

    Full Text Available Central nervous system (CNS diseases are difficult to treat because of the blood-brain barrier (BBB, which prevents most drugs from entering into the brain. Intranasal (i.n. administration is a promising approach for drug delivery to the brain, bypassing the BBB; however, its application has been restricted to particularly potent substances and it does not offer localized delivery to specific brain sites. Focused ultrasound (FUS in combination with microbubbles can deliver drugs to the brain at targeted locations. The present study proposed to combine these two different platform techniques (FUS+i.n. for enhancing the delivery efficiency of intranasally administered drugs at a targeted location. After i.n. administration of 40 kDa fluorescently-labeled dextran as the model drug, FUS targeted at one region within the caudate putamen of mouse brains was applied in the presence of systemically administered microbubbles. To compare with the conventional FUS technique, in which intravenous (i.v. drug injection is employed, FUS was also applied after i.v. injection of the same amount of dextran in another group of mice. Dextran delivery outcomes were evaluated using fluorescence imaging of brain slices. The results showed that FUS+i.n. enhanced drug delivery within the targeted region compared with that achieved by i.n. only. Despite the fact that the i.n. route has limited drug absorption across the nasal mucosa, the delivery efficiency of FUS+i.n. was not significantly different from that of FUS+i.v.. As a new drug delivery platform, the FUS+i.n. technique is potentially useful for treating CNS diseases.

  13. Pharmacokinetic evaluation of intranasally administered vinyl polymer-coated lorazepam microparticles in rabbits.

    Science.gov (United States)

    Zhao, Yanjun; Brown, Marc B; Khengar, Rajeshree H; Traynor, Matthew J; Barata, Pedro; Jones, Stuart A

    2012-06-01

    The intranasal (IN) administration of lorazepam is desirable in order to maximize speed of onset and minimise carry-over sedation; however, this benzodiazepine is prone to chemical hydrolysis and poor airway retention, and thus, innovative epithelial presentation is required. The aim of this study was to understand how the in situ self-assembly of a mucoretentive delivery system, formed by the dissolution of vinyl polymer-coated microparticles in the nasal mucosa, would influence lorazepam pharmacokinetics (PK). IN administration of the uncoated lorazepam powder (particle size, 6.7 ± 0.1 μm) generated a biphasic PK profile, which was indicative of sequential intranasal and oral absorption (n = 6; dose, 5 mg/kg). Coating the drug with the vinyl polymer, MP1 (9.9 ± 0.5 μm with 38.8 ± 14.0%, w/w lorazepam) and MP2 (10.7 ± 0.1 μm with 47.0 ± 1.0%, w/w lorazepam), allowed rapid systemic absorption (MP1, T (max) 14.2 ± 4.9 min; MP2, T (max) 9.3 ± 3.8 min) in rabbits and modified the PK profiles in a manner that suggested successful nasal retention. The poly(vinyl pyrrolidone)-rich MP2 system provided the best comparative bioavailability, it prolonged the early-phase nasal drug absorption and minimised drug mucociliary clearance, which correlated well with the intermolecular hydrogen-bond-driven vinyl polymer interactions observed in vitro.

  14. Protection of inactive intranasal ántrax vaccine to Bacillus anthracis infection

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    Adin Priadi

    2010-06-01

    Full Text Available Ánthrax is an endemic zoonotic disease distributed in many parts of Indonesia. Although vaccination program has been implemented in many areas, cases are still frequently reported. Farmers are reluctant to vaccinate their livestock since spore vaccine used in the field often cause side effects and death of the animals. To overcome this problem, an inactive vaccine composes of Bacillus anthracis toxins, cell wall and capsule subunits was developed. B. anthracis Sterne strain (34F2 was selected to produce toxins and cell walls. Local Bacillus anthracis isolated from Citaringgul was used to produce capsule as the Polymerase Chain Reaction (PCR revealed that this isolate poses cap gene encoding for capsule. Two vaccines compose of 15 μg toxoid, 30 μg of capsule, 15 μg of cell wall and 30 μg toxoid, 60 μg of capsule, 15 μg of cell walls were designated as vaccine I and vaccine II respectively. For each experiment, 10 mice were nasally immunized by placing 5 μl of vaccine into each nare 3 times at 2-week intervals. A group of 10 mice were unvaccinated and used as control. Blood was collected fortnightly to monitor antibody responses. All mice were challenged with 2 x 105 B. anthracis Sterne spores injected subcutaneously two weeks after the last vaccination. Two weeks after vaccination of antibodies to B. anthracis toxin, capsule and cell wall were detected in dot-blot assay. Mice that were immunised intranasally with chitosan adjuvanted vaccine developed high IgG responses in sera as detected by ELISA, and the response was dose dependent. Vaccine II gave better response than vaccine I. Vaccine I and II protected mice from challenge at a rate of 60 and 80% respectively. This results showed that intranasal B. anthracis vaccine composes of toxin, capsule and cell wall with chitosan as an adjuvant gave a good protection against B. anthracis Sterne spores challenge in mice.

  15. Thiolated chitosan nanoparticles enhance anti-inflammatory effects of intranasally delivered theophylline

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    Mohapatra Shyam S

    2006-08-01

    Full Text Available Abstract Background Chitosan, a polymer derived from chitin, has been used for nasal drug delivery because of its biocompatibility, biodegradability and bioadhesiveness. Theophylline is a drug that reduces the inflammatory effects of allergic asthma but is difficult to administer at an appropriate dosage without causing adverse side effects. It was hypothesized that adsorption of theophylline to chitosan nanoparticles modified by the addition of thiol groups would improve theophylline absorption by the bronchial epithelium and enhance its anti-inflammatory effects. Objectives We sought to develop an improved drug-delivery matrix for theophylline based on thiolated chitosan, and to investigate whether thiolated chitosan nanoparticles (TCNs can enhance theophylline's capacity to alleviate allergic asthma. Methods A mouse model of allergic asthma was used to test the effects of theophylline in vivo. BALB/c mice were sensitized to ovalbumin (OVA and OVA-challenged to produce an inflammatory allergic condition. They were then treated intranasally with theophylline alone, chitosan nanoparticles alone or theophylline adsorbed to TCNs. The effects of theophylline on cellular infiltration in bronchoalveolar lavage (BAL fluid, histopathology of lung sections, and apoptosis of lung cells were investigated to determine the effectiveness of TCNs as a drug-delivery vehicle for theophylline. Results Theophylline alone exerts a moderate anti-inflammatory effect, as evidenced by the decrease in eosinophils in BAL fluid, the reduction of bronchial damage, inhibition of mucus hypersecretion and increased apoptosis of lung cells. The effects of theophylline were significantly enhanced when the drug was delivered by TCNs. Conclusion Intranasal delivery of theophylline complexed with TCNs augmented the anti-inflammatory effects of the drug compared to theophylline administered alone in a mouse model of allergic asthma. The beneficial effects of theophylline in

  16. Evaluation of subcutaneous versus mucosal (intranasal) allergen-specific rush immunotherapy in experimental feline asthma.

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    Lee-Fowler, Tekla M; Cohn, Leah A; DeClue, Amy E; Spinka, Christine M; Reinero, Carol R

    2009-05-15

    Rush immunotherapy (RIT) is effective for the treatment of experimental feline allergic asthma. In humans, the safety profile of immunotherapy is improved by delivering allergen by a mucosal route. We hypothesized that mucosal (intranasal) RIT would have similar efficacy to subcutaneous RIT with improved safety. Twelve cats sensitized and challenged with Bermuda grass allergen (BGA) were randomized to receive subcutaneous (SC) or intranasal (IN) RIT. Increasing doses of BGA (20-200 microg) were administered over 24h followed by 200 microg BGA weekly as maintenance. Adverse reactions were recorded. Clinical respiratory scores after BGA aerosol challenge, bronchoalveolar lavage fluid (BALF) % eosinophils, and cytokine concentrations were measured before RIT (day 1) and at months 1, 3 and 6 (M1, M3, M6). More adverse events were recorded with SC RIT (n=12) compared with IN RIT (n=6). Respiratory scores were lower by M6 compared with D1 in both the groups. The % BALF eosinophils declined significantly after RIT for both groups (mean+/-SEM, SC RIT D1 62+/-12, M6 9+/-4; IN RIT D1 54+/-9, M6 14+/-6). The BALF IL-4:IFN-gamma ratio significantly decreased over time in the IN RIT group (mean+/-SEM, D1 2.4+/-0.2, M6 1.0+/-0.2). While both protocols decreased eosinophilic airway inflammation, the SC RIT protocol did not cause life-threatening adverse events and demonstrated more consistent resolution of clinical signs after allergen challenge. Either protocol could be considered for the treatment of feline allergic asthma.

  17. Intranasal exposure to amorphous nanosilica particles could activate intrinsic coagulation cascade and platelets in mice

    Science.gov (United States)

    2013-01-01

    Background Nanomaterials with particle sizes coagulation system. Methods We used nanosilica particles with diameters of 30, 70, or 100 nm (nSP30, nSP70, or nSP100 respectively), and conventional microscale silica particles with diameters of 300 or 1000 nm (mSP300 or mSP1000, respectively). BALB/c mice were intranasally exposed to nSP30, nSP70, nSP100, mSP300, or mSP1000 at concentrations of 500 μg/mouse for 7 days. After 24 hours of last administration, we performed the in vivo transmission electron microscopy analysis, hematological examination and coagulation tests. Results In vivo transmission electron microscopy analysis showed that nanosilica particles with a diameter coagulation tests showed that platelet counts decreased and that the activated partial thromboplastin time was prolonged in nSP30 or nSP70-treated groups of mice, indicating that nanosilica particles might have activated a coagulation cascade. In addition, in in vitro activation tests of human plasma, nanosilica particles had greater potential than did conventional microscale silica particles to activate coagulation factor XII. In nanosilica-particle-treated groups, the levels of soluble CD40 ligand, and von Willebrand factor which are involved in stimulating platelets tended to slightly increase with decreasing particle size. Conclusions These results suggest that intranasally administered nanosilica particles with diameters of 30 and 70 nm could induce abnormal activation of the coagulation system through the activation of an intrinsic coagulation cascade. This study provides information to advance the development of safe and effective nanosilica particles. PMID:23958113

  18. A new brain drug delivery strategy: focused ultrasound-enhanced intranasal drug delivery.

    Science.gov (United States)

    Chen, Hong; Chen, Cherry C; Acosta, Camilo; Wu, Shih-Ying; Sun, Tao; Konofagou, Elisa E

    2014-01-01

    Central nervous system (CNS) diseases are difficult to treat because of the blood-brain barrier (BBB), which prevents most drugs from entering into the brain. Intranasal (i.n.) administration is a promising approach for drug delivery to the brain, bypassing the BBB; however, its application has been restricted to particularly potent substances and it does not offer localized delivery to specific brain sites. Focused ultrasound (FUS) in combination with microbubbles can deliver drugs to the brain at targeted locations. The present study proposed to combine these two different platform techniques (FUS+i.n.) for enhancing the delivery efficiency of intranasally administered drugs at a targeted location. After i.n. administration of 40 kDa fluorescently-labeled dextran as the model drug, FUS targeted at one region within the caudate putamen of mouse brains was applied in the presence of systemically administered microbubbles. To compare with the conventional FUS technique, in which intravenous (i.v.) drug injection is employed, FUS was also applied after i.v. injection of the same amount of dextran in another group of mice. Dextran delivery outcomes were evaluated using fluorescence imaging of brain slices. The results showed that FUS+i.n. enhanced drug delivery within the targeted region compared with that achieved by i.n. only. Despite the fact that the i.n. route has limited drug absorption across the nasal mucosa, the delivery efficiency of FUS+i.n. was not significantly different from that of FUS+i.v.. As a new drug delivery platform, the FUS+i.n. technique is potentially useful for treating CNS diseases.

  19. Formulation and evaluation of in situ gelling systems for intranasal administration of gastrodin.

    Science.gov (United States)

    Cai, Zheng; Song, Xiangrong; Sun, Feng; Yang, Zhaoxiang; Hou, Shixiang; Liu, Zhongqiu

    2011-12-01

    Gastrodin is the major bioactive constituent of the traditional Chinese drug "Tianma." It is used in the treatment of some nervous system diseases and can be transported to the brain via intranasal administration. In the current paper, the development of a novel ion-activated in situ gelling system for the nasal delivery of gastrodin is discussed. An in situ perfusion model was used to determine the absorption-rate constant of gastrodin through rat nasal mucosa. The optimal formulation was determined by measuring the critical cation concentration, anti-dilution capacity, gel expansion coefficient, water-holding capacity, and adhesive capacity. The best formulation consisted of 10% gastrodin, 0.5% deacetylated gellan gum as the gelatinizer, and 0.03% ethylparaben as the preservative. The rheological properties of gastrodin nasal in situ gels were also investigated. The viscosity and elasticity sharply increased at temperatures below 25°C. When physiological concentrations of cations were added into the preparation, the mixture gelled into a semi-solid. The results of an accelerated stability test show that gastrodin nasal in situ gels can be stable for more than 2 years. Mucociliary toxicity was evaluated using the in situ toad palate model and the rat nasal mucociliary method; both models demonstrated no measurable ciliotoxicity. Pharmacodynamic studies suggest that similar acesodyne and sedative effects were induced following intranasal administration of 50 mg/kg gastrodin nasal in situ gels or oral administration of 100 mg/kg gastrodin solution. The in situ gel preparation is a safe and effective nasal delivery system for gastrodin.

  20. Evaluation of Intranasal Midazolam as an Anesthetic Premedication in Preschool Children

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    Sh Behdad

    2005-10-01

    Full Text Available Introduction: Preoperative psycho emotional preparation of patients is one of the principle purposes of anesthesia which can be achieved by administration of premedications. Children should receive premedication before entering the operating room due to their dependence on parents and the fear and anxiety of separation from parents. Different drugs are administered for this purpose, but considering children's sensitivity, it is wise to use the most effective and comfortable medication with least side effects. Midazolam is a rapid onset, short acting and water soluble benzodiazapine which can be administered by oral, intravenous, intramuscular, rectal or intranasal routes. The purpose of this study was to evaluate the result of intranasal midazolam administration (0.2 mg/kg as a premedication in children aged 2-6 years.( Min dose and enough time Methods: In this randomized prospective study, 100 children aged between 2-6 years old in class ASA 1 and candidates of surgery were divided into two groups; case and control. The control group received several nasal drops of normal saline, while the case group received 0.2 mg/kg nasal midazolam 20 minutes before anesthesia induction. Results: Twenty minutes after administration of the nasal drops, 14% in the control group and 68% in the case group were alert and calm. (P value=0.0 . Mask acceptance during induction of anesthesia in control and case group was 14%and 72%, respectively (P value >0.00 The recovery time in the case group was longer (P value >0.5, but no complications (nausea, vomiting, respiratory and cardiovascular problems were seen in either group. Conclusion: Nasal midazolam with its anxiolytic, tranquilizing effects and no respiratory or cardiovascular complications is a safe drug and being better than parenteral drugs is acceptable by children.

  1. Early Intranasal Vasopressin Administration Impairs Partner Preference in Adult Male Prairie Voles (Microtus ochrogaster

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    Trenton C. Simmons

    2017-06-01

    Full Text Available Research supports a modulatory role for arginine vasopressin (AVP in the expression of socially motivated behaviors in mammals. The acute effects of AVP administration are demonstrably pro-social across species, providing the justification for an ever-increasing measure of clinical interest over the last decade. Combining these results with non-invasive intranasal delivery results in an attractive system for offering intranasal AVP (IN-AVP as a therapeutic for the social impairments of children with autism spectrum disorder. But, very little is known about the long-term effects of IN-AVP during early development. In this experiment, we explored whether a single week of early juvenile administration of IN-AVP (low = 0.05 IU/kg, medium = 0.5 IU/kg, high = 5.0 IU/kg could impact behavior across life in prairie voles. We found increases in fecal boli production during open field and novel object recognition testing for the medium dose in both males and females. Medium-dose females also had significantly more play bouts than control when exposed to novel conspecifics during the juvenile period. Following sexual maturity, the medium and high doses of IN-AVP blocked partner preference formation in males, while no such impairment was found for any of the experimental groups in females. Finally, the high-dose selectively increased adult male aggression with novel conspecifics, but only after extended cohabitation with a mate. Our findings confirm that a single week of early IN-AVP treatment can have organizational effects on behavior across life in prairie voles. Specifically, the impairments in pair-bonding behavior experienced by male prairie voles should raise caution when the prosocial effects of acute IN-AVP demonstrated in other studies are extrapolated to long-term treatment.

  2. Pharmacokinetics of Intranasal Scopolamine Gel Formulation During Antiorthostatic Bed Rest, a Microgravity Analog

    Science.gov (United States)

    Singh, Rajendra P.; Daniels, Vernie R.; Crady, Camille J.; Derendorf, H.; Putcha, L.

    2011-01-01

    Statement of Purpose, Innovation or Hypothesis: Space Motion sickness (SMS) is a long-standing problem for astronauts on both short and long duration space flights. Scopolamine (SCOP) is frequently used for the treatment of motion sickness (MS), and is available as transdermal patch and tablet dosage forms. These formulations of SCOP are ineffective for the treatment of SMS. Intranasal dosage forms are noninvasive with rapid absorption and enhanced bioavailability, thus allowing precise and reduced dosing in addition to offering rescue and treatment options. An intranasal gel dosage formulation of scopolamine (INSCOP) was developed and pharmacokinetics (PK) and bioavailability were determined in clinical trials with human subjects under IND guidelines.Description of Methods and Materials: The present clinical trial compares PK and bioavailability of INSCOP in 12 normal, healthy subjects (6 male/ 6 female) during ambulation (AMB) and antiorthostaticbed rest (ABR) used as a ground-based microgravity analog. Subjects received 0.2 mg and 0.4 mg doses of INSCOP during AMB and ABR in a 4-way crossover design.Data and Results: Results indicated no difference between AMB and ABR in PK parameters after 0.2 mg dose, Clearance (Cls) decreased with a concomitant increase in maximum concentration and area under concentration-versus-time curve (AUC) during ABR after the 0.4 mg dose.Interpretation, Conclusion or Significance: The difference in AUC and Cls at the higher (0.4 mg) but not the lower dose (0.2 mg) during ABR suggests that ABR may affect metabolism and/or clearance of INSCOP at higher doses . These results indicate that dosing adjustment may be required for treatment of SMS with INSCOP in space.

  3. Experimental induction of malignant catarrhal fever in pigs with ovine herpesvirus 2 by intranasal nebulization.

    Science.gov (United States)

    Li, Hong; Brooking, Angela; Cunha, Cristina W; Highland, Margaret A; O'Toole, Donal; Knowles, Donald P; Taus, Naomi S

    2012-10-12

    Malignant catarrhal fever (MCF), a frequently fatal herpesviral disease primarily of ruminant species, has been sporadically reported in pigs. All cases of naturally occurring porcine MCF reported to date have been linked to ovine herpesvirus 2 (OvHV-2), a gammaherpesvirus in the genus Macavirus carried by sheep. Experimental induction of MCF by aerosolization of the virus in nasal secretions collected from infected sheep has been successful in bison, cattle and rabbits. The goals of this study were to determine the susceptibility of pigs to MCF following experimental intranasal inoculation of OvHV-2, and to characterize the disease. Twelve pigs in four groups were nebulized with 10(5), 10(6), 10(7), or 10(8) DNA copies of OvHV-2 from sheep nasal secretions. Three control pigs were nebulized with nasal secretions from uninfected sheep. Three additional pigs were inoculated intravenously with 10(7) DNA copies of OvHV-2 to evaluate this route of infection with cell-free virus. Seven of twelve intranasally challenged pigs became infected with OvHV-2. Five of these seven, all in higher dose groups, developed MCF. Lesions resembled those reported in natural cases of porcine MCF. The most striking and consistent histological lesions were in trachea, lung, kidney and brain. These comprised mucopurulent tracheitis, interstitial pneumonia, necrotizing arteritis-periarteritis, and nonpurulent meningoencephalitis. No infection was established in the intravenously challenged or control groups. The study showed that MCF can be experimentally induced in pigs by aerosol challenge using sheep nasal secretions containing OvHV-2. Domestic pigs are a natural clinically susceptible host for sheep-associated MCF. They represent a useful, cost-effective model for MCF research. Published by Elsevier B.V.

  4. Study protocol of a randomised controlled trial of intranasal ketamine compared with intranasal fentanyl for analgesia in children with suspected, isolated extremity fractures in the paediatric emergency department

    Science.gov (United States)

    Reynolds, Stacy L; Studnek, Jonathan R; Bryant, Kathleen; VanderHave, Kelly; Grossman, Eric; Moore, Charity G; Young, James; Hogg, Melanie; Runyon, Michael S

    2016-01-01

    Introduction Fentanyl is the most widely studied intranasal (IN) analgesic in children. IN subdissociative (INSD) ketamine may offer a safe and efficacious alternative to IN fentanyl and may decrease overall opioid use during the emergency department (ED) stay. This study examines the feasibility of a larger, multicentre clinical trial comparing the safety and efficacy of INSD ketamine to IN fentanyl and the potential role for INSD ketamine in reducing total opioid medication usage. Methods and analysis This double-blind, randomised controlled, pilot trial will compare INSD ketamine (1 mg/kg) to IN fentanyl (1.5 μg/kg) for analgesia in 80 children aged 4–17 years with acute pain from a suspected, single extremity fracture. The primary safety outcome for this pilot trial will be the frequency of cumulative side effects and adverse events at 60 min after drug administration. The primary efficacy outcome will be exploratory and will be the mean reduction of pain scale scores at 20 min. The study is not powered to examine efficacy. Secondary outcome measures will include the total dose of opioid pain medication in morphine equivalents/kg/hour (excluding study drug) required during the ED stay, number and reason for screen failures, time to consent, and the number and type of protocol deviations. Patients may receive up to 2 doses of study drug. Ethics and dissemination This study was approved by the US Food and Drug Administration, the local institutional review board and the study data safety monitoring board. This study data will be submitted for publication regardless of results and will be used to establish feasibility for a multicentre, non-inferiority trial. Trial registration number NCT02521415. PMID:27609854

  5. Assessing the Subjective and Physiological Effects of Intranasally Administered Crushed Extended-Release Morphine Formulations with and without a Sequestered Naltrexone Core in Recreational Opioid Users

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    Beatrice Setnik

    2013-01-01

    Full Text Available OBJECTIVE: To evaluate the pharmacodynamic (PD effects of morphine sulfate and naltrexone hydrochloride extended-release (MSN capsules compared with controlled-release morphine sulfate (MS and placebo when crushed and administered intranasally.

  6. In vivo toxicity and immunogenicity of wheat germ agglutinin conjugated poly(ethylene glycol)-poly(lactic acid) nanoparticles for intranasal delivery to the brain.

    Science.gov (United States)

    Liu, Qingfeng; Shao, Xiayan; Chen, Jie; Shen, Yehong; Feng, Chengcheng; Gao, Xiaoling; Zhao, Yue; Li, Jingwei; Zhang, Qizhi; Jiang, Xinguo

    2011-02-15

    Biodegradable polymer-based nanoparticles have been widely studied to deliver therapeutic agents to the brain after intranasal administration. However, knowledge as to the side effects of nanoparticle delivery system to the brain is limited. The aim of this study was to investigate the in vivo toxicity and immunogenicity of wheat germ agglutinin (WGA) conjugated poly(ethylene glycol)-poly(lactic acid) nanoparticles (WGA-NP) after intranasal instillation. Sprague-Dawley rats were intranasally given WGA-NP for 7 continuous days. Amino acid neurotransmitters, lactate dehydrogenase (LDH) activity, reduced glutathione (GSH), acetylcholine, acetylcholinesterase activity, tumor necrosis factor α (TNF-α) and interleukin-8 (IL-8) in rat olfactory bulb (OB) and brain were measured to estimate the in vivo toxicity of WGA-NP. Balb/C mice were intranasally immunized by WGA-NP and then WGA-specific antibodies in serum and nasal wash were detected by indirect ELISA. WGA-NP showed slight toxicity to brain tissue, as evidenced by increased glutamate level in rat brain and enhanced LDH activity in rat OB. No significant changes in acetylcholine level, acetylcholinesterase activity, GSH level, TNF-α level and IL-8 level were observed in rat OB and brain for the WGA-NP group. WGA-specific antibodies in mice serum and nasal wash were not increased after two intranasal immunizations of WGA-NP. These results demonstrate that WGA-NP is a safe carrier system for intranasal delivery of therapeutic agents to the brain.

  7. Limited evidence for intranasal fentanyl in the emergency department and the prehospital setting--a systematic review

    DEFF Research Database (Denmark)

    Hansen, Morten Sejer; Dahl, Jørgen Berg

    2013-01-01

    The intranasal (IN) mode of application may be a valuable asset in non-invasive pain management. Fentanyl demonstrates pharmacokinetic and pharmacodynamic properties that are desirable in the management of acute pain, and IN fentanyl may be of value in the prehospital setting. The aim of this sys......The intranasal (IN) mode of application may be a valuable asset in non-invasive pain management. Fentanyl demonstrates pharmacokinetic and pharmacodynamic properties that are desirable in the management of acute pain, and IN fentanyl may be of value in the prehospital setting. The aim...... of this systematic review was to evaluate the current evidence for the use of IN fentanyl in the emergency department (ED) and prehospital setting....

  8. Comparación de la efectividad del midazolam en niños: via oral y via intranasal

    OpenAIRE

    Castro Jerí, Esmeralda Soledad; Facultad de Estomatología, Universidad Peruana Cayetano Heredia. Lima,; Díaz-Pizán, Maria Elena; Facultad de Estomatología, Universidad Peruana Cayetano Heredia. Lima,; Vargas Machuca, Mónica Valdivieso; Facultad de Estomatología, Universidad Peruana Cayetano Heredia. Lima,

    2014-01-01

    El propósito del presente estudio fue evaluar la efectividad de dos formas de administración demidazolam, vía oral e intranasal en la modificación de la conducta de niños en edad preescolarquienes recibieron tratamiento dental. Participaron 20 niños con edades entre los 22 a 68meses, quienes recibieron midazolam en dosis de 0,5mg/kg de peso administrado por vía oral y0,2 mg/kg de peso administrado por vía intranasal. A todos los niños se les registró la presiónarterial, frecuencia cardiaca y ...

  9. Brain delivery of small interfering ribonucleic acid and drugs through intranasal administration with nano-sized polymer micelles

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    Kanazawa T

    2015-01-01

    Full Text Available Takanori Kanazawa School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan Abstract: Recently, the development of effective strategies for enhancing drug delivery to the brain has been a topic of great interest in both clinical and pharmaceutical fields. In this review, we summarize our studies evaluating nose-to-brain delivery of drugs and small interfering ribonucleic acids in combination with cell-penetrating peptide-modified polymer micelles. Our findings show that the use of polymer micelles with surface modification with Tat peptide in the intranasal administration enables the non-invasive delivery of therapeutic agents to the brain by increasing the transfer of the administered drug or small interfering ribonucleic acid to the central nervous system from the nasal cavity. Keywords: nose-to-brain, polymer micelles, cell-penetrating peptide, intranasal administration, nucleic acid

  10. Intranasal administration of human umbilical cord mesenchymal stem cells-conditioned medium enhances vascular remodeling after stroke.

    Science.gov (United States)

    Zhao, Qiuchen; Hu, Jinxia; Xiang, Jie; Gu, Yuming; Jin, Peisheng; Hua, Fang; Zhang, Zunsheng; Liu, Yonghai; Zan, Kun; Zhang, Zuohui; Zu, Jie; Yang, Xinxin; Shi, Hongjuan; Zhu, Jienan; Xu, Yun; Cui, Guiyun; Ye, Xinchun

    2015-10-22

    Stem cell-based treatments have been reported to be a potential strategy for stroke. However, tumorigenic potential and low survival rates of transplanted cells could attenuate the efficacy of the stem cell-based treatments. The application of stem cell-condition medium (CM) may be a practicable approach to conquer these limitations. In this study, we investigated whether intranasal administration of human umbilical cord mesenchymal stem cells (hUCMSCs)-CM has the therapeutic effects in rats after stroke. Adult male rats were subjected to middle cerebral artery occlusion (MCAo) and were treated by intranasal routine with or without hUCMSCs-CM (1 ml/kg/d), starting 24h after MCAo and daily for 14 days. Neurological functional tests, blood brain barrier (BBB) leakage, were measured. Angiogenesis and angiogenic factor expression were measured by immunohistochemistry, and Western blot, respectively. hUCMSCs-CM treatment of stroke by intranasal routine starting 24h after MCAo in rats significantly enhances BBB functional integrity and promotes functional outcome but does not decrease lesion volume compared to rats in DMEM/F12 medium control group and saline control group. Treatment of ischemic rats with hUCMSCs-CM by intranasal routine also significantly decreases the levels of Ang2 and increases the levels of both Ang1 and Tie2 in the ischemic brain. To take together, increased expression of Ang1 and Tie2 and decreased expression of Ang2, induced by hUCMSCs-CM treatment, contribute to vascular remodeling in the ischemic brain which plays an important role in functional outcome after stroke.

  11. A Randomized, Controlled Trial of Intranasal Oxytocin as an Adjunct to Behavioral Therapy for Autism Spectrum Disorder

    Science.gov (United States)

    2015-10-01

    AWARD NUMBER: W81XWH-12-1-0543 TITLE: “A Randomized, Controlled Trial of Intranasal Oxytocin as an Adjunct to Behavioral Therapy for Autism... Behavioral Therapy for Autism Spectrum Disorder” 5b. GRANT NUMBER W81XWH-12-1-0543 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) John Gabrieli, Ph.D; Aude...Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The primary objectives of this clinical study are test the hypotheses that (1) cognitive behavioral

  12. Intranasal brain-derived neurotrophic factor protects brain from ischemic insult via modulating local inflammation in rats.

    Science.gov (United States)

    Jiang, Y; Wei, N; Lu, T; Zhu, J; Xu, G; Liu, X

    2011-01-13

    Inflammation plays a vital role in the pathogenesis of ischemic stroke. Brain-derived neurotrophic factor (BDNF) may protect brain tissues from ischemic injury. In this study, we investigated whether intranasal BDNF exerted neuroprotection against ischemic insult by modulating the local inflammation in rats with ischemic stroke. Rats were subjected to temporary occlusion of the right middle cerebral artery (120 min) and intranasal BDNF or vehicle was adminstrated 2 h after reperfusion. Infarct volume and neuron injury were measured using triphenyltetrazolium chloride, Nissl staining and TUNEL assay, respectively. Microglia were detected by immunohistofluorescence. Tumor necrosis factor-α, interleukin10 and mRNAs were evaluated by enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction. DNA-binding activity of nuclear factor-kappa B was measured by electrophoretic mobility shift assay. BDNF level in brain tissues was markedly raised following intranasal administration. There were more Nissl positive and less TUNEL positive neurons in BDNF group than in control group while intranasal BDNF did not reduce the infarct volume significantly (n=6, 0.27±0.04 vs. 0.24±0.05, P>0.05). BDNF increased the number of activated microglia (OX-42 positive) and phagocytotic microglia (ED1 positive). BDNF suppressed tumor necrosis factor-α and mRNA expression while increasing the interleukin10 and mRNA expression. BDNF also increased DNA-binding activity of nuclear factor-kappa B (n=6, 49.78±1.23 vs. 52.89±1.64, PBDNF might protect the brain against ischemic insult by modulating local inflammation via regulation of the levels of cellular, cytokine and transcription factor in the experimental stroke.

  13. MIDAZOLAM SEDATION IN PAEDIATRICS: COMPARATIVE STUDY OF INTRANASAL VERSUS SUBLINGUAL MIDAZOLAM ATOMIZER SPRAY IN PAEDIATRIC PATIENTS UNDERGOING MAGNETIC RESONANCE IMAGING

    Directory of Open Access Journals (Sweden)

    Santhisree

    2014-05-01

    Full Text Available INTRODUCTION: Magnetic Resonance Imaging (MRI causes a great amount of anxiety to both parents and child. Fear of unpleasant procedures and separation from parents may result in lasting and untoward psychological consequences in children. So sedation and anxiolysis is required for children undergoing even for minor diagnostic procedures. OBJECTIVES: The objectives of our study was to compare safety, onset of sedation, degree of sedation produced by intranasal and sublingual administration of midazolam for premedication in children of 4-10 years undergoing MRI. MATERIALS AND METHODS: In this prospective randomized double blind study, the intranasal and sublingual administration of midazolam in pediatric patients who were to undergo MRI was evaluated in 60 children who were aged between 4-10 years with ASA physical status I and II by using a newer midazolam spray. The patients were divided into two groups of 30 patients each and they received Midazolam 0.3 mg/kg. Either intranasally or sublingually in a randomized manner. The heart rate, oxygen saturation (SPO2, respiratory rate and the degree of sedation before and at 3 minutes intervals, recovery score, MRI image quality were recorded and compared. RESULTS: The respiratory rate, heart rate and the oxygen saturation was found from the baseline in both the groups (p >0.05. A sedation score of >3 (approx. was achieved in both the groups within 10 minutes of drug administration. The recovery score did not differ significantly between the two groups (p >0.05. CONCLUSION: Both the intranasal and sublingual administration of Midazolam as sedative is safe and equally effective in pediatric patients.

  14. Intranasal organic dust exposure-induced airway adaptation response marked by persistent lung inflammation and pathology in mice

    OpenAIRE

    Poole, Jill A.; Wyatt, Todd A; Oldenburg, Peter J.; Elliott, Margaret K.; West, William W.; Sisson, Joseph H.; Von Essen, Susanna G.; Romberger, Debra J.

    2009-01-01

    Organic dust exposure in agricultural environments results in an inflammatory response that attenuates over time, but repetitive exposures can result in chronic respiratory disease. Animal models to study these mechanisms are limited. This study investigated the effects of single vs. repetitive dust-induced airway inflammation in mice by intranasal exposure method. Mice were exposed to swine facility dust extract (DE) or saline once and once daily for 1 and 2 wk. Dust exposure resulted in inc...

  15. Immunogenicity and protective efficacy of an elastase-dependent live attenuated swine influenza virus vaccine administered intranasally in pigs.

    Science.gov (United States)

    Masic, Aleksandar; Lu, Xinya; Li, Junwei; Mutwiri, George K; Babiuk, Lorne A; Brown, Earl G; Zhou, Yan

    2010-10-01

    Influenza A virus is an important respiratory pathogen of swine that causes significant morbidity and economic impact on the swine industry. Vaccination is the first choice for prevention and control of influenza infections. Live attenuated influenza vaccines (LAIV) are approved for use in humans and horses and their application provides broad protective immunity, however no LAIV against swine influenza virus (SIV) exists in the market. Previously we reported that an elastase-dependent mutant SIV A/Sw/Sk-R345V (R345V) derived from A/Sw/Saskatchewan/18789/02 (H1N1) (SIV/Sk02) is highly attenuated in pigs. Two intratracheal administrations of R345V induced strong cell-mediated and humoral immune responses and provided a high degree of protection to antigenically different SIV infection in pigs. Here we evaluated the immunogenicity and the protective efficacy of R345V against SIV infection by intranasal administration, the more practical route for vaccination of pigs in the field. Our data showed that intranasally administered R345V live vaccine is capable of inducing strong antigen-specific IFN-γ response from local tracheo-bronchial lymphocytes and antibody responses in serum and respiratory mucosa after two applications. Intranasal vaccination of R345V provided pigs with complete protection not only from parental wild type virus infection, but also from homologous antigenic variant A/Sw/Indiana/1726/88 (H1N1) infection. Moreover, intranasal administration of R345V conferred partial protection from heterologous subtypic H3N2 SIV infection in pigs. Thus, R345V elastase-dependent mutant SIV can serve as a live vaccine against antigenically different swine influenza viruses in pigs.

  16. A Randomized, Controlled Trial of Intranasal Oxytocin as an Adjunct to Behavioral Therapy for Autism Spectrum Disorder

    Science.gov (United States)

    2016-10-01

    active placebo behavioral treatment of 12 sessions of relaxation training, and placebo medication; (2) Group 2 (CBT/placebo), who will receive the...randomized to receive either social skills training or a stress management/ relaxation therapy, and will be randomized to receive either intranasal oxytocin...structural image edits for Freesurfer processing stream, and preliminary analysis of functional task activation to verify data quality and expected

  17. Intranasal Delivery of A Novel Amnion Cell Secretome Prevents Neuronal Damage and Preserves Function In A Mouse Multiple Sclerosis Model

    Science.gov (United States)

    Khan, Reas S.; Dine, Kimberly; Bauman, Bailey; Lorentsen, Michael; Lin, Lisa; Brown, Helayna; Hanson, Leah R.; Svitak, Aleta L.; Wessel, Howard; Brown, Larry; Shindler, Kenneth S.

    2017-01-01

    The ability of a novel intranasally delivered amnion cell derived biologic to suppress inflammation, prevent neuronal damage and preserve neurologic function in the experimental autoimmune encephalomyelitis animal model of multiple sclerosis was assessed. Currently, there are no existing optic nerve treatment methods for disease or trauma that result in permanent vision loss. Demyelinating optic nerve inflammation, termed optic neuritis, induces permanent visual dysfunction due to retinal ganglion cell damage in multiple sclerosis and experimental autoimmune encephalomyelitis. ST266, the biological secretome of Amnion-derived Multipotent Progenitor cells, contains multiple anti-inflammatory cytokines and growth factors. Intranasally administered ST266 accumulated in rodent eyes and optic nerves, attenuated visual dysfunction, and prevented retinal ganglion cell loss in experimental optic neuritis, with reduced inflammation and demyelination. Additionally, ST266 reduced retinal ganglion cell death in vitro. Neuroprotective effects involved oxidative stress reduction, SIRT1-mediated mitochondrial function promotion, and pAKT signaling. Intranasal delivery of neuroprotective ST266 is a potential novel, noninvasive therapeutic modality for the eyes, optic nerves and brain. The unique combination of biologic molecules in ST266 provides an innovative approach with broad implications for suppressing inflammation in autoimmune diseases, and for preventing neuronal damage in acute neuronal injury and chronic neurodegenerative diseases such as multiple sclerosis. PMID:28139754

  18. Limited susceptibility and lack of systemic infection by an H3N2 swine influenza virus in intranasally inoculated chickens.

    Science.gov (United States)

    Thomas, Colleen; Manin, Timofey B; Andriyasov, Artem V; Swayne, David E

    2008-09-01

    Chickens were intranasally inoculated with the swine influenza virus (SIV) A/swine/NC/307408/04 (H3N2) (NC/04 SIV) to determine the infectivity of a North American SIV for chickens, as well as the possibility of chicken meat serving as a transmission vehicle for SIV. White leghorn (WL) layer-type chickens were used for initial pathotyping and infectivity tests, and a more comprehensive intranasal pathogenesis study was done with white Plymouth rock (WPR) broiler-type chickens. None of the NC/04 SIV-inoculated WL or WPR chickens displayed clinical signs. Serologic tests showed that the virus was able to infect both intranasally inoculated WL and WPR chickens, but the antibody titers were low, suggesting inefficient replication. Some of the NC/04 SIV-inoculated WL chickens shed low levels of virus, mostly from the alimentary tract, but viral shedding was not detected in NC/04 SIV-inoculated WPR chickens. The comprehensive pathogenesis study demonstrated that the virus did not cause systemic infections in WPR chickens, and feeding breast and thigh meat from the NC/04 SIV-inoculated WPR to WL chickens did not transmit NC/04 SIV.

  19. Brain cytokine and chemokine mRNA expression in mice induced by intranasal instillation with ultrafine carbon black.

    Science.gov (United States)

    Tin-Tin-Win-Shwe; Yamamoto, Shoji; Ahmed, Sohel; Kakeyama, Masaki; Kobayashi, Takahiro; Fujimaki, Hidekazu

    2006-05-25

    Ambient air ultrafine particles (UFPs) have gained enormous attention to many researchers with recent evidence showing them to have more hazardous effects on human health than larger ambient particles. Studies focusing the possibility of effects on brain are quite limited. To examine the effect of ultrafine carbon black (ufCB) on mice brain, we instilled 125 microg of 14 nm or 95 nm CB into the nostrils of 8-week-old male BALB/c mice, once a week for 4 weeks. Four hours after the last instillation, we collected olfactory bulb and hippocampus and detected the expression of cytokine and chemokine mRNA by quantitative real-time PCR method. In this study, we found the induction of proinflammatory cytokines (interleukin-1 beta and tumor necrosis factor-alpha and chemokines (monocyte chemoattractant protein-1/CCL2, macrophage inflammatory protein-1 alpha/CCL3), and monokine induced interferon-gamma/CXC chemokine ligand (CXCL9) mRNA in brain olfactory bulb, not in the hippocampus of mice instilled with 14 nm ufCB intranasally. We suggest that the intranasal instillation of ufCB may influence the brain immune function depending on their size. To our knowledge, this is the first study to demonstrate region-specific brain cytokine and chemokine mRNA-induction in mice triggered by intranasal instillation of specific-sized ufCB, in a physiologically relevant condition.

  20. Mucosal vaccination by the intranasal route. Nose-associated lymphoid tissue (NALT)-Structure, function and species differences.

    Science.gov (United States)

    Pabst, Reinhard

    2015-08-26

    The advantage of mucosal vaccination in viral and bacterial infections in different age groups is of enormous clinical relevance. The advantages and potential hazards of intranasal vaccination have always to be considered. The intranasal route for vaccination is very successful for some antigens. Specific adjuvants are necessary. In the nose of rodents there is a structured lymphoid tissue (nose-associated lymphoid tissue (NALT)). This abbreviation should not be used for nasopharynx-associated lymphoid tissue, as this includes parts of the tonsils. In children lymphoid tissue is more dispersed in the nose and not concentrated at the bottom of the dorsal nose ducts as in rodents. There are no data on organized lymphoid tissue in the nose of adults. In NALT of rodents there is a unique structure of adhesion molecule expression; the postnatal development and the different composition of T and B lymphocytes in comparison with Peyer's patches document the uniqueness of this lymphoid organ. There is also a mucosa in the nose with antigen-presenting dendritic cells. Thus, it is often unclear whether intranasal vaccination is initiated via NALT or the diffuse nasal mucosa. There are still many open questions e. g., which adjuvant is necessary for a specific virus, bacterium or other allergen, how many doses are critical for an effective nasal vaccination. Species differences are of major importance when extrapolating results from rodents to humans.

  1. Intranasal salcatonin (salmon calcitonin). A review of its pharmacological properties and role in the management of postmenopausal osteoporosis.

    Science.gov (United States)

    Plosker, G L; McTavish, D

    1996-05-01

    Osteoporosis is a common problem among postmenopausal women and is associated with significant morbidity, mortality and costs primarily resulting from osteoporotic fractures. Salcatonin (salmon calcitonin) inhibits osteoclastic bone resorption and is approximately 40 to 50 times more potent than human calcitonin. In most randomised trials in which intranasal salcatonin (usually 50 to 200 IU/day plus oral calcium supplements) was administered for 1 to 5 years to postmenopausal women for prevention of osteoporosis, bone mineral density or content of the lumbar spine increased by approximately 1 to 3% from baseline. In contrast, postmenopausal women receiving only oral calcium supplements typically had reductions in bone mineral density or content of about 3 to 6%. The difference between treatment groups was statistically significant in essentially all studies. Although changes in bone mineral density or content were broadly similar in studies of postmenopausal women with established osteoporosis to those in postmenopausal women receiving therapy for prevention of the disease, studies in women with established osteoporosis did not usually demonstrate statistically significant differences between treatment groups. Also in postmenopausal women with established osteoporosis, intranasal salcatonin reduced pain and/or analgesic consumption in some trials and, in a limited number of studies of relatively short duration (i.e. transient, usually involving local reactions such as nasal discomfort, rhinorrhoea or rhinitis. Thus, for postmenopausal women unable or unwilling to tolerate long term hormone replacement therapy, intranasal salcatonin is an attractive alternative for the management of osteoporosis.

  2. One time intranasal vaccination with a modified vaccinia Tiantan strain MVTT(ZCI) protects animals against pathogenic viral challenge.

    Science.gov (United States)

    Yu, Wenbo; Fang, Qing; Zhu, Weijun; Wang, Haibo; Tien, Po; Zhang, Linqi; Chen, Zhiwei

    2010-02-25

    To combat variola virus in bioterrorist attacks, it is desirable to develop a noninvasive vaccine. Based on the vaccinia Tiantan (VTT) strain, which was historically used to eradicate the smallpox in China, we generated a modified VTT (MVTT(ZCI)) by removing the hemagglutinin gene and an 11,944bp genomic region from HindIII fragment C2L to F3L. MVTT(ZCI) was characterized for its host cell range in vitro and preclinical safety and efficacy profiles in mice. Despite replication-competency in some cell lines, unlike VTT, MVTT(ZCI) did not cause death after intracranial injection or body weight loss after intranasal inoculation. MVTT(ZCI) did not replicate in mouse brain and was safe in immunodeficient mice. MVTT(ZCI) induced neutralizing antibodies via the intranasal route of immunization. One time intranasal immunization protected animals from the challenge of the pathogenic vaccinia WR strain. This study established proof-of-concept that the attenuated replicating MVTT(ZCI) may serve as a safe noninvasive smallpox vaccine candidate.

  3. Using Gelatin Nanoparticle Mediated Intranasal Delivery of Neuropeptide Substance P to Enhance Neuro-Recovery in Hemiparkinsonian Rats.

    Directory of Open Access Journals (Sweden)

    Ying-Zheng Zhao

    Full Text Available Intranasal administration of phospholipid-based gelatin nanoparticles (GNP was prepared to investigate the neuro-recovery effects of neuropeptide Substance P (SP on hemiparkinsonian rats.The SP-loaded gelatin nanoparticles (SP-GNP were prepared by a water-in-water emulsion method and possessed high stability, encapsulating efficiency and loading capacity. PC-12 cells were used to examine the growth enhancement of SP-GNP in vitro by MTT assays and flow cytometry (FCM. The therapeutic effects of SP-GNP on 6-hydroxydopamine (6-OHDA induced hemiparkinsonian rats were assessed by quantifying rotational behavior and the levels of tyrosine hydroxylase (TH, phosphorylated c-Jun protein (p-c-Jun and Caspase-3 (Cas-3 expressed in substantia nigra (SN region of hemiparkinsonian rats.PC-12 cells under SP-GNP treatment showed better cell viability and lower degree of apoptosis than those under SP solution treatment. Hemiparkinsonian rats under intranasal SP-GNP administration demonstrated better behavioral improvement, higher level of TH in SN along with much lower extent of p-c-Jun and Cas-3 than those under intranasal SP solution administration and intravenous SP-GNP administration.With the advantages of GNP and nose-to-brain pathway, SP can be effectively delivered into the damaged SN region and exhibit its neuro-recovery function through the inhibition on JNK pathway and dopaminergic neuron apoptosis.

  4. Therapeutic efficacy of intranasally delivered mesenchymal stem cells in a rat model of Parkinson disease.

    Science.gov (United States)

    Danielyan, Lusine; Schäfer, Richard; von Ameln-Mayerhofer, Andreas; Bernhard, Felix; Verleysdonk, Stephan; Buadze, Marine; Lourhmati, Ali; Klopfer, Tim; Schaumann, Felix; Schmid, Barbara; Koehle, Christoph; Proksch, Barbara; Weissert, Robert; Reichardt, Holger M; van den Brandt, Jens; Buniatian, Gayane H; Schwab, Matthias; Gleiter, Christoph H; Frey, William H

    2011-02-01

    Safe and effective cell delivery remains one of the main challenges in cell-based therapy of neurodegenerative disorders. Graft survival, sufficient enrichment of therapeutic cells in the brain, and avoidance of their distribution throughout the peripheral organs are greatly influenced by the method of delivery. Here we demonstrate for the first time noninvasive intranasal (IN) delivery of mesenchymal stem cells (MSCs) to the brains of unilaterally 6-hydroxydopamine (6-OHDA)-lesioned rats. IN application (INA) of MSCs resulted in the appearance of cells in the olfactory bulb, cortex, hippocampus, striatum, cerebellum, brainstem, and spinal cord. Out of 1 × 10⁶ MSCs applied intranasally, 24% survived for at least 4.5 months in the brains of 6-OHDA rats as assessed by quantification of enhanced green fluorescent protein (EGFP) DNA. Quantification of proliferating cell nuclear antigen-positive EGFP-MSCs showed that 3% of applied MSCs were proliferative 4.5 months after application. INA of MSCs increased the tyrosine hydroxylase level in the lesioned ipsilateral striatum and substantia nigra, and completely eliminated the 6-OHDA-induced increase in terminal deoxynucleotidyl transferase (TdT)-mediated 2'-deoxyuridine, 5'-triphosphate (dUTP)-biotin nick end labeling (TUNEL) staining of these areas. INA of EGFP-labeled MSCs prevented any decrease in the dopamine level in the lesioned hemisphere, whereas the lesioned side of the control animals revealed significantly lower levels of dopamine 4.5 months after 6-OHDA treatment. Behavioral analyses revealed significant and substantial improvement of motor function of the Parkinsonian forepaw to up to 68% of the normal value 40-110 days after INA of 1 × 10⁶ cells. MSC-INA decreased the concentrations of inflammatory cytokines-interleukin-1β (IL-1β), IL-2, -6, -12, tumor necrosis factor (TNF), interferon-γ (IFN-γ, and granulocyte-macrophage colony-stimulating factor (GM-CSF)-in the lesioned side to their

  5. Selective CNS Uptake of the GCP-II Inhibitor 2-PMPA following Intranasal Administration.

    Directory of Open Access Journals (Sweden)

    Rana Rais

    Full Text Available Glutamate carboxypeptidase II (GCP-II is a brain metallopeptidase that hydrolyzes the abundant neuropeptide N-acetyl-aspartyl-glutamate (NAAG to NAA and glutamate. Small molecule GCP-II inhibitors increase brain NAAG, which activates mGluR3, decreases glutamate, and provide therapeutic utility in a variety of preclinical models of neurodegenerative diseases wherein excess glutamate is presumed pathogenic. Unfortunately no GCP-II inhibitor has advanced clinically, largely due to their highly polar nature resulting in insufficient oral bioavailability and limited brain penetration. Herein we report a non-invasive route for delivery of GCP-II inhibitors to the brain via intranasal (i.n. administration. Three structurally distinct classes of GCP-II inhibitors were evaluated including DCMC (urea-based, 2-MPPA (thiol-based and 2-PMPA (phosphonate-based. While all showed some brain penetration following i.n. administration, 2-PMPA exhibited the highest levels and was chosen for further evaluation. Compared to intraperitoneal (i.p. administration, equivalent doses of i.n. administered 2-PMPA resulted in similar plasma exposures (AUC0-t, i.n./AUC0-t, i.p. = 1.0 but dramatically enhanced brain exposures in the olfactory bulb (AUC0-t, i.n./AUC0-t, i.p. = 67, cortex (AUC0-t, i.n./AUC0-t, i.p. = 46 and cerebellum (AUC0-t, i.n./AUC0-t, i.p. = 6.3. Following i.n. administration, the brain tissue to plasma ratio based on AUC0-t in the olfactory bulb, cortex, and cerebellum were 1.49, 0.71 and 0.10, respectively, compared to an i.p. brain tissue to plasma ratio of less than 0.02 in all areas. Furthermore, i.n. administration of 2-PMPA resulted in complete inhibition of brain GCP-II enzymatic activity ex-vivo confirming target engagement. Lastly, because the rodent nasal system is not similar to humans, we evaluated i.n. 2-PMPA also in a non-human primate. We report that i.n. 2-PMPA provides selective brain delivery with micromolar concentrations. These studies

  6. Intranasal infection with Chlamydia abortus induces dose-dependent latency and abortion in sheep.

    Directory of Open Access Journals (Sweden)

    David Longbottom

    Full Text Available BACKGROUND: Latency is a key feature of the animal pathogen Chlamydia abortus, where infection remains inapparent in the non-pregnant animal and only becomes evident during a subsequent pregnancy. Often the first sign that an animal is infected is abortion occurring late in gestation. Despite this, little is understood of the underlying mechanisms that control latency or the recrudescence of infection that occurs during subsequent pregnancy. The aim of this study was to develop an experimental model of latency by mimicking the natural route of infection through the intranasal inoculation of non-pregnant sheep with C. abortus. METHODOLOGY/PRINCIPAL FINDINGS: Three groups of sheep (groups 1, 2 and 3 were experimentally infected with different doses of C. abortus (5×10(3, 5×10(5 and 5×10(7 inclusion forming units (IFU, respectively prior to mating and monitored over 2 breeding cycles for clinical, microbiological, pathological, immunological and serological outcomes. Two further groups received either negative control inoculum (group 4a,b or were inoculated subcutaneously on day 70 of gestation with 2×10(6 IFU C. abortus (group 5. Animals in groups 1, 2 and 5 experienced an abortion rate of 50-67%, while only one animal aborted in group 3 and none in group 4a,b. Pathological, microbiological, immunological and serological analyses support the view that the maternal protective immune response is influenced by initial exposure to the bacterium. CONCLUSIONS/SIGNIFICANCE: The results show that intranasal administration of non-pregnant sheep with a low/medium dose of C. abortus results in a latent infection that leads in a subsequent pregnancy to infection of the placenta and abortion. In contrast a high dose stimulates protective immunity, resulting in a much lower abortion rate. This model will be useful in understanding the mechanisms of infection underlying latency and onset of disease, as well as in the development of novel therapeutics and

  7. Intranasal sufentanil/midazolam versus ketamine/midazolam for analgesia/sedation in the pediatric population prior to undergoing multiple dental extractions under general anesthesia: a prospective, double-blind, randomized comparison.

    Science.gov (United States)

    Roelofse, J A; Shipton, E A; de la Harpe, C J; Blignaut, R J

    2004-01-01

    This article details a double-blind, randomized study evaluating the efficacy and safety of intranasal sufentanil and intranasal midazolam (S/M) when compared with intranasal ketamine and intranasal midazolam (K/M) for sedation and analgesia in pediatric patients undergoing dental surgery. Fifty healthy ASA status 1 children aged 5-7 years, weighing 15-20 kg, and having 6 or more teeth extracted, were randomly allocated to 2 groups of 25 patients each (n = 50). In the S/M group, 25 children received intranasal sufentanil 20 microg, and intranasal midazolam 0.3 mg/kg 20 minutes before the induction of anesthesia. In the K/M group, 25 children received intranasal ketamine 5 mg/kg and intranasal midazolam 0.3 mg/kg 20 minutes before the induction of anesthesia. Sevoflurane in nitrous oxide and oxygen was used for induction and maintenance of anesthesia. This study demonstrated the safety and efficacy of both methods with ease of administration, combined with a rapid onset of action. Both groups were equally sedated. A smooth mask induction of anesthesia was experienced in the majority of children. Effective postoperative analgesia for multiple dental extractions was provided. The intranasal administration of drugs for sedation and analgesia has some promising features in preschool children undergoing multiple dental extractions.

  8. Intranasal immunisation with recombinant adenovirus vaccines protects against a lethal challenge with pneumonia virus of mice.

    Science.gov (United States)

    Maunder, Helen E; Taylor, Geraldine; Leppard, Keith N; Easton, Andrew J

    2015-11-27

    Pneumonia virus of mice (PVM) infection of BALB/c mice induces bronchiolitis leading to a fatal pneumonia in a dose-dependent manner, closely paralleling the development of severe disease during human respiratory syncytial virus infection in man, and is thus a recognised model in which to study the pathogenesis of pneumoviruses. This model system was used to investigate delivery of the internal structural proteins of PVM as a potential vaccination strategy to protect against pneumovirus disease. Replication-deficient recombinant human adenovirus serotype 5 (rAd5) vectors were constructed that expressed the M or N gene of PVM pathogenic strain J3666. Intranasal delivery of these rAd5 vectors gave protection against a lethal challenge dose of PVM in three different mouse strains, and protection lasted for at least 20 weeks post-immunisation. Whilst the PVM-specific antibody response in such animals was weak and inconsistent, rAd5N primed a strong PVM-specific CD8(+) T cell response and, to a lesser extent, a CD4(+) T cell response. These findings suggest that T-cell responses may be more important than serum IgG in the observed protection induced by rAd5N.

  9. Focused ultrasound-enhanced intranasal brain delivery of brain-derived neurotrophic factor

    Science.gov (United States)

    Chen, Hong; Yang, Georgiana Zong Xin; Getachew, Hoheteberhan; Acosta, Camilo; Sierra Sánchez, Carlos; Konofagou, Elisa E.

    2016-06-01

    The objective of this study was to unveil the potential mechanism of focused ultrasound (FUS)-enhanced intranasal (IN) brain drug delivery and assess its feasibility in the delivery of therapeutic molecules. Delivery outcomes of fluorescently-labeled dextrans to mouse brains by IN administration either before or after FUS sonication were compared to evaluate whether FUS enhances IN delivery by active pumping or passive diffusion. Fluorescence imaging of brain slices found that IN administration followed by FUS sonication achieved significantly higher delivery than IN administration only, while pre-treatment by FUS sonication followed by IN administration was not significantly different from IN administration only. Brain-derived neurotrophic factor (BDNF), a promising neurotrophic factor for the treatment of many central nervous system diseases, was delivered by IN followed by FUS to demonstrate the feasibility of this technique and compared with the established FUS technique where drugs are injected intravenously. Immunohistochemistry staining of BDNF revealed that FUS-enhanced IN delivery achieved similar locally enhanced delivery as the established FUS technique. This study suggested that FUS enhances IN brain drug delivery by FUS-induced active pumping of the drug and demonstrated that FUS-enhanced IN delivery is a promising technique for noninvasive and localized delivery of therapeutic molecules to the brain.

  10. Thermosensitive PLA based nanodispersion for targeting brain tumor via intranasal route.

    Science.gov (United States)

    Jain, Darshana S; Bajaj, Amrita N; Athawale, Rajani B; Shikhande, Shruti S; Pandey, Abhijeet; Goel, Peeyush N; Gude, Rajiv P; Patil, Satish; Raut, Preeti

    2016-06-01

    Delivery of drugs to the brain via nasal route has been studied by many researchers. However, low residence time, mucociliary clearance and enzymatically active environment of nasal cavity pose many challenges to successful nasal delivery of drugs. We aim to deliver methotrexate by designing thermosensitive nanodispersion exhibiting enhanced residence time in nasal cavity and bypassing the blood brain barrier (BBB). PLA nanoparticles were developed using solvent evaporation technique. The developed nanoparticles were further dispersed in prepared thermosensitive vehicle of poloxamer 188 and Carbopol 934 to impart the property of increased residence time. The formulated nanoparticles demonstrated no interaction with the simulated nasal fluids (SNF), mucin, serum proteins and erythrocytes which demonstrate the safety of developed formulation for nasal administration. The penetration property of nanoparticles though the nasal mucosa was higher than the pure drug due to low mucociliary clearance. The developed nanoparticles diffused though the membrane pores and rapidly distributed into the brain portions compared to the pure drug. There was detectable and quantifiable amount of drug seen in the brain as demonstrated by in vivo brain distribution studies with considerably low amount of drug deposition in the lungs. The pharmacokinetic parameters demonstrated the enhancement in circulation half life, area under curve (AUC) and Cmax of the drug when administered intranasal in encapsulated form. Thus, the thermosensitive nanodispersions are surely promising delivery systems for delivering anticancer agents though the nasal route for potential treatment of brain tumors.

  11. The Phage Lysin PlySs2 Decolonizes Streptococcus suis from Murine Intranasal Mucosa

    Science.gov (United States)

    Gilmer, Daniel B.; Schmitz, Jonathan E.; Thandar, Mya; Euler, Chad W.; Fischetti, Vincent A.

    2017-01-01

    Streptococcus suis infects pigs worldwide and may be zoonotically transmitted to humans with a mortality rate of up to 20%. S. suis has been shown to develop in vitro resistance to the two leading drugs of choice, penicillin and gentamicin. Because of this, we have pursued an alternative therapy to treat these pathogens using bacteriophage lysins. The bacteriophage lysin PlySs2 is derived from an S. suis phage and displays potent lytic activity against most strains of that species including serotypes 2 and 9. At 64 μg/ml, PlySs2 reduced multiple serotypes of S. suis by 5 to 6-logs within 1 hour in vitro and exhibited a minimum inhibitory concentration (MIC) of 32 μg/ml for a S. suis serotype 2 strain and 64 μg/ml for a serotype 9 strain. Using a single 0.1-mg dose, the colonizing S. suis serotype 9 strain was reduced from the murine intranasal mucosa by >4 logs; a 0.1-mg dose of gentamicin reduced S. suis by 5-logs. While resistance to gentamicin was induced after systematically increasing levels of gentamicin in an S. suis culture, the same protocol resulted in no observable resistance to PlySs2. Thus, PlySs2 has both broad and high killing activity against multiple serotypes and strains of S. suis, making it a possible tool in the control and prevention of S. suis infections in pigs and humans. PMID:28046082

  12. Intranasal immunization against dental caries with a Streptococcus mutans-enriched fimbrial preparation.

    Science.gov (United States)

    Fontana, M; Dunipace, A J; Stookey, G K; Gregory, R L

    1999-05-01

    Streptococcus mutans has been identified as the major etiological agent of human dental caries. The first step in the initiation of infection by this pathogenic bacterium is its attachment (i.e., through bacterial surface proteins such as glucosyltransferases, P1, glucan-binding proteins, and fimbriae) to a suitable receptor. It is hypothesized that a mucosal vaccine against a combination of S. mutans surface proteins would protect against dental caries by inducing specific salivary immunoglobulin A (IgA) antibodies which may reduce bacterial pathogenesis and adhesion to the tooth surface by affecting several adhesins simultaneously. Conventional Sprague-Dawley rats, infected with S. mutans at 18 to 20 days of age, were intranasally immunized with a mixture of S. mutans surface proteins, enriched for fimbriae and conjugated with cholera toxin B subunit (CTB) plus free cholera toxin (CT) at 13, 15, 22, 29, and 36 days of age (group A). Control rats were either not immunized (group B) or immunized with adjuvant alone (CTB and CT [group C]). At the termination of the study (when rats were 46 days of age), immunized animals (group A) had significantly (P dental caries.

  13. Safety and efficacy of adjunctive intranasal mitomycin C and triamcinolone in endonasal endoscopic dacryocystorhinostomy.

    Science.gov (United States)

    Li, Emmy Y; Cheng, Andy C; Wong, Alex C; Sze, Amy M; Yuen, Hunter K

    2016-02-01

    One of the common causes of failure in dacryocystorhinostomy for nasolacrimal duct obstruction (NLDO) is mucosal scarring and fibrosis around the ostium. Steroid and mitomycin C (MMC) can potentially reduce scarring by their action on the inflammatory and proliferative phase of wound healing, respectively. The purpose of this study is to evaluate the safety and efficacy of combined usage of adjunctive MMC and intranasal triamcinolone (TA) in endonasal endoscopic dacryocystorhinostomy (EE-DCR). This is a retrospective interventional case series. All patients underwent mechanical EE-DCR in two regional hospitals in Hong Kong from January 2005 to December 2006 were included. All received intraoperative MMC application for 5 min and gelfoam soaked with TA onto the ostium. Main outcome measures include the anatomical and functional success rate at follow-up at least 6 months after operation. Other outcomes include complications occurred during and after operation. A total of 73 EE-DCR were performed in 69 patients. Three patients had simultaneous bilateral DCR; one had sequential DCRs for both sides. At the last follow-up, anatomical success was achieved in 68 cases (93 %) and both anatomical with functional success in 67 cases (92 %). No major complication was observed. Minor complications included asymptomatic mucosal adhesion between the nasal septum and lateral nasal wall in one patient and moderate secondary hemorrhage in another. EE-DCR with adjunctive MMC and TA is a safe and successful procedure for the treatment of NLDO.

  14. Low-dose intranasal versus oral midazolam for routine body MRI of claustrophobic patients.

    Science.gov (United States)

    Tschirch, Frank T C; Göpfert, Kerstin; Fröhlich, Johannes M; Brunner, Genevieve; Weishaupt, Dominik

    2007-06-01

    The purpose of this study was to assess prospectively the potential of low-dose intranasal midazolam compared to oral midazolam in claustrophobic patients undergoing routine body magnetic resonance imaging (MRI). Seventy-two adult claustrophobic patients referred for body MRI were randomly assigned to one of two treatment groups (TG1 and TG2). The 36 patients of TG1 received 7.5 mg midazolam orally 15 min before MRI, whereas the 36 patients of TG2 received one (or, if necessary, two) pumps of a midazolam nasal spray into each nostril immediately prior to MRI (in total, 1 or 2 mg). Patients' tolerance, anxiety and sedation were assessed using a questionnaire and a visual analogue scale immediately before and after MRI. Image quality was evaluated using a five-point-scale. In TG1, 18/36 MRI examinations (50%) had to be cancelled, the reduction of anxiety was insufficient in 12/18 remaining patients (67%). In TG2, 35/36 MRI examinations (97%) were completed successfully, without relevant adverse effects. MRI image quality was rated higher among patients of TG2 compared to TG1 (pclaustrophobic patients in a broad spectrum of body MRI. Its anxiolytic effect is superior to that of the orally administrated form.

  15. Intranasal immunization with nontypeable Haemophilus influenzae outer membrane vesicles induces cross-protective immunity in mice.

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    Sandro Roier

    Full Text Available Haemophilus influenzae is a Gram-negative human-restricted bacterium that can act as a commensal and a pathogen of the respiratory tract. Especially nontypeable H. influenzae (NTHi is a major threat to public health and is responsible for several infectious diseases in humans, such as pneumonia, sinusitis, and otitis media. Additionally, NTHi strains are highly associated with exacerbations in patients suffering from chronic obstructive pulmonary disease. Currently, there is no licensed vaccine against NTHi commercially available. Thus, this study investigated the utilization of outer membrane vesicles (OMVs as a potential vaccine candidate against NTHi infections. We analyzed the immunogenic and protective properties of OMVs derived from various NTHi strains by means of nasopharyngeal immunization and colonization studies with BALB/c mice. The results presented herein demonstrate that an intranasal immunization with NTHi OMVs results in a robust and complex humoral and mucosal immune response. Immunoprecipitation revealed the most important immunogenic proteins, such as the heme utilization protein, protective surface antigen D15, heme binding protein A, and the outer membrane proteins P1, P2, P5 and P6. The induced immune response conferred not only protection against colonization with a homologous NTHi strain, which served as an OMV donor for the immunization mixtures, but also against a heterologous NTHi strain, whose OMVs were not part of the immunization mixtures. These findings indicate that OMVs derived from NTHi strains have a high potential to act as a vaccine against NTHi infections.

  16. Midazolam intranasal para la sedación preanestésica pediátrica

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    Joaquín L. de la Lastra Rodríguez

    1995-12-01

    Full Text Available El ingreso hospitalario y un tratamiento quirúrgico pueden crear en los niños temor, ansiedad y trastornos emocionales al abandonar la atmósfera de seguridad y confianza del hogar y estar en el ambiente desconocido del hospital. La medicación preanestésica logra la reducción de la ansiedad y disminuye su respuesta. En el presente trabajo se utilizó con este fin el midazolam al 0,5 % (dormicum en dosis de 0,2 a 0,3 mg por kg de peso corporal administrado por vía intranasal, con la finalidad de observar las ventajas de este método en 30 niños menores de 5 años de edad. Se logró una sedación rápida y de corta duración y no se observó ninguna complicación.

  17. Intranasal delivery of cholera toxin induces th17-dominated T-cell response to bystander antigens.

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    Jee-Boong Lee

    Full Text Available Cholera toxin (CT is a potent vaccine adjuvant, which promotes mucosal immunity to protein antigen given by nasal route. It has been suggested that CT promotes T helper type 2 (Th2 response and suppresses Th1 response. We here report the induction of Th17-dominated responses in mice by intranasal delivery of CT. This dramatic Th17-driving effect of CT, which was dependent on the B subunit, was observed even in Th1 or Th2-favored conditions of respiratory virus infection. These dominating Th17 responses resulted in the significant neutrophil accumulation in the lungs of mice given CT. Both in vitro and in vivo treatment of CT induced strongly augmented IL-6 production, and Th17-driving ability of CT was completely abolished in IL-6 knockout mice, indicating a role of this cytokine in the Th17-dominated T-cell responses by CT. These data demonstrate a novel Th17-driving activity of CT, and help understand the mechanisms of CT adjuvanticity to demarcate T helper responses.

  18. In vivo Brain Delivery of v-myc Overproduced Human Neural Stem Cells via the Intranasal Pathway: Tumor Characteristics in the Lung of a Nude Mouse

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    Eun Seong Lee

    2015-01-01

    Full Text Available We aimed to monitor the successful brain delivery of stem cells via the intranasal route and to observe the long-term consequence of the immortalized human neural stem cells in the lungs of a nude mouse model. Stably immortalized HB1.F3 human neural stem cells with firefly luciferase gene (F3-effluc were intranasally delivered to BALB/c nude mice. Bioluminescence images were serially acquired until 41 days in vivo and at 4 hours and 41 days ex vivo after intranasal delivery. Lungs were evaluated by histopathology. After intranasal delivery of F3-effluc cells, the intense in vivo signals were detected in the nasal area, migrated toward the brain areas at 4 hours (4 of 13, 30.8%, and gradually decreased for 2 days. The brain signals were confirmed by ex vivo imaging (2 of 4, 50%. In the mice with initial lung signals (4 of 9, 44.4%, the lung signals disappeared for 5 days but reappeared 2 weeks later. The intense lung signals were confirmed to originate from the tumors in the lungs formed by F3-effluc cells by ex vivo imaging and histopathology. We propose that intranasal delivery of immortalized stem cells should be monitored for their successful delivery to the brain and their tumorigenicity longitudinally.

  19. Pathogenesis and host response in Syrian hamsters following intranasal infection with Andes virus.

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    David Safronetz

    2011-12-01

    Full Text Available Hantavirus pulmonary syndrome (HPS, also referred to as hantavirus cardiopulmonary syndrome (HCPS, is a rare but frequently fatal disease caused by New World hantaviruses. In humans HPS is associated with severe pulmonary edema and cardiogenic shock; however, the pathogenesis of this disease remains unclear largely due to a lack of suitable animal models for the study of disease progression. In this study we monitored clinical, virological, pathophysiological parameters and host immunological responses to decipher pathological factors and events in the lethal Syrian hamster model of HPS following intranasal inoculation of Andes virus. Transcriptional profiling of the host gene responses demonstrated a suppression of innate immune responses in most organs analyzed during the early stage of infection, except for in the lung which had low level activation of several pro-inflammatory genes. During this phase Andes virus established a systemic infection in hamsters, with viral antigen readily detectable in the endothelium of the majority of tissues analyzed by 7-8 days post-inoculation. Despite wide-spread infection, histological analysis confirmed pathological abnormalities were almost exclusively found in the lungs. Immediately preceding clinical signs of disease, intense activation of pro-inflammatory and Th1/Th2 responses were observed in the lungs as well as the heart, but not in peripheral organs, suggesting that localized immune-modulations by infection is paramount to pathogenesis. Throughout the course of infection a strong suppression of regulatory T-cell responses was noted and is hypothesized to be the basis of the aberrant immune activations. The unique and comprehensive monitoring of host immune responses to hantavirus infection increases our understanding of the immuno-pathogenesis of HPS and will facilitate the development of treatment strategies targeting deleterious host immunological responses.

  20. Intranasal Cerebrolysin Attenuates Learning and Memory Impairments in D-galactose-Induced Senescence in Mice.

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    Pourmemar, Ehsan; Majdi, Alireza; Haramshahi, Morteza; Talebi, Mahnaz; Karimi, Pouran; Sadigh-Eteghad, Saeed

    2017-01-01

    Neurotrophic factors are currently being considered as pro-cognitive therapeutic approaches for management of cognitive deficits. This study aims to evaluate the effects of intranasal (i.n.) or intraperitoneal (i.p.) administration of Cerebrolysin (CBL) (as a mixture of neurotrophic factors) on the d-galactose-induced oxidative stress, apoptosis and memory as well as learning impairment in mice. For this purpose, CBL (1, 2.5, 5 ml/kg/i.p.) or (1 ml/kg/i.n.), were administrated daily in d-galactose-received (100 mg/kg/subcutaneous (s.c.)) mice model of aging for eight weeks. Spatial and recognition memories were assessed by the Morris water maze and novel object recognition tasks. Brain and blood of animals were analysed for oxidative stress biomarkers including malondialdehyde, total antioxidant capacity, glutathione peroxidase and superoxide dismutase. Apoptosis rate in the hippocampus was evaluated by TUNEL staining of brain tissue. 5 ml/kg/i.p. dose of CBL increased the locomotor activity but, 1 ml/kg/i.p. dose didn't show detectable behavioural or molecular effects on aged mice. Treatment with 2.5 ml/kg/i.p. and 1 ml/kg/i.n. doses attenuated d-galactose-impaired spatial and recognition memories. Results showed an obvious increase in the antioxidant biomarkers and decrease in the malondialdehyde levels both in the blood and brain of aged mice in 2.5 ml/kg/i.p. dose, and only in the brain in 1 ml/kg/i.n. dose of CBL. Anti-apoptotic effects also were seen in the same dose/rout of CBL administration in aged animals. This study proves the usefulness of i.n. CBL administration as a non-invasive and efficient method of drug delivery to the brain to improve aging-induced oxidative stress, apoptosis and learning as well as memory impairment.

  1. Treatment with intranasal iloprost reduces disease manifestations in a murine model of previously established COPD.

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    Lammi, Matthew R; Ghonim, Mohamed A; Pyakurel, Kusma; Naura, Amarjit S; Ibba, Salome V; Davis, Christian J; Okpechi, Samuel C; Happel, Kyle I; deBoisblanc, Bennett P; Shellito, Judd; Boulares, A Hamid

    2016-04-01

    Pulmonary endothelial prostacyclin appears to be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). The effect of treatment with a prostacyclin analog in animal models of previously established COPD is unknown. We evaluated the short- and long-term effect of iloprost on inflammation and airway hyperresponsiveness (AHR) in a murine model of COPD. Nineteen mice were exposed to LPS/elastase, followed by either three doses of intranasal iloprost or saline. In the long-term treatment experiment, 18 mice were exposed to LPS/elastase and then received 6 wk of iloprost or were left untreated as controls. In the short-term experiment, iloprost did not change AHR but significantly reduced serum IL-5 and IFN-γ. Long-term treatment with iloprost for both 2 and 6 wk significantly improved AHR. After 6 wk of iloprost, there was a reduction in bronchoalveolar lavage (BALF) neutrophils, serum IL-1β (30.0 ± 9.2 vs. 64.8 ± 7.4 pg/ml, P = 0.045), IL-2 (36.5 ± 10.6 vs. 83.8 ± 0.4 pg/ml, P = 0.01), IL-10 (75.7 ± 9.3 vs. 96.5 ± 3.5 pg/ml, P = 0.02), and nitrite (15.1 ± 5.4 vs. 30.5 ± 10.7 μmol, P = 0.01). Smooth muscle actin (SMA) in the lung homogenate was also significantly reduced after iloprost treatment (P = 0.02), and SMA thickness was reduced in the small and medium blood vessels after iloprost (P iloprost significantly reduced systemic inflammation in an LPS/elastase COPD model. Long-term iloprost treatment also reduced AHR, serum nitrite, SMA, and BALF neutrophilia. These data encourage future investigations of prostanoid therapy as a novel treatment for COPD patients. Copyright © 2016 the American Physiological Society.

  2. Intranasal application of the alpha2-adrenoceptor agonist BHT-920 produces decongestion in the cat.

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    Mcleod, R L; Erickson, C H; Mingo, G G; Hey, J A

    2001-01-01

    The effect of alpha2-selective adrenoreceptor activation on nasal cavity dimension in an experimental model of congestion has not been defined. Presently, we used acoustic rhinometry to evaluate the decongestant activity of BHT-920, a selective alpha2-adrenergic agonist against nasal congestion produced by intranasal compound 48/80. Administration of the mast cell liberator compound 48/80 (1%) into a nasal passageway decreased ipsilateral volume and minimum cross-sectional area by 73 +/- 4% and 42 +/- 6%, respectively. The congestant effect of compound 48/80 was blocked by topical BHT-920 (0.3 and 1%) in a dose related manner. In addition, the decrease in minimum cross-sectional area produced by compound 48/80 was attenuated after topical BHT-920 treatment. As a comparison we also evaluated the topical decongestant activity effects of the alpha1-adrenergic agonist phenylephrine, and the nonselective alpha-agonist oxymetazoline. Both phenylephrine (0.1-1.0%) and oxymetazoline (0.01-0.3%) produced decongestion. The blood pressure effects of these three drugs also were evaluated. At doses of 0.3 and 1.0%, BHT-920 did not produce hypertension. In contrast, oxymetaZoline (0.01-0.1%) produced a transient hypertension that peaked at 15 minutes and fully recovered 45 minutes after administration. The hypertensive effect of phenylephrine at 0.3 and 1.0% lasted over 60 minutes. The present findings indicate that selective alpha2-agonists may produce decongestant activity with an improved cardiovascular profile compared with current sympathomimetic drugs such as phenylephrine.

  3. Evaluation of intranasal oxygen supplementation in mules anesthetized with the combination of ketamine, butorphanol, and guaifenesin

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    T.J.C. Módolo

    Full Text Available ABSTRACT Hypoxemia is a major complication of field anesthesia and no studies regarding this occurrence in mules has been done. Thus, the aim of this study was to evaluate intranasal oxygen supplementation (IOS in mules (Equus caballus x Equus asinus anesthetized with ketamine/butorphanol/guaifenesin combination. For this, we used six male, adult mules (322±29kg which underwent premedication (MPA with 0.2mg/kg of midazolam intramuscularly after 15 minutes, 0.02mg/kg detomidine IV 5 minutes after, induction IV with combination of ketamine (2mg/mL, butorphanol (22.5mg/mL, and guaifenesin (50mg/mL (K/B/G until lateral decumbency. Maintenance was done with the same anesthetic combination. The animals were submitted twice to the protocol described above, 20 days apart, forming two groups. CG: MPA, induction (0.92±0.24mL/kg (mean±SD, and maintenance (2.2±0.2mL/kg/h without SIO; TG: MPA, induction (0.98±0.17mL/kg, and maintenance (2.3±0.4mL/kg/h with IOS flow 40mL/kg/h. During anesthesia arterial blood was collected every 20 minutes (T0, T20, T40, and T60 for blood gas analysis. Data analyzed by ANOVA followed by the Bonferroni test. P<0.05 was considered significant. Hypoxemia of the animals in the CG in periods (59±5; 55±5; 53±7; 49±8 with lower averages than the TG (160±4, 115±34, 92±25, 81±19 was observed, demonstrating that IOS increases PaO2 avoiding the occurrence of hypoxemia.

  4. Allergic rhinoconjunctivitis in the Australian population: burden of disease and attitudes to intranasal corticosteroid treatment.

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    Katelaris, Constance H; Sacks, Raymond; Theron, Paul N

    2013-01-01

    Allergic rhinoconjunctivitis (AR/C) is a global health problem causing significant morbidity and has a major impact on quality of life (QOL) and health expenditure. Despite the widespread prevalence, the overall health impact of AR/C may be underappreciated. The results of a survey designed to capture the burden of allergic rhinitis within the Asia-Pacific region have been published recently. Of particular note when evaluating treatment in this region was the fact that despite the value of intranasal corticosteroid (INCS) use, only a small percentage of patients used them. Whether this same trend is present within the population of Australian sufferers is unknown. This study examines the burden of AR/C and explores use of, and attitudes, to INCS sprays in the Australian population. Three hundred three completed interviews from adults and children who had physician-diagnosed AR/C and who were symptomatic or had received treatment in the previous 12 months were analyzed for QOL measures and attitudes to INCS use. Most patients surveyed had received their diagnosis from a general practitioner (GP), and in most cases, a GP provided the majority of ongoing medical care. Only 8% of respondents had consulted a relevant specialist. Diagnostic tests had not been performed in 55% of respondents. The major symptoms causing most distress were nasal congestion and ocular symptoms. The burden of AR/C was considerable; 42% described significant work or school interference because of symptoms, one-third reporting moderate-to-extreme interference with sleep. Despite the significant impact on QOL reported by this sample, 17% had never used INCS and 27% had not used them in the previous 12 months. Respondents' knowledge about INCSs was poor. AR/C is a common disease associated with significant morbidity and impairment of QOL. Improvement in diagnosis, management, and patient education is needed.

  5. Intranasal Immunization with Pressure Inactivated Avian Influenza Elicits Cellular and Humoral Responses in Mice.

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    Shana P C Barroso

    Full Text Available Influenza viruses pose a serious global health threat, particularly in light of newly emerging strains, such as the avian influenza H5N1 and H7N9 viruses. Vaccination remains the primary method for preventing acquiring influenza or for avoiding developing serious complications related to the disease. Vaccinations based on inactivated split virus vaccines or on chemically inactivated whole virus have some important drawbacks, including changes in the immunogenic properties of the virus. To induce a greater mucosal immune response, intranasally administered vaccines are highly desired as they not only prevent disease but can also block the infection at its primary site. To avoid these drawbacks, hydrostatic pressure has been used as a potential method for viral inactivation and vaccine production. In this study, we show that hydrostatic pressure inactivates the avian influenza A H3N8 virus, while still maintaining hemagglutinin and neuraminidase functionalities. Challenged vaccinated animals showed no disease signs (ruffled fur, lethargy, weight loss, and huddling. Similarly, these animals showed less Evans Blue dye leakage and lower cell counts in their bronchoalveolar lavage fluid compared with the challenged non-vaccinated group. We found that the whole inactivated particles were capable of generating a neutralizing antibody response in serum, and IgA was also found in nasal mucosa and feces. After the vaccination and challenge we observed Th1/Th2 cytokine secretion with a prevalence of IFN-γ. Our data indicate that the animals present a satisfactory immune response after vaccination and are protected against infection. Our results may pave the way for the development of a novel pressure-based vaccine against influenza virus.

  6. Intranasal ketamine for procedural sedation and analgesia in children: A systematic review

    Science.gov (United States)

    2017-01-01

    Background Ketamine is commonly used for procedural sedation and analgesia (PSA) in children. Evidence suggests it can be administered intranasally (IN). We sought to review the evidence for IN ketamine for PSA in children. Methods We performed a systematic review of randomized trials of IN ketamine in PSA that reported any sedation-related outcome in children 0 to 19 years. Trials were identified through electronic searches of MEDLINE (1946–2016), EMBASE (1947–2016), Google Scholar (2016), CINAHL (1981–2016), The Cochrane Library (2016), Web of Science (2016), Scopus (2016), clinical trial registries, and conference proceedings (2000–2016) without language restrictions. The methodological qualities of studies and the overall quality of evidence were evaluated using the Cochrane Collaboration’s Risk of Bias tool, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system, respectively. Results The review included 7 studies (n = 264) of children ranging from 0 to 14 years. Heterogeneity in study design precluded meta-analysis. Most studies were associated with a low or unclear risk of bias and outcome-specific ratings for quality of evidence were low or very low. In four of seven studies, IN ketamine provided superior sedation to comparators and resulted in adequate sedation for 148/175 (85%) of participants. Vomiting was the most common adverse effect; reported by 9/91 (10%) of participants. Conclusions IN ketamine administration is well tolerated and without serious adverse effects. Although most participants were deemed adequately sedated with IN ketamine, effectiveness of sedation with respect to superiority over comparators was inconsistent, precluding a recommendation for PSA in children. PMID:28319161

  7. Brain targeted nanoparticulate drug delivery system of rasagiline via intranasal route.

    Science.gov (United States)

    Mittal, Deepti; Md, Shadab; Hasan, Quamrul; Fazil, Mohammad; Ali, Asgar; Baboota, Sanjula; Ali, Javed

    2016-01-01

    The aim of the present study was to prepare and evaluate a rasagiline-loaded chitosan glutamate nanoparticles (RAS-CG-NPs) by ionic gelation of CG with tripolyphosphate anions (TPP). RAS-loaded CG-NPs were characterized for particle size, size distribution, encapsulation efficiency and in vitro drug release. The mean particles size, polydispersity index (PDI) and encapsulation efficiency was found to be 151.1 ± 10.31, 0.380 ± 0.01 and 96.43 ± 4.23, respectively. Biodistribution of RAS formulations in the brain and blood of mice following intranasal (i.n.) and intravenous (i.v.) administration was performed using HPLC analytical method. The drug concentrations in brain following the i.n. of CG-NPs were found to be significantly higher at all the time points compared to both drug (i.n.) and drug CG-NPs (i.v.). The Cmax (999.25 ng/ml) and AUC (2086.60 ng h/ml) of formulation CG-NPs (i.n) were found to be significantly higher than CG-NPs (i.v.) and RAS solution (i.n.). The direct transport percentage (DTP%) values of RAS-loaded CG-NPs (i.n.) as compared to drug solution (i.n.) increased from 66.27 ± 1.8 to 69.27 ± 2.1%. The results showed significant enhancement of bioavailability in brain, after administration of the RAS-loaded CG-NPs which could be a substantial achievement of direct nose to brain targeting in Parkinson's disease therapy.

  8. Improving intranasal delivery of neurological nanomedicine to the olfactory region using magnetophoretic guidance of microsphere carriers

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    Xi J

    2015-02-01

    guidance, neurological nanomedicine, intranasal drug delivery, microsphere carrier

  9. Intranasal Immunization with Pressure Inactivated Avian Influenza Elicits Cellular and Humoral Responses in Mice.

    Science.gov (United States)

    Barroso, Shana P C; Nico, Dirlei; Nascimento, Danielle; Santos, Ana Clara V; Couceiro, José Nelson S S; Bozza, Fernando A; Ferreira, Ana M A; Ferreira, Davis F; Palatnik-de-Sousa, Clarisa B; Souza, Thiago Moreno L; Gomes, Andre M O; Silva, Jerson L; Oliveira, Andréa C

    2015-01-01

    Influenza viruses pose a serious global health threat, particularly in light of newly emerging strains, such as the avian influenza H5N1 and H7N9 viruses. Vaccination remains the primary method for preventing acquiring influenza or for avoiding developing serious complications related to the disease. Vaccinations based on inactivated split virus vaccines or on chemically inactivated whole virus have some important drawbacks, including changes in the immunogenic properties of the virus. To induce a greater mucosal immune response, intranasally administered vaccines are highly desired as they not only prevent disease but can also block the infection at its primary site. To avoid these drawbacks, hydrostatic pressure has been used as a potential method for viral inactivation and vaccine production. In this study, we show that hydrostatic pressure inactivates the avian influenza A H3N8 virus, while still maintaining hemagglutinin and neuraminidase functionalities. Challenged vaccinated animals showed no disease signs (ruffled fur, lethargy, weight loss, and huddling). Similarly, these animals showed less Evans Blue dye leakage and lower cell counts in their bronchoalveolar lavage fluid compared with the challenged non-vaccinated group. We found that the whole inactivated particles were capable of generating a neutralizing antibody response in serum, and IgA was also found in nasal mucosa and feces. After the vaccination and challenge we observed Th1/Th2 cytokine secretion with a prevalence of IFN-γ. Our data indicate that the animals present a satisfactory immune response after vaccination and are protected against infection. Our results may pave the way for the development of a novel pressure-based vaccine against influenza virus.

  10. Therapeutic effects of intranasal cyclosporine for eosinophilic rhinosinusitis with nasal polyps in a mouse model.

    Science.gov (United States)

    Chang, Dong-Yeop; Joo, Yeon-Hee; Kim, Seong-Jae; Kim, Jin Hyun; Jung, Myeong Hee; Kim, Dae Woo; Jeon, Sea-Yuong; Kim, Sang-Wook

    2015-01-01

    Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) is a principally type 2 T helper cell (Th2)-mediated inflammatory disease. Systemic corticosteroids currently represent the most effective treatment for CRSwNP, but their long-term use is constrained due to their detrimental side effects. Long-term use of topical steroids is safe, but their efficacy is often limited. Topical cyclosporine has proven to be safe and effective for Th2-mediated diseases such as allergic conjunctivitis. It was hypothesized that topical cyclosporine would be an effective novel drug for the treatment of CRSwNP; its therapeutic efficacy was assessed using a previously established mouse model. After induction of eosinophilic CRSwNP in four-week-old BALB/c mice according to previous protocols, the therapeutic effects of intranasal cyclosporine were evaluated and compared with those of triamcinolone acetonide (TAC). Histopathologic changes were evaluated using hematoxylin and eosin for polyp formation and Sirius red staining for eosinophilic infiltration. The production of cytokines in sinonasal tissues, including tumor necrosis factor (TNF), interleukin (IL)-2, interferon (IFN)-γ, IL-4, IL-5, IL-13, and IL-17A, was measured using a cytometric bead array. The number of polyp-like lesions was reduced significantly only by systemic TAC, but the degree of eosinophilic infiltration was decreased significantly by topical cyclosporine, the potency of which was similar to that of topical or systemic TAC. Except for IFN-γ, the majority of measured cytokines were reduced significantly by topical cyclosporine, although their effects on IL-2 and IL-13 were less potent than those of systemic TAC. Topical cyclosporine might be an effective drug for the management of CRSwNP.

  11. Immunogenicity of a West Nile Virus DIII-Cholera Toxin A2/B Chimera after Intranasal Delivery

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    Juliette K. Tinker

    2014-04-01

    Full Text Available West Nile virus (WNV causes potentially fatal neuroinvasive disease and persists at endemic levels in many parts of the world. Despite advances in our understanding of WNV pathogenesis, there remains a significant need for a human vaccine. The domain III (DIII region of the WNV envelope protein contains epitopes that are the target of neutralizing antibodies. We have constructed a chimeric fusion of the non-toxic cholera toxin (CT CTA2/B domains to DIII for investigation as a novel mucosally-delivered WNV vaccine. Purification and assembly of the chimera, as well as receptor-binding and antigen delivery, were verified by western blot, GM1 ELISA and confocal microscopy. Groups of BALB/c mice were immunized intranasally with DIII-CTA2/B, DIII, DIII mixed with CTA2/B, or CTA2/B control, and boosted at 10 days. Analysis of serum IgG after 14 and 45 days revealed that mucosal immunization with DIII-CTA2/B induced significant DIII-specific humoral immunity and drove isotype switching to IgG2a. The DIII-CTA2/B chimera also induced antigen-specific IgM and IgA responses. Bactericidal assays indicate that the DIII-CTA2/B immunized mice produced DIII-specific antibodies that can trigger complement-mediated killing. A dose escalation resulted in increased DIII-specific serum IgG titers on day 45. DIII antigen alone, in the absence of adjuvant, also induced significant systemic responses after intranasal delivery. Our results indicate that the DIII-CTA2/B chimera is immunogenic after intranasal delivery and merits further investigation as a novel WNV vaccine candidate.

  12. Neuroticism modulates the effects of intranasal vasopressin treatment on the neural response to positive and negative social interactions.

    Science.gov (United States)

    Feng, Chunliang; DeMarco, Ashley C; Haroon, Ebrahim; Rilling, James K

    2015-07-01

    Neuroticism is a fundamental personality trait associated with proneness to feel negative affect. Here we ask how Neuroticism influences the neural response to positive and negative social interactions and how Neuroticism modulates the effect of intranasal oxytocin (OT) and vasopressin (AVP) on the neural response to social interactions. In a double-blind, placebo-controlled study, 153 male participants were randomized to receive 24 IU intranasal OT, 20 IU AVP or placebo. Afterwards, they were imaged with fMRI while playing an iterated Prisoner's Dilemma Game. On a different day, subjects completed the NEO personality inventory to measure Neuroticism. Neuroticism was positively correlated with the neural response to negative social interactions in the anterior cingulate cortex/medial prefrontal cortex and with the neural response to positive social interactions in the insula, indicating that Neuroticism modulates neuropsychological processing of both negative and positive social interactions. Neuroticism did not modulate the effect of intranasal OT treatment on the neural response to either positive or negative social interactions. On the other hand, AVP treatment significantly interacted with Neuroticism to modulate the BOLD response to both positive and negative social interactions. Specifically, AVP increased anterior cingulate cortex/medial prefrontal cortex and lateral temporal lobe responses to negative social interactions to a greater extent in participants scoring high rather than low on Neuroticism. AVP also increased the insula response to positive social interactions to a greater extent in participants scoring high rather than low on Neuroticism. These results imply that AVP may increase emotion regulation in response to negative social interactions and the salience of positive social interactions to a greater extent in individuals high compared to low in Neuroticism. The current findings urge caution against uniform clinical application of nonapeptides

  13. Immunogenicity of a West Nile virus DIII-cholera toxin A2/B chimera after intranasal delivery.

    Science.gov (United States)

    Tinker, Juliette K; Yan, Jie; Knippel, Reece J; Panayiotou, Panos; Cornell, Kenneth A

    2014-04-22

    West Nile virus (WNV) causes potentially fatal neuroinvasive disease and persists at endemic levels in many parts of the world. Despite advances in our understanding of WNV pathogenesis, there remains a significant need for a human vaccine. The domain III (DIII) region of the WNV envelope protein contains epitopes that are the target of neutralizing antibodies. We have constructed a chimeric fusion of the non-toxic cholera toxin (CT) CTA2/B domains to DIII for investigation as a novel mucosally-delivered WNV vaccine. Purification and assembly of the chimera, as well as receptor-binding and antigen delivery, were verified by western blot, GM1 ELISA and confocal microscopy. Groups of BALB/c mice were immunized intranasally with DIII-CTA2/B, DIII, DIII mixed with CTA2/B, or CTA2/B control, and boosted at 10 days. Analysis of serum IgG after 14 and 45 days revealed that mucosal immunization with DIII-CTA2/B induced significant DIII-specific humoral immunity and drove isotype switching to IgG2a. The DIII-CTA2/B chimera also induced antigen-specific IgM and IgA responses. Bactericidal assays indicate that the DIII-CTA2/B immunized mice produced DIII-specific antibodies that can trigger complement-mediated killing. A dose escalation resulted in increased DIII-specific serum IgG titers on day 45. DIII antigen alone, in the absence of adjuvant, also induced significant systemic responses after intranasal delivery. Our results indicate that the DIII-CTA2/B chimera is immunogenic after intranasal delivery and merits further investigation as a novel WNV vaccine candidate.

  14. Intranasal administration of human MSC for ischemic brain injury in the mouse: in vitro and in vivo neuroregenerative functions.

    Directory of Open Access Journals (Sweden)

    Vanessa Donega

    Full Text Available Intranasal treatment with C57BL/6 MSCs reduces lesion volume and improves motor and cognitive behavior in the neonatal hypoxic-ischemic (HI mouse model. In this study, we investigated the potential of human MSCs (hMSCs to treat HI brain injury in the neonatal mouse. Assessing the regenerative capacity of hMSCs is crucial for translation of our knowledge to the clinic. We determined the neuroregenerative potential of hMSCs in vitro and in vivo by intranasal administration 10 d post-HI in neonatal mice. HI was induced in P9 mouse pups. 1×10(6 or 2×10(6 hMSCs were administered intranasally 10 d post-HI. Motor behavior and lesion volume were measured 28 d post-HI. The in vitro capacity of hMSCs to induce differentiation of mouse neural stem cell (mNSC was determined using a transwell co-culture differentiation assay. To determine which chemotactic factors may play a role in mediating migration of MSCs to the lesion, we performed a PCR array on 84 chemotactic factors 10 days following sham-operation, and at 10 and 17 days post-HI. Our results show that 2×10(6 hMSCs decrease lesion volume, improve motor behavior, and reduce scar formation and microglia activity. Moreover, we demonstrate that the differentiation assay reflects the neuroregenerative potential of hMSCs in vivo, as hMSCs induce mNSCs to differentiate into neurons in vitro. We also provide evidence that the chemotactic factor CXCL10 may play an important role in hMSC migration to the lesion site. This is suggested by our finding that CXCL10 is significantly upregulated at 10 days following HI, but not at 17 days after HI, a time when MSCs no longer reach the lesion when given intranasally. The results described in this work also tempt us to contemplate hMSCs not only as a potential treatment option for neonatal encephalopathy, but also for a plethora of degenerative and traumatic injuries of the nervous system.

  15. Neurotoxicity of low-dose repeatedly intranasal instillation of nano- and submicron-sized ferric oxide particles in mice

    Science.gov (United States)

    Wang, Bing; Feng, Weiyue; Zhu, Motao; Wang, Yun; Wang, Meng; Gu, Yiqun; Ouyang, Hong; Wang, Huajian; Li, Ming; Zhao, Yuliang; Chai, Zhifang; Wang, Haifang

    2009-01-01

    Olfactory tract has been demonstrated to be an important portal for inhaled solid nanoparticle transportation into the central nervous system (CNS). We have previously demonstrated that intranasally instilled Fe2O3 nanoparticles could transport into the CNS via olfactory pathway. In this study, we investigated the neurotoxicity and size effect of repeatedly low-dose (130 μg) intranasal exposure of nano- and submicron-sized Fe2O3 particles (21 nm and 280 nm) to mice. The biomarkers of oxidative stress, activity of nitric oxide synthases and release of monoamine neurotransmitter in the brain were studied. Our results showed that significant oxidative stress was induced by the two sizes of Fe2O3 particles. The activities of GSH-Px, Cu,Zn-SOD, and cNOS significantly elevated and the total GSH and GSH/GSSG ratio significantly decreased in the olfactory bulb and hippocampus after the nano- and submicron-sized Fe2O3 particle treatment ( p < 0.05). The nano-sized Fe2O3 generally induced greater alteration and more significant dose-effect response than the submicron-sized particle did. Some slight perturbation of monoamine neurotransmitters were found in the hippocampus after exposure to the two sizes of Fe2O3 particle. The TEM image showed that some ultrastructural alterations in nerve cells, including neurodendron degeneration, membranous structure disruption and lysosome increase in the olfactory bulb, slight dilation in the rough endoplasmic reticulum and lysosome increase in the hippocampus were induced by the nano-sized Fe2O3 treatment. In contrast, in the submicron-sized Fe2O3 treated mice, slightly swollen mitochondria and some vacuoles were observed in the olfactory bulb and hippocampus, respectively. These results indicate that intranasal exposure of Fe2O3 nanoparticles could induce more severe oxidative stress and nerve cell damage in the brain than the larger particle did. This is the first study to compare the neurotoxicity of nano- and submicron-sized Fe2O3

  16. Study on Intranasal Administration of Traditional Chinese Medicine%中药经鼻腔给药研究

    Institute of Scientific and Technical Information of China (English)

    邬伟魁; 张海燕; 宋伟; 贺娅; 李芳; 郑琴; 杨明

    2011-01-01

    主要对中药经鼻腔给药研究进行文献整理和分析.研究表明,中药经鼻腔给药可以在鼻腔起局部治疗作用,或经鼻吸收后向脑内递药发挥中枢治疗作用,还可以起到治疗全身性疾病的作用.综述了近年来中药经鼻腔给药的实验研究及临床运用,主要包括鼻用制剂国内现状、中药经鼻腔给药基础实验研究(给药途径的选择、剂型的选择、辅料的选择、体外释药评价、药代动力学研究、药效学研究、脑靶向性、安全评价)、中药鼻用制剂的临床观察实例研究,并对其进行了展望,以期为中药经鼻腔给药临床疾病治疗应用和中药鼻用制剂新药开发提供参考.%The field of intranasal administration of traditional Chinese medicine is illustrated in this review article. Intranasal administration of traditional Chinese medicine has a local effect on nasal cavity,or delivered from nose to brain to show a centralnervons treatment as well as works in curing systemic diseases. This paper makes an overview of expenrimental study ( the route of administration, dosage form selection, the choice of excipients, evaluation of drug release in vitro, pharmacokinetics, pharmacodynaraics, brain targeting, safety evaluation ) and clinical applications on intranasal administration of Chinese Medicine in recent years and has a bright future, expecting to provide reference for new drug of intranasal preparation of traditional Chinese medicine.

  17. The comparison of the quality of life and intranasal edema between the patients with or without nasal packing after septoplasty.

    Science.gov (United States)

    Kayahan, B; Ozer, S; Suslu, A E; Ogretmenoglu, O; Onerci, M

    2017-03-01

    Septoplasty is one of the most common operations performed in otolaryngology and anterior nasal packing is done routinely to prevent postoperative bleeding, septal hematoma or nasal synechia. Currently, transseptal sutures have gained a broader application area, not only for preventing the complications such as septal hematoma and bleeding but also closing any accidental tears of septal mucosa and providing additional support for the cartilage pieces retained in septoplasty. We evaluated the quality of life of the patients in early postoperative period (in the first postoperative week), intranasal edema with endoscopic examination and the intranasal changes with acoustic rhinometry. We performed a prospective and randomized study with patients undergoing septoplasty without inferior turbinectomy. As packing material, there were two groups: in group A, gauze in a glove finger and in group B, Doyle splint were used, and in the additional group C, only transseptal suture with 4/0 vicryl among the cartilaginous septum was performed. The patients were invited to control examinations on the postoperative 2nd, 4th and 7th days to evaluate the scores from 1 to 5 on the questionnaire for the pain, nasal fullness, sneezing, epiphora, difficulty in swallowing and sleep disturbances. The patients were also administered an endoscopic nasal examination for the purpose of detecting the intranasal edema, and acoustic rhinometry was performed during the control examinations to detect the intranasal changes. Total occluding packing was found to cause much more frequent and higher scores of epiphora, sneezing, difficulty in swallowing, but mainly, the pain compared to in silicone packing with airway and transseptal suture only. Although the silicone packing with airway was found to be much more comfortable, it also led to sneezing and epiphora. The patients without nasal packing had more comfortable period especially in the early postoperative days (the first 4 days). However, 1

  18. Awake, long-term intranasal insulin treatment does not affect object memory, odor discrimination, or reversal learning in mice.

    Science.gov (United States)

    Bell, Genevieve A; Fadool, Debra Ann

    2017-05-15

    Intranasal insulin delivery is currently being used in clinical trials to test for improvement in human memory and cognition, and in particular, for lessening memory loss attributed to neurodegenerative diseases. Studies have reported the effects of short-term intranasal insulin treatment on various behaviors, but less have examined long-term effects. The olfactory bulb contains the highest density of insulin receptors in conjunction with the highest level of insulin transport within the brain. Previous research from our laboratory has demonstrated that acute insulin intranasal delivery (IND) enhanced both short- and long-term memory as well as increased two-odor discrimination in a two-choice paradigm. Herein, we investigated the behavioral and physiological effects of chronic insulin IND. Adult, male C57BL6/J mice were intranasally treated with 5μg/μl of insulin twice daily for 30 and 60days. Metabolic assessment indicated no change in body weight, caloric intake, or energy expenditure following chronic insulin IND, but an increase in the frequency of meal bouts selectively in the dark cycle. Unlike acute insulin IND, which has been shown to cause enhanced performance in odor habituation/dishabituation and two-odor discrimination tasks in mice, chronic insulin IND did not enhance olfactometry-based odorant discrimination or olfactory reversal learning. In an object memory recognition task, insulin IND-treated mice did not perform differently than controls, regardless of task duration. Biochemical analyses of the olfactory bulb revealed a modest 1.3 fold increase in IR kinase phosphorylation but no significant increase in Kv1.3 phosphorylation. Substrate phosphorylation of IR kinase downstream effectors (MAPK/ERK and Akt signaling) proved to be highly variable. These data indicate that chronic administration of insulin IND in mice fails to enhance olfactory ability, object memory recognition, or a majority of systems physiology metabolic factors - as reported to

  19. Neurotoxicity of low-dose repeatedly intranasal instillation of nano- and submicron-sized ferric oxide particles in mice

    Energy Technology Data Exchange (ETDEWEB)

    Wang Bing; Feng Weiyue, E-mail: fengwy@mail.ihep.ac.cn; Zhu Motao; Wang Yun; Wang Meng [Chinese Academy of Sciences, Laboratory for Bio-Environmental Effects of Nanomaterials and Nanosafety and Key Laboratory of Nuclear Analytical Techniques, Institute of High Energy Physics (China); Gu Yiqun [Maternity Hospital of Haidian District (China); Ouyang Hong; Wang Huajian; Li Ming; Zhao Yuliang, E-mail: zhaoyuliang@mail.ihep.ac.cn; Chai Zhifang [Chinese Academy of Sciences, Laboratory for Bio-Environmental Effects of Nanomaterials and Nanosafety and Key Laboratory of Nuclear Analytical Techniques, Institute of High Energy Physics (China); Wang Haifang [Peking University, College of Chemistry and Molecular Engineering (China)

    2009-01-15

    Olfactory tract has been demonstrated to be an important portal for inhaled solid nanoparticle transportation into the central nervous system (CNS). We have previously demonstrated that intranasally instilled Fe{sub 2}O{sub 3} nanoparticles could transport into the CNS via olfactory pathway. In this study, we investigated the neurotoxicity and size effect of repeatedly low-dose (130 {mu}g) intranasal exposure of nano- and submicron-sized Fe{sub 2}O{sub 3} particles (21 nm and 280 nm) to mice. The biomarkers of oxidative stress, activity of nitric oxide synthases and release of monoamine neurotransmitter in the brain were studied. Our results showed that significant oxidative stress was induced by the two sizes of Fe{sub 2}O{sub 3} particles. The activities of GSH-Px, Cu,Zn-SOD, and cNOS significantly elevated and the total GSH and GSH/GSSG ratio significantly decreased in the olfactory bulb and hippocampus after the nano- and submicron-sized Fe{sub 2}O{sub 3} particle treatment (p < 0.05). The nano-sized Fe{sub 2}O{sub 3} generally induced greater alteration and more significant dose-effect response than the submicron-sized particle did. Some slight perturbation of monoamine neurotransmitters were found in the hippocampus after exposure to the two sizes of Fe{sub 2}O{sub 3} particle. The TEM image showed that some ultrastructural alterations in nerve cells, including neurodendron degeneration, membranous structure disruption and lysosome increase in the olfactory bulb, slight dilation in the rough endoplasmic reticulum and lysosome increase in the hippocampus were induced by the nano-sized Fe{sub 2}O{sub 3} treatment. In contrast, in the submicron-sized Fe{sub 2}O{sub 3} treated mice, slightly swollen mitochondria and some vacuoles were observed in the olfactory bulb and hippocampus, respectively. These results indicate that intranasal exposure of Fe{sub 2}O{sub 3} nanoparticles could induce more severe oxidative stress and nerve cell damage in the brain than the

  20. In vivo trafficking and immunostimulatory potential of an intranasally-administered primary dendritic cell-based vaccine

    Directory of Open Access Journals (Sweden)

    Shankar Nathan

    2010-12-01

    Full Text Available Abstract Background Coccidioidomycosis or Valley fever is caused by a highly virulent fungal pathogen: Coccidioides posadasii or immitis. Vaccine development against Coccidioides is of contemporary interest because a large number of relapses and clinical failures are reported with antifungal agents. An efficient Th1 response engenders protection. Thus, we have focused on developing a dendritic cell (DC-based vaccine for coccidioidomycosis. In this study, we investigated the immunostimulatory characteristics of an intranasal primary DC-vaccine in BALB/c mouse strain that is most susceptible to coccidioidomycosis. The DCs were transfected nonvirally with Coccidioides-Ag2/PRA-cDNA. Expression of DC-markers, Ag2/PRA and cytokines were studied by flow cytometry, dot-immunoblotting and cytometric bead array methods, respectively. The T cell activation was studied by assessing the upregulation of activation markers in a DC-T cell co-culture assay. For trafficking, the DCs were co-transfected with a plasmid DNA encoding HSV1 thymidine kinase (TK and administered intranasally into syngeneic mice. The trafficking and homing of TK-expressing DCs were monitored with positron emission tomography (PET using 18F-FIAU probe. Based on the PET-probe accumulation in vaccinated mice, selected tissues were studied for antigen-specific response and T cell phenotypes using ELISPOT and flow cytometry, respectively. Results We found that the primary DCs transfected with Coccidioides-Ag2/PRA-cDNA were of immature immunophenotype, expressed Ag2/PRA and activated naïve T cells. In PET images and subsequent biodistribution, intranasally-administered DCs were found to migrate in blood, lung and thymus; lymphocytes showed generation of T effector memory cell population (TEM and IFN-γ release. Conclusions In conclusion, our results demonstrate that the intranasally-administered primary DC vaccine is capable of inducing Ag2/PRA-specific T cell response. Unique approaches

  1. Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Anagnostou Evdokia

    2012-12-01

    Full Text Available Abstract Background There are no effective medications for the treatment of social cognition/function deficits in autism spectrum disorder (ASD, and adult intervention literature in this area is sparse. Emerging data from animal models and genetic association studies as well as early, single-dose intervention studies suggest that the oxytocin system may be a potential therapeutic target for social cognition/function deficits in ASD. The primary aim of this study was to examine the safety/therapeutic effects of intranasal oxytocin versus placebo in adults with ASD, with respect to the two core symptom domains of social cognition/functioning and repetitive behaviors. Methods This was a pilot, randomized, double-blind, placebo-controlled, parallel design trial of intranasal oxytocin versus placebo in 19 adults with ASD (16 males; 33.20 ± 13.29 years. Subjects were randomized to 24 IU intranasal oxytocin or placebo in the morning and afternoon for 6 weeks. Measures of social function/cognition (the Diagnostic Analysis of Nonverbal Accuracy and repetitive behaviors (Repetitive Behavior Scale Revised were administered. Secondary measures included the Social Responsiveness Scale, Reading-the-Mind-in-the-Eyes Test and the Yale Brown Obsessive Compulsive Scale – compulsion subscale and quality of life (World Health Organization Quality of Life Questionnaire – emotional/social subscales. Full-information maximum-likelihood parameter estimates were obtained and tested using mixed-effects regression analyses. Results Although no significant changes were detected in the primary outcome measures after correcting for baseline differences, results suggested improvements after 6 weeks in measures of social cognition (Reading-the-Mind-in-the-Eyes Test, p = 0.002, d = 1.2, and quality of life (World Health Organization Quality of Life Questionnaire – emotion, p = 0.031, d = 0.84, both secondary measures. Oxytocin was well tolerated and no serious adverse

  2. Intramuscular Priming and Intranasal Boosting Induce Strong Genital Immunity Through Secretory IgA in Minipigs Infected with Chlamydia trachomatis

    DEFF Research Database (Denmark)

    Lorenzen, Emma; Follmann, Frank; Bøje, Sarah;

    2015-01-01

    International efforts in developing a vaccine against Chlamydia trachomatis have highlighted the need for novel immunization strategies for the induction of genital immunity. In this study, we evaluated an intramuscular (IM) prime/intranasal boost vaccination strategy in a Göttingen Minipig model...... with a reproductive system very similar to humans. The vaccine was composed of C. trachomatis subunit antigens formulated in the Th1/Th17 promoting CAF01 adjuvant. IM priming immunizations with CAF01 induced a significant cell-mediated interferon gamma and interleukin 17A response and a significant systemic high...

  3. Intramuscular Priming and Intranasal Boosting Induce Strong Genital Immunity Through Secretory IgA in Minipigs Infected with Chlamydia trachomatis

    DEFF Research Database (Denmark)

    Lorenzen, Emma; Follmann, Frank; Bøje, Sarah

    2015-01-01

    -titered neutralizing IgG response. Following genital challenge, intranasally boosted groups mounted an accelerated, highly significant genital IgA response that correlated with enhanced bacterial clearance on day 3 post infection. By detecting antigen-specific secretory component (SC), we showed that the genital IgA...... was locally produced in the genital mucosa. The highly significant inverse correlation between the vaginal IgA SC response and the chlamydial load suggests that IgA in the minipig model is involved in protection against C. trachomatis. This is important both for our understanding of protective immunity...

  4. Current status of lectin-based cancer diagnosis and therapy

    Directory of Open Access Journals (Sweden)

    Fohona S. Coulibaly

    2017-01-01

    Full Text Available Lectins are carbohydrate recognizing proteins originating from diverse origins in nature, including animals, plants, viruses, bacteria and fungus. Due to their exceptional glycan recognition property, they have found many applications in analytical chemistry, biotechnology and surface chemistry. This manuscript explores the current use of lectins for cancer diagnosis and therapy. Moreover, novel drug delivery strategies aiming at improving lectin’s stability, reducing their undesired toxicity and controlling their non-specific binding interactions are discussed. We also explore the nanotechnology application of lectins for cancer targeting and imaging. Although many investigations are being conducted in the field of lectinology, there is still a limited clinical translation of the major findings reported due to lectins stability and toxicity concerns. Therefore, new investigations of safe and effective drug delivery system strategies for lectins are warranted in order to take full advantage of these proteins.

  5. Cancer Biomarker Discovery: Lectin-Based Strategies Targeting Glycoproteins

    Directory of Open Access Journals (Sweden)

    David Clark

    2012-01-01

    Full Text Available Biomarker discovery can identify molecular markers in various cancers that can be used for detection, screening, diagnosis, and monitoring of disease progression. Lectin-affinity is a technique that can be used for the enrichment of glycoproteins from a complex sample, facilitating the discovery of novel cancer biomarkers associated with a disease state.

  6. The diagnostic contribution of computed tomography in intranasal carcinoma with retrobulbar, oral and brain invasion in a canine: case report; Contribuicao da tomografia computadorizada no diagnostico de carcinoma intranasal com invasao retrobular, oral e cerebral em canino: relato de caso

    Energy Technology Data Exchange (ETDEWEB)

    Zardo, Karen Maciel, E-mail: kmz@bol.com.br; Belotta, Alexandra Frey; Babicsak, Viviam Rocco; Machado, Vania Maria de Vasconcelos [Universidade Estadual Paulista Julio de Mesquita Filho (FMVZ/UNESP), Botucatu, SP (Brazil). Faculdade de Medicina Veterinaria e Zootecnia. Dept. de Reproducao Animal e Radiologia Veterinaria; Zanoni, Diogo Souza; Costa, Denis Carvalho [Universidade Estadual Paulista Julio de Mesquita Filho (FMVZ/UNESP), Botucatu, SP (Brazil). Faculdade de Medicina Veterinaria e Zootecnia. Dept. de Clinica Veterinaria

    2012-07-01

    Intranasal tumors are uncommon and in most cases are malignant, aggressive and with low to moderate potential for metastasis. Clinical signs are usually caused by progressive obstruction of the upper airways. The test cytopathological also is a diagnosis method, but the definitive diagnosis is made by histopathological. Computed tomography (CT) is recommended to treatment planning. A poodle was attended at the veterinary hospital with a clinical history of epistaxis and nasal and ocular secretions, seizures and severe dyspnoea. The animal underwent to radiographic examination of the chest and skull as well as helical computed tomography of the nasal cavity and brain before and after the administration of intravenous contrast. The CT findings revealed an expansive bilateral nasal cavity neoformation, with involvement of the retrobulbar space, right frontal sinus, brain and oral cavity, suggesting a neoplastic or an infectious process. The CT examination allowed the material collection, directly from the mass, to cytological examination, providing the diagnosis of carcinoma. CT also allowed the determination of the unfavorable prognosis of the patient and the treatment planning which not included the surgical excision of the neoformation. Although CT was not conclusive in the diagnosis of carcinoma, it was essential to accurately define the extent of the lesion, to guide the collection of material directly from the tumor and to determine the prognosis of the animal, proving to be an extremely useful tool in cases of tumors intranasal in dogs. (author)

  7. Enhanced mucosal and systemic immune response with squalane oil-containing multiple emulsions upon intranasal and oral administration in mice.

    Science.gov (United States)

    Shahiwala, Aliasgar; Amiji, Mansoor M

    2008-05-01

    The objective of this study was to develop and evaluate squalane oil-containing water-in-oil-in-water (W/O/W) multiple emulsion for mucosal administration of ovalbumin (OVA) as a model candidate vaccine in BALB/c mice. Control and optimized OVA-containing W/O/W emulsion (OVA-Emul) and chitosan-modified W/O/W emulsion (OVA-Emul-Chi) formulations were administered intranasally and orally at an OVA dose of 100 mug. The mucosal and systemic immune responses were evaluated after the first and second immunization. The OVA-Emul formulations resulted in higher immunoglobulin-G (IgG) and immunoglobulin-A (IgA) responses as compared with aqueous solution. In addition, significant IgG and IgA responses were observed after the second immunization dose using the emulsions with both routes of administration. Intranasal vaccination was more effective in generating the systemic OVA-specific IgG response than the mucosal OVA-specific IgA response. Oral immunizations, on the other hand, showed a much higher systemic IgG and mucosal IgA responses as compared with the nasally treated groups. The results of this study show that squalane oil-containing W/O/W multiple emulsion formulations can significantly enhance the local and systemic immune responses, especially after oral administration, and may be adopted as a better alternative in mucosal delivery of prophylactic and therapeutic vaccines.

  8. Intramuscular Priming and Intranasal Boosting Induce Strong Genital Immunity Through Secretory IgA in Minipigs Infected with Chlamydia trachomatis

    Science.gov (United States)

    Lorenzen, Emma; Follmann, Frank; Bøje, Sarah; Erneholm, Karin; Olsen, Anja Weinreich; Agerholm, Jørgen Steen; Jungersen, Gregers; Andersen, Peter

    2015-01-01

    International efforts in developing a vaccine against Chlamydia trachomatis have highlighted the need for novel immunization strategies for the induction of genital immunity. In this study, we evaluated an intramuscular (IM) prime/intranasal boost vaccination strategy in a Göttingen Minipig model with a reproductive system very similar to humans. The vaccine was composed of C. trachomatis subunit antigens formulated in the Th1/Th17 promoting CAF01 adjuvant. IM priming immunizations with CAF01 induced a significant cell-mediated interferon gamma and interleukin 17A response and a significant systemic high-titered neutralizing IgG response. Following genital challenge, intranasally boosted groups mounted an accelerated, highly significant genital IgA response that correlated with enhanced bacterial clearance on day 3 post infection. By detecting antigen-specific secretory component (SC), we showed that the genital IgA was locally produced in the genital mucosa. The highly significant inverse correlation between the vaginal IgA SC response and the chlamydial load suggests that IgA in the minipig model is involved in protection against C. trachomatis. This is important both for our understanding of protective immunity and future vaccination strategies against C. trachomatis and genital pathogens in general. PMID:26734002

  9. Intramuscular priming and intranasal boosting induce strong genital immunity through secretory IgA in minipigs infected with Chlamydia trachomatis

    Directory of Open Access Journals (Sweden)

    Emma eLorenzen

    2015-12-01

    Full Text Available International efforts in developing a vaccine against Chlamydia trachomatis have highlighted the need for novel immunization strategies for the induction of genital immunity. In this study, we evaluated an intramuscular prime/intranasal boost vaccination strategy in a Göttingen Minipig model with a reproductive system very similar to humans. The vaccine was composed of C. trachomatis subunit antigens formulated in the Th1/Th17 promoting CAF01 adjuvant. Intramuscular priming immunizations with CAF01 induced a significant cell-mediated IFN-ɣ and IL-17A response and a significant systemic high-titered neutralizing IgG response. Following genital challenge, intranasally boosted groups mounted an accelerated, highly significant genital IgA response that correlated with enhanced bacterial clearance on day 3 post infection. By detecting antigen-specific secretory component (SC, we showed that the genital IgA was locally produced in the genital mucosa. The highly significant inverse correlation between the vaginal IgA SC response and the chlamydial load suggest that IgA in the minipig model is involved in protection against C. trachomatis. This is important both for our understanding of protective immunity and future vaccination strategies against C. trachomatis and genital pathogens in general.

  10. Intranasal complications in women with osteoporosis under treatment with nasal calcitonin spray: case reports and review of the literature.

    Science.gov (United States)

    Chatziavramidis, Angelos; Mantsopoulos, Konstantinos; Gennadiou, Dimosthenis; Sidiras, Thomas

    2008-09-01

    To describe the nasal side effects of postmenopausal women suffering from osteoporosis and being treated with intranasal calcitonine (InC). Two women who presented with nasal complaints, were diagnosed as having nasal septum perforation and septum-concha inferior synechiae respectively. Both were receiving treatment with InC for postmenopausal osteoporosis. A medline search for similar side effects of InC revealed a range of nasal symptoms and several factors that could induce these symptoms. Exclusion of other causative conditions leads us to attribute the nasal findings to the use of InC. The literature mentions mild and usually reversible side effects from use of InC. Substances included in the calcitonine spray (preservatives, accelerators of absorption), the development of antibodies against the hormone and possible implication of coexisting diseases or medications to the provocation of nasal side effects, are discussed. Intranasal administration of calcitonine is an established therapy for postmenopausal osteoporosis and other skeletal diseases. The side effects from its use are commonly local, mild and transient, but there is not sufficient information on how this process begins. An ENT examination before and during therapy with InC would be beneficial to patients for the recognition and prevention of serious side effects.

  11. Intranasal "painless" human Nerve Growth Factor [corrected] slows amyloid neurodegeneration and prevents memory deficits in App X PS1 mice.

    Directory of Open Access Journals (Sweden)

    Simona Capsoni

    Full Text Available Nerve Growth Factor (NGF is being considered as a therapeutic candidate for Alzheimer's disease (AD treatment but the clinical application is hindered by its potent pro-nociceptive activity. Thus, to reduce systemic exposure that would induce pain, in recent clinical studies NGF was administered through an invasive intracerebral gene-therapy approach. Our group demonstrated the feasibility of a non-invasive intranasal delivery of NGF in a mouse model of neurodegeneration. NGF therapeutic window could be further increased if its nociceptive effects could be avoided altogether. In this study we exploit forms of NGF, mutated at residue R100, inspired by the human genetic disease HSAN V (Hereditary Sensory Autonomic Neuropathy Type V, which would allow increasing the dose of NGF without triggering pain. We show that "painless" hNGF displays full neurotrophic and anti-amyloidogenic activities in neuronal cultures, and a reduced nociceptive activity in vivo. When administered intranasally to APPxPS1 mice ( n = 8, hNGFP61S/R100E prevents the progress of neurodegeneration and of behavioral deficits. These results demonstrate the in vivo neuroprotective and anti-amyloidogenic properties of hNGFR100 mutants and provide a rational basis for the development of "painless" hNGF variants as a new generation of therapeutics for neurodegenerative diseases.

  12. Evaluation of protein stability and in vitro permeation of lyophilized polysaccharides-based microparticles for intranasal protein delivery.

    Science.gov (United States)

    Cho, Hyun-Jong; Balakrishnan, Prabagar; Chung, Suk-Jae; Shim, Chang-Koo; Kim, Dae-Duk

    2011-09-15

    Biocompatible microparticles prepared by lyophilization were developed for intranasal protein delivery. To test for the feasibility of this formulation, stability of the incorporated protein and enhancement of in vitro permeation across the nasal epithelium were evaluated. Lyophilization was processed with hydroxypropylmethylcellulose (HPMC) or water soluble chitosan (WCS) as biocompatible polymers, hydroxypropyl-β-cyclodextrin (HP-β-CD) and d-alpha-tocopheryl poly(ethylene glycol 1000) succinate (TPGS 1000) as permeation enhancers, sugars as cryoprotectants and lysozyme as the model protein. As a result, microparticles ranging from 6 to 12μm were developed where the maintenance of the protein conformation was verified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), circular dichroism and fluorescence intensity detection. Moreover, in vitro bioassay showed that the lysozyme activity was preserved during the preparation process while exhibiting less cytotoxicity in primary human nasal epithelial (HNE) cells. Results of the in vitro release study revealed slower release rate in these microparticles compared to that of the lysozyme itself. On the other hand, the in vitro permeation study exhibited a 9-fold increase in absorption of lysozyme when prepared in lyophilized microparticles with HPMC, HP-β-CD and TPGS 1000 (F4-2). These microparticles could serve as efficient intranasal delivery systems for therapeutic proteins. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Intranasal Administration of Novel Chitosan Nanoparticle/DNA Complexes Induces Antibody Response to Hepatitis B Surface Antigen in Mice.

    Science.gov (United States)

    Lebre, F; Borchard, G; Faneca, H; Pedroso de Lima, M C; Borges, O

    2016-02-01

    The generation of strong pathogen-specific immune responses at mucosal surfaces where hepatitis B virus (HBV) transmission can occur is still a major challenge. Therefore, new vaccines are urgently needed in order to overcome the limitations of existing parenteral ones. Recent studies show that this may be achieved by intranasal immunization. Chitosan has gained attention as a nonviral gene delivery system; however, its use in vivo is limited due to low transfection efficiency mostly related to strong interaction between the negatively charged DNA and the positively charged chitosan. We hypothesize that the adsorption of negatively charged human serum albumin (HSA) onto the surface of the chitosan particles would facilitate the intracellular release of DNA, enhancing transfection activity. Here, we demonstrate that a robust systemic immune response was induced after vaccination using HSA-loaded chitosan nanoparticle/DNA (HSA-CH NP/DNA) complexes. Furthermore, intranasal immunization with HSA-CH NP/DNA complexes induced HBV specific IgA in nasal and vaginal secretions; no systemic or mucosal responses were detected after immunization with DNA alone. Overall, our results show that chitosan-based DNA complexes elicited both humoral and mucosal immune response, making them an interesting and valuable gene delivery system for nasal vaccination against HBV.

  14. Intranasal administration of proteoliposome-derived cochleates from Vibrio cholerae O1 induce mucosal and systemic immune responses in mice.

    Science.gov (United States)

    Acevedo, Reinaldo; Callicó, Adriana; del Campo, Judith; González, Elizabeth; Cedré, Bárbara; González, Lissette; Romeu, Belkis; Zayas, Caridad; Lastre, Miriam; Fernández, Sonsire; Oliva, Reynaldo; García, Luis; Pérez, José Luis; Pérez, Oliver

    2009-12-01

    Conservative estimates place the death toll from cholera at more than 100,000 persons each year. A particulate mucosal vaccine strategy combining antigens and immune stimulator molecules from Vibrio cholerae to overcome this problem is described. Proteoliposomes extracted from V. cholerae O1 were transformed into cochleates (AFCo2, Adjuvant Finlay cochleate 2) through a calcium inducible rotary dialysis method. Light microscopy was carried out and tubules of 16.25+/-4.57 microm in length were observed. Western blots were performed to verify the immunochemical properties of the main AFCo2 incorporated antigens, revealing full recognition of the outer membrane protein U (OmpU), lipopolysaccharide (LPS), and mannose-sensitive hemagglutinin (MSHA) antigens. AFCo2 were administered by the intranasal route using a two or three dose schedule and the immune response against V. cholerae antigens was assessed. Three AFCo2 doses were required to induce significant (p<0.05), antigen specific IgA in saliva (1.34+/-0.135) and feces (0.60+/-0.089). While, two or three doses of AFCo2 or proteoliposomes induce similar specific IgG and vibriocidal activity responses in sera. These results show for the first time that AFCo2 can be obtained from V. cholerae O1 proteoliposomes and have the potential to protect against the pathogen when administered intranasally.

  15. Intranasally administered oxytocin affects how dogs (Canis familiaris) react to the threatening approach of their owner and an unfamiliar experimenter.

    Science.gov (United States)

    Hernádi, Anna; Kis, Anna; Kanizsár, Orsolya; Tóth, Katinka; Miklósi, Bernadett; Topál, József

    2015-10-01

    Fear and aggression are among the most prominent behavioural problems in dogs. Oxytocin has been shown to play a role in regulating social behaviours in humans including fear and aggression. As intranasal oxytocin has been found to have some analogous effects in dogs and humans, here we investigated the effect of oxytocin on dogs' behaviour in the Threatening Approach Test. Dogs, after having received intranasal administration of oxytocin (OT) or placebo (PL), showed the same reaction to an unfamiliar experimenter, but OT pretreated dogs showed a less friendly first reaction compared to the PL group when the owner was approaching. Individual differences in aggression (measured via questionnaire) also modulated dogs' first reaction. Moreover, subjects that received OT looked back more at the human (owner/experimenter) standing behind them during the threatening approach. These results suggest that oxytocin has an effect on dogs' response to the threatening cues of a human, but this effect is in interaction with other factors such as the identity of the approaching human and the 'baseline' aggression of the dogs.

  16. Formulations for Intranasal Delivery of Pharmacological Agents to Combat Brain Disease: A New Opportunity to Tackle GBM?

    Directory of Open Access Journals (Sweden)

    Stefaan W. van Gool

    2013-08-01

    Full Text Available Despite recent advances in tumor imaging and chemoradiotherapy, the median overall survival of patients diagnosed with glioblastoma multiforme does not exceed 15 months. Infiltration of glioma cells into the brain parenchyma, and the blood-brain barrier are important hurdles to further increase the efficacy of classic therapeutic tools. Local administration methods of therapeutic agents, such as convection enhanced delivery and intracerebral injections, are often associated with adverse events. The intranasal pathway has been proposed as a non-invasive alternative route to deliver therapeutics to the brain. This route will bypass the blood-brain barrier and limit systemic side effects. Upon presentation at the nasal cavity, pharmacological agents reach the brain via the olfactory and trigeminal nerves. Recently, formulations have been developed to further enhance this nose-to-brain transport, mainly with the use of nanoparticles. In this review, the focus will be on formulations of pharmacological agents, which increase the nasal permeation of hydrophilic agents to the brain, improve delivery at a constant and slow release rate, protect therapeutics from degradation along the pathway, increase mucoadhesion, and facilitate overall nasal transport. A mounting body of evidence is accumulating that the underexplored intranasal delivery route might represent a major breakthrough to combat glioblastoma.

  17. Brain targeting by intranasal drug delivery (INDD): a combined effect of trans-neural and para-neuronal pathway.

    Science.gov (United States)

    Mustafa, Gulam; Alrohaimi, Abdulmohsen H; Bhatnagar, Aseem; Baboota, Sanjula; Ali, Javed; Ahuja, Alka

    2016-01-01

    The effectiveness of intranasal drug delivery for brain targeting has emerged as a hope of remedy for various CNS disorders. The nose to brain absorption of therapeutic molecules claims two effective pathways, which include trans-neuronal for immediate action and para-neuronal for delayed action. To evaluate the contribution of both the pathways in absorption of therapeutic molecules and nanocarriers, lidocaine, a nerve-blocking agent, was used to impair the action potential of olfactory nerve. An anti-Parkinson drug ropinirole was covalently complexes with (99m)Tc in presence of SnCl2 using in-house developed reduction technology. The radiolabeled formulations were administered intranasally in lidocaine challenged rabbit and rat. The qualitative and quantitative outcomes of neural and non-neural pathways were estimated using gamma scintigraphy and UHPLC-MS/MS, respectively. The results showed a significant (p ≤ 0.005) increase in radioactivity counts and drug concentration in the brain of rabbit and rat compared to the animal groups challenged with lidocaine. This concludes the significant contribution (p ≤ 0.005) of trans-neuronal and para-neuronal pathway in nose to brain drug delivery. Therefore, results proved that it is an art of a formulator scientist to make the drug carriers to exploit the choice of absorption pathway for their instant and extent of action.

  18. Intranasal cotinine improves memory, and reduces depressive-like behavior, and GFAP+ cells loss induced by restraint stress in mice.

    Science.gov (United States)

    Perez-Urrutia, Nelson; Mendoza, Cristhian; Alvarez-Ricartes, Nathalie; Oliveros-Matus, Patricia; Echeverria, Florencia; Grizzell, J Alex; Barreto, George E; Iarkov, Alexandre; Echeverria, Valentina

    2017-09-01

    Posttraumatic stress disorder (PTSD), chronic psychological stress, and major depressive disorder have been found to be associated with a significant decrease in glial fibrillary acidic protein (GFAP) immunoreactivity in the hippocampus of rodents. Cotinine is an alkaloid that prevents memory impairment, depressive-like behavior and synaptic loss when co-administered during restraint stress, a model of PTSD and stress-induced depression, in mice. Here, we investigated the effects of post-treatment with intranasal cotinine on depressive- and anxiety-like behaviors, visual recognition memory as well as the number and morphology of GFAP+ immunoreactive cells, in the hippocampus and frontal cortex of mice subjected to prolonged restraint stress. The results revealed that in addition to the mood and cognitive impairments, restraint stress induced a significant decrease in the number and arborization of GFAP+ cells in the brain of mice. Intranasal cotinine prevented these stress-derived symptoms and the morphological abnormalities GFAP+ cells in both of these brain regions which are critical to resilience to stress. The significance of these findings for the therapy of PTSD and depression is discussed. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Intranasal Administration of Maleic Anhydride-Modified Human Serum Albumin for Pre-Exposure Prophylaxis of Respiratory Syncytial Virus Infection

    Directory of Open Access Journals (Sweden)

    Zhiwu Sun

    2015-02-01

    Full Text Available Respiratory syncytial virus (RSV is the leading cause of pediatric viral respiratory tract infections. Neither vaccine nor effective antiviral therapy is available to prevent and treat RSV infection. Palivizumab, a humanized monoclonal antibody, is the only product approved to prevent serious RSV infection, but its high cost is prohibitive in low-income countries. Here, we aimed to identify an effective, safe, and affordable antiviral agent for pre-exposure prophylaxis (PrEP of RSV infection in children at high risk. We found that maleic anhydride (ML-modified human serum albumin (HSA, designated ML-HSA, exhibited potent antiviral activity against RSV and that the percentages of the modified lysines and arginies in ML- are correlated with such anti-RSV activity. ML-HSA inhibited RSV entry and replication by interacting with viral G protein and blocking RSV attachment to the target cells, while ML-HAS neither bound to F protein, nor inhibited F protein-mediated membrane fusion. Intranasal administration of ML-HSA before RSV infection resulted in significant decrease of the viral titers in the lungs of mice. ML-HSA shows promise for further development into an effective, safe, affordable, and easy-to-use intranasal regimen for pre-exposure prophylaxis of RSV infection in children at high risk in both low- and high-income countries.

  20. Surgical Site Infections Following Bimaxillary Orthognathic, Osseous Genioplasty, and Intranasal Surgery: A Retrospective Cohort Study.

    Science.gov (United States)

    Posnick, Jeffrey C; Choi, Elbert; Chavda, Anish

    2017-03-01

    Frequency estimates of surgical site infection (SSI) after orthognathic surgery vary considerably. The purpose of this study was to determine the incidence and site of SSIs and associated risk factors after bimaxillary orthognathic, osseous genioplasty, and intranasal surgery. The authors executed a retrospective cohort study of patients with a bimaxillary developmental dentofacial deformity (DFD) and symptomatic chronic obstructive nasal breathing. All patients underwent at a minimum Le Fort I osteotomy, bilateral sagittal ramus osteotomies (SROs), septoplasty, inferior turbinate reduction, and osseous genioplasty. The primary outcome variable studied was the incidence and site of SSI. Predictor variables were type and extent of prophylactic antibiotic used, demographic (age and gender), and anatomic (pattern of DFD, surgical site, and presence of third molar). Two hundred sixty-two patients met the inclusion criteria. Their average age at surgery was 25 years (range, 13 to 63 yr) and there were 134 female patients (51%). The major presenting patterns of DFD included long face (30%) and maxillary deficiency (25%). Forty percent of patients undergoing an SRO and 47% of those undergoing a Le Fort I osteotomy underwent simultaneous removal of a third molar. Ninety percent of patients received cefazolin or cephalexin antibiotics. Overall, 5 of 1,048 (0.5%) osteotomy sites sustained an infection, including 1 chin and 4 ramus SSIs. There were no delays in bone healing. Fixation hardware removal was not required in any patient who developed an infection. Two of the 25 patients (8%) given clindamycin prophylaxis developed an SSI, whereas 3 of 237 patients (1%) receiving cefazolin did. Three of the 4 patients who developed an SRO SSI underwent simultaneous removal of an erupted or partially erupted mandibular third molar (P < .05). In this study, the incidence of SSI was limited to 1% of patients who were given cefazolin or cephalexin extended for 5 days. The removal of

  1. Comparison of intranasal ketamine versus IV morphine in reducing pain in patients with renal colic.

    Science.gov (United States)

    Farnia, Mohammad Reza; Jalali, Alireza; Vahidi, Elnaz; Momeni, Mehdi; Seyedhosseini, Javad; Saeedi, Morteza

    2017-03-01

    Various drugs have been used to relieve abdominal pain in patients with renal colic. Ketamine is a popular choice as an analgesic. To compare the effectiveness of intranasal (IN) ketamine versus intravenous (IV) morphine in reducing pain in patients with renal colic. A randomized double-blind controlled trial was performed in 53 patients with renal colic recruited from the emergency department (ED) in 2015. Finally, 40 patients were enrolled in this study. Patients in the ketamine group received IN ketamine 1 mg/kg and IV placebo while patients in the control group received IV morphine 0.1mg/kg and IN placebo. Our goal was to assess visual analogue scale (VAS) changes between the 2 groups. Patients' VAS scores were reported before and 5, 15, 30min after drug injection. Before drug administration, the mean±SD VAS score was 7.40±1.18 in the morphine group (group A) and 8.35±1.30 in the ketamine group (group B) (P-value=0.021). After adjustment by the appropriate analysis, the mean±SD VAS score in group (A) and (B) at 5min were (6.07±0.47 vs 6.87±0.47; mean difference -0.79, 95% confidence interval (CI) -1.48 to -1.04) (P-value=0.025), at 15 and 30min, the mean±SD VAS score in group (A) and (B) were (5.24±0.49 vs 5.60±0.49; mean difference -0.36, 95% CI -1.08 to 0.34) and (4.02±0.59 vs 4.17±0.59; mean difference -0.15, 95% CI -1.02 to 0.71) (P-value=0.304 and 0.719) respectively. IN ketamine may be effective in decreasing pain in renal colic. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Comparative Usability Study of a Novel Auto-Injector and an Intranasal System for Naloxone Delivery.

    Science.gov (United States)

    Edwards, Evan T; Edwards, Eric S; Davis, Erin; Mulcare, Maureen; Wiklund, Michael; Kelley, Glen

    2015-06-01

    The standard of care for reversal of opioid-induced respiratory depression associated with opioid overdose is injectable naloxone. This study compared the usability of two naloxone delivery devices, a naloxone auto-injector (NAI) and a naloxone intranasal delivery system (NXN), in the administration of naloxone during a simulated opioid overdose emergency. NAI (EVZIO (®) ; kaleo, Inc., Richmond, VA, USA) is a Food and Drug Administration approved single-use pre-filled auto-injector containing 0.4 mg of naloxone. Study participants were randomly assigned to administer naloxone using NAI and NXN, sequentially. The primary endpoint was successful administration of a simulated dose of naloxone into a mannequin during a simulated opioid emergency, both before and after receiving training. Secondary endpoints included using the NAI or NXN in accordance with the instructions-for-use and the comparative measurement of successful completion time of administration for both NAI and NXN. A total of 42 healthy participants aged 18-65 years were enrolled in the study. The proportion of participants able to successfully administer a simulated dose of naloxone was significantly greater for NAI compared to NXN both before (90.5% vs. 0.0%, respectively, P < 0.0001) and after (100% vs. 57.1%, respectively, P < 0.0001) participant training. The proportion of participants able to administer a simulated dose of naloxone in accordance with the instructions-for-use was also significantly greater for NAI compared to NXN before (85.7% vs. 0.0%, respectively, P < 0.0001) and after (100% vs. 0.0%, respectively, P < 0.0001) participant training. The average time to task completion for administration attempt before training was 0.9 ± 0.25 min for NAI versus 6.0 ± 4.76 min for NXN and after training was 0.5 ± 0.15 min for NAI versus 2.0 ± 2.15 min for NXN. Laypersons experienced substantially greater success administering a simulated dose of naloxone, both before and

  3. Systemic and Mucosal Antibody Responses to Soluble and Nanoparticle-Conjugated Antigens Administered Intranasally

    Directory of Open Access Journals (Sweden)

    Savannah E. Howe

    2016-10-01

    Full Text Available Nanoparticles (NPs are increasingly being used for drug delivery, as well as antigen carriers and immunostimulants for the purpose of developing vaccines. In this work, we examined how intranasal (i.n. priming followed by i.n. or subcutaneous (s.c. boosting immunization affects the humoral immune response to chicken ovalbumin (Ova and Ova conjugated to 20 nm NPs (NP-Ova. We show that i.n. priming with 20 mg of soluble Ova, a dose known to trigger oral tolerance when administered via gastric gavage, induced substantial systemic IgG1 and IgG2c, as well as mucosal antibodies. These responses were further boosted following a s.c. immunization with Ova and complete Freund’s adjuvant (Ova+CFA. In contrast, 100 µg of Ova delivered via NPs induced an IgG1-dominated systemic response, and primed the intestinal mucosa for secretion of IgA. Following a secondary s.c. or i.n. immunization with Ova+CFA or NP-Ova, systemic IgG1 titers significantly increased, and serum IgG2c and intestinal antibodies were induced in mice primed nasally with NP-Ova. Only Ova- and NP-Ova-primed mice that were s.c.-boosted exhibited substantial systemic and mucosal titers for up to 6 months after priming, whereas the antibodies of i.n.-boosted mice declined over time. Our results indicate that although the amount of Ova delivered by NPs was 1000-fold less than Ova delivered in soluble form, the antigen-specific antibody responses, both systemic and mucosal, are essentially identical by 6 months following the initial priming immunization. Additionally, both i.n.- and s.c.-boosting strategies for NP-Ova-primed mice were capable of inducing a polarized Th1/Th2 immune response, as well as intestinal antibodies; however, it is only by using a heterogeneous prime-boost strategy that long-lasting antibody responses were initiated. These results provide valuable insight for future mucosal vaccine development, as well as furthering our understanding of mucosal antibody responses.

  4. An Evaluation of Intranasal Sufentanil and Dexmedetomidine for Pediatric Dental Sedation

    Directory of Open Access Journals (Sweden)

    James M. Hitt

    2014-03-01

    Full Text Available Conscious or moderate sedation is routinely used to facilitate the dental care of the pre- or un-cooperative child. Dexmedetomidine (DEX has little respiratory depressant effect, possibly making it a safer option when used as an adjunct to either opioids or benzodiazepines. Unlike intranasal (IN midazolam, IN application of DEX and sufentanil (SUF does not appear to cause much discomfort. Further, although DEX lacks respiratory depressive effects, it is an α2-agonist that can cause hypotension and bradycardia when given in high doses or during prolonged periods of administration. The aim of this feasibility study was to prospectively assess IN DEX/SUF as a potential sedation regimen for pediatric dental procedures. After IRB approval and informed consent, children (aged 3–7 years; n = 20 from our dental clinic were recruited. All patients received 2 μg/kg (max 40 μg of IN DEX 45 min before the procedure, followed 30 min later by 1 μg/kg (max 20 μg of IN SUF. An independent observer rated the effects of sedation using the Ohio State University Behavior Rating Scale (OSUBRS and University of Michigan Sedation Scale (UMSS. The dentist and the parent also assessed the efficacy of sedation. Dental procedures were well tolerated and none were aborted. The mean OSUBRS procedure score was 2.1, the UMSS procedure score was 1.6, and all scores returned to baseline after the procedure. The average dentist rated quality of sedation was 7.6 across the 20 subjects. After discharge, parents reported one child with prolonged drowsiness and one child who vomited at home. The use of IN DEX supplemented with IN SUF provided both an effective and tolerable form of moderate sedation. Although onset and recovery are slower than with oral (PO midazolam and transmucosal fentanyl, the quality of the sedation may be better with less risk of respiratory depression. Results from this preliminary study showed no major complications from IN delivery of these agents.

  5. Intranasal Pharmacokinetic Data for Triptans Such as Sumatriptan and Zolmitriptan Can Render Area Under the Curve (AUC) Predictions for the Oral Route: Strategy Development and Application

    DEFF Research Database (Denmark)

    Srinivas, Nuggehally R.; Syed, Muzeeb

    2016-01-01

    Limited pharmacokinetic sampling strategy may be useful for predicting the area under the curve (AUC) for triptans and may have clinical utility as a prospective tool for prediction. Using appropriate intranasal pharmacokinetic data, a Cmax vs. AUC relationship was established by linear regression...

  6. A stepped wedge design for testing an effect of intranasal insulin on cognitive development of children with Phelan-McDermid syndrome : A comparison of different designs

    NARCIS (Netherlands)

    Van den Heuvel, Edwin R; Zwanenburg, Renée J; Van Ravenswaaij-Arts, Conny Ma

    This paper compares the power of the parallel group design, the matched-pairs design, and several options for the stepped wedge and delayed start designs for testing a possible effect of intranasal insulin with respect to placebo on developmental growth of children with a rare disorder like

  7. LIPOSOMES AS AN IMMUNOADJUVANT SYSTEM FOR STIMULATION OF MUCOSAL AND SYSTEMIC ANTIBODY-RESPONSES AGAINST INACTIVATED MEASLES-VIRUS ADMINISTERED INTRANASALLY TO MICE

    NARCIS (Netherlands)

    DEHAAN, A; TOMEE, JFC; HUCHSHORN, JP; WILSCHUT, J

    1995-01-01

    This paper reports on the immune-stimulatory activity of liposomes in an inactivated whole measles virus vaccine preparation administered intranasally to mice. Liposomes, simply mixed with inactivated whole measles virus, significantly stimulated the serum IgG response relative to the response to th

  8. MUCOSAL IMMUNOADJUVANT ACTIVITY OF LIPOSOMES - INDUCTION OF SYSTEMIC IGG AND SECRETORY IGA RESPONSES IN MICE BY INTRANASAL IMMUNIZATION WITH AN INFLUENZA SUBUNIT VACCINE AND COADMINISTERED LIPOSOMES

    NARCIS (Netherlands)

    DEHAAN, A; GEERLIGS, HJ; HUCHSHORN, JP; VANSCHARRENBURG, GJM; PALACHE, AM; WILSCHUT, J

    This paper reports on a novel immunonadjuvant activity of liposomes. An influenza subunit preparation, containing the isolated viral surface antigens, was incorporated in a liposomal formulation. Administration of this vaccine to mice via the intranasal (i.n.) route resulted in a stimulated serum

  9. Evaluation of a liposome-supplemented intranasal influenza subunit vaccine in a murine model system : Induction of systemic and local mucosal immunity

    NARCIS (Netherlands)

    de Haan, A; van Scharrenburg, GJM; Masihi, KN; Wilschut, J

    2000-01-01

    This study reports on the mucosal immunoadjuvant activity of liposomes in an experimental influenza subunit vaccine administered intranasally (i.n.) to mice. Antibody responses induced by the i.n. liposomal vaccine were compared to those induced by an influenza infection or by subcutaneous (s.c.) in

  10. MUCOSAL IMMUNOADJUVANT ACTIVITY OF LIPOSOMES - INDUCTION OF SYSTEMIC IGG AND SECRETORY IGA RESPONSES IN MICE BY INTRANASAL IMMUNIZATION WITH AN INFLUENZA SUBUNIT VACCINE AND COADMINISTERED LIPOSOMES

    NARCIS (Netherlands)

    DEHAAN, A; GEERLIGS, HJ; HUCHSHORN, JP; VANSCHARRENBURG, GJM; PALACHE, AM; WILSCHUT, J

    1995-01-01

    This paper reports on a novel immunonadjuvant activity of liposomes. An influenza subunit preparation, containing the isolated viral surface antigens, was incorporated in a liposomal formulation. Administration of this vaccine to mice via the intranasal (i.n.) route resulted in a stimulated serum Ig

  11. 胰岛素鼻黏膜给药系统的研究进展%Progress of the intranasal administration of insulin

    Institute of Scientific and Technical Information of China (English)

    李莹; 段晓品; 毛世瑞

    2012-01-01

    Objective To review the new administration routes of insulin and the development of intranasal delivery system. Methods According to thirty-six recent relevant literatures, the new routes and the development of intranasal delivery system of insulin were summarized. The new routes of insulin administration,the characteristics of intranasal delivery and some strategies to improve the bioavailability of insulin after nasal administration were summarized. Results It seems that the addition of safe absorption enhancers or water-insoluble powders into insulin formulation can dramatically improve the bioavailability of insulin after nasal administration. Conclusions The intranasal administration of insulin in the pharmaceutical field is promising.%目的 综述胰岛素近年来鼻黏膜给药的相关信息.方法 查阅国内外相关文献36篇,进行相关分析、归纳和总结.结果 综述出鼻黏膜给药的特点以及提高鼻黏膜生物利用度的诸多方法.在胰岛素制剂中加入安全高效的吸收促进剂或水不溶性粉末将会很大程度上提高其生物利用度.结论 胰岛素鼻黏膜给药在药学领域将会有广阔的发展前景.

  12. Bacterium-like particles supplemented with inactivated influenza antigen induce cross-protective influenza-specific antibody responses through intranasal administration

    NARCIS (Netherlands)

    de Haan, Aalzen; Haijema, Bert Jan; Voorn, Petra; Meijerhof, Tjarko; van Roosmalen, Maarten L.; Leenhouts, Kees

    2012-01-01

    Administration of influenza vaccines through the intranasal (IN) route forms an attractive alternative to conventional intramuscular (IM) injection. It is not only a better accepted form of vaccine administration but it also has the potential to induce, in addition to systemic antibodies, local prot

  13. Intranasal Vaccination Affords Localization and Persistence of Antigen-Specific CD8⁺ T Lymphocytes in the Female Reproductive Tract.

    Science.gov (United States)

    Singh, Shailbala; Schluns, Kimberly S; Yang, Guojun; Anthony, Scott M; Barry, Michael A; Sastry, K Jagannadha

    2016-03-17

    Immunization strategies generating large numbers of antigen-specific T cells in the female reproductive tract (FRT) can provide barrier protection against sexually-transmitted pathogens, such as the human immunodeficiency virus (HIV) and human papillomaviruses (HPV). The kinetics and mechanisms of regulation of vaccine-induced adaptive T cell-mediated immune responses in FRT are less well defined. We present here evidence for intranasal delivery of the model antigen ovalbumin (OVA) along with alpha-galactosylceramide adjuvant as a protein vaccine to induce significantly higher levels of antigen-specific effector and memory CD8⁺ T cells in the FRT, relative to other systemic and mucosal tissues. Antibody blocking of the CXCR3 receptor significantly reduced antigen-specific CD8⁺ T cells subsequent to intranasal delivery of the protein vaccine suggesting an important role for the CXCR3 chemokine-receptor signaling for T cell trafficking. Further, intranasal vaccination with an adenoviral vector expressing OVA or HIV-1 envelope was as effective as intramuscular vaccination for generating OVA- or ENV-specific immunity in the FRT. These results support the application of the needle-free intranasal route as a practical approach to delivering protein as well as DNA/virus vector-based vaccines for efficient induction of effector and memory T cell immunity in the FRT.

  14. Bacterium-like particles supplemented with inactivated influenza antigen induce cross-protective influenza-specific antibody responses through intranasal administration

    NARCIS (Netherlands)

    de Haan, Aalzen; Haijema, Bert Jan; Voorn, Petra; Meijerhof, Tjarko; van Roosmalen, Maarten L.; Leenhouts, Kees

    2012-01-01

    Administration of influenza vaccines through the intranasal (IN) route forms an attractive alternative to conventional intramuscular (IM) injection. It is not only a better accepted form of vaccine administration but it also has the potential to induce, in addition to systemic antibodies, local

  15. An observational feasibility study to assess the safety and effectiveness of intranasal fentanyl for radiofrequency ablations of the lumbar facet joints

    Science.gov (United States)

    Bartoszek, Michael W; McCoart, Amy; Hong, Kyung-soo Jason; Haley, Chelsey; Highland, Krista Beth; Plunkett, Anthony R

    2017-01-01

    Purpose The purpose of the present observational, feasibility study is to assess the preliminary safety and effectiveness of intranasal fentanyl for lumbar facet radiofrequency ablation procedures. Patients and methods This cohort observational study included 23 adult patients. Systolic and diastolic blood pressures, heart rate, oxygen saturation percent, Pasero Opioid-Induced Sedation Scale score, and the Defense and Veterans Pain Rating Scale pain score were assessed prior to the procedure and intranasal fentanyl (100 μg) administration and every 15 minutes after administration, up to 60 minutes post administration. Follow-up of patient satisfaction with pain control and treatment was assessed 24 hours after discharge. The primary outcome was safety as evidenced by adverse events. Secondary outcomes included the above-mentioned vital signs and pain ratings. Results No adverse events occurred in the present study and all participants maintained an acceptable level of awareness throughout the assessment period. One-way repeated measures analyses of covariance tests with Bonferroni-adjusted means indicated that oxygen saturation, blood pressure, and heart rate changed from baseline, whereas pain scores were lower at post-administration levels compared with baseline. Finally, the majority of participants reported being satisfied with pain control and treatment. Conclusion Preliminary evidence indicates that intranasal fentanyl is safe and effective for lumbar facet radiofrequency ablation procedures. Future rigorous randomized control trials are needed to confirm the present results and to examine the effects of intranasal fentanyl on intraoperative and postoperative opioid use.

  16. Intranasal Delivery of Recombinant AAV Containing BDNF Fused with HA2TAT: a Potential Promising Therapy Strategy for Major Depressive Disorder.

    Science.gov (United States)

    Ma, Xian-cang; Liu, Peng; Zhang, Xiao-ling; Jiang, Wen-hui; Jia, Min; Wang, Cai-xia; Dong, Ying-ying; Dang, Yong-hui; Gao, Cheng-ge

    2016-03-03

    Depression is a disturbing psychiatric disease with unsatisfied therapy. Not all patients are sensitive to anti-depressants currently in use, side-effects are unavoidable during therapy, and the cases with effectiveness are always accompanied with delayed onset of clinical efficacy. Delivering brain-derived neurotrophic factor (BDNF) to brain seems to be a promising therapy. However, a better approach to delivery is still rudimentary. The purpose of our present work is to look for a rapid-onset and long-lasting therapeutic strategy for major depressive disorder (MDD) by effectively delivering BDNF to brain. BDNF, fused with cell-penetrating peptides (TAT and HA2), was packaged in adenovirus associated virus (AAV) to construct the BDNF-HA2TAT/AAV for intranasally delivering BDNF to central nervous system (CNS) via nose-brain pathway. Intranasal administration of BDNF-HA2TAT/AAV to normal mice displayed anti-depression effect in forced swimming test when the delivery lasted relatively longer. The AAV applied to mice subjected to chronic mild stress (CMS) through intranasal administration for 10 days also alleviated depression-like behaviors. Western-blotting analysis revealed that BDNF-HA2TAT/AAV nasal administration enhanced hippocampal BDNF content. These results indicate intranasal administration of constructed BDNF-HA2TAT/AAV exerts anti-depression effect in CMS mice by increasing hippocampal BDNF, suggesting that this strategy holds a promising therapeutic potential for MDD.

  17. Pathogenesis of infection with 2009 pandemic H1N1 influenza virus in isogenic guinea pigs after intranasal or intratracheal inoculation.

    Science.gov (United States)

    Wiersma, Lidewij C M; Vogelzang-van Trierum, Stella E; van Amerongen, Geert; van Run, Peter; Nieuwkoop, Nella J; Ladwig, Mechtild; Banneke, Stefanie; Schaefer, Hubert; Kuiken, Thijs; Fouchier, Ron A M; Osterhaus, Albert D M E; Rimmelzwaan, Guus F

    2015-03-01

    To elucidate the pathogenesis and transmission of influenza virus, the ferret model is typically used. To investigate protective immune responses, the use of inbred mouse strains has proven invaluable. Here, we describe a study with isogenic guinea pigs, which would uniquely combine the advantages of the mouse and ferret models for influenza virus infection. Strain 2 isogenic guinea pigs were inoculated with H1N1pdm09 influenza virus A/Netherlands/602/09 by the intranasal or intratracheal route. Viral replication kinetics were assessed by determining virus titers in nasal swabs and respiratory tissues, which were also used to assess histopathologic changes and the number of infected cells. In all guinea pigs, virus titers peaked in nasal secretions at day 2 after inoculation. Intranasal inoculation resulted in higher virus excretion via the nose and higher virus titers in the nasal turbinates than intratracheal inoculation. After intranasal inoculation, infectious virus was recovered only from nasal epithelium; after intratracheal inoculation, it was recovered also from trachea, lung, and cerebrum. Histopathologic changes corresponded with virus antigen distribution, being largely limited to nasal epithelium for intranasally infected guinea pigs and more widespread in the respiratory tract for intratracheally infected guinea pigs. In summary, isogenic guinea pigs show promise as a model to investigate the role of humoral and cell-mediated immunities to influenza and their effect on virus transmission.

  18. The protoxin Cry1Ac of Bacillus thuringiensis improves the protection conferred by intranasal immunization with Brucella abortus RB51 in a mouse model.

    Science.gov (United States)

    González-González, Edith; García-Hernández, Ana Lilia; Flores-Mejía, Raúl; López-Santiago, Rubén; Moreno-Fierros, Leticia

    2015-02-25

    Brucellosis is a zoonotic disease affecting many people and animals worldwide. Preventing this infection requires improving vaccination strategies. The protoxin Cry1Ac of Bacillus thuringiensis is an adjuvant that, in addition to increasing the immunogenicity of different antigens, has shown to be protective in different models of parasitic infections. The objective of the present study was to test whether the intranasal co-administration of pCry1Ac with the RB51 vaccine strain of Brucella abortus confers protection against an intranasal challenge with the virulent strain B. abortus 2308 in BALB/c mice. The results showed that co-administration of pCry1Ac and RB51, increased the immunoprotection conferred by the vaccine as evidenced by the following: (1) decrease of the splenic bacterial load when challenged intranasally with the virulent strain; (2) greater in vivo cytotoxic activity in response to the transference of previously infected cells; (3) further proliferation of cytotoxic TCD8+ cells in response to stimulation with heat-inactivated bacteria; (4) increased production of TNF-α and IFN-γ; and (5) significant IgG2a response. These results indicate that the use of the Cry1Ac protein as a mucosal adjuvant via the intranasal route can be a promising alternative for improving current RB51 vaccine against brucellosis.

  19. Intranasal immunization of mice with recombinant Streptococcus gordonii expressing NadA of Neisseria meningitidis induces systemic bactericidal antibodies and local IgA.

    Science.gov (United States)

    Ciabattini, Annalisa; Giomarelli, Barbara; Parigi, Riccardo; Chiavolini, Damiana; Pettini, Elena; Aricò, Beatrice; Giuliani, Marzia M; Santini, Laura; Medaglini, Donata; Pozzi, Gianni

    2008-08-05

    NadA and NhhA, two surface proteins of serogroup B Neisseria meningitidis identified as candidate vaccine antigens, were expressed on the surface of the human oral commensal bacterium Streptococcus gordonii. Recombinant strains were used to immunize BALB/c mice by the intranasal route and the local and systemic immune response was assessed. Mice were inoculated with recombinant bacteria administered alone or with LTR72, a partially inactivated mutant of Escherichia coli heat-labile enterotoxin, as a mucosal adjuvant. Intranasal immunization with live bacteria expressing NadA induced a significant serum antibody response, with a prevalence of the IgG2a subclass, bactericidal activity in the sera of 71% of animals, and a NadA-specific IgA response in nasal and bronchoalveolar lavages. A formalin-inactivated recombinant strain of S. gordonii expressing NadA was also administered intranasally, inducing a systemic and mucosal humoral response comparable to that of live bacteria. The administration of recombinant bacteria with the mucosal adjuvant LTR72 stimulated a stronger systemic antibody response, protective in 85% of sera, while did not increase the local IgA response. Recombinant S. gordonii expressing NhhA induced a systemic but not mucosal antibody response. These data support the role of NadA as vaccine candidate against serogroup B meningococci, and the use of S. gordonii as vector for intranasal vaccination.

  20. Efficacy of a modified live intranasal bovine respiratory syncytial virus vaccine in three-week-old calves experimentally challenged with BRSV

    NARCIS (Netherlands)

    Vangeel, I.; Antonis, A.F.G.; Fluess, M.; Peters, A.R.; Harmeyer, S.S.

    2005-01-01

    Bovine respiratory syncytial virus (BRSV) is a widespread cause of lower respiratory tract disease in cattle. Calves less than four months of age are often involved in outbreaks of respiratory disease. We evaluated the efficacy of a single intranasal dose of a bivalent modified live vaccine containi

  1. A comparative study to evaluate the effect of intranasal dexmedetomidine versus oral alprazolam as a premedication agent in morbidly obese patients undergoing bariatric surgery

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    Lakshmi Jayaraman

    2013-01-01

    Full Text Available Background: Morbidly obese patients with obstructive sleep apnea are extremely sensitive to sedative premedication. Intranasal dexmedetomidine is painless and quick acting. Intranasal dexmedetomidine can be used for premedication as it produces adequate sedation and also obtund hemodynamic response to laryngoscopy and tracheal intubation. Materials and Methods: Forty morbidly obese patients with BMI > 35 were chosen and divided into two groups. Group DEX received intranasal dexmedetomidine 1 mcg/kg (ideal body weight while other group (AZ received oral alprazolam 0.5 mg. Sedation scale, heart rate and the mean arterial pressure was assessed in both the groups at 0 hour, 45 minutes, during laryngoscopy and tracheal intubation. Results: The demographic profile, baseline heart rate, means arterial pressure, oxygen saturation and sedation scale was comparable between the two groups. The sedation scores, after 45 min, were statistically significant between the two groups i.e., 2.40 ± 1.09 in the AZ group as compared to 3.20 ± 1.79 in DEX group P value 0.034. The heart rate, mean arterial pressure and oxygen saturation were statistically similar between the two groups, after 45 min. The heart rate was significantly lower in the DEX group as compared to the AZ group. There was no statistical difference in the mean arterial pressure between the two groups either during laryngoscopy or tracheal intubation. Conclusion: Intranasal dexmedetomidine is a better premedication agent in morbidly obese patients than oral alprazolam.

  2. Comparison of intranasal dexmedetomidine and dexmedetomidine-ketamine for premedication in pediatrics patients: A randomized double-blind study

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    Bhat, Ravi; Santhosh, M.C.B.; Annigeri, Venkatesh M.; Rao, Raghavendra P.

    2016-01-01

    Background: Goal of premedication in pediatric anesthesia are relieving pre and postoperative anxiety, good parental separation, and smooth induction of anesthesia. Anxiety can produce aggressive reactions, increased distress, increased postoperative pain and postoperative agitation. The benzodiazepine, midazolam, is the most frequently used premedication in pediatric anesthesia. Midazolam has a number of beneficial effects when used as premedication in children: Sedation, fast onset, and limited duration of action. Though midazolam has a number of beneficial effects, it is far from an ideal premedicant having untoward side effects such as paradoxical reaction, respiratory depression, cognitive impairment, amnesia, and restlessness. Dexmedetomidine is a newer α-2-agonist, which can be used as premedicant. Aims: To compare the level of sedation, parental separation, mask acceptance, postoperative recovery of intranasal premedication with dexmedetomidine and dexmedetomidine-ketamine combination in pediatric patients. Settings and Design: Prospective randomized double-blind study. Subjects and Methods: After written informed consent from the patient's parents or legal guardian, 54 children of American Society of Anesthesiologists physical status I or II, aged between 1 and 6 years, scheduled to undergo elective minor surgery were enrolled. In group D patient received 1 μg/kg dexmedetomidine intranasally and in group DK received 1 μg/kg dexmedetomidine and 2 mg/kg ketamine intranasally. Patients were assessed every 10 min for the level of sedation, parenteral separation, heart rate, and oxygen saturation by an independent observer. Mask acceptance and postoperative agitation were noted using an appropriate scale. Statistical Analysis Used: Pearson Chi-square analysis to determine differences between two groups with respect to separation anxiety and acceptance of the anesthesia mask. Percentages used to represent frequencies. The level of significance was set at P< 0

  3. Intranasal delivery of hypoxia-preconditioned bone marrow-derived mesenchymal stem cells enhanced regenerative effects after intracerebral hemorrhagic stroke in mice.

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    Sun, Jinmei; Wei, Zheng Zachory; Gu, Xiaohuan; Zhang, James Ya; Zhang, Yongbo; Li, Jimei; Wei, Ling

    2015-10-01

    Intracerebral hemorrhagic stroke (ICH) causes high mortality and morbidity with very limited treatment options. Cell-based therapy has emerged as a novel approach to replace damaged brain tissues and promote regenerative processes. In this study we tested the hypothesis that intranasally delivered hypoxia-preconditioned BMSCs could reach the brain, promote tissue repair and improve functional recovery after ICH. Hemorrhagic stroke was induced in adult C57/B6 mice by injection of collagenase IV into the striatum. Animals were randomly divided into three groups: sham group, intranasal BMSC treatment group, and vehicle treatment group. BMSCs were pre-treated with hypoxic preconditioning (HP) and pre-labeled with Hoechst before transplantation. Behavior tests, including the mNSS score, rotarod test, adhesive removal test, and locomotor function evaluation were performed at varying days, up to 21days, after ICH to evaluate the therapeutic effects of BMSC transplantation. Western blots and immunohistochemistry were performed to analyze the neurotrophic effects. Intranasally delivered HP-BMSCs were identified in peri-injury regions. NeuN+/BrdU+ co-labeled cells were markedly increased around the hematoma region, and growth factors, including BDNF, GDNF, and VEGF were significantly upregulated in the ICH brain after BMSC treatment. The BMSC treatment group showed significant improvement in behavioral performance compared with the vehicle group. Our data also showed that intranasally delivered HP-BMSCs migrated to peri-injury regions and provided growth factors to increase neurogenesis after ICH. We conclude that intranasal administration of BMSC is an effective treatment for ICH, and that it enhanced neuroregenerative effects and promoted neurological functional recovery after ICH. Overall, the investigation supports the potential therapeutic strategy for BMSC transplantation therapy against hemorrhagic stroke. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Delayed intranasal delivery of hypoxic-preconditioned bone marrow mesenchymal stem cells enhanced cell homing and therapeutic benefits after ischemic stroke in mice.

    Science.gov (United States)

    Wei, Ning; Yu, Shan Ping; Gu, Xiaohuan; Taylor, Tammi M; Song, Denise; Liu, Xin-Feng; Wei, Ling

    2013-01-01

    Stem cell transplantation therapy has emerged as a potential treatment for ischemic stroke and other neurodegenerative diseases. Effective delivery of exogenous cells and homing of these cells to the lesion region, however, have been challenging issues that hinder the efficacy and efficiency of cell-based therapy. In the present investigation, we tested a delayed treatment of noninvasive and brain-targeted intranasal delivery of bone marrow mesenchymal stem cells (BMSCs) in a mouse focal cerebral ischemia model. The investigation tested the feasibility and effectiveness of intranasal delivery of BMSCs to the ischemic cortex. Hypoxia preconditioning (HP) of BMSCs was performed before transplantation in order to promote their survival, migration, and homing to the ischemic brain region after intranasal transplantation. Hoechst dye-labeled normoxic- or hypoxic-pretreated BMSCs (1 × 10(6) cells/animal) were delivered intranasally 24 h after stroke. Cells reached the ischemic cortex and deposited outside of vasculatures as early as 1.5 h after administration. HP-treated BMSCs (HP-BMSCs) showed a higher level of expression of proteins associated with migration, including CXC chemokine receptor type 4 (CXCR4), matrix metalloproteinase 2 (MMP-2), and MMP-9. HP-BMSCs exhibited enhanced migratory capacities in vitro and dramatically enhanced homing efficiency to the infarct cortex when compared with normoxic cultured BMSCs (N-BMSCs). Three days after transplantation and 4 days after stroke, both N-BMSCs and HP-BMSCs decreased cell death in the peri-infarct region; significant neuroprotection of reduced infarct volume was seen in mice that received HP-BMSCs. In adhesive removal test of sensorimotor functional assay performed 3 days after transplantation, HP-BMSC-treated mice performed significantly better than N-BMSC- and vehicle-treated animals. These data suggest that delayed intranasal administration of stem cells is feasible in the treatment of stroke and hypoxic

  5. Urinary and plasma oxytocin changes in response to MDMA or intranasal oxytocin administration.

    Science.gov (United States)

    Francis, Sunday M; Kirkpatrick, Matthew G; de Wit, Harriet; Jacob, Suma

    2016-12-01

    The neuropeptide oxytocin (OT) has received increased experimental attention for its putative role in both normal social functioning and several psychiatric disorders that are partially characterized by social dysfunction (e.g., autism spectrum disorders: ASD). Many human experimental studies measure circulating plasma levels of OT in order to examine the relationship between the hormone and behavior. Urinary OT (uOT) assays offer a simple, easy, and non-invasive method to measure peripheral hormone levels, but the correspondence between uOT and plasma OT (pOT) levels is unclear. Here, we conducted two within-subjects, double-blind studies exploring changes in uOT and pOT levels following administration of two drugs: MDMA, an oxytocin-releasing drug (Study 1), and intranasal oxytocin (INOT: Study 1 and 2). In Study 1, 14 adult participants (2 females) were each administered either oral 1.5mg/kg MDMA or 40IU INOT across two different study sessions. In Study 2, 10 male participants (adolescents and young adults) diagnosed with ASD received either 40IU INOT or placebo across two different sessions. In both studies, blood and urine samples were collected before and after drug administration at each study session. For Study 1, 10 participants provided valid plasma and urine samples for the MDMA session, and 8 provided valid samples for the INOT session. For Study 2, all 10 participants provided valid samples for both INOT and placebo sessions. Pre- and post-administration levels of pOT and uOT were compared. Additionally, correlations between percent change from baseline uOT and pOT levels were examined. Study 1: Plasma OT and uOT levels significantly increased after administration of MDMA and INOT. Furthermore, uOT levels were positively correlated with pOT levels following administration of MDMA (r=0.57, p=0.042) but not INOT (r=0.51, p=0.097). Study 2: There was a significant increase in uOT levels after administration of INOT, but not after administration of

  6. Pharmacotherapeutics of Intranasal Scopolamine: FDA Regulations and Procedures for Clinical Applications

    Science.gov (United States)

    Das, H.; Daniels, V. R.; Vaksman, Z.; Boyd, J. L.; Buckey, J. C.; Locke, J. P.; Putcha, L.

    2007-01-01

    Space Motion Sickness (SMS) is commonly experienced by astronauts and often requires treatment with medications during the early flight days of a space mission. Bioavailability of oral (PO) SMS medications is often low and highly variable; additionally, physiological changes in a microgravity environment exacerbate variability and decrease bioavailability. These factors prompted NASA to develop an intranasal dosage form of scopolamine (INSCOP) suitable for the treatment of SMS. However, to assure safety and efficacy of treatment in space, NASA physicians prescribe commercially available pharmaceutical products only. Development of a pharmaceutical preparation for clinical use must follow distinct clinical phases of testing, phase I through IV to be exact, before it can be approved by the FDA for approval for clinical use. After a physician sponsored Investigative New Drug (IND) application was approved by the FDA, a phase I clinical trial of INSCOP formulation was completed in normal human subjects and results published. The current project includes three phase II clinical protocols for the assessment of pharmacokinetics and pharmacodynamics (PK/PD), efficacy, and safety of INSCOP. Three clinical protocols that were submitted to FDA to accomplish the project objectives: 1) 002-A, a FDA Phase II dose ranging study with four dose levels between 0.1 and 0.4 mg in 12 subjects to assess PK/PD, 2) 002-B, a phase II clinical efficacy study in eighteen healthy subjects to compare efficacy of 0.2 (low dose) and 0.4 mg (high dose) INSCOP for prophylactic treatment of motion-induces (off-axis vertical rotation) symptoms, and (3) 002-C, a phase II clinical study with twelve subjects to determine bioavailability and pharmacodynamics of two doses (0.2 and 0.4 mg) of INSCOP in simulated microgravity, antiorthostatic bedrest. All regulatory procedures were competed that include certification for Good laboratory Procedures by Theradex , clinical documentation, personnel training

  7. RETRACTED: Effect of intranasal oxytocin administration on psychiatric symptoms: A meta-analysis of placebo-controlled studies.

    Science.gov (United States)

    Hofmann, Stefan G; Fang, Angela; Brager, Daniel N

    2015-08-30

    This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the authors and Editor-in-Chief of the journal. It was brought to the authors' attention that there were several significant data analytic errors linked to the data entry and the software program that was used in the published meta-analysis comparing the effect of intranasal oxytocin versus placebo administration on psychiatric symptoms. Correcting these errors changed the main result of this study. The authors greatly apologize to the journal, the reviewers, and readers for the errors in the original article, and would like to thank the readers who brought the errors to their attention. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Plasmid DNA Vaccine Co-Immunisation Modulates Cellular and Humoral Immune Responses Induced by Intranasal Inoculation in Mice.

    Directory of Open Access Journals (Sweden)

    Deborah F L King

    Full Text Available An effective HIV vaccine will likely require induction of both mucosal and systemic cellular and humoral immune responses. We investigated whether intramuscular (IM delivery of electroporated plasmid DNA vaccine and simultaneous protein vaccinations by intranasal (IN and IM routes could be combined to induce mucosal and systemic cellular and humoral immune responses to a model HIV-1 CN54 gp140 antigen in mice.Co-immunisation of DNA with intranasal protein successfully elicited both serum and vaginal IgG and IgA responses, whereas DNA and IM protein co-delivery did not induce systemic or mucosal IgA responses. Cellular IFNγ responses were preserved in co-immunisation protocols compared to protein-only vaccination groups. The addition of DNA to IN protein vaccination reduced the strong Th2 bias observed with IN protein vaccination alone. Luminex analysis also revealed that co-immunisation with DNA and IN protein induced expression of cytokines that promote B-cell function, generation of TFH cells and CCR5 ligands that can reduce HIV infectivity.These data suggest that while IN inoculation alone elicits both cellular and humoral responses, co-administration with homologous DNA vaccination can tailor these towards a more balanced Th1/Th2 phenotype modulating the cellular cytokine profile while eliciting high-levels of antigen-specific antibody. This work provides insights on how to generate differential immune responses within the same vaccination visit, and supports co-immunisation with DNA and protein by a mucosal route as a potential delivery strategy for HIV vaccines.

  9. Construction and preliminary immunobiological characterization of a novel, non-reverting, intranasal live attenuated whooping cough vaccine candidate.

    Science.gov (United States)

    Cornford-Nairns, Renee; Daggard, Grant; Mukkur, Trilochan

    2012-06-01

    We describe the construction and immunobiological properties of a novel whooping cough vaccine candidate, in which the aroQ gene, encoding 3-dehydroquinase, was deleted by insertional inactivation using the kanamycin resistance gene cassette and allelic exchange using a Bordetella suicide vector. The aroQ B. pertussis mutant required supplementation of media to grow but failed to grow on an unsupplemented medium. The aroQ B. pertussis mutant was undetectable in the trachea and lungs of mice at days 6 and 12 post-infection, respectively. Antigen-specific antibody isotypes IgG1 and IgG2a, were produced, and cell-mediated immunity [CMI], using interleukin-2 and interferon-gamma as indirect indicators, was induced in mice vaccinated with the aroQ B. pertussis vaccine candidate, which were substantially enhanced upon second exposure to virulent B. pertussis. Interleukin- 12 was also produced in the aroQ B. pertussis-vaccinated mice. On the other hand, neither IgG2a nor CMI-indicator cytokines were produced in DTaP-vaccinated mice, although the CMI-indicator cytokines became detectable post-challenge with virulent B. pertussis. Intranasal immunization with one dose of the aroQ B. pertussis mutant protected vaccinated mice against an intranasal challenge infection, with no pathogen being detected in the lungs of immunized mice by day 7 post-challenge. B. pertussis aroQ thus constitutes a safe, non-reverting, metabolite-deficient vaccine candidate that induces both humoral and cellmediated immune responses with potential for use as a single-dose vaccine in adolescents and adults, in the first instance, with a view to disrupting the transmission cycle of whooping cough to infants and the community.

  10. Serum and mucosal immunologic responses in children following the administration of a new inactivated intranasal anti-influenza vaccine.

    Science.gov (United States)

    Greenbaum, E; Furst, A; Kiderman, A; Stewart, B; Levy, R; Schlesinger, M; Morag, A; Zakay-Rones, Z

    2001-09-01

    Children are at considerable risk for influenza infection and may constitute the main vector for transmitting the virus to adults in the community. At present, the use of available vaccines in children is limited mainly because of a fear of side effects from the injection. Intranasal immunization was assessed as a painless, side effect-free method of facilitating the enrollment of children in vaccination programs. One intranasal dose of a trivalent inactive whole virus vaccine containing 20 microg of the three recommended seasonal viral strains was administered to 28 children recruited over two separate winter periods (1997/1998 and 1998/1999). No adverse effects were recorded. Serum IgG responses were determined by the hemagglutination inhibition (HI) method and nasal IgA responses by enzyme-linked immunosorbent assay (ELISA). In both study period seasons, 77.7%-94.4% of children were found to be immune. There was a 3.7 x and 4.7 x increase in geometric mean titer (GMT) for A/H3N2 strains, 1.9 x and 3.9 x for A/H1N1 strains, and a 3.2 x and 1.7 x for B strains in 1997/1998 and 1998/1999, respectively. The increase in GMT, as well as fourfold increases in titer level, was higher when calculated among the nonimmune children prior to vaccination. Of these, 50%-87.5% became immune following immunization. Local antibody response to the three viral strains was detected in 50%-55% of the immunized children. Also, 83.3%, 73.3%, and 61.1% of the vaccinees exhibited a mucosal and/or serum antibody response to the A/Beijing, A/Sydney, and B/Harbin strains, respectively. This mucosal response may forestall influenza development in its early stages, thereby contributing significantly to the reduction of influenza spread in the community.

  11. Virus detection by PCR following vaccination of naive calves with intranasal or injectable multivalent modified-live viral vaccines.

    Science.gov (United States)

    Walz, Paul H; Newcomer, Benjamin W; Riddell, Kay P; Scruggs, Daniel W; Cortese, Victor S

    2017-09-01

    We evaluated duration of PCR-positive results following administration of modified-live viral (MLV) vaccines to beef calves. Twenty beef calves were randomly assigned to either group 1 and vaccinated intranasally with a MLV vaccine containing bovine alphaherpesvirus 1 (BoHV-1), bovine respiratory syncytial virus (BRSV), and bovine parainfluenza virus 3 (BPIV-3), or to group 2 and vaccinated subcutaneously with a MLV vaccine containing bovine viral diarrhea virus 1 and 2 (BVDV-1, -2), BoHV-1, BRSV, and BPIV-3. Deep nasopharyngeal swabs (NPS) and transtracheal washes (TTW) were collected from all calves, and whole blood was collected from group 2 calves and tested by PCR. In group 1, the proportions of calves that tested PCR-positive to BVDV, BoHV-1, BRSV, and BPIV-3 on any sample at any time were 0%, 100%, 100%, and 10%, respectively. In group 1 calves, 100% of calves became PCR-positive for BoHV-1 by day 3 post-vaccination and 100% of calves became PCR-positive for BRSV by day 7 post-vaccination. In group 2, the proportions of calves that tested positive to BVDV, BoHV-1, BRSV, and BPIV-3 on any sample at any time were 50%, 40%, 10%, and 0%, respectively. All threshold cycle (Ct) values were >30 in group 2 calves, irrespective of virus; however, Ct values PCR-positive results for BoHV-1 and BRSV. All calves were PCR-negative for all viruses after day 28. Following intranasal MLV viral vaccination, PCR results and Ct values for BRSV and BoHV-1 suggest that attempts to differentiate vaccine virus from natural infection is unreliable.

  12. Comparative pharmacokinetics of tetramethylpyrazine phosphate in rat plasma and extracellular fluid of brain after intranasal, intragastric and intravenous administration

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    Dongmei Meng

    2014-02-01

    Full Text Available The purpose of this study was to compare the pharmacokinetic profiles of tetramethylpyrazine phosphate (TMPP in plasma and extracellular fluid of the cerebral cortex of rats via three delivery routes: intranasal (i.n., intragastric (i.g. and intravenous (i.v. administration. After i.n., i.g. and i.v. administration of a single-dose at 10 mg/kg, cerebral cortex dialysates and plasma samples drawn from the carotid artery were collected at timed intervals. The concentration of TMPP in the samples was analyzed by HPLC. The area under the concentration–time curve (AUC and the ratio of the AUCbrain to the AUCplasma (drug targeting efficiency, DTE was calculated to evaluate the brain targeting efficiency of the drug via these different routes of administration. After i.n. administration, TMPP was rapidly absorbed to reach its peak plasma concentration within 5 min and showed a delayed uptake into cerebral cortex (tmax=15 min. The ratio of the AUCbrain dialysates value between i.n. route and i.v. injection was 0.68, which was greater than that obtained after i.g. administration (0.43. The systemic bioavailability obtained with i.n. administration was greater than that obtained by the i.g. route (86.33% vs. 50.39%, whereas the DTE of the nasal route was 78.89%, close to that of oral administration (85.69%. These results indicate that TMPP is rapidly absorbed from the nasal mucosa into the systemic circulation, and then crosses the blood–brain barrier (BBB to reach the cerebral cortex. Intranasal administration of TMPP could be a promising alternative to intravenous and oral approaches.

  13. Subclinical infection without encephalitis in mice following intranasal exposure to Nipah virus-Malaysia and Nipah virus-Bangladesh.

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    Dups, Johanna; Middleton, Deborah; Long, Fenella; Arkinstall, Rachel; Marsh, Glenn A; Wang, Lin-Fa

    2014-06-02

    Nipah virus and Hendra virus are closely related and following natural or experimental exposure induce similar clinical disease. In humans, encephalitis is the most serious outcome of infection and, hitherto, research into the pathogenesis of henipavirus encephalitis has been limited by the lack of a suitable model. Recently we reported a wild-type mouse model of Hendra virus (HeV) encephalitis that should facilitate detailed investigations of its neuropathogenesis, including mechanisms of disease recrudescence. In this study we investigated the possibility of developing a similar model of Nipah virus encephalitis. Aged and young adult wild type mice did not develop clinical disease including encephalitis following intranasal exposure to either the Malaysia (NiV-MY) or Bangladesh (NiV-BD) strains of Nipah virus. However viral RNA was detected in lung tissue of mice at euthanasia (21 days following exposure) accompanied by a non-neutralizing antibody response. In a subsequent time course trial this viral RNA was shown to be reflective of an earlier self-limiting and subclinical lower respiratory tract infection through successful virus re-isolation and antigen detection in lung. There was no evidence for viremia or infection of other organs, including brain. Mice develop a subclinical self-limiting lower respiratory tract infection but not encephalitis following intranasal exposure to NiV-BD or NiV-MY. These results contrast with those reported for HeV under similar exposure conditions in mice, demonstrating a significant biological difference in host clinical response to exposure with these viruses. This finding provides a new platform from which to explore the viral and/or host factors that determine the neuroinvasive ability of henipaviruses.

  14. Intranasal delivery of bone marrow mesenchymal stem cells improved neurovascular regeneration and rescued neuropsychiatric deficits after neonatal stroke in rats.

    Science.gov (United States)

    Wei, Zheng Zachory; Gu, Xiaohuan; Ferdinand, Anwar; Lee, Jin Hwan; Ji, Xiaoya; Ji, Xun Ming; Yu, Shan Ping; Wei, Ling

    2015-01-01

    Neonatal stroke is a major cause of mortality and long-term morbidity in infants and children. Currently, very limited therapeutic strategies are available to protect the developing brain against ischemic damage and promote brain repairs for pediatric patients. Moreover, children who experienced neonatal stroke often have developmental social behavior problems. Cellular therapy using bone marrow mesenchymal stem cells (BMSCs) has emerged as a regenerative therapy after stroke. In the present investigation, neonatal stroke of postnatal day 7 (P7) rat pups was treated with noninvasive and brain-specific intranasal delivery of BMSCs at 6 h and 3 days after stroke (1 × 10(6)cells/animal). Prior to transplantation, BMSCs were subjected to hypoxic preconditioning to enhance their tolerance and regenerative properties. The effects on regenerative activities and stroke-induced sensorimotor and social behavioral deficits were specifically examined at P24 of juvenile age. The BMSC treatment significantly reduced infarct size and blood-brain barrier disruption, promoted angiogenesis, neurogenesis, neurovascular repair, and improved local cerebral blood flow in the ischemic cortex. BMSC-treated rats showed better sensorimotor and olfactory functional recovery than saline-treated animals, measured by the adhesive removal test and buried food finding test. In social behavioral tests, we observed functional and social behavioral deficits in P24 rats subjected to stroke at P7, while the BMSC treatment significantly improved the performance of stroke animals. Overall, intranasal BMSC transplantation after neonatal stroke shows neuroprotection and great potential as a regenerative therapy to enhance neurovascular regeneration and improve functional recovery observed at the juvenile stage of development.

  15. Ocular immune responses in steers following intranasal vaccination with recombinant Moraxella bovis cytotoxin adjuvanted with polyacrylic acid.

    Science.gov (United States)

    Angelos, John A; Edman, Judy M; Chigerwe, Munashe

    2014-02-01

    Infectious bovine keratoconjunctivitis (IBK) caused by Moraxella bovis is the most common eye disease of cattle. The pathogenesis of M. bovis requires the expression of pili that enable the organism to attach to the ocular surface and an RTX (repeats in the structural toxin) toxin (cytotoxin or hemolysin), which is cytotoxic to corneal epithelial cells. In this pilot study, ocular mucosal immune responses of steers were measured following intranasal (i.n.) vaccination with a recombinant M. bovis cytotoxin adjuvanted with polyacrylic acid. Beef steers were vaccinated with either 500 μg (n = 3) or 200 μg (n = 3) of recombinant M. bovis cytotoxin plus adjuvant. Control group steers (n = 2) were vaccinated with adjuvant alone, and all steers were given a booster on day 21. Antigen-specific tear IgA and tear IgG, tear cytotoxin-neutralizing antibody responses, and serum cytotoxin-neutralizing antibody responses were determined in samples collected prevaccination and on days 14, 28, 42, and 55. Changes in tear antigen-specific IgA levels from day 0 to days 28, 42, and 55 were significantly different between groups; however, in post hoc comparisons between individual group pairs at the tested time points, the differences were not significant. Our results suggest that i.n. vaccination of cattle with recombinant M. bovis cytotoxin adjuvanted with polyacrylic acid effects changes in ocular antigen-specific IgA concentrations. The use of intranasally administered recombinant M. bovis cytotoxin adjuvanted with polyacrylic acid could provide an alternative to parenteral vaccination of cattle for immunoprophylaxis against IBK.

  16. Intranasal Oxytocin Affects Amygdala Functional Connectivity after Trauma Script-Driven Imagery in Distressed Recently Trauma-Exposed Individuals.

    Science.gov (United States)

    Frijling, Jessie L; van Zuiden, Mirjam; Koch, Saskia B J; Nawijn, Laura; Veltman, Dick J; Olff, Miranda

    2016-04-01

    Approximately 10% of trauma-exposed individuals go on to develop post-traumatic stress disorder (PTSD). Neural emotion regulation may be etiologically involved in PTSD development. Oxytocin administration early post-trauma may be a promising avenue for PTSD prevention, as intranasal oxytocin has previously been found to affect emotion regulation networks in healthy individuals and psychiatric patients. In a randomized double-blind placebo-controlled between-subjects functional magnetic resonance (fMRI) study, we assessed the effects of a single intranasal oxytocin administration (40 IU) on seed-based amygdala resting-state FC with emotion regulation areas (ventromedial prefrontal cortex (vmPFC), ventrolateral prefrontal cortex (vlPFC)), and salience processing areas (insula, dorsal anterior cingulate cortex (dACC)) in 37 individuals within 11 days post trauma. Two resting-state scans were acquired; one after neutral- and one after trauma-script-driven imagery. We found that oxytocin administration reduced amygdala-left vlPFC FC after trauma script-driven imagery, compared with neutral script-driven imagery, whereas in PL-treated participants enhanced amygdala-left vlPFC FC was observed following trauma script-driven imagery. Irrespective of script condition, oxytocin increased amygdala-insula FC and decreased amygdala-vmPFC FC. These neural effects were accompanied by lower levels of sleepiness and higher flashback intensity in the oxytocin group after the trauma script. Together, our findings show that oxytocin administration may impede emotion regulation network functioning in response to trauma reminders in recently trauma-exposed individuals. Therefore, caution may be warranted in administering oxytocin to prevent PTSD in distressed, recently trauma-exposed individuals.

  17. Utility of intranasal Ketamine and Midazolam to perform gastric aspirates in children: a double-blind, placebo controlled, randomized study

    Science.gov (United States)

    2014-01-01

    Background We performed a prospective, randomized, placebo-controlled study aimed to evaluate the efficacy and safety of a sedation protocol based on intranasal Ketamine and Midazolam (INKM) administered by a mucosal atomizer device in uncooperative children undergoing gastric aspirates for suspected tuberculosis. Primary outcome: evaluation of Modified Objective Pain Score (MOPS) reduction in children undergoing INKM compared to the placebo group. Secondary outcomes: evaluation of safety of INKM protocol, start time sedation effect, duration of sedation and evaluation of parents and doctors’ satisfaction about the procedure. Methods In the sedation group, 19 children, mean age 41.5 months, received intranasal Midazolam (0.5 mg/kg) and Ketamine (2 mg/kg). In the placebo group, 17 children received normal saline solution twice in each nostril. The child’s degree of sedation was scored using the MOPS. A questionnaire was designed to evaluate the parents’ and doctors’ opinions on the procedures of both groups. Results Fifty-seven gastric washings were performed in the sedation-group, while in the placebo-group we performed 51 gastric aspirates. The degree of sedation achieved by INMK enabled all procedures to be completed without additional drugs. The mean duration of sedation was 71.5 min. Mean MOPS was 3.5 (range 1-8) in the sedation-group, 7.2 (range 4-9) in the placebo-group (p <0.0001). The questionnaire revealed high levels of satisfaction by both doctors and parents in the sedation-group compared to the placebo-group. The only side effect registered was post-sedation agitation in 6 procedures in the sedation group (10.5%). Conclusions Our experience suggests that atomized INKM makes gastric aspirates more acceptable and easy to perform in children. Trial registration Unique trial Number: UMIN000010623; Receipt Number: R000012422. PMID:24598046

  18. Evaluating the immunogenicity of an intranasal vaccine against nicotine in mice using the Adjuvant Finlay Proteoliposome (AFPL1).

    Science.gov (United States)

    Fraleigh, Nya L; Boudreau, Justin; Bhardwaj, Nitin; Eng, Nelson F; Murad, Yanal; Lafrenie, Robert; Acevedo, Reinaldo; Oliva, Reynaldo; Diaz-Mitoma, Francisco; Le, Hoang-Thanh

    2016-08-01

    Tobacco smoking is recognized as a global pandemic resulting in 6 million deaths per year. Despite a variety of anti-smoking products available to aid with tobacco cessation, the majority of people who attempt to quit smoking relapse within 6 months due to the addictive nature of nicotine. An immunotherapy approach could offer a promising treatment option by inducing a potent selective antibody response against nicotine in order to block its distribution to the brain and its addictive effects in the central nervous system. Our nicotine vaccine candidate was administered intranasally using the Neisseria meningitidis serogroup B Adjuvant Finlay Proteoliposome 1 (AFPL1) as a part of the delivery system. This system was designed to generate a robust immune response by stimulating IL-1β production through Toll-like receptor 4 (TLR4), a potent mechanism for mucosal immunity. The vaccine induced high antibody titers in mice sera in addition to inducing mucosal antibodies. The efficacy of our vaccine was demonstrated using in vivo challenge experiments with radioactive [(3)H]-nicotine, followed by an analysis of nicotine distribution in the lung, liver, blood and brain. Our results were encouraging as the nicotine concentration in the brain tissue of mice vaccinated with our candidate vaccine was four times lower than in non-vaccinated controls; suggesting that the anti-nicotine antibodies were able to block nicotine from crossing the blood brain barrier. In summary, we have developed a novel nicotine vaccine for the treatment of tobacco addiction by intranasal administration and also demonstrated that the AFPL1 can be used as a potential adjuvant for this vaccine design.

  19. Inmunización intranasal con AFCo1 induce respuesta inmune de memoria, sistemica y mucosal en ratones neonatal

    Directory of Open Access Journals (Sweden)

    Julio A. Balboa

    2009-08-01

    Full Text Available Neonates have a poorly developed immune system. Respiratory pathogens cause disease during early periods of live. Consequently, it is important to develop protective vaccines that induce immunity and immunological memory against respiratory pathogens early in life. Intranasal (i.n. route could be an effective via for immunization. Therefore, we explored the effectiveness of AF (Adjuvant Finlay PL1 (Proteoliposome from Neisseria meningitidis serogroup B and its derivate Cochleate (AFCo1 by nasal route in neonatal mice. They were immunized i.n. 3 times 7 days apart and anti PL systemic and mucosal antibody response were measured by ELISA. In addition, a prime-boost strategy was used to evaluate the humoral immune response in neonate mice. The 3 doses of AFPL1 or AFCo1 induced significant levels of anti PL IgG antibodies in comparison whit control, but AFCo1 (2017 U/mL was significantly higher than AFPL1 (1107 U/mL. AFCo1 and AFPL1 induced a predominant Th1 pattern with IgG2a/IgG1 >1 by i.n. immunization and AFCo1 induced a high anti PL IgA saliva response in saliva. Interestingly, one nasally prime at 7 days of born and a memory one boost i.n. dose 9 weeks later with AFCo1 or AFPL1 showed similar specific IgG levels and IgG2a/IgG1 relation than 3 i.n. doses in adult mice. In conclusion, these results represent the first report of neonatal intranasal vaccination using AFCo1 capable to induce systemic and mucosal immunity and priming for memory.

  20. Do delivery routes of intranasally administered oxytocin account for observed effects on social cognition and behavior? A two-level model.

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    Quintana, Daniel S; Alvares, Gail A; Hickie, Ian B; Guastella, Adam J

    2015-02-01

    Accumulating evidence demonstrates the important role of oxytocin (OT) in the modulation of social cognition and behavior. This has led many to suggest that the intranasal administration of OT may benefit psychiatric disorders characterized by social dysfunction, such as autism spectrum disorders and schizophrenia. Here, we review nasal anatomy and OT pathways to central and peripheral destinations, along with the impact of OT delivery to these destinations on social behavior and cognition. The primary goal of this review is to describe how these identified pathways may contribute to mechanisms of OT action on social cognition and behavior (that is, modulation of social information processing, anxiolytic effects, increases in approach-behaviors). We propose a two-level model involving three pathways to account for responses observed in both social cognition and behavior after intranasal OT administration and suggest avenues for future research to advance this research field.

  1. ADMINISTRACIÓN DE INSULINA POR VÍA INTRANASAL Y MEMORIA DECLARATIVA: REVISIÓN SISTEMÁTICA DE LA LITERATURA Intranasal insulin administration and declarative memory: A systematic review

    Directory of Open Access Journals (Sweden)

    Andrés Jagua Gualdrón

    2008-12-01

    Full Text Available Antecedentes. La insulina participa de los procesos de formación de la memoria y los defectos en su señalización podrían estar relacionados con el déficit cognitivo y las enfermedades neurode-generativas como la enfermedad de Alzheimer. Objetivo. Evaluar la relación entre la administración de la insulina por vía intranasal y la memoria declarativa en estudios en humanos. Material y métodos. Se realizó una búsqueda intensiva y sistemática de estudios publicados entre enero de 1997 y diciembre del 2008 a través de las bases de datos MEDLINE, Cochrane, DynaMed y LILACS. Los estudios fueron sometidos a dos pruebas de calidad metodológica, se les realizó un análisis crítico y se aplicó estadística básica. Resultados. Se hallaron cinco artículos que incluían 252 personas. De ellos 143 tenían diagnóstico probable de la enfermedad de Alzheimer o alteración cognitiva leve. Los estudios reportan mejoría en las tareas de la memoria a corto y largo plazo en los grupos que recibieron la insulina comparados con quienes recibieron el placebo. Conclusión. Los estudios son pocos y difíciles de comparar. Sin embargo tras este análisis puede sugerirse que la insulina actúa durante la formación de la memoria declarativa y podría emplearse en el tratamiento de los trastornos de la memoria.Background. Insulin acts in memory formation and its signal impairment can be related with mild cognitive impairment and neurodegenerative diseases like Alzheimer's disease. Objective. To evaluate the relationship between intranasal insulin administration and declarative memory in studies with human. Materials and methods. A systematic search of studies published from January 1997 to december 2008 through electronic databases MEDLINE, DynaMed, Cochrane and LIlACS. Articles were evaluated with two tests for methodological validity and a basic statistical analysis was performed. Results. We find five articles that include 252 persons. 143 have

  2. Unde venis? Amebiasis presenting as appendicitis.

    Science.gov (United States)

    Wilson, Dennis A; Wilson, Gerald A; Bryan, Charles S

    2013-06-01

    A returning traveler presenting with fever accompanied by abdominal "pre