Hill, Dolores E.; Dubey, J.P.; Abbott, Rachel C.; van Riper, Charles; Enright, Elizabeth A.; Abbott, Rachel C.; van Riper, Charles; Enright, Elizabeth A.
Toxoplasmosis (Toxoplasma gondii), one of the better known and more widespread zoonotic diseases, originated in wildlife species and is now well established as a human malady. Food- and waterborne zoonoses, such as toxoplasmosis, are receiving increasing attention as components of disease emergence and resurgence. Toxoplasmosis is transmitted to humans via consumption of contaminated food or water, and nearly one-third of humanity has been exposed to this parasite. The role of wildlife in this transmission process is becoming more clearly known and is outlined in this report. This zoonotic disease also causes problems in wildlife species across the globe. Future generations of humans will continue to be jeopardized by toxoplasmosis infections in addition to many of the other zoonotic diseases that have emerged during the past century. Through monitoring toxoplasmosis infection levels in wildlife populations, we will be better able to predict future human infection levels of this important zoonotic disease.
... you get it?Toxoplasmosis (say: tox-oh-plaz-moh-sis) is an infection caused by a tiny ... warm water, especially before you eat or prepare food.Wash your hands thoroughly after handling raw meat, ...
... mothers become infected for the first time during pregnancy. Problems can include damage to the brain, eyes, and other organs. You can get toxoplasmosis from Waste from an infected cat Eating contaminated meat that is raw or not ...
... is infected. Tests your doctor may recommend include: Amniocentesis. In this procedure, which may be done safely ... the fluid to check for evidence of toxoplasmosis. Amniocentesis carries a slight risk of miscarriage and minor ...
an acute infection. The use of a Toxoplasma-specific IgG-avidity ratio, differentiated Western blots and two-dimensional immunoblots usually resolves diagnostic problems. There is no consensus on the best strategy to control congenital toxoplasmosis. Recent European prospective, but descriptive, studies...... in pregnant women and newborn children with congenital toxoplasmosis. Atovaquone is the most promising new drug available, but is not yet approved for use in pregnant women and small children. Udgivelsesdato: 2007-Jun...
Full Text Available Introduction. Toxoplasma gondii is an intracellular protozoan that infects approximately one-third of the world’s population. Infection in human generally occurs through consuming food or drink contaminated with oocysts and tissue cysts from undercooked meat. Although latent infection with Toxoplasma gondii is among the most prevalent of human infections, it has been generally assumed that, except for congenital transmission, it is asymptomatic. Different conditions such as, number of parasite, virulence of the organism, genetic background, sex, and immunological status seem to affect the course of infection The demonstration that Toxoplasma infections can alter behavior, reproductive function in patients has led to a reconsideration of this assumption. During chronic acquired toxoplasmosis (САT identified the regularities of changes in the ratio of the immune system and the basal levels of sex hormones available informative methods, which made it possible to evaluate the severity of the flow chart and predict treatment outcome without resorting to complex research methods. Found that the host-parasite relationships and clinical manifestations of chronic toxoplasmosis depend largely on protective and adaptive responses and compensatory abilities of the human body. Material & methods. 112 patients attended in the 6 Department of Kharkiv Regional Infectious Diseases Hospital №22 (Department of Medical Parasitology and Tropical Diseases of Kharkiv Medical Academy of Postgraduate Education, in Kharkiv, Ukraine were enrolled in the study. Forty four patients (39,3±4,6% were male and sixty eight (60,7±4,6% were female. The age of the patients was 18 till 72 years. Results & discussion. All of 112 CAT patients had subjective clinical symptoms in various combinations: increased fatigue 99,1 ± 0,9%, headache and tiredness 95,5 ± 1,9%, pain in the liver 88,4 ± 3,1%, bitter taste in the mouth 93,8 ± 2,2%, muscle pain 81,3 ± 3,7% and joint pain
12 Figure 12.41 Toxoplasma cyst with bradyzoites (arrow) in white pulp of spleen of patient with congenital toxoplasmosis. H&E x260 Figure 12.40...neutrophils in biopsied brain of patient with toxoplasmosis. H&E x765 Figure 12.55 Two Toxoplasma cysts in nerve fiber layer of retina. PAS x260 Figure...12.76 Toxoplasma organisms (arrows) parasitize individual heart muscle fibers . H&E x250 Figure 12.77 Toxoplasma organisms in heart muscle fiber . Note
Yang, Zhaoshou; Ahn, Hye-Jin; Nam, Ho-Woo
Mouse models of chronic toxoplasmosis and atopic dermatitis (AD) were combined to clarify the effect of opportunistic Toxoplasma gondii infection on the development of AD. AD was induced as a chronic contact hypersensitivity (CHS) with repeated challenge of 2,4,6-trinitro-1-chlorobenzene (TNCB) on the dorsal skin of mice. TNCB induced skin thickness increases in both normal and toxoplasmic mice. The changing patterns were different from the sigmoidal which saturated at 20 days in normal mice to the convex saturated at 12 days in toxoplasmic mice with the crossing at 18 days. Compared to normal mice, toxoplasmic mice presented CHS more severely in earlier times and then moderately in later times. These data suggest that host immune modification by T. gondii infection enhances CHS in early times of atopic stimulation but soothes the reaction of CHS in later times in mouse model.
Full Text Available Toxoplasma gondii is an intracellular protozoan parasite that infects human and animals. Toxoplasma parasites are isolated from different parts of animals even from semen but there are little information about the effect of toxoplasmosis on fertility in animals and humans. In present study, the effect of chronic toxoplasmosis on serum levels of testosterone in men was studied.In this case-control study, 1026 men referred to Arak Post Marriage Center were selected. Three ml of blood samples were collected and sera separated by centrifugation at room temperature. These sera were analyzed for detection of anti-T. gondii IgG antibody. Next 365 positive sera were selected as cases and also the same number of negative sera (365 as controls. Finally the level of testosterone was analyzed for the cases and controls samples.Serological tests on the sera of 1,026 men in Arak City showed that 365 of them had anti-Toxoplasma antibody. Comparison of testosterone concentration in case and control groups showed that testosterone concentration in case group was less than control group and this difference was statistically significant (P<0.05.The chronic toxoplasmosis could affect reproductive parameters in men.
Vikrant Sudan; A K Tewari; R Singh; Harkirat Singh
Objective:To compare histopathology and PCR based detection in diagnosis of experimentally induced toxoplasmosis of RH human strain of the parasite in murine models. Methods:A comparison of histopathology and PCR based detection was done to diagnose experimentally induced toxoplasmosis in ten inbred swiss albino mice after intraperitoneal inoculation of 100 tachyzoites of laboratory mantained human RH strain of the parasite. Tissue samples from lung, liver, spleen, brain, heart and kidney were taken and processed for histopathological examination while all the samples also were subjected to PCR, using primers directed to the multicopy of SAG 3 gene, in dublicates. Results: Histopathology revealed presence of tachyzoites only in liver while along with lung, liver, spleen and brain tissue yielded desired positive PCR amplicons. Conclusions:The SAG 3 based PCR is able to diagnose toxoplasmosis in those tissues which are declared negative by histopathological assay.
Оксана Вячеславовна Боброва
Full Text Available The great number of treatment schemes of toxoplasmosis predetermines the question for clinician how to choose the most effective therapy regimen. Aim. Detection of the criteria of prognostication of efficiency of the treatment patients with the chronic acquired toxoplasmosis (CAT in an acute phase before and after the complex therapy. Methods. For attaining the set aim we examined 143 patients (92 women and 51 men 18-75 years old with CAT in an acute phase.For evaluation of efficiency of the complex antiparasitic pathogenetic therapy and the character of dynamics of the studying indicators there was carried out the repeat examination of 143 patients in 1-2 and 5-6 month after the end of treatment.Results. An efficiency of considered treatment regimens depends on an initial pathogenetic determinant specific for each of them and its calculation allows prognosticate and individualize the treatment of patients.Conclusions. The immunological parameters, data of clinical blood analysis and biochemical indicators of the liver function and also the clinical-anamnestic indicators have the predictor properties that allows use it for prognosis of efficiency of CAT treatment. An efficiency of the different treatment regimens of toxoplasmosis can be prognosticated on the base of initial values of parameters of homeostasis of patient’s organism.An efficiency of elaborated algorithms of prognosis of efficiency of the different regimens of CAT therapy was 86,7-90% at the reliability ≥95%, that allows recommend it for clinical use.The use of prognostic algorithms allows individualize the treatment of patients with CAT.
Full Text Available Recent studies correlate chronic Toxoplasma gondii (T. gondii infection with behavioral changes in rodents; additionally, seropositivity in humans is reported to be associated with behavioral and neuropsychiatric diseases. In this study we investigated whether the described behavioral changes in a murine model of chronic toxoplasmosis are associated with changes in synaptic plasticity and brain neuronal circuitry. In mice chronically infected with T. gondii, magnetic resonance imaging (MRI data analysis displayed the presence of heterogeneous lesions scattered throughout all brain areas. However, a higher density of lesions was observed within specific regions such as the somatosensory cortex (SSC. Further histopathological examination of these brain areas indicated the presence of activated resident glia and recruited immune cells accompanied by limited alterations of neuronal viability. In vivo diffusion-tensor MRI analysis of neuronal fiber density within the infected regions revealed connectivity abnormalities in the SSC. Altered fiber density was confirmed by morphological analysis of individual, pyramidal and granule neurons, showing a reduction in dendritic arbor and spine density within the SSC, as well as in the hippocampus. Evaluation of synapse efficacy revealed diminished levels of two key synaptic proteins, PSD95 and synaptophysin, within the same brain areas, indicating deficits in functionality of the synaptic neurotransmission in infected mice. Our results demonstrate that persistent T. gondii infection in a murine model results in synaptic deficits within brain structures leading to disturbances in the morphology of noninfected neurons and modified brain connectivity, suggesting a potential explanation for the behavioral and neuropsychiatric alterations.
Anatomic, histopathologic, and MRI/SPET studies of autistic spectrum disorders (ASD) patients' brains confirm existence of very early developmental deficits. In congenital and chronic murine toxoplasmosis several cerebral anomalies also have been reported, and worldwide, approximately two billion people are chronically infected with T. "gondii"…
Autism Spectrum Disorders May Be Due to Cerebral Toxoplasmosis Associated with Chronic Neuroinflammation Causing Persistent Hypercytokinemia that Resulted in an Increased Lipid Peroxidation, Oxidative Stress, and Depressed Metabolism of Endogenous and Exogenous Substances
Worldwide, approximately 2 billion people are chronically infected with "Toxoplasma gondii" with largely yet unknown consequences. Patients with autism spectrum disorders (ASD) similarly as mice with chronic toxoplasmosis have persistent neuroinflammation, hypercytokinemia with hypermetabolism associated with enhanced lipid peroxidation, and…
Xiao, Jianchun; Li, Ye; Prandovszky, Emese; Kannan, Geetha; Viscidi, Raphael P; Pletnikov, Mikhail V; Yolken, Robert H
There is marked variation in the human response to Toxoplasma gondii infection. Epidemiological studies indicate associations between strain virulence and severity of toxoplasmosis. Animal studies on the pathogenic effect of chronic infection focused on relatively avirulent strains (e.g. type II) because they can easily establish latent infections in mice, defined by the presence of bradyzoite-containing cysts. To provide insight into virulent strain-related severity of human toxoplasmosis, we established a chronic model of the virulent type I strain using outbred mice. We found that type I-exposed mice displayed variable outcomes ranging from aborted to severe infections. According to antibody profiles, we found that most of mice generated antibodies against T. gondii organism but varied greatly in the production of antibodies against matrix antigen MAG1. There was a strong correlation between MAG1 antibody level and brain cyst burden in chronically infected mice (r = 0.82, p = 0.0021). We found that mice with high MAG1 antibody level displayed lower weight, behavioral changes, altered levels of gene expression and immune activation. The most striking change in behavior we discovered was a blunted response to amphetamine-trigged locomotor activity. The extent of most changes was directly correlated with levels of MAG1 antibody. These changes were not found in mice with less cyst burden or mice that were acutely but not chronically infected. Our finding highlights the critical role of cyst burden in a range of disease severity during chronic infection, the predictive value of MAG1 antibody level to brain cyst burden and to changes in behavior or other pathology in chronically infected mice. Our finding may have important implications for understanding the heterogeneous effects of T. gondii infections in human.
Full Text Available In a study of congenital transmission during acute infection of Toxoplasma gondii, 23 pregnant Balb/c mice were inoculated orally with two cysts each of the P strain. Eight mice were inoculated 6-11 days after becoming pregnant (Group 1. Eight mice inoculated on the 10th-15th day of pregnancy (Group 2 were treated with 100 mg/kg/day of minocycline 48 h after inoculation. Seven mice inoculated on the 10th-15th day of pregnancy were not treated and served as a control (Group 3. Congenital transmission was evaluated through direct examination of the brains of the pups or by bioassay and serologic tests. Congenital transmission was observed in 20 (60.6% of the 33 pups of Group 1, in one (3.6% of the 28 pups of Group 2, and in 13 (54.2% of the 24 pups of Group 3. Forty-nine Balb/c mice were examined in the study of congenital transmission of T. gondii during chronic infection. The females showed reproductive problems during this phase of infection. It was observed accentuated hypertrophy of the endometrium and myometrium. Only two of the females gave birth. Our results demonstrate that Balb/c mice with acute toxoplasmosis can be used as a model for studies of congenital T. gondii infection. Our observations indicate the potential of this model for testing new chemotherapeutic agents against congenital toxoplasmosis.
... feces, or things that could be contaminated by insects exposed to cat feces (cockroaches, flies, etc.). Also, ... More Anemia Bleeding into the skin Blindness and vision loss Hepatomegaly Intrauterine growth restriction Retina Toxoplasmosis Review ...
Schlüter, Dirk; Däubener, Walter; Schares, Gereon; Groß, Uwe; Pleyer, Uwe; Lüder, Carsten
Toxoplasma gondii is an extremely sucessfull protozoal parasite which infects almost all mamalian species including humans. Approximately 30% of the human population worldwide is chronically infected with T. gondii. In general, human infection is asymptomatic but the parasite may induce severe disease in fetuses and immunocompromised patients. In addition, T. gondii may cause sight-threatening posterior uveitis in immunocompetent patients. Apart from few exceptions, humans acquire T. gondii from animals. Both, the oral uptake of T. gondii oocysts released by specific hosts, i.e. felidae, and of cysts persisting in muscle cells of animals result in human toxoplasmosis. In the present review, we discuss recent new data on the cell biology of T. gondii and parasite diversity in animals. In addition, we focus on the impact of these various parasite strains and their different virulence on the clinical outcome of human congenital toxoplasmosis and T. gondii uveitis.
Introducción: La toxoplasmosis causada por el Toxoplasma gondii se transmite a los humanos de manera transplacentaria, entre otras. Se estima que infecta a un tercio de la población mundial y está asociado con infección congénita y abortos. Solo son sintomáticos del 10 al 20% de los casos. Caso clínico: Se presenta el caso de un recién nacido pretérmino referido a un hospital de mayor complejidad. Durante la hospitalización se realiza el diagnóstico de toxoplasmosis congénita con diversas...
Irina Clara Delgado Varela
Full Text Available Background: Toxoplasmosis is the most widespread zoonosis worldwide. Its prevalence can double in rural populations in relation to urban populations, and it is different in persons of different races within the same community. Objective: To determine the characteristics of toxoplasmosis infection in Charavalle community, Bermúdez municipality, Sucre State, Venezuelan Republic. Methods: A descriptive, cross-sectional study was developed between April and September 2006. Through observation and interview the primary data on the 343 patients selected through simple sampling was obtained. The studied population was classified according to socio-demographic variables, the serum presence of IgG antibodies anti-Toxoplasma gondii was determine through indirect hemagglutination and the main risk factors l inked to toxoplasmosis infection were identified. Results: There was a prevalence of the age group between 16 and 30 years, mainly females in the Stratum III of socioeconomic level. Serological prevalence rate of antibodies IgG anti-Toxoplasma gondii was 63, 56/100 inhabitants and the most significant risk factors were: cohabitation with dogs and cats, raw vegetables and fruit intake, and no drinkable water intake. Conclusions: Results largely agree with other researches on the same subject.
Peterson, J L; Willard, M D; Lees, G E; Lappin, M R; Dieringer, T; Floyd, E
Lymphocytic-plasmacytic enteritis, a chronic inflammatory intestinal disease, was diagnosed in 2 cats. In 1 cat, recurrence of clinical signs after initiating treatment was attributed to relapse of the inflammatory intestinal disease, but was found to be attributable to relapsing toxoplasmosis secondary to immunosuppressive drug therapy. Treatment with clindamycin resolved the recurrent toxoplasmosis. In the second cat, clinical signs of toxoplasmosis did not develop, but serologic testing yielded evidence of active toxoplasmosis. Treatment with clindamycin caused the titers to decrease. Relapsing toxoplasmosis may be responsible for apparent resistance to treatment in cats for inflammatory intestinal disease being treated with immunosuppressive drugs.
Full Text Available ABSTRACT Introduction: The global protozoan parasite, Toxoplasma gondii, infects many warm-blooded animals and humans by employing different transmission routes. There have been some recent studies on the probable relevance of infectious agents and diabetes. Therefore, we conducted a systematic review and meta-analysis to identify the possible association between chronic toxoplasmosis and diabetes mellitus. Methods: This study was conducted following the general methodology recommended for systematic reviews and meta-analysis. Nine English literature databases (Google scholar, PubMed, Scopus, Web of science, Science Direct, Ovid, ProQuest, IngentaConnect, and Wiley Online Library were searched, up to January 2016. Random effects model was used to determine odds ratios and their 95% confidence intervals. Results: Our review resulted in a total of seven publications meeting the inclusion criteria. Because of significant heterogeneity, we estimated a common OR by a random effects model at 1.10 (95% CI = 0.13-9.57 with p = 0.929 and 2.39 (95% CI = 1.20-4.75 with p = 0.013 for type 1 and type 2 diabetes mellitus, respectively. Conclusion: Despite the limitations such as low number of studies, this meta-analysis suggests chronic toxoplasmosis as a possible risk factor for type 2 DM. However, based on random effects model no statistically significant association was observed between T. gondii and type 1 DM. It is highly recommended for researchers to carry out more accurate studies aiming to better understand this association.
Screening tests of various kinds of compounds were carried out with the purpose of obtaining new drugs for toxoplasmosis . Compounds tested were 66...Nitro-4’-formylamino-difenylsulfone might be effective in treatments of human toxoplasmosis . (Author)
Organophosphate induced chronic neurotoxicity: Health, environmental and risk exposure issues in developing nations of the world. ... show that many agents considered toxic and banned in many parts of the industrialized world are still in ...
Torres-Morales, Elizabeth; Taborda, Laura; Cardona, Nestor; De-la-Torre, Alejandra; Sepulveda-Arias, Juan Carlos; Patarroyo, Manuel Alfonso; Gomez-Marin, Jorge Enrique
We determined the specific lymphocyte proliferative response and cytokine profile production regarding Toxoplasma P30 (2017 from virulent and non-virulent strain) and ROP18 protein-derived peptides (from clonal lineages I, II and III) in 19 patients having ocular toxoplasmosis, five suffering chronic asymptomatic infection, nine with congenital toxoplasmosis and eight Toxoplasma negative people. A Beckman Coulter FC500 flow cytometer was used for determining antigen-specific T cells (CD3+ CD4+ or CD3+ CD8+ cells) in peripheral blood culture. IFN γ and IL10 levels were determined in culture supernatants. Specific CD4+ and CD8+ T cell response to total antigen and P30- and ROP18-derived peptides was observed in infected people. Ocular toxoplasmosis patients had a preferential Th2 response after antigenic stimulation. Non-virulent peptide 2017 was able to shift response toward Th1 in congenitally infected children and virulent peptide 2017 induced a Th2 response in chronically infected, asymptomatic people. An immune response in human toxoplasmosis after ex vivo antigenic stimulation was Th1- or Th2-skewed, depending on a patient's clinical condition. Colombian ocular toxoplasmosis patients' immune response was Th2-skewed, regardless of the nature of antigen stimulus.
Zare-Bidaki, Mohammad; Hakimi, Hamid; Abdollahi, Seyyed Hossein; Zainodini, Nahid; Arababadi, Mohammad Kazemi; Kennedy, Derek
Toxoplasma species are obligate intracellular protozoan which are responsible for induction of several forms of Toxoplasmosis in humans. The mechanisms responsible for the progression of the prolonged forms of Toxoplasmosis and associated pathologies are yet to be identified. However, previous studies proposed that immunological and genetic parameters may play important roles in the etiology and complexity of Toxoplasmosis. Pathogen recognition receptors (PRRs) recognize microbial antigens and induce immune responses against parasites, including toxoplasma species. Toll like receptors (TLRs) are PRRs which recognize toxoplasma as a pathogenic parasite and activate immune cells. It has been reported that the TLR4 is a critical innate immune cell receptor in toxoplasma detection and subsequently activates immune responses using either MYD88 or TRIF pathways. This review collates recent information regarding the role of TLR4 and its related signaling molecules with Toxoplasmosis.
Full Text Available ABSTRACT. Toxoplasmosis is one zoonosis caused by toxoplasmosis gondii that can infected pets and human.Infection in woman pregnant, frequently asymptomatic. While impact at this disease woman pregnant for herpregnancy, specially at third trimester pregnant were hidrocephalus, chorioretinitis, deaf or epilepsi.Toxoplasmosis is a disease caused by toxoplasma gondii, transmitted to human by eating food under cooked,infected meat or handling soil or cat feces that contain the parasite. The route of infection in to human by aquiredor congenital variation impact of congenital toxoplasmosis were chorioretinitis, hydrocephalus, intracranialcalcificatio. Laboratorys tests are very important of clinical sign is asymtomatic. Test that commonly usedmoreanti toxoplasma Ig G, Ig M, Ig A and Aviditas Anti Toxoplasma. Primmary and secondary prevention is important.Treatment to toxoplasmosis with spiramycine is effective. Toxoplasmosis infection prevention could be done byavoid risk factor of toxoplasmosis ie not eating raw specially undercooked meat, not contact with animal'sinfected. Toxoplasmosis treatment in pregnancy is needed include abortion and antibiotic support to infant couldbe done according to discussion from doctor, patients and her husband.Key words: Toxoplasmosis, pregnancy
Khryanin, A A; Reshetnikov, O V; Kuvshinova, I N
The up-to-date literature and original data on the epidemiology, diagnosis and treatment of toxoplasmosis are presented. Particular attention is paid to the parasite infection during pregnancy. Spiramycin is the drug of choice for acute toxoplasmosis in pregnant women.
Winter-Messiers, Mary Ann
The author describes her fears and struggles as she came to terms, as an American expatriate in France, with a medical diagnosis of Toxoplasmosis. This condition led to her birthing a son with Asperger's Syndrome. She tells of plunging herself into research to learn more about Toxoplasmosis, the number of things that could be seriously wrong with…
Toxoplasmosis is a worldwide health problem. Infection of a pregnant woman can result in severe fetal morbidity or in subclinical neonatal infection; most subclinical cases will develop ocular and neurological sequelae. Fetal infection and clinical outcome is related to when in pregnancy toxoplasmosis was acquired. The risk of transmission increases from 14% in the first trimester to 29% in the second and 59% in the third. Conversely, clinical damage decreases from about 80% in the first to 10% in the third trimester, but up to 50% of patients with subclinical congenital toxoplasmosis will develop neurologic and ocular sequelae. Congenital toxoplasmosis can be prevented by identification of non immune women at the beginning of pregnancy, by giving information on how to avoid the infection and by a serological follow-up until the delivery. Serological follow-up is based on repeated testing for specific IgG and IgM, but other serologic methods are necessary to differentiate between acute and chronic infections and possibly on a single serum sample. Procedures to detect fetal infection are ultrasound examination, cordocentesis and amniocentesis; prenatal diagnosis relies on demonstration of toxoplasma in fetal blood or amniotic fluid by mouse inoculation. Very promising results have recently obtained by the PCR-method applied to amniotic fluid samples. All strongly suspected cases of acquired toxoplasmosis in pregnancy have to be treated.
Hampton, Marissa Martinez
Acute infection of toxoplasmosis during pregnancy is detrimental to the developing fetus. In the United States, approximately 1 in 10,000 live births are affected by congenital toxoplasmosis. Although multifactorial in etiology, maternal infection is primarily attributed to the consumption of contaminated meat or water. Infection and transmission to the fetus may result in devastating neurologic impairment. Screening methods for all pregnant women should be implemented in routine prenatal care. This article will highlight the inherent dangers of congenital toxoplasmosis, while including general care of the fetus for prevention of transmission, medical management, and long-term outcomes.
Hiszczyńska-Sawicka, Elżbieta; Gatkowska, Justyna M; Grzybowski, Marcin M; Długońska, Henryka
Toxoplasma gondii is a cosmopolitan protozoan parasite that infects a wide range of mammal and bird species. Common infection leads to high economic (e.g., abortions in sheep) and human (e.g., congenital toxoplasmosis or neurotoxoplasmosis in humans) losses. With one exception (Toxovax for sheep), there are no vaccines to prevent human or animal toxoplasmosis. The paper presents the current state and challenges in the development of a vaccine against toxoplasmosis, designed for farm animals either bred for consumption or commonly kept on farms and involved in parasite transmission. So far, the trials have mostly revolved around conventional vaccines and, compared with the research using laboratory animals (mainly mice), they have not been very numerous. However, the results obtained are promising and could be a good starting point for developing an effective vaccine to prevent toxoplasmosis.
Eissa, Maha M; Barakat, Ashraf M A; Amer, Eglal I; Younis, Layla K
Toxoplasmosis is a zoonotic protozoal disease affecting more than a billion people worldwide. The shortfalls of the current treatment options necessitate the development of non-toxic and well-tolerated, efficient alternatives especially against the cyst form. The current study was undertaken to investigate, for the first time, the potential potency of miltefosine against Toxoplasma gondii infection in acute and chronic experimental toxoplasmosis. Results showed that there is no evidence of anti-parasitic activity of miltefosine against T. gondii tachyzoites in acute experimental toxoplasmosis. However, anti-parasitic activity of miltefosine against T. gondii cyst stage in chronic experimental toxoplasmosis could not be excluded as demonstrated by significant reduction in brain cyst burden. Moreover, considerable morphological changes in the cysts were revealed by light and electron microscopy study and also by amelioration of pathological changes in the brain. Future studies should focus on enhancement of anti-toxoplasma activity of miltefosine against chronic toxoplasmosis using formulation based nanotechnology. To the best of our knowledge, this is the first study highlighting efficacy of miltefosine against chronic toxoplasmosis, thus, increasing the list of diseases that can be targeted by this drug.
Dziadek, Bozena; Brzostek, Anna
Toxoplasmosis is a globally distributed foodborne zoonosis caused by a protozoan parasite Toxoplasma gondii. Usually asymptomatic in immunocompetent humans, toxoplasmosis is a serious clinical and veterinary problem often leading to lethal damage in an infected host. In order to overcome the exceptionally strong clinical and socio-economic impact of Toxoplasma infection, the construction of an effective vaccine inducing full immunoprotection against the parasite is an urgent issue. In the last two decades many live attenuated, subunit and DNA-based vaccines against toxoplasmosis have been studied, however only partial protection conferred by vaccination against chronic as well as acute infection has been achieved. Among various immunization strategies, no viable subunit vaccines based on recombinant secretory (ROP2, ROP4 and GRA4) and surface (SAG1) T. gondii proteins have been found as attractive tools for further studies. This is due to their high, but still partial, protective efficacy correlated with the induction of cellular and humoral immune responses.
Chaudhry, Shahnaz Akhtar; Gad, Nanette; Koren, Gideon
Question Congenital toxoplasmosis is a dangerous fetal infection. Why is routine screening for Toxoplasma gondii infection during pregnancy not available for most Canadians? Answer Low prevalence of the infection, high cost associated with testing, low sensitivity of screening tests, false-positive test results, and limitations of treatment effectiveness are all cited as reasons for not routinely screening for T gondii infection in Canada. Currently, screening for the detection of T gondii is only performed in Nunavik and other parts of northern Quebec owing to the high prevalence of infection in this region. Congenital toxoplasmosis causes neurologic or ocular disease (leading to blindness), as well as cardiac and cerebral anomalies.
Kravetz, Jeffrey D; Federman, Daniel G
Pregnant women who acquire infection from Toxoplasma gondii usually remain asymptomatic, although they can still transmit the infection to their fetuses with severe consequences. Given the asymptomatic nature of most Toxoplasma infections, primary prevention in pregnant women may lower the risk of congenital toxoplasmosis. Both consumption of undercooked meat and unprotected contact with soil are independent risk factors for T. gondii seroconversion during pregnancy, while contact with cat litter may pose a risk in certain situations. However, many pregnant women lack knowledge of these risk factors. This article reviews toxoplasmosis infection in pregnancy, with an emphasis on risk factors and appropriate counseling of pregnant women.
CHEN Xiao-guang; WU Kun; LUN Zhao-rong
@@ Toxoplasmosis, caused by Toxoplasma gondii (T. gondii), an obligate intracellular parasite, is a globally distributed zoonosis. It is estimated that one third of population has been infected by this parasite worldwide. In some regions of Europe, the serum antibodies against T. gondii were detected in more than 80% of the examined population.
Petersen, E.; Kijlstra, A.; Stanford, M.
Retinal infection with Toxoplasma gondii is the most important cause of posterior uveitis, whereby prevalence and incidence of ocular symptoms after infection depend on socio-economic factors and the circulating parasite genotypes. Ocular toxoplasmosis is more common in South America, Central Americ
Petersen, E.; Kijlstra, A.; Stanford, M.
Retinal infection with Toxoplasma gondii is the most important cause of posterior uveitis, whereby prevalence and incidence of ocular symptoms after infection depend on socio-economic factors and the circulating parasite genotypes. Ocular toxoplasmosis is more common in South America, Central Americ
Prömpeler, H J; Vogt, A; Petersen, E E
Even today, toxoplasmosis infection during pregnancy is an unsolved problem. In studies of 2206 pregnant women, toxoplasmosis specific IgM-antibodies have been detected in 69 cases (3.1%). Using more sophisticated serological techniques only 12 active toxoplasmosis cases needing therapy remained. Decisive discrimination criteria of the various tests were exact time of the examination as well as the level of the antibody titer. Although only 12 toxoplasmosis infections were treated, no connatal infections have been observed. On the other hand, in some outpatients, referred to our clinic, cases of severe connatal toxoplasmosis infections were found although they had undergone therapy. To solve the problem of toxoplasmosis, we recommend a general screening before pregnancy if possible. For optimal results of this screening, serologic reference laboratories and efficient sonography units must be established to obtain, when required, umbilical venous blood.
Full Text Available The immunopathogenesis of toxoplasmosis during pregnancy is not completely understood. This paper will try to discuss the most frequently asked questions about the immunopathogeny of congenital toxoplasmosis: differential virulence of Toxoplasma isolates, genetic susceptibility to infection, facilitation of placental transfer, models of congenital toxoplasmosis, and transmission in seropositive hosts. Most published data suggest a role of the genetic background of the host and of the parasite. Models of congenital toxoplasmosis have been evaluated, but it appears that the conclusion drawn would be barely appropriate to understand the pathogenesis in pregnant women.
The immunopathogenesis of toxoplasmosis during pregnancy is not completely understood. This paper will try to discuss the most frequently asked questions about the immunopathogeny of congenital toxoplasmosis: differential virulence of Toxoplasma isolates, genetic susceptibility to infection, facilitation of placental transfer, models of congenital toxoplasmosis, and transmission in seropositive hosts. Most published data suggest a role of the genetic background of the host and of the parasite. Models of congenital toxoplasmosis have been evaluated, but it appears that the conclusion drawn would be barely appropriate to understand the pathogenesis in pregnant women.
Machala, L; Kodym, P; Malý, M; Geleneky, M; Beran, O; Jilich, D
In humans, toxoplasmosis mostly occurs as a latent infection, but in immunocompromised individuals, the agent may reactivate and cause severe to life-threatening disease. HIV positive individuals and transplant recipients, in particular hematopoietic stem cell transplant and heart transplant recipients, are at highest risk. The disease most often affects the central nervous system but can involve any organ. Because of the alteration of the immune response in these patients, the serodiagnosis is not reliable and direct detection of the causative agent is needed--namely by microscopy and DNA PCR. If inadequately treated or left untreated, toxoplasmosis generally has a fatal prognosis in immunocompromised patients and therefore, the treatment must be started as early and energetically as possible. The gold standard both in the treatment of reactivation and secondary prophylaxis is the pyrimethamine-sulfadiazine combination while co-trimoxazole can be used in the primary prophylaxis for high-risk patients.
Mittal, Veena; Ichhpujani, R L
Toxplasmosis is an important zoonotic disease caused by protozoan parasite Toxoplasma gondii. The disease affects one-third of the total world population. Transmission of the disease is mainly by ingestion of food or water contaminated with oocysts. Congenital toxoplasmosis occurs from the transplacental passage of the parasite from mother to fetus. In most adults it does not cause serious illness, but it can cause blindness and mental retardation in congenitally infected children, and it is ...
João M Furtado
Full Text Available Toxoplasmosis, a disease described worldwide, which is caused by the protozoan Toxoplasma gondii, commonly involves the retina. The disease has a higher impact in immunocompromised individuals and in congenital infection because of the severity of central nervous system involvement. Although simple prophylactic measures could reduce transmission, T. gondii seroprevalence is still high, especially in South America. Educational campaigns and the development of new drugs to prevent primary infection could potentially reduce the burden of the disease.
Full Text Available The present review provides general information about the parasitic infection of toxoplasmosis and describes the ways of its transmission. It outlines the importance of the consequences of toxoplasmosis infection and the methods of its prevention. The review traces the harmful effects of the disease on human and animal organisms, the causes and stages of development of the disease. The review specifically focuses on the ocular manifestations of toxoplasmosis which can cause ocular lesions, inflammation and scarring. Herein are described the ways toxoplasmosis can damage the eyes causing chorioretinitis, nystagmus, microphthalmia, etc. Furthermore, the review addresses the problem of how congenital and acquired toxoplasmosis affects eyes. The ocular symptoms of toxoplasmosis include weakened or blurred vision, eyeballs pain, ocular sensitivity to light, etc. The harmful effects of toxoplasmosis to pregnant women and immunocompromised patients have been delineated. Some of the disease manifestations include jaundice, rash, asphyxia, etc. The review traces the diagnostic work-up and comments on common tests for toxoplasmosis, such as taking of blood serum samples. The review ends with the treatment of the disease and of its ocular manifestations in particular, for example application of intravitreous injection. The prevention of the infection is extremely important for pregnant women, immunocompromised patients and patients with AIDS.
Full Text Available Introduction & Objective: Toxoplasmosis is one of the most widespread parasitic infections in the human beings and other warm-blooded animals that can cause chronic infection in adults, fatal illness in immunodeficient patients and abortion in pregnant women or congenital abnormalities in fetus. The aim of this study was determination of the prevalence of toxoplasmosis in primigrvida women in Hamadan.Materials & Methods: In this cross sectional study a total of 576 primigravida women, who admitted to the health centers were selected by cluster random sampling method. Data for epidemiological factors was collected by a questionnaire and serum samples were collected for detection of total antibodies against Toxoplasma gondii. The titer of ≥ 1:20 regarded as positive. The relationship between variables analyzed by chi² test.Results: In this study seroprevalence was 33.5%. Higher seropositivity observed in illiterate subgroup and lower infection rate was found in high school educated subgroup. Our study showed statistically significant relationship between seropositivity and age, fresh and undercooked meat and rate of vegetables consumption (P0.05. Conclusion: This study indicated that seropositivity for toxoplasmosis in this area is lower than northern parts and higher than central and eastern parts of Iran. Our study showed that about one-third of individuals were seropositive and because of the importance of toxoplasmosis in primigravida women and immonucompromized patients, health education is necessary for prevention of toxoplasmosis.
Kaparos, Nikolaos; Favrat, Bernard; D'Acremont, Valérie
Toxoplasmosis is an infectious disease caused by the intracellular parasite Toxoplasma gondii. In Switzerland about a third of the population has antibodies against this pathogen and has thus already been in contact with the parasite or has contracted the disease. Immunocompetent patients are usually asymptomatic (80-90%) during primary infection. The most common symptom is neck or occipital lymphadenopathy. Serology is the diagnostic gold standard in immunocompetent individuals. The presence of IgM antibodies is however not sufficient to make a definite diagnosis of acute toxoplasmosis. Distinction between acute and chronic toxoplasmosis requires additional serological tests (IgG avidity test). If required, the most used and probably most effective treatment is the combination of pyrimethamine and sulfadiazine, with folinic acid.
Recent studies have demonstrated that screening and treatment for toxoplasmosis during gestation result in a decrease of vertical transmission and clinical sequelae. Early treatment was associated with improved outcomes. Thus, laboratory methods should aim for early identification of infants with congenital toxoplasmosis (CT). Diagnostic approaches should include, at least, detection of Toxoplasma IgG, IgM, and IgA and a comprehensive review of maternal history, including the gestational age ...
Rubina Kumari Baithalu
Full Text Available Anthropozoonotic parasite Toxoplasma gondii causes widespread human and animal diseases, mostly involving central nervous system. Human acquires toxoplasmosis from cats, from consuming raw or undercooked meat and from vertical transmission to the fetus through placenta from mother during pregnancy. Socio-epidemiological as well as unique environmental factors also plays a significant role in transmission of this infection. Preventive measures should be taken into account the importance of culture, tradition, and beliefs of people in various communities more than solving poverty and giving health education. Therefore the focus of this article is to create public awareness regarding sense of responsibility of looking after pets to prevent such an important zoonotic disease. [Vet. World 2010; 3(5.000: 247-249
Christ, F.; Steudel, H.; Klotz, D.
Since 1982 (Hauser and co-workers), literature has reported focal cerebral tissue charges in AIDS patients whose diagnosis was unclear at first but which could be identified finally as florid toxoplasmosis encephalitis by biopsy and autopsy. It was found that the value of otherwise reliable serological tests (KBR, Sabin-Feldmann tests, etc.) is questionable in patients with severely impaired or incompetent immune systems, and, in particular, that a negative or uncharacteristic test result may not preclude any opportunistic infection process. Furthermore, isolation of Toxoplasma gondii or specific antibodies from the cerebrospinal fluid will be successful in exceptional cases only. In patients with AIDS or lymphadenopathy syndrome, the differential diagnosis will have to include - first and foremost - reactivated toxoplasma infection (not newly acquired, as a rule) if central neurological symptoms occur.
Mirlesse, V; Jacquemard, F; Daffos, F
Congenital toxoplasmosis results from contamination of the foetus by Toxoplasma gondii during pregnancy. It is a frequent and severe condition calling for close surveillance of mothers at risk. During the last few years, numerous advances have been made in the diagnosis and treatment of toxoplasmosis. Its diagnosis in the mother is now more reliable due to improvements in serological techniques, while in the foetus the use of foetal vascular techniques has made it possible to detect those who are infected. Owing to a new and effective therapeutic method certain foetuses can now be treated successfully in utero, so that induced abortion is reserved to cases with severe and early toxoplasmosis. The contribution of new molecular biology techniques to advances in this ever moving field is explained.
Sonar S. S. and Brahmbhatt M.N.
Full Text Available Toxoplasmosis is an important infection caused by single celled parasite Toxoplasma gondii which is one of the world's most common parasites. Toxoplasmosis is considered to be the third leading cause of death attributed to food-borne illness in the United States. Most people affected never develop signs and symptoms. But for infants born to infected mothers and for people with compromised immune systems, toxoplasmosis can cause extremely serious complications. Toxoplasmosis was first described in 1908 from a small rodent. The parasite infects almost all worm blooded animals and serological evidence indicates that it is one of the most common of humans’ infections throughout the world. The disease is transmitted mainly by ingestion of infective stage of the parasite, organ transplant as well as blood transfusion in addition to the transplacental transmission which is very common. Toxoplasmosis can be presented in various forms of clinical manifestations depending on the immune status of the patient causing life threatening disease in AIDS patient. Pregnant women, cat owners, veterinarians, abattoir workers, children, cooks, butchers are considered as high risk group. Timely treatment of man and animals with proper antibiotic, hygienic measures, proper disinfection, mass education and vaccination are the measures to curtail the disease. [Veterinary World 2010; 3(9.000: 436-439
Full Text Available Toxoplasmosis is a common worldwide parasitic infection that caused by Toxoplasma gondii. The clinical progress is generally asymptomatic in patient with normal immune system, on the other hand severe clinical presentations seen in patients with immune deficiency or pregnancy. Congenital toxoplasmosis can emerge due to contamination during pregnancy but 6-8 weeks prior to pregnancy are also at risk. Infants with toxoplasmosis have some clinical semptoms such as chorioretinitis, epilepsia, hypotonia, psychomotor disorders, mental retardation, encephalitis, microcephaly, hydrocephalus, intracranial calcifications, hepatosplenomegaly. Early diagnosis during pregnancy and subsequent treatment. may prevent malformations. Toxoplasmosis diagnosis during pregnancy is mostly based on IgM and IgG antibody screening tests. While IgM indicates the acute infection, it disappears in early period and can be detected in low consantrations through long ages. Therefore IgG avidity test takes more place in the diagnosis of toxoplasmosis during pregnancy. High avidity levels indicate acquired infection prior than 16 weeks, so that it is recommended to perform the test in the first trimester. Low IgG avidity level may indicate a newly onset infection. Amniotic fluid T.gondii PCR, anomaly screening with ultrasonography, Toxoplasma gondii cyst dying with Wright-Giemsa dye in plasental and fetal tissue are the other diagnostic tools can be performed during pregnancy. Avidity test methods during the 16 weeks of pregnancy reduce repeating serum analysis, amniotic fluid PCR reguirement, unnecessary antibiotic treatments and noncompulsory abortus. [TAF Prev Med Bull 2012; 11(6.000: 767-772
Silva-dos-Santos, Priscila Pinto; Barros, Geisa Baptista; Mineo, José Roberto; de Oliveira Silva, Deise Aparecida; Menegaz, Mauro Hygino Weinert; Serufo, José Carlos; Dietze, Reynaldo; Martins-Filho, Olindo de Assis; Lemos, Elenice Moreira
In the present study we evaluated the performance of a flow cytometry-based algorithm as a new serological approach to detect antibodies to T. gondii and specific IgG avidity to diagnose acute toxoplasmosis. The results showed that using FC-AFTA-IgM assay, all serum samples from patients with acute toxoplasmosis demonstrated seropositivity, whereas 90% of patients with chronic infection and 100% of non-infected individuals presented negative results. Thus, only 10% of patients with chronic toxoplasmosis showed residual IgM, in contrast with other methodologies used to diagnosis acute toxoplasmosis. On the order hand, FC-AFTA-IgG assay as well as FC-AFTA-IgG subclasses is unlikely to discriminate acute from chronic toxoplasmosis. We have also evaluated the performance of FC-AFTA-IgG avidity as a tool to exclude chronic toxoplasmosis in patients with positive FC-AFTA-IgM. Our data showed an excellent performance of FC-AFTA-IgG avidity employing the cut-off of 60% for Avidity Index (AI) with sensitivity and specificity of 100%. All serum samples from patients presenting acute toxoplasmosis showed low avidity index (AI≤60%), whereas all chronic patients showed high avidity index (AI>60%). The outstanding performance indexes of this novel flow cytometry-based algorithm support its use as a non-conventional alternative serological approach to diagnose human acute toxoplasmosis.
Pomares, Christelle; Montoya, Jose G
Recent studies have demonstrated that screening and treatment for toxoplasmosis during gestation result in a decrease of vertical transmission and clinical sequelae. Early treatment was associated with improved outcomes. Thus, laboratory methods should aim for early identification of infants with congenital toxoplasmosis (CT). Diagnostic approaches should include, at least, detection of Toxoplasma IgG, IgM, and IgA and a comprehensive review of maternal history, including the gestational age at which the mother was infected and treatment. Here, we review laboratory methods for the diagnosis of CT, with emphasis on serological tools. A diagnostic algorithm that takes into account maternal history is presented.
Yogish S Kamath
Full Text Available We report an atypical presentation of Toxoplasma retinochoroiditis with associated scleritis in a young and immunocompetent patient. The diagnosis was done on the basis of Polymerase chain reaction of vitreous sample, and the clinical response to specific treatment. This case highlights the unusual presentation of ocular toxoplasmosis as scleritis.
Di Mario, Simona; Basevi, Vittorio; Gagliotti, Carlo; Spettoli, Daniela; Gori, Gianfranco; D'Amico, Roberto; Magrini, Nicola
Congenital toxoplasmosis is considered a rare but potentially severe infection. Prenatal education about congenital toxoplasmosis could be the most efficient and least harmful intervention, yet its effectiveness is uncertain. To assess the effects of prenatal education for preventing congenital toxoplasmosis. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2015), and reference lists of relevant papers, reviews and websites. Randomized and quasi-randomized controlled trials of all types of prenatal education on toxoplasmosis infection during pregnancy. Cluster-randomized trials were eligible for inclusion. Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Two cluster-randomized controlled trials (RCTs) (involving a total of 5455 women) met the inclusion criteria. The two included trials measured the effectiveness of the intervention in different ways, which meant that meta-analysis of the results was not possible. The overall quality of the two studies, as assessed using the GRADE approach, was low, with high risk of detection and attrition bias in both included trials.One trial (432 women enrolled) conducted in Canada was judged of low methodological quality. This trial did not report on any of the review's pre-specified primary outcomes and the secondary outcomes reported results only as P values. Moreover, losses to follow-up were high (34%, 147 out of 432 women initially enrolled). The authors concluded that prenatal education can effectively change pregnant women's behavior as it increased pet, personal and food hygiene. The second trial conducted in France was also judged of low methodological quality. Losses to follow-up were also high (44.5%, 2233 out of 5023 women initially enrolled) and differential (40% in the intervention group and 52% in the control group). The authors concluded that prenatal education for congenital toxoplasmoses has a
Scerra, S; Coignard-Biehler, H; Lanternier, F; Suarez, F; Charlier-Woerther, C; Bougnoux, M-E; Gilquin, J; Lecuit, M; Hermine, O; Lortholary, O
Toxoplasmosis can be a severe opportunistic infection in patients with acquired immunodeficiency syndrome (AIDS), and also among solid organ transplant and allogeneic hematopoietic stem cell transplant (HSCT) patients. Patients with low-grade or chronic hematologic malignancies are treated with increasing immunosuppressive regimens and, therefore, represent an emerging population at risk for opportunistic diseases. We report here two cases of disseminated toxoplasmosis occurring in non-allografted hematologic patients with chronic lymphoproliferations. A review of 44 cases from the literature reveals that toxoplasmosis occurs increasingly in indolent B cell lymphoproliferative disorders. Aggressive lymphoproliferations, adenosine analogs, autologous HSCT, and the absence of chemoprophylaxis are the main risk factors for opportunistic toxoplasmosis. The central nervous system is the main organ involved. Fever is only present in half of all cases. Latent Toxoplasma cysts reactivation (LTCR) is the most common, but primary infection occurs in about 20% of cases. Global mortality is over 50%.
Du Thanh, A
In the recently published 2013 revision of the guidelines of urticaria, chronic urticaria (CU) gathers chronic spontaneous urticaria (CSU) and inducible urticaria (IU), and excludes pseudourticarial rashes with more than 24h-lasting rash or more than 72h-lasting angiœdema. Activity and psychosocial impact of the disease must be measured with validated scores such as Urticaria and Angioedema Activity Scores, Urticaria Control Test, CU-Q2OL, AE-QOL. Although an allergic cause is generaly absent in CU, pathomecanisms remain elusive even since the well-known role of mast cell degranulation and the presence of autoantibodies anti-FcRεI or anti-IgE. Coagulation pathways may be involved, at least as an amplifying phenomenon. Mean duration of CU is 1 to 4 years, but many patients still have symptoms after 10 years, some predictive factors being known as severity, angioedema, a positive autologous serum test, inducible urticaria. Recommended routine diagnosic tests are validated provocation tests for IU (and cryoproteins for cold urticaria), blood cell count and CRP for CSU, since a thorough history and a normal detailed physical examination should avoid unnecessary tests. Management of CU has been improved by the off-label use of increased dosages of second generation anti- H1 antihistamines, but a subsequent therapeutic intensification may be necessary in some cases. Educational program may prevent this intensification. Independent studies evaluating available molecules are needed, along with more fundamental research studies.
Toxoplasmosis is a serious and life-threatening disease in humans with a high prevalence in immunocompromised persons. The disease has a wide spectrum, depending on the immune status of the person. A CNS manifestation of toxoplasmosis in an immunocompetent person is very rare and often undetected. Our case of CNS toxoplasmosis in an immunocompetent person emphasizes the radiological diagnosis, which was further confirmed by advanced microbiology technique.
Rajoo Ramachandran, MBBS, MD
Full Text Available Toxoplasmosis is a serious and life-threatening disease in humans with a high prevalence in immunocompromised persons. The disease has a wide spectrum, depending on the immune status of the person. A CNS manifestation of toxoplasmosis in an immunocompetent person is very rare and often undetected. Our case of CNS toxoplasmosis in an immunocompetent person emphasizes the radiological diagnosis, which was further confirmed by advanced microbiology technique.
Introduction Neuroretinitis (NR) is considered to be an inflammatory condition which is characterized by optic disc edema and, as a result, formation of a macular star figure. NR is an atypical presentation of toxoplasmosis infection, and such cases are quite rare. Case Presentation A 13-year-old girl presented with painless subacute visual loss in her right eye for a week at Khatam-Al-Anbia eye hospital in Mashhad, Iran. Following comprehensive evaluation, a diagnosis of toxoplasmic NR was m...
Saadatnia, Geita; Golkar, Majid
Toxoplasmosis is a worldwide infection caused by the intracellular parasite Toxoplasma gondii. At least a third of the world human population are infected with the parasite, making it one of the most successful parasitic infections. Primary maternal infection may cause health-threatening sequelae for the foetus, or even cause death in uterus. Reactivation of a latent infection in immune deficiency conditions such as AIDS and organ transplantation can cause fatal toxoplasmic encephalitis. Toxoplasmosis is a major cause of retinochoroiditis, especially in individuals with an impaired immune system. Despite the usually 'asymptomatic' nature of the infection, a significant burden imposed by the parasite necessitates the implementation of effective means for the prevention, diagnosis, and management of this disease. Laboratory diagnosis, i.e. PCR and serologic assays, plays the main role in the diagnosis of congenital infection and assists in the confirmatory diagnosis of toxoplasmic encephalitis and ocular toxoplasmosis. Here, we briefly review general aspects of Toxoplasma infection and focus on the diagnostic methods currently used in medical laboratories for the diagnosis of Toxoplasma infection.
Dziadek, Bozena; Gatkowska, Justyna; Brzostek, Anna; Dziadek, Jaroslaw; Dzitko, Katarzyna; Grzybowski, Marcin; Dlugonska, Henryka
The great clinical and economical impact of Toxoplasma gondii infections makes the development of an effective vaccine for controlling toxoplasmosis an extremely important aim. In the presented study, we evaluate the protective and immunogenic properties of three recombinant subunit vaccines composed of rROP2+rGRA4+rSAG1, rROP2+rROP4+rGRA4 and rROP2+rROP4+rSAG1 proteins of T. gondii in an experimental toxoplasmosis model in the C3H/HeJ and C57BL/6 mouse strains. All three recombinant vaccines induced partial protection as measured by the reduction of brain cyst burden following challenge with five tissue cysts of the low virulence DX T. gondii strain. The level of protection was dependent on the antigen composition of the vaccine and the genetic background of the laboratory animals. The strongest protection against chronic toxoplasmosis was induced in both C3H/HeJ and C57BL/6 mice by the mixture of rhoptry proteins rROP2 and rROP4 combined with tachyzoite major protein rSAG1. The average parasite burden in these groups of mice was reduced by 71% and 90%, respectively, compared to non-vaccinated mice. The observed protective effect was related to the vaccine-induced cellular and humoral immune responses, as measured by the antigen-induced release of the Th1 cytokines IFN-γ and IL-2, the antigen-stimulated proliferation of spleen cells of vaccinated animals in comparison to control animals and the development of systemic antigen-specific IgG1 and IgG2a (C3H/HeJ) or IgG2c (C57BL/6) antibodies. Our studies show that recombinant rROP2, rROP4, rGRA4 and rSAG1 antigens may be promising candidates for a subunit vaccine against toxoplasmosis. Additionally, we demonstrate that the ideal composition of vaccine antigens can be equally effective in mice with different genetic backgrounds and variable levels of innate resistance to toxoplasmosis, resulting in strong protection against T. gondii invasion.
Toxoplasma gondii is widely distributed in wild and domestic animals. The present chapter reviews toxoplasmosis in wild and domestic animals. Coverage in wild animal species is limited to confirmed cases of toxoplasmosis, cases with parasite isolation, cases with parasite detection by PCR, and exper...
Hoekstra, F.; Buzing, C.; Sporken, J.M.J.; Erasmus, C.E.; Flier, M. van der; Semmekrot, B.A.
Two infants with congenital toxoplasmosis are presented. A girl born prematurely was treated postnatally after the mother had received antimicrobial treatment during pregnancy for acute toxoplasmosis. Apart from being small for gestational age, she remained without symptoms and treatment was ceased
Hoekstra, F.; Buzing, C.; Sporken, J.M.J.; Erasmus, C.E.; Flier, M. van der; Semmekrot, B.A.
Two infants with congenital toxoplasmosis are presented. A girl born prematurely was treated postnatally after the mother had received antimicrobial treatment during pregnancy for acute toxoplasmosis. Apart from being small for gestational age, she remained without symptoms and treatment was ceased
Jurk, Diana; Wilson, Caroline; Passos, Joao F.; Oakley, Fiona; Correia-Melo, Clara; Greaves, Laura; Saretzki, Gabriele; Fox, Chris; Lawless, Conor; Anderson, Rhys; Hewitt, Graeme; Pender, Sylvia L. F.; Fullard, Nicola; Nelson, Glyn; Mann, Jelena; van de Sluis, Bart; Mann, Derek A.; von Zglinicki, Thomas
Chronic inflammation is associated with normal and pathological ageing. Here we show that chronic, progressive low-grade inflammation induced by knockout of the nfkb1 subunit of the transcription factor NF-kappa B induces premature ageing in mice. We also show that these mice have reduced regenerati
Jurk, Diana; Wilson, Caroline; Passos, Joao F.; Oakley, Fiona; Correia-Melo, Clara; Greaves, Laura; Saretzki, Gabriele; Fox, Chris; Lawless, Conor; Anderson, Rhys; Hewitt, Graeme; Pender, Sylvia L. F.; Fullard, Nicola; Nelson, Glyn; Mann, Jelena; van de Sluis, Bart; Mann, Derek A.; von Zglinicki, Thomas
Chronic inflammation is associated with normal and pathological ageing. Here we show that chronic, progressive low-grade inflammation induced by knockout of the nfkb1 subunit of the transcription factor NF-kappa B induces premature ageing in mice. We also show that these mice have reduced regenerati
Experimental Toxoplasmosis in Rats Induced Orally with Eleven Strains of Toxoplasma gondii of Seven Genotypes: Tissue Tropism, Tissue Cyst Size, Neural Lesions, Tissue Cyst Rupture without Reactivation, and Ocular Lesions.
Dubey, Jitender P; Ferreira, Leandra R; Alsaad, Mohammad; Verma, Shiv K; Alves, Derron A; Holland, Gary N; McConkey, Glenn A
The protozoan parasite Toxoplasma gondii is one of the most widely distributed and successful parasites. Toxoplasma gondii alters rodent behavior such that infected rodents reverse their fear of cat odor, and indeed are attracted rather than repelled by feline urine. The location of the parasite encysted in the brain may influence this behavior. However, most studies are based on the highly susceptible rodent, the mouse. Latent toxoplasmosis was induced in rats (10 rats per T. gondii strains) of the same age, strain, and sex, after oral inoculation with oocysts (natural route and natural stage of infection) of 11 T. gondii strains of seven genotypes. Rats were euthanized at two months post inoculation (p.i.) to investigate whether the parasite genotype affects the distribution, location, tissue cyst size, or lesions. Tissue cysts were enumerated in different regions of the brains, both in histological sections as well in saline homogenates. Tissue cysts were found in all regions of the brain. The tissue cyst density in different brain regions varied extensively between rats with many regions highly infected in some animals. Overall, the colliculus was most highly infected although there was a large amount of variability. The cerebral cortex, thalamus, and cerebellum had higher tissue cyst densities and two strains exhibited tropism for the colliculus and olfactory bulb. Histologically, lesions were confined to the brain and eyes. Tissue cyst rupture was frequent with no clear evidence for reactivation of tachyzoites. Ocular lesions were found in 23 (25%) of 92 rat eyes at two months p.i. The predominant lesion was focal inflammation in the retina. Tissue cysts were seen in the sclera of one and in the optic nerve of two rats. The choroid was not affected. Only tissue cysts, not active tachyzoite infections, were detected. Tissue cysts were seen in histological sections of tongue of 20 rats but not in myocardium and leg muscle. This study reevaluated in depth the
Full Text Available In this study, forming of experimental toxoplasmosis in white turkeys; clinical, pathological and serological determination of tissue lesions, aimed to compare them and determine pathogenesis. For these purposes, a total of 120 two months old white turkeys were divided into groups as oral and parenteral infections and also their controls. The oral group was infected with 0.5 mL of Toxoplasma gondii RH strain inoculum suspension contains 106 tachyzoites while its control group was given 0.5 mL of saline. The parenteral group were divided into four groups as intraperitoneal (IP, intramuscular (IM, intravenous (IV and cloacal (C. Each parenteral route was divided into two groups and one control group for inoculums given 105 and 104 tachyzoites in 0.5 mL. These two control groups were also given 0.5 mL saline as indicated above. Due to acute toxoplasmosis, death occurred in three white turkeys given tachyzoites IP 105 showed neurological clinical symptoms as torticollis, ataxia, and tremor. In the histopahologic examination of these three turkeys, T. gondii tissue cysts were detected in the brain. Also, one of given 105 tachyzoites IP group in the brain and one given 104 tachyzoites IV group in the liver were observed tissue cysts associated with toxoplasmosis. The turkeys in all infection groups were found seropositive in both Sabin-Feldman Dye Test (SFDT and Indirect Hemagglutination Test (IHA. The statistical difference between SFDT and IHA was insignificantly for the both parenteral infection groups (P>0.05 while the difference was found significantly for the orally infected group (P<0.05. In conclusion in the present study, the tissue cysts of T. gondii were microscopically seen in brain and liver of the experimental infected white turkeys.
Full Text Available Evidence that prevention, diagnosis and treatment of toxoplasmosis is beneficial developed as follows: anti-parasitic agents abrogate Toxoplasma gondiitachyzoite growth, preventing destruction of infected, cultured, mammalian cells and cure active infections in experimental animals, including primates. They treat active infections in persons who are immune-compromised, limit destruction of retina by replicating parasites and thereby treat ocular toxoplasmosis and treat active infection in the fetus and infant. Outcomes of untreated congenital toxoplasmosis include adverse ocular and neurologic sequelae described in different countries and decades. Better outcomes are associated with treatment of infected infants throughout their first year of life. Shorter intervals between diagnosis and treatment in utero improve outcomes. A French approach for diagnosis and treatment of congenital toxoplasmosis in the fetus and infant can prevent toxoplasmosis and limit adverse sequelae. In addition, new data demonstrate that this French approach results in favorable outcomes with some early gestation infections. A standardized approach to diagnosis and treatment during gestation has not yet been applied generally in the USA. Nonetheless, a small, similar experience confirms that this French approach is feasible, safe, and results in favorable outcomes in the National Collaborative Chicago-based Congenital Toxoplasmosis Study cohort. Prompt diagnosis, prevention and treatment reduce adverse sequelae of congenital toxoplasmosis.
Li, Zhi Hua; Guo, Fu You; Wang, Zhong Quan; Cui, Jing
Toxoplasmosis is a serous parasitic zoonosis caused by the protozoan Toxoplasma gondii worldwide. Human beings acquire the disease by eating infected meat containing T. gondii cysts, by ingesting water or vegetables contaminated with oocysts shed in the feces of an infected cat, and by transmission from mother to fetus. Cerebral toxoplasmosis is one of the most serious complications in immunocompromised individuals such as HIV-infected patients, with a high mortality rate, whereas the incidence of cerebral toxoplasmosis is extremely rare in immunocompetent persons. Due to the low incidence and the high rate of misdiagnosis, cerebral toxoplasmosis was occasionally described in sporadic cases. (1) Furthermore, the diagnosis of cerebral toxoplasmosis is rather difficult because the clinical manifestations are non-specific and are not sufficiently characteristic for a definite diagnosis. It mimics several other infectious diseases or primary central nervous system (CNS) tumor. (2) In the present study, we reported an exceedingly rare cerebral toxoplasmosis with obvious space-occupying lesion occurring in the left temporal lobe of an immunocompetent adult patient. To our knowledge, this is the first report of successful treatment of acquired cerebral toxoplasmosis in China.
L. Yu. Barycheva
Full Text Available We examined 69 infants with clinically manifested forms of congenital toxoplasmosis diagnosed in theStavropolregion in the period from 1992 to 2012. The clinical course was characterized by a predominance of severe forms of congenial toxoplasmosis, high mortality rate (39,1%, predominant damage the central nervous system (100% and adverse neurological outcome. Surviving children developed disabilities at the outcome of congenital toxoplasmosis such as hydrocephaly (71,4%, microcephaly (9,5%, cerebral palsy (52,4%, episindroma (16,7%, mental retardation (19,0 % complete or partial blindness (28,6%.
Full Text Available Although toxoplasmosis is one of the most widely spread infections in the world, types that involve the skin are extremely rare. However, skin lesions are not specific; moreover, they are quite diverse, which makes the diagnosis of cutaneous toxoplasmosis rather difficult. Thus, differential diagnosis should include a number of other diseases. We present a case of a 43-year-old immunocompetent man with multiple livid erythematous papules and nodules with yellowish discharge that involved the skin of the body and the extremities. By using electro-chemiluminescence immunoassay, immunoglobulin G antibodies to Toxoplasma gondii were detected in the serum, confirming the diagnosis of toxoplasmosis. The treatment with pyrimethamine and trimethoprim-sulfamethoxazole led to complete resolution of skin lesions. In conclusion, although rare in the dermatological practice, cutaneous toxoplasmosis should be considered in all patients presenting with lymphadenopathy, non-specific skin eruptions, especially nodular and colliquative, blood eosinophilia and histological findigs revealing abundant eosinophilic inflitrations.
Although toxoplasmosis is one of the most widely spread infections in the world, types that involve the skin are extremely rare. However, skin lesions are not specific; moreover, they are quite diverse, which makes the diagnosis of cutaneous toxoplasmosis rather difficult. Thus, differential diagnosis should include a number of other diseases. We present a case of a 43-year-old immunocompetent man with multiple livid erythematous papules and nodules with yellowish discharge that involved the ...
Toxoplasmosis is a serous parasitic zoonosis caused by the protozoan Toxoplasma gondii worldwide. Human beings acquire the disease by eating infected meat containing T. gondii cysts, by ingesting water or vegetables contaminated with oocysts shed in the feces of an infected cat, and by transmission from mother to fetus. Cerebral toxoplasmosis is one of the most serious complications in immunocompromised individuals such as HIV-infected patients, with a high mortality rate, whereas the inciden...
Cheng, Jiangfei; Lv, Suping; Nie, Shangfei; Liu, Jing; Tong, Shoufang; Kang, Ning; Xiao, Yanyan; Dong, Qiaoxiang [Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms (China); Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou, 325035 (China); Huang, Changjiang, E-mail: firstname.lastname@example.org [Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms (China); Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou, 325035 (China); Yang, Dongren, E-mail: email@example.com [Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms (China); Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou, 325035 (China)
Highlights: • PFOS chronic exposure induces sex-dependent hepatic steotosis in zebrafish. • PFOS interferes with β-oxidation, lipid synthesis, and lipid hepatic export process. • Zebrafish could be used as an alternative model for PFOS chronic toxicity screening. - Abstract: Perfluorooctane sulfonate (PFOS), one persistent organic pollutant, has been widely detected in the environment, wildlife and human. Currently few studies have documented the effects of chronic PFOS exposure on lipid metabolism, especially in aquatic organisms. The underlying mechanisms of hepatotoxicity induced by chronic PFOS exposure are still largely unknown. The present study defined the effects of chronic exposure to low level of PFOS on lipid metabolism using zebrafish as a model system. Our findings revealed a severe hepatic steatosis in the liver of males treated with 0.5 μM PFOS as evidenced by hepatosomatic index, histological assessment and liver lipid profiles. Quantitative PCR assay further indicated that PFOS significantly increase the transcriptional expression of nuclear receptors (nr1h3, rara, rxrgb, nr1l2) and the genes associated with fatty acid oxidation (acox1, acadm, cpt1a). In addition, chronic PFOS exposure significantly decreased liver ATP content and serum level of VLDL/LDL lipoprotein in males. Taken together, these findings suggest that chronic PFOS exposure induces hepatic steatosis in zebrafish via disturbing lipid biosynthesis, fatty acid β-oxidation and excretion of VLDL/LDL lipoprotein, and also demonstrate the validity of using zebrafish as an alternative model for PFOS chronic toxicity screening.
Full Text Available Vascular endothelial growth factor (VEGF, epidermal growth factor (EGF and monocyte chemotactic protein-1 (MCP-1 have previously been suggested to be potential biomarkers for chronic stress induced exhaustion. The knowledge about VEGF has increased during the last decades and supports the contention that VEGF plays an important role in stress and depression. There is scarce knowledge on the possible relationship of EGF and MCP-1 in chronic stress and depression. This study further examines the role of VEGF, EGF and MCP-1 in women with chronic stress induced exhaustion and healthy women during a follow-up period of two years.Blood samples were collected from 105 women with chronic stress induced exhaustion on at least 50% sick leave for at least three months, at inclusion (T0, after 12 months (T12 and after 24 months (T24. Blood samples were collected at inclusion (T0 in 116 physically and psychiatrically healthy women. The plasma levels of VEGF, EGF and MCP-1 were analyzed using Biochip Array Technology. Women with chronic stress induced exhaustion had significantly higher plasma levels of VEGF and EGF compared to healthy women at baseline, T12 and at T24. There was no significant difference in plasma levels of MCP-1. Plasma levels of VEGF and EGF decreased significantly in women with chronic stress induced exhaustion during the two years follow-up.The replicated findings of elevated levels of VEGF and EGF in women with chronic stress induced exhaustion and decreasing plasma levels of VEGF and EGF during the two years follow-up add important knowledge to the pathophysiology of chronic stress induced exhaustion.
Bautista, G; Ramos, A; Forés, R; Regidor, C; Ruiz, E; de Laiglesia, A; Navarro, B; Bravo, J; Portero, F; Sanjuan, I; Fernández, M N; Cabrera, R
Toxoplasmosis is a devastating opportunistic infection that can affect immunocompromised patients such as cord blood transplantation (CBT) recipients. The clinical characteristics of 4 toxoplasmosis CBT patients treated at our institution are reviewed, together with 5 cases collected from the literature. The rate of toxoplasmosis in our hospital was 6% in CBT recipients and 0.2% in other types of allogeneic hematopoietic stem cell transplantation (P < 0.001). Five patients (56%) presented disseminated toxoplasmosis and 4 patients (44%) had localized infection in the central nervous system. In 5 of the 9 patients considered (56%), cytomegalovirus viral replication had been detected before the clinical onset of toxoplasmosis. Seven patients (78%) had previously developed graft-versus-host disease. All patients who exhibited disseminated disease died due to Toxoplasma infection. Pre-transplant serology was positive in 1 patient, negative in 3 patients, and not performed in another. Only 1 of these 5 patients with disseminated disease had received Toxoplasma prophylaxis with cotrimoxazole. It could be concluded that mortality in CBT patients with disseminated toxoplasmosis is unacceptably high. The negative results of serology in the majority of these cases, and its unspecific clinical presentation, makes diagnosis exceedingly difficult. Better diagnostic tests and prophylaxis strategy are needed in CBT recipients.
Chicharro, P; Rodríguez, P; de Argila, D
Omalizumab is a recombinant humanized monoclonal antibody that inhibits immunoglobulin E. It has been approved for the treatment of severe asthma and chronic spontaneous urticaria refractory to other treatments. Its use in the management of chronic inducible urticaria (a type triggered by certain stimuli) is still considered off-label, although this use has been discussed in some consensus papers. This review brings together case reports and case series describing the use of omalizumab to treat chronic inducible urticaria. We analyze the most important aspects of the cases and the outcomes reported. The results seem to position omalizumab as a potentially effective, safe treatment alternative in some cases of chronic inducible urticaria. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.
Sepúlveda-Arias, Juan C; Gómez-Marin, Jorge E; Bobić, Branko; Naranjo-Galvis, Carlos A; Djurković-Djaković, Olgica
Toxoplasma gondii is a protozoan parasite with worldwide distribution that infects more than one third of the global population. Primary infection in immunocompetent individuals is usually asymptomatic; however, different organs can be affected in immunocompromised individuals leading to the development of encephalitis, myocarditis or pneumonitis. The prevalence of infection with Toxoplasma as well as its genetic structure varies geographically and for that reason travel may be considered as a risk factor to acquire the infection. As toxoplasmosis is a foodborne disease, health care providers should give health education on prevention measures to all prospective travelers in order to decrease the risk of infection in endemic areas. This review presents an overview of the infection with T. gondii with some considerations for travelers to and from endemic zones.
... preventing this condition: Do not eat undercooked meat. Wash hands after handling raw meat. Keep children's play areas free from cat and dog feces. Wash your hands thoroughly after touching soil that may be contaminated ...
... the Neglected Parasitic Infections , a group of five parasitic diseases that have been targeted by CDC for public ... 10, 2013 Content source: Global Health - Division of Parasitic Diseases Email Recommend Tweet YouTube Instagram Listen Watch RSS ...
Mangot, Ajish G
Toxoplasma gondii is one of the well-studied parasites because of its medical and veterinary importance, and its suitability as a model for cell biology and molecular studies. Latent toxoplasmosis in an immunocompetent host was considered benign until recently. The importance of this parasite has been steadily rising in the field of psychiatry and neurology as it has been implicated in numerous neuropsychiatric disorders. Researchers in India have unfortunately restricted themselves to finding the prevalence of toxoplasma antibodies in special populations and animals. On the other hand, there has been increasing research interest worldwide in T. gondii for its effects on human behaviour, manifestations of which range from psychoses and neuroses to Alzheimer's and Parkinson's disease. Toxoplasma infected organisms may be akin to living zombies. From changing the core natural defensive behaviour in mice to changing personality & leading to neuropsychiatric disorders in humans, Toxoplasma brings about subtle but significant & specific changes in its host. Surprisingly there is severe dearth of such studies from India even though prevalence rates of latent Toxoplasma infection are comparable, or in some regions, higher to those found elsewhere in the world. The potential for identifying Toxoplasma induced behavioural alterations is enormous in this part of the world which could have future treatment implications. It's high time that we move beyond researching the obvious and involve ourselves in more rigorous, novel and stimulating studies in the future.
Götze, Sebastian; Azzouz, Nahid; Tsai, Yu-Hsuan; Groß, Uwe; Reinhardt, Anika; Anish, Chakkumkal; Seeberger, Peter H; Varón Silva, Daniel
Around 2 billion people worldwide are infected with the apicomplexan parasite Toxoplasma gondii which induces a variety of medical conditions. For example, primary infection during pregnancy can result in fetal death or mental retardation of the child. Diagnosis of acute infections in pregnant women is challenging but crucially important as the drugs used to treat T. gondii infections are potentially harmful to the unborn child. Better, faster, more reliable, and cheaper means of diagnosis by using defined antigens for accurate serological tests are highly desirable. Synthetic pathogen-specific glycosylphosphatidylinositol (GPI) glycan antigens are diagnostic markers and have been used to distinguish between toxoplasmosis disease states using human sera.
Toxoplasmosis has gained particular attention in the AIDS era as the most common opportunistic encephalitis in HIV-infected patients. Since there are important parallels between the human and rodent infection, experimental murine toxoplasmosis is widely used to study the immune reactions to this protozoal parasite. Oral application of low-virulent Toxoplasma (T.) gondii cysts leads to a biphasic disease characterized by an acute, generalized phase followed by a chronic stage confined to the brain, where an encephalitis with persistence of the parasite develops. Immunity to T. gondii is T cell mediated, and there is increasing evidence for a critical role of cytokines for an effective immune response. In order to address the functional role of interferon (IFN)-gamma in toxoplasmosis, we took advantage of mice lacking the IFN-gamma-receptor. Inactivation of the IFN-gamma-receptor rendered mice highly susceptible to T. gondii, and they died of a fulminant acute toxoplasmosis. Among the various organs affected, hepatitis was severe enough to cause death. In contrast to wild type animals, IFN-gamma-receptor-deficient mice were unable to activate their macrophages as evidenced by a lack of major histocompatibility complex (MHC) class II antigen induction and the absence of an upregulation of tumor necrosis factor (TNF)-alpha and inducible nitric oxide synthase (iNOS) mRNA transcripts, two macrophage effector molecules. These observations prompted the investigation of TNF- and TNF-receptor-mediated effects in toxoplasmosis by use of mice deficient in either the TNF-receptor type 1 (TNFR1) and/or the TNF-receptor type 2 (TNFR2). The lethal outcome of T. gondii-infected TNFR1/2- and TNFR1-deficient mice, but not of TNFR2-deficient and wild type animals, illustrated the important role of TNF-alpha and TNFR1-mediated signalling, respectively, in this infection. Histopathology attributed death of TNFR1- and TNFR1/2-deficient mice to a severe, necrotizing encephalitis
Full Text Available Se observan complicaciones neurológicas en 40% de enfermos con SIDA. De estos, en 10% puede ser la manifestation inicial de la enfermedad. En otro 11% pueden aparecer trastornos del movimiento. Comunicamos el primer caso de hemicorea asociada a toxoplasmosis cerebral y SIDA en nuestro pais. Hombre de 26 anos, con diagnostico de SIDA y toxoplasmosis cerebral. Habia comenzado con crisis motoras simples de hemicuerpo izquierdo, con generalization secundaria y luego perdida de fuerza progresiva en dicho hemicuerpo. La RMN de cérebro mostro una lesion frontal derecha y otra temporo-occipital izquierda, con gran edema perilesional y efecto de masa. Las serologias para HIV y toxoplasmosis fueron positivas. Comenzo tratamiento con sulfadiazina y pirimetamina. Al duodecimo dia aparecieron movimientos involuntários dei pie izquierdo, coreicos, que se extendieron mas tarde a todo ese miembro inferior y luego al hemicuerpo. Nueva RMN de cérebro mostro disminucion dei edema y efecto de masa de las lesiones. Sin embargo, se observo una nueva lesion a nivel peduncular derecho. Movimientos involuntarios en pacientes con toxoplasmosis cerebral comenzaron a describirse recientemente solo en pacientes con SIDA. El presente seria el decimotercer caso de la literatura mundial y el primero en nuestro pais de hemicorea asociada a toxoplasmosis y SIDA.
Matowicka-Karna, Joanna; Kemona, Halina
Toxoplasmosis is a worldwide infection caused by the intracellular parasite Toxoplasma gondii. At least a third of the world human population is infected with the parasite, making it one of the most successful parasitic infections. Primary maternal infection may cause health-threatening sequelae for the fetus, or even cause death of the uterus. Reactivation of a latent infection in immune deficiency conditions such as AIDS and organ transplantation can cause fatal toxoplasmic encephalitis. Toxoplasmosis is a major cause of chorioretinitis, especially in individuals with impaired immune systems. In the acute phase, directly after invading the body, T. gondii begins to multiply rapidly. In the majority of cases acquired toxoplasmosis is asymptomatic. In the second week of infection, specific IgM antibodies are present in the blood. IgE antibodies appear at the same time, slightly preceding specific IgA antibodies. The concentration of IgE can be one of the parameters used for diagnosing an infection with T. gondii. Laboratory diagnosis, i.e. IgE and serologic assays, plays the main role in the diagnosis of congenital infection and assists in the confirmatory diagnosis of toxoplasmic encephalitis and ocular toxoplasmosis. This article is a review of IgE in toxoplasmosis.
Kaneto, C N; Costa, A J; Paulillo, A C; Moraes, F R; Murakami, T O; Meireles, M V
To evaluate chicken toxoplasmosis both as an economic and a public health subject, 84 broiler chicks of a commercial strain, 30 days old, were distributed into seven groups of 12 birds (three replications of four chicks) experimentally infected with three developing T. gondii stages of the P strain as follows: tachyzoites, intravenous (two groups: 5.0 x 10(5) and 5.0 x 10(6)), cysts, per os (two groups: 1.0 x 10(2) and 1.0 x 10(3)) and oocysts, per os (three groups: 5.0 x 10(2), 5.0 x 10(3) and 5.0 x 10(4)). Twelve chicks received only a placebo (control group). During the next 30 days the following parameters were estimated: productivity (weight gain and feed conversion), clinical signs, including rectal temperature and parasitemia (bioassay). No clinical signs suggesting toxoplasmosis were seen and no statistical differences on productivity standards were found in comparison between inoculated and control chicks. However, fowls inoculated with tachyzoites and oocysts occasionally showed hyperthermia. Some haematological changes were detected in fowls inoculated with T. gondii. Anatomo-histopathological changes were not observed. From 14 parasitemias detected, 35.7% appeared on the 5th day after inoculation and 57.1% of them resulted from oocysts inoculation. After 30-35 days all birds were slaughtered: fragments from 12 organs or tissues from each of them were subjected to artificial peptic digestion and after that injected into T. gondii antibody-free mice (IIFR). T. gondii was detected in brain (12), pancreas (five), spleen (five), retina (five), kidney (two), heart (four), proventriculus (three), liver (two), intestine (two), lung (one), and skeletal muscle (one). Similar to observations with parasitemia, from 42 T. gondii isolations, 59.5% came from chicks which had received oocysts. It can thus be inferred that the developing form, expelled by cats, is the most important for T. gondii chicken infection and that brain is the most infected organ in birds
Lantz, O; Jouvin, M H; De Vernejoul, M C; Druet, P
Renal fluoride toxicity in human beings is difficult to assess in the literature. Although experimental studies and research on methoxyflurane toxicity have shown frank renal damage, observations of renal insufficiency related to chronic fluoride exposure are scarce. We report a case of fluoride intoxication related to potomania of Vichy water, a highly mineralized water containing 8.5 mg/L of fluoride. Features of fluoride osteosclerosis were prominent and end-stage renal failure was present. The young age of the patient, the long duration of high fluoride intake, and the absence of other cause of renal insufficiency suggest a causal relationship between fluoride intoxication and renal failure.
Zun Xiang; Jian-Min Si; Huai-De Huang
AIM: To establish an experimental animal model of chronic gastritis in a short term and to investigate the effects of several potential inflammation-inducing factors on rat gastric mucosa.METHODS: Twenty-four healthy, male SD rats were treated with intragastric administration of 600 mL/L alcohol, 20mmol/L sodium deoxycholate and 0.5 g/L ammonia (factor A), forage containing low levels of vitamins (factor B), and/or indomethacin (factor C), according to an L8(27)orthogonal design. After 12 wk, gastric antral and body mucosae were pathologically examined.RESULTS: Chronic gastritis model was successfully induced in rats treated with factor A for 12 wk. After the treatment of animals, the gastric mucosal inflammation was significantly different from that in controls, and the number of pyloric glands at antrum and parietal cells at body were obviously reduced (P＜0.01). Indomethacin induced gastritis but without atrophy, and short-term vitamin deficiency failed to induce chronic gastritis and gastric atrophy, In addition,indomethacin and vitamin deficiency had no synergistic effect in inducing gastritis with the factor A. No atypical hyperplasia and intestinal metaplasia in the gastric antrum and body were observed in all rats studied.CONCLUSION: Combined intragastric administration of 600 mL/L alcohol, 20 mmol/L sodium deoxycholate and 0.5 g/L ammonia induces chronic gastritis and gastric atrophy in rats. Indomethacin induces chronic gastritis only.The long-term roles of these factors in gastric inflammation and carcinogenesis need to be further elucidated.
Varicella occurring in pregnancy can be dangerous for the fetus, the mother, and the newborn. The fetus may experience multiple system damage. The mother and newborn are at increased risk for varicella pneumonia with a 9% and 20% fatality rate, respectively. The recent introduction of the varicella vaccine will affect the occurrence of gestational infection. Toxoplasmosis is rarely dangerous for the pregnant woman, yet the fetus and newborn may be at risk for chorioretinitis, hydrocephalus, intracranial calcifications, and convulsions. The greatest challenge in the management of toxoplasmosis in pregnancy is diagnosis of the asymptomatic newborn before damage occurs. Strategies to prevent toxoplasmosis should be taught to every pregnant woman as part of parental care.
Toxoplasma gondii is a globally distributed parasite that infects all mammals, including one third of the world population. Long known to cause disease in the developing foetus and in immunosuppressed individuals, a body of data that has emerged in the past decades suggests its role in human pathology may be even more important. The WHO and FAO have recently established toxoplasmosis as a foodborne infection of global concern, with a disease burden the greatest of all parasitic infections. Transmission of toxoplasmosis occurs by ingesting tissue cysts from undercooked meat and meat products, and oocysts from the environment with contaminated fresh produce or water. This review provides an update on the current understanding of toxoplasmosis, focusing on the risk of infection from food of animal origin, with particular reference to the risk in Serbia and the region of South-East Europe.
G. V. Celano
Full Text Available Toxoplasmosis, parasitic pathology supported by Toxoplasma gondii, is a typical example of multi-issue and inter-disciplinary on which, with equal intensity, converge the interests of various branches of human and veterinary medicine. The aim of research was the assessment of risk communication to pregnant women by doctors gynecologists involved in ASL’s territorial about toxoplasmosis, which can have serious effects on pregnancy and the unborn child. The results acquired during the investigation showed the need to develop and implement appropriate information campaigns and proper nutrition education.
Dubey, J P
Toxoplasma gondii affects most species of warm-blooded animals, including birds. There is considerable confusion regarding the identity of T. gondii-like parasites and the diagnosis of toxoplasmosis in wild birds. In this review, T. gondii-like infections in different species of wild birds are reviewed with particular reference to prevalences, clinical signs, pathology, diagnosis, and treatment. Although subclinical T. gondii infections are prevalent in many avian species, toxoplasmosis can be clinically severe in pigeons and canaries. Blindness associated with T. gondii in canaries is reviewed in detail.
Stec, S; Dabrowska, M; Zaborska, B; Bielicki, P; Maskey-Warzechowska, M; Tarnowski, W; Chazan, R; Kulakowski, P
The present case study reports a case of chronic cough and cough syncope associated with frequent premature ventricular complexes (PVCs). Careful analysis of cough-related symptoms and ECG monitoring led to the suspicion of PVC-induced cough. A coincidence between PVCs and episodes of cough was also documented by a portable multichannel recorder. Moreover, Doppler echocardiography revealed a PVC-induced transient increase in the pulmonary artery blood flow. After exclusion of other possible aetiologies, complete relief of chronic cough and cough syncope was achieved by radiofrequency ablation of the arrhythmogenic focus located in the right ventricular outflow tract. Premature ventricular complexes should be considered as a cause of chronic cough and cough syncope and an interdisciplinary cooperation can lead to successful diagnosis and treatment of this condition.
Full Text Available Mateusz Spałek Department of Radiotherapy I, The Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland Abstract: Chronic radiation dermatitis is a late side effect of skin irradiation, which may deteriorate patients’ quality of life. There is a lack of precise data about its incidence; however, several risk factors may predispose to the development of this condition. It includes radiotherapy dose, fractionation, technique, concurrent systemic therapy, comorbidities, and personal and genetic factors. Chronic radiation dermatitis is mostly caused by the imbalance of proinflammatory and profibrotic cytokines. Clinical manifestation includes changes in skin appearance, wounds, ulcerations, necrosis, fibrosis, and secondary cancers. The most severe complication of irradiation is extensive radiation-induced fibrosis (RIF. RIF can manifest in many ways, such as skin induration and retraction, lymphedema or restriction of joint motion. Diagnosis of chronic radiation dermatitis is usually made by clinical examination. In case of unclear clinical manifestation, a biopsy and histopathological examination are recommended to exclude secondary malignancy. The most effective prophylaxis of chronic radiation dermatitis is the use of proper radiation therapy techniques to avoid unnecessary irradiation of healthy skin. Treatment of chronic radiation dermatitis is demanding. The majority of the interventions are based only on clinical practice. Telangiectasia may be treated with pulse dye laser therapy. Chronic postirradiation wounds need special dressings. In case of necrosis or severe ulceration, surgical intervention may be considered. Management of RIF should be complex. Available methods are rehabilitative care, pharmacotherapy, hyperbaric oxygen therapy, and laser therapy. Future challenges include the assessment of late skin toxicity in modern irradiation techniques. Special attention should be paid on genomics and
Summary Narcolepsy is a chronic neurological disorder, characterized by uncontrollable excessive daytime sleepiness, cataplectic episodes, sleep paralysis, hypnagogic hallucinations, and night time sleep disruption. The paper reviewed the related literature and reported a case of long-term drinking induced narcolepsy which was significantly improved after treatment with paroxetine and dexzopiclone.
Herman, S E M; Niemann, C U; Farooqui, M
Ibrutinib and other targeted inhibitors of B-cell receptor signaling achieve impressive clinical results for patients with chronic lymphocytic leukemia (CLL). A treatment-induced rise in absolute lymphocyte count (ALC) has emerged as a class effect of kinase inhibitors in CLL and warrants further...
Dubey, J P; Hotea, I; Olariu, T R; Jones, J L; Dărăbuş, G
Infections by the protozoan parasite Toxoplasma gondii are widely prevalent in humans and other animals worldwide. However, information from eastern European countries is sketchy. In many eastern European countries, including Romania, it has been assumed that chronic T. gondii infection is a common cause of infertility and abortion. For this reason, many women in Romania with these problems were needlessly tested for T. gondii infection. Most papers on toxoplasmosis in Romania were published in Romanian in local journals and often not available to scientists in other countries. Currently, the rate of congenital infection in Romania is largely unknown. In addition, there is little information on genetic characteristics of T. gondii or prevalence in animals and humans in Romania. In the present paper we review prevalence, clinical spectrum and epidemiology of T. gondii in humans and animals in Romania. This knowledge should be useful to biologists, public health workers, veterinarians and physicians.
Meroni, V; Genco, F
Toxoplasmosis in pregnancy is usually subclinic or associated with non specific symptoms. Diagnosis and timing of infection are usually based on serological tests. In this short review we tried to summarize the serological patterns we can encounter and to discuss the interpretation of test results.
... a s t is O : wAnneIrmsportant What role do cats play in the spread of toxoplasmosis? Cats get Toxoplasma infection by eating infected rodents, birds ... animals, or anything contaminated with feces from another cat that is shedding the microscopic parasite in its ...
M.A.E. Conyn-van Spaendock (Marina)
textabstractIn this thesis the results of a large-scale study of preventive measures against toxoplasma infections in pregnant women are reported. Literature on Toxoplasma gondii, toxoplasma infections and toxoplasmosis is discussed in chapter 1. Special attention is directed toward the epidemiologi
Bossart, Gregory D.; Mignucci-Ginannoni, Antonio A.; Rivera-Guzman, Antonio L.; Jimenez-Marrero, Nilda M.; Camus, Alvin C.; Bonde, Robert K.; Dubey, Jitender P.; Reif, John S.
Necropsies were conducted on 4 Antillean manatees Trichechus manatus manatus that were stranded in single events on the coastal beaches of Puerto Rico from August 2010 to August 2011. Three manatees were emaciated and the gastrointestinal tracts were devoid of digesta. Microscopically, all manatees had severe widespread inflammatory lesions of the gastrointestinal tract and heart with intralesional tachyzoites consistent with Toxoplasma gondii identified by histological, ultrastructural and immunohistochemical techniques. The gastrointestinal lesions included severe, multifocal to diffuse, chronic-active enteritis, colitis and/or gastritis often with associated ulceration, necrosis and hemorrhage. Enteric leiomyositis was severe and locally extensive in all cases and associated with the most frequently observed intralesional protozoans. Moderate to severe, multifocal, chronic to chronic-active, necrotizing myocarditis was also present in all cases. Additionally, less consistent inflammatory lesions occurred in the liver, lung and a mesenteric lymph node and were associated with fewer tachyzoites. Sera (n = 30) collected from free-ranging and captive Puerto Rican manatees and a rehabilitated/released Puerto Rican manatee from 2003 to 2012 were tested for antibodies for T. gondii. A positive T. gondii antibody titer was found in 2004 in 1 (3%) of the free-ranging cases tested. Disease caused by T. gondii is rare in manatees. This is the first report of toxoplasmosis in Antillean manatees from Puerto Rico. Additionally, these are the first reported cases of disseminated toxoplasmosis in any sirenian. The documentation of 4 cases of toxoplasmosis within one year and the extremely low seroprevalence to T. gondiisuggest that toxoplasmosis may be an emerging disease in Antillean manatees from Puerto Rico.
Bossart, Gregory D; Mignucci-Giannoni, Antonio A; Rivera-Guzman, Antonio L; Jimenez-Marrero, Nilda M; Camus, Alvin C; Bonde, Robert K; Dubey, Jitender P; Reif, John S
Necropsies were conducted on 4 Antillean manatees Trichechus manatus manatus that were stranded in single events on the coastal beaches of Puerto Rico from August 2010 to August 2011. Three manatees were emaciated and the gastrointestinal tracts were devoid of digesta. Microscopically, all manatees had severe widespread inflammatory lesions of the gastrointestinal tract and heart with intralesional tachyzoites consistent with Toxoplasma gondii identified by histological, ultrastructural and immunohistochemical techniques. The gastrointestinal lesions included severe, multifocal to diffuse, chronic-active enteritis, colitis and/or gastritis often with associated ulceration, necrosis and hemorrhage. Enteric leiomyositis was severe and locally extensive in all cases and associated with the most frequently observed intralesional protozoans. Moderate to severe, multifocal, chronic to chronic-active, necrotizing myocarditis was also present in all cases. Additionally, less consistent inflammatory lesions occurred in the liver, lung and a mesenteric lymph node and were associated with fewer tachyzoites. Sera (n = 30) collected from free-ranging and captive Puerto Rican manatees and a rehabilitated/released Puerto Rican manatee from 2003 to 2012 were tested for antibodies for T. gondii. A positive T. gondii antibody titer was found in 2004 in 1 (3%) of the free-ranging cases tested. Disease caused by T. gondii is rare in manatees. This is the first report of toxoplasmosis in Antillean manatees from Puerto Rico. Additionally, these are the first reported cases of disseminated toxoplasmosis in any sirenian. The documentation of 4 cases of toxoplasmosis within one year and the extremely low seroprevalence to T. gondii suggest that toxoplasmosis may be an emerging disease in Antillean manatees from Puerto Rico.
Stock, Ann-Kathrin; Dajkic, Danica; Köhling, Hedda Luise; von Heinegg, Evelyn Heintschel; Fiedler, Melanie; Beste, Christian
Latent infection with Toxoplasma gondii has repeatedly been shown to be associated with behavioral changes that are commonly attributed to a presumed increase in dopaminergic signaling. Yet, virtually nothing is known about its effects on dopamine-driven reward processing. We therefore assessed behavior and event-related potentials in individuals with vs. without latent toxoplasmosis performing a rewarded control task. The data show that otherwise healthy young adults with latent toxoplasmosis show a greatly diminished response to monetary rewards as compared to their non-infected counterparts. While this selective effect eliminated a toxoplasmosis-induced speed advantage previously observed for non-rewarded behavior, Toxo-positive subjects could still be demonstrated to be superior to Toxo-negative subjects with respect to response accuracy. Event-related potential (ERP) and source localization analyses revealed that this advantage during rewarded behavior was based on increased allocation of processing resources reflected by larger visual late positive component (LPC) amplitudes and associated activity changes in the right temporo-parietal junction (BA40) and left auditory cortex (BA41). Taken together, individuals with latent toxoplasmosis show superior behavioral performance in challenging cognitive control situations but may at the same time have a reduced sensitivity towards motivational effects of rewards, which might be explained by the presumed increase in dopamine.
Full Text Available Subramaniam Suresh1, Saidin Nor-Masniwati1, Muhd Nor Nor-Idahriani1, Wan-Hitam Wan-Hazabbah1, Mohamed Zeehaida2, Embong Zunaina11Department of Ophthalmology, 2Department of Medical Microbiology and Parasitology, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, MalaysiaBackground: The purpose of this study was to evaluate the immunoglobulin (Ig G avidity of serological toxoplasmosis testing in patients with ocular inflammation and to determine the clinical manifestations of ocular toxoplasmosis.Methods: A retrospective review of all patients presenting with ocular inflammation to the Hospital Universiti Sains Malaysia, Kelantan, Malaysia between 2005 and 2009 was undertaken. Visual acuity, clinical manifestations at presentation, toxoplasmosis antibody testing, and treatment records were analyzed.Results: A total of 130 patients with ocular inflammation were reviewed retrospectively. The patients had a mean age of 38.41 (standard deviation 19.24, range 6–83 years. Seventy-one patients (54.6% were found to be seropositive, of whom five (3.8% were both IgG and IgM positive (suggestive of recently acquired ocular toxoplasmosis while one (0.8% showed IgG avidity ≤40% (suggestive of recently acquired ocular toxoplasmosis and 65 patients (50.0% showed IgG avidity >40% (suggestive of reactivation of toxoplasmosis infection. Chorioretinal scarring as an ocular manifestation was significantly more common in patients with seropositive toxoplasmosis (P = 0.036. Eighteen patients (13.8% were diagnosed as having recent and/or active ocular toxoplasmosis based on clinical manifestations and serological testing.Conclusion: Ocular toxoplasmosis is a clinical diagnosis, but specific toxoplasmosis antibody testing helps to support the diagnosis and to differentiate between reactivation of infection and recently acquired ocular toxoplasmosis.Keywords: ocular toxoplasmosis, chorioretinal scar, toxoplasmosis antibody, IgG avidity test
Meira, Cristina da Silva; Pereira-Chioccola, Vera Lucia; Vidal, José Ernesto; Motoie, Gabriela; Costa-Silva, Thaís Alves da; Gava, Ricardo
This study was to follow IFN-γ, TNF-α and IL-10 modulation of peripheral blood mononuclear cells (PBMC) from HIV/cerebral toxoplasmosis patients (CT) during specific treatment. The results were compared with two other groups: HIV patients that had CT at least one year before (P/CT) and individuals with chronic toxoplasmosis (CHR). Blood samples (63) collected from three groups were analyzed. CT, 15 patients (3 blood samples collected one day before Toxoplasma gondii treatment; 7 and 15days during the treatment). P/CT, 5 patients (one blood sample collected at least, one year after the treatment). CHR, 13 individuals with chronic toxoplasmosis (one blood sample). Cytokine levels were assessed by ELISA after PBMC stimulation with T. gondii antigen. CT patients had low IFN-γ; discrete increase at 7th and 15th days; and the levels were recovered in cured patients (P/CT). CT patients had high TNF-α in the beginning of the treatment. TNF-α levels decrease during the treatment (7th and 15th) and in those patients who were treated (P/CT). IL-10 levels were almost similar in CT and P/CT groups but low when compared with CHR individuals. The evolution of the infection was correlated to restoration of IFN-γ response and a decrease of the inflammation. The evaluation of the immune response can provide valuable information and better monitoring of patients during specific treatment.
The immune system plays an important role in the pathogenesis of periodontal diseases. The host may modulate periodontal inflammatory reactions and it determines variances in the individual susceptibility and in the periodontal disease progression speed. Osteoporosis and alcoholism are described as risk indicators of periodontal disease among the systemic acquired factors. Objective: The current study aims to analyze chronic alcohol consumption influence on induced periodontitis in rats prese...
Schneider, Claudia; Döcke, Wolf-Dietrich F; Zollner, Thomas M; Röse, Lars
Due to the steadily increasing incidence of atopic dermatitis (AD), especially in children, there is a high medical need for new therapies and improved animal models. In mice, trimellitic anhydride (TMA) is routinely used to trigger T-cell-dependent contact hypersensitivity (CHS) reactions. In this study, we compared the standard acute TMA-induced CHS in Balb/c mice with subacute and chronic models of TMA-induced ear inflammation. Compared to the acute model, the chronic CHS model more closely reflects characteristics of AD, such as typical morphological changes of the inflamed skin, strong infiltration with T cells, major histocompatibility complex II-positive cells, eosinophils, and mast cells, a T-helper cell-type (Th) 2 cytokine profile and a strong increase of serum IgE levels. Moreover, a strong lymph node involvement with T-helper cell dominance and a mixed Th1/Th2 T-cell differentiation and activation pattern was demonstrated. Importantly, as demonstrated by successful therapy with prednisolone, the chronic TMA-induced CHS model, in contrast to acute and subacute models, made prolonged therapeutic treatment of a pre-established skin inflammation possible. Altogether, we present an improved model of mouse T-cell-dependent skin inflammation for AD. We hope this model will enhance the predictive value of animal models for therapeutic treatment of atopic eczema.
Full Text Available P Holland Alday,1 Joseph Stone Doggett1,2 1Division of Infectious Diseases, Oregon Health & Science University, 2Portland Veterans Affairs Medical Center, Portland, OR, USA Abstract: Toxoplasma gondii causes fatal and debilitating brain and eye diseases. Medicines that are currently used to treat toxoplasmosis commonly have toxic side effects and require prolonged courses that range from weeks to more than a year. The need for long treatment durations and the risk of relapsing disease are in part due to the lack of efficacy against T. gondii tissue cysts. The challenges for developing a more effective treatment for toxoplasmosis include decreasing toxicity, achieving therapeutic concentrations in the brain and eye, shortening duration, eliminating tissue cysts from the host, safety in pregnancy, and creating a formulation that is inexpensive and practical for use in resource-poor areas of the world. Over the last decade, significant progress has been made in identifying and developing new compounds for the treatment of toxoplasmosis. Unlike clinically used medicines that were repurposed for toxoplasmosis, these compounds have been optimized for efficacy against toxoplasmosis during preclinical development. Medicines with enhanced efficacy as well as features that address the unique aspects of toxoplasmosis have the potential to greatly improve toxoplasmosis therapy. This review discusses the facets of toxoplasmosis that are pertinent to drug design and the advances, challenges, and current status of preclinical drug research for toxoplasmosis. Keywords: Toxoplasma gondii, therapeutics, preclinical medicine, experimental medicine, mechanism of action, Apicomplexa
Alday, P Holland; Doggett, Joseph Stone
Toxoplasma gondii causes fatal and debilitating brain and eye diseases. Medicines that are currently used to treat toxoplasmosis commonly have toxic side effects and require prolonged courses that range from weeks to more than a year. The need for long treatment durations and the risk of relapsing disease are in part due to the lack of efficacy against T. gondii tissue cysts. The challenges for developing a more effective treatment for toxoplasmosis include decreasing toxicity, achieving therapeutic concentrations in the brain and eye, shortening duration, eliminating tissue cysts from the host, safety in pregnancy, and creating a formulation that is inexpensive and practical for use in resource-poor areas of the world. Over the last decade, significant progress has been made in identifying and developing new compounds for the treatment of toxoplasmosis. Unlike clinically used medicines that were repurposed for toxoplasmosis, these compounds have been optimized for efficacy against toxoplasmosis during preclinical development. Medicines with enhanced efficacy as well as features that address the unique aspects of toxoplasmosis have the potential to greatly improve toxoplasmosis therapy. This review discusses the facets of toxoplasmosis that are pertinent to drug design and the advances, challenges, and current status of preclinical drug research for toxoplasmosis. PMID:28182168
Song, Dongmei; Fang, Guoqiang; Greenberg, Harly; Liu, Shu Fang
Obstructive sleep apnea (OSA) is highly prevalent in the USA and is recognized as an independent risk factor for atherosclerotic cardiovascular disease. Identification of atherosclerosis risk factor attributable to OSA may provide opportunity to develop preventive measures for cardiovascular risk reduction. Chronic intermittent hypoxia (CIH) is a prominent feature of OSA pathophysiology and may be a major mechanism linking OSA to arteriosclerosis. Animal studies demonstrated that CIH exposure facilitated high-cholesterol diet (HCD)-induced atherosclerosis, accelerated the progression of existing atherosclerosis, and induced atherosclerotic lesions in the absence of other atherosclerosis risk factors, demonstrating that CIH is an independent causal factor of atherosclerosis. Comparative studies revealed major differences between CIH-induced and the classic HCD-induced atherosclerosis. Systemically, CIH was a much weaker inducer of atherosclerosis. CIH and HCD differentially activated inflammatory pathways. Histologically, CIH-induced atherosclerotic plaques had no clear necrotic core, contained a large number of CD31+ endothelial cells, and had mainly elastin deposition, whereas HCD-induced plaques had typical necrotic cores and fibrous caps, contained few endothelial cells, and had mainly collagen deposition. Metabolically, CIH caused mild, but HCD caused more severe dyslipidemia. Mechanistically, CIH did not, but HCD did, cause macrophage foam cell formation. NF-κB p50 gene deletion augmented CIH-induced, but not HCD-induced atherosclerosis. These differences reflect the intrinsic differences between the two types of atherosclerosis in terms of pathological nature and underlying mechanisms and support the notion that CIH-induced atherosclerosis is a new paradigm that differs from the classic HCD-induced atherosclerosis.
Alzoubi, Karem H; Khabour, Omar F; Albawaana, Amal S; Alhashimi, Farah H; Athamneh, Rabaa Y
Sleep deprivation is associated with oxidative stress that causes learning and memory impairment. Tempol is a nitroxide compound that promotes the metabolism of many reactive oxygen species (ROS) and has antioxidant and neuroprotective effect. The current study investigated whether chronic administration of tempol can overcome oxidative stress and prevent learning and memory impairment induced by sleep deprivation. Sleep deprivation was induced in rats using multiple platform model. Tempol was administered to rats via oral gavages. Behavioral studies were conducted to test the spatial learning and memory using radial arm water maze. The hippocampus was dissected; antioxidant biomarkers (GSH, GSSG, GSH/GSSG ratio, GPx, SOD, and catalase) were assessed. The result of this project revealed that chronic sleep deprivation impaired both short and long term memory (Psleep deprivation induced reduction in the hippocampus activity of catalase, GPx, and SOD (Psleep deprived rats treated with tempol as compared with only sleep deprived rats (Psleep deprivation induced memory impairment, and treatment with tempol prevented this impairment probably through normalizing antioxidant mechanisms in the hippocampus.
Smith, E; Pers, C; Aschow, C;
We estimate the frequency of central nervous system (CNS) toxoplasmosis in Danish AIDS patients and evaluate the diagnostic accuracy using the following criteria for acceptance of the diagnosis: either (1) the demonstration of Toxoplasma gondii in brain tissue or (2) one or more hypodense or ring......-enhancing lesions on computerized axial tomography (CAT) scan and a neurologic and CAT scan improvement in response to 2 weeks of treatment. From 1981 until July 1990 266 patients were diagnosed with AIDS at Hvidovre Hospital, Copenhagen and 29 (11%) were treated, suspected for CNS toxoplasmosis. 17 patients had...... the diagnosis confirmed but since 5 patients, who were never treated, were diagnosed at autopsy, the overall cumulated incidence was 8% (22/266 patients). The overall diagnostic accuracy was 59% (17/29 patients) showing some changes over time. Among patients diagnosed with AIDS in 1988 or later, the accuracy...
Tramullas, Mónica; Dinan, Timothy G; Cryan, John F
Experimental and clinical evidence has shown that chronic stress plays an important role in the onset and/or exacerbation of symptoms of functional gastrointestinal disorders. Here, we aimed to investigate whether exposure to a chronic and temporally unpredictable psychosocial stressor alters visceral and somatic nociception as well as anxiety-related behaviour. In male C57BL/6J mice, chronic stress was induced by repeated exposure to social defeat (SD, 2 h) and overcrowding (OC, 24 h) during 19 consecutive days. Visceral and somatic nociception was evaluated by colorectal distension and a hot plate, respectively. The social interaction test was used to assess social anxiety. Mice exposed to psychosocial stress developed visceral hyperalgesia and somatic hypoalgesia 24 h following the last stress session. SD/OC mice also exhibited social anxiety-like behaviour. All these changes were also associated with physiological alterations, measured as a decreased faecal pellet output and hypothalamic-pituitary-adrenal (HPA) axis disruption. Taken together, these data confirm that this mouse model of chronic psychosocial stress may be useful for studies on the pathophysiological mechanisms underlying such stress-associated disorders and to further test potential therapies.
Full Text Available In the last years, many clinical studies have revealed that some cisplatin-treated cancer survivors have a significantly increased risk of cardiovascular events, being cisplatin-induced cardiovascular toxicity an increasing concern. The aim of the present work was to evaluate the cardiovascular alterations induced by different chronic cisplatin treatments, and to identify some of the mechanisms involved. Direct blood pressure, basal cardiac (left ventricle and coronary arteries and vascular (aortic and mesenteric functions were evaluated in chronic (5 weeks saline- or cisplatin-treated male Wistar rats. Three different doses of cisplatin were tested (1, 2, and 3 mg/kg/week. Alterations in cardiac and vascular tissues were also investigated by immunohistochemistry, Western Blot, and or quantitative RT-PCR analysis. Cisplatin treatment provoked a significant modification of arterial blood pressure, heart rate, and basal cardiac function at the maximum dose tested. However, vascular endothelial dysfunction occurred at lower doses. The expression of collagen fibers and conexin-43 were increased in cardiac tissue in cisplatin-treated rats with doses of 2 and 3 mg/kg/week. The expression of endothelial nitric oxide synthase was also modified in cardiac and vascular tissues after cisplatin treatment. In conclusion, chronic cisplatin treatment provokes cardiac and vascular toxicity in a dose-dependent manner. Besides, vascular endothelial dysfunction occurs at lower doses than cardiac and systemic cardiovascular toxicity. Moreover, some structural changes in cardiac and vascular tissues are also patent even before any systemic cardiovascular alterations.
Rakhshandeh Alipanahi; Sima Sayyahmelli
Papillitis and complicating acute toxoplasma retinochoroiditis, are unusual and atypical features of toxoplasmosis. This report presents a female with unusual acute papillitis. This patient had an active toxoplasmic chorioretinitis lesion that appeared to involve the optic nerve head and a major blood vessel as well as central nervous systems (CNS). Papillitis may be secondary to juxtapapillary retinitis (Jensen choroiditis). Very rarely, the optic nerve head may be the primary site of involv...
Nianhong Lu, Caihong Liu, Jiangyuan Wang, Ying Ding, Qing Ai Department of Clinical Laboratory, The First Hospital of Jilin University, Changchun, People’s Republic of China Abstract: Toxoplasmosis complicating lung cancer has been described only rarely. Here, we report a case of acute Toxoplasma gondii infection in a patient with squamous lung cancer. A 64-year-old woman was admitted to our hospital with a history of cough of 6 months' duration and chest pain of 1 week&...
Avelino, Mariza M; Amaral, Waldemar N; Rodrigues, Isolina M X; Rassi, Alan R; Gomes, Maria B F; Costa, Tatiane L; Castro, Ana M
Control programs have been executed in an attempt to reduce vertical transmission and the severity of congenital infection in regions with a high incidence of toxoplasmosis in pregnant women. We aimed to evaluate whether treatment of pregnant women with spiramycin associated with a lack of monitoring for toxoplasmosis seroconversion affects the prognosis of patients. We performed a prospective cohort study with 246 newborns (NB) at risk for congenital toxoplasmosis in Goiânia (Brazil) between October 2003 and October 2011. We analyzed the efficacy of maternal treatment with spiramycin. A total of 40.7% (66/162) of the neonates were born seriously infected. Vertical transmission associated with reactivation during pregnancy occurred in 5.5% (9/162) of the NB, with one showing severe infection (systemic). The presence of specific immunoglobulins (fetal IgM and NB IgA) suggested the worst prognosis. Treatment of pregnant women by spiramycin resulted in reduced vertical transmission. When infected pregnant women did not undergo proper treatment, the risk of severe infection (neural-optical) in NB was significantly increased. Fetal IgM was associated with ocular impairment in 48.0% (12/25) of the fetuses and neonatal IgA-specific was related to the neuro-ophthalmologic and systemic forms of the disease. When acute toxoplasmosis was identified in the postpartum period, a lack of monitoring of seronegative pregnant women resulted in a higher risk of severe congenital infection. Treatment of pregnant women with spiramycin reduces the possibility of transmission of infection to the fetus. However, a lack of proper treatment is associated with the onset of the neural-optical form of congenital infection. Primary preventive measures should be increased for all pregnant women during the prenatal period and secondary prophylaxis through surveillance of seroconversion in seronegative pregnant woman should be introduced to reduce the severity of congenital infection in the
Pohorecky, L.A. (Rutgers Univ., Piscataway, NJ (USA))
Previous research from this laboratory indicated that noradrenergic mechanisms might mediate ethanol diuresis. Experiments described here examined changes in sensitivity of noradrenergic mechanisms in animals chronically treated with ethanol. Norepinephrine hydrochloride (0-12 ug intracerebroventricularly) produced dose-dependent diuresis in control and ethanol treated rats on the first day of treatment. Tolerance to ethanol diuresis was present after 10 day of ethanol treatment. Lack of responsiveness to norepinephrine-induced diuresis was evident only on the 20th day of treatment in both the ethanol and dextrin-maltose groups of rats. These results indicate a temporal dissociation between the tolerance to ethanol-induced and norepinephrine-induced diuresis and suggest that norepinephrine may not play a primary role in the development of tolerance to the diuretic action of ethanol.
Full Text Available Nianhong Lu, Caihong Liu, Jiangyuan Wang, Ying Ding, Qing Ai Department of Clinical Laboratory, The First Hospital of Jilin University, Changchun, People’s Republic of China Abstract: Toxoplasmosis complicating lung cancer has been described only rarely. Here, we report a case of acute Toxoplasma gondii infection in a patient with squamous lung cancer. A 64-year-old woman was admitted to our hospital with a history of cough of 6 months' duration and chest pain of 1 week’s duration. Further examination revealed multiple swollen lymph nodes, palpable on the top of the right collarbone and without tenderness. The chest X-ray, bronchoscopy, and computed tomography scan confirmed squamous carcinoma of the right lung. The Wright-stained bronchoalveolar-lavage fluid cytology diagnosis was positive for T. gondii and tachyzoites were detected. All of them were of free type (ectocytic, without intracellular parasites. Serological examination revealed that the anti-T. gondii immunoglobulin (Ig M and IgG antibodies were positive. Unfortunately the patient did not continue treatment and was lost to follow-up. Toxoplasmosis is a life-threatening opportunistic infection in patients with lung cancer. Prompt recognition of T. gondii infection among cancer patients with subsequent targeted treatment of toxoplasmosis could help alleviate symptoms and improve survival. Keywords: lung cancer, Toxoplasma gondii, bronchoalveolar-lavage fluid, tachyzoite
Palmer, R G; Varonos, S; Doré, C J; Denman, A M; Ansell, B M
Sister chromatid exchanges, a sensitive measure of chromosome damage, were counted in peripheral blood lymphocytes from 23 patients with juvenile chronic arthritis receiving long term, low dose chlorambucil treatment. Thirty five patients with juvenile chronic arthritis who had not been treated with cytotoxic drugs served as controls. All of the treated patients have cells with abnormal sister chromatid exchange frequencies. Damage is related to the daily dose and may, in part, be determined by the duration of treatment. Sister chromatid exchanges from nine patients who had received chlorambucil at some time in the past remained high for at least five months after stopping the drug. Long term follow up will determine whether sister chromatid exchange analysis can help predict those most at risk of drug induced malignancies. Images Fig. 1 PMID:4073932
Avital F. Barak
Full Text Available The outcome and quality of life of chronic myeloid leukemia (CML patients has remarkably changed with the treatment of tyrosine kinase inhibitors (TKIs. Currently, hematopoietic stem cell transplantation (HSCT is considered mainly as a third line salvage therapy in cases of TKIs resistance or intolerance. Here we describe a patient with chronic phase CML who developed both resistance and late occurrence of s severe thrombocytopenia on first and second generation TKIs and eventually underwent HSCT. Although the mechanism of the myelosuppression is not fully understood, we showed for the first time the development of dose dependent platelet antibodies in the presence of TKIs, suggesting the possibility of TKIs induced thrombocytopenia. Our case emphasizes that late development of severe myelosuppression during imatinib treatment is probably an important indication for consideration of early HSCT.
Calamy, L; Goudjil, F; Godineau, N; Bolot, P
Congenital toxoplasmosis is a potentially serious fetal infection associated with maternal seroconversion or a reactivation of toxoplasmosis during pregnancy. We report the case of congenital toxoplasmosis with severe neurological injury with normal prenatal obstetric ultrasounds in a mother infected with HIV at the AIDS stage and previously immunized against toxoplasmosis.
Capobiango, Jaqueline Dario; Breganó, Regina Mitsuka; Navarro, Italmar Teodorico; Rezende Neto, Claudio Pereira; Casella, Antônio Marcelo Barbante; Mori, Fabiana Maria Ruiz Lopes; Pagliari, Sthefany; Inoue, Inácio Teruo; Reiche, Edna Maria Vissoci
This study describes the characteristics of 31 children with congenital toxoplasmosis children admitted to the University Hospital of Londrina, Southern Brazil, from 2000 to 2010. In total, 23 (85.2%) of the mothers received prenatal care but only four (13.0%) were treated for toxoplasmosis. Birth weight was diagnosis and treatment of toxoplasmosis during pregnancy to reduce congenital toxoplasmosis and its consequences.
Valdés R,Enrique; Quiroz V.,Lorena; Parra C,Mauro
Se presenta un caso clínico con diagnóstico final de toxoplasmosis connatal, destacando la pesquisa de hallazgos ultrasonográficos de rara ocurrencia. Se presenta la experiencia del Hospital Clínico de la Universidad de Chile, proponiendo una aproximación actualizada al diagnóstico y tratamiento de la toxoplasmosis durante el embarazo
Kijlstra, A.; Pedersen, E.
Despite large advances in the field of ocular toxoplasmosis, large gaps still exist in our knowledge concerning the epidemiology and pathophysiology of this potentially blinding infectious disease. Although ocular toxoplasmosis is considered to have a high health burden, still little is known about
Khazaie, Habibolah; Ghadami, Mohammad Rasoul; Masoudi, Maryam
Abstract: Post-traumatic stress disorder is related to a wide range of medical problems, with a majority of neurological, psychological, cardiovascular, respiratory, gastrointestinal disorders, diabetes, as well as sleep disorders. Although the majority of studies reveal the association between PTSD and sleep disturbances, there are few studies on the assessment of sleep disruption among veterans with PTSD. In this review, we attempt to study the sleep disorders including insomnia, nightmare, sleep-related breathing disorders, sleep-related movement disorders and parasomnias among veterans with chronic war-induced PTSD. It is an important area for further research among veterans with PTSD. PMID:27093088
Mattos, Cinara C B; Meira, Cristina S; Ferreira, Ana I C; Frederico, Fábio B; Hiramoto, Roberto M; Almeida, Gildásio C; Mattos, Luiz C; Pereira-Chioccola, Vera L
This prospective study evaluated the value of laboratorial diagnosis in ocular toxoplasmosis analyzing peripheral blood samples from a group of Brazilian patients by immunologic and molecular methods. We analyzed blood samples from 184 immunocompetent patients with ocular disorders divided into 2 groups: Group I, composed of samples from 49 patients with ocular toxoplasmosis diagnosed by clinical features; Group II, samples from 135 patients with other ocular diseases. Samples were assayed by conventional polymerase chain reaction (cnPCR), real-time PCR (qPCR) for Toxoplasma gondii, indirect immunofluorescence reaction (IF), avidity test (crude tachyzoite lysate as antigen), and excreted-secreted tachyzoite proteins as antigen (ESA-ELISA). cnPCR and qPCR profiles were concordant in all samples. Positive PCR was shown in 40.8% of group I patients. The majority of the positive blood samples (75%) were taken from patients with toxoplasmic retinochoroiditis scars, and the others (25%), from patients with retinal exudative lesions. Despite that 86 of the 135 patients from Group II had asymptomatic toxoplasmosis, all DNA blood samples had negative PCR. Concordant results were shown in the data obtained by serologic methods. Around 24% of the patients with ocular toxoplasmosis had high antibody titers determined by ESA-ELISA and IF. Anti-ESA antibodies are shown principally in patients with active infection. Collectively, these data demonstrate the presence of tachyzoites in the blood of patients with chronic infection, supporting the idea of recurrent disease. Circulating parasites in blood of immunocompetent individuals may be associated with the reactivation of the ocular disease.
Full Text Available The interleukin (IL-2R alpha chain (CD25 is expressed on regulatory T cells (Treg, which constitute more than 85% of the CD25+ T cell population in a naïve mouse. CD25 is also expressed on effector T cells in mice suffering from an acute infection by the obligate intracellular protozoan parasite, Toxoplasma gondii. Lethal toxoplasmosis is accompanied by a significant loss of Treg in mice naturally susceptible to toxoplasmosis. The present study was done to explore the role of Treg cells using an anti-CD25 antibody-mediated depletion in mice naturally resistant to toxoplasmosis. Although a significant decrease in the percentage of Treg cells was observed following anti-CD25 monoclonal antibody injections, the depletion of CD25+ cells during acute toxoplasmosis did not significantly increase the mortality of Swiss OF1 mice and no significant difference was observed in the brain parasitic load between the mice in the depleted-infected and isotype-infected groups. We found no significant difference between the titres of total IgG in the sera of the mice from the two groups in the chronic phase. However, CD25+ cells depletion was followed by significantly higher levels of IL-12 in the serum of depleted mice than in that of mice injected with the isotype control antibody.
Feng, Biao; Ruiz, Michael Anthony; Chakrabarti, Subrata
Oxidative stress plays an important role in the development and progression of chronic diabetic complications. Diabetes causes mitochondrial superoxide overproduction in the endothelial cells of both large and small vessels. This increased superoxide production causes the activation of several signal pathways involved in the pathogenesis of chronic complications. In particular, endothelial cells are major targets of glucose-induced oxidative damage in the target organs. Oxidative stress activates cellular signaling pathways and transcription factors in endothelial cells including protein kinase C (PKC), c-Jun-N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), forkhead box O (FOXO), and nuclear factor kappa-B (NF-κB). Oxidative stress also causes DNA damage and activates DNA nucleotide excision repair enzymes including the excision repair cross complimenting 1(ERCC1), ERCC4, and poly(ADP-ribose) polymerase (PARP). Augmented production of histone acetyltransferase p300, and alterations of histone deacetylases, including class III deacetylases sirtuins, are also involved in this process. Recent research has found that small noncoding RNAs, like microRNA, are a new kind of regulator associated with chronic diabetic complications. There are extensive and complicated interactions and among these molecules. The purpose of this review is to demonstrate the role of oxidative stress in the development of diabetic complications in relation to epigenetic changes such as acetylation and microRNA alterations.
Meira, Cristina S; Pereira-Chioccola, Vera L; Vidal, José E; de Mattos, Cinara C Brandão; Motoie, Gabriela; Costa-Silva, Thais A; Gava, Ricardo; Frederico, Fábio B; de Mattos, Luiz C
This study analyzed the synthesis of Interferon gamma (IFN-γ), Tumor Necrosis Factor alpha (TNF-α), and Interleukin 10 (IL-10) in chronically infected patients which developed the symptomatic disease as cerebral or ocular toxoplasmosis. Blood from 61 individuals were divided into four groups: Cerebral toxoplasmosis/AIDS patients (CT/AIDS group) (n = 15), ocular toxoplasmosis patients (OT group) (n = 23), chronic toxoplasmosis individuals (CHR group) (n = 13) and healthy individuals (HI group) (n = 10). OT, CHR, and HI groups were human immunodeficiency virus (HIV) seronegative. The diagnosis was made by laboratorial (PCR and ELISA) and clinical subjects. For cytokine determination, peripheral blood mononuclear cells (PBMC) of each patient were isolated and stimulated in vitro with T. gondii antigen. IFN-γ, TNF-α, and IL-10 activities were determined by ELISA. Patients from CT/AIDS and OT groups had low levels of IFN-γ when were compared with those from CHR group. These data suggest the low resistance to develop ocular lesions by the low ability to produce IFN-γ against the parasite. The same patients, which developed ocular or cerebral toxoplasmosis had higher TNF-α levels than CHR individuals. High TNF-α synthesis contribute to the inflammatory response and damage of the choroid and retina in OT patients and in AIDS patients caused a high inflammatory response as the TNF-α synthesis is not affected since monocytes are the major source this cytokine in response to soluble T. gondii antigens. IL-10 levels were almost similar in CT/AIDS and OT patients but low when compared with CHR individuals. The deviation to Th2 immune response including the production of anti-inflammatory cytokines, such as IL-10 may promote the parasite's survival causing the tissue immune destruction. IL-10 production in T. gondii-infected brains may support the persistence of parasites as down-regulating the intracerebral immune response. All these indicate that OT and CT
Toxoplasmose congênita em filho de mãe cronicamente infectada com reativação de retinocoroidite na gestação Congenital toxoplasmosis from a chronically infected woman with reactivation of retinochoroiditis during pregnancy an underestimated event?
Gláucia M. Q. Andrade
Full Text Available OBJETIVO: Apresentar um caso raro de toxoplasmose congênita de uma mãe imunocompetente com infecção crônica que teve reativação da doença ocular durante a gestação. DESCRIÇÃO: O recém-nascido estava assintomático no nascimento e foi identificado através de triagem neonatal (IgM anti-Toxoplasma gondii em sangue seco entre outros 190 bebês com toxoplasmose congênita durante um período de 7 meses. Sua mãe tinha tido um episódio não tratado de reativação de retinocoroidite toxoplásmica durante a gestação, com títulos de IgG estáveis e resultados negativos para IgM. Os resultados de IgM e IgG no soro do recém-nascido e o teste de immunoblotting para IgG foram positivos, e detectou-se lesões retinocoroideanas ativas na periferia da retina. O recém-nascido foi tratado com sulfadiazina, pirimetamina e ácido folínico. Aos 14 meses de vida, a criança permanecia assintomática, com regressão das lesões retinocoroideanas e persistência de IgG. COMENTÁRIOS: É possível que a triagem neonatal sistemática em áreas com alta prevalência de infecção possa identificar esses casos.OBJECTIVES: To report a rare case of congenital toxoplasmosis from an immunocompetent mother with chronic infection who had reactivation of ocular disease during pregnancy. DESCRIPTIONS:The newborn was asymptomatic at birth and identified by neonatal screening (IgM anti-Toxoplasma gondii in dried blood among other 190 infants with congenital toxoplasmosis during a 7-month period. His mother had had a non-treated episode of reactivation of toxoplasmic retinochoroiditis during pregnancy, with stable IgG titers and negative IgM results. Results of IgM and IgG in the newborn’s serum, as well as IgG immunoblotting were positive and active retinochoroidal lesions were detected in his peripheral retina. The neonate was treated with sulfadiazine, pyrimethamine and folinic acid. At 14 months of life, the child remained asymptomatic, with regression of
Barakat, Ashraf Mohamed; Salem, Lobna Mohamed Ali; El-Newishy, Adel M Abdel-Aziz; Shaapan, Raafat Mohamed; El-Mahllawy, Ehab Kotb
Toxoplasmosis is one of the most common diseases prevalent in the world, caused by a coccidian parasite Toxoplasma gondii which infects humans, animals and birds. Poultry consider reliable human source of food in addition it is considered an intermediate host in transmission of the disease to humans. Trails of isolation of local T. gondii chicken strain through bioassay of the suspected infected chicken tissues in mice was carried out and the isolated strain was confirmed as being T. gondii using Polymerase Chain Reaction (PCR). Seroprevalence of antibodies against T. gondii in chicken sera in six Egyptian governorates were conducted by enzyme linked immune-sorbent assay (ELISA) using the isolated chicken strain antigen. Moreover, comparison between the prevalence rates in different regions of the Egyptian governorates were been estimated. Isolation of local T. gondii chicken strain was accomplished from chicken tissues and confirmed by PCR technique. The total prevalence rate was 68.8% comprised of 59.5, 82.3, 67.1, 62.2, 75 and 50% in El Sharkia, El Gharbia, Kafr El sheikh, Cairo, Quena and Sohag governorates, respectively. The prevalence rates were higher among Free Range (FR) (69.5%) than commercial farm Chickens (C) (68.5%); while, the prevalence rate was less in Upper Egypt than Lower Egypt governorates and Cairo. This study is the first was used antigen from locally isolated T. gondii chicken strain for the diagnosis of chicken toxoplasmosis. The higher seroprevalence particularly in free range chickens (house-reared) refers to the public health importance of chickens as source of zoonotic toxoplasmosis to human.
Yongquan Pan; Peng Zhang; Junqing Yang; Qiang Su
A preliminary study has found that the 5-lipoxygenase inhibitor, caffeic acid, has a marked protective effect on acute brain injury induced by intracerebroventricular microinjection of aluminum.In this experiment, chronic brain injury and neuronal degeneration model was established in rats by chronic oral administration of aluminum, and then intervened using caffeic acid. Results showed that caffeic acid can downregulate chronic aluminum overload-induced 5-lipoxygenase mRNA and protein expression, and repair the aluminum overload-induced hippocampal neuronal damage andspatial orientation impairment. It is suggested that direct intervention of 5-lipoxygenase expression has a neuroprotective role in the degeneration induced by chronic aluminum overload brain injury model.
Alipanahi, Rakhshandeh; Sayyahmelli, Sima
Papillitis and complicating acute toxoplasma retinochoroiditis, are unusual and atypical features of toxoplasmosis. This report presents a female with unusual acute papillitis. This patient had an active toxoplasmic chorioretinitis lesion that appeared to involve the optic nerve head and a major blood vessel as well as central nervous systems (CNS). Papillitis may be secondary to juxtapapillary retinitis (Jensen choroiditis). Very rarely, the optic nerve head may be the primary site of involvement. This case report illustrates a rare presentation of acute papillitis in a young immunocompetent female. PMID:21887084
Full Text Available Papillitis and complicating acute toxoplasma retinochoroiditis, are unusual and atypical features of toxoplasmosis. This report presents a female with unusual acute papillitis. This patient had an active toxoplasmic chorioretinitis lesion that appeared to involve the optic nerve head and a major blood vessel as well as central nervous systems (CNS. Papillitis may be secondary to juxtapapillary retinitis (Jensen choroiditis. Very rarely, the optic nerve head may be the primary site of involvement. This case report illustrates a rare presentation of acute papillitis in a young immunocompetent female.
Full Text Available A seven-year-old female spayed Schnauzer was presented with cutaneous ulcerated nodular lesions shortly after the beginning of an immunosuppressive treatment for immune-mediated hemolytic disease. Cytology was performed and a great number of neutrophils and banana-shaped organisms were observed. Biopsy showed a neutrophilic and histiocytic dermatitis and panniculitis with myriads of intralesional bradyzoites cysts and tachyzoites. PCR analysis was positive for Toxoplasma gondii and negative for Neospora caninum. Immunohistochemistry confirmed intralesional T. gondii antigens. This study reports a rare case of cutaneous toxoplasmosis in an immunosuppressed dog.
Ren, Zhenyu; Yang, Bing; Yang, Bin; Shi, Le; Sun, Qing-Li; Sun, A-Ping; Lu, Lin; Liu, Xiaoguang; Zhao, Rongsheng; Zhai, Suodi
Combined pharmacological treatments are the most used approach for neuropathic pain. Carbamazepine, an antiepileptic agent, is generally used as a third-line treatment for neuropathic pain and can be considered an option only when patients have not responded to the first- and second-line medications. In the case presented herein, a patient with neuropathic pain was treated using a combined pharmacological regimen. The patient's pain deteriorated, despite increasing the doses of opioids, when carbamazepine was discontinued, potentially because carbamazepine withdrawal disrupted the balance that was achieved by the multifaceted pharmacological regimen, thus inducing hyperalgesia. Interestingly, when carbamazepine was prescribed again, the patient's pain was successfully managed. Animal research has reported that carbamazepine can potentiate the analgesic effectiveness of morphine in rodent models of neuropathic pain and postoperative pain. This clinical case demonstrates that carbamazepine may have a synergistic effect on the analgesic effectiveness of morphine and may inhibit or postpone opioid-induced hyperalgesia. We postulate that a probable mechanism of action of carbamazepine may involve -aminobutyric acid-ergic potentiation and the interruption of glutamatergic function via N-methyl-D-aspartate receptors. Further research is warranted to clarify the analgesic action of carbamazepine and its potential use for the prevention of opioid-induced hyperalgesia in chronic neuropathic pain patients.
Full Text Available La transmisión de la infección por Toxoplasma gondii de la madre al hijo ocurre cuando la madre se infecta por primera vez en el transcurso del embarazo. Tanto el diagnóstico prenatal, como el del primer año de vida se basa en pruebas serológicas; y la mayoría de las veces es necesario realizar más de una de estas pruebas ya que tienen distintos porcentajes de sensibilidad y/o especificidad así como distintos niveles de complejidad. El recién nacido requiere seguimiento serológico en el primer año de vida o hasta que se descarte el diagnóstico de toxoplasmosis congénita. El diagnóstico temprano de la infección, en la mujer embarazada, permite un tratamiento oportuno y se indica con el propósito de reducir la tasa de transmisión y el daño congénito. Es posible que con un programa activo, de prevención y tratamiento temprano, se pueda reducir la tasa de incidencia de la toxoplasmosis congénita de alrededor del 5 por mil nacimientos a 0.5 por mil. El objetivo de este consenso fue revisar la literatura científica para la prevención, el diagnóstico y el tratamiento de la toxoplasmosis congénita, para que se pueda implementar en nuestro país.The mother-to-child transmission in Toxoplasma gondii infection occurs only when the infection is acquired for the first time during pregnancy. The prenatal and early postnatal diagnosis can only be achieved by serological testing. Serologic tests have different sensitivities, specificities and complexities, so that different tests in more than one blood sample are necessary for the diagnosis. Serological follow-up of the infants should be conducted during the first year of life or until the diagnosis of congenital toxoplasmosis can be ruled out. Treatment recommendations try to reduce the transmission rate and the risk of congenital damage. Congenital toxoplasmosis incidence rate is approximately 5 per 1000 births, but can be reduced to 0.5 per 1000 with an active screening program. The
Full Text Available Chronic lymphocytic leukemia is an indolent disorder with an increased infectious risk remaining one of the main causes of death. Development of therapies with higher safety profile is thus a challenging issue. Docosahexaenoic acid (DHA, 22:6 is an omega-3 fatty acid, a natural compound of normal cells, and has been shown to display antitumor potency in cancer. We evaluated the potential in vitro effect of DHA in primary CLL cells. DHA induces high level of in vitro apoptosis compared to oleic acid in a dose-dependent and time-dependent manner. Estimation of IC50 was only of 4.813 μM, which appears lower than those reported in solid cancers. DHA is highly active on CLL cells in vitro. This observation provides a rationale for further studies aiming to understand its mechanisms of action and its potent in vivo activity.
Full Text Available Shree Ram Ghimire,1 Sarita Parajuli2 1Department of Psychiatry, National Medical College, Birgunj, 2Department of Anesthesiology, Kathmandu National Medical College, Anamnagar, Kathmandu, Nepal Abstract: Chronic organophosphate (OP-induced neuropsychiatric disorder is a rare condition following prolonged exposure to OP compounds. Due to the lack of valid diagnostic tools and criteria, very few cases are seen in clinical practice and are often misdiagnosed. Misdiagnosis can lead to inappropriate treatment that may increase the risk of morbidity or suicidality. In this paper, we present the case of a 35-year-old male who needed support in breathing from a mechanical ventilator and developed neuropsychiatric behavioral problems following ingestion of OP compounds, which lead to suicidality. The patient was treated by the psychiatric team with antipsychotic and antidepressants and improved following the regular use of medication. Keywords: COPIND, mood liability, suicidal thoughts
Bakht, F R; Gentry, L O
Toxoplasmosis is usually asymptomatic in pregnant women but poses a risk of severe effects on the fetus. One to eight of every 1,000 pregnant women become infected, and the infection is transmitted to the fetus in approximately 40 percent of these cases. The risk of transmission rises with increasing gestational age at the time of initial infection. Congenital infection with toxoplasmosis may lead to serious sequelae, such as blindness, mental retardation, neurologic deficits and deafness. Prevention of morbidity from toxoplasmosis depends on prevention of the infection in pregnant women, plus early recognition and aggressive treatment of maternal infections.
Full Text Available Toxoplasmosis has been reported to occur in several animals and humans causing different clinical manifestations. The study was conducted to determine the frequency of Toxoplasma gondii antibodies (IgG in water buffalo (Bubalus bubalis across farms in Trinidad using a latex agglutination test. Of a total of 333 water buffalo tested, 26 (7.8% were seropositive for T. gondii antibodies. Seropositivity for toxoplasmosis was statistically significantly (P0.05; χ2. This is the first documentation of toxoplasmosis in water buffalo in Trinidad.
Persad, Anil; Charles, Roxanne; Adesiyun, Abiodun A.
Toxoplasmosis has been reported to occur in several animals and humans causing different clinical manifestations. The study was conducted to determine the frequency of Toxoplasma gondii antibodies (IgG) in water buffalo (Bubalus bubalis) across farms in Trinidad using a latex agglutination test. Of a total of 333 water buffalo tested, 26 (7.8%) were seropositive for T. gondii antibodies. Seropositivity for toxoplasmosis was statistically significantly (P 0.05; χ2). This is the first documentation of toxoplasmosis in water buffalo in Trinidad. PMID:22195295
Full Text Available Background: Toxoplasmosis is a parasitic disease caused by the protozoan Toxoplasma gondii. The aim of this study was investigate the prevalence of toxoplasmosis among young women who referred to check up for toxoplasmosis attended in Shahid Beheshti hospital, Hamadan during 2013-2014.Materials and Methods: This study was performed on 2523 pregnant women who referred to laboratory of Shahid Beheshti hospital in Hamadan province (western of Iran during 2013-2014. Age, level of education and place of residence were recorded in the relevant forms. Antibodies serum levels for all samples were examined by ELISA. IgG titer equals and more than 1:200 was presumed as seropositive. Data were analyzed using by SPSS version 19.0 software.Results: 26.1% of IgG seropositive persons were city residents while 32.3% of them lived at village and suburb of city. 1.4% and 1.1% of at risk persons (based on IgG titration were city and village residents, respectively. 1.3% and 1.9% of IgM seropositives were city and village residents, respectively. The percentage of at risk persons of city and village (based on IgM titration were 0.3% and 0.6%, in a row. 29.7% of IgG seropositives did not have academic education while 30.4% of them graduated from high school, at least. The seropositive IgM percentage of non-academic educated persons and graduated/academic ones were 1.7% and 1.4%, respectively.Conclusion: Our funding indicates the association between age of women and their level of education with percentage of contamination and prevalence. IgM seropositive is lesser than IgG. It means that toxoplasmosis is chronic or there is previous contact. To avoid the risk of toxoplasmosis infection particularly in pregnant women should be examined and the necessary preventive measures and training for young women should be presented.
Sebnem Ustun; Umit Aksoy; Hande Dagci; Galip Ersoz
AIM: It is known that toxoplasmosis rarely leads to various liver pathologies, most common of which is granulomatose hepatitis in patients having normal immune systems. Patients who have cirrhosis of the liver are subject to a variety of cellular as well as humoral immunity disordes. Therefore, it may be considered that toxoplasmosis can cause more frequent and more severe diseases in patients with cirrhosis and is capable of changing the course of the disease. The aim of this study was to investigate the frequency of METHODS: Serum samples were taken from 108 patients with cirrhosis under observation in the Hepatology Polyclinic of the Gastroenterology Clinic, and a control group made up of 50 healthy blood donors. IFAT and ELISA methods were used to investigate the IgG and IgM antibodies, which had developed from these sera.RESULTS: Toxoplasma IgG and IgM antibody positivity was found in 74 (68.5%) of the 108 cirrhotic patients and 24 (48%) of the 50 people in the control group. The difference between them was significant (P＜0.05).CONCLUSION: In conclusion, it was found that the toxoplasma sero-prevalence in the cirrhotic patients in this study was higher. Cirrhotic patients are likely to form a toxoplasma risk group, More detailed studies are needed on this subject.
Davoust, B; Mediannikov, O; Roqueplo, C; Perret, C; Demoncheaux, J-P; Sambou, M; Guillot, J; Blaga, R
Toxoplasma gondii is an obligate, intracellular, parasitic protozoan within the phylum Apicomplexa that causes toxoplasmosis in mammalian hosts (including humans) and birds. We used modified direct agglutination test for the screening of the animals' sera collected in Senegal. In total, 419 animals' sera have been studied: 103 bovines, 43 sheep, 52 goats, 63 horses, 13 donkeys and 145 dogs. The collection of sera was performed in four different regions of Senegal: Dakar, Sine Saloum, Kedougou and Basse Casamance from 2011 to 2013. We have revealed antibodies in 13% of bovines, 16% of sheep, 15% of goats, 30% of horses, 23% of donkeys and 67% of dogs. Private dogs from villages were more often to have the anti-Toxoplasma antibodies compared to security society-owned dogs from Dakar. It may be explained by different meal consumed by dogs (factory-produced meal for dogs from Dakar vs. irregular sources for village dogs). Intense circulation of T. gondii in the studied zone may explain the unusually high seroprevalence among horses and donkeys. Tropical climate with high temperature and humidity is favorable for the conservation of oocysts of T. gondii. Results presented here may contribute to the evaluation of the risks of toxoplasmosis in humans in Senegal.
Zhengxiu Su; Hongguo Zhu; Menghuan Zhang; Liangliang Wang; Hanchang He; Shaoling Jiang; Fan Fan Hou; Aiqing Li
Heart damage is widely present in patients with chronic kidney disease. Salt diet is the most important environmental factor affecting development of chronic renal failure and cardiovascular diseases. The proteins involved in chronic kidney disease -induced heart damage, especially their posttranslational modifications, remain largely unknown to date. Sprague-Dawley rats underwent 5/6 nephrectomy (chronic renal failure model) or sham operation were treated for 2 weeks with a normal-(0.4% NaCl...
Metabolic, Immune, Epigenetic, Endocrine and Phenotypic Abnormalities Found in Individuals with Autism Spectrum Disorders, Down Syndrome and Alzheimer Disease May Be Caused by Congenital and/or Acquired Chronic Cerebral Toxoplasmosis
"Toxoplasma gondii" is a protozoan parasite that infects about a third of human population. It is generally believed that in immunocompetent hosts, the parasite infection takes usually asymptomatic course and induces self-limiting disease, but in immunocompromised individuals may cause significant morbidity and mortality. "T. gondii" uses sulfated…
Metabolic, Immune, Epigenetic, Endocrine and Phenotypic Abnormalities Found in Individuals with Autism Spectrum Disorders, Down Syndrome and Alzheimer Disease May Be Caused by Congenital and/or Acquired Chronic Cerebral Toxoplasmosis
"Toxoplasma gondii" is a protozoan parasite that infects about a third of human population. It is generally believed that in immunocompetent hosts, the parasite infection takes usually asymptomatic course and induces self-limiting disease, but in immunocompromised individuals may cause significant morbidity and mortality. "T. gondii" uses sulfated…
Conclusion: There was no statistically significant difference in comparing positive se-rology of toxoplasmosis, between the two groups. However, to obtain a perfect result, a larger sample size are required.
Full Text Available Many existing therapies in autoimmune diseases are based on systemic suppression of inflammation, the observed side effects illustrate the need for more specific interventions. Regulatory T cells (Treg are pivotal controllers of (autoaggressive immune responses, and decreased Treg numbers and/or functioning have been associated with autoimmune disease. Especially antigen-specific targeting of Treg would enable tailor made interventions, while obviating negative side effects of general immuno-suppression. Self-antigens that participate in inflammation, irrespective of the etiology of the different autoimmune diseases, are held to be candidate antigens for such interventions. Rather than tolerance induction to disease inciting self-antigens, which are frequently unknown, general self-antigens expressed at sites of inflammation would allow targeting of disease independent, but inflammatory-site specific, regulatory mechanisms. Preferably, such self-antigens should be abundantly expressed and up-regulated at the inflammatory site. Heat shock proteins show several of these characteristics.The development of antigen-specific Treg inducing vaccines is a major novel goal in the field of immunotherapy in autoimmune diseases. Progress is hampered by the lack of effective antigens and by the fact that other factors such as dose, route and the presence or absence of an adjuvant, turned out to be critical unknowns, with respect to effective induction of Treg. The use of a Treg inducing adjuvant might be required to achieve effective regulatory responses, in the case of ongoing inflammation. Future goals will be the optimization of natural Treg expansion (or the induction of adaptive Treg without loss of their suppressive function or the concomitant induction of non-regulatory T cells. Here, we discuss the potential use of protein/peptide-based vaccines combined with Treg inducing adjuvants for the development of therapeutic vaccines against chronic
Work, T.M.; Massey, J.G.; Lindsay, D.S.; Dubey, J.P.
Toxoplasma gondii was found in endemic Hawaiian birds, including 2 nene geese (Nesochen sandvicensis), 1 red-footed booby (Sula sula), and an introduced bird, the Erckels francolin (Francolinus erckelii). All 4 birds died of disseminated toxoplasmosis; the parasite was found in sections of many organs, and the diagnosis was confirmed by immunohistochemical staining with antia??T. gondiia??specific polyclonal antibodies. This is the first report of toxoplasmosis in these species of birds.
Toxoplasmosis, caused by the obligate intracellular protozoan Toxoplasma gondii, is an important zoonosis with medical and veterinary importance worldwide. The disease is mainly contracted by ingesting undercooked or raw meat containing viable tissue cysts, or by ingesting food or water contaminated with oocysts. The diagnosis and genetic characterization of T. gondii infection is crucial for the surveillance, prevention and control of toxoplasmosis. Traditional approaches for the diagnosis o...
BACKGROUND AND AIM: Infection with the protozoan parasite Toxoplasma gondii has a worldwide distribution. Congenital infection is the most important part of the disease burden due to Toxoplasma infection in humans. Early diagnosis of maternal infection helps to prevent severe complications of toxoplasmosis. In the present study, three PCR assays (conventional, nested & quantitative) were evaluated for diagnosis of recent toxoplasmosis based on detection of Toxoplasma B1 gene. MATERIAL AND...
Retinochoroiditis is the most common ocular manifestation of congenital toxoplasmosis, but other associated ophthalmological pathologies can also occur. Ophthalmologists are rarely able to distinguish between toxoplasmic retinochoroiditis due to infection acquired before or after birth, unless other clinical or serological indications are present. This article reports a case of a 3-year-old boy with abnormalities suggestive of congenital toxoplasmosis. The clinical and complementary examinati...
Alessandra G Commodaro
Full Text Available Ocular toxoplasmosis is the most common cause of posterior uveitis worldwide. The infection can be acquired congenitally or postnatally and ocular lesions may present during or years after the acute infection occur. Current treatment controls ocular infection and inflammation, but does not prevent recurrences. We present a review and update on ocular toxoplasmosis and address misconceptions still found in the current medical literature.
Abholz, H H
Using data from international literature makes it possible to calculate for Germany benefit and harm of a screening for toxoplasmosis in pregnancy. On the basis of these data harm of such a screening is much greater than benefit. Taking the reported number of congenital toxoplasmosis in Germany as the base for such a calculation of harm and benefit makes the ratio of benefit and harm even worse.
van Valen, Evelien; Wekking, Ellie; van der Laan, Gert; Sprangers, Mirjam; van Dijk, Frank
Worldwide millions of workers are exposed to organic solvents. Long term exposure leads in some workers to the development of Chronic Solvent induced Encephalopathy (CSE). The first reports about CSE came from the European Nordic countries in the 1970s. In spite of decades of experience with this disease, little is known about the course and prognostic factors of CSE. To provide an overview of the evidence about the course and prognostic factors of CSE. A systematic review was conducted. Databases PubMed, PsycINFO (1970-2008) and EMBASE (1980-2008) were searched with the search strategy: solvent AND follow up AND (encephalopathy OR chronic intoxication). Inclusion criteria were: written in English, study population of CSE patients, follow-up time of at least 1 year. Included articles were assessed on methodological quality. Sixty unique articles were retrieved of which sixteen met the inclusion criteria. Data extraction provided information about domains of neurology, neuropsychology, physical and mental health perceptions, and social consequences. In a number of studies no significant changes, and in other studies improvement of functioning could be measured. Prognostic factors resulting from included studies were summarized for each domain indicating a potential positive influence of younger age and lower exposure variables. Due to the large heterogeneity of methodology no levels of evidence could be obtained. This review shows that there is a need for future research that addresses a variety of domains of functioning, hopefully resulting in an overall prognostic model for CSE. Studies in this review are in agreement about CSE being a non-progressive disease in which no severe deterioration of functioning occurs after diagnosis. In a number of studies no significant changes, and in other studies improvement of functioning could be measured. Presumably cessation of exposure might be one of the causal factors for the non-progressive character of the disease as has
Oge F Amadi
Full Text Available Toxoplasmosis is the most serious manifestation of infection, resulting from the vertical transmission of Toxoplasma gondii (T. gondii transplacentally, from a parasitemic mother to her offspring. It could also be acquired. Case Presentation: E.B is a 17-month-old female baby who presented with recurrent fever x 16/12., chronic cough x 16/12, recurrent stooling x 15/12, recurrent ear discharge x 15/12, failure to gain weight x 15/12, and delayed developmental milestones. Examination revealed an acutely ill- or chronically ill-looking child in mild respiratory distress, afebrile (36.5°C, anicteric, acyanozed, moderately pale, well hydrated with generalized lymphadenopathy (axillary, inguinal, cervical, no digital clubbing, and no pedal fullness. Computed tomography (CT scan revealed bilateral basal ganglia calcifications with a focal cystic area in the left basal ganglia; bilateral multifocal intracerebral hypodensities were noted from the frontal to the occipital lobes at different levels bilaterally, with calcifications limited to the basal ganglia. Serological test revealed the patient′s serum to be positive for toxoplasma immunoglobulin G (IgG. Conclusion: Toxoplasmosis, though rare, can cause mortality and morbidity in children. Thus, a high index of suspicion is warranted in management.
Toxoplasmosis acquired during pregnancy is a serious disease that may significantly affect fetal development and cause irreversible or therapeutically hardly influenced damage to the newborn. Early and correct diagnosis of the disease in the mother is essential for determining prognosis and further diagnostic and therapeutic procedures. The case study combines a number of factors to be encountered in clinical practice which may complicate diagnostic considerations. One of them is the existence of a rare phenomenon of reinfection - its possible effects on prenatal screening and other interpretations of such findings. Another problem is the evaluation of the origin of sonographically confirmed fetopathy in relation to Toxoplasma etiology and the choice of next steps that should follow in this situation. Finally, the text discusses the selection of postnatal examinations so that they sufficiently contribute to decision-making about the newborn's treatment initiation.
Hsieh, Chia-Wei; Lee, Jeen-Wei; Liao, En-Chih; Tsai, Jaw-Ji
There are currently no diagnostic methods in vitro for aspirin-induced chronic urticaria (AICU) except for the provocation test in vivo. To identify disease markers for AICU, we investigated the single nucleotide polymorphism (SNP) of the promoter loci of high-affinity IgE receptor (FcεRIα) and CD203c expression level in Chinese patients with AICU. We studied two genotypic and allelic frequencies of rs2427827 (-344C/T) and rs2251746 (-66T/C) gene polymorphisms of FcεRIα in 20 patients with AICU, 52 subjects with airway hypersensitivity without aspirin intolerance, and 50 controls in a Chinese population. The results showed that the frequencies of two SNPs (-344C>T, -66C>T) were similar to the normal controls. The allele frequency of -344CC was significantly higher in the patients with AICU compared to those with airway sensitivity (p=0.019). We also studied both histamine release and CD203c expression on KU812 cells to assess aspirin-induced basophil activation. We found that the activity of basophil activation of AICU was significantly higher in the patients with AICU compared to those with airway hypersensitivity without aspirin intolerance. The mean fluorescence intensity of the CD203c expression were 122.5±5.2 vs. 103.3±3.3 respectively, (phistamine release were 31.3%±7.4% vs. -24.0%±17.5%, (phistamine release were significantly up-regulated by aspirin, they were not affected by anti-IgE antibodies. These results suggest that a single SNP of FcεRIα (-344C>T) is less likely to develop AICU and the basophil activation activity in the sera by measuring CD203c expression can be applicable to confirm the diagnosis of AICU.
Kozielewicz, Dorota; Halota, Waldemar
Thyroid function disorders affect between 5% and 15% of patients treated with IFNα and RBV for chronic hepatitis C. Women and patients with thyroid peroxidase antibodies (TPOAb) found before the treatment are at risk of developing the disorders (46.1% vs. 5.4%). The spectrum of IFNα-induced thyroiditis (IIT) includes two groups. Disorders with an autoimmune background are: presence of thyroid autoantibodies without clinical disease, Hashimoto's disease and Graves' disease. The second group comprises diseases caused by the direct toxic effect of IFNα on the thyroid gland, i.e. destructive thyroiditis and non-autoimmune hypothyroidism. Thyroid diseases are not an absolute contraindication for IFNα and RBV therapy. In patients diagnosed with thyroid dysfunction, before the antiviral therapy it is necessary to achieve euthyreosis. Thyroid function disorders may occur at any moment of the therapy. The earliest have been observed in the 4th week of treatment, and the latest 12 months after its termination. During the therapy, in order to diagnose IIT early, it is recommended to determine TSH level every 2-3 months depending on the presence of TPOAb before the treatment. The diagnosis and treatment of thyroid function disorders should be conducted in co-operation with an endocrinologist.
Bhatia, Nitish; Jaggi, Amteshwar Singh; Singh, Nirmal; Anand, Preet; Dhawan, Ravi
The present study was designed to investigate the role of curcumin in chronic stress and chronic unpredictable stress-induced memory deficits and alteration of functional homeostasis in mice. Chronic stress was induced by immobilizing the animal for 2 h daily for 10 days, whereas chronic unpredictable stress was induced by employing a battery of stressors of variable magnitude and time for 10 days. Curcumin was administered to drug-treated mice prior to induction of stress. Body weight, adrenal gland weight, ulcer index and biochemical levels of glucose, creatine kinase, cholesterol, corticosterone, thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) were evaluated to assess stress-induced functional changes. Memory deficits were evaluated using the elevated plus maze (EPM) model. Chronic stress and chronic unpredictable stress significantly increased the levels of corticosterone, glucose and creatine kinase and decreased cholesterol levels. Moreover, chronic stress and chronic unpredictable stress resulted in severe memory deficits along with adrenal hypertrophy, weight loss and gastric ulceration. Chronic stress and chronic unpredictable stress also increased oxidative stress assessed in terms of increase in TBARS and decrease in GSH levels. Pretreatment with curcumin (25 and 50 mg/kg p.o.) attenuated chronic stress and chronic unpredictable stress-associated memory deficits, biochemical alterations, pathological outcomes and oxidative stress. It may be concluded that curcumin-mediated antioxidant actions and decrease in corticosterone secretion are responsible for its adaptogenic and memory restorative actions in chronic and chronic unpredictable stress.
Ukamaka Celestina Fuh
Conclusion: Patients with POT were rather old and some risk factors were modifiable, therefore health education for preventing the transmission of toxoplasmosis and provision of sanitary water may help reduce the incidence of ocular toxoplasmosis.
Iglesias Rozas, José Rafael, 1942-
Veinticinco imágenes de una infección de citomegalovirus y una toxoplasmosis cerebral en un paciente con sida. Twenty-five pictures of a cytomegalovirus infection and a cerebral toxoplasmosis in a patient with AIDS.
Boyer, Kenneth; Hill, Dolores; Mui, Ernest; Wroblewski, Kristen; Karrison, Theodore; Dubey, J. P.; SAUTTER, MARI; Noble, A. Gwendolyn; Withers, Shawn; Swisher, Charles; Heydemann, Peter; Hosten, Tiffany; Babiarz, Jane; Lee, Daniel; Meier, Paul
Undetected contamination of food and water by oocysts causes human infections in North America. Risks often are unrecognized. Education alone cannot prevent suffering and economic consequences associated with congenital toxoplasmosis. Prenatal screening can facilitate prevention and treatment of congenital toxoplasmosis.
To generate a protective vaccine against toxoplasmosis, multistage vaccines and usage of challenging models mimicking natural route of infection are critical cornerstones. In this study, we generated a BAG1 and GRA1 multistage vaccine that induced strong immune response in which the protection was not at anticipated level. In addition, the murine model was orally challenged with tissue cysts to mimic natural route of infection.
Rajapakse, Senaka; Chrishan Shivanthan, Mitrakrishnan; Samaranayake, Nilakshi; Rodrigo, Chaturaka; Deepika Fernando, Sumadhya
The efficacy of different treatment regimens in clinical syndromes of toxoplasmosis were assessed by conducting a systematic review of published randomized clinical trials through extensive searches in MEDLINE, EMBASE, and SCOPUS with no date limits, as well as manual review of journals. Outcome measures varied depending on the clinical entity of toxoplasmosis. Risk of bias was evaluated and quality of evidence was graded. Fourteen randomized trials were included of which one was a non-comparative study. One well-designed trial showed that trimethoprim-sulphamethoxazole was more effective than placebo for clinical recovery of toxoplasmic lymphadenopathy in immunocompetent hosts. For toxoplasmic encephalopathy, efficacy of pyrimethamine+sulphadiazine and trimethoprim+sulphamethoxazole were similar, whereas pyrimethamine+sulphadiazine versus pyrimathamine+clindamycin showed no difference, irrespective of the outcome. Intravitreal clindamycin+dexamethasone and conventional treatment with oral pyrimethamine+sulphadiazine had similar efficacy with regard to all outcome measures in ocular toxoplasmosis, and intravitreal therapy was found to be safe. Adverse effects seemed more common with pyrimethamine+sulphadiazine. Most trials for encephalitis and ocular manifestations had a high risk of bias and were of poor methodological quality. There were no trials evaluating drugs for toxoplasmosis in pregnancy, or for congenital toxoplasmosis. Pyrimethamine+sulphadiazine is an effective therapy for treatment of toxoplasmic encephalitis; trimethoprim+sulphamethoxazole and pyrimethamine+clindamycin are possible alternatives. Treatment with either oral or intravitreal antibiotics seems reasonable for ocular toxoplasmosis. Overall, trial evidence for the efficacy of these drugs for toxoplasmosis is poor, and further well-designed trials are needed.
Rajapakse, Senaka; Chrishan Shivanthan, Mitrakrishnan; Samaranayake, Nilakshi; Rodrigo, Chaturaka; Deepika Fernando, Sumadhya
The efficacy of different treatment regimens in clinical syndromes of toxoplasmosis were assessed by conducting a systematic review of published randomized clinical trials through extensive searches in MEDLINE, EMBASE, and SCOPUS with no date limits, as well as manual review of journals. Outcome measures varied depending on the clinical entity of toxoplasmosis. Risk of bias was evaluated and quality of evidence was graded. Fourteen randomized trials were included of which one was a non-comparative study. One well-designed trial showed that trimethoprim-sulphamethoxazole was more effective than placebo for clinical recovery of toxoplasmic lymphadenopathy in immunocompetent hosts. For toxoplasmic encephalopathy, efficacy of pyrimethamine+sulphadiazine and trimethoprim+sulphamethoxazole were similar, whereas pyrimethamine+sulphadiazine versus pyrimathamine+clindamycin showed no difference, irrespective of the outcome. Intravitreal clindamycin+dexamethasone and conventional treatment with oral pyrimethamine+sulphadiazine had similar efficacy with regard to all outcome measures in ocular toxoplasmosis, and intravitreal therapy was found to be safe. Adverse effects seemed more common with pyrimethamine+sulphadiazine. Most trials for encephalitis and ocular manifestations had a high risk of bias and were of poor methodological quality. There were no trials evaluating drugs for toxoplasmosis in pregnancy, or for congenital toxoplasmosis. Pyrimethamine+sulphadiazine is an effective therapy for treatment of toxoplasmic encephalitis; trimethoprim+sulphamethoxazole and pyrimethamine+clindamycin are possible alternatives. Treatment with either oral or intravitreal antibiotics seems reasonable for ocular toxoplasmosis. Overall, trial evidence for the efficacy of these drugs for toxoplasmosis is poor, and further well-designed trials are needed. PMID:23816507
Full Text Available There are currently no diagnostic methods in vitro for aspirin-induced chronic urticaria (AICU except for the provocation test in vivo. To identify disease markers for AICU, we investigated the single nucleotide polymorphism (SNP of the promoter loci of high-affinity IgE receptor (FcεRIα and CD203c expression level in Chinese patients with AICU. We studied two genotypic and allelic frequencies of rs2427827 (–344C/T and rs2251746 (–66T/C gene polymorphisms of FcεRIα in 20 patients with AICU, 52 subjects with airway hypersensitivity without aspirin intolerance, and 50 controls in a Chinese population. The results showed that the frequencies of two SNPs (–344C>T, –66C>T were similar to the normal controls. The allele frequency of –344CC was significantly higher in the patients with AICU compared to those with airway sensitivity (p = 0.019. We also studied both histamine release and CD203c expression on KU812 cells to assess aspirin-induced basophil activation. We found that the activity of basophil activation of AICU was significantly higher in the patients with AICU compared to those with airway hypersensitivity without aspirin intolerance. The mean fluorescence intensity of the CD203c expression were 122.5 ± 5.2 vs. 103.3 ± 3.3 respectively, (p < 0.05, and the percentages of histamine release were 31.3% ± 7.4% vs. −24.0% ± 17.5%, (p < 0.05 respectively. Although the mean fluorescence intensity of CD203c expression and the percentage of histamine release were significantly up-regulated by aspirin, they were not affected by anti-IgE antibodies. These results suggest that a single SNP of FcεRIα (–344C>T is less likely to develop AICU and the basophil activation activity in the sera by measuring CD203c expression can be applicable to confirm the diagnosis of AICU.
Objective: Green tea proposes anti-inflammatory properties which may attenuate chronic inflammation-induced fibrosis of vessels. This study evaluated whether green tea polyphenols (GTP) can avert fibrosis or vascular disruption along with mechanisms in rats with chronic inflammation. Treatments: Fo...
Overbeek, Saskia A.; Braber, Saskia; Koelink, Pim J.; Henricks, Paul A. J.; Mortaz, Esmaeil; Loi, Adele T. LoTam; Jackson, Patricia L.; Garssen, Johan; Wagenaar, Gerry T. M.; Timens, Wim; Koenderman, Leo; Blalock, J. Edwin; Kraneveld, Aletta D.; Folkerts, Gert
Background: Cigarette smoking induces inflammatory responses in all smokers and is the major risk factor for lung disease such as chronic obstructive pulmonary disease (COPD). In this progressive disease, chronic inflammation in the lung contributes to lung tissue destruction leading to the formatio
Egyed, M N; Shlosberg, A; Eilat, A; Malkinson, M
The acute and chronic symptoms seen in ducks following Ammi majus induced photosensitisation are described. The acute changes were inflammatory in nature whereas the chronic changes included severe deformities of the beak and footwebs, mydriasis and eccentric location of the pupil.
Retmanasari, Annisa; Widartono, Barandi Sapta; Wijayanti, Mahardika Agus; Artama, Wayan Tunas
Toxoplasmosis is a zoonosis caused by Toxoplasma gondii. Risk factors include consumption of undercooked meat, raw vegetables, and unfiltered water. This study aims to determine the seroprevalence and spatial distribution of toxoplasmosis in Middle Java, Indonesia, using an EcoHealth approach, combined with geographic information system (GIS). A total of 630 participants were randomly selected from seven districts. Each participant completed a questionnaire and provided a blood sample. The seroprevalence of toxoplasmosis was 62.5%. Of those who were seropositive, 90.1% were IgG+, and 9.9% were IgG+ and IgM+. Several risk factors were identified, including living at elevations of ≤200 m, compared with >200 m (OR = 56.2; P Java has a high prevalence of toxoplasmosis and identified some important environmental, ecological, and demographic risk factors. When researching diseases, such as toxoplasmosis, where animal hosts, human lifestyle, and environmental factors are involved in transmission, an EcoHealth method is essential to ensure a fully collaborative approach to developing interventions to reduce the risk of transmission in high-risk populations.
Full Text Available Purpose: Branch retinal artery occlusion (BRAO, while not uncommon in elderly patient populations, is rare in children and adolescents. We report a case of a BRAO secondary to toxoplasmosis in this demographic. Case: A previously healthy 17-year-old male developed a unilateral BRAO in conjunction with inflammation and increased intraocular pressure. Family history was positive for cerebrovascular accidents in multiple family members at relatively young ages. The patient had a hypercoagulable workup as well as a cardiovascular workup which were both normal. A rheumatologic workup was unremarkable. By 3 weeks, a patch of retinitis was more easily distinguished from the BRAO and the diagnosis of ocular toxoplasmosis was made. Treatment was started with prednisone and azithromycin with subsequent improvement in vision. Toxoplasma antibody levels were elevated for IgG and negative for IgM, IgA, and IgE. The etiology of the BRAO was attributed to ocular toxoplasmosis. Conclusions: Vascular occlusions are rare in toxoplasmosis. This is the third case report of a BRAO in a patient in the pediatric population. The diagnosis of ocular toxoplasmosis should be considered in young patients with retinal artery occlusions associated with inflammation.
Chiang, Elizabeth; Goldstein, Debra A; Shapiro, Michael J; Mets, Marilyn B
Branch retinal artery occlusion (BRAO), while not uncommon in elderly patient populations, is rare in children and adolescents. We report a case of a BRAO secondary to toxoplasmosis in this demographic. A previously healthy 17-year-old male developed a unilateral BRAO in conjunction with inflammation and increased intraocular pressure. Family history was positive for cerebrovascular accidents in multiple family members at relatively young ages. The patient had a hypercoagulable workup as well as a cardiovascular workup which were both normal. A rheumatologic workup was unremarkable. By 3 weeks, a patch of retinitis was more easily distinguished from the BRAO and the diagnosis of ocular toxoplasmosis was made. Treatment was started with prednisone and azithromycin with subsequent improvement in vision. Toxoplasma antibody levels were elevated for IgG and negative for IgM, IgA, and IgE. The etiology of the BRAO was attributed to ocular toxoplasmosis. Vascular occlusions are rare in toxoplasmosis. This is the third case report of a BRAO in a patient in the pediatric population. The diagnosis of ocular toxoplasmosis should be considered in young patients with retinal artery occlusions associated with inflammation.
Basso, W; Edelhofer, R; Zenker, W; Möstl, K; Kübber-Heiss, A; Prosl, H
Manuls or Pallas' cats (Felis manul, syn. Otocolobus manul) are endangered wild cats from Central Asia kept and bred in many zoos. Despite good breeding success young cats frequently die from acute toxoplasmosis. From 1998 to 2002, a breeding pair in the Schönbrunn Zoo in Vienna, Austria, gave birth to 24 kittens; 58 % of kittens died between the 2nd and the 14th week of life, mostly due to acute toxoplasmosis. The epidemiology of toxoplasmosis in Pallas' cats was examined and a control strategy to protect the kittens from fatal toxoplasmosis was developed. One 12-week-old kitten from a litter of 6 born in 2001 died of generalized toxoplasmosis. This kitten had shed T. gondii oocysts that were bioassayed in mice. Toxoplasma gondii was isolated in tissue culture inoculated with tissues of these mice. The surviving animals were immediately treated with clindamycin for 16 weeks; they acquired a natural infection and seroconverted by the end of this time without clinical signs.
Liu, Quan; Wang, Ze-Dong; Huang, Si-Yang; Zhu, Xing-Quan
Toxoplasmosis, caused by the obligate intracellular protozoan Toxoplasma gondii, is an important zoonosis with medical and veterinary importance worldwide. The disease is mainly contracted by ingesting undercooked or raw meat containing viable tissue cysts, or by ingesting food or water contaminated with oocysts. The diagnosis and genetic characterization of T. gondii infection is crucial for the surveillance, prevention and control of toxoplasmosis. Traditional approaches for the diagnosis of toxoplasmosis include etiological, immunological and imaging techniques. Diagnosis of toxoplasmosis has been improved by the emergence of molecular technologies to amplify parasite nucleic acids. Among these, polymerase chain reaction (PCR)-based molecular techniques have been useful for the genetic characterization of T. gondii. Serotyping methods based on polymorphic polypeptides have the potential to become the choice for typing T. gondii in humans and animals. In this review, we summarize conventional non-DNA-based diagnostic methods, and the DNA-based molecular techniques for the diagnosis and genetic characterization of T. gondii. These techniques have provided foundations for further development of more effective and accurate detection of T. gondii infection. These advances will contribute to an improved understanding of the epidemiology, prevention and control of toxoplasmosis.
Dubey, J P; Tiao, N; Gebreyes, W A; Jones, J L
Toxoplasmosis caused by the protozoan parasite, Toxoplasma gondii, is a worldwide zoonosis. In this paper published information on toxoplasmosis in humans and other animals in Ethiopia is reviewed. Limited data indicate that the prevalence of T. gondii in humans in Ethiopia is very high, up to 41% of children aged 1-5 years were reported to be seropositive. There is little information on seroprevalence data in pregnant women and no data on congenital toxoplasmosis in children. About 1 million adults in Ethiopia are considered to be infected with HIV with less than one-third likely receive highly active antiviral therapy. Based on a conservative T. gondii seroprevalence of 50%, thousands might die of concurrent opportunistic infections, including toxoplasmosis. However, exact figures are not available, and most serological surveys are not current. Serological surveys indicate up to 79% of goats and sheep have T. gondii antibodies. However, there is no information on losses due to toxoplasmosis in livestock or the presence of viable T. gondii in any host in Ethiopia.
Sánchez, Víctor; de-la-Torre, Alejandra; Gómez-Marín, Jorge Enrique
The role of the virulent gene ROP18 polymorphisms is not known in human toxoplasmosis. A total of 320 clinical samples were analyzed. In samples positive for ROP18 gene, we determined by an allele specific PCR, if patients got the upstream insertion positive ROP18 sequence Toxoplasma strain (mouse avirulent strain) or the upstream insertion negative ROP18 sequence Toxoplasma strain (mouse virulent strain). We designed an ELISA assay for antibodies against ROP18 derived peptides from the three major clonal lineages of Toxoplasma. 20 clinical samples were of quality for ROP18 allele analysis. In patients with ocular toxoplasmosis, a higher inflammatory reaction on eye was associated to a PCR negative result for the upstream region of ROP18. 23.3%, 33% and 16.6% of serums from individuals with ocular toxoplasmosis were positive for type I, type II and type III ROP18 derived peptides, respectively but this assay was affected by cross reaction. The absence of Toxoplasma ROP18 promoter insertion sequence in ocular toxoplasmosis was correlated with severe ocular inflammatory response. Determination of antibodies against ROP18 protein was not useful for serotyping in human toxoplasmosis.
Full Text Available Toxoplasmosis is caused by infection with the obligate intracellular parasite Toxoplasma gondii. Toxoplasmosis is generally a late complication of HIV infection and usually occurs in patients with CD4 + T-cell counts below 200/μl. Co-trimoxazole (trimethoprim plus sulfamethoxazole is the most common drug used in India for the treatment of AIDS-associated cerebral toxoplasmosis. Other alternative drugs used for the treatment of cerebral toxoplasmosis are clindamycin plus pyrimethamine and clarithromycin with pyrimethamine.A 30-year-old male known case of retroviral disease presented to Kasturba Medical College, India, with complaints of fever, headache and vomiting. Computed tomography scan of his brain showed irregular ring enhancing lesion in the right basal ganglia. Toxoplasma serology revealed raised IgG antibody levels. Based on the CT features and serology, diagnosis of cerebral toxoplasmosis was made. He was treated with clindamycin alone as he had historyof sulfonamide allergy. The patient was symptomatically better after 48 hours. After 21 days, repeat CT of brain was done which was normal. The patient showed good clinical improvement within 48 hours and the lesion resolved completely within 3 weeks. The authors recommend using clindamycin without pyrimethamine in resource poor settings and in patients who do not tolerate sulfa drugs.
Haugan, Ketil; Miyamoto, Takuya; Takeishi, Yasuchika; Kubota, Isao; Nakayama, Jun; Shimojo, Hisashi; Hirose, Masamichi
Chronic atrial dilation is associated with atrial conduction velocity slowing and an increased risk of developing atrial tachyarrhythmias. Rotigaptide (ZP123) is a selective gap junction modifier that increases cardiac gap junctional intercellular communication. We hypothesised that rotigaptide treatment would increase atrial conduction velocity and reduce the inducibility to atrial tachyarrhythmias in a model of chronic volume overload induced chronic atrial dilatation characterized by atrial conduction velocity slowing. Chronic volume overload was created in Japanese white rabbits by arterio-venous shunt formation. Atrial conduction velocity and atrial tachyarrhythmias inducibility were examined in Langendorff-perfused chronic volume overload hearts (n=12) using high-resolution optical mapping before and after treatment with rotigaptide. Moreover, expression levels of atrial gap junction proteins (connexin40 and connexin43) were examined in chronic volume overload hearts (n=6) and compared to sham-operated controls (n=6). Rotigaptide treatment significantly increased atrial conduction velocity in chronic volume overload hearts, however, rotigaptide did not decrease susceptibility to the induction of atrial tachyarrhythmias. Protein expressions of Cx40 and Cx43 were decreased by 32% and 72% (P<0.01), respectively, in chromic volume overload atria compared to control. To conclude, rotigaptide increased atrial conduction velocity in a rabbit model of chromic volume overload induced atrial conduction velocity slowing. The demonstrated effect of rotigaptide on atrial conduction velocity did not prevent atrial tachyarrhythmias inducibility. Whether rotigaptide may possess antiarrhythmic efficacy in other models of atrial fibrillation remains to be determined.
Grzybowski, Marcin M; Dziadek, Bożena; Gatkowska, Justyna M; Dzitko, Katarzyna; Długońska, Henryka
Toxoplasmosis is one of the most common parasitic infections worldwide. An effective vaccine against human and animal toxoplasmosis is still needed to control this parasitosis. The polymorphic rhoptry proteins, ROP5 and ROP18, secreted by Toxoplasma gondii during the invasion of the host cell have been recently considered as promising vaccine antigens, as they appear to be the major determinants of T. gondii virulence in mice. The goal of this study was to evaluate their immunogenic and immunoprotective activity after their administration (separately or both recombinant proteins together) with the poly I:C as an adjuvant. Immunization of BALB/c and C3H/HeOuJ mice generated both cellular and humoral specific immune responses with some predominance of IgG1 antibodies. The spleen cells derived from vaccinated animals reacted to the parasite's native antigens. Furthermore, the immunization led to a partial protection against acute and chronic toxoplasmosis. These findings confirm the previous assumptions about ROP5 and ROP18 antigens as valuable components of a subunit vaccine against toxoplasmosis.
Hilda Fátima de Jesus Pena
Full Text Available Abstract The objective of the study was to report on a fatal case of feline toxoplasmosis with coinfection with the feline leukemia virus (FeLV. A domestic cat (Felis silvestris catus presented intense dyspnea and died three days later. In the necropsy, the lungs were firm, without collapse and with many white areas; moderate lymphadenomegaly and splenomegaly were also observed. The histopathological examination showed severe necrotic interstitial bronchopneumonia and mild necrotic hepatitis, associated with intralesional cysts and tachyzoites of Toxoplasma gondii that were positive by anti-T. gondii immunohistochemical (IHC evaluation. The bone marrow showed chronic myeloid leukemia and the neoplastic cells were positive by anti-FeLV IHC evaluation. DNA extracted from lungs was positive for T. gondii by PCR targeting REP-529. T. gondii was characterized by PCR-RFLP and by the microsatellites technique. ToxoDB-PCR-RFLP #10, i.e. the archetypal type I, was identified. Microsatellite analysis showed that the strain was a variant of type I with two atypical alleles. This was the first time that a T. gondii clonal type I genotype was correlated with a case of acute toxoplasmosis in a host in Brazil.
Chen, J; Winston, J H; Sarna, S K
The role of inflammation in inducing visceral hypersensitivity (VHS) in ulcerative colitis patients remains unknown. We tested the hypothesis that acute ulcerative colitis-like inflammation does not induce VHS. However, it sets up molecular conditions such that chronic stress following inflammation exaggerates single-unit afferent discharges to colorectal distension. We used dextran sodium sulfate (DSS) to induce ulcerative colitis-like inflammation and a 9-day heterotypic chronic stress protocol in rats. DSS upregulated Nav1.8 mRNA in colon-responsive dorsal root ganglion (DRG) neurons, TRPV1 in colonic muscularis externae (ME) and BDNF in spinal cord without affecting the spike frequency in spinal afferents or VMR to CRD. By contrast, chronic stress did not induce inflammation but it downregulated Kv1.1 and Kv1.4 mRNA in DRG neurons, and upregulated TRPA1 and nerve growth factor in ME, which mediated the increase of spike frequency and VMR to CRD. Chronic stress following inflammation exacerbated spike frequency in spinal afferent neurons. TRPA1 antagonist suppressed the sensitization of afferent neurons. DSS-inflammation did not affect the composition or excitation thresholds of low-threshold and high-threshold fibers. Chronic stress following inflammation increased the percent composition of high-threshold fibers and lowered the excitation threshold of both types of fibers. We conclude that not all types of inflammation induce VHS, whereas chronic stress induces VHS in the absence of inflammation.
Başaran, Özge; Çakar, Nilgün; Gür, Gökçe; Kocabaş, Abdullah; Gülhan, Belgin; Çaycı, Fatma Şemsa; Çelikel, Banu Acar
Polyarteritis nodosa (PAN) is a vasculitis characterized by inflammatory necrosis of medium-sized arteries. Juvenile PAN and Kawasaki disease (KD) both cause vasculitis of the medium-sized arteries, and share common features. They have overlapping clinical features. Treatment should be managed according to the severity of symptoms and persistence of clinical manifestations. Herein is described the case of a 14-year-old boy first diagnosed with KD, who then fulfilled the criteria for juvenile PAN due to the development of severe myalgia, persistent fever, polyneuropathy and coronary arterial dilatation. He also had acute toxoplasmosis at the onset of vasculitis symptoms. The final diagnosis was of juvenile PAN associated with toxoplasmosis infection. Toxoplasma infection can be considered as an etiological agent for PAN and other vasculitis syndromes. Awareness of toxoplasmosis-related PAN facilitates early diagnosis, and instigation of appropriate treatment.
Jones, Jeffrey L; Parise, Monica E; Fiore, Anthony E
Toxoplasma gondii is a leading cause of severe foodborne illness in the United States. Population-based studies have found T. gondii infection to be more prevalent in racial/ethnic minority and socioeconomically disadvantaged groups. Soil contaminated with cat feces, undercooked meat, and congenital transmission are the principal sources of infection. Toxoplasmosis-associated illnesses include congenital neurologic and ocular disease; acquired illness in immunocompetent persons, most notably ocular disease; and encephalitis or disseminated disease in immunosuppressed persons. The association of T. gondii infection with risk for mental illness is intriguing and requires further research. Reduction of T. gondii in meat, improvements in hygiene and food preparation practices, and reduction of environmental contamination can prevent toxoplasmosis, but more research is needed on how to implement these measures. In addition, screening and treatment may help prevent toxoplasmosis or reduce the severity of disease in some settings.
Zahir, Fadoua; Abdellaoui, Meriem; Younes, Samar; Benatiya, Idriss A; Tahri, Hicham
Retinochoroiditis is the most common ocular manifestation of congenital toxoplasmosis, but other associated ophthalmological pathologies can also occur. Ophthalmologists are rarely able to distinguish between toxoplasmic retinochoroiditis due to infection acquired before or after birth, unless other clinical or serological indications are present. This article reports a case of a 3-year-old boy with abnormalities suggestive of congenital toxoplasmosis. The clinical and complementary examinations are discussed. The education of pregnant women is crucial for the prevention of congenital toxoplasmosis. Awareness of antenatal and postnatal presenting signs and symptoms is important for clinicians, because early diagnosis and treatment may minimize sequelae. Untreated, the majority of affected infants will develop chorioretinitis, deafness and/or neurological symptoms.
Sibalić, D; Durković-Daković, O; Bobić, B
On the occasion of the thirty-five years of systematic research of toxoplasmosis, a review of the present knowledge of the role of toxoplasmosis in pregnancy is presented. Diagnostic procedures and the interpretation of the results of laboratory examinations are particularly stressed. The main conclusion is that in a population exposed to the infection in the way as was in the cases studied, the prevention of congenital toxoplasmosis can be achieved through a serologic follow-up of all pregnant women starting from the moment when pregnancy is established. The purpose of such screening is to identify those pregnant women who are not immunized (who are then advised to follow certain hygienic and dietetic measures) and those who are primoinfected in pregnancy. As the latter are at risk for transmitting the infection to their fetuses, they receive specific therapy and their fetuses are carefully controlled by ultrasound and other methods for the antenatal diagnosis of intrauterine infection.
Pinzan, Camila Figueiredo; Sardinha-Silva, Aline; Almeida, Fausto; Lai, Livia; Lopes, Carla Duque; Lourenço, Elaine Vicente; Panunto-Castelo, Ademilson; Matthews, Stephen; Roque-Barreira, Maria Cristina
Toxoplasmosis, a zoonotic disease caused by Toxoplasma gondii, is an important public health problem and veterinary concern. Although there is no vaccine for human toxoplasmosis, many attempts have been made to develop one. Promising vaccine candidates utilize proteins, or their genes, from microneme organelle of T. gondii that are involved in the initial stages of host cell invasion by the parasite. In the present study, we used different recombinant microneme proteins (TgMIC1, TgMIC4, or TgMIC6) or combinations of these proteins (TgMIC1-4 and TgMIC1-4-6) to evaluate the immune response and protection against experimental toxoplasmosis in C57BL/6 mice. Vaccination with recombinant TgMIC1, TgMIC4, or TgMIC6 alone conferred partial protection, as demonstrated by reduced brain cyst burden and mortality rates after challenge. Immunization with TgMIC1-4 or TgMIC1-4-6 vaccines provided the most effective protection, since 70% and 80% of mice, respectively, survived to the acute phase of infection. In addition, these vaccinated mice, in comparison to non-vaccinated ones, showed reduced parasite burden by 59% and 68%, respectively. The protective effect was related to the cellular and humoral immune responses induced by vaccination and included the release of Th1 cytokines IFN-γ and IL-12, antigen-stimulated spleen cell proliferation, and production of antigen-specific serum antibodies. Our results demonstrate that microneme proteins are potential vaccines against T. gondii, since their inoculation prevents or decreases the deleterious effects of the infection.
Camila Figueiredo Pinzan
Full Text Available Toxoplasmosis, a zoonotic disease caused by Toxoplasma gondii, is an important public health problem and veterinary concern. Although there is no vaccine for human toxoplasmosis, many attempts have been made to develop one. Promising vaccine candidates utilize proteins, or their genes, from microneme organelle of T. gondii that are involved in the initial stages of host cell invasion by the parasite. In the present study, we used different recombinant microneme proteins (TgMIC1, TgMIC4, or TgMIC6 or combinations of these proteins (TgMIC1-4 and TgMIC1-4-6 to evaluate the immune response and protection against experimental toxoplasmosis in C57BL/6 mice. Vaccination with recombinant TgMIC1, TgMIC4, or TgMIC6 alone conferred partial protection, as demonstrated by reduced brain cyst burden and mortality rates after challenge. Immunization with TgMIC1-4 or TgMIC1-4-6 vaccines provided the most effective protection, since 70% and 80% of mice, respectively, survived to the acute phase of infection. In addition, these vaccinated mice, in comparison to non-vaccinated ones, showed reduced parasite burden by 59% and 68%, respectively. The protective effect was related to the cellular and humoral immune responses induced by vaccination and included the release of Th1 cytokines IFN-γ and IL-12, antigen-stimulated spleen cell proliferation, and production of antigen-specific serum antibodies. Our results demonstrate that microneme proteins are potential vaccines against T. gondii, since their inoculation prevents or decreases the deleterious effects of the infection.
Katsube, Takanori; Wang, Bing; Tanaka, Kaoru; Ninomiya, Yasuharu; Varès, Guillaume; Kawagoshi, Taiki; Shiomi, Naoko; Kubota, Yoshihisa; Liu, Qiang; Morita, Akinori; Nakajima, Tetsuo; Nenoi, Mitsuru
Both ionizing radiation (IR) and psychological stress (PS) cause detrimental effects on humans. A recent study showed that chronic restraint-induced PS (CRIPS) diminished the functions of Trp53 and enhanced radiocarcinogenesis in Trp53-heterozygous (Trp53(+/-)) mice. These findings had a marked impact on the academic field as well as the general public, particularly among residents living in areas radioactively contaminated by nuclear accidents. In an attempt to elucidate the modifying effects of CRIPS on radiation-induced health consequences in Trp53 wild-type (Trp53(+/+)) animals, investigations involving multidisciplinary analyses were performed. We herein demonstrated that CRIPS induced changes in the frequency of IR-induced chromosomal aberrations (CAs) in splenocytes. Five-week-old male Trp53(+/+) C57BL/6J mice were restrained for 6h per day for 28 consecutive days, and total body irradiation (TBI) at a dose of 4Gy was performed on the 8th day. Metaphase chromosome spreads prepared from splenocytes at the end of the 28-day restraint regimen were painted with fluorescence in situ hybridization (FISH) probes for chromosomes 1, 2, and 3. The results obtained showed that CRIPS alone did not induce CAs, while TBI caused significant increases in CAs, mostly translocations. Translocations appeared at a lower frequency in mice exposed to TBI plus CRIPS than in those exposed to TBI alone. No significant differences were observed in the frequencies of the other types of CAs (insertions, dicentrics, and fragments) visualized with FISH between these experimental groups (TBI+CRIPS vs. TBI). These results suggest that CRIPS does not appear to synergize with the clastogenicity of IR.
Gómez-Marin, Jorge Enrique; de-la-Torre, Alejandra; Angel-Muller, Edith; Rubio, Jorge; Arenas, Jaime; Osorio, Elkin; Nuñez, Lilian; Pinzon, Lyda; Mendez-Cordoba, Luis Carlos; Bustos, Agustin; de-la-Hoz, Isabel; Silva, Pedro; Beltran, Monica; Chacon, Leonor; Marrugo, Martha; Manjarres, Cristina; Baquero, Hernando; Lora, Fabiana; Torres, Elizabeth; Zuluaga, Oscar Elias; Estrada, Monica; Moscote, Lacides; Silva, Myriam Teresa; Rivera, Raul; Molina, Angie; Najera, Shirley; Sanabria, Antonio; Ramirez, Maria Luisa; Alarcon, Claudia; Restrepo, Natalia; Falla, Alejandra; Rodriguez, Tailandia; Castaño, Giovanny
Aims To determine the incidence of congenital toxoplasmosis in Colombian newborns from 19 hospital or maternal child health services from seven different cities of five natural geographic regions (Caribbean, Central, Andean, Amazonia and Eastern). Materials and Methods We collected 15,333 samples from umbilical cord blood between the period of March 2009 to May 2010 in 19 different hospitals and maternal-child health services from seven different cities. We applied an IgM ELISA assay (Vircell, Spain) to determine the frequency of IgM anti Toxoplasma. The results in blood cord samples were confirmed either by western blot and repeated ELISA IgM assay. In a sub-sample of 1,613 children that were negative by the anti-Toxoplasma IgM assay, the frequency of specific anti-Toxoplasma IgA by the ISAGA assay was determined. All children with positive samples by IgM, IgA, clinical diagnosis or treatment during pregnancy were recalled for confirmatory tests after day 10 of life. Results 61 positive samples for specific IgM (0.39%) and 9 positives for IgA (0.5%) were found. 143 questionnaires were positive for a clinical diagnosis or treatment for toxoplasmosis during pregnancy. 109 out of the 218 children that had some of the criteria for postnatal confirmatory tests were followed. Congenital toxoplasmosis infection was confirmed in 15 children: 7 were symptomatic, and three of them died before the first month of life (20% of lethality). A significant correlation was found between a high incidence of markers for congenital toxoplasmosis and higher mean annual rainfall for the city. Conclusions Incidence for congenital toxoplasmosis is significantly different between hospitals or maternal child health services from different cities in Colombia. Mean annual rainfall was correlated with incidence of congenital toxoplasmosis. PMID:21655304
Jorge Enrique Gómez-Marin
Full Text Available AIMS: To determine the incidence of congenital toxoplasmosis in Colombian newborns from 19 hospital or maternal child health services from seven different cities of five natural geographic regions (Caribbean, Central, Andean, Amazonia and Eastern. MATERIALS AND METHODS: We collected 15,333 samples from umbilical cord blood between the period of March 2009 to May 2010 in 19 different hospitals and maternal-child health services from seven different cities. We applied an IgM ELISA assay (Vircell, Spain to determine the frequency of IgM anti Toxoplasma. The results in blood cord samples were confirmed either by western blot and repeated ELISA IgM assay. In a sub-sample of 1,613 children that were negative by the anti-Toxoplasma IgM assay, the frequency of specific anti-Toxoplasma IgA by the ISAGA assay was determined. All children with positive samples by IgM, IgA, clinical diagnosis or treatment during pregnancy were recalled for confirmatory tests after day 10 of life. RESULTS: 61 positive samples for specific IgM (0.39% and 9 positives for IgA (0.5% were found. 143 questionnaires were positive for a clinical diagnosis or treatment for toxoplasmosis during pregnancy. 109 out of the 218 children that had some of the criteria for postnatal confirmatory tests were followed. Congenital toxoplasmosis infection was confirmed in 15 children: 7 were symptomatic, and three of them died before the first month of life (20% of lethality. A significant correlation was found between a high incidence of markers for congenital toxoplasmosis and higher mean annual rainfall for the city. CONCLUSIONS: Incidence for congenital toxoplasmosis is significantly different between hospitals or maternal child health services from different cities in Colombia. Mean annual rainfall was correlated with incidence of congenital toxoplasmosis.
Full Text Available Acquired and congenital toxoplasmosis are frequently complicated by ocular toxoplasmosis. The diagnosis relies on clinical aspects, response to specific treatment and results of biological assays. The incidence and the prevalence of this complication are difficult to establish precisely and depend on the prevalence of the parasite infection in the general population, and are affected by factors such as type of exposure to the parasite, genetic backgrounds of the parasite and the host, and type of immune response elicited by the parasite.
Pfaff, Nicole Franzen; Tillett, Jackie
Listeriosis and toxoplasmosis are foodborne illnesses that can have long-term consequences when contracted during pregnancy. Listeriosis is implicated in stillbirth, preterm labor, newborn sepsis, and meningitis, among other complications. Toxoplasmosis is associated with blindness, cognitive delays, seizures, and hearing loss, among other significant disabilities. Healthcare providers who understand the fundamentals of Listeria and Toxoplasma infection will have the tools to identify symptoms and high-risk behaviors, educate women to make safer decisions, and provide anticipatory guidance if a pregnant woman would become infected with either of these foodborne illnesses.
Logar, J; Novak-Antolic, Z; Zore, A
In the period from 1981 to 1994, serological screening for toxoplasmosis was carried out in 20,953 pregnant women in Slovenia. Seropositivity among pregnant women was found to have decreased from 52% in the 1980s to 37% in the recent period, 1991-94, while during the same period the incidence of suspected primary infections acquired in pregnancy rose from 0.33% to 0.75%. These latest figures ought to promote an informed debate on the possible need for obligatory serological screening of pregnant women in Slovenia for toxoplasmosis.
Coluccia, Daniel; Wolf, Oliver T; Kollias, Spyros; Roozendaal, Benno; Forster, Adrian; de Quervain, Dominique J-F
Conditions with chronically elevated glucocorticoid levels are usually associated with declarative memory deficits. Considerable evidence suggests that long-term glucocorticoid exposure may cause cognitive impairment via cumulative and long-lasting influences on hippocampal function and morphology. However, because elevated glucocorticoid levels at the time of retention testing are also known to have direct impairing effects on memory retrieval, it is possible that such acute hormonal influences on retrieval processes contribute to the memory deficits found with chronic glucocorticoid exposure. To investigate this issue, we examined memory functions and hippocampal volume in 24 patients with rheumatoid arthritis who were treated either chronically (5.3 +/- 1.0 years, mean +/- SE) with low to moderate doses of prednisone (7.5 +/- 0.8 mg, mean +/- SE) or without glucocorticoids. In both groups, delayed recall of words learned 24 h earlier was assessed under conditions of either elevated or basal glucocorticoid levels in a double-blind, placebo-controlled crossover design. Although the findings in this patient population did not provide evidence for harmful effects of a history of chronic prednisone treatment on memory performance or hippocampal volume per se, acute prednisone administration 1 h before retention testing to either the steroid or nonsteroid group impaired word recall. Thus, these findings indicate that memory deficits observed under chronically elevated glucocorticoid levels result, at least in part, from acute and reversible glucocorticoid effects on memory retrieval.
Kondo, Kazuma; Yamada, Naohito; Suzuki, Yusuke; Toyoda, Kaoru; Hashimoto, Tatsuji; Takahashi, Akemi; Kobayashi, Akio; Shoda, Toshiyuki; Kuno, Hideyuki; Sugai, Shoichiro
Acetaminophen (APAP) is a commonly used and effective analgesic and antipyretic agent. However, some patients encounter hepatotoxicity after repeated APAP dosing at therapeutic doses. In the present study, we focused on the nutritional state as one of the risk factors of APAP-induced chronic hepatotoxicity in humans and investigated the contribution of undernourishment to susceptibility to APAP-induced chronic hepatotoxicity using an animal model mimicking undernourished patients. Rats were divided into 2 groups: the ad libitum fed (ALF) and the restricted fed (RF) rats and were assigned to 3 groups (n = 8/group) for each feeding condition. The animals were given APAP at 0, 300 and 500mg/kg for 99 days under each feeding condition. Plasma and urinary glutathione-related metabolites and liver function parameters were measured during the dosing period and hepatic glutathione levels were measured at the end of the dosing period. In the APAP-treated ALF rats hepatic glutathione levels were increased and hepatic function parameters were not changed, but in the APAP-treated RF rats hepatic glutathione levels were decreased at 500mg/kg and hepatic function parameters were increased at 300 and 500mg/kg. Moreover the urinary endogenous metabolite profile after long-term treatment with APAP in the ALF and RF rats was similar to that in human non-responders and responders to APAP-induced chronic hepatotoxicity, respectively. In conclusion, the RF rats were more sensitive to APAP-induced chronic hepatotoxicity than the ALF rats and were considered to be a useful model to estimate the contribution of the nutritional state of patients to APAP-induced chronic hepatotoxicity.
Guang-Liang Jiang; Wha Bin Im; Yariv Donde; Larry A Wheeler
AIM: To investigate EP4-selective agonist effect on indomethacin-induced gastric lesions and on the spontaneous healing of chronic gastric ulcers. METHODS: In a mouse model of gastric bleeding with high dose of indomethacin (20 mg/kg), an EP4-selective agonist was administered orally. Stomach lesions and gastric mucous regeneration were monitored. In a mouse model of chronic gastric ulcer induced by acetic acid, EP4 agonist effect on the healing of chronic gastric ulcer was evaluated in the presence or absence of low dose indomethacin (3 mg/kg). In cultured human gastric mucous cells, EP4 agonist effect on indomethacininduced apoptosis was assessed by flow cytometry. RESULTS: The EP4-selective agonist reduced high dose indomethacin-induced acute hemorrhagic damage and promoted mucous epithelial regeneration. Low-dose indomethacin aggravated ulcer bleeding and inflammation, and delayed the healing of the established chronic gastric ulcer. The EP4 agonist, when applied locally, not only offset indomethacin-induced gastric bleeding and inflammation, but also accelerated ulcer healing. In the absence of indomethacin, the EP4 agonist even accelerated chronic gastric ulcer healing and suppressed inflammatory cell infiltration in the granulation tissue. In vitro , the EP4 agonist protected human gastric mucous cells from indomethacin-induced apoptosis. CONCLUSION: EP4-selective agonist may prevent indomethacin-induced gastric lesions and promote healing of existing and indomethacin-aggravated gastric ulcers, via promoting proliferation and survival of mucous epithelial cells.
Víctor A. Castillo; Gámbaro, Germán; Sinatra Verónica
Resúmen La tiroiditis subaguda es causada por la acción de agentes infecciosos. Clínicamente se observa bocio, disfonía y disfagia. Respecto a la función tiroidea, puede haber hipertirotoxinemia debida a la ruptura de folículos, en tanto que la concentración de TSH se mantiene normal y la captación de yodo está disminuída. El objetivo del presente trabajo fue investigar si la toxoplasmosis en perros puede afectar la morfología y función tiroidea. Se estudiaron 8 perros con toxoplasmosis comp...
Zlatković, Jelena; Todorović, Nevena; Tomanović, Nada; Bošković, Maja; Djordjević, Snežana; Lazarević-Pašti, Tamara; Bernardi, Rick E; Djurdjević, Aleksandra; Filipović, Dragana
Chronic exposure to stress contributes to the etiology of mood disorders, and the liver as a target organ of antidepressant and antipsychotic drug metabolism is vulnerable to drug-induced toxicity. We investigated the effects of chronic administration of fluoxetine (15mg/kg/day) or clozapine (20mg/kg/day) on liver injury via the measurement of liver enzymes, oxidative stress and histopathology in rats exposed to chronic social isolation (21days), an animal model of depression, and controls. The activity of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the liver content of carbonyl groups, malonyldialdehyde (MDA), reduced glutathione (GSH), cytosolic glutathione S-transferase (GST) and nitric oxide (NO) metabolites were determined. We also characterized nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2) and CuZn-superoxide dismutase (CuZnSOD) protein expression as well as histopathological changes. Increased serum ALT activity in chronically-isolated and control animals treated with both drugs was found while increased AST activity was observed only in fluoxetine-treated rats (chronically-isolated and controls). Increased carbonyl content, MDA, GST activity and decreased GSH levels in drug-treated controls/chronically-isolated animals suggest a link between drugs and hepatic oxidative stress. Increased NO levels associated with NF-κB activation and the concomitant increased COX-2 expression together with compromised CuZnSOD expression in clozapine-treated chronically-isolated rats likely reinforce oxidative stress, observed by increased lipid peroxidation and GSH depletion. In contrast, fluoxetine reduced NO levels in chronically-isolated rats. Isolation induced oxidative stress but histological changes were similar to those observed in vehicle-treated controls. Chronic administration of fluoxetine in both chronically-isolated and control animals resulted in more or less normal hepatic architecture, while clozapine in both groups
Brain plasticity associated with anomia recovery in aphasia is poorly understood. Here, I review four recent studies from my lab that focused on brain modulation associated with long-term anomia outcome, its behavioral treatment, and the use of transcranial brain stimulation to enhance anomia treatment success in individuals with chronic aphasia…
Abbas, Shabber Agha; Bhatti, Hammad; Braver, Yvonne; Ali, Sayed K.
Pulmonary adverse events are common abnormalities associated with the use of dasatinib in chronic myeloid leukemia. We present a case of a 69-year-old man who suddenly developed a rare chylothorax pulmonary adverse event following 10 months of dasatinib treatment.
Ferreira, A I C; De Mattos, C C Brandão; Frederico, F B; Meira, C S; Almeida, G C; Nakashima, F; Bernardo, C R; Pereira-Chioccola, V L; De Mattos, L C
The aim of this study was to investigate risk factors for ocular toxoplasmosis (OT) in patients who received medical attention at a public health service. Three hundred and forty-nine consecutive patients, treated in the Outpatient Eye Clinic of Hospital de Base, São José do Rio Preto, São Paulo state, Brazil, were enrolled in this study. After an eye examination, enzyme-linked immunosorbent assay (ELISA) was used to determine anti-Toxoplasma gondii antibodies. The results showed that 25.5% of the patients were seronegative and 74.5% were seropositive for IgG anti-T. gondii antibodies; of these 27.3% had OT and 72.7% had other ocular diseases (OOD). The presence of cats or dogs [odds ratio (OR) 2.22, 95% confidence interval (CI) 1.24-3.98, P = 0.009] and consumption of raw or undercooked meat (OR 1.77, 95% CI 1.05-2.98, P = 0.03) were associated with infection but not with the development of OT. Age (OT 48.2 ± 21.2 years vs. OOD: 69.5 ± 14.7 years, P < 0.0001) and the low level of schooling/literacy (OT vs. OOD: OR 0.414, 95% CI 0.2231-0.7692, P = 0.007) were associated with OT. The presence of dogs and cats as well as eating raw/undercooked meat increases the risk of infection, but is not associated with the development of OT.
Susanna S. Nagel
Full Text Available A 10-year-old domestic short hair cat was referred for investigation of anorexia and polydipsia of 3 days’ duration. Clinically the cat was obese, pyrexic (39.8 °C, had acute abdominal pain and severe bilirubinuria. Haematology and serum biochemistry revealed severe panleukopenia, thrombocytopenia, markedly elevated alanine aminotransferase (ALT and five-fold increased pre-prandial bile acids. Ultrasonographic evaluation of the abdomen did not identify any abnormalities. Serum tests for feline immunodeficiency virus (FIV and feline leukaemia virus (FeLV were negative. Broad-spectrum antibiotic treatment for infectious hepatitis was to no avail; the cat deteriorated and died 72 h after admission. Necropsy revealed mild icterus and anaemia, severe multifocal hepatic necrosis, serofibrinous hydrothorax, pulmonary oedema and interstitial pneumonia. Histopathology confirmed the macroscopic findings and revealed multifocal microgranulomata in the brain and myocardium, as well as areas of necrosis in lymph nodes and multifocally in splenic red pulp. Long bone shaft marrow was hyperplastic with a predominance of leukocyte precursors and megakaryocytes and splenic red pulp showed mild extramedullary haemopoiesis. Immunohistochemical staining for Toxoplasma gondii was strongly positive, with scattered cysts and tachyzoites in the liver, lymph nodes, spleen, lungs, brain, salivary glands and intracellularly in round cells in occasional blood vessels. Immunohistochemical staining for corona virus on the same tissues was negative, ruling out feline infectious peritonitis (FIP. Polymerase chain reaction (PCR on formalin-fixed paraffin-wax embedded tissues was positive for Toxoplasma sp., but attempts at sequencing were unsuccessful. This was the first case report of fulminant disseminated toxoplasmosis in South Africa, in which detailed histopathology in an apparently immunocompetent cat was described.
Hermida Pérez, J A; Bermejo Hernandez, Á; Sobenes Gutierrez, R
Toxoplasmosis is an infection of worldwide distribution caused by Toxoplasma gondii, and infects a large proportion of the world population. Only under certain circumstances of severe immunosuppression can the parasite reactivate and cause disease. The most common form of presentation of this pathology in patients with positive HIV is the brain abscess. One of the extra-cerebral forms is toxoplasmic chorioretinitis, which could lead to a chronic active form of a slowly progressive retinitis. Diagnosis is made by observing the eye fundus and confirmed by the scarring obtained after specific treatment. We report a case of a patient with diabetes and positive HIV, in whom a toxoplasmic scar injury was detected in the annual retinography follow-up. A conservative therapeutic approach was decided, with regular check-ups for possible detection of disease activation.
Maria del C. Contreras
Full Text Available A series of already published and unpublished seroepidemiological surveys for toxoplasmosis, carried out in Chile in 1982-1994, is reviewed, expanded and analyzed. The surveys included 76,317 apparently healthy individuals of different ages (0.57% of the country's total population, from 309 urban and rural-periurban localities. Urban groups were integrated by blood donors, delivering mothers and middle grade schoolchildren, while rural-periurban individuals corresponded to unselected family groups. Blood samples were collected in filter paper. The presence of antibodies to Toxoplasma gondii was determined by the indirect hemagglutination test (IHAT, titers > 16 were considered positive. The test resulted positive in 28,124 (36.9% of the surveyed people. Two hundred and six (0.3% individuals presented IHAT titers > 1000, probably corresponding to acute or reactivated infections. A progressive increase of positive IHAT from northern to southern regions of the country was noted, phenomenom probably related to geographical conditions and to a higher production and consumption of different types of meat in the latter regions. It is postulated that ingestion of T. gondii cysts by humans is epidemiologically as important as ingestion of oocysts. The results presented stress the epidemiological importance of toxoplasmosis in humans, and warn about eventual implications in immunocompromised patients and in transplacental transmission, organ transplants and transfusions.En este trabajo se revisa, se amplía y se analiza en conjunto una serie de encuestas seroepidemiológicas sobre toxoplasmosis efectuadas en Chile entre 1982 y 1994, utilizando la reacción de hemaglutinación indirecta (RHAI. El estudio incluyó 76.317 personas aparentemente sanas de diferentes edades (0,57% de la problación total del país, procedentes de 309 localidades urbanas y rural-periurbanas. Los grupos urbanos estuvieron constituídos por donantes de sangre, parturientas y
Peter M.S. Chang; Yee-Yung Ng
The overall incidence of amiodarone-induced thyroid dysfunction ranges from 2% to 24%. One third to half of patients with hypothyroidism have anemia due to some decrease in normal red blood cell mass and erythropoietin (EPO) resistance. Therefore, for patients with chronic renal disease under medication with amiodarone, early regular thyroid function test should be checked in order to avoid amiodarone-induced hypothyroidism and EPO-resistant anemia. If amiodarone-induced hypothyroidism and EP...
Klaren, V.N.A.; Kijlstra, A.
Toxoplasmosis is a common parasitic zoonosis and an important cause of abortions, mental retardation, encephalitis, blindness, and death worldwide. Although a large body of literature has emerged on the subject in the past decades, many questions about the pathogenesis and treatment of the disease r
Carral, Liliana; Kaufer, Federico; Olejnik, Patricia; Freuler, Cristina; Durlach, Ricardo
The prevention of congenital toxoplasmosis is based on providing information to women, serologic diagnosis and treatment of the infected mother and child. In this article we present the results of 12 years of implementation of a congenital toxoplasmosis prevention program in which we measured the mother's infection incidence rate, the transmission rate and the number and severity of infection in newborns. The study was performed on 12035 pregnant women in the period 2000-2011. The prevalence rate of antibodies against Toxoplasma gondii was 18.33% (2206/12035). Thirty-seven out of 9792 susceptible women presented acute infection and the mother's infection incidence rate was 3.78 per 1000 births. The transplacental transmission rate was 5.4% (2/37). Two newborns presented congenital toxoplasmosis infection, one had no clinical signs while the other presented strabismus and chorioretinitis. Thirty-five infected mothers and the two children with congenital infection were treated. The transmission rates obtained allow consider this prevention program as a valid resource to minimize the impact of congenital toxoplasmosis.
Kijlstra, A.; Jongert, E.
One-third of the human world population is infected with the protozoan parasite Toxoplasma gondii. Recent calculations of the disease burden of toxoplasmosis rank this foodborne disease at the same level as salmonellosis or campylobacteriosis. The high disease burden in combination with disappointin
Klaren, V.N.A.; Kijlstra, A.
Toxoplasmosis is a common parasitic zoonosis and an important cause of abortions, mental retardation, encephalitis, blindness, and death worldwide. Although a large body of literature has emerged on the subject in the past decades, many questions about the pathogenesis and treatment of the disease
Full Text Available Background. Gestational toxoplasmosis is acquired during pregnancy and involves a risk of the parasite crossing the placenta, thereby leading to foetal infection, which can lead to serious sequelae in children, mainly chorioretinitis, cerebral calcification, hydrocephalus and intellectual disability. Objective. Determining the prevalence of maternal and neonatal toxoplasmosis in women attending the Engativa and La Victoria hospitals in Bogota, Colombia, for delivery. Correlating the results with those of a national multicentre study. Determining IgM and IgA anti-toxoplasma prevalence in newborn (NB umbilical cord blood. Materials and methods. This was a cohort study, which was approved by the participating institutions' ethics committees. The patients signed informed consent forms and filled out a survey requesting demographic and prenatal care data. A blood sample was taken from the umbilical cord on delivery for determining anti-toxoplasma IgM. Anti-toxoplasma IgA was also measured in a subset of patients. Children suspected of having either clinical or serological congenital toxoplasmosis were followed-up for 12 months. Results. The study involved taking 3,224 NB umbilical cord blood samples between April 1st 2009 and July 16th 2010. Positive anti-toxoplasma IgG was found in 28.2% of pregnant women (26.1-29.8 95%CI. Anti-toxoplasma IgM was determined in 558 pregnant women and found positive in 34 patients (i.e. 1.1 per 100 NB gestational toxoplasmosis incidence. Nine blood samples were positive (7 for IgM and 2 for IgA. Five of the NB studied (0.15% were positive for IgG after 12 months' follow-up, thereby confirming a diagnosis of congenital toxoplasmosis accounting for 1 in every 645 live births. Conclusion. This study showed that 70% of the pregnant women were not infected with T. gondii in the chosen hospitals in Bogotá. Gestational toxoplasmosis frequency was around 1% and 0.6% for congenital toxoplasmosis.
Full Text Available Introduction. Health education of women of childbearing age has been shown to be an acceptable approach to the prevention of toxoplasmosis, the most frequent congenitally transmitted parasitic infection. Objective. The aim of this study was to evaluate the Internet as a source of health education on toxoplasmosis in pregnancy. Methods. A group of 100 pregnant women examined in the National Reference Laboratory for Toxoplasmosis was surveyed by a questionnaire on the source of their information on toxoplasmosis. We also analyzed information offered by websites in the Serbian and Croatian languages through the Google search engine, using “toxoplasmosis” as a keyword. The 23 top websites were evaluated for comprehensiveness and accuracy of information on the impact of toxoplasmosis on the course of pregnancy, diagnosis and prevention. Results. Having knowledge on toxoplasmosis was confirmed by 64 (64.0% examined women, 40.6% (26/64 of whom learned about toxoplasmosis through the Internet, 48.4% from physicians, and 10.9% from friends. Increase in the degree of education was found to be associated with the probability that pregnant women would be informed via the Internet (RR=3.15, 95% CI=1.27-7.82, p=0.013. Analysis of four interactive websites (allowing users to ask questions showed that routes of infection were the most common concern, particularly the risk presented by pet cats and dogs, followed by the diagnosis of infection (who and when should be tested, and how should the results be interpreted. Of 20 sites containing educational articles, only seven were authorized and two listed sources. Evaluation confirmed that information relevant to pregnant women was significantly more accurate than comprehensive, but no site gave both comprehensive and completely accurate information. Only four sites (20% were good sources of information for pregnant women. Conclusion. Internet has proved itself as an important source of information. However
Laura Andrea León A
Full Text Available Here we report the effects of subchronic 3, 4 methylenedioximethamphetamine (MDMA on the elevated plusmaze, a widely used animal model of anxiety. Rats exposed to a mild chronic stress (MCS protocol received intracerebroventricular microinjections of the selective serotonin reuptake inhibitor (SSRI – fluoxetine (2.0 ug/ul or MDMA, (2.0 ug/ul for seven days. On the eighth day rats were tested in the elevated plus-maze. Our results showed that sub chronic MDMA interacted with MCS leading to a decrease in anxiety related behaviors including: percentage of open arms entries (F [2, 26] = 4.00; p = 0.031, time spent in the open arms (F [2, 26] = 3.656; p = 0.040 and time spent in the open arms extremities (F [2, 26] = 5.842; p = 0.008. These results suggest a potential effect of MDMA in the reversion of the emotional significance of aversive stimuli.
Brain plasticity associated with anomia recovery in aphasia is poorly understood. Here, I review four recent studies from my lab that focused on brain modulation associated with long-term anomia outcome, its behavioral treatment, and the use of transcranial brain stimulation to enhance anomia treatment success in individuals with chronic aphasia caused by left hemisphere stroke. In a study that included 15 participants with aphasia who were compared to a group of 10 normal control subjects, w...
Liu, Chunping; Shen, Haitao; Yi, Li; Shao, Peilu; Soulika, Athena M; Meng, Xinxing; Xing, Lingxiao; Yan, Xia; Zhang, Xianghong
Our previous studies showed oral gavage of aflatoxin G₁ (AFG₁) induced lung adenocarcinoma in NIH mice. We recently found that a single intratracheal administration of AFG₁ caused chronic inflammatory changes in rat alveolar septum. Here, we examine whether oral gavage of AFG₁ induces chronic lung inflammation and how it contributes to carcinogenesis. We evaluated chronic lung inflammatory responses in Balb/c mice after oral gavage of AFG₁ for 1, 3 and 6 months. Inflammatory responses were heightened in the lung alveolar septum, 3 and 6 months after AFG₁ treatment, evidenced by increased macrophages and lymphocytes infiltration, up-regulation of NF-κB and p-STAT3, and cytokines production. High expression levels of superoxide dismutase (SOD-2) and hemoxygenase-1 (HO-1), two established markers of oxidative stress, were detected in alveolar epithelium of AFG₁-treated mice. Promoted alveolar type II cell (AT-II) proliferation in alveolar epithelium and angiogenesis, as well as increased COX-2 expression were also observed in lung tissues of AFG₁-treated mice. Furthermore, we prolonged survival of the mice in the above model for another 6 months to examine the contribution of AFG₁-induced chronic inflammation to lung tumorigenesis. Twelve months later, we observed that AFG₁ induced alveolar epithelial hyperplasia and adenocarcinoma in Balb/c mice. Up-regulation of NF-κB, p-STAT3, and COX-2 was also induced in lung adenocarcinoma, thus establishing a link between AFG₁-induced chronic inflammation and lung tumorigenesis. This is the first study to show that oral administration of AFG₁ could induce chronic lung inflammation, which may provide a pro-tumor microenvironment to contribute to lung tumorigenesis.
Conrad, Cheryl D
The hippocampus, a limbic structure important in learning and memory, is particularly sensitive to chronic stress and to glucocorticoids. While glucocorticoids are essential for an effective stress response, their oversecretion was originally hypothesized to contribute to age-related hippocampal degeneration. However, conflicting findings were reported on whether prolonged exposure to elevated glucocorticoids endangered the hippocampus and whether the primate hippocampus even responded to glucocorticoids as the rodent hippocampus did. This review discusses the seemingly inconsistent findings about the effects of elevated and prolonged glucocorticoids on hippocampal health and proposes that a chronic stress history, which includes repeated elevation of glucocorticoids, may make the hippocampus vulnerable to potential injury. Studies are described to show that chronic stress or prolonged exposure to glucocorticoids can compromise the hippocampus by producing dendritic retraction, a reversible form of plasticity that includes dendritic restructuring without irreversible cell death. Conditions that produce dendritic retraction are hypothesized to make the hippocampus vulnerable to neurotoxic or metabolic challenges. Of particular interest is the finding that the hippocampus can recover from dendritic retraction without any noticeable cell loss. When conditions surrounding dendritic retraction are present, the potential for harm is increased because dendritic retraction may persist for weeks, months or even years, thereby broadening the window of time during which the hippocampus is vulnerable to harm, called the 'glucocorticoid vulnerability hypothesis'. The relevance of these findings is discussed with regard to conditions exhibiting parallels in hippocampal plasticity, including Cushing's disease, major depressive disorder (MDD), and post-traumatic stress disorder (PTSD).
Rajaii, Mehrangiz; Pourhassan, Aboulfazl; Asle-Rahnamaie-Akbari, Najibeh; Aghebati, Leili; Xie, Juliana Ling; Goldust, Mohammad; Naghavi-Behzad, Mohammad
Toxoplasma gondii causes the most common parasitic infection in the world. Congenital transmission, prenatal mortality and abortion are major problems of T. gondii. Prevalence of toxoplasmosis is high in Iran, especially in Azerbaijan. The current literature reviewed in this paper reveal results pertaining to various regions of Iran. The present cross-sectional e-study was designed to evaluate the seroprevalence of toxoplasmosis in childbearing women in Northwest Iran. We evaluated 1659 women in childbearing age from several cities in Northwestern Iran (Tabriz, Maragheh, Ahar, Marand, Sarab, Miane) from July 2009 to August 2010. Women aged between 20 and 40 years and seeking prenatal care were enrolled in the study. The subjects' sera were probed with indirect fluorescent antibody (IFA). A total of 1659 subjects were examined. Titres ranged from 1:100 to 1:800. In all, 899 subjects (54.13%) were seropositive. The highest frequency of seropositivity was shown in 1:200 dilution (36.08%) and in subjects from Maragheh (84% of 211 subjects). There was a direct linear relationship between seropositivity and age (p 0.001). Also, seroprevalence of toxoplasmosis was higher in subjects with primary school/lower educational level (p 0.001) and subjects living in rural regions (p 0.001). Overall, more than 50% of women in childbearing age were seropositive for toxoplasmosis in northwestern Iran. Increasing seroprevalence of toxoplasmosis with age was a predictable result due to longer exposure to the parasite. The relationship between increasing seroprevalence and lower educational level as well as living in rural areas is in line with the latest epidemiological findings, which also show such relationships due to lower socioeconomic status.
Full Text Available Abstract Background About 30% of the population worldwide are infected with the protozoan parasite Toxoplasma gondii. Latent toxoplasmosis has many specific behavioral and physiological effects on the human organism. Modified reactivity of the immune system has been suggested to play a key role in many of these effects. For example, the immunosuppression hypothesis explains the higher probability of the birth of male offspring observed in Toxoplasma-positive humans and mice by the protection of the (more immunogenic male embryos against abortion. Methods Here we searched for indices of immunosuppression in Toxoplasma-positive subjects by comparing clinical records of immunology outpatients. Results Our cohort study showed that the male patients with latent toxoplasmosis had decreased and the Toxoplasma-positive women had increased leukocyte, NK-cell and monocyte counts in comparison with controls. The B-cell counts were reduced in both Toxoplasma-positive men and women. The difference between Toxoplasma-positive and Toxoplasma-negative subjects diminished with the decline of the specific Toxoplasma antibody titre (a proxy for the length of infection, which is consistent with the observed decreasing strength of the effect of latent toxoplasmosis on human reproduction. The prevalence of toxoplasmosis in 128 male patients was unusually low (10.9% which contrasted with normal prevalence in 312 female patients (23.7% and in general population Prague (20-30%. Conclusions Latent toxoplasmosis has immunomodulatory effects in human and probably protects men against some classes of immunopathological diseases. The main limitation of the present study was the absence of the data on the immunoreactivity of immune cells subpopulations. Therefore further studies are needed to search for indices of immunosuppression in human using more specific markers.
Full Text Available En los últimos 5 anos hemos tratado 112 casos de toxoplasmosis. La mayor parte presentaba abortos o coriorretinitis; algunos presentaban meningo-encefalitis, miocarditis y otras formas. Ocho por ciento de los pacientes presentaban dos cuadros anatomoclínicos de toxoplasmosis. Se administro en forma alterna pirimetamina, sulfametopirazina o espiramicina durante períodos prolongados, practicando reacción de Sabin y Feldman cada tres meses. La meta es negativizar la prueba serológica, la cual generalmente logramos. Clinicamente se aprecia curación al observar la desaparición de los fenômenos inflamatorios en el fondo del ojo, la desaparición de adenopatías u otros signos clínicos, ó el desarrollo de embarazos normales con productos normales en mujeres abortadoras. Considerando los graves problemas que hemos visto en hijos de madres con toxoplasmosis, preferimos tratar a éstas antes de nuevos embarazos.Along the last five years we have treated 112 cases of toxoplasmosis. The majority of them had abortion or corioretinitis; a few had meningo-encephalities, miocarditis or other forms: 8% o f the patients had two anatomoclinical pictures at the same time. The patients received pyrimethamine, sulphametopyrazine, or spiromycine on alternating periods for several months. A Sabin and Feldman test was repeated every three months. The target was obtaining negative serology, th is was accomplished on the majority of the cases. From the clinical stand point cure was supported by disapearance of inflamatory findings on the fundus, disappearing of adenopathy or other signs, as for the achievement of normal pregnancies with normal children in women with repeated abortion. Taking into account the serious secuelae that we have seen on children from mothers with toxoplasmosis, we prefer to treat the women before new pregnancies.
Zhao, Ting Ting; Shin, Keon Sung; Park, Hyun Jin; Kim, Kyung Sook; Lee, Kung Eun; Cho, Yoon Jeong; Lee, Myung Koo
This study investigated the effects of (-)-sesamin on memory deficits induced by chronic electric footshock (EF)-induced stress in mice. Mice were treated with (-)-sesamin (25 and 50mg/kg, p.o., daily for 21day) prior to chronic EF stress (0.6mA, 1s every 5s for 3min, daily for 21day). Transfer retention latencies in the elevated plus maze test and N-methyl-d-aspartate (NMDA) receptor (type 1) phosphorylation in the hippocampus increased with chronic EF stress, and they were reduced by treatment with (-)-sesamin at both doses. Phosphorylation of extracellular signal-regulated kinase (ERK1/2) and cyclic AMP-responsive element binding protein (CREB), which were reduced by chronic EF stress, were increased by treatment with (-)-sesamin. Retention latencies in the passive avoidance test and dopamine levels in the substantia nigra-striatum were also reduced by chronic EF stress, and similarly recovered with (-)-sesamin treatment. These results suggest that (-)-sesamin ameliorates the effects of chronic EF stress-induced spatial and habit learning memory deficits by modulating both NMDA receptor and dopaminergic neuronal systems.
Peter M.S. Chang
Full Text Available The overall incidence of amiodarone-induced thyroid dysfunction ranges from 2% to 24%. One third to half of patients with hypothyroidism have anemia due to some decrease in normal red blood cell mass and erythropoietin (EPO resistance. Therefore, for patients with chronic renal disease under medication with amiodarone, early regular thyroid function test should be checked in order to avoid amiodarone-induced hypothyroidism and EPO-resistant anemia. If amiodarone-induced hypothyroidism and EPO-resistant anemia occur in patients with chronic renal failure, early thyroxine should be given instead of waiting for spontaneous recovery by amiodarone discontinuation only. Here, we report a patient with chronic renal failure who developed EPO-resistant anemia after amiodarone treatment for arrhythmia. The hemoglobin level responded to EPO therapy rapidly after thyroxine administration and amiodarone discontinuation.
Mizoguchi, Kazushige; Ikeda, Ryuji; Shoji, Hirotaka; Tanaka, Yayoi; Jin, Xue-Long; Kase, Yoshio; Takeda, Shuichi; Maruyama, Wakako; Tabira, Takeshi
Anxiety is frequently observed in several neuropsychiatric disorders, and stress is thought to precipitate or exacerbate anxiety. In this study, the anxiolytic action of a herbal medicine, saikokaryukotsuboreito, (SRBT) was examined in normal healthy rats using the elevated plus-maze test. Moreover, the improving effect of SRBT on chronic stress-induced anxiety was also examined. Single administration of SRBT did not have anxiolytic action in normal rats. Repeated administration of SRBT significantly improved chronic stress-induced anxiety. On the other hand, single administration of a typical anxiolytic, diazepam, had anxiolytic action in normal rats but repeated administration did not improve chronic stress-induced anxiety. These results suggest that SRBT does not have anxiolytic activity equivalent to that of diazepam but has potency for improving stress-related anxiety. This finding provides information important for the treatment of anxiety.
Meira, Cristina S; Vidal, José E; Costa-Silva, Thais A; Motoie, Gabriela; Gava, Ricardo; Hiramoto, Roberto M; Pereira-Chioccola, Vera L
Cerebral toxoplasmosis is the most common neurological opportunistic disease manifested in HIV infected patients. Excretory/secretory antigens (ESA) are serological markers for the diagnosis of reactivation of the infection in HIV-infected patients with cerebral toxoplasmosis. Immunosuppressed patients develop high antibody titers for ESA. However, little is known about the humoral response for these antigens. The present study analyzed the profile of antibody recognition against ESA in comparison with tachyzoite lysate antigen (TLA) in 265 sera and 270 cerebrospinal fluid (CSF) samples from infected patients with Toxoplasma gondii and or HIV and in sera of 50 healthy individuals. The samples of sera and CSF were organized in 8 groups. The sera sample groups were: Group I - Se/CT/AIDS (patients with cerebral toxoplasmosis/AIDS) with 58 samples; Group II - Se/ONinf/AIDS/PosT (patients with AIDS/other neuroinfections/positive toxoplasmosis) with 49 samples; Group III - Se/ONinf/AIDS/NegT (patients with AIDS/other neuroinfections/negative toxoplasmosis) with 58 samples; Group IV - Se/PosT/NegHIV (individuals with asymptomatic toxoplasmosis/negative HIV) with 50 samples and Group V - Se/NegT/NegHIV (healthy individuals/negative toxoplasmosis and HIV) with 50 samples. The CSF sample groups were: Group VI - CSF/CT/AIDS (patients with cerebral toxoplasmosis/AIDS) with 99 samples; Group VII - CSF/ONinf/AIDS/PosT (patients with AIDS/other neuroinfections/positive toxoplasmosis) with 112 samples, and Group VIII - CSF/ONinf/AIDS/NegT (patients with AIDS/other neuroinfections/negative toxoplasmosis) with 59 samples. Levels of IgM, IgA, IgE, IgG and subclasses were determined by ELISA against TLA and ESA antigens. IgM, IgA or IgE antibodies against ESA or TLA were not detected in sera from patients with toxoplasmosis suggesting that all patients were in chronic phase of the infection. High levels of IgG1 against TLA were found in sera samples from groups I, II and IV and in CSF
Naik, Dhaval K; Martelli, Matthew G; Gonzalo, David Hernandez; Sharma, Anil K; Pannu, Davinderbir
Olmesartan use has been associated with chronic diarrhoea and weight loss due to severe sprue-like enteropathy, yet this is still not well known among clinicians. We present the unique case of an 84-year-old Filipino woman diagnosed with olmesartan-induced sprue-like enteropathy after an extensive work up for chronic diarrhoea, and without improvement despite multiple empiric treatments for nearly 15 months. Withdrawal of olmesartan resulted in clinical and histological improvement. This case provides further evidence for olmesartan-induced sprue-like enteropathy, and emphasises the importance of its awareness and recognition among gastroenterologists and primary care physicians alike. 2015 BMJ Publishing Group Ltd.
Papadopoulos, George; Kramer, Carolyn D; Slocum, Connie S; Weinberg, Ellen O; Hua, Ning; Gudino, Cynthia V; Hamilton, James A; Genco, Caroline A
Chronic inflammation is a major driver of pathological tissue damage and a unifying characteristic of many chronic diseases in humans including neoplastic, autoimmune, and chronic inflammatory diseases. Emerging evidence implicates pathogen-induced chronic inflammation in the development and progression of chronic diseases with a wide variety of clinical manifestations. Due to the complex and multifactorial etiology of chronic disease, designing experiments for proof of causality and the establishment of mechanistic links is nearly impossible in humans. An advantage of using animal models is that both genetic and environmental factors that may influence the course of a particular disease can be controlled. Thus, designing relevant animal models of infection represents a key step in identifying host and pathogen specific mechanisms that contribute to chronic inflammation. Here we describe a mouse model of pathogen-induced chronic inflammation at local and systemic sites following infection with the oral pathogen Porphyromonas gingivalis, a bacterium closely associated with human periodontal disease. Oral infection of specific-pathogen free mice induces a local inflammatory response resulting in destruction of tooth supporting alveolar bone, a hallmark of periodontal disease. In an established mouse model of atherosclerosis, infection with P. gingivalis accelerates inflammatory plaque deposition within the aortic sinus and innominate artery, accompanied by activation of the vascular endothelium, an increased immune cell infiltrate, and elevated expression of inflammatory mediators within lesions. We detail methodologies for the assessment of inflammation at local and systemic sites. The use of transgenic mice and defined bacterial mutants makes this model particularly suitable for identifying both host and microbial factors involved in the initiation, progression, and outcome of disease. Additionally, the model can be used to screen for novel therapeutic strategies
李庆云; 黄绍光; 吴华成; 程齐俭; 项轶; 万欢英
Objective To establish a smoke-induced chronic bronchitis rat model and evaluate the pathological change semi-quantitatively, and study the characteristics of the inflammatory cells in the bronchoalveolar lavage fluid (BALF) in various stages. Methods Chronic bronchitis sequential rat model was established by passively inhaling smoke mixture. Experiments were performed in 30 young male Sprague-Dawley rats, which comprised 5 groups in random, i.e.,4 chronic bronchitis model groups and I control group. After stained with hematoxylin and eosin, the specimens were studied by semi-quantitative method to evaluate the morphologic changes in various stages. Meanwhile, the inflammatory cells of the BALF and the activity of myeloperoxidase ( MPO ) of lung tissue were analysed. Results During the process of the chronic bronchitis, the pathologic score was increasing as time went on, and the typical morphologic changes of chronic bronchitis emerged in the group 7 weeks. The total number of inflammatory cells in BALF was increasing as time went on, correlated with the pathologic scores ( P ＜ 0. 01 ).And the percentage of lymphocyte increased as well as positively correlated with pathologic scores ( P ＜ 0. 05 ),whereas that of macrophage decreased and negatively correlated with pathologic scores (P ＜0. 05). The MPO lever of lung tissue was correlated with the pathologic scores ( P ＜ 0. 01 ). But the percentage of the neutrophil in the BALF was just in a high level during the first week, then it maintained relatively lower. Conclusion Smoke-induced chronic bronchitis is a slowly progressive inflammation process. The model we established is convenient and simple for the longitudinal study on the inflammatory process of chronic bronchitis and the therapy in the early stage. The semi-quantitative evaluation for the pathological change is with much more value. During the inflammatory sequential process of early stage of chronic bronchitis, the cellular characteristics are
Martino, Julieta; Holmes, Amie L.; Xie, Hong; Wise, Sandra S.; Wise, John Pierce
Particulate hexavalent chromium (Cr(VI)) is a well-established human lung carcinogen. Lung tumors are characterized by structural and numerical chromosome instability. Centrosome amplification is a phenotype commonly found in solid tumors, including lung tumors, which strongly correlates with chromosome instability. Human lung cells exposed to Cr(VI) exhibit centrosome amplification but the underlying phenotypes and mechanisms remain unknown. In this study, we further characterize the phenotypes of Cr(VI)-induced centrosome abnormalities. We show that Cr(VI)-induced centrosome amplification correlates with numerical chromosome instability. We also show chronic exposure to particulate Cr(VI) induces centrosomes with supernumerary centrioles and acentriolar centrosomes in human lung cells. Moreover, chronic exposure to particulate Cr(VI) affects the timing of important centriolar events. Specifically, chronic exposure to particulate Cr(VI) causes premature centriole disengagement in S and G2 phase cells. It also induces premature centrosome separation in interphase. Altogether, our data suggest that chronic exposure to particulate Cr(VI) targets the protein linkers that hold centrioles together. These centriolar linkers are important for key events of the centrosome cycle and their premature disruption might underlie Cr(VI)-induced centrosome amplification. PMID:26293554
Zheng, H; Xiao, W H; Bennett, G J
Many of the most effective anti-cancer drugs induce a dose-limiting peripheral neuropathy that compromises therapy. Evidence from animal models of chemotherapy-induced painful peripheral neuropathy produced by the taxane agent, paclitaxel, and the platinum-complex agent, oxaliplatin, indicate that they produce neuropathy via a common mechanism-a toxic effect on the mitochondria in primary afferent sensory neurons. Bortezomib is from the proteasome-inhibitor class of chemotherapeutics. It also produces a dose-limiting peripheral neuropathy, but its effects on neuronal mitochondria are unknown. To investigate this, we developed a model of bortezomib-induced painful peripheral neuropathy in the rat and assessed mitochondrial function (respiration and ATP production) in sciatic nerve samples harvested at two time points: day 7, which is three days after treatment and before pain appears, and day 35, which is one month post-treatment and the time of peak pain severity. We found significant deficits in Complex I-mediated and Complex II-mediated respiration, and in ATP production at both time points. Prophylactic treatment with acetyl-L-carnitine, which has previously been shown to prevent paclitaxel- and oxaliplatin-induced mitochondrial dysfunction and pain, completely blocked bortezomib's effects on mitochondria and pain. These results suggest that mitotoxicity may be the core pathology for all chemotherapy-induced peripheral neuropathy and that drugs that protect mitochondrial function may be useful chemotherapy adjuncts.
Submental mass secondary to toxoplasmosis is not common in clinical work. A diagnosis of toxoplasmosis is rarely considered by physicians. Here we describe a 50-year-old woman presented with a progressive, painful, submental and left neck swelling for 1 month. After having obtained an insufficient evidence from the fine-needle biopsy, the patient finally received an excisional biopsy which highly indicated the possibility of lymphadenopathy consistent with toxoplasmosis. Diagnosis of toxoplas...
Quiones Tapia, D.; Ramos Amador, A.; Monereo Alonso, A.
We report a case of cerebral toxoplasmosis in a patient with stage IV C[sub 1] AIDS who presented hyperdense CT images 13 days after beginning antitoxoplasma treatment. These lesions could be caused by calcifications or blood. The attenuation values lead us to believe that they are calcium. Intracranial calcification in adult cerebral toxoplasmosis is an uncommon finding. Its presence in AIDS patients should not suggest any etiology other than toxoplasmosis. (Author) 16 refs.
Exposure to extremely-low-frequency (ELF) electric or magnetic fields has been postulated as a potentially contributing factor in depression. Epidemiologic studies have yielded positive correlations between magnetic- and/or electric-field strengths in local environments and the incidence of depression-related suicide. Chronic exposure to ELF electric or magnetic fields can disrupt normal circadian rhythms in rat pineal serotonin-N-acetyltransferase activity as well as in serotonin and melatonin concentrations. Such disruptions in the circadian rhythmicity of pineal melatonin secretion have been associated with certain depressive disorders in human beings. In the rat, ELF fields may interfere with tonic aspects of neuronal input to the pineal gland, giving rise to what may be termed functional pinealectomy. If long-term exposure to ELF fields causes pineal dysfunction in human beings as it does in the rat, such dysfunction may contribute to the onset of depression or may exacerbate existing depressive disorders. 85 references.
Kijlstra, Aize; Petersen, Eskild
Despite large advances in the field of ocular toxoplasmosis, large gaps still exist in our knowledge concerning the epidemiology and pathophysiology of this potentially blinding infectious disease. Although ocular toxoplasmosis is considered to have a high health burden, still little is known about its exact prevalence and how it affects the quality of life. The epidemiology of toxoplasmosis depends on local habits throughout the globe, and changes are likely in view of increased meat consumption in developing countries and demands for higher animal welfare in the Western world. Water is increasingly seen as an important risk factor and more studies are needed to quantitate and control the role of water exposure (drinking, swimming). Tools are now becoming available to study both the human host as well as parasite genetic factors in the development of ocular toxoplasmosis. Further research on the role of Toxoplasma strains as well as basic studies on parasite virulence is needed to explain why Toxoplasma associated eye disease is so severe in some countries, such as Brazil. Although genetic analysis of the parasite represents the gold standard, further developments in serotyping using peptide arrays may offer practical solutions to study the role of parasite strains in the pathogenesis of Toxoplasma retinochoroiditis. More research is needed concerning the pathways whereby the parasite can infect the retina. Once in the retina further tissue damage may be due to parasite virulence factors or could be caused by an aberrant host immune response. Local intraocular immune responses are nowadays used for diagnostic procedures. Future developments may include the use of Raman technology or the direct visualization of a Toxoplasma cyst by optical coherence tomography (OCT). With the availability of ocular fluid specimens obtained for diagnostic purposes and the development of advanced proteomic techniques, a biomarker fingerprint that is unique for an eye with
Coder, Brandon D; Wang, Hongjun; Ruan, Linhui; Su, Dong-Ming
Thymic involution and the subsequent amplified release of autoreactive T cells increase the susceptibility toward developing autoimmunity, but whether they induce chronic inflammation with advanced age remains unclear. The presence of chronic low-level proinflammatory factors in elderly individuals (termed inflammaging) is a significant risk factor for morbidity and mortality in virtually every chronic age-related disease. To determine how thymic involution leads to the persistent release and activation of autoreactive T cells capable of inducing inflammaging, we used a Foxn1 conditional knockout mouse model that induces accelerated thymic involution while maintaining a young periphery. We found that thymic involution leads to T cell activation shortly after thymic egress, which is accompanied by a chronic inflammatory phenotype consisting of cellular infiltration into non-lymphoid tissues, increased TNF-α production, and elevated serum IL-6. Autoreactive T cell clones were detected in the periphery of Foxn1 conditional knockout mice. A failure of negative selection, facilitated by decreased expression of Aire rather than impaired regulatory T cell generation, led to autoreactive T cell generation. Furthermore, the young environment can reverse age-related regulatory T cell accumulation in naturally aged mice, but not inflammatory infiltration. Taken together, these findings identify thymic involution and the persistent activation of autoreactive T cells as a contributing source of chronic inflammation (inflammaging).
Barboza, Luisa; Salmen, Siham; Goncalves, Loredana; Colmenares, Melisa; Peterson, Darrell; Montes, Henry; Cartagirone, Raimondo; Gutiérrez, Maria del Carmen; Berrueta, Lisbeth
T cell response against HBV is vigorous in patients with acute hepatitis who clear the virus, whereas it is weak and narrowly focused in patients with chronic disease. We report that following incubation with HBcAg, a population of CD4+FoxP3+ cells expressing phenotypic markers of both natural and induced Tregs, can be antigen-induced from peripheral mononuclear cells. Conversely, naive and naturally immune subjects did not increase CD4+FoxP3+ Tregs following stimulation with HBcAg, supporting the idea that natural Tregs are able to respond specifically to HBV antigen. Furthermore, increased frequencies of antigen-induced CD4+FoxP3+IL-10+ Tregs correlated with viral load, suggesting that antigen-induced Tregs could contribute to an inadequate response against the virus, leading to chronic infection and support the view that specific natural Tregs may be implicated in host immune tolerance during HBV infection.
Memel, D.S.; DeRogatis, A.J.; William, D.C. (St. Luke' s-Roosevelt Hospital Center, New York, NY (USA))
A 38-year-old man with AIDS presented with fever of unknown origin, splenomegaly, anemia, and thrombocytopenia. Admission laboratory data revealed a positive toxoplasmosis titer in the blood. The initial chest x-ray showed small bilateral pleural effusions, a normal cardiac silhouette, no infiltrates, and no interstitial edema. Ga-67 imaging revealed markedly abnormal uptake in the myocardium. A diagnosis of toxoplasmosis myocarditis was made based on laboratory and imaging data. The patient was treated for toxoplasmosis. No myocardial uptake of tracer was demonstrated on a follow-up Ga-67 scan, performed after completion of treatment for toxoplasmosis.
Full Text Available PURPOSE: Toxoplasmosis is the most common cause of posterior infectious uveitis worldwide. It is often impossible to determine its congenital or acquired nature. Interleukin-2 (IL-2 in peripheral blood has been described as a possible marker for acquired toxoplasmosis. The purpose of this study is to evaluate the histopathological characteristics of ocular toxoplasmosis cases using CD25 as a marker for the expression of interleukin-2. METHODS: Ten formalin-fixed, paraffin-embedded enucleated globes from ten immunocompetent patients with clinical diagnosis of toxoplasmosis were evaluated. Four patients had the acquired form of ocular toxoplasmosis (positive IgM while six were IgM negative and IgG positive for toxoplasmosis. Histopathological slides were reviewed for the extension of the retinal necrosis, number of toxo cysts, the granulomatous inflammatory reaction, the presence of T and B cells within the choroid and the IL-2 expression. Immunohistochemistry using monoclonal antibodies was performed to observe the expression of CD4, CD8, CD20, CD25, and CD68. RESULTS: The histopathological evaluation disclosed no differences between acquired and the other ocular toxoplasmosis cases regarding the characteristics studied. However, CD25 showed a higher expression of IL-2 on the 4 acquired cases of ocular toxoplasmosis compared to the remainders. CONCLUSIONS: To the best of our knowledge, this is the first report showing that the use of CD25 as a marker for interleukin-2 could differentiate acquired ocular toxoplasmosis.
Masamed, R. [Department of Radiological Sciences, UCLA Medical Center, Los Angeles, CA (United States)], E-mail: firstname.lastname@example.org; Meleis, A. [Princeton University, New Jersey, CA (United States); Lee, E.W. [Department of Radiological Sciences, UCLA Medical Center, Los Angeles, CA (United States); Hathout, G.M. [Department of Radiological Sciences, UCLA Medical Center, Los Angeles, CA (United States); Department of Neuroradiology, Olive View UCLA Medical Center, Los Angeles, CA (United States); Department of Neuroradiology, West L.A. VA Medical Center, Los Angeles, CA (United States)
Toxoplasmosis can have catastrophic consequences in immunocompromised patients if left untreated. Accurate diagnosis is difficult, as there is substantial overlap between the imaging findings and presenting clinical syndromes of cerebral toxoplasmosis and primary central nervous system lymphoma. This paper reviews the previously described and fairly well-known post-contrast computed tomography (CT) and T1-weighted (W) magnetic resonance imaging (MRI) target signs seen in toxoplasmosis. In addition, it offers a new imaging sign, the T2W/FLAIR (fluid attenuated inversion recovery) target sign, which is often seen in clinical practice but not well-published, as an aid to the diagnosis of cerebral toxoplasmosis.
Negrón-Oyarzo, Ignacio; Aboitiz, Francisco; Fuentealba, Pablo
Chronic stress-related psychiatric diseases, such as major depression, posttraumatic stress disorder, and schizophrenia, are characterized by a maladaptive organization of behavioral responses that strongly affect the well-being of patients. Current evidence suggests that a functional impairment of the prefrontal cortex (PFC) is implicated in the pathophysiology of these diseases. Therefore, chronic stress may impair PFC functions required for the adaptive orchestration of behavioral responses. In the present review, we integrate evidence obtained from cognitive neuroscience with neurophysiological research with animal models, to put forward a hypothesis that addresses stress-induced behavioral dysfunctions observed in stress-related neuropsychiatric disorders. We propose that chronic stress impairs mechanisms involved in neuronal functional connectivity in the PFC that are required for the formation of adaptive representations for the execution of adaptive behavioral responses. These considerations could be particularly relevant for understanding the pathophysiology of chronic stress-related neuropsychiatric disorders. PMID:26904302
Full Text Available Chronic stress-related psychiatric diseases, such as major depression, posttraumatic stress disorder, and schizophrenia, are characterized by a maladaptive organization of behavioral responses that strongly affect the well-being of patients. Current evidence suggests that a functional impairment of the prefrontal cortex (PFC is implicated in the pathophysiology of these diseases. Therefore, chronic stress may impair PFC functions required for the adaptive orchestration of behavioral responses. In the present review, we integrate evidence obtained from cognitive neuroscience with neurophysiological research with animal models, to put forward a hypothesis that addresses stress-induced behavioral dysfunctions observed in stress-related neuropsychiatric disorders. We propose that chronic stress impairs mechanisms involved in neuronal functional connectivity in the PFC that are required for the formation of adaptive representations for the execution of adaptive behavioral responses. These considerations could be particularly relevant for understanding the pathophysiology of chronic stress-related neuropsychiatric disorders.
Su, Zhengxiu; Zhu, Hongguo; Zhang, Menghuan; Wang, Liangliang; He, Hanchang; Jiang, Shaoling; Hou, Fan Fan; Li, Aiqing
Heart damage is widely present in patients with chronic kidney disease. Salt diet is the most important environmental factor affecting development of chronic renal failure and cardiovascular diseases. The proteins involved in chronic kidney disease -induced heart damage, especially their posttranslational modifications, remain largely unknown to date. Sprague-Dawley rats underwent 5/6 nephrectomy (chronic renal failure model) or sham operation were treated for 2 weeks with a normal-(0.4% NaCl), or high-salt (4% NaCl) diet. We employed TiO2 enrichment, iTRAQ labeling and liquid-chromatography tandem mass spectrometry strategy for phosphoproteomic profiling of left ventricular free walls in these animals. A total of 1724 unique phosphopeptides representing 2551 non-redundant phosphorylation sites corresponding to 763 phosphoproteins were identified. During normal salt feeding, 89 (54%) phosphopeptides upregulated and 76 (46%) phosphopeptides downregulated in chronic renal failure rats relative to sham rats. In chronic renal failure rats, high salt intake induced upregulation of 84 (49%) phosphopeptides and downregulation of 88 (51%) phosphopeptides. Database searches revealed that most of the identified phospholproteins were important signaling molecules such as protein kinases, receptors and phosphatases. These phospholproteins were involved in energy metabolism, cell communication, cell differentiation, cell death and other biological processes. The Search Tool for the Retrieval of Interacting Genes analysis revealed functional links among 15 significantly regulated phosphoproteins in chronic renal failure rats compared to sham group, and 23 altered phosphoproteins induced by high salt intake. The altered phosphorylation levels of two proteins involved in heart damage, lamin A and phospholamban were validated. Expression of the downstream genes of these two proteins, desmin and SERCA2a, were also analyzed.
Full Text Available Reduced responsiveness to positive stimuli is a core symptom of depression, known as anhedonia. In the present study, we assessed the expression of anhedonia in our chronic stress mouse model using a subset of read-out parameters. In line with this, we investigated in how far chronic stress would affect the facilitating effect of post-training self-administration of sugar, as we previously observed in naïve mice. Male C57BL/6J mice were repeatedly and at unpredictable times exposed to rats (no physical contact over the course of two weeks. Following novelty exploration, (non- spatial learning and memory processes with and without post-training sugar acting as reinforcer, emotionality, reward sensitivity and corticosterone levels were determined. We found that (1 the effects of chronic stress persisted beyond the period of the actual rat exposure. (2 Post-training self-administration of sugar as reinforcer improved spatial performance in naïve mice, whereas (3 in stressed mice sugar partially "normalized" the impaired performance to the level of controls without sugar. Chronic stress (4 increased behavioral inhibition in response to novelty; (5 induced dynamic changes in the pattern of circadian corticosterone secretion during the first week after rat stress and (6 increased the intake of sucrose and water. (7 Chronic stress and sugar consumed during spatial training facilitated the memory for the location of the sucrose bottle weeks later. Concluding, our chronic stress paradigm induces the expression of anhedonia in mice, at different levels of behavior. The behavioral inhibition appears to be long lasting in stressed mice. Interestingly, sugar consumed in close context with spatial learning partially rescued the stress-induced emotional and cognitive impairments. This suggests that reward can ameliorate part of the negative consequences of chronic stress on memory.
Full Text Available Heart damage is widely present in patients with chronic kidney disease. Salt diet is the most important environmental factor affecting development of chronic renal failure and cardiovascular diseases. The proteins involved in chronic kidney disease -induced heart damage, especially their posttranslational modifications, remain largely unknown to date. Sprague-Dawley rats underwent 5/6 nephrectomy (chronic renal failure model or sham operation were treated for 2 weeks with a normal-(0.4% NaCl, or high-salt (4% NaCl diet. We employed TiO2 enrichment, iTRAQ labeling and liquid-chromatography tandem mass spectrometry strategy for phosphoproteomic profiling of left ventricular free walls in these animals. A total of 1724 unique phosphopeptides representing 2551 non-redundant phosphorylation sites corresponding to 763 phosphoproteins were identified. During normal salt feeding, 89 (54% phosphopeptides upregulated and 76 (46% phosphopeptides downregulated in chronic renal failure rats relative to sham rats. In chronic renal failure rats, high salt intake induced upregulation of 84 (49% phosphopeptides and downregulation of 88 (51% phosphopeptides. Database searches revealed that most of the identified phospholproteins were important signaling molecules such as protein kinases, receptors and phosphatases. These phospholproteins were involved in energy metabolism, cell communication, cell differentiation, cell death and other biological processes. The Search Tool for the Retrieval of Interacting Genes analysis revealed functional links among 15 significantly regulated phosphoproteins in chronic renal failure rats compared to sham group, and 23 altered phosphoproteins induced by high salt intake. The altered phosphorylation levels of two proteins involved in heart damage, lamin A and phospholamban were validated. Expression of the downstream genes of these two proteins, desmin and SERCA2a, were also analyzed.
Xu, Chunfang; Shen, Jiaqing; Zhang, Jing; Jia, Zhenyu; He, Zhilong; Zhuang, Xiaohui; Xu, Ting; Shi, Yuqi; Zhu, Shunying; Wu, Mingyuan; Han, Wei
Chronic pancreatitis (CP) is a common disease in the department of gastroenterology, with the main symptoms of exocrine and/or endocrine insufficiency and abdominal pain. The pathogenic mechanism of CP is still not fully clarified and the aims of treatment now are to relieve symptoms. In this study, we attempted to find a connection between interleukin-1β (IL-1β) and interleukin-1 receptor antagonist (IL-1Ra) in trinitrobenzene sulfonic acid (TNBS)-induced chronic pancreatitis, and then the therapeutic effect of recombinant IL-1Ra was also detected in the CP model. Chronic pancreatitis was induced by intraductal infusion of TNBS in SD rats followed by a consecutive administration of rIL-1Ra, and the histological changes and collagen content in the pancreas were measured, as well as the abdominal hypersensitivity. We found that rhIL-1Ra could attenuate the severity of chronic pancreatic injury, modulate the extracellular matrix secretion, focal proliferation and apoptosis, and cellular immunity in TNBS-induced CP. Interestingly, rIL-1Ra could also block the pancreatitis-induced referred abdominal hypersensitivity. In conclusion, IL-1Ra may play a protective role in CP and rIL-1Ra would be a potential therapeutic target for the treatment of CP, while its possible mechanisms and clinical usage still need further investigation.
Hoe, Alex khoo cheen; Feng, Lee Yeong [Dept. of Nuclear Medicine, Penang Hospital, Georgetown (Malaysia)
Tenofovir, used in the treatment of chronic hepatitis B and HIV, is known for its side effects on the kidneys and bones. We share interesting images of a patient with tenofovir-induced osteomalacia on Technetium-99 m hydroxymethyelene (Tc-99 m HDP) bone scintigraphy. Pattern recognition of this bone scintigraphy and correlation with the clinical history is essential to avoid misdiagnosis.
Neerhof, M.G.; Synowiec, S.; Khan, S.; Thaete, L.G.
Objective. To evaluate the pathophysiology of chronic nitric oxide synthase (NOS) inhibition-induced fetal growth restriction (FGR) in the rat. Methods. Timed-pregnant rats received L-NAME (2.5 mg/kg/h) with or without endothelin (ET-1) receptor A (ETA) antagonist from day 14 to 21 of gestation. In
Gao, Yuan; Su, Peizhu; Wang, Chuqiong; Zhu, Kongqin; Chen, Xiaolan; Liu, Side; He, Jiman
Chronic growth hormone (GH) therapy has been shown to cause insulin resistance, but the mechanism remains unknown. PTEN, a tumor suppressor gene, is a major negative regulator of insulin signaling. In this study, we explored the effect of chronic GH on insulin signaling in the context of PTEN function. Balb/c healthy mice were given recombinant human or bovine GH intraperitoneally for 3 weeks. We found that phosphorylation of Akt was significantly decreased in chronic GH group and the expression of PTEN was significantly increased. We further examined this effect in the streptozotocin-induced Type I diabetic mouse model, in which endogenous insulin secretion was disrupted. Insulin/PI3K/Akt signaling was impaired. However, different from the observation in healthy mice, the expression of PTEN did not increase. Similarly, PTEN expression did not significantly increase in chronic GH-treated mice with hypoinsulinemia induced by prolonged fasting. We conducted in-vitro experiments in HepG2 cells to validate our in-vivo findings. Long-term exposure to GH caused similar resistance of insulin/PI3K/Akt signaling in HepG2 cells; and over-expression of PTEN enhanced the impairment of insulin signaling. On the other hand, disabling the PTEN gene by transfecting the mutant PTEN construct C124S or siPTEN, disrupted the chronic GH induced insulin resistance. Our data demonstrate that PTEN plays an important role in chronic-GH-induced insulin resistance. These findings may have implication in other pathological insulin resistance.
Cummings, Patricia L; Kuo, Tony; Javanbakht, Marjan; Sorvillo, Frank
Few studies have quantified toxoplasmosis mortality, associated medical conditions, and productivity losses in the United States. We examined national multiple cause of death data and estimated productivity losses caused by toxoplasmosis during 2000-2010. A matched case-control analysis examined associations between comorbid medical conditions and toxoplasmosis deaths. In total, 789 toxoplasmosis deaths were identified during the 11-year study period. Blacks and Hispanics had the highest toxoplasmosis mortality compared with whites. Several medical conditions were associated with toxoplasmosis deaths, including human immunodeficiency virus (HIV), lymphoma, leukemia, and connective tissue disorders. The number of toxoplasmosis deaths with an HIV codiagnosis declined from 2000 to 2010; the numbers without such a codiagnosis remained static. Cumulative disease-related productivity losses for the 11-year period were nearly $815 million. Although toxoplasmosis mortality has declined in the last decade, the infection remains costly and is an important cause of preventable death among non-HIV subgroups.
Castillo, Víctor A.:
Full Text Available Resúmen La tiroiditis subaguda es causada por la acción de agentes infecciosos. Clínicamente se observa bocio, disfonía y disfagia. Respecto a la función tiroidea, puede haber hipertirotoxinemia debida a la ruptura de folículos, en tanto que la concentración de TSH se mantiene normal y la captación de yodo está disminuída. El objetivo del presente trabajo fue investigar si la toxoplasmosis en perros puede afectar la morfología y función tiroidea. Se estudiaron 8 perros con toxoplasmosis comprobada (título de anticuerpos por aglutinación directa [AD] > 1/128. La palpación tiroidea impresionó bocio, confirmado por ecografía de la glándula. La medición de TSH fue normal, en tanto que la tiroxina resultó normal en 4 casos, elevada en 3 y disminuída en un caso, sin signos de tirotoxicosis ni de hipotiroidismo respectivamente. Los perros fueron tratados con clindanmicina (12,5 mg/kg oral cada 12 hs por 30 días, siendo reevaluada la función y morfología tiroidea. En los 8 casos hubo remisión de los signos tiroideos y normalización de la tiroxina, al igual que la signología clínica. Se halló una correlación positiva entre título de anticuerpos AD y el volúmen tiroideo (r = 0,78, p160 %. Se concluye que la toxoplasmosis afecta la morfología tiroidea pudiéndose alterar su funcionamiento y desencadenar tiroiditis autoinmune en individuos predispuestos. Abstract Subacute thyroiditis is caused by the action of infectious agents Clinically, goitre, dysphonia and dysphagia can be observed. Hyperthyroxinemia may be present, while thyrotropine (TSH concentration stays normal and iodine uptake is reduced frequently. The objective of the present work was to investigate if toxoplasmosis in dogs can affect thyroid morphology and function. The study was conducted on eight dogs with proven high T. gondii titres (Direct aglutination 160% in spite of being euthyroid during the acute period of toxoplasmosis. In conclusion, toxoplasmosis
Auer, Herbert; Vander-Möse, Angelika; Picher, Otto; Aspöck, Horst
In 1983 the Osterreichische Gesellschaft für Qualitätssicherung und Standardisierung medizinisch-diagnostischer Untersuchungen (OQUASTA) has invited the Department of Medical Parasitology of the Clinical Institute of Hygiene and Medical Microbiology, University of Vienna (today: Medical University of Vienna), to establish an external quality assessment service on the detection of specific antibodies against Toxoplasma gondii, one of the most prevalent protozoic parasites in the world. The objective of this project was the support of Austrian laboratories in standardising their test methods for the detection of specific antibodies against T. gondii. Between 1983 and 2004, 45 collaborating studies were carried out. During this period, the number of participating laboratories has increased from 10 in 1983 to about 50 in recent years. In total, the test results produced by the laboratories matched with the nominal values in more than 90%. On the examples of three human cases we demonstrate that externally validated serological methods alone, despite their great benefit, are not enough for a sufficient serodiagnosis of toxoplasmosis; unusually complicated serological situations do arise and can only be met by the knowledge about special tests, the application of an appropriate examination strategy and -- last but not least -- by many years of experience.
Quist, C F; Dubey, J P; Luttrell, M P; Davidson, W R
Toxoplasmosis was diagnosed in a free-ranging wild turkey (Meleagris gallopavo) from West Virginia (USA) in June 1993. Gross findings included emaciation, splenomegaly, multifocal necrotizing hepatitis and splenitis, and crusting dermatitis on the head and neck. Histologically, multifocal necrosis with mononuclear inflammation was present in kidney, liver, spleen, heart, lungs, and pancreas. Toxoplasma gondii was confirmed in sections of liver by avidin-biotin immunohistochemical analysis. Subsequently, a retrospective serosurvey of wild turkeys for T. gondii antibodies was conducted using turkey sera collected between 1984 and 1989. An antibody prevalence of 10% was detected in 130 birds from 21 locations in the southeastern United States. While wild turkeys in the Southeast have T. gondii antibodies, this is only the second natural case of fatal toxoplasmosis reported; it appears that wild turkeys infrequently develop clinical disease when infected with T. gondii.
Dumas, N; Kawai, K; Cazaux, M; Seguela, J P
Specificities of Japan by geography, culture, and low incidence for Toxoplasmosis were examined in this epidemiological study. 1 731 human sera were examined by several immunological tests but these results are related with Agglutination-Latex test. The sera came from North (Hokkaido), Middle (Tokyo area) and South (Okinawa). The ratio for the whole Japan towards Toxoplasmosis is 24.7% but the increase of antibodies with age is late: rate of positivity 4.6% up to 17 years old and nearly 30% after 30 years old. Cats, business, climate do not seem to influence the human infection. It is consumption of meat and particularly raw meat which influence the results: 40.8% positive results among eaters of raw meat and 22% among those not eating meat or eating it well cooked.
Dietrich, U.; Doerfler, A.; Forsting, M. [Department of Neuroradiology, University Hospital, Essen (Germany); Maschke, M. [Department of Neurology, University Hospital Essen (Germany); Prumbaum, M. [Department of Bone Marrow Transplantation, University Hospital Essen (Germany)
Toxoplasma encephalitis was confirmed by biopsy in three patients with bone marrow (BMT) or peripheral blood stem-cell transplantation (PBSCT). All had MRI before antimicrobial therapy. The intensity of contrast enhancement was very variable. One patient had one large, moderately enhancing cerebral lesion and several smaller almost nonenhancing lesions. The second had small nodular and haemorrhagic lesions without any enhancement. The third had late cerebral toxoplasmosis and showed multiple lesions with marked contrast enhancement. The moderate or absent contrast enhancement in the two patients in the early phase of cerebral toxoplasmosis may be related to a poor immunological response, with a low white blood cell count in at least one patient. Both received higher doses of prednisone than the patient with late infection, leading to a reduced inflammatory response. In patients with a low leukocyte count and/or high doses of immunosuppressive therapy, typical contrast enhancement may be absent. (orig.)
Hohlfeld, P; Biedermann, K; Extermann, P; Gyr, T
Maternal infection with Toxoplasma gondii acquired during pregnancy occurs in more than 500 women per year in Switzerland. Systematic screening at the beginning of pregnancy allows the introduction of health education programs. The screening during pregnancy is performed to diagnose primary maternal infections and to propose prenatal diagnosis and treatment. The administration of specific antibiotherapy during pregnancy (spiramycine or the association of pyrimethamine and sulfonamides) significantly reduces the risk of fetal infection. Prenatal diagnosis of congenital toxoplasmosis is possible and reliable. It avoids unnecessary termination of pregnancy when the fetus is not infected and specific therapy in case of infection (association of pyrimethamine and sulfonamides). Prenatal treatment may be proposed without prenatal diagnosis as of the 16th week of gestation. In any case, prenatal treatment seems to reduce the incidence of severe congenital toxoplasmosis.
Lloyd, Christopher; Stidworthy, Mark F
A juvenile cheetah (Acinonyx jubatus) died with rapidly progressive pyrexia, tachypnea, abdominal effusion, and hepatomegaly. Postmortem examination revealed lesions consistent with acute disseminated infection with Toxoplasma gondii. The presence of this organism was confirmed in multiple organs by immunohistochemistry and polymerase chain reaction. To the best of our knowledge, we propose this to be the first reported case of primary acute disseminated toxoplasmosis in a cheetah.
Elizabeth Chiang; GOLDSTEIN, DEBRA A.; Shapiro, Michael J.; Mets, Marilyn B.
Purpose: Branch retinal artery occlusion (BRAO), while not uncommon in elderly patient populations, is rare in children and adolescents. We report a case of a BRAO secondary to toxoplasmosis in this demographic. Case: A previously healthy 17-year-old male developed a unilateral BRAO in conjunction with inflammation and increased intraocular pressure. Family history was positive for cerebrovascular accidents in multiple family members at relatively young ages. The patient had a hypercoagulable...
Petty, L A; Qamar, S; Ananthanarayanan, V; Husain, A N; Murks, C; Potter, L; Kim, G; Pursell, K; Fedson, S
We describe a case of cardiac toxoplasmosis diagnosed by routine endomyocardial biopsy in a patient with trimethoprim-sulfamethoxazole (TMP-SMX) intolerance on atovaquone prophylaxis. Data are not available on the efficacy of atovaquone as Toxoplasma gondii prophylaxis after heart transplantation. In heart transplant patients in whom TMP-SMX is not an option, other strategies may be considered, including the addition of pyrimethamine to atovaquone.
Toxoplasmosis is caused by a coccidian parasite, Toxoplasma gondii. The parasite is highly prevalent both in humans and in warm-blooded animals. Cat family animals are definitive host, and these animals excrete the infective oocysts in their feces. Humans, though not definitive host, get infection by consuming water or food contaminated with cat feces. Rarely, infection can also take place through transfusing the infected blood, through transplantation of infected organs, or transplacentally ...
Toxoplasmosis is a parasitic disease widely distributed throughout the world, infecting a wide variety of animal species including humans. In Mexico, this parasite has been detected in different parts of the country, particularly in the tropical areas where the parasite can remain infective for long periods of time due to the environmental conditions (i.e. high temperature and humidity over the whole year). Several epidemiological studies have been conducted in both human and animal populatio...
Full Text Available Toxoplasmosis is an infection of warm-blooded vertebrates caused by the obligate intracellular protozoan parasite, Toxoplasma gondii. It is one of the most common parasitic diseases of humans, infecting approximately one-third of the world’s population. In persons with advanced HIV, toxoplasmosis represents a major opportunistic infection of the central nervous system. Approximately two-thirds of all people living with HIV live in sub-Saharan Africa. In areas such as this, toxoplasmosis could theoretically pose a huge threat. There is little known about T. gondii prevalence in humans in Africa. Geographically, prevalences vary widely on this continent, as observed in other parts of the world. There is limited historical information about the disease in South Africa. More knowledge is needed at a regional level about the risk of toxoplasmosis, diagnostic issues, and measures to reduce the risk to susceptible persons. The seroprevalence of T. gondii in selected populations, namely HIV-positive and HIV-negative individuals, and a more general sample biased towards pregnant women, was therefore investigated and found to be 9.8% (37/376, 12.8% (48/376 and 6.4% (32/497 respectively. Compared with historical data from South Africa, the prevalence has decreased substantially; however, the incidence of clinical disease is unknown, despite the very high burden of HIV and AIDS cases (5.9 million and 0.7 million, respectively in 2009. This study provided information relating to the diagnosis and current seroprevalence of T. gondii in South Africa. Many questions still remain to be answered however, to fully understand the impact of this parasite on the country’s population.
Full Text Available Background: Toxoplasma gondii is an obligate intracellular protozoan parasite which can infect human and animals. Acquired toxoplasmosis during pregnancy can lead to fetal infection, which may ultimately result in loss of fetus or lesion in brain and eyes. This study was performed to evaluate the seroepidemiological status of toxoplasmosis in pregnant women in Ilam City, western Iran. Methods: In this cross-sectional study, 553 blood samples were collected from pregnant women. Sera were separated by blood centrifugation at 3000 rpm for 5 min and frozen at -20 °C until use. The samples were tested for IgG antibody by Indirect Immunoflourecence antibody test (IFA. Results: Out of the 553 pregnant women, 247 were positive for T. gondii IgG antibodies and 306 were negative. The mean age of women was 21 and the seropositive rate of latent T. gondii infection was 44.8%. Conclusion: About half of the married women in the present study were at risk of infection with T.gondii, so preventive method should be considered. Keywords: Seroepidemiology, Toxoplasmosis, IFA, Iran.
Sykes, David; Rychtář, Jan
The protozoan Toxoplasma gondii is a parasite often found in wild and domestic cats, and it is the cause of the disease toxoplasmosis. More than 60 million people in the United States carry the parasite, and the Centers for Disease Control have placed toxoplasmosis in their disease classification group Neglected Parasitic Infections as one of five parasitic diseases targeted as priorities for public health action. In recent years, there has been significant progress toward the development of a practical vaccine, so vaccination programs may soon be a viable approach to controlling the disease. Anticipating the availability of a toxoplasmosis vaccine, we are interested in determining when cat owners should vaccinate their own pets. We have created a mathematical model describing the conditions under which vaccination is advantageous. Our model can be used to predict the average vaccination level in the population. We find that there is a critical vaccine cost threshold above which no one will use the vaccine. A vaccine cost slightly below this threshold, however, results in high usage of the vaccine, and consequently in a significant reduction in population seroprevalence. Not surprisingly, we find that populations may achieve herd immunity only if the cost of vaccine is zero.
Cassius Schnell Palhano Silva
Full Text Available Infection caused by Toxoplasma gondii, toxoplasmosis, is one of the most frequent zoonoses in the world; it normally affects both genders equally. Humans are one of several possible intermediate hosts, and the disease is oligosymptomatic in most cases. Vertical transmission is an important cause of fetal malformation and sequels in newborns. Approximately 10% of postnatal cases present multiple manifestations, ranging from low fever and mild lymphadenopathy to severe encephalitis. In moderate cases, lesions such as retinochoroiditis may emerge during acute infection or even years later. We analyzed 313 cases of toxoplasmosis from 1992 to 2004, including 261 acute cases. Most patients were women (68.1%, and 39% of these were pregnant. Among acute infection cases, 64.8% presented symptomatic disease; the most frequent manifestations were lymphadenomegaly (59.8%, fever (27.2%, headache (10.7%, asthenia (10%, weight loss (8.4%, myalgia (8%, retinochoroiditis (3.4% and hepatosplenomegaly (1.5%. Although ocular lesions by T. gondii are well documented as a possible consequence of postnatal infection, two patients developed retinochoroiditis only two years after primary infection. This demonstrates the need for toxoplasmosis case surveillance, even long after acute manifestations.
Vidigal Paula Vieira Teixeira
Full Text Available Toxoplasmosis is one of the most common infections all over the world. Most cases are asymptomatic, except in immunosuppressed individuals and fetuses, which can be seriously damaged. Prenatal diagnosis should be made as soon as possible since treatment of the mother can minimize fetal sequelae. Our aim in this study was to test the polymerase chain reaction technique (PCR in 86 samples of amniotic fluid from women who seroconverted during pregnancy. DNA was amplified using external primers and, in a second step, internal primers, in a nested PCR system. Samples were also inoculated into mice and the newborn were evaluated by T. gondii serology, skull x-ray, transfontanel ultrasound, fundoscopic examination, lumbar puncture and clinical examination. PCR was positive in seven cases and negative in 79. Among PCR-positive cases, two were negative by inoculation into mice and by clinical evaluation; among PCR-negative ones, three had clinical evidence of toxoplasmosis and one was positive after inoculation into mice. PCR showed values of sensitivity = 62.5% and specificity = 97.4%; the values of inoculation into mice where 42.9% and 100%, respectively. Although PCR should not be used alone for prenatal diagnosis of congenital toxoplasmosis, it is a promising method and deserves more studies to improve its efficacy.
Full Text Available En los últimos 5 anos hemos tratado 112 casos de toxoplasmosis. La mayor parte presentaba abortos o coriorretinitis; algunos presentaban meningo-encefalitis, miocarditis y otras formas. Ocho por ciento de los pacientes presentaban dos cuadros anatomoclínicos de toxoplasmosis. Se administro en forma alterna pirimetamina, sulfametopirazina o espiramicina durante períodos prolongados, practicando reacción de Sabin y Feldman cada tres meses. La meta es negativizar la prueba serológica, la cual generalmente logramos. Clinicamente se aprecia curación al observar la desaparición de los fenômenos inflamatorios en el fondo del ojo, la desaparición de adenopatías u otros signos clínicos, ó el desarrollo de embarazos normales con productos normales en mujeres abortadoras. Considerando los graves problemas que hemos visto en hijos de madres con toxoplasmosis, preferimos tratar a éstas antes de nuevos embarazos.
Parthsarathy, Vadivel; Hölscher, Christian
Chronic inflammation in the brain is found in a range of neurodegenerative diseases such as Parkinson's or Alzheimer's disease. We have recently shown that analogues of the glucagon-like polypeptide 1 (GLP-1) such as liraglutide have potent neuroprotective properties in a mouse model of Alzheimer's disease. We also found a reduction of activated microglia in the brain. This finding suggests that GLP-1 analogues such as liraglutide have anti-inflammatory properties. To further characterise this property, we tested the effects of liraglutide on the chronic inflammation response induced by exposure of the brain to 6 Gy (X-ray). Animals were injected i.p. with 25 nmol/kg once daily for 30 days. Brains were analysed for cytokine levels, activated microglia and astrocyte levels, and nitrite levels as a measure for nitric oxide production and protein expression of iNOS. Exposure of the brain to 6 Gy induced a pronounced chronic inflammation response in the brain. The activated microglia load in the cortex and dentate gyrus region of hippocampus (Pbrains of animals treated with liraglutide. The results demonstrate that liraglutide is effective in reducing a number of parameters linked to the chronic inflammation response. Liraglutide or similar GLP-1 analogues may be a suitable treatment for reducing the chronic inflammatory response in the brain found in several neurodegenerative conditions. Copyright © 2012 Elsevier B.V. All rights reserved.
Wei, Qin; Bian, Yeping; Yu, Fuchao; Zhang, Qiang; Zhang, Guanghao; Li, Yang; Song, Songsong; Ren, Xiaomei; Tong, Jiayi
Chronic intermittent hypoxia is considered to play an important role in cardiovascular pathogenesis during the development of obstructive sleep apnea (OSA). We used a well-described OSA rat model induced with simultaneous intermittent hypoxia. Male Sprague Dawley rats were individually placed into plexiglass chambers with air pressure and components were electronically controlled. The rats were exposed to intermittent hypoxia 8 hours daily for 5 weeks. The changes of cardiac structure and function were examined by ultrasound. The cardiac pathology, apoptosis, and fibrosis were analyzed by H&E staining, TUNNEL assay, and picosirius staining, respectively. The expression of inflammation and fibrosis marker genes was analyzed by quantitative real-time PCR and Western blot. Chronic intermittent hypoxia/low pressure resulted in significant increase of left ventricular internal diameters (LVIDs), end-systolic volume (ESV), end-diastolic volume (EDV), and blood lactate level and marked reduction in ejection fraction and fractional shortening. Chronic intermittent hypoxia increased TUNNEL-positive myocytes, disrupted normal arrangement of cardiac fibers, and increased Sirius stained collagen fibers. The expression levels of hypoxia induced factor (HIF)-1α, NF-kB, IL-6, and matrix metallopeptidase 2 (MMP-2) were significantly increased in the heart of rats exposed to chronic intermittent hypoxia. In conclusion, the left ventricular function was adversely affected by chronic intermittent hypoxia, which is associated with increased expression of HIF-1α and NF-kB signaling molecules and development of cardiac inflammation, apoptosis and fibrosis.
Pruimboom, Leo; Raison, Charles L; Muskiet, Frits A J
In recent years, it has become clear that chronic systemic low-grade inflammation is at the root of many, if not all, typically Western diseases associated with the metabolic syndrome. While much focus has been given to sedentary lifestyle as a cause of chronic inflammation, it is less often appreciated that chronic inflammation may also promote a sedentary lifestyle, which in turn causes chronic inflammation. Given that even minor increases in chronic inflammation reduce brain volume in otherwise healthy individuals, the bidirectional relationship between inflammation and sedentary behaviour may explain why humans have lost brain volume in the last 30,000 years and also intelligence in the last 30 years. We review evidence that lack of physical activity induces chronic low-grade inflammation and, consequently, an energy conflict between the selfish immune system and the selfish brain. Although the notion that increased physical activity would improve health in the modern world is widespread, here we provide a novel perspective on this truism by providing evidence that recovery of normal human behaviour, such as spontaneous physical activity, would calm proinflammatory activity, thereby allocating more energy to the brain and other organs, and by doing so would improve human health.
Full Text Available In recent years, it has become clear that chronic systemic low-grade inflammation is at the root of many, if not all, typically Western diseases associated with the metabolic syndrome. While much focus has been given to sedentary lifestyle as a cause of chronic inflammation, it is less often appreciated that chronic inflammation may also promote a sedentary lifestyle, which in turn causes chronic inflammation. Given that even minor increases in chronic inflammation reduce brain volume in otherwise healthy individuals, the bidirectional relationship between inflammation and sedentary behaviour may explain why humans have lost brain volume in the last 30,000 years and also intelligence in the last 30 years. We review evidence that lack of physical activity induces chronic low-grade inflammation and, consequently, an energy conflict between the selfish immune system and the selfish brain. Although the notion that increased physical activity would improve health in the modern world is widespread, here we provide a novel perspective on this truism by providing evidence that recovery of normal human behaviour, such as spontaneous physical activity, would calm proinflammatory activity, thereby allocating more energy to the brain and other organs, and by doing so would improve human health.
Full Text Available The present study was designed to investigate the ameliorative potential of Ocimumsanctum and its saponin rich fraction in chronic constriction injury-induced neuropathic pain in rats. The chronic constriction injury was induced by placing four loose ligatures around the sciatic nerve, proximal to its trifurcation. The mechanical hyperalgesia, cold allodynia, paw heat hyperalgesia and cold tail hyperalgesia were assessed by performing the pinprick, acetone, hot plate and cold tail immersion tests, respectively. Biochemically, the tissue thio-barbituric acid reactive species, super-oxide anion content (markers of oxidative stress and total calcium levels were measured. Chronic constriction injury was associated with the development of mechanical hyperalgesia, cold allodynia, heat and cold hyperalgesia along with an increase in oxidative stress and calcium levels. However, administration of Ocimumsanctum (100 and 200 mg/kg p.o. and its saponin rich fraction (100 and 200 mg/kg p.o. for 14 days significantly attenuated chronic constriction injury-induced neuropathic pain as well as decrease the oxidative stress and calcium levels. It may be concluded that saponin rich fraction of Ocimum sanctum has ameliorative potential in attenuating painful neuropathic state, which may be attributed to a decrease in oxidative stress and calcium levels.
Full Text Available Chlamydia pneumoniae (CP lung infection can induce chronic lung inflammation and is associated with not only acute asthma but also COPD exacerbations. However, in mouse models of CP infection, most studies have investigated specifically the acute phase of the infection and not the longer-term chronic changes in the lungs. We infected C57BL/6 mice with 5 × 10(5 CP intratracheally and monitored inflammation, cellular infiltrates and cytokine levels over time to investigate the chronic inflammatory lung changes. While bacteria numbers declined by day 28, macrophage numbers remained high through day 35. Immune cell clusters were detected as early as day 14 and persisted through day 35, and stained positive for B, T, and follicular dendritic cells, indicating these clusters were inducible bronchus associated lymphoid tissues (iBALTs. Classically activated inflammatory M1 macrophages were the predominant subtype early on while alternatively activated M2 macrophages increased later during infection. Adoptive transfer of M1 but not M2 macrophages intratracheally 1 week after infection resulted in greater lung inflammation, severe fibrosis, and increased numbers of iBALTS 35 days after infection. In summary, we show that CP lung infection in mice induces chronic inflammatory changes including iBALT formations as well as fibrosis. These observations suggest that the M1 macrophages, which are part of the normal response to clear acute C. pneumoniae lung infection, result in an enhanced acute response when present in excess numbers, with greater inflammation, tissue injury, and severe fibrosis.
Binns-Loveman, Karen M; Kaplowitz, Mark R; Fike, Candice D
Devising therapies that might prevent the onset or progression of pulmonary hypertension in newborns has received little attention. Our major objective was to determine whether sildenafil, a selective phosphodiesterase inhibitor, prevents the development of an early stage of chronic hypoxia-induced pulmonary hypertension in newborn pigs. Another objective was to determine whether sildenafil causes pulmonary vasodilation without systemic vasodilation in piglets with chronic pulmonary hypertension. Piglets were raised in room air (control, n = 5) or 10-11% O(2) (hypoxic, n = 17) for 3 days. Some piglets (n = 4) received oral sildenafil, 12 mg/kg/day, throughout exposure to hypoxia. All piglets were anesthetized and catheterized, and pulmonary arterial pressure (Ppa), pulmonary wedge pressure (Pw), aortic pressure (Ao), and cardiac output (CO) were measured. Then for some piglets raised in hypoxia for 3 days, a single oral sildenafil dose (3 mg/kg, n = 6) or placebo (n = 5) was given, and hemodynamic measurements were repeated. For piglets raised in hypoxia for 3 days, mean Ppa and calculated PVR were elevated above respective values in control piglets. Mean Ppa and PVR did not differ between piglets that received sildenafil throughout exposure to hypoxia and those that did not. For piglets with chronic hypoxia-induced pulmonary hypertension that received a single oral dose of sildenafil, mean Ppa and PVR decreased, while mean Pw, CO, mean Ao, and systemic vascular resistance remained the same. All hemodynamic measurements were unchanged after placebo. Oral sildenafil did not influence the early stage of chronic hypoxia-induced pulmonary hypertension in newborn piglets. However, a single oral dose of sildenafil caused pulmonary vasodilation, without systemic vasodilation, in piglets with chronic hypoxia-induced pulmonary hypertension, which may have therapeutic implications.
Russo, M; Carmellino, S
Congenital toxoplasmosis may develop after maternal primary infection during pregnancy. The infection is usually asymptomatic in pregnant women but poses a risk of severe effects on the fetus. In Italy the incidence is about 6 per thousand. The infection is transmitted to the fetus in approximately 50 percent of such cases. The risk of transmission rises with growing gestational age at the time of primary infection; on the contrary, the seriousness of the effect on the fetuses becomes less active with more advanced pregnancies. Infants with congenital toxoplasmosis are mostly asymptomatic at birth but long-term studies have indicated that up to 85% of them will develop serious sequelae as severe impairment of vision, mental retardation and deafness during the months or the years after the birth. Preventing congenital toxoplasmosis is fundamental. All seronegative women should be encouraged to observe good dietary and general health regulations until delivery. Today the diagnosis in the mother is more reliable because of the improvements in serological techniques. Moreover, it is possible to identify infected fetuses by prenatal procedures such as ultrasonography, amniocentesis and cordocentesis, of which the last two consent to detect the parasite and/or specific antibodies. Recently a polymerase chain reaction (PCR) assay has been developed for the detection of Toxoplasma in the amniotic fluid. Adequate serological screening of pregnant and prenatal diagnosis can be helpful in reducing the incidence of congenital toxoplasmosis; furthermore abortion should be reserved only to cases with severe toxoplasmosis revealed by ultrasonography. Early recognition of pregnant infection and a specific treatment could reduce the parasitic colonization in the placenta by more than 60% and prevent infection in the fetus. If the fetal infection has already occurred, maternal treatment may modify the fetal disease. Spiramycin as immediate treatment of maternal primary infection is
Claudio Cesar Jaguaribe Ekman
Full Text Available Foodborne diseases represent operational risks in industrial restaurants. We described an outbreak of nine clustered cases of acute illness resembling acute toxoplasmosis in an industrial plant with 2300 employees. These patients and another 36 similar asymptomatic employees were diagnosed with anti-T. gondii IgG titer and avidity by ELISA. We excluded 14 patients based on high IgG avidity and chronic toxoplasmosis: 13 from controls and one from acute disease other than T. gondii infection. We also identified another three asymptomatic employees with T.gondii acute infection and also anti-T. gondii IgM positive as remaining acute cases. Case control study was conducted by interview in 11 acute infections and 20 negative controls. The ingestion of green vegetables, but not meat or water, was observed to be associated with the incidence of acute disease. These data reinforce the importance of sanitation control in industrial restaurants and also demonstrate the need for improvement in quality control regarding vegetables at risk for T. gondii oocyst contamination. We emphasized the accurate diagnosis of indexed cases and the detection of asymptomatic infections to determine the extent of the toxoplasmosis outbreak.
Brenier-Pinchart, Marie-Pierre; Capderou, Elodie; Bertini, Rose-Laurence; Bailly, Sébastien; Fricker-Hidalgo, Hélène; Varlet-Marie, Emmanuelle; Murat, Jean-Benjamin; Sterkers, Yvon; Touafek, Fériel; Bastien, Patrick; Pelloux, Hervé
Early detection of Toxoplasma tachyzoites circulating in blood using PCR is recommended for immunosuppressed patients at high risk for disseminated toxoplasmosis. Using a toxoplasmosis mouse model, we show that the sensitivity of detection is higher using buffy coat isolated from a large blood volume than using whole blood for this molecular monitoring.
Al-Sheyab, Nihaya A; Obaidat, Mohammad M; Bani Salman, Alaa E; Lafi, Shawkat Q
Foodborne toxoplasmosis is a leading cause of foodborne deaths and hospitalization worldwide. The level of exposure to Toxoplasma gondii is influenced by culture and eating habits. There is a scarcity of data about women's knowledge and perception of this disease. The aim of this study was to determine toxoplasmosis knowledge and preventive practices of young childbearing age women in Jordan. A descriptive cross-sectional study recruited a random sample of 1,390 undergraduate university female students and was stratified based on place of residency. About half of students (51.1%) reported having "ever" heard or read about toxoplasmosis, and almost all students (98.6%) had never been tested for toxoplasmosis. Overall, there was a lack of awareness about toxoplasmosis, its risk factors, symptoms, and timing of infection, and preventive practices. High percentages of females reported a high level of hygienic practices related to hand washing after gardening, changing cat litter, and handling raw meat. However, 16.7% of students reported eating raw meat, 26.5% usually eat traditional herbs, and 17.2% drink untreated spring water. This study establishes a baseline for the awareness levels about toxoplasmosis among young women in Jordan. These findings highlight the urgent need for toxoplasmosis awareness and preventive education for childbearing females. An effective education and outreach program should cover important topics concerning risk factors, high-risk foods, and preventive measures against toxoplasmosis.
Gale, S D; Brown, B L; Erickson, L D; Berrett, A; Hedges, D W
Latent infection from Toxoplasma gondii (T. gondii) is widespread worldwide and has been associated with cognitive deficits in some but not all animal models and in humans. We tested the hypothesis that latent toxoplasmosis is associated with decreased cognitive function in a large cross-sectional dataset, the National Health and Nutrition Examination Survey (NHANES). There were 4178 participants aged 20-59 years, of whom 19.1% had IgG antibodies against T. gondii. Two ordinary least squares (OLS) regression models adjusted for the NHANES complex sampling design and weighted to represent the US population were estimated for simple reaction time, processing speed and short-term memory or attention. The first model included only main effects of latent toxoplasmosis and demographic control variables, and the second added interaction terms between latent toxoplasmosis and the poverty-to-income ratio (PIR), educational attainment and race-ethnicity. We also used multivariate models to assess all three cognitive outcomes in the same model. Although the models evaluating main effects only demonstrated no association between latent toxoplasmosis and the cognitive outcomes, significant interactions between latent toxoplasmosis and the PIR, between latent toxoplasmosis and educational attainment, and between latent toxoplasmosis and race-ethnicity indicated that latent toxoplasmosis may adversely affect cognitive function in certain groups.
Undseth, Øystein; Gerlyng, Per; Goplen, Anne K; Holter, Ellen S; von der Lippe, Elisabeth; Dunlop, Oona
An immunocompetent young man became critically ill with multi-organ failure due to primary toxoplasmosis. Although treated successfully, he relapsed after 1 y with bilateral toxoplasmic chorioretinitis. Severe disseminated toxoplasmosis rarely occurs in immunocompetent patients and may reflect an increased risk of relapse. Secondary prophylaxis must be considered.
Yarmohmmadi, Fatemeh; Rahimi, Nastaran; Faghir-Ghanesefat, Hedyeh; Javadian, Nina; Abdollahi, Alireza; Pasalar, Parvin; Jazayeri, Farahnaz; Ejtemaeemehr, Shahram; Dehpour, Ahmad Reza
The detrimental cardio-toxic effect of doxorubicin, an effective chemotherapeutic agent, limited its clinical use. It has been claimed that doxorubicin cardio-toxicity occurs through calcium ions (Ca(2+)) overload and reactive oxygen species production. Agmatine, an endogenous imidazoline receptor agonist, induce uptake of cytosolic Ca(2+) and cause an increase in activity of calcium pumps, including Ca(2+)-ATPase. Also it shows self-scavenging effect against reactive oxygen species production. Therefore, present study was designed to investigate the effects of agmatine against chronic cardio-toxicity of doxorubicin in rats. Male wistar rats were intraperitoneally injected with doxorubicin and agmatine four times a week for a month. Agmatine significantly alleviate the adverse effect of doxorubicin on left ventricular papillary muscle stimulation threshold and contractibility. Chronic co-administration of agmatine with doxorubicin blocked electrocardiographic changes induced by doxorubicin. In addition, agmatine improved body weight and decreased the mortality rate of animals by doxorubicin. Moreover, reversing the doxorubicin induced myocardial lesions was observed in animals treated by agmatine. A significant rise in the total antioxidant capacity of rat plasma was achieved in agmatine-treated animals in comparison to doxorubicin. To conclude, agmatine may improve therapeutic outcomes of doxorubicin since it exerts protective effects against doxorubicin-induced chronic cardiotoxicity in rats. Copyright © 2016 Elsevier B.V. All rights reserved.
Geraghty, Anna C; Muroy, Sandra E; Zhao, Sheng; Bentley, George E; Kriegsfeld, Lance J; Kaufer, Daniela
Whereas it is well established that chronic stress induces female reproductive dysfunction, whether stress negatively impacts fertility and fecundity when applied prior to mating and pregnancy has not been explored. In this study, we show that stress that concludes 4 days prior to mating results in persistent and marked reproductive dysfunction, with fewer successful copulation events, fewer pregnancies in those that successfully mated, and increased embryo resorption. Chronic stress exposure led to elevated expression of the hypothalamic inhibitory peptide, RFamide-related peptide-3 (RFRP3), in regularly cycling females. Remarkably, genetic silencing of RFRP3 during stress using an inducible-targeted shRNA completely alleviates stress-induced infertility in female rats, resulting in mating and pregnancy success rates indistinguishable from non-stress controls. We show that chronic stress has long-term effects on pregnancy success, even post-stressor, that are mediated by RFRP3. This points to RFRP3 as a potential clinically relevant single target for stress-induced infertility.
Full Text Available Chronic alcohol ingestion increases the risk of developing acute respiratory distress syndrome (ARDS, a severe form of acute lung injury, characterized by alveolar epithelial and endothelial barrier disruption and intense inflammation. Alcohol abuse is also associated with a higher incidence of sepsis or pneumonia resulting in a higher rate of admittance to intensive care, longer inpatient stays, higher healthcare costs, and a 2–4 times greater mortality rate. Chronic alcohol ingestion induced severe oxidative stress associated with increased ROS generation, depletion of the critical antioxidant glutathione (GSH, and oxidation of the thiol/disulfide redox potential in the alveolar epithelial lining fluid and exhaled breath condensate. Across intracellular and extracellular GSH pools in alveolar type II cells and alveolar macrophages, chronic alcohol ingestion consistently induced a 40–60 mV oxidation of GSH/GSSG suggesting that the redox potentials of different alveolar GSH pools are in equilibrium. Alcohol-induced GSH depletion or oxidation was associated with impaired functions of alveolar type II cells and alveolar macrophages but could be reversed by restoring GSH pools in the alveolar lining fluid. The aims of this paper are to address the mechanisms for alcohol-induced GSH depletion and oxidation and the subsequent effects in alveolar barrier integrity, modulation of the immune response, and apoptosis.
Bustillo, Jorge L; Diaz, Jose D; Pacheco, Idarmes C; Gritz, David C
Serological studies indicate that rates of ocular toxoplasmosis (OT) vary geographically, with higher rates in tropical regions. Little is known about population-based rates of active OT. We aimed to describe the epidemiology of OT in Central Cuba. This large-population, cross-sectional cohort study used a prospective database at a large regional referral centre in Central Cuba. The patient database was searched for all patients who presented with OT during the 12-month study period from 1 April 2011 to 31 March 2012. Inclusion criteria were the clinical diagnosis of OT, characterised by focal retinochoroidal inflammation and a response to therapy as expected. Gender-stratified and age-stratified study population data from the 2012 Cuban Census were used to calculate incidence rates and prevalence ratios. Among 279 identified patients with OT, 158 presented with active OT. Of these, 122 new-onset and 36 prior-onset cases were confirmed. Based on the total population in the Sancti Spiritus province (466,106 persons), the overall incidence of active OT was 26.2 per 100,000 person-years (95% CI 21.7 to 31.3) with an annual prevalence ratio of 33.9 per 100,000 persons (95% CI 28.8 to 39.6). The incidence of active OT was lowest in the oldest age group and highest in patients aged 25-44 years (4.5 and 42.1 per 100,000 person-years, respectively). This first report describing population-based rates of OT in the Cuban population highlights the importance of patient age as a likely risk factor for OT. Disease rates were found to be highest in females and young to middle-aged adults. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Full Text Available INTRODUCTION: Glucocorticoids are commonly used as therapeutic agents in many acute and chronic inflammatory and auto-immune diseases. The current study investigated the effects of methylprednisolone (a synthetic glucocorticoid on aortic distensibility and vascular resistance in lipopolysaccharide-induced chronic inflammation in male Wistar rats. METHODS: Chronic inflammation was induced by implanting a subcutaneous slow-release ALZET osmotic pump (1 mg kg(-1 day(-1 lipopolysaccharide for either 2 or 4 weeks. Arterial wave transit time (τ was derived to describe the elastic properties of aortas using the impulse response function of the filtered aortic input impedance spectra. RESULTS: Long-term lipopolysaccharide challenge enhanced the expression of advanced glycation end products (AGEs in the aortas. Lipopolysaccharide also upregulated the inducible form of nitric oxide synthase to produce high levels of nitric oxide (NO, which resulted in vasodilation, as evidenced by the fall in total peripheral resistance (Rp . However, lipopolysaccharide challenge did not influence the elastic properties of aortas, as shown by the unaltered τ. The NO-mediated vascular relaxation may counterbalance the AGEs-induced arterial stiffening so that the aortic distensibility remained unaltered. Treating lipopolysaccharide-challenged rats with methylprednisolone prevented peripheral vasodilation because of its ability to increase Rp . However, methylprednisolone produced an increase in aorta stiffness, as manifested by the significant decline in τ. The diminished aortic distensibility by methylprednisolone paralleled a significant reduction in NO plasma levels, in the absence of any significant changes in AGEs content. CONCLUSION: Methylprednisolone stiffens aortas and elastic arteries in lipopolysaccharide-induced chronic inflammation in rats, for NO activity may be dominant as a counteraction of AGEs.
Emelia, O; Rahana, A R; Mohamad Firdaus, A; Cheng, H S; Nursyairah, M S; Fatinah, A S; Azmawati, M N; Siti, N A M; Aisah, M Y
An accurate diagnosis for toxoplasmosis is crucial for pregnant women as this infection may lead to severe sequelae in the fetus. The value of IgG avidity assay as a tool to determine acute and chronic toxoplasmosis during pregnancy was evaluated in Universiti Kebangsaan Malaysia Medical Centre (UKMMC). In this study, 281 serum samples from 281 pregnant women in various trimesters were collected. These samples were assayed using specific anti-Toxoplasma IgM and IgG antibodies, followed by IgG avidity test. The overall seroprevalence of toxoplasmosis in pregnant women was 35.2% (33.5% for anti-Toxoplasma IgG and 1.8% for both anti-Toxoplasma IgG and IgM antibodies). Of 5 (1.8%) serum samples positive for IgM ELISA, 4 had high-avidity antibodies, suggesting past infection and one sample with borderline avidity index. Two samples with low avidity were from IgM negative serum samples. The IgG avidity assay exhibited an excellent specificity of 97.6% and a negative predictive value (NPV) of 95.6%. The study also demonstrated no significant correlation between avidity indexes of the sera with IgG (r=0.12, p=0.24) and IgM (r=-0.00, p=0.98), suggesting the complementary needs of the two tests for a better diagnosis outcome. These findings highlight the usefulness of IgG avidity assay in excluding a recently acquired toxoplasmosis infection in IgM-positive serum sample.
Paulo J. Nogueira
Full Text Available The effects of chronic mild prenatal stress on leukocyte infiltration into the airways was investigated in rat offspring. The chronic prenatal stress consisted of transitory and variable changes in the rat's living conditions. Offspring at adult age were actively sensitized (day 0 and intratracheally challenged (day 14 with ovalbumin. Bronchoalveolar lavage was performed in the offspring at 48 h after intratracheal challenge with ovalbumin. A significant increase in total leukocyte infiltration was observed in the nonstressed offspring group and this was associated with a marked recruitment of eosinophils without a significant effect on the influx of neutrophils and mononuclear cells. In the prenatal stressed offspring, the counts of both total leukocyte and eosinophils, as well as mononuclear cells, was increased by 50% compared to the non-stressed offspring. We provide here the first experimental evidence that chronic mild unpredictable prenatal stress produces a marked increase in the allergen-induced airway inflammation in the rat offspring.
Crinnion, Walter J
Sauna therapy has been used for hundreds of years in the Scandinavian region as a standard health activity. Studies document the effectiveness of sauna therapy for persons with hypertension, congestive heart failure, and for post-myocardial infarction care. Some individuals with chronic obstructive pulmonary disease (COPD), chronic fatigue, chronic pain, or addictions also find benefit. Existing evidence supports the use of saunas as a component of depuration (purification or cleansing) protocols for environmentally-induced illness. While far-infrared saunas have been used in many cardiovascular studies, all studies applying sauna for depuration have utilized saunas with radiant heating units. Overall, regular sauna therapy (either radiant heat or far-infrared units) appears to be safe and offers multiple health benefits to regular users. One potential area of concern is sauna use in early pregnancy because of evidence suggesting that hyperthermia might be teratogenic.
Fernandez-Cruz, E; Escartin, P; Bootello, A; Kreisler, M; Segovia de Arana, J M
We have used a cytoplasmic enzyme system in the study of the in vitro cytotoxic activity of human peripheral blood leucocytes against isolated liver cells in patients with chronic liver diseases. Lymphocytes from primary biliary cirrhosis and chronic active liver disease patients were shown to have an in vitro capacity to induce a cytolitic effect on isolated hepatocytes, as demonstrated by the enhanced release of lactate dehydrogenase (LDH), a cytoplasmic marker enzyme. No significant LDH release was seen with control lymphocytes of normal persons or with lymphocytes from patients with alcoholic cirrhosis. Our results corroborate, in a different assay system, by a simple, reproducible and different method, that lymphocyte-mediated liver cell damage "in vitro" occurs in both primary biliary cirrhosis and chronic active liver disease. PMID:657588
Li, Bo; Zou, Jian; Wang, Wei-Ya; Liu, Shi-Xi
Submental mass secondary to toxoplasmosis is not common in clinical work. A diagnosis of toxoplasmosis is rarely considered by physicians. Here we describe a 50-year-old woman presented with a progressive, painful, submental and left neck swelling for 1 month. After having obtained an insufficient evidence from the fine-needle biopsy, the patient finally received an excisional biopsy which highly indicated the possibility of lymphadenopathy consistent with toxoplasmosis. Diagnosis of toxoplasmosis was finally established by a combination of the pathological criteria, together with the positive serological finding. According to review the clinical presentations, pathological characteristics, diagnostic standard and treatment of this disease, the article aims to remind otolaryngologists who are evaluating a neck mass should be aware of the infectious cause of lymphadenopathy and the possibility of toxoplasmosis.
Osthoff, M; Chew, E; Bajel, A; Kelsey, G; Panek-Hudson, Y; Mason, K; Szer, J; Ritchie, D; Slavin, M
Toxoplasmosis is increasingly diagnosed after hematopoietic stem cell transplantation (HSCT) and is associated with considerable morbidity and mortality. In the majority of cases, reactivation of latent disease secondary to impaired cellular and humoral immunity after HSCT is believed to be the main pathogenetic mechanism. Hence, primary toxoplasmosis is rarely considered in the differential diagnosis of infections after HSCT in a recipient who is seronegative for Toxoplasma gondii pre-transplant. We herein report a seronegative patient with acute T-cell lymphoblastic leukemia, who developed primary disseminated toxoplasmosis 5 months after HSCT from a seronegative unrelated donor. A review of all reported cases of primary toxoplasmosis after HSCT revealed significantly increased morbidity and mortality. Patients with negative pre-transplant Toxoplasma serology should therefore be considered at risk for toxoplasmosis after allogeneic HSCT. Possible prevention and monitoring strategies for seronegative recipients are reviewed and discussed in detail.
Pautassi, Ricardo Marcos; Godoy, Juan Carlos; Molina, Juan Carlos
The analysis of chronic tolerance to ethanol in adult and adolescent rats has yielded mixed results. Tolerance to some effects of ethanol has been reported in adolescents, yet other studies found adults to exhibit greater tolerance than adolescents or comparable expression of the phenomena at both ages. Another unanswered question is how chronic ethanol exposure affects subsequent ethanol-mediated motivational learning at these ages. The present study examined the development of chronic tolerance to ethanol's hypothermic and motor stimulating effects, and subsequent acquisition of ethanol-mediated odor conditioning, in adolescent and adult male Wistar rats given every-other-day intragastric administrations of ethanol. Adolescent and adult rats exhibited lack of tolerance to the hypothermic effects of ethanol during an induction phase; whereas adults, but not adolescents, exhibited a trend towards a reduction in hypothermia at a challenge phase (Experiment 1). Adolescents, unlike adults, exhibited ethanol-induced motor activation after the first ethanol administration. Adults, but not adolescents, exhibited conditioned odor aversion by ethanol. Subsequent experiments conducted only in adolescents (Experiment 2, Experiment 3 and Experiment 4) manipulated the context, length and predictability of ethanol administration. These manipulations did not promote the expression of ethanol-induced tolerance. This study indicated that, when moderate ethanol doses are given every-other day for a relatively short period, adolescents are less likely than adults to develop chronic tolerance to ethanol-induced hypothermia. This resistance to tolerance development could limit long-term maintenance of ethanol intake. Adolescents, however, exhibited greater sensitivity than adults to the acute motor stimulating effects of ethanol and a blunted response to the aversive effects of ethanol. This pattern of response may put adolescents at risk for early initiation of ethanol intake.
Capobiango, Jaqueline Dario; Pagliari, Sthefany; Pasquali, Aline Kuhn Sbruzzi; Nino, Beatriz; Ferreira, Fernanda Pinto; Monica, Thaís Cabral; Tschurtschenthaler, Nely Norder; Navarro, Italmar Teodorico; Garcia, João Luis; Mitsuka-Breganó, Regina; Reiche, Edna Maria Vissoci
The aim of this study was to evaluate an enzyme-linked immunoassay with recombinant rhoptry protein 2 (ELISA-rROP2) for its ability to detect Toxoplasma gondii ROP2-specific IgG in samples from pregnant women. The study included 236 samples that were divided into groups according to serological screening profiles for toxoplasmosis: unexposed (n = 65), probable acute infection (n = 48), possible acute infection (n = 58) and exposed to the parasite (n = 65). When an indirect immunofluorescence assay forT. gondii-specific IgG was considered as a reference test, the ELISA-rROP2 had a sensitivity of 61.8%, specificity of 62.8%, predictive positive value of 76.6% and predictive negative value of 45.4% (p = 0.0002). The ELISA-rROP2 reacted with 62.5% of the samples from pregnant women with probable acute infection and 40% of the samples from pregnant women with previous exposure (p = 0.0180). Seropositivity was observed in 50/57 (87.7%) pregnant women with possible infection. The results underscored that T. gondii rROP2 is recognised by specific IgG antibodies in both the acute and chronic phases of toxoplasmosis acquired during pregnancy. However, the sensitivity of the ELISA-rROP2 was higher in the pregnant women with probable and possible acute infections and IgM reactivity.
Ya-Lei Ning; Nan Yang; Xing Chen; Zi-Ai Zhao; Xiu-Zhu Zhang; Xing-Yun Chen; Ping Li
Objective:To investigate the effects of three different ways of chronic caffeine administration on blastinduced memory dysfunction and to explore the underlying mechanisms.Methods:Adult male C57BL/6 mice were used and randomly divided into five groups:control:without blast exposure,con-water:administrated with water continuously before and after blast-induced traumatic brain injury (bTBI),con-caffeine:administrated with caffeine continuously for 1 month before and after bTBI,pre-caffeine:chronically administrated with caffeine for 1 month before bTBI and withdrawal after bTBI,post-caffeine:chronically administrated with caffeine after bTBI.After being subjected to moderate intensity of blast injury,mice were recorded for learning and memory performance using Morris water maze (MWM) paradigms at 1,4,and 8 weeks post-blast injury.Neurological deficit scoring,glutamate concentration,proinflammatory cytokines production,and neuropathological changes at 24 h,1,4,and 8 weeks post-bTBI were examined to evaluate the brain injury in early and prolonged stages.Adenosine A1 receptor expression was detected using qPCR.Results:All of the three ways of chronic caffeine exposure ameliorated blast-induced memory deficit,which is correlated with the neuroprotective effects against excitotoxicity,inflammation,astrogliosis and neuronal loss at different stages of injury.Continuous caffeine treatment played positive roles in both early and prolonged stages of bTBI;pre-bTBl and post-bTBl treatment of caffeine tended to exert neuroprotective effects at early and prolonged stages of bTBI respectively.Up-regulation of adenosine A1 receptor expression might contribute to the favorable effects of chronic caffeine consumption.Conclusion:Since caffeinated beverages are widely consumed in both civilian and military personnel and are convenient to get,the results may provide a promising prophylactic strategy for blast-induced neurotrauma and the consequent cognitive impairment.
Udi E Ghitza
Full Text Available Over the past two decades, a steeply growing number of persons with chronic non-cancer pain have been using opioid analgesics chronically to treat it, accompanied by a markedly increased prevalence of individuals with opioid-related misuse, opioid use disorders, emergency department visits, hospitalizations, admissions to drug treatment programs, and drug overdose deaths. This opioid misuse and overdose epidemic calls for well-designed randomized-controlled clinical trials into more skillful and appropriate pain management and for developing effective analgesics which have lower abuse liability and are protective against stress induced by chronic non-cancer pain. However, incomplete knowledge regarding effective approaches to treat various types of pain has been worsened by an under-appreciation of overlapping neurobiological mechanisms of stress, stress-induced relapse to opioid use, and chronic non-cancer pain in patients presenting for care for these conditions. This insufficient knowledge base has unfortunately encouraged common prescription of conveniently-available opioid pain-relieving drugs with abuse liability, as opposed to treating underlying problems using team-based multidisciplinary, patient-centered, collaborative-care approaches for addressing pain and co-occurring stress and risk for opioid use disorder. This paper reviews recent neurobiological findings regarding overlapping mechanisms of stress-induced relapse to opioid misuse and chronic non-cancer pain, and then discusses these in the context of key outstanding evidence gaps and clinical-treatment research directions which may be pursued to fill these gaps. Such research directions, if conducted through well-designed randomized controlled trials, may substantively inform clinical practice in general medical settings on how to effectively care for patients presenting with pain-related distress and these common co-occurring conditions.
Park, Paula E; Schlosburg, Joel E; Vendruscolo, Leandro F; Schulteis, Gery; Edwards, Scott; Koob, George F
Opioids represent effective drugs for the relief of pain, yet chronic opioid use often leads to a state of increased sensitivity to pain that is exacerbated during withdrawal. A sensitization of pain-related negative affect has been hypothesized to closely interact with addiction mechanisms. Neuro-adaptive changes occur as a consequence of excessive opioid exposure, including a recruitment of corticotropin-releasing factor (CRF) and norepinephrine (NE) brain stress systems. To better understand the mechanisms underlying the transition to dependence, we determined the effects of functional antagonism within these two systems on hyperalgesia-like behavior during heroin withdrawal utilizing models of both acute and chronic dependence. We found that passive or self-administered heroin produced a significant mechanical hypersensitivity. During acute opioid dependence, systemic administration of the CRF1 receptor antagonist MPZP (20 mg/kg) alleviated withdrawal-induced mechanical hypersensitivity. In contrast, several functional adrenergic system antagonists (clonidine, prazosin, propranolol) failed to alter mechanical hypersensitivity in this state. We then determined the effects of chronic MPZP or clonidine treatment on extended access heroin self-administration and found that MPZP, but not clonidine, attenuated escalation of heroin intake, whereas both drugs alleviated chronic dependence-associated hyperalgesia. These findings suggest that an early potentiation of CRF signaling occurs following opioid exposure that begins to drive both opioid-induced hyperalgesia and eventually intake escalation.
Zhao, Ting Ting; Shin, Keon Sung; Park, Hyun Jin; Yi, Bo Ram; Lee, Kyung Eun; Lee, Myung Koo
This study investigated the effects of (-)-sesamin on chronic electric footshock (EF) stress-induced anxiety disorders in mice. Mice were treated with (-)-sesamin (25 and 50 mg/kg) orally once a day for 21 days prior to exposure to EF stress (0.6 mA, 1 s every 5 s, 3 min). Mice treated with (-)-sesamin (25 and 50 mg/kg) exhibited less severe decreases in the number of open arm entries and time spent on open arms in the elevated plus-maze test and the distance traveled in the open field test following exposure to chronic EF stress. Similarly, mice treated with (-)-sesamin exhibited significantly less severe decreases in brain levels of dopamine, norepinephrine, and serotonin following exposure to chronic EF stress. Increases in serum levels of corticosterone and expression of c-Fos were also less pronounced in mice treated with (-)-sesamin (25 and 50 mg/kg). These results suggest that (-)-sesamin may protect against the effects of chronic EF stress-induced anxiety disorders by modulating dopamine, norepinephrine, and serotonin levels, c-Fos expression, and corticosterone levels.
Gutiérrez-Rebolledo, Gabriel Alfonso; Galar-Martínez, Marcela; García-Rodríguez, Rosa Virginia; Chamorro-Cevallos, Germán A; Hernández-Reyes, Ana Gabriela; Martínez-Galero, Elizdath
One of the major mechanisms in the pathogenesis of chronic inflammation is the excessive production of reactive oxygen and reactive nitrogen species, and therefore, oxidative stress. Spirulina (Arthrospira) maxima has marked antioxidant activity in vivo and in vitro, as well as anti-inflammatory activity in certain experimental models, the latter activity being mediated probably by the antioxidant activity of this cyanobacterium. In the present study, chronic inflammation was induced through injection of Freund's complete adjuvant (CFA) in rats treated daily with Spirulina (Arthrospira) maxima for 2 weeks beginning on day 14. Joint diameter, body temperature, and motor capacity were assessed each week. On days 0 and 28, total and differential leukocyte counts and serum oxidative damage were determined, the latter by assessing lipid peroxidation and protein carbonyl content. At the end of the study, oxidative damage to joints was likewise evaluated. Results show that S. maxima favors increased mobility, as well as body temperature regulation, and a number of circulating leukocytes, lymphocytes, and monocytes in specimens with CFA-induced chronic inflammation and also protects against oxidative damage in joint tissue as well as serum. In conclusion, the protection afforded by S. maxima against development of chronic inflammation is due to its antioxidant activity.
Gutiérrez-Rebolledo, Gabriel Alfonso; Galar-Martínez, Marcela; García-Rodríguez, Rosa Virginia; Chamorro-Cevallos, Germán A.; Hernández-Reyes, Ana Gabriela
Abstract One of the major mechanisms in the pathogenesis of chronic inflammation is the excessive production of reactive oxygen and reactive nitrogen species, and therefore, oxidative stress. Spirulina (Arthrospira) maxima has marked antioxidant activity in vivo and in vitro, as well as anti-inflammatory activity in certain experimental models, the latter activity being mediated probably by the antioxidant activity of this cyanobacterium. In the present study, chronic inflammation was induced through injection of Freund's complete adjuvant (CFA) in rats treated daily with Spirulina (Arthrospira) maxima for 2 weeks beginning on day 14. Joint diameter, body temperature, and motor capacity were assessed each week. On days 0 and 28, total and differential leukocyte counts and serum oxidative damage were determined, the latter by assessing lipid peroxidation and protein carbonyl content. At the end of the study, oxidative damage to joints was likewise evaluated. Results show that S. maxima favors increased mobility, as well as body temperature regulation, and a number of circulating leukocytes, lymphocytes, and monocytes in specimens with CFA-induced chronic inflammation and also protects against oxidative damage in joint tissue as well as serum. In conclusion, the protection afforded by S. maxima against development of chronic inflammation is due to its antioxidant activity. PMID:25599112
Yan, Zhi-Qiang; Chen, Jun; Xing, Guo-Xiang; Huang, Jian-Guo; Hou, Xiang-Hong; Zhang, Yong
To investigate the effects of salidroside on cognitive dysfunction induced by chronic cerebral hypoperfusion in rats. Male Sprague-Dawley rats (n = 36) were divided into three groups (n = 12 per group): sham operation; bilateral permanent occlusion of the common carotid arteries (2-VO); 2-VO + salidroside. Rats received 20 mg/kg per day salidroside or vehicle intraperitoneal injection beginning the day before surgery and continuing until 34 days postoperatively. Cognitive function was evaluated by Morris water maze test and hippocampal long-term potentiation (LTP) measurement. Hippocampal neuronal apoptosis was evaluated via immunofluorescence. Chronic cerebral hypoperfusion caused marked cognitive deficit and LTP inhibition. These effects were largely ameliorated by salidroside administration. Salidroside prevented caspase-3 activation, increased the ratio of Bax/Bcl-2, and reversed hippocampal neuronal loss induced by chronic cerebral hypoperfusion. Salidroside prevents cognitive deficits caused by chronic cerebral hypoperfusion in rats, and alleviates apoptosis in the hippocampal CA1 area. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
Full Text Available In the present study we examined gross changes in the mass of whole adrenal glands and that of the adrenal cortex, as well as the serum corticosterone and glucose level of mature male Wistar rats subjected to three different treatments: animals subjected to chronic restraint-stress, animals injected with lithium (Li and chronically stressed rats treated with Li. Under all three conditions we observed hypertrophy of whole adrenals, as well as the adrenal cortices. Chronic restraint stress, solely or in combination with Li treatment, significantly elevated the corticosterone level, but did not change the blood glucose level. Animals treated only with Li exhibited an elevated serum corticosterone level and blood glucose level. The aim of our study was to investigate the modulation of the chronic stress-induced effect on the blood glucose level by lithium, as a possible mechanism of avoiding the damage caused by chronic stress. Our results showed that lithium is an agent of choice which may help to reduce stress-elevated corticosterone and replenish exhausted glucose storages in an organism.
Laurence, A; Houdelier, C; Calandreau, L; Arnould, C; Favreau-Peigné, A; Leterrier, C; Boissy, A; Lumineau, S
Animals perceiving repeated aversive events can become chronically stressed. Chronic activation of the hypothalamic-pituitary-adrenal (HPA) axis can have deleterious consequences on physiological parameters (e.g. BW, blood chemistry) and behaviour (e.g. emotional reactivity, stereotypies, cognition). Environmental enrichment (EE) can be a mean to reduce animal stress and to improve welfare. The aim of this study was first, to assess the effects of EE in battery cages on the behaviour of young Japanese quail and second, to evaluate the impact of EE on quail exposed to chronic stress. The experiment involved quail housed in EE cages and submitted or not to a chronic stress procedure (CSP) (EE cages, control quail: n=16, CSP quail: n=14) and quail housed in standard cages and exposed or not to the CSP (standard non-EE cages, control quail: n=12, CSP quail: n=16). Our procedure consisted of repeated aversive events (e.g. ventilators, delaying access to food, physical restraint, noise) presented two to five times per 24 h, randomly, for 15 days. During CSP, EE improved quail's welfare as their stereotypic pacing decreased and they rested more. CSP decreased exploration in all quail. After the end of CSP, quail presented increased emotional reactivity in emergence test. However, the effect of EE varied with test. Finally, chronic stress effects on comfort behaviours in the emergence test were alleviated by EE. These results indicate that EE can alleviate some aspects of behavioural alterations induced by CSP.
Miyakawa, T; Sumiyoshi, S; Deshimaru, M; Hattori, E; Shikai, I
Experimental alcoholism was produced in rats by supplying them with 15% ethanol as the only source of liquid for a whole year. Histopathological examination revealed that Purkinje cells and granule cells in the cerebellum mainly showed such changes as decrease of ER, ribosomes and severe atrophy of the nerve cells. It might be speculated that these changes were caused by the disturbance of protein synthesis in the nerve cells induced by chronic alcohol effect.
Full Text Available Hepatic adverse effects occur very rarely with alpha-interferon therapy. A case of acute hepatitis induced by alpha-interferon in a 33-year-old man with chronic hepatitis C is described. The patient developed acute hepatitis with very high aminotransferase activity and jaundice. After discontinuing alpha-interferon therapy, hepatitis resolved rapidly. The immune-mediated mechanism is the most probable cause of this hepatitis.
Kuo, Hsiao-I; Paulus, Walter; Batsikadze, Giorgi; Jamil, Asif; Kuo, Min-Fang; Nitsche, Michael A
Serotonin affects memory formation via modulating long-term potentiation (LTP) and depression (LTD). Accordingly, acute selective serotonin reuptake inhibitor (SSRI) administration enhanced LTP-like plasticity induced by transcranial direct current stimulation (tDCS) in humans. However, it usually takes some time for SSRI to reduce clinical symptoms such as anxiety, negative mood, and related symptoms of depression and anxiety disorders. This might be related to an at least partially different effect of chronic serotonergic enhancement on plasticity, as compared with single-dose medication. Here we explored the impact of chronic application of the SSRI citalopram (CIT) on plasticity induced by tDCS in healthy humans in a partially double-blinded, placebo (PLC)-controlled, randomized crossover study. Furthermore, we explored the dependency of plasticity induction from the glutamatergic system via N-methyl-D-aspartate receptor antagonism. Twelve healthy subjects received PLC medication, combined with anodal or cathodal tDCS of the primary motor cortex. Afterwards, the same subjects took CIT (20 mg/day) consecutively for 35 days. During this period, four additional interventions were performed (CIT and PLC medication with anodal/cathodal tDCS, CIT and dextromethorphan (150 mg) with anodal/cathodal tDCS). Plasticity was monitored by motor-evoked potential amplitudes elicited by transcranial magnetic stimulation. Chronic application of CIT increased and prolonged the LTP-like plasticity induced by anodal tDCS for over 24 h, and converted cathodal tDCS-induced LTD-like plasticity into facilitation. These effects were abolished by dextromethorphan. Chronic serotonergic enhancement results in a strengthening of LTP-like glutamatergic plasticity, which might partially explain the therapeutic impact of SSRIs in depression and other neuropsychiatric diseases.
Ivan Kraus; Dinko Vitezic
Hepatic adverse effects occur very rarely with alpha-interferon therapy. A case of acute hepatitis induced by alpha-interferon in a 33-year-old man with chronic hepatitis C is described. The patient developed acute hepatitis with very high aminotransferase activity and jaundice. After discontinuing alpha-interferon therapy, hepatitis resolved rapidly. The immune-mediated mechanism is the most probable cause of this hepatitis.
Full Text Available Hypothalamus-pituitary-adrenal (HPA hyperactivity is observed in many patients suffering from depression and the mechanism underling the dysfunction of HPA axis is not well understood. Chronic stress has a causal relationship with the hyperactivity of HPA axis. Stress induces the over-synthesis of glucocorticoids, which will arrive at all the body containing the brain. It is still complicated whether glucocorticoids account for chronic stress-induced HPA axis hyperactivity and in which part of the brain the glucocorticoids account for chronic stress-induced HPA axis hyperactivity. Here, we demonstrated that glucocorticoids were indispensable and sufficient for chronic stress-induced hyperactivity of HPA axis. Although acute glucocorticoids elevation in the hippocampus and hypothalamus exerted a negative regulation of HPA axis, we found that chronic glucocorticoids elevation in the hippocampus but not in the hypothalamus accounted for chronic stress-induced hyperactivity of HPA axis. Chronic glucocorticoids exposure in the hypothalamus still exerted a negative regulation of HPA axis activity. More importantly, we found mineralocorticoid receptor (MR - neuronal nitric oxide synthesis enzyme (nNOS - nitric oxide (NO pathway mediated the different roles of glucocorticoids in the hippocampus and hypothalamus in regulating HPA axis activity. This study suggests that the glucocorticoids in the hippocampus play an important role in the development of HPA axis hyperactivity and the glucocorticoids in the hypothalamus can't induce hyperactivity of HPA axis, revealing new insights into understanding the mechanism of depression.
Zhu, Li-Juan; Liu, Meng-Ying; Li, Huan; Liu, Xiao; Chen, Chen; Han, Zhou; Wu, Hai-Yin; Jing, Xing; Zhou, Hai-Hui; Suh, Hoonkyo; Zhu, Dong-Ya; Zhou, Qi-Gang
Hypothalamus-pituitary-adrenal (HPA) hyperactivity is observed in many patients suffering from depression and the mechanism underling the dysfunction of HPA axis is not well understood. Chronic stress has a causal relationship with the hyperactivity of HPA axis. Stress induces the over-synthesis of glucocorticoids, which will arrive at all the body containing the brain. It is still complicated whether glucocorticoids account for chronic stress-induced HPA axis hyperactivity and in which part of the brain the glucocorticoids account for chronic stress-induced HPA axis hyperactivity. Here, we demonstrated that glucocorticoids were indispensable and sufficient for chronic stress-induced hyperactivity of HPA axis. Although acute glucocorticoids elevation in the hippocampus and hypothalamus exerted a negative regulation of HPA axis, we found that chronic glucocorticoids elevation in the hippocampus but not in the hypothalamus accounted for chronic stress-induced hyperactivity of HPA axis. Chronic glucocorticoids exposure in the hypothalamus still exerted a negative regulation of HPA axis activity. More importantly, we found mineralocorticoid receptor (MR) - neuronal nitric oxide synthesis enzyme (nNOS) - nitric oxide (NO) pathway mediated the different roles of glucocorticoids in the hippocampus and hypothalamus in regulating HPA axis activity. This study suggests that the glucocorticoids in the hippocampus play an important role in the development of HPA axis hyperactivity and the glucocorticoids in the hypothalamus can't induce hyperactivity of HPA axis, revealing new insights into understanding the mechanism of depression.
Yu, Xiao; Xu, Yanyan; Zhang, Shanshan; Sun, Jian; Liu, Peiyi; Xiao, Lin; Tang, Yuhan; Liu, Liegang; Yao, Ping
Emerging evidence suggested mitophagy activation mitigates ethanol-induced liver injury. However, the effect of ethanol on mitophagy is inconsistent. Importantly, the understanding of mitophagy status after chronic ethanol consumption is limited. This study evaluated the effect of quercetin, a naturally-occurring flavonoid, on chronic ethanol-induced mitochondrial damage focused on mitophagy. An ethanol regime to mice for 15 weeks (accounting for 30% of total calories) led to significant mitochondrial damage as evidenced by changes of the mitochondrial ultrastructure, loss of mitochondrial membrane potential and remodeling of membrane lipid composition, which was greatly attenuated by quercetin (100 mg/kg.bw). Moreover, quercetin blocked chronic ethanol-induced mitophagy suppression as denoted by mitophagosomes-lysosome fusion and mitophagy-related regulator elements, including LC3II, Parkin, p62 and voltage-dependent anion channel 1 (VDAC1), paralleling with increased FoxO3a nuclear translocation. AMP-activated protein kinase (AMPK) and extracellular signal regulated kinase 2 (ERK2), instead of AKT and Sirtuin 1, were involved in quercetin-mediated mitophagy activation. Quercetin alleviated ethanol-elicited mitochondrial damage through enhancing mitophagy, highlighting a promising preventive strategy for alcoholic liver disease.
Ma, Shuai; Li, Xin-Yan; Gong, Nian; Wang, Yong-Xiang
Spinal D-amino acid oxidase (DAAO) is an FAD-dependent peroxisomal flavoenzyme which mediates the conversion of neutral and polar D-amino acids (including D-serine) to the corresponding α-keto acids, and simultaneously produces hydrogen peroxide and ammonia. This study has aimed to explore the potential contributions of spinal DAAO and its mediated hydrogen peroxide/D-serine metabolism to the development of morphine-induced hyperalgesia. Bi-daily subcutaneous injections of morphine to mice over 7 days induced thermal hyperalgesia as measured by both the hot-plate and tail-immersion tests, and spinal astroglial activation with increased spinal gene expression of DAAO, glial fibrillary acidic protein (GFAP) and pro-inflammatory cytokines (interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α)). Subcutaneous injections of the potent DAAO inhibitor CBIO (5-chloro-benzo[D]isoxazol-3-ol) prevented and reversed the chronic morphine-induced hyperalgesia. CBIO also inhibited both astrocyte activation and the expression of pro-inflammatory cytokines. Intrathecal injection of the hydrogen peroxide scavenger PBN (phenyl-N-tert-butylnitrone) and of catalase completely reversed established morphine hyperalgesia, whereas subcutaneous injections of exogenous D-serine failed to alter chronic morphine-induced hyperalgesia. These results provided evidence that spinal DAAO and its subsequent production of hydrogen peroxide rather than the D-serine metabolism contributed to the development of morphine-induced hyperalgesia.
Kim, Hyun Jee
The objective of this study was to investigate whether berberine could ameliorate allodynia induced by chronic constriction injury (CCI) of the sciatic nerve in rats. After inducement of CCI, significant increases in the number of paw lifts from a cold plate test (cold allodynia) and decreased paw withdrawal threshold in the von Frey hair stimulation test (mechanical allodynia) were observed. However, these cold and mechanical allodynia were markedly alleviated by berberine administration in a dose-dependent manner. Sciatic nerve myeloperoxidase and malondialdehyde activities were also attenuated by berberine administration. Continuous injection for 7 days induced no development of tolerance. The antiallodynic effect of 20 mg/kg berberine was comparable to that of amitriptyline 10 mg/kg. This study demonstrated that berberine could mitigate allodynia induced by CCI, a neuropathic pain model, and it suggested that the anti-inflammatory and antioxidative properties of berberine contributed to the antiallodynic effect in the CCI model.
The number of senile patients with therapy resistant bronchial asthma, chronic pulmonary emphysema increases due to the habit of smoking and increased number of older people, and these inflammatory pulmonary diseases are the leading causes of death worldwide. Rhinoviruses cause the majority of common colds, and provoke exacerbations of bronchial asthma and chronic pulmonary emphysema. Here, I review the pathogenesis and management of rhinovirus infection-induced exacerbation of senile bronchial asthma and chronic pulmonary emphysema.
Tae Young Oh; Chang Yell Shin; Yong Sung Sohn; Dong Hwan Kim; Byoung Ok Ahn; Eun Bang Lee; Cho Hyun Park
AIM: To investigate the therapeutic effects of DA-9601 on sodium taurocholate (TCA)-induced chronic reflux gastritis in SD rats.METHODS: In this study, we have investigated the therapeutic effects of DA-9601 on chronic erosive and atrophic gastritis induced by 6 mo of TCA administration (5 mmol/L in drinking water) in SD rats. RESULTS: Four weeks of DA-9601 administration (0.065%, 0.216% in rat chow), following the withdrawal of TCA treatment, resulted in a significant decrease in total length of erosions in rats in a dose-dependent manner. Furthermore, the indicators of atrophic gastritis, such as reduced mucosal thickness and reduction in the number of parietal cells, were improved by the administration of DA-9601 in a dose-related manner. DA-9601 also attenuated inflammatory cell infiltration and the proliferation of collagenous fiber in the gastric mucosa. The improvement in the reduction of the gastric mucus was observed in the rats receiving a high dose of DA-9601 (0.216%). The therapeutic effect of DA-9601 on experimental chronic erosive gastritis was superior to that of rebamipide (1.08% in rat chow). Biochemical analyses showed increased mucosal prostaglandin E2 and reduced glutathione levels by DA-9601 treatment. CONCLUSION: We suggest that DA-9601 is apromising agent for the treatment of chronic erosive and atrophic gastritis with an etiological factor of bile reflux. Increasedmucosal prostaglandin E2 and reduced glutathione by DA-9601 treatment may be therapeutic mechanisms for chronic erosive and atrophic gastritis.
Ulrich-Lai, Yvonne M; Figueiredo, Helmer F; Ostrander, Michelle M; Choi, Dennis C; Engeland, William C; Herman, James P
The adrenal gland is an essential stress-responsive organ that is part of both the hypothalamic-pituitary-adrenal axis and the sympatho-adrenomedullary system. Chronic stress exposure commonly increases adrenal weight, but it is not known to what extent this growth is due to cellular hyperplasia or hypertrophy and whether it is subregion specific. Moreover, it is not clear whether increased production of adrenal glucocorticoid after chronic stress is due to increased sensitivity to adrenocorticotropic hormone (ACTH) vs. increased maximal output. The present studies use a 14-day chronic variable stress (CVS) paradigm in adult male rats to assess the effects of chronic stress on adrenal growth and corticosterone steroidogenesis. Exogenous ACTH administration (0-895 ng/100 g body wt) to dexamethasone-blocked rats demonstrated that CVS increased maximal plasma and adrenal corticosterone responses to ACTH without affecting sensitivity. This enhanced function was associated with increased adrenal weight, DNA and RNA content, and RNA/DNA ratio after CVS, suggesting that both cellular hyperplasia and hypertrophy occurred. Unbiased stereological counting of cells labeled for Ki67 (cell division marker) or 4,6-diamidino-2-phenylindole (nuclear marker), combined with zone specific markers, showed that CVS induced hyperplasia in the outer zona fasciculata, hypertrophy in the inner zona fasciculata and medulla, and reduced cell size in the zona glomerulosa. Collectively, these results demonstrate that increased adrenal weight after CVS is due to hyperplasia and hypertrophy that occur in specific adrenal subregions and is associated with increased maximal corticosterone responses to ACTH. These chronic stress-induced changes in adrenal growth and function may have implications for patients with stress-related disorders.
Tramullas, Monica; Finger, Beate C; Moloney, Rachel D; Golubeva, Anna V; Moloney, Gerard; Dinan, Timothy G; Cryan, John F
Functional gastrointestinal disorders, which have visceral hypersensitivity as a core symptom, are frequently comorbid with stress-related psychiatric disorders. Increasing evidence points to a key role for toll-like receptor 4 (TLR4) in chronic pain states of somatic origin. However, the central contribution of TLR4 in visceral pain sensation remains elusive. With pharmacological and genetic approaches, we investigated the involvement of TLR4 in the modulation of visceral pain. The TLR4-deficient and wild-type mice were exposed to chronic stress. Visceral pain was evaluated with colorectal distension. Protein expression levels for TLR4, Cd11b, and glial fibrillary acidic protein (glial cells markers) were quantified in the lumbar region of the spinal cord, prefrontal cortex (PFC), and hippocampus. To evaluate the effect of blocking TLR4 on visceral nociception, TAK-242, a selective TLR4 antagonist, was administered peripherally (intravenous) and centrally (intracerebroventricular and intra-PFC) (n = 10-12/experimental group). The TLR4 deficiency reduced visceral pain and prevented the development of chronic psychosocial stress-induced visceral hypersensitivity. Increased expression of TLR4 coupled with enhanced glia activation in the PFC and increased levels of proinflammatory cytokines were observed after chronic stress in wild-type mice. Administration of a TLR4 specific antagonist, TAK-242, attenuated visceral pain sensation in animals with functional TLR4 when administrated centrally and peripherally. Moreover, intra-PFC TAK-242 administration also counteracted chronic stress-induced visceral hypersensitivity. Our results reveal a novel role for TLR4 within the PFC in the modulation of visceral nociception and point to TLR4 as a potential therapeutic target for the development of drugs to treat visceral hypersensitivity. © 2013 Society of Biological Psychiatry Published by Society of Biological Psychiatry All rights reserved.
Baou, M.; Kohlhaas, S.L.; Butterworth, M.; Vogler, M.; Dinsdale, D.; Walewska, R.; Majid, A.; Eldering, E.; Dyer, M.J.S.; Cohen, G.M.
Background Bortezomib has been successfully used in the treatment of multiple myeloma and has been proposed as a potential treatment for chronic lymphocytic leukemia. In this study we investigated the mechanism by which bortezomib induces apoptosis in chronic lymphocytic leukemia cells. Design and M
Numata, T.; Yamamoto, S.; Yamura, T.
The mite antigen-induced histamine release from leucocytes of chronic urticarial patients was enhanced in the presence of deuterium oxide, which stabilizes microtubules. This enhancing effect of deuterium oxide on the histamine release from leucocytes may provide a useful means for the detection of allergens in vitro in chronic urticaria.
Full Text Available Case summary A 6-year-old female spayed Birman cat presented with a history of weight loss, stiff and short-strided gait in the pelvic limbs and reluctance to jump, progressing to non-ambulatory tetraparesis over 6 weeks. Poor body condition, dehydration and generalised muscle wastage were evident on general examination. Neurological examination revealed mildly depressed mental status, non-ambulatory flaccid tetraparesis and severely decreased proprioception and spinal reflexes in all four limbs. The neuroanatomical localisation was to the peripheral nervous system. Haematology, feline immunodeficiency virus/feline leukaemia virus serology, serum biochemistry, including creatine kinase and thyroxine, thoracic radiographs and abdominal ultrasound did not reveal significant abnormalities. Electromyography revealed fibrillation potentials and positive sharp waves in axial and appendicular muscles. Decreased motor conduction velocities and compound muscle action potential amplitudes were detected in ulnar and sciatic–tibial nerves. Residual latency was increased in the sciatic–tibial nerve. Histologically, several intramuscular nerve branches were depleted of myelinated fibres and a few showed mononuclear infiltrations. Toxoplasma gondii serology titres were compatible with active toxoplasmosis. Four days after treatment initiation with oral clindamycin the cat recovered the ability to walk. T gondii serology titres and neurological examination were normal after 11 and 16 weeks, respectively. Clindamycin was discontinued after 16 weeks. One year after presentation the cat showed mild relapse of clinical signs and seroconversion, which again resolved following treatment with clindamycin. Relevance and novel information To our knowledge, this is the first report of distal polyneuropathy associated with toxoplasmosis in a cat. This case suggests the inclusion of toxoplasmosis as a possible differential diagnosis for acquired polyneuropathies in
Messerer, L; Bouzbid, S; Gourbdji, E; Mansouri, R; Bachi, F
The aim of the study was to estimate the seroprevalence and risk factors of toxoplasmosis in pregnant women in the department of Annaba, Algeria. We performed a cross-sectional study with analytical purposes. The study was collaboration between the laboratory of Parasitology-Mycology, Faculty of Medicine of Annaba and Parasite Biology Department at the Pasteur Institute of Algeria. A total of 1028 pregnant women who underwent prenatal diagnosis/visit were included over a period of 4 years from January 2006 to December 2009. Immunoglobulin G and M were assayed, using the microparticle enzyme method. The avidity test was used to determine the date of contamination according to age of pregnancy. Search for the parasite was made by inoculation of the placenta and cord blood in white mice. The study compared mother-to-child serological profiles using Western Blot (WB) IgG and IgM. Direct (not well-cooked meat) and indirect (presence of cat, gardening) indicators were recorded to search for parasite exposure. Seroprevalence was 47.8 % (95 % CI: 44.8 to 51.0) and the rate of active toxoplasmosis was 1.1 % (95 % CI 0.6 to 1.8). According to their immune status, this was the first serology for 41 % (CI95 %: 38.0-44.0) of women; 12 % (CI95 %: 10.5-14.6) of primiparous women had only one serology test during their entire pregnancy. Major risk factors were consumption of poorly-cooked meat and exposure to cats. Toxoplasmosis during pregnancy is a serious issue and an effective prevention program is needed. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
Holder, Renee M; Rhee, Diane
Opioid analgesics are frequently prescribed and play an important role in chronic pain management. Opioid-induced bowel dysfunction, which includes constipation, hardened stool, incomplete evacuation, gas, and nausea and vomiting, is the most common adverse event associated with opioid use. Mu-opioid receptors are specifically responsible for opioid-induced bowel dysfunction, resulting in reduced peristaltic and secretory actions. Agents that reverse these actions in the bowel without reversing pain control in the central nervous system may be preferred over traditional laxatives. The efficacy and safety of these agents in chronic noncancer pain were assessed from publications identified through Ovid and PubMed database searches. Trials that evaluated the safety and efficacy of oral agents for opioid-induced constipation or opioid-induced bowel dysfunction, excluding laxatives, were reviewed. Lubiprostone and naloxegol are approved in the United States by the Food and Drug Administration for use in opioid-induced constipation. Axelopran (TD-1211) and sustained-release naloxone have undergone phase 2 and phase 1 studies, respectively, for the same indication. Naloxegol and axelopran are peripherally acting μ-opioid receptor antagonists. Naloxone essentially functions as a peripherally acting μ-opioid receptor antagonist when administered orally in a sustained-release formulation. Lubiprostone is a locally acting chloride channel (CIC-2) activator that increases secretions and peristalsis. All agents increase spontaneous bowel movements and reduce other bowel symptoms compared with placebo in patients with noncancer pain who are chronic opioid users. The most common adverse events were gastrointestinal in nature, and none of the drugs were associated with severe adverse or cardiovascular events. Investigations comparing these agents to regimens using standard laxative and combination therapy and trials in special populations and patients with active cancer are
Bonaventura, Daniella; Tirapelli, Carlos R; de Oliveira, Ana Maria
This study investigates the effects of chronic methionine intake on bradykinin (BK)-relaxation. Vascular reactivity experiments were performed on carotid rings from male Wistar rats. Treatment with methionine (0.1, 1 or 2 g kg(-1) per day) for 8 and 16 weeks, but not for 2 and 4 weeks, reduced the relaxation induced by BK. Indomethacin, a non-selective cyclooxygenase (COX) inhibitor, and SQ29548, a selective thromboxane A(2) (TXA(2))/prostaglandin H(2) (PGH(2)) receptor antagonist prevented the reduction in BK-relaxation observed in the carotid from methionine-treated rats. Conversely, AH6809, a selective prostaglandin F(2alpha) (PGF(2alpha)) receptor antagonist did not alter BK-relaxation in the carotid from methionine-treated rats. The nitric oxide synthase (NOS) inhibitors L-NAME, L-NNA and 7-nitroindazole reduced the relaxation induced by BK in carotids from control and methionine-treated rats. In summary, we found that chronic methionine intake impairs the endothelium-dependent relaxation induced by BK and this effect is due to an increased production of endothelial vasoconstrictor prostanoids (possibly TXA(2)) that counteracts the relaxant action displayed by the peptide.
Pérez-Rendón González, J.; Moreno Montañez, T.; Becerra Martell, C.; Martínez Cruz, Setefilla
Se realiza un estudio sobre seroprevalencia de la toxoplasmosis humana en Córdoba, mediante inmunofluorescencia indirecta y hemaglutinación indirecta. La muestra encuestada se compone de 443 sueros, 356 personas supuestamente sanas (estudiantes fundamentalmente) y 87, consideradas de “alto riesgo” (enfermos del Hospital “Reina Sofía”). La positividad obtenida para el total de la muestra ha sido del 43,79 % con IFI y 53,50 % para HAI. Con respecto al sexo, la prevale...
Broytman, Oleg; Braun, Rudolf K; Morgan, Barbara J; Pegelow, David F; Hsu, Pei-Ning; Mei, Linda S; Koya, Ajay K; Eldridge, Marlowe; Teodorescu, Mihaela
Obstructive sleep apnea aggravates asthma, but its mechanisms are unknown. Chronic intermittent hypoxia is one hallmark feature of sleep apnea. In this study, we tested the effects of chronic intermittent hypoxia on allergen-induced inflammation in rats. Four groups (n = 9-11/group) of ovalbumin (OVA)-sensitized Brown-Norway rats underwent intermittent hypoxia (10% oxygen, 30 cycles/h, 10 h/d) or normoxia for 30 days concurrent with weekly OVA or vehicle challenges. Lung physiology, differential leukocyte counts from bronchoalveolar lavage, and histology (Picro Sirius Red staining for collagen content) were compared between groups 2 days after the last challenge. Gene expression in bronchoalveolar lavage cells was quantified by quantitative PCR. Compared with normoxia, chronic intermittent hypoxia reduced the FEV0.1/FVC ratio (P = 0.005), peak expiratory flow (P = 0.002), and mean midexpiratory flow (P = 0.004), predominantly in medium and large airways; decreased the baseline eosinophil number (P = 0.01) and amplified the effect of OVA on monocyte number (P = 0.02 for the interaction); in proximal airways, increased (P = 0.008), whereas in distal airways it decreased (P = 0.004), collagen density; induced qualitative emphysematous changes in lung periphery; and increased expression of the M2 macrophage marker YM-1 and augmented OVA-induced expression of plasminogen activator inhibitor-1. Chronic intermittent hypoxia alters immune response to allergen toward a more TH-1-predominant cellular phenotype with collagen deposition and matrix degradation, leading to airflow limitation. These findings highlight the potential of sleep apnea to aggravate airway dysfunction in patients with preexistent asthma.
Laure Stella Ghoma Linguissi; Bolni Marius Nagalo; Cyrille Bisseye; Thrse S Kagon; Mahamoudou Sanou; Issoufou Tao; Victoire Benao; Jacques Simpor; Bibiane Kon
Objective:To evaluate the prevalence of toxoplasmosis and rubella among pregnant women at Ouagadougou in Burkina Faso. Methods: All patient sera were tested for rubella and toxoplasmosis anti-IgG using commercial ELISA kits (PlateliaTM Rubella IgG and Platelia™Toxo IgG). The presence of anti-rubella and anti-toxoplasmosis IgM in serum samples was tested using commercial ELISA kits Platelia Rubella IgM and Platelia Toxo IgM. Results:Among all the pregnant women tested for toxoplasmosis and rubella, their prevalence were 20.3%and 77.0%, respectively. Pregnant women in the age group of 18-25 years showed the highest frequency of anti-toxoplasmosis (34.5%) and anti-rubella IgG (84.6%). The prevalence of anti-toxoplasma and anti-rubella IgG decreased between 2006 and 2008 from 32.7%to 12.1%and 84.6%to 65.0%, respectively. There was no significant association between age and the mean titer of anti-toxoplasmosis IgG among pregnant women. Conclusions: The diagnosis of toxoplasmosis and rubella is necessary in pregnant women in Burkina Faso because of the low immunization coverage rate of rubella and the high level of exposure to these two infections which can be harmful to the newborn if contracted by women before the third trimester of pregnancy.
Full Text Available Gastroesophageal reflux (GER has been reported as a cause of chronic cough (CC in the United States. It has been reported that 5–21% of CC cases are induced by GER. In Japan, however, detailed clinical features of CC induced by GER have not been described. The present study reports on six Japanese patients with GER-induced CC. The subjects were all females, with a mean age of 72 years. The average body mass index was 37 kg/m2, indicating obesity. No abnormalities were found with regard to concentrations of C-reactive protein, peripheral eosinophil counts, serum IgE concentrations, serum titers of cold agglutinins or antibodies to Mycoplasma pneumoniae, chest radiograph findings, respiratory function tests or blood gas analyses. Bronchial biopsy was performed in three patients and showed chronic inflammation characterized by lymphocytic infiltration, squamous metaplasia and mucosal basement membrane thickening. In the study population (Japanese patients, GER-induced CC tended to occur in elderly obese women and may be attributable to airway inflammation.
Objective To investigate Fos expression in rat lumbarsacral spinal cord and medulla oblongata induced by chronic colonic inflammation. Methods Thirty-three male Sprague-Dawley rats were randomly divided into two groups: experimental group: colonic inflammation was induced in seventeen rats by intraluminal administration of trinitrobenzenesulfonic acid (TNBS); control group: saline was administered intraluminally in sixteen rats; After 3, 7, 14 and 28 days of administration, lumbarsacral spinal cord and medulla oblongata were removed and processed for Fos immunohistochemistry. Results Fos-immunoreactive (Fos-IR) neurons induced by TNBS administration were primarily distributed in deep laminae (laminae Ⅲ-Ⅳ,Ⅴ-Ⅵ) in the spinal dorsal horn and in medullary visceral zone (MVZ) in the medulla oblongata. The number of Fos-IR cells in the spinal cord and MVZ in rats after 7 and 14 days of TNBS administration were significantly higher than that in the control rats (P<0.05). After 28 days of TNBS instillation, the number of Fos-IR neurons in MVZ decreased and became comparable to the control group. However, the number of Fos cells in the spinal cord in some rats were still significantly increased compared with the control rats (P<0.05). Conclusion Fos-IR neurons after colonic inflammation recovery may play an important role in the development of visceral hypersensitivity. Medulla oblongata was a less important structure than the spinal cord in inducing visceral hypersensitivity after chronic colonic inflammation.
Full Text Available Chronic glucocorticoid exposure is known to cause depression and metabolic disorders. It is critical to improve abnormal metabolic status as well as depressive-like behaviors in patients with long-term glucocorticoid therapy. This study aimed to investigate the effects of resveratrol on the depressive-like behaviors and metabolic abnormalities induced by chronic corticosterone injection. Male ICR mice were administrated corticosterone (40 mg/kg by subcutaneous injection for three weeks. Resveratrol (50 and 100 mg/kg, fluoxetine (20 mg/kg and pioglitazone (10 mg/kg were given by oral gavage 30 min prior to corticosterone administration. The behavioral tests showed that resveratrol significantly reversed the depressive-like behaviors induced by corticosterone, including the reduced sucrose preference and increased immobility time in the forced swimming test. Moreover, resveratrol also increased the secretion of insulin, reduced serum level of glucose and improved blood lipid profiles in corticosterone-treated mice without affecting normal mice. However, fluoxetine only reverse depressive-like behaviors, and pioglitazone only prevent the dyslipidemia induced by corticosterone. Furthermore, resveratrol and pioglitazone decreased serum level of glucagon and corticosterone. The present results indicated that resveratrol can ameliorate depressive-like behaviors and metabolic abnormalities induced by corticosterone, which suggested that the multiple effects of resveratrol could be beneficial for patients with depression and/or metabolic syndrome associated with long-term glucocorticoid therapy.
Full Text Available Background. This study investigated whether quercetin could alleviate vascular calcification in experimental chronic renal failure rats induced by adenine. Methods. 32 adult male Wistar rats were randomly divided into 4 groups fed normal diet, normal diet with quercetin supplementation (25 mg/kg·BW/d, 0.75% adenine diet, or adenine diet with quercetin supplementation. All rats were sacrificed after 6 weeks of intervention. Serum renal functions biomarkers and oxidative stress biomarkers were measured and status of vascular calcification in aorta was assessed. Furthermore, the induced nitric oxide synthase (iNOS/p38 mitogen activated protein kinase (p38MAPK pathway was determined to explore the potential mechanism. Results. Adenine successfully induced renal failure and vascular calcification in rat model. Quercetin supplementation reversed unfavorable changes of phosphorous, uric acid (UA and creatinine levels, malonaldehyde (MDA content, and superoxide dismutase (SOD activity in serum and the increases of calcium and alkaline phosphatase (ALP activity in the aorta (P<0.05 and attenuated calcification and calcium accumulation in the medial layer of vasculature in histopathology. Western blot analysis showed that iNOS/p38MAPK pathway was normalized by the quercetin supplementation. Conclusions. Quercetin exerted a protective effect on vascular calcification in adenine-induced chronic renal failure rats, possibly through the modulation of oxidative stress and iNOs/p38MAPK pathway.
Park, JuHyung; Lee, NaYun; Cho, YongHo; Yang, YeongAe
[Purpose] The purpose of this study was to investigate the impact that modified constraint-induced movement therapy has on upper extremity function and the daily life of chronic stroke patients. [Subjects and Methods] Modified constraint-induced movement therapy was conduct for 2 stroke patients with hemiplegia. It was performed 5 days a week for 2 weeks, and the participants performed their daily living activities wearing mittens for 6 hours a day, including the 2 hours of the therapy program. The assessment was conducted 5 times in 3 weeks before and after intervention. The upper extremity function was measured using the box and block test and a dynamometer, and performance daily of living activities was assessed using the modified Barthel index. The results were analyzed using a scatterplot and linear regression. [Results] All the upper extremity functions of the participants all improved after the modified constraint-induced movement therapy. Performance of daily living activities by participant 1 showed no change, but the results of participant 2 had improved after the intervention. [Conclusion] Through the results of this research, it was identified that modified constraint-induced movement therapy is effective at improving the upper extremity functions and the performance of daily living activities of chronic stroke patients.
Li, Yu-Cheng; Liu, Ya-Min; Shen, Ji-Duo; Chen, Jun-Jie; Pei, Yang-Yi; Fang, Xiao-Yan
Chronic glucocorticoid exposure is known to cause depression and metabolic disorders. It is critical to improve abnormal metabolic status as well as depressive-like behaviors in patients with long-term glucocorticoid therapy. This study aimed to investigate the effects of resveratrol on the depressive-like behaviors and metabolic abnormalities induced by chronic corticosterone injection. Male ICR mice were administrated corticosterone (40 mg/kg) by subcutaneous injection for three weeks. Resveratrol (50 and 100 mg/kg), fluoxetine (20 mg/kg) and pioglitazone (10 mg/kg) were given by oral gavage 30 min prior to corticosterone administration. The behavioral tests showed that resveratrol significantly reversed the depressive-like behaviors induced by corticosterone, including the reduced sucrose preference and increased immobility time in the forced swimming test. Moreover, resveratrol also increased the secretion of insulin, reduced serum level of glucose and improved blood lipid profiles in corticosterone-treated mice without affecting normal mice. However, fluoxetine only reverse depressive-like behaviors, and pioglitazone only prevent the dyslipidemia induced by corticosterone. Furthermore, resveratrol and pioglitazone decreased serum level of glucagon and corticosterone. The present results indicated that resveratrol can ameliorate depressive-like behaviors and metabolic abnormalities induced by corticosterone, which suggested that the multiple effects of resveratrol could be beneficial for patients with depression and/or metabolic syndrome associated with long-term glucocorticoid therapy.
Full Text Available Inflammation of the prostate is strongly correlated with development of lower urinary tract symptoms and several studies have implicated prostatic fibrosis in the pathogenesis of bladder outlet obstruction. It has been postulated that inflammation induces prostatic fibrosis but this relationship has never been tested. Here, we characterized the fibrotic response to inflammation in a mouse model of chronic bacterial-induced prostatic inflammation. Transurethral instillation of the uropathogenic E. coli into C3H/HeOuJ male mice induced persistent prostatic inflammation followed by a significant increase in collagen deposition and hydroxyproline content. This fibrotic response to inflammation was accompanied with an increase in collagen synthesis determined by the incorporation of 3H-hydroxyproline and mRNA expression of several collagen remodeling-associated genes, including Col1a1, Col1a2, Col3a1, Mmp2, Mmp9, and Lox. Correlation analysis revealed a positive correlation of inflammation severity with collagen deposition and immunohistochemical staining revealed that CD45+VIM+ fibrocytes were abundant in inflamed prostates at the time point coinciding with increased collagen synthesis. Furthermore, flow cytometric analysis demonstrated an increased percentage of these CD45+VIM+ fibrocytes among collagen type I expressing cells. These data show-for the first time-that chronic prostatic inflammation induces collagen deposition and implicates fibrocytes in the fibrotic process.
卜小宁; 王辰; 庞宝森
Objectives To assess the hemodynamic, oxygen-dynamic and ventilative effects of Zafirlukast in chronic obstructive pulmonary disease (COPD) induced chronic cor pulmonale at acute exacerbation stage and the mechanisms of Zafirlukast efficacy.Methods Eleven cases of chronic cor pulmonale at acute exacerbation were examinted using Swan-Ganz catheter and peripheral intra-artery catheter. The hemodynamic, oxygen-dynamic parameters and respiratory rate, plasma endothelium-1 (ET-1) level, and urea leukotriene E4 (LTE4) level were measured before and at the 1st, 3rd, 5th, 7th, 9th, 12th hour after taking 40 mg Zafirlukast orally. Artarial and mixed venous blood gas analyses were done correspondingly.Results The average pulmonary arterial pressure (mPAP) and pulmonary vascular resistance index (PVRI) were lowered at the 3rd hour after taking Zafirlukast by 23% and 36.5%, respectively. They returned to the baseline around 12th hour. Respiratory rate decreased significantly within the 3rd-7th hour after taking Zafirlukast. LTE4 and ET-1 levels lowered at the 3rd hour and showed a positive correlation with change of mPAP. Conclusions Zafirlukast can reduce mPAP, pulmonary vascular resistance (PVR) and does not affect the ambulatory blood pressure monitoring (ABPM) and oxygenation in cases of chronic cor pulmonale at acute exacerbation stage. Zafirlukast may play a role as an alternative to decrease PAP in COPD patients.
Yang, C; Liu, C; Zhou, Q; Xie, Y C; Qiu, X M; Feng, X
The aim of the study was to elucidate the therapeutic effects of Atracylodes rhizome polysaccharide on adenine-induced chronic renal failure in rats. Fifty male Sprague Dawley rats were selected and randomly divided in to 5 groups (n=10 rats per group): The normal control group, the chronic renal failure pathological control group, the dexamethasone treatment group and two Atracylodes rhizome polysaccharide treatment groups, treated with two different concentrations of the polysaccharide, the Atracylodes rhizome polysaccharide high group and the Atracylodes rhizome polysaccharide low group. All the rats, except those in the normal control group were fed adenine-enriched diets, containing 10 g adenine per kg food for 3 weeks. After being fed with adenine, the dexamethasone treatment group, Atracylodes rhizome polysaccharide high group and Atracylodes rhizome polysaccharide low group rats were administered the drug orally for 2 weeks. On day 35, the kidney coefficient of the rats and the serum levels of creatinine, blood urea nitrogen, total protein and hemalbumin were determined. Subsequent to experimentation on a model of chronic renal failure in rats, the preparation was proven to be able to reduce serum levels of creatinine, blood urea nitrogen and hemalbumin levels (Prenal function. Atracylodes rhizome polysaccharide had reversed the majority of the indices of chronic renal failure in rats.
Fei-Fei Wang; Qian Wang; Yong Chen; Qiang Lin; Hui-Bao Gao; Ping Zhang
Several studies have suggested that stress and ageing exert inhibitory effects on rat Leydig cells.In a pattern similar to the normal process of Leydig cell ageing,stress-mediated increases in glucocorticoid levels inhibit steroidogenic enzyme expression that then results in decreased testosterone secretion.We hypothesized that chronic stress accelerates the degenerative changes associated with ageing in Leydig cells.To test this hypothesis,we established a model of chronic stress to evaluate stress-induced morphological and functional alterations in Brown Norway rat Leydig cells; additionally,intracellular lipofuscin levels,reactive oxygen species (ROS)levels and DNA damage were assessed.The results showed that chronic stress accelerated ageing-related changes:ultrastructural alterations associated with ageing,cellular lipofuscin accumulation,increased ROS levels and more extensive DNA damage were observed.Additionally,testosterone levels were decreased.This study sheds new light on the idea that chronic stress contributes to the degenerative changes associated with ageing in rat Leydig cells in vivo.
Full Text Available Abstract Background Non-alcoholic fatty liver disease (NAFLD, which is characterized by hepatic steatosis, can be reversed by early treatment. Several case reports have indicated that the administration of recombinant growth hormone (GH could improve fatty liver in GH-deficient patients. Here, we investigated whether chronic exogenous GH levels could improve hepatic steatosis induced by a high-fat diet in rats, and explored the underlying mechanisms. Results High-fat diet-fed rats developed abdominal obesity, fatty liver and insulin resistance. Chronic exogenous GH improved fatty liver, by reversing dyslipidaemia, fat accumulation and insulin resistance. Exogenous GH also reduced serum tumour necrosis factor-alpha (TNF-alpha levels, and ameliorated hepatic lipid peroxidation and oxidative stress. Hepatic fat deposition was also reduced by exogenous GH levels, as was the expression of adipocyte-derived adipokines (adiponectin, leptin and resistin, which might improve lipid metabolism and hepatic steatosis. Exogenous GH seems to improve fatty liver by reducing fat weight, improving insulin sensitivity and correcting oxidative stress, which may be achieved through phosphorylation or dephosphorylation of a group of signal transducers and activators of hepatic signal transduction pathways. Conclusions Chronic exogenous GH has positive effects on fatty liver and may be a potential clinical application in the prevention or reversal of fatty liver. However, chronic secretion of exogenous GH, even at a low level, may increase serum glucose and insulin levels in rats fed a standard diet, and thus increase the risk of insulin resistance.
Xu, Pan; Wang, Kezhu; Lu, Cong; Dong, Liming; Chen, Yixi; Wang, Qiong; Shi, Zhe; Yang, Yanyan; Chen, Shanguang; Liu, Xinmin
Chronic mild or unpredictability stress produces a persistent depressive-like state. The main symptoms of depression include weight loss, despair, anhedonia, diminished motivation and mild cognition impairment, which could influence the ability of reward-related learning. In the present study, we aimed to evaluate the effects of chronic restraint stress on the performance of reward-related learning of rats. We used the exposure of repeated restraint stress (6h/day, for 28days) to induce depression-like behavior in rats. Then designed tasks including Pavlovian conditioning (magazine head entries), acquisition and maintenance of instrumental conditioning (lever pressing) and goal directed learning (higher fixed ratio schedule of reinforcement) to study the effects of chronic restraint stress. The results indicated that chronic restraint stress influenced rats in those aspects including the acquisition of a Pavlovian stimulus-outcome (S-O) association, the formation and maintenance of action-outcome (A-O) causal relation and the ability of learning in higher fixed ratio schedule. In conclusion, depression could influence the performances in reward-related learning obviously and the series of instrumental learning tasks may have potential as a method to evaluate cognitive changes in depression.
Xu, Shangcheng; Wang, Pei; Zhang, Huiliang; Gong, Guohua; Gutierrez Cortes, Nicolas; Zhu, Weizhong; Yoon, Yisang; Tian, Rong; Wang, Wang
Mitochondrial permeability transition pore (mPTP) is involved in cardiac dysfunction during chronic β-adrenergic receptor (β-AR) stimulation. The mechanism by which chronic β-AR stimulation leads to mPTP openings is elusive. Here, we show that chronic administration of isoproterenol (ISO) persistently increases the frequency of mPTP openings followed by mitochondrial damage and cardiac dysfunction. Mechanistically, this effect is mediated by phosphorylation of mitochondrial fission protein, dynamin-related protein 1 (Drp1), by Ca2+/calmodulin-dependent kinase II (CaMKII) at a serine 616 (S616) site. Mutating this phosphorylation site or inhibiting Drp1 activity blocks CaMKII- or ISO-induced mPTP opening and myocyte death in vitro and rescues heart hypertrophy in vivo. In human failing hearts, Drp1 phosphorylation at S616 is increased. These results uncover a pathway downstream of chronic β-AR stimulation that links CaMKII, Drp1 and mPTP to bridge cytosolic stress signal with mitochondrial dysfunction in the heart. PMID:27739424
Tania N. Crotti
Full Text Available The field of osteoimmunology has emerged in response to the range of evidences demonstrating the close interrelationship between the immune system and bone metabolism. This is pertinent to immune-mediated diseases, such as rheumatoid arthritis and periodontal disease, where there are chronic inflammation and local bone erosion. Periprosthetic osteolysis is another example of chronic inflammation with associated osteolysis. This may also involve immune mediation when occurring in a patient with rheumatoid arthritis (RA. Similarities in the regulation and mechanisms of bone loss are likely to be related to the inflammatory cytokines expressed in these diseases. This review highlights the role of immune-related factors influencing bone loss particularly in diseases of chronic inflammation where there is associated localized bone loss. The importance of the balance of the RANKL-RANK-OPG axis is discussed as well as the more recently appreciated role that receptors and adaptor proteins involved in the immunoreceptor tyrosine-based activation motif (ITAM signaling pathway play. Although animal models are briefly discussed, the focus of this review is on the expression of ITAM associated molecules in relation to inflammation induced localized bone loss in RA, chronic periodontitis, and periprosthetic osteolysis, with an emphasis on the soluble and membrane bound factor osteoclast-associated receptor (OSCAR.
Rabea Pangerti Jekti
Full Text Available Toxoplasmosis disebabkan oleh parasit Toxoplasma gondii. Diperkirakan sekitar 30 - 50% populasi dunia telah terinfeksi oleh toxoplasma, sebagian besar tanpa gejala. Penderita dengan kekebalan tubuh yang kuat apabila terinfeksi T. gondii pada umumnya tidak mengalami keadaan patologik yang nyata walaupun pada beberapa kasus dapat juga mengalami pembesaran kelenjar limfe, rasa lelah yang berlebihan, miokarditis akut, miositis hingga radang otak. Analisis ini bertujuan untuk mengukur hubungan kekebalan tubuh (titer antibodi pada wanita usia subur terhadap kejadian toxoplasmosis dan faktor risiko tingkat kekebalan tubuh. . Analisis ini menggunakan data potong lintang Riskesdas 2007. Subjek adalah wanita usia subur (WUS yang berusia 15-45 tahun. Kekebalan terhadap toxoplasmosis dilihat dengan mengukur kadar immunoglobulin G (IgG melalui tehnik ELISA (toxolisa. Subjek dikatakan tidak memiliki kekebalan terhadap toxoplasmosis jika toxolisanya <32 IU Sampel yang terpilih di analisis lebih lanjut untuk mengetahui faktor demografi, risiko, dan perilaku yang berhubungan dengan status kekebalan toksoplasmosis. Jumlah sampel yang terpilih dan mempunyai data yang lengkap sejumlah 6068 subjek dari 10521 women in repeoductive age. Hasil menunjukkan bahwa 63,7% memiliki kekebalan, dan 36,3% tidak memiliki kekebalan terhadap toxoplasmosis. WUS yang berusia 15-17 tahun mempunyai risiko yang lebih tinggi untuk tidak memiliki kekebalan toxoplasmosis yaitu sebesar 26% (ORs=1,26, 95% CI 1,03-1,55, p=0,027, begitu juga dengan WUS yang berstatus Ibu Rumah Tangga (IRT dan pelajaryaitu 16% (ORs=1,16, 95% CI 1,04-1,30, p=0,007, dan WUS yang berstatus kawin yaitu 30% (ORs=1,30, 95% CI 1,13-1,49, p=0,000. WUS yang berusia 15-17 tahun, berstatus kawin, dan IRT serta pelajar, merupakan kelompok yang berisiko tidak memiliki kekebalan terhadap toxoplasmosis, sehingga perlu kewaspadaan untuk meningkatkan upaya pencegahan dan perlindungan terhadap toxoplasmosis. Kata kunci
Full Text Available Abstract Background In male patients suffering from chronic pain, opioid administration induces severe hypogonadism, leading to impaired physical and psychological conditions such as fatigue, anaemia and depression. Hormone replacement therapy is rarely considered for these hypogonadic patients, notwithstanding the various pharmacological solutions available. Methods To treat hypogonadism and to evaluate the consequent endocrine, physical and psychological changes in male chronic pain patients treated with morphine (epidural route, we tested the administration of testosterone via a gel formulation for one year. Hormonal (total testosterone, estradiol, free testosterone, DHT, cortisol, pain (VAS and other pain questionnaires, andrological (Ageing Males' Symptoms Scale - AMS and psychological (POMS, CES-D and SF-36 parameters were evaluated at baseline (T0 and after 3, 6 and 12 months (T3, T6, T12 respectively. Results The daily administration of testosterone increased total and free testosterone and DHT at T3, and the levels remained high until T12. Pain rating indexes (QUID progressively improved from T3 to T12 while the other pain parameters (VAS, Area% remained unchanged. The AMS sexual dimension and SF-36 Mental Index displayed a significant improvement over time. Conclusions In conclusion, our results suggest that a constant, long-term supply of testosterone can induce a general improvement of the male chronic pain patient's quality of life, an important clinical aspect of pain management.
Muresanu, Dafin Fior; Zimmermann-Meinzingen, Sibilla; Sharma, Hari Shanker
Whole body hyperthermia (WBH) aggravates brain edema formation and cell damage in chronic hypertensive rats compared with normotensive animals. In this investigation, we examined the influence of cerebrolysin on WBH-induced edema formation and brain pathology in hypertensive and normotensive rats. Rats subjected to 4 h WBH at 38 degrees C in a biological oxygen demand (BOD) incubator showed breakdown of the blood-brain barrier (BBB), reduced cerebral blood flow (CBF), edema formation and cell injuries in several parts of the brain. These effects were further aggravated in chronic hypertensive rats (two-kidney one clip model (2K1C), for 4 weeks) subjected to WBH. Pretreatment with cerebrolysin (5 mL/kg, 24 h and 30 min before heat stress) markedly attenuated the BBB dysfunction and brain pathology in normal animals. However, in hypertensive animals, a high dose of cerebrolysin (10 mL/kg, 24 h and 30 min before heat stress) was needed to attenuate WBH-induced BBB dysfunction and brain pathology. These observations indicate that heat stress could affect differently in normal and hypertensive conditions. Furthermore, our results suggest that patients suffering from various chronic cardiovascular diseases may respond differently to hyperthermia and to neuroprotective drugs, e.g., cerebrolysin not reported earlier.
Origlia, Nicola; Migliori, Massimiliano; Panichi, Vincenzo; Filippi, Cristina; Bertelli, Aldo; Carpi, Angelo; Giovannini, Luca
Cyclosporine (CyA) is an immunosuppressive agent used after solid organ transplantation, but its clinical use is limited by side effects, the most important of which is nephrotoxicity. In a previous work we demonstrated that L-propionylcarnitine (L-PC), a propionyl ester of L-carnitine, is able to prevent CyA-induced acute nephrotoxicity reducing lipid peroxidation in the isolated and perfused rat kidney. CyA administration was associated with a dose dependent increase in renovascular resistance prevented by a pretreatment with L-PC. The aim of the present study was to confirm L-PC protective effect, previously described in vitro, in an in vivo rat model. Chronic nephrotoxicity study was carried out for 28 days. L-PC was administered (i.p. 25 mg/kg b.w.) since the first day, while CyA treatment was performed for the last 21 days (by oral administration 25 mg/kg b.w.). We demonstrate that L-PC was able to significantly lower blood pressure in CyA treated animals and to prevent CyA induced decrease in creatinine clearance. Moreover renal tissue analysis revealed that L-PC was able to reduce lipid hydroperoxide content and morphological abnormalities associated to chronic CyA administration. In conclusion our study demonstrated for the first time in vivo that L-PC protects against functional and tissue damage associated to chronic CyA administration.
Nevitt, Benjamin N; Robinson, Narda; Kratz, Gail; Johnston, Matthew S
Management of trauma-induced chronic torticollis in raptors has historically been challenging. Euthanasia is common in affected birds because of their inability to maintain normal cervical position, although they may be able to function normally. To assess effectiveness of physical therapy of the neck and head as an adjunct treatment for this condition, a case-control study was done in raptors admitted to the Rocky Mountain Raptor Program from 2003 to 2010. Eleven cases were identified with a diagnosis of chronic torticollis resulting from traumatic brain injury. Five cases were treated with physical therapy of the head and neck, and 6 control cases did not receive any physical therapy for the torticollis. Of the control cases, 0 of 6 had resolution of the torticollis, 0 of 6 were released, and 5 of 6 were euthanatized. Of the treated cases, 4 of 5 had complete resolution of the torticollis and 5 of 5 were released. Resolution of torticollis differed significantly between cases receiving physical therapy and controls. These results indicate that physical therapy should be used as an adjunctive therapy in cases of chronic torticollis induced by trauma in raptors because it results in better resolution of the torticollis and increased likelihood of release.
Rathore, Kusum; Wang, Hwa-Chain Robert
Sporadic breast cancers are mainly attributable to long-term exposure to environmental factors, via a multi-year, multi-step, and multi-path process of tumorigenesis involving cumulative genetic and epigenetic alterations in the chronic carcinogenesis of breast cells from a non-cancerous stage to precancerous and cancerous stages. Epidemiologic and experimental studies have suggested that green tea components may be used as preventive agents for breast cancer control. In our research, we have developed a cellular model that mimics breast cell carcinogenesis chronically induced by cumulative exposures to low doses of environmental carcinogens. In this study, we used our chronic carcinogenesis model as a target system to investigate the activity of green tea catechin extract (GTC) at non-cytotoxic levels in intervention of cellular carcinogenesis induced by cumulative exposures to pico-molar 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and benzo[a]pyrene (B[a]P). We identified that GTC, at a non-cytotoxic, physiologically achievable concentration of 2.5 µg/mL, was effective in suppressing NNK- and B[a]P-induced cellular carcinogenesis, as measured by reduction of the acquired cancer-associated properties of reduced dependence on growth factors, anchorage-independent growth, increased cell mobility, and acinar-conformational disruption. We also detected that intervention of carcinogen-induced elevation of reactive oxygen species (ROS), increase of cell proliferation, activation of the ERK pathway, DNA damage, and changes in gene expression may account for the mechanisms of GTC's preventive activity. Thus, GTC may be used in dietary and chemoprevention of breast cell carcinogenesis associated with long-term exposure to low doses of environmental carcinogens.
Fu, Wan; Xie, Heng; Laudon, Moshe; Zhou, Shouhong; Tian, Shaowen; You, Yong
Previous studies have demonstrated that piromelatine (a melatonin and serotonin 5-HT1A and 5-HT1D agonist) exerts an antidepressant activity in rodent models of acute stress and improves cognitive impairments in a rat model of Alzheimer's disease (AD). However, the role of piromelatine in chronic stress-induced memory dysfunction remains unclear. The aim of this study was to determine whether piromelatine ameliorates chronic mild stress (CMS)-induced memory deficits and explore the underlying mechanisms. Rats were exposed randomly to chronic mild stressors for 7 weeks to induce anhedonia (reflected by a significant decrease in sucrose intake), which was used to select rats vulnerable (CMS-anhedonic, CMSA) or resistant (CMS-resistant, CMSR) to stress. Piromelatine (50 mg/kg) was administered daily during the last 2 weeks of CMS. The tail suspension and forced swimming tests were adopted to further characterize vulnerable and resilient rats. The Y-maze and novel object recognition (NOR) tests were used to evaluate memory performance. Brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), phosphorylated CREB (pCREB), and cytogenesis were measured in the hippocampus. We found that only CMSA rats displayed significant increases in immobility time in the tail suspension and forced swimming tests; memory deficits in the Y-maze and NOR tests; significant decreases in hippocampal BDNF, CREB, and pCREB expression; and cytogenesis. All these anhedonia-associated effects were reversed by piromelatine. Piromelatine ameliorates memory deficits associated with CMS-induced anhedonia in rats and this effect may be mediated by restoring hippocampal BDNF, CREB, and cytogenesis deficits.
Holmes, Philip V; Reiss, Jenny I; Murray, Patrick S; Dishman, Rod K; Spradley, Jessica M
Our laboratory has previously reported that chronic, voluntary exercise diminishes seizure-related behaviors induced by convulsant doses of kainic acid. The present experiments tested the hypothesis that exercise exerts this protective effect through a mechanism involving suppression of glutamate release in the hippocampal formation. Following three weeks of voluntary wheel running or sedentary conditions, rats were injected with 10 mg/kg of kainic acid, and hippocampal glutamate was measured in real time using a telemetric, in vivo voltammetry system. A separate experiment measured electroencephalographic (EEG) activity following kainic acid treatment. Results of the voltammetry experiment revealed that the rise in hippocampal glutamate induced by kainic acid is attenuated in exercising rats compared to sedentary controls, indicating that the exercise-induced protection against seizures involves regulation of hippocampal glutamate release. The findings reveal the potential benefit of regular exercise in the treatment and prevention of seizure disorders and suggest a possible neurobiological mechanism underlying this effect.
Hasselbach, H C; Fickenscher, H; Nölle, B; Roider, J
Necrotising retinopathy in immunocompromised hosts is characterised by an unfavourable course often with unspecific clinical features. Therefore, differential diagnosis can be critical. A case of an initially therapy-resistant, necrotizing retinopathy is presented in a 65-year-old immunocompromised male patient suffering from chronic B-cell leukemia. Despite demonstration of cytomegalovirus and Varicella-Zoster-Virus DNA by polymerase chain reaction in vitreous, aqueous humour samples and from retinal biopsy with specific antiviral therapy, a progression of retinal necrosis was noted. Finally Toxoplasma gondii DNA was detected and retinal necrosis resolved after specific treatment. However, visual acuity remains poor because of optic nerve atrophy. The polymerase chain reaction is an important diagnostic tool for differential diagnosis in immunocompromised patients suffering from necrotising retinopathy. If resistance to therapy is noted atypical ocular toxoplasmosis should be considered. The presented case report shows that even multiple infections are possible in the same host.
Marcos Gontijo da Silva
Full Text Available Toxoplasmosis is a parasitary disease that presents high rates of gestational and congenital infection worldwide being therefore considered a public health problem and a neglected disease.To determine the prevalence of toxoplasmosis amongst pregnant women and vertical transmission of Toxoplasma gondii in their newborns attended in the Basic Units of Health (BUH from the city of Gurupi, state of Tocantins, Brazil.A prevalence study was performed, including 487 pregnant women and their newborns attended in the BUH of the urban zone of the city of Gurupi, state of Tocantins, Brazil, during the period from February 2012 to February 2014. The selection of the pregnant women occurred by convenience. In the antenatal admission they were invited to participate in this study. Three samples of peripheral blood were collected for the detection of specific anti-T. gondii IgG, IgM and IgA through ELISA, for the polimerase chain reaction (PCR and IgG avidity during pregnancy. When IgM antibodies were detected the fetal and newborn infection investigation took place. The newborn was investigated right after birth and after one year of age through serology and PCR to confirm/exclude the vertical transmission. The analyses were performed in the Studies of the Host-Parasite Relationship Laboratory (LAERPH, IPTSP-UFG, Goiania, state of Goias, Brazil. The results were inserted in a data bank in Epi-Info 3.3.2 statistic software in which the analysis was performed with p≤5%.The toxoplasmosis infection was detected in 68.37% (333/487, CI95%: 64.62-72.86. The toxoplasmosis chronic infection prevalence was of 63.03% (307/487, CI95%: 58.74-67.32. The prevalence of maternal acute infection was of 5.33% (26/487; CI95%: 3.3-7.3 suspected by IgM antibodies detection in the peripheral blood. The prevalence of confirmed vertical transmission was of 28% (7/25; CI95%: 10.4-45.6.These results show an elevated prevalence of toxoplasmosis in pregnant women and vertical
Stoicea, Nicoleta; Russell, Daric; Weidner, Greg; Durda, Michael; Joseph, Nicholas C; Yu, Jeffrey; Bergese, Sergio D
Chronic pain patients receiving opioid drugs are at risk for opioid-induced hyperalgesia (OIH), wherein opioid pain medication leads to a paradoxical pain state. OIH involves central sensitization of primary and secondary afferent neurons in the dorsal horn and dorsal root ganglion, similar to neuropathic pain. Gabapentin, a gamma-aminobutyric acid (GABA) analog anticonvulsant used to treat neuropathic pain, has been shown in animal models to reduce fentanyl hyperalgesia without compromising analgesic effect. Chronic pain patients have also exhibited lower opioid consumption and improved pain response when given gabapentin. However, few human studies investigating gabapentin use in OIH have been performed in recent years. In this review, we discuss the potential mechanisms that underlie OIH and provide a critical overview of interventional therapeutic strategies, especially the clinically-successful drug gabapentin, which may reduce OIH.
Full Text Available Chronic pain patients receiving opioid drugs are at risk for opioid-induced hyperalgesia (OIH, wherein opioid pain medication leads to a paradoxical pain state. OIH involves central sensitization of primary and secondary afferent neurons in the dorsal horn and dorsal root ganglion, similar to neuropathic pain. Gabapentin, a gamma-aminobutyric acid (GABA analogue anticonvulsant used to treat neuropathic pain, has been shown in animal models to reduce fentanyl hyperalgesia without compromising analgesic effect. Chronic pain patients have also exhibited lower opioid consumption and improved pain response when given gabapentin. However, few human studies investigating gabapentin use in OIH have been performed in recent years. In this review, we discuss the potential mechanisms that underlie OIH and provide a critical overview of interventional therapeutic strategies, especially the clinically-successful drug gabapentin, which may reduce OIH.
Work, Thierry M.; Massey, J. Gregory; Rideout, Bruce A.; Gardiner, Chris H.; Ledig, David B.; Kwok, O.C.H.; Dubey, J.P.
The ‘Alala (Corvus hawaiiensis) is the most endangered corvid in the world, and intensive efforts are being made to reintroduce it to its former native range in Hawaii. We diagnosed Toxoplasma gondii infection in five free-ranging ‘Alala. One ‘Alala, recaptured from the wild because it was underweight and depressed, was treated with diclazuril (10 mg/kg) orally for 10 days. Antibodies were measured before and after treatment by the modified agglutination test (MAT) using whole T. gondii tachyzoites fixed in formalin and mercaptoethanol. The MAT titer decreased four-fold from an initial titer of 1:1,600 with remarkable improvement in physical condition. Lesions of toxoplasmosis also were seen in two partially scavenged carcasses and in a third fresh intact carcass. Toxoplasma gondii was confirmed immunohistochemically by using anti-T. gondii specific serum. The organism was also cultured by bioassay in mice from tissues of one of these birds and the brain of a fifth ‘Alala that did not exhibit lesions. The life cycle of the parasite was experimentally completed in cats. This is the first record of toxoplasmosis in ‘Alala, and the parasite appears to pose a significant threat and management challenge to reintroduction programs for ‘Alala in Hawaii.
Carteret, M.; Petit, E.; Granat, O.; Marichez, M.; Gilquin, J. [Hopital Saint-Joseph, 69 - Lyon (France)
Toxoplasmosis is the most common brain parasitic infection in acquired immunodeficiency syndrome (AIDS). Spinal cord localizations are still rare (2 cases with cerebral involvement, 2 cases without). A case of both spinal cord and cerebral involvement is reported. Magnetic resonance imaging (MR imaging) was performed because of sensory level (L 1). A focal conus medullaris enlargement was seen, iso intense on T 1 weighted images. This lesion was hyperintense on T 2 weighted sequence, and was homogeneously enhanced after Gadolinium on T 1 weighted images. A medullary oedema was noted. A toxoplasmosis treatment was initiated, without cortico therapy. MR imaging performed one month later (D 30), while important clinical improvements were seen, pointed out normal thickness of conus medullaris, without enhancement after Gadolinium. Disease lesions in AIDS with focal spinal cord processes are reviewed, and diagnostic work-up is discussed. Spinal cord single lesion, associated or not with brain involvements should be treated as a toxoplasmic infection, with MR imaging follow up. This work up should avoid medullary biopsy, still required in case of treatment failure. Cerebral involvements, with multiples lesions can mask medullary localization. (authors). 8 refs., 2 figs.
Yan-Bo Zeng; Bing Huang; Shun-Hai Zhu; Hui Dong; Hong-Yu Han; Lian-Lian Jiang; Quan Wang; Jun Cheng; Qi-Ping Zhao; Wei-Jiao Ma
Objective: To identify more effective and less toxic drugs to treat animal toxoplasmosis.Methods:Efficacy of seven kinds of sulfonamides against Toxoplasma gondii (T. gondii) in an acute murine model was evaluated. The mice used throughout the study were randomly assigned to many groups (10 mice each), which either remained uninfected or were infected intraperitoneally with tachyzoites of T. gondii (strains RH and CN). All groups were then treated with different sulfonamides and the optimal treatment protocol was determined candidates. Sulfadiazine-sodium (SD) was used for comparison. Results: The optimal therapy involved gavaging mice twice per day with 250 mg/kg bw of sulfachloropyrazine-sodium (SPZ) for five days. Using this protocol, the average survival time and the time-point of 50% fatalities were prolonged significantly compared with SD treatment. Treatment with SPZ protected 40% of mice from death, and the heart and kidney tissue of these animals was parasite-free, as determined by nested-PCR. SPZ showed excellent therapeutic effects in the treatment of T. gondii in an acute murine model and is therefore a promising drug candidate for the treatment and prevention of T. gondii in animals. Conclusions: It can be concluded that the effective drug sulfachloropyrazine may be the new therapeutic options against animal toxoplasmosis.
Devenny, James J; Godonis, Helen E; Harvey, Susan J; Rooney, Suzanne; Cullen, Mary J; Pelleymounter, Mary Ann
Dapagliflozin is a potent and selective sodium glucose cotransporter-2 (SGLT2) inhibitor which promotes urinary glucose excretion and induces weight loss. Since metabolic compensation can offset a negative energy balance, we explored the potential for a compensatory physiological response to the weight loss induced by dapagliflozin. Dapagliflozin was administered (0.5-5 mpk; p.o.) to diet-induced obese (DIO) rats with or without ad libitum access to food for 38 days. Along with inducing urinary glucose excretion, chronic administration of dapagliflozin dose-dependently increased food and water intake relative to vehicle-treated controls. Despite this, it reduced body weight by 4% (relative to controls) at the highest dose. The degree of weight loss was increased by an additional 9% if hyperphagia was prevented by restricting food intake to that of vehicle controls. Neither oxygen consumption (vO2) or the respiratory exchange ratio (RER) were altered by dapagliflozin treatment alone. Animals treated with dapagliflozin and pair-fed to vehicle controls (5 mpk PF-V) showed a reduction in RER and an elevation in nonfasting β-hydroxybutyrate (BHBA) relative to ad libitum-fed 5 mpk counterparts. Fasting BHBA was elevated in the 1 mpk, 5 mpk, and 5 mpk PF-V groups. Serum glucose was reduced in the fasted, but not the unfasted state. Insulin was reduced in the non-fasted state. These data suggest that in rodents, the persistent urinary glucose excretion induced by dapagliflozin was accompanied by compensatory hyperphagia, which attenuated the weight loss induced by SGLT2 inhibition. Therefore, it is possible that dapagliflozin-induced weight loss could be enhanced with dietary intervention.
Laura R. Hoyt
Full Text Available Alcohol use disorders are common both in the United States and globally, and are associated with a variety of co-morbid, inflammation-linked diseases. The pathogenesis of many of these ailments are driven by the activation of the NLRP3 inflammasome, a multi-protein intracellular pattern recognition receptor complex that facilitates the cleavage and secretion of the pro-inflammatory cytokines IL-1β and IL-18. We hypothesized that protracted exposure of leukocytes to ethanol would amplify inflammasome activation, which would help to implicate mechanisms involved in diseases associated with both alcoholism and aberrant NLRP3 inflammasome activation. Here we show that long-term ethanol exposure of human peripheral blood mononuclear cells and a mouse macrophage cell line (J774 amplifies IL-1β secretion following stimulation with NLRP3 agonists, but not with AIM2 or NLRP1b agonists. The augmented NRLP3 activation was mediated by increases in iNOS expression and NO production, in conjunction with increases in mitochondrial membrane depolarization, oxygen consumption rate, and ROS generation in J774 cells chronically exposed to ethanol (CE cells, effects that could be inhibited by the iNOS inhibitor SEITU, the NO scavenger carboxy-PTIO, and the mitochondrial ROS scavenger MitoQ. Chronic ethanol exposure did not alter K+ efflux or Zn2+ homeostasis in CE cells, although it did result in a lower intracellular concentration of NAD+. Prolonged administration of acetaldehyde, the product of alcohol dehydrogenase (ADH mediated metabolism of ethanol, mimicked chronic ethanol exposure, whereas ADH inhibition prevented ethanol-induced IL-1β hypersecretion. Together, these results indicate that increases in iNOS and mitochondrial ROS production are critical for chronic ethanol-induced IL-1β hypersecretion, and that protracted exposure to the products of ethanol metabolism are probable mediators of NLRP3 inflammasome hyperactivation.
Full Text Available Abstract Background Chronic neuropathic pain is an intractable pain with few effective treatments. Moderate cold stimulation can relieve pain, and this may be a novel train of thought for exploring new methods of analgesia. Transient receptor potential melastatin 8 (TRPM8 ion channel has been proposed to be an important molecular sensor for cold. Here we investigate the role of TRPM8 in the mechanism of chronic neuropathic pain using a rat model of chronic constriction injury (CCI to the sciatic nerve. Results Mechanical allodynia, cold and thermal hyperalgesia of CCI rats began on the 4th day following surgery and maintained at the peak during the period from the 10th to 14th day after operation. The level of TRPM8 protein in L5 dorsal root ganglion (DRG ipsilateral to nerve injury was significantly increased on the 4th day after CCI, and reached the peak on the 10th day, and remained elevated on the 14th day following CCI. This time course of the alteration of TRPM8 expression was consistent with that of CCI-induced hyperalgesic response of the operated hind paw. Besides, activation of cold receptor TRPM8 of CCI rats by intrathecal application of menthol resulted in the inhibition of mechanical allodynia and thermal hyperalgesia and the enhancement of cold hyperalgesia. In contrast, downregulation of TRPM8 protein in ipsilateral L5 DRG of CCI rats by intrathecal TRPM8 antisense oligonucleotide attenuated cold hyperalgesia, but it had no effect on CCI-induced mechanical allodynia and thermal hyperalgesia. Conclusions TRPM8 may play different roles in mechanical allodynia, cold and thermal hyperalgesia that develop after nerve injury, and it is a very promising research direction for the development of new therapies for chronic neuroapthic pain.
Dhungana, Hiramani; Malm, Tarja; Denes, Adam; Valonen, Piia; Wojciechowski, Sara; Magga, Johanna; Savchenko, Ekaterina; Humphreys, Neil; Grencis, Richard; Rothwell, Nancy; Koistinaho, Jari
Ischemic stroke is confounded by conditions such as atherosclerosis, diabetes, and infection, all of which alter peripheral inflammatory processes with concomitant impact on stroke outcome. The majority of the stroke patients are elderly, but the impact of interactions between aging and inflammation on stroke remains unknown. We thus investigated the influence of age on the outcome of stroke in animals predisposed to systemic chronic infection. Th1-polarized chronic systemic infection was induced in 18-22 month and 4-month-old C57BL/6j mice by administration of Trichuris muris (gut parasite). One month after infection, mice underwent permanent middle cerebral artery occlusion and infarct size, brain gliosis, and brain and plasma cytokine profiles were analyzed. Chronic infection increased the infarct size in aged but not in young mice at 24 h. Aged, ischemic mice showed altered plasma and brain cytokine responses, while the lesion size correlated with plasma prestroke levels of RANTES. Moreover, the old, infected mice exhibited significantly increased neutrophil recruitment and upregulation of both plasma interleukin-17α and tumor necrosis factor-α levels. Neither age nor infection status alone or in combination altered the ischemia-induced brain microgliosis. Our results show that chronic peripheral infection in aged animals renders the brain more vulnerable to ischemic insults, possibly by increasing the invasion of neutrophils and altering the inflammation status in the blood and brain. Understanding the interactions between age and infections is crucial for developing a better therapeutic regimen for ischemic stroke and when modeling it as a disease of the elderly.
Person, Rachel J.; Tokar, Erik J.; Xu, Yuanyuan; Orihuela, Ruben; Ngalame, Ntube N. Olive; Waalkes, Michael P., E-mail: email@example.com
Cadmium is a known human lung carcinogen. Here, we attempt to develop an in vitro model of cadmium-induced human lung carcinogenesis by chronically exposing the peripheral lung epithelia cell line, HPL-1D, to a low level of cadmium. Cells were chronically exposed to 5 μM cadmium, a noncytotoxic level, and monitored for acquired cancer characteristics. By 20 weeks of continuous cadmium exposure, these chronic cadmium treated lung (CCT-LC) cells showed marked increases in secreted MMP-2 activity (3.5-fold), invasion (3.4-fold), and colony formation in soft agar (2-fold). CCT-LC cells were hyperproliferative, grew well in serum-free media, and overexpressed cyclin D1. The CCT-LC cells also showed decreased expression of the tumor suppressor genes p16 and SLC38A3 at the protein levels. Also consistent with an acquired cancer cell phenotype, CCT-LC cells showed increased expression of the oncoproteins K-RAS and N-RAS as well as the epithelial-to-mesenchymal transition marker protein Vimentin. Metallothionein (MT) expression is increased by cadmium, and is typically overexpressed in human lung cancers. The major MT isoforms, MT-1A and MT-2A were elevated in CCT-LC cells. Oxidant adaptive response genes HO-1 and HIF-1A were also activated in CCT-LC cells. Expression of the metal transport genes ZNT-1, ZNT-5, and ZIP-8 increased in CCT-LC cells culminating in reduced cadmium accumulation, suggesting adaptation to the metal. Overall, these data suggest that exposure of human lung epithelial cells to cadmium causes acquisition of cancer cell characteristics. Furthermore, transformation occurs despite the cell's ability to adapt to chronic cadmium exposure. - Highlights: • Chronic cadmium exposure induces cancer cell characteristics in human lung cells. • This provides an in vitro model of cadmium-induced human lung cell transformation. • This occurred with general and lung specific changes typical for cancer cells. • These findings add insight to the
Éder Ricardo Biasoli
Full Text Available Objective: Understand the effect of chronic alcohol on the progression of periodontitis induced in Fischer-344 rats.Methods: For the study, 22 Fischer-344 rats, two months old were used, divided into groups: alcohol (n=8, ligature (n=7 and control (n=7. On the first day, the animals in the alcohol group were exposed to ingestion of a water solution containing 20% alcohol (size/size, up to day 90. After thirty days from the beginning of the experiment, the animals in the alcohol group and the ligature group were submitted to the placement of a silk thread around the right maxillary second molar. Nothing was performed on the left side, serving as control. All the groups were submitted to euthanasia 60 days after ligature placement. To assess the destruction of periodontitis, a radiographic exam was used to measure the destruction of bone height. Results: The results of the study showed that on the side in which periodontitis was induced, the group that ingested alcohol suffered an increase in destruction, with statistical differences when compared with the ligature and control groups and increased bone destruction in the ligature group when compared to control. Conclusion: Within the limitations of the study, it was concluded that chronic alcohol consumption by Fischer-344 rats led to greater progression of induced periodontitis.
Chikazawa, Seishiro; Nakazawa, Takafumi; Hori, Yasutomo; Hoshi, Fumio; Kanai, Kazutaka; Ito, Naoyuki; Orino, Koichi; Watanabe, Kiyotaka; Higuchi, Seiichi
In veterinary medicine, hyperferritinemia is often observed in dogs with various diseases (e.g., histiocytic sarcoma and immune-mediated hemolytic anemia) without evidence of iron overload. The mechanism underlying hyperferritinemia development is not well understood. Anemia caused by inflammation is termed as anemia of chronic disease (ACD), and experimentally induced ACD is known to cause slight hyperferritinemia. However, almost all these studies were based on short-term acute inflammation. Hepcidin, a protein mainly produced by hepatocytes, is thought to be a key regulator in iron release from reticuloendothelial cells (RECs), and its expression is related to ACD. We hypothesized that in the case of long-term ACD, iron deposition in RECs increases through hepcidin, causing a diachronic increase in serum ferritin levels. In the present study, we used a canine model with repeated subcutaneous administration of turpentine oil every 3 days over a period of 42 days (15 injections) and induced long-term inflammatory conditions; furthermore, we evaluated the change in serum ferritin concentration. Hypoproliferative anemia, bone marrow iron deposition and hypoferremia, which are characteristic of ACD, were observed on administering the turpentine injections. Hepatic iron content, hepatic hepcidin mRNA expression and serum ferritin concentration increased during the early period after turpentine injection, but returned to normal levels later. These results show that experimentally induced long-term ACD caused hypoproliferative anemia without sustained increase in hepcidin expression and did not cause systemic iron overload. Thus, chronic inflammation may not contribute greatly to increase in hyperferritinemia.
Yoshiharu Motoo; Hisatsugu Mouri; Koushiro Ohtsubo; Yasushi Yamaguchi; Hiroyuki Watanabe; Norio Sawabu
AIM: Ribavirin (RBV) shows a strong antiviral effect on hepatitis C virus when used in combination with interferon.However, RBV-induced anemia is a major problem in this therapy. It would be of great clinical importance to ameliorate the anemia without reducing the RBV dose.We report here that, Ninjinyoeito (NYT), a herbal medicine can reduce the RBV-induced anemia.METHODS: Twenty-three patients with chronic hepatitis C were treated with interferon alpha 2b plus RBV with (NYT group) or without (control group) NYT by a randomized selection. Eighteen patients completed the treatment schedule, and hemato-biochemical and virological effects were evaluated.RESULTS: There was no significant difference in biochemical and virological responses between the two groups. However, anemia was significantly reduced in the NYT group compared with the control group. The maximal decrease of Hb in the NYT group (2.59±1.10 g/dL)was significantly (P= 0.026) smaller than that in the control group (3.71±0.97 g/dL). There was no significant difference in serum glutathione peroxidase activity, serum RBV concentration, and Th1/Th2 balance between the two groups. There was no specific adverse effect in NYT administration.CONCLUSION: These results suggest that NYT could be used as a supportive remedy to reduce the RBV-induced anemia in the treatment of chronic hepatitis C.
Wei, Ruifen; Luo, Guangying; Sun, Zilong; Wang, Shaolin; Wang, Jundong
Previous studies have indicated that fluoride (F) can affect testicular toxicity in humans and rodents. However, the mechanism underlying F-induced testicular toxicity is not well understood. This study was conducted to evaluate the sperm quality, testicular histomorphology and inflammatory response in mice followed F exposure. Healthy male mice were randomly divided into four groups with sodium fluoride (NaF) at 0, 25, 50, 100 mg/L in the drinking water for 180 days. At the end of the exposure, significantly increased percentage of spermatozoa abnormality was found in mice exposed to 50 and 100 mg/L NaF. Disorganized spermatogenic cells, vacuoles in seminiferous tubules and loss and shedding of sperm cells were also observed in the NaF treated group. In addition, chronic F exposure increased testicular interleukin-17(IL-17), interleukin-17 receptor C (IL-17RC), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in transcriptional levels, as well as IL-17 and TNF-α levels in translational levels. Interestingly, we observed that F treated group elevated testicular inducible nitric oxide synthase (iNOS) mRNA level and nitric oxide (NO) concentration. Taken together, these results indicated that testicular inflammatory response could contribute to chronic F exposure induced testicular toxicity in mice.
Buerfent, Benedikt C; Gondorf, Fabian; Wohlleber, Dirk; Schumak, Beatrix; Hoerauf, Achim; Hübner, Marc P
Sepsis initially starts with a systemic inflammatory response (SIRS phase) and is followed by a compensatory anti-inflammatory response syndrome (CARS) that causes impaired adaptive T-cell immunity, immune paralysis and an increased susceptibility to secondary infections. In contrast, parasitic filariae release thousands of microfilariae into the peripheral blood without triggering inflammation, as they induce regulatory, anti-inflammatory host responses. Hence, we investigated the impact of chronic filarial infection on adaptive T-cell responses during the SIRS and CARS phases of a systemic bacterial infection and analysed the development of T-cell paralysis following a subsequent adenovirus challenge in BALB/c mice. Chronic filarial infection impaired adenovirus-specific CD8+ T-cell cytotoxicity and interferon-γ responses in the absence of a bacterial challenge and led to higher numbers of splenic CTLA-4+ CD4+ T cells, whereas splenic T-cell expression of CD69 and CD62 ligand, serum cytokine levels and regulatory T-cell frequencies were comparable to naive controls. Irrespective of filarial infection, the SIRS phase dominated 6–24 hr after intravenous Escherichia coli challenge with increased T-cell activation and pro-inflammatory cytokine production, whereas the CARS phase occurred 6 days post E. coli challenge and correlated with high levels of transforming growth factor-β and increased CD62 ligand T-cell expression. Escherichia coli-induced impairment of adenovirus-specific CD8+ T-cell cytotoxicity and interferon-γ production was not additionally impaired by chronic filarial infection. This suggests that filarial immunoregulation does not exacerbate E. coli-induced T-cell paralysis. PMID:25521437
Samantaray, Supriti; Knaryan, Varduhi H; Patel, Kaushal S; Mulholland, Patrick J; Becker, Howard C; Banik, Naren L
Chronic alcohol consumption causes multifaceted damage to the central nervous system (CNS), underlying mechanisms of which are gradually being unraveled. In our previous studies, activation of calpain, a calcium-activated neutral protease has been found to cause detrimental alterations in spinal motor neurons following ethanol (EtOH) exposure in vitro. However, it is not known whether calpain plays a pivotal role in chronic EtOH exposure-induced structural damage to CNS in vivo. To test the possible involvement of calpain in EtOH-associated neurodegenerative mechanisms the present investigation was conducted in a well-established mouse model of alcohol dependence - chronic intermittent EtOH (CIE) exposure and withdrawal. Our studies indicated significant loss of axonal proteins (neurofilament light and heavy, 50-60%), myelin proteins (myelin basic protein, 20-40% proteolipid protein, 25%) and enzyme (2', 3'-cyclic-nucleotide 3'-phosphodiesterase, 21-55%) following CIE in multiple regions of brain including hippocampus, corpus callosum, cerebellum, and importantly in spinal cord. These CIE-induced deleterious effects escalated after withdrawal in each CNS region tested. Increased expression and activity of calpain along with enhanced ratio of active calpain to calpastatin (sole endogenous inhibitor) was observed after withdrawal compared to EtOH exposure. Pharmacological inhibition of calpain with calpeptin (25 μg/kg) prior to each EtOH vapor inhalation significantly attenuated damage to axons and myelin as demonstrated by immuno-profiles of axonal and myelin proteins, and Luxol Fast Blue staining. Calpain inhibition significantly protected the ultrastructural integrity of axons and myelin compared to control as confirmed by electron microscopy. Together, these findings confirm CIE exposure and withdrawal induced structural alterations in axons and myelin, predominantly after withdrawal and corroborate calpain inhibition as a potential protective strategy against
Kushwah, Neetu; Jain, Vishal; Deep, Satayanarayan; Prasad, Dipti; Singh, Shashi Bala; Khan, Nilofar
Hypoxic exposure results in several pathophysiological conditions associated with nervous system, these include acute and chronic mountain sickness, loss of memory, and high altitude cerebral edema. Previous reports have also suggested the role of hypoxia in pathogenesis of depression and related psychological conditions. On the other hand, sub lethal intermittent hypoxic exposure induces protection against future lethal hypoxia and may have beneficial effect. Therefore, the present study was designed to explore the neuroprotective role of intermittent hypobaric hypoxia (IHH) in Unpredictable Chronic Mild Stress (UCMS) induced depression like behaviour in rats. The IHH refers to the periodic exposures to hypoxic conditions interrupted by the normoxic or lesser hypoxic conditions. The current study examines the effect of IHH against UCMS induced depression, using elevated plus maze (EPM), open field test (OFT), force swim test (FST), as behavioural paradigm and related histological and molecular approaches. The data indicated the UCMS induced depression like behaviour as evident from decreased exploration activity in OFT with increased anxiety levels in EPM, and increased immobility time in the FST; whereas on providing the IHH (5000m altitude, 4hrs/day for two weeks) these behavioural changes were ameliorated. The morphological and molecular studies also validated the neuroprotective effect of IHH against UCMS induced neuronal loss and decreased neurogenesis. Here, we also explored the role of Brain-Derived Neurotrophic Factor (BDNF) in anticipatory action of IHH against detrimental effect of UCMS as upon blocking of BDNF-TrkB signalling the beneficial effect of IHH was nullified. Taken together, the findings of our study demonstrate that the intermittent hypoxia has a therapeutic potential similar to an antidepressant in animal model of depression and could be developed as a preventive therapeutic option against this pathophysiological state.
Full Text Available Hypoxic exposure results in several pathophysiological conditions associated with nervous system, these include acute and chronic mountain sickness, loss of memory, and high altitude cerebral edema. Previous reports have also suggested the role of hypoxia in pathogenesis of depression and related psychological conditions. On the other hand, sub lethal intermittent hypoxic exposure induces protection against future lethal hypoxia and may have beneficial effect. Therefore, the present study was designed to explore the neuroprotective role of intermittent hypobaric hypoxia (IHH in Unpredictable Chronic Mild Stress (UCMS induced depression like behaviour in rats. The IHH refers to the periodic exposures to hypoxic conditions interrupted by the normoxic or lesser hypoxic conditions. The current study examines the effect of IHH against UCMS induced depression, using elevated plus maze (EPM, open field test (OFT, force swim test (FST, as behavioural paradigm and related histological and molecular approaches. The data indicated the UCMS induced depression like behaviour as evident from decreased exploration activity in OFT with increased anxiety levels in EPM, and increased immobility time in the FST; whereas on providing the IHH (5000m altitude, 4hrs/day for two weeks these behavioural changes were ameliorated. The morphological and molecular studies also validated the neuroprotective effect of IHH against UCMS induced neuronal loss and decreased neurogenesis. Here, we also explored the role of Brain-Derived Neurotrophic Factor (BDNF in anticipatory action of IHH against detrimental effect of UCMS as upon blocking of BDNF-TrkB signalling the beneficial effect of IHH was nullified. Taken together, the findings of our study demonstrate that the intermittent hypoxia has a therapeutic potential similar to an antidepressant in animal model of depression and could be developed as a preventive therapeutic option against this pathophysiological state.
Brandt, Claus; Pedersen, Bente K
and exert their effects on signalling pathways involved in fat oxidation and glucose uptake. By mediating anti-inflammatory effects in the muscle itself, myokines may also counteract TNF-driven insulin resistance. In conclusion, exercise-induced myokines appear to be involved in mediating both systemic......Chronic inflammation is involved in the pathogenesis of insulin resistance, atherosclerosis, neurodegeneration, and tumour growth. Regular exercise offers protection against type 2 diabetes, cardiovascular diseases, colon cancer, breast cancer, and dementia. Evidence suggests that the protective...
Martinez, Eduardo; Alvi, Raza; Venkatram, Sindhaghatta; Diaz-Fuentes, Gilda
Cocaine is used by approximately 1.5 million Americans each month and up to 69% of the cocaine seized contains levamisole. The real incidence of cocaine-levamisole induced neutropenia is unclear but probably underestimated. Associated complications include fever, thrombocytopenia, skin-vasculitis disorders, and rarely kidney injury. We present a young male, with chronic active cocaine use presenting with recurrent episodes of febrile neutropenia and thrombocytopenia. He underwent extensive work-up and was treated with many antibiotics and we suspect that his neutropenia and thrombocytopenia were caused by recurrent cocaine-levamisole use.
Full Text Available Cocaine is used by approximately 1.5 million Americans each month and up to 69% of the cocaine seized contains levamisole. The real incidence of cocaine-levamisole induced neutropenia is unclear but probably underestimated. Associated complications include fever, thrombocytopenia, skin-vasculitis disorders, and rarely kidney injury. We present a young male, with chronic active cocaine use presenting with recurrent episodes of febrile neutropenia and thrombocytopenia. He underwent extensive work-up and was treated with many antibiotics and we suspect that his neutropenia and thrombocytopenia were caused by recurrent cocaine-levamisole use.
In the chronical experiment of treating with sulfur dioxide(SO2) inhalation, Micronuclei(MN) frequencies in the polychromatophilic erythroblasts(PCE) of mouse bone marrow and the frequencies of cells with MN were significantly increased in dose-dependent manner. There is a significant difference between the male and the female animals. The results also showed that SO2 inhibited urethone-induced MN formation, it is a antagonistic joint action to Urethone. These results furtherly confirm that SO2 inhalation is a clastogenetic and genotoxic agent to mammalian cells, and the combination roles of SO2 and other mutagens are complexity.
Tørring, N; Jensen, L V; Wen, J G
composition. RESULTS: Treatment with EGF increased the weight of the ventral prostate, relative to body weight, by 50% compared with placebo (p coagulating glands were affected by EGF. Prostate tissue showed a significant increase in the volume...... was not affected by chronic EGF administration. CONCLUSIONS: EGF selectively induces growth of the ventral lobe of the prostate in newborn rats, in a pattern comparable to normal physiological growth. It may be hypothesized that the physiological growth of the prostate is directly correlated to endogenous activity...
Maryam Norouzi; Seyyed Javad Seyyed Tabaei; Maryam Niyyati; Vafa Saber; Hamed Behniafar
... of a wide range hosts called intermediate host. The protozoon is a food-borne and worldwide parasite that can cause serious complications such as abortion in pregnant women, encephalitis, and ocular toxoplasmosis...
Full Text Available Lapatinib is an oral, small-molecule, dual tyrosine kinase inhibitor of epidermal growth factor receptors (EGFR, or ErbB/Her in solid tumors. Little is known about the effect of lapatinib on leukemia. Using human chronic myelogenous leukemia (CML K562 cells as an experimental model, we found that lapatinib simultaneously induced morphological changes resembling apoptosis, autophagy, and megakaryocytic differentiation. Lapatinib-induced apoptosis was accompanied by a decrease in mitochondrial transmembrane potential and was attenuated by the pancaspase inhibitor z-VAD-fmk, indicating a mitochondria-mediated and caspase-dependent pathway. Lapatinib-induced autophagic cell death was verified by LC3-II conversion, and upregulation of Beclin-1. Further, autophagy inhibitor 3-methyladenine as well as autophagy-related proteins Beclin-1 (ATG6, ATG7, and ATG5 shRNA knockdown rescued the cells from lapatinib-induced growth inhibition. A moderate number of lapatinib-treated K562 cells exhibited features of megakaryocytic differentiation. In summary, lapatinib inhibited viability and induced multiple cellular events including apoptosis, autophagic cell death, and megakaryocytic differentiation in human CML K562 cells. This distinct activity of lapatinib against CML cells suggests potential for lapatinib as a therapeutic agent for treatment of CML. Further validation of lapatinib activity in vivo is warranted.
Song, D; Fang, G; Mao, S-Z; Ye, X; Liu, G; Gong, Y; Liu, S F
Chronic intermittent hypoxia (CIH) causes atherosclerosis in mice fed a high cholesterol diet (HCD). The mechanisms by which CIH promotes atherosclerosis are incompletely understood. This study defined the mechanistic role of NF-κB pathway in CIH+HCD induced atherosclerosis. Wild type (WT) and mice deficient in the p50 subunit of NF-κB (p50-KO) were fed normal chow diet (ND) or HCD, and exposed to sham or CIH. Atherosclerotic lesions on the en face aortic preparation and cross-sections of aortic root were examined. In WT mice, neither CIH nor HCD exposure alone caused, but CIH+HCD caused evident atherosclerotic lesions on both preparations after 20weeks of exposure. WT mice on ND and exposed to CIH for 35.6weeks did not develop atherosclerotic lesions. P50 gene deletion diminished CIH+HCD induced NF-κB activation and abolished CIH+HCD induced atherosclerosis. P50 gene deletion inhibited vascular wall inflammation, reduced hepatic TNF-α level, attenuated the elevation in serum cholesterol level and diminished macrophage foam cell formation induced by CIH+HCD exposure. These results demonstrate that inhibition of NF-κB activation abrogates the activation of three major atherogenic mechanisms associated with an abolition of CIH+HCD induced atherosclerosis. NF-κB may be a central common pathway through which CIH+HCD exposure activates multiple atherogenic mechanisms, leading to atherosclerosis.
Subauste, C.S.; Ajzenberg, D.; Kijlstra, A.
Toxoplasma gondii is a major cause of chronic parasitic infection in the world. This protozoan can cause retino-choroiditis in newborns and in adults, both immunocompetent and immunodeficient. This disease tends to be recurrent and can lead to severe visual impairment. The authors review current kno
Yun LIAO; Rui WANG; Xi-can TANG
AIM: To study the effects of centrophenoxine (CPH, meclofenoxate) on chronic cerebral hypoperfusion induced deficits in rats. METHODS: Chronic hypoperfusion in rats was performed by permanent bilateral ligation of the common carotid arteries. Morris water maze was used to measure spatial memory performance. Spectrophotometrical techniques were used to assay SOD, GPx activities, MDA content, TXB2, and 6-keto-PGF1α levels. Morphological change was examined by HE staining. The expression of Bax and p53 protein were assayed by immunohistochemistry analysis. RESULTS: Chronic hypoperfusion in rats resulted in spatial memory impairments shown by longer escape latency and shorter time spent in the target quadrant. These behavioral dysfunction were accompanied by increase in SOD and GPx activities, the content of MDA, the levels of pro-inflammatory mediators (TXB2, 6-keto-PGF1α), overexpression of Bax and P53 protein, and delayed degeneration of neurons in cortex and hippocampus. Oral administration of CPH (100 mg/kg, once per day for 37 d) markedly improved the memory impairment, reduced the increase in antioxidant enzyme activities, MDA content and the levels of pro-inflammatory mediators to their normal levels, and attenuated neuronal damage. CONCLUSION: The abilities of CPH to attenuate memory deficits and neuronal damage after ischemia may be beneficial in cerebrovascular type dementia.
Full Text Available Prenatal exposure to sodium valproate (VPA, a widely used anti-epileptic drug, is related to a series of dysfunctions, such as deficits in language and communication. Clinical and animal studies have indicated that the effects of VPA are related to the concentration and to the exposure window, while the neurobehavioral effects of VPA have received limited research attention. In the current study, to analyze the neurobehavioral effects of VPA, zebrafish at 24 hours post-fertilization (hpf were treated with early chronic exposure to 20 μM VPA for 7 hours per day for 6 days or with early acute exposure to 100 μM VPA for 7 hours. A battery of behavioral screenings was conducted at 1 month of age to investigate social preference, locomotor activity, anxiety and behavioral response to light change. A social preference deficit was only observed in animals with chronic VPA exposure. Acute VPA exposure induced a change in the locomotor activity, while chronic VPA exposure did not affect locomotor activity. Neither exposure procedure influenced anxiety or the behavioral response to light change. These results suggested that VPA has the potential to affect some behaviors in zebrafish, such as social behavior and the locomotor activity, and that the effects were closely related to the concentration and the exposure window. Additionally, social preference seemed to be independent from other simple behaviors.
Full Text Available Two confirmed cases of fatal disseminated toxoplasmosis occurred in an urban zoological collection of meerkats (Suricata suricatta. Both cases are suspected to be the result of feral cats gaining access to the enclosure. Toxoplasmosis has rarely been documented in meerkats. Subsequent to prophylactic treatment of all the animals and structural changes being implemented within the enclosure, no new cases have been recorded to date. Very little information is available on the disease in viverrids.
Yahya A Al-Zahrani
Full Text Available A 24-year-old healthy male presented with a chief complaint of blurred vision in the right eye for 1-week. Fundus examination indicated right exudative retinal detachment and choroidal ischemia. The patient responded well to anti-toxoplasmosis medications and steroids. Exudative retinal detachment and choroidal ischemia are atypical presentations of ocular toxoplasmosis. However, both conditions responded well to anti.parasitic therapy with steroid.
Dubey, J P; Lago, E G; Gennari, S M; Su, C; Jones, J L
Infections by the protozoan parasite Toxoplasma gondii are widely prevalent in humans and animals in Brazil. The burden of clinical toxoplasmosis in humans is considered to be very high. The high prevalence and encouragement of the Brazilian Government provides a unique opportunity for international groups to study the epidemiology and control of toxoplasmosis in Brazil. Many early papers on toxoplasmosis in Brazil were published in Portuguese and often not available to scientists in English-speaking countries. In the present paper we review prevalence, clinical spectrum, molecular epidemiology, and control of T. gondii in humans and animals in Brazil. This knowledge should be useful to biologists, public health workers, veterinarians, and physicians. Brazil has a very high rate of T. gondii infection in humans. Up to 50% of elementary school children and 50-80% of women of child-bearing age have antibodies to T. gondii. The risks for uninfected women to acquire toxoplasmosis during pregnancy and fetal transmission are high because the environment is highly contaminated with oocysts. The burden of toxoplasmosis in congenitally infected children is also very high. From limited data on screening of infants for T. gondii IgM at birth, 5-23 children are born infected per 10 000 live births in Brazil. Based on an estimate of 1 infected child per 1000 births, 2649 children with congenital toxoplasmosis are likely to be born annually in Brazil. Most of these infected children are likely to develop symptoms or signs of clinical toxoplasmosis. Among the congenitally infected children whose clinical data are described in this review, several died soon after birth, 35% had neurological disease including hydrocephalus, microcephaly and mental retardation, 80% had ocular lesions, and in one report 40% of children had hearing loss. The severity of clinical toxoplasmosis in Brazilian children may be associated with the genetic characteristics of T. gondii isolates prevailing in
Busemann, Christoph; Ribback, Silvia; Zimmermann, Kathrin; Sailer, Verena; Kiefer, Thomas; Schmidt, Christian A; Schulz, Katrin; Steinmetz, Ivo; Dombrowski, Frank; Dölken, Gottfried; Krüger, William H
Toxoplasmosis is a rare but possibly underestimated complication following allogeneic stem cell transplantation with a high mortality rate. One reason might be the limitation of the diagnostic instruments relying mainly on imaging and molecular-based techniques. In this report, we present three cases of toxoplasmosis identified among 155 allograft recipients treated at Greifswald University Hospital. Widely disseminated toxoplasmosis was detected post-mortem in two patients allografted for high-risk multiple myeloma. Clinical signs suspicious for toxoplasmosis occurred after days +32 and +75, respectively. In one case, serology and conventional Toxoplasma gondii PCR, targeting the B1 gene, revealed negative results, while in the other patient, toxoplasmosis was not investigated. Both patients received pentamidine for Pneumocystis jirovecii pneumonia (PcP) prophylaxis. The third patient, a 68-year-old woman allografted for AML, developed cerebral toxoplasmosis from day +395 after allogeneic SCT with typical signs in magnetic resonance tomography. Toxoplasma DNA was amplified from one of two samples of cerebrospinal fluid. The patient died of disseminated toxoplasmosis despite immediate initiation of therapy. Retrospective comparative testing of clinical specimens by the conventional T. gondii PCR and by a real-time PCR targeting a 529-bp genomic fragment suggests a higher sensitivity of the latter method in our patients. In conclusion, we suggest a rigorous real-time PCR monitoring for high-risk patients or patients with signs of infections suspicious for toxoplasmosis, even though low-copy results are presently difficult to interpret. Our reported cases might also encourage the use of trimethoprim-sufmethoxazole instead of pentamidine for PcP prophylaxis in those patients.
Toxoplasmosis is the most common opportunistic infection of the central nervous system in patients with acquired immunodeficiency syndrome (AIDS). Clinical presentation of cerebral toxoplasmosis in these patients includes headache, focal neurological deficits and seizures. Prompt diagnosis and appropriate therapy results in rapid clinical and radiological improvement as well as good outcome for patients. In this article, we report two cases with stroke-like presentation of cerebral toxoplasmo...
Al-Zahrani, Yahya A; Al-Dhibi, Hassan A; Al-Abdullah, Abdulelah A
A 24-year-old healthy male presented with a chief complaint of blurred vision in the right eye for 1-week. Fundus examination indicated right exudative retinal detachment and choroidal ischemia. The patient responded well to anti-toxoplasmosis medications and steroids. Exudative retinal detachment and choroidal ischemia are atypical presentations of ocular toxoplasmosis. However, both conditions responded well to anti.parasitic therapy with steroid.
Luciana Macedo de Resende
Full Text Available Aims: To describe the auditory and language outcomes of children with early diagnosis and treatment for congenital toxoplasmosis. Methods: A cross-sectional study included all children diagnosed with congenital toxoplasmosis, through the Minas Gerais State Neonatal Screening Program, from September 2006 to March 2007. All children received early treatment, initiated before the age of 2.5 months, and were periodically assisted by a team of specialists including pediatricians, ophthalmologists and speech-language therapists and audiologists. Hearing function was evaluated with the following procedures: tympanometry, transient evoked otoacoustic emissions, distortion product otoacoustic emissions, behavioral observation audiometry, and brainstem auditory evoked potentials. Hearing function and sensitivity was estimated and audiological results were classified as normal, conductive hearing loss, sensory-neural hearing loss and central dysfunction. Language performance was assessed and classified as normal or abnormal, according to test results. The following variables were studied: audiological results, neurological and ophthalmological conditions, language performance and presence of risk indicator for hearing loss other than congenital toxoplasmosis. Univariate analysis was conducted using the chi-square or Fisher’s Exact test. Results: From September 2006 to March 2007, 106 children were diagnosed with congenital toxoplasmosis through the neonatal screening program, and were included in the study. Data analysis showed normal hearing in 60 children (56.6%, while 13 children (12.3% had conductive hearing loss, four children (3.8% had sensory-neural hearing loss and 29 children (27.4% presented central hearing dysfunction. There was association between hearing problems and language deficits. The comparison between children with additional risks for hearing loss other than toxoplasmosis and children who only presented toxoplasmosis as a risk factor
Full Text Available Gingival enlargement is a common clinical feature of gingival and periodontal diseases. Currently, more than 20 prescription medications are associated with gingival enlargement. Although the mechanisms of action may be different, the clinical and microscopic appearance of drug-induced gingival enlargement is similar with any drug. Gingival enlargement produces esthetic changes, and clinical symptoms including pain, tenderness, bleeding, speech disturbances, abnormal tooth movement, dental occlusion problems, enhancement of caries development and periodontal disorders. Sodium valproate is considered to produce gingival enlargement, but very rarely. This case report features sodium valproate induced gingival enlargement in a patient with pre-existing chronic periodontitis, who came to the Dental Department, Chinmaya Mission Hospital, Bangalore. The case is special as the patient did not develop the enlargement in spite of taking phenytoin for 1 year and developed enlargement with sodium valproate within 6 months.
Gingival enlargement is a common clinical feature of gingival and periodontal diseases. Currently, more than 20 prescription medications are associated with gingival enlargement. Although the mechanisms of action may be different, the clinical and microscopic appearance of drug-induced gingival enlargement is similar with any drug. Gingival enlargement produces esthetic changes, and clinical symptoms including pain, tenderness, bleeding, speech disturbances, abnormal tooth movement, dental occlusion problems, enhancement of caries development and periodontal disorders. Sodium valproate is considered to produce gingival enlargement, but very rarely. This case report features sodium valproate induced gingival enlargement in a patient with pre-existing chronic periodontitis, who came to the Dental Department, Chinmaya Mission Hospital, Bangalore. The case is special as the patient did not develop the enlargement in spite of taking phenytoin for 1 year and developed enlargement with sodium valproate within 6 months.
Savransky, Vladimir; Bevans, Shannon; Nanayakkara, Ashika; Li, Jianguo; Smith, Philip L; Torbenson, Michael S; Polotsky, Vsevolod Y
Obstructive sleep apnea (OSA) causes chronic intermittent hypoxia (CIH) during sleep. OSA is associated with nonalcoholic steatohepatitis (NASH) in obese individuals and may contribute to progression of nonalcoholic fatty liver disease from steatosis to NASH. The purpose of this study was to examine whether CIH induces inflammatory changes in the liver in mice with diet-induced hepatic steatosis. C57BL/6J mice (n = 8) on a high-fat, high-cholesterol diet were exposed to CIH for 6 mo and were compared with mice on the same diet exposed to intermittent air (control; n = 8). CIH caused liver injury with an increase in serum ALT (461 +/- 58 U/l vs. 103 +/- 16 U/l in the control group; P diet.
Nemmar, Abderrahim; Al-Salam, Suhail; Yuvaraju, Priya; Beegam, Sumaya; Yasin, Javed; Ali, Badreldin H
Water-pipe tobacco smoking is becoming prevalent in all over the world including Western countries. There are limited data on the cardiovascular effects of water-pipe smoke (WPS), in particular following chronic exposure. Here, we assessed the chronic cardiovascular effects of nose-only WPS exposure in C57BL/6 mice. The duration of the session was 30 minutes/day, 5 days/week for 6 consecutive months. Control mice were exposed to air. WPS significantly increased systolic blood pressure. The relative heart weight and plasma concentrations of troponin-I and B-type natriuretic peptide were increased in mice exposed to WPS. Arterial blood gas analysis showed that WPS caused a significant decrease in [Formula: see text] and an increase in [Formula: see text] WPS significantly shortened the thrombotic occlusion time in pial arterioles and venules and increased the number of circulating platelet. Cardiac lipid peroxidation, measured as thiobarbituric acid-reactive substances, was significantly increased, while superoxide dismutase activity, total nitric oxide activity, and glutathione concentration were reduced by WPS exposure. Likewise, immunohistochemical analysis of the heart revealed an increase in the expression of inducible nitric oxide synthase and cytochrome c by cardiomyocytes of WPS-exposed mice. Moreover, hearts of WPS-exposed mice showed the presence of focal interstitial fibrosis. WPS exposure significantly increased heart DNA damage assessed by Comet assay. We conclude that chronic nose-only exposure to WPS impairs cardiovascular homeostasis. Our findings provide evidence that long-term exposure to WPS is harmful to the cardiovascular system and supports interventions to control the spread of WPS, particularly amid youths.NEW & NOTEWORTHY No data are available on the chronic cardiovascular effects of water-pipe smoke (WPS). Our findings provide experimental evidence that chronic exposure to WPS increased blood pressure, relative heart weight, troponin I, and
Full Text Available A cross-sectional study was conducted to determine the seroepidemiology of Toxoplasma gondii infection among individuals who have close contact with animals. The association between plausible risk factors and the seropositivity for Toxoplasma was examined. A total of 312 blood samples were collected form veterinarians(38, veterinary technicians(45, veterinary students(194 and pet owners(35 from several veterinary hospitals and clinics in the area of Klang Valley, Malaysia. About 4cc of blood samples drawn from agreed participants were processed for measurement of anti-Toxoplasma IgG and IgM antibodies as well as avidity test of Toxoplasma IgG by ELISA.Meanwhile, the demographic profiles and possible risk factors of these participants were also recorded in the standardized data collection sheets.Overall seroprevalence of toxoplasmosis was observed in 62 (19.9%participants where 7(18.4% veterinarians, 15(33.3%veterinary technicians, 29(14.9%veterinary students and 11(31.4% pet owners were infected. Out of 19.9% positive samples for toxoplasmosis, 18.3% of these samples were positive for IgG antibody, 1.0% was positive for IgM antibody and 0.6% were positive for both IgG and IgM antibodies.Positive samples for IgM antibody and for both IgG and IgM antibodies were further analysed by IgG avidity test. Out of 5 samples tested for avidity test, 4 samples showed a high avidity results which means infection occurred in the past whereas only 1 sample showed a recently acquired infection. Univariate analysis showed that age group, gender,study population, gardening, task performance and working duration were significantly associated with seropositivity of toxoplasmosis. Further analysis by multivariate analysis using logistic regression showed that age group more than or equal to 30 years old (OR=0.34, 95% CI=0.18-0.63, p=0.001and working or study duration more than 10 years in handling with animals(OR=5.07, 95% CI=1.80-14.24, p=0.002were identified as
Chen, Jinglou; Du, Lifen; Li, Jingjing; Song, Hongping
Cadmium (Cd) pollution is a serious environmental problem. Kidney is a main target organ of Cd toxicity. This study was undertaken to investigate the potential protective effects of epigallocatechin-3-gallate (EGCG) against chronic renal injury and fibrosis induced by CdCl2. Rat model was induced by exposing to 250 mg/L CdCl2 through drinking water. The renal function was evaluated by detecting the levels of blood urea nitrogen (BUN) and serum creatinine (SCR). The oxidative stress was measured by detecting the levels of malondialdehyde (MDA), nitric oxide (NO), reduced glutathione/oxidized glutathione (GSH/GSSG) and renal enzymatic antioxidant status. Additionally, the renal levels of transforming growth factor-β1 (TGF-β1), Smad3, phosphorylation-Smad3 (pp-Smad3), α-smooth muscle actin (α-SMA), vimentin and E-cadherin were measured by western blot assay. Renal levels of microRNA-21 (miR-21), miR-29a/b/c and miR-192 were measured by quantitative RT-PCR. It was found that EGCG ameliorated the CdCl2-induced renal injury, inhibited the level of oxidative stress, normalized renal enzymatic antioxidant status and E-cadherin level, as well as attenuated the over generation of TGF-β1, pp-Smad3, vimentin and α-SMA. EGCG also decreased the production of miR-21 and miR-192, and enhanced the levels of miR-29a/b/c. These results showed that EGCG could attenuate Cd induced chronic renal injury.
Full Text Available BACKGROUND: To mitigate the cardiotoxicity of anthracycline antibiotics without compromising their anticancer activities is still an issue to be solved. We previously demonstrated that schisandrin B (Sch B could protect against doxorubicin (Dox-induced acute cardiotoxicity via enhancing cardiomyocytic glutathione redox cycling that could attenuate oxidative stress generated from Dox. In this study, we attempted to prove if Sch B could also protect against Dox-induced chronic cardiotoxicity, a more clinically relevant issue, without compromising its anticancer activity. METHODOLOGY: Rat was given intragastrically either vehicle or Sch B (50 mg/kg two hours prior to i.p. Dox (2.5 mg/kg weekly over a 5-week period with a cumulative dose of Dox 12.5 mg/kg. At the 6th and 12th week after last dosing, rats were subjected to cardiac function measurement, and left ventricles were processed for histological and ultrastructural examination. Dox anticancer activity enhanced by Sch B was evaluated by growth inhibition of 4T1, a breast cancer cell line, and S180, a sarcoma cell line, in vitro and in vivo. PRINCIPAL FINDINGS: Pretreatment with Sch B significantly attenuated Dox-induced loss of cardiac function and damage of cardiomyocytic structure. Sch B substantially enhanced Dox cytotoxicities toward S180 in vitro and in vivo in mice, and increased Dox cytotoxcity against 4T1 in vitro. Although we did not observe this enhancement against the implanted 4T1 primary tumor, the spontaneous metastasis to lung was significantly reduced in combined treatment group than Dox alone group. CONCLUSION: Sch B is capable of protecting Dox-induced chronic cardiotoxicity and enhancing its anticancer activity. To the best of our knowledge, Sch B is the only molecule ever proved to function as a cardioprotective agent as well as a chemotherapeutic sensitizer, which is potentially applicable for cancer treatment.
Full Text Available Heavy alcohol consumption has detrimental neurologic effects, inducing widespread neuronal loss in both fetuses and adults. One proposed mechanism of ethanol-induced cell loss with sufficient exposure is an elevation in concentrations of bioactive lipids that mediate apoptosis, including the membrane sphingolipid metabolites ceramide and sphingosine. While these naturally-occurring lipids serve as important modulators of normal neuronal development, elevated levels resulting from various extracellular insults have been implicated in pathological apoptosis of neurons and oligodendrocytes in several neuroinflammatory and neurodegenerative disorders. Prior work has shown that acute administration of ethanol to developing mice increases levels of ceramide in multiple brain regions, hypothesized to be a mediator of fetal alcohol-induced neuronal loss. Elevated ceramide levels have also been implicated in ethanol-mediated neurodegeneration in adult animals and humans. Here, we determined the effect of chronic voluntary ethanol consumption on lipid profiles in brain and peripheral tissues from adult alcohol-preferring (P rats to further examine alterations in lipid composition as a potential contributor to ethanol-induced cellular damage. P rats were exposed for 13 weeks to a 20% ethanol intermittent-access drinking paradigm (45 ethanol sessions total or were given access only to water (control. Following the final session, tissues were collected for subsequent chromatographic analysis of lipid content and enzymatic gene expression. Contrary to expectations, ethanol-exposed rats displayed substantial reductions in concentrations of ceramides in forebrain and heart relative to non-exposed controls, and modest but significant decreases in liver cholesterol. qRT-PCR analysis showed a reduction in the expression of sphingolipid delta(4-desaturase (Degs2, an enzyme involved in de novo ceramide synthesis. These findings indicate that ethanol intake levels
Park, S; Scheffler, T L; Gunawan, A M; Shi, H; Zeng, C; Hannon, K M; Grant, A L; Gerrard, D E
Muscle contraction stimulates glucose transport independent of insulin. Glucose uptake into muscle cells is positively related to skeletal muscle-specific glucose transporter (GLUT-4) expression. Therefore, our objective was to determine the effects of the contraction-mediated signals, calcium and AMP-activated protein kinase (AMPK), on glucose uptake and GLUT-4 expression under acute and chronic conditions. To accomplish this, we used pharmacological agents, cell culture, and pigs possessing genetic mutations for increased cytosolic calcium and constitutively active AMPK. In C2C12 myotubes, caffeine, a sarcoplasmic reticulum calcium-releasing agent, had a biphasic effect on GLUT-4 expression and glucose uptake. Low-concentration (1.25 to 2 mM) or short-term (4 h) caffeine treatment together with the AMPK activator, 5-aminoimidazole-4-carboxamide-1-beta-D-ribonucleoside (AICAR), had an additive effect on GLUT-4 expression. However, high-concentration (2.5 to 5 mM) or long-term (4 to 30 h) caffeine treatment decreased AMPK-induced GLUT-4 expression without affecting cell viability. The negative effect of caffeine on AICAR-induced GLUT-4 expression was reduced by dantrolene, which desensitizes the ryanodine receptor. Consistent with cell culture data, increases in GLUT-4 mRNA and protein expression induced by AMPK were blunted in pigs possessing genetic mutations for both increased cytosolic calcium and constitutively active AMPK. Altogether, these data suggest that chronic exposure to elevated cytosolic calcium concentration blocks AMPK-induced GLUT-4 expression in skeletal muscle.
Godfrey, Jessica; Jeanguenin, Lisa; Castro, Norma; Olney, Jeffrey J; Dudley, Jason; Pipkin, Joseph; Walls, Stanley M; Wang, Wei; Herr, Deron R; Harris, Greg L; Brasser, Susan M
Heavy alcohol consumption has detrimental neurologic effects, inducing widespread neuronal loss in both fetuses and adults. One proposed mechanism of ethanol-induced cell loss with sufficient exposure is an elevation in concentrations of bioactive lipids that mediate apoptosis, including the membrane sphingolipid metabolites ceramide and sphingosine. While these naturally-occurring lipids serve as important modulators of normal neuronal development, elevated levels resulting from various extracellular insults have been implicated in pathological apoptosis of neurons and oligodendrocytes in several neuroinflammatory and neurodegenerative disorders. Prior work has shown that acute administration of ethanol to developing mice increases levels of ceramide in multiple brain regions, hypothesized to be a mediator of fetal alcohol-induced neuronal loss. Elevated ceramide levels have also been implicated in ethanol-mediated neurodegeneration in adult animals and humans. Here, we determined the effect of chronic voluntary ethanol consumption on lipid profiles in brain and peripheral tissues from adult alcohol-preferring (P) rats to further examine alterations in lipid composition as a potential contributor to ethanol-induced cellular damage. P rats were exposed for 13 weeks to a 20% ethanol intermittent-access drinking paradigm (45 ethanol sessions total) or were given access only to water (control). Following the final session, tissues were collected for subsequent chromatographic analysis of lipid content and enzymatic gene expression. Contrary to expectations, ethanol-exposed rats displayed substantial reductions in concentrations of ceramides in forebrain and heart relative to non-exposed controls, and modest but significant decreases in liver cholesterol. qRT-PCR analysis showed a reduction in the expression of sphingolipid delta(4)-desaturase (Degs2), an enzyme involved in de novo ceramide synthesis. These findings indicate that ethanol intake levels achieved by
Lu, Huaixiu; Xu, Minguang; Wang, Feng; Liu, Shisen; Gu, Jing; Lin, Songshan; Zhao, Lisheng
Periodontitis is a common chronic inflammatory disease. Recent studies have shown that chronic stress (CS) might modulate periodontal disease, but there are few models of CS-induced periodontitis, and the underlying mechanisms are unclear. The present study established a rat model of periodontitis associated with CS induced by nylon thread ligatures. The severity of periodontitis was evaluated in this model by radiographic and pathological examination. The inflammatory reaction indicated by the elevated serum levels of interleukin (IL)-1β, IL-6 and IL-8 was assessed by enzyme-linked immunosorbent assay. Toll-like receptor-4 (TLR4) and glucocorticoid receptor-α (GR-α) expressions were detected by reverse transcriptase-PCR and western blotting. Open-field tests and serum corticosterone were used to evaluate CS. The results showed that CS induced behavioral changes and increased corticosterone levels of the animals with periodontitis. CS stimulation markedly increased alveolar bone loss, periodontal pocket depth and the number of plaques. It also enhanced the inflammatory reaction. These results suggest that CS accelerated the ligature-induced pathological changes associated with periodontitis. Further analysis of the mechanisms involved showed that GR-α expression was significantly downregulated in periodontal tissues of the animals undergoing CS. Blocking GR-α signaling in lipopolysaccharide and corticosteroid-treated human periodontal ligament fibroblast cells in vitro significantly upregulated the expression of p-Akt (protein kinase B) and TLR4, promoted nuclear factor-κB activity and increased levels of IL-1β, IL-6 and IL-8. This research suggests that CS might accelerate the pathological progression of periodontitis by a GR-α signaling-mediated inflammatory response and that this may be a potential therapeutic target for the treatment of periodontal disease, particularly in patients with CS.
Poisson, C; Stefani, J; Manens, L; Delissen, O; Suhard, D; Tessier, C; Dublineau, I; Guéguen, Y
Uranium is a heavy metal naturally found in the earth's crust that can contaminate the general public population when ingested. The acute effect and notably the uranium nephrotoxicity are well known but knowledge about the effect of chronic uranium exposure is less clear. In a dose-response study we sought to determine if a chronic exposure to uranium is toxic to the kidneys and the liver, and what the anti-oxidative system plays in these effects. Rats were contaminated for 3 or 9 months by uranium in drinking water at different concentrations (0, 1, 40, 120, 400, or 600 mg/L). Uranium tissue content in the liver, kidneys, and bones was linear and proportional to uranium intake after 3 and 9 months of contamination; it reached 6 μg per gram of kidney tissues for the highest uranium level in drinking water. Nevertheless, no histological lesions of the kidney were observed, nor any modification of kidney biomarkers such as creatinine or KIM-1. After 9 months of contamination at and above the 120-mg/L concentration of uranium, lipid peroxidation levels decreased in plasma, liver, and kidneys. Glutathione concentration increased in the liver for the 600-mg/L group, in the kidney it increased dose dependently, up to 10-fold, after 9 months of contamination. Conversely, chronic uranium exposure irregularly modified gene expression of antioxidant enzymes and activities in the liver and kidneys. In conclusion, chronic uranium exposure did not induce nephrotoxic effects under our experimental conditions, but instead reinforced the antioxidant system, especially by increasing glutathione levels in the kidneys.
Ciappuccini, R; Ansemant, T; Maillefert, J-F; Tavernier, C; Ornetti, P
We report for the first time an unusual musculoskeletal adverse effect of aspartame in two patients. A 50-year-old woman had been suffering from widespread pain and fatigue for more than 10 years leading to the diagnosis of fibromyalgia. During a vacation in a foreign country, she did not suffer from painful symptoms since she had forgotten to take her aspartame. All of the symptoms reappeared in the days following her return when she reintroduced aspartame into her daily diet. Thus, aspartame was definitively excluded from her diet, resulting in a complete regression of the fibromyalgia symptoms. A 43-year-old man consulted for a 3-year history of bilateral forearm, wrist, and hand and cervical pain with various unsuccessful treatments. A detailed questioning allowed to find out that he had been taking aspartame for three years. The removal of aspartame was followed by a complete regression of pain, without recurrence. We believe that these patients' chronic pain was due to the ingestion of aspartame, a potent flavouring agent, widely used in food as a calorie-saver. The benefit/ risk ratio of considering the diagnosis of aspartame-induced chronic pain is obvious: the potential benefit is to cure a disabling chronic disease, to spare numerous laboratory and imaging investigations, and to avoid potentially harmful therapies; the potential risk is to temporarily change the patient's diet. Thus, practitioners should ask patients suffering from fibromyalgia about their intake of aspartame. In some cases, this simple question might lead to the resolution of a disabling chronic disease.
Jiantao Wang; Jian Ge; A.A. Sadun; T.T. Lam
Purpose:To set up the Sharma's chronic intraocular hypertension model and investigate the intraocular pressure (lOP) as well as the optic nerve damage of this model in rat.Methods:The operations of the chronic intraocular hypertension model were performed as described by Sharma in 60 male Lewis albino rats. IOP was measured using the TonoPen XL immediately after surgery and then at 5 day, 2 week or 4 week intervals. Cresyl violet staining of whole-mounted retinas was used to label retinal ganglion cells (RGCs),then RGCs were counted. Paraphenylenediamine (PPD) staining was performed in the semi-thin cross sections of optic nerve of rat, in order to know whether the axons of optic nerve were degenerated or not. Results:There were 47 rats with higher IOP after the episcleral veins cauterized in 60rats. The ratio of elevated IOP was 78.3%. The IOPs were stable in 4 weeks. After cresyl violet staining, the RGCs loss was 11.0% and 11.3% was found in the central and peripheral retina respectively after 2 weeks of increased IOP. After 4 weeks of increased lOP, the loss of RGCs was 17% for the central retina and 24.6% for the peripheral retina. In the retinas without higher IOP, there was no loss of RGCs. PPD staining showed that optic nerve of rat with about 5.3% damage of axons located at the superior temporal region. Region of affected optic nerve 1 mm posterior to the globe by light microscope showed evidence of damaged axons with axonal swelling and myelin debris.Conclusion:Sharma's chronic intraocular hypertension model is a reproducible and effective glaucoma model, which mimics human glaucoma with chronically elevation IOP and induced RGCs loss and damage of optic nerve. Eye Science 2004;20:25-29.
Liclican, Elvira L.; Nguyen, Van; Sullivan, Aaron B.
Purpose. Cyclooxygenase (COX)-derived prostaglandin E2 (PGE2) is a prevalent and established mediator of inflammation and pain in numerous tissues and diseases. Distribution and expression of the four PGE2 receptors (EP1-EP4) can dictate whether PGE2 exerts an anti-inflammatory or a proinflammatory and/or a proangiogenic effect. The role and mechanism of endogenous PGE2 in the cornea, and the regulation of EP expression during a dynamic and complex inflammatory/reparative response remain to be clearly defined. Methods. Chronic or acute self-resolving inflammation was induced in mice by corneal suture or epithelial abrasion, respectively. Reepithelialization was monitored by fluorescein staining and neovascularization quantified by CD31/PECAM-1 immunofluorescence. PGE2 formation was analyzed by lipidomics and polymorphonuclear leukocyte (PMN) infiltration quantified by myeloperoxidase activity. Expression of EPs and inflammatory/angiogenic mediators was assessed by real-time PCR and immunohistochemistry. Mice eyes were treated with PGE2 (100 ng topically, three times a day) for up to 7 days. Results. COX-2, EP-2, and EP-4 expression was upregulated with chronic inflammation that correlated with increased corneal PGE2 formation and marked neovascularization. In contrast, acute abrasion injury did not alter PGE2 or EP levels. PGE2 treatment amplified PMN infiltration and the angiogenic response to chronic inflammation but did not affect wound healing or PMN infiltration after epithelial abrasion. Exacerbated inflammatory neovascularization with PGE2 treatment was independent of the VEGF circuit but was associated with a significant induction of the eotaxin-CCR3 axis. Conclusions. These findings place the corneal PGE2 circuit as an endogenous mediator of inflammatory neovascularization rather than general inflammation and demonstrate that chronic inflammation selectively regulates this circuit at the level of biosynthetic enzyme and receptor expression. PMID:20610836
Eileen M Bauer
Full Text Available Evidence suggests a role of both innate and adaptive immunity in the development of pulmonary arterial hypertension. The complement system is a key sentry of the innate immune system and bridges innate and adaptive immunity. To date there are no studies addressing a role for the complement system in pulmonary arterial hypertension.Immunofluorescent staining revealed significant C3d deposition in lung sections from IPAH patients and C57Bl6/J wild-type mice exposed to three weeks of chronic hypoxia to induce pulmonary hypertension. Right ventricular systolic pressure and right ventricular hypertrophy were increased in hypoxic vs. normoxic wild-type mice, which were attenuated in C3-/- hypoxic mice. Likewise, pulmonary vascular remodeling was attenuated in the C3-/- mice compared to wild-type mice as determined by the number of muscularized peripheral arterioles and morphometric analysis of vessel wall thickness. The loss of C3 attenuated the increase in interleukin-6 and intracellular adhesion molecule-1 expression in response to chronic hypoxia, but not endothelin-1 levels. In wild-type mice, but not C3-/- mice, chronic hypoxia led to platelet activation as assessed by bleeding time, and flow cytometry of platelets to determine cell surface P-selectin expression. In addition, tissue factor expression and fibrin deposition were increased in the lungs of WT mice in response to chronic hypoxia. These pro-thrombotic effects of hypoxia were abrogated in C3-/- mice.Herein, we provide compelling genetic evidence that the complement system plays a pathophysiologic role in the development of PAH in mice, promoting pulmonary vascular remodeling and a pro-thrombotic phenotype. In addition we demonstrate C3d deposition in IPAH patients suggesting that complement activation plays a role in the development of PAH in humans.
Full Text Available Opioids, acting at μ opioid receptors, are commonly used for pain management. Chronic opioid treatment induces cellular adaptations, which trigger long-term side effects, including constipation mediated by enteric neurons. We tested the hypothesis that chronic opioid treatment induces alterations of μ opioid receptor signaling in enteric neurons, which are likely to serve as mechanisms underlying opioid-induced constipation. In cultured rat enteric neurons, either untreated (naïve or exposed to morphine for 4 days (chronic, we compared the effect of morphine and DAMGO (D-Ala2,MePhe4,Gly-ol5 enkephalin on μ opioid receptor internalization and downstream signaling by examining the activation of the mitogen-activated protein kinase/extracellular signal-regulated kinases 1 and 2 (MAPK/ERK pathway, cAMP accumulation and transcription factor cAMP Response Element-Binding protein (CREB expression. μ opioid receptor internalization and MAPK/ERK phosphorylation were induced by DAMGO, but not morphine in naïve neurons, and by both opioids in chronic neurons. MAPK/ERK activation was prevented by the receptor antagonist naloxone, by blocking receptor trafficking with hypertonic sucrose, dynamin inhibitor, or neuronal transfection with mutated dynamin, and by MAPK inhibitor. Morphine and DAMGO inhibited cAMP in naïve and chronic enteric neurons, and induced desensitization of cAMP signaling. Chronic morphine treatment suppressed desensitization of cAMP and MAPK signaling, increased CREB phosphorylation through a MAPK/ERK pathway and induced delays of gastrointestinal transit, which was prevented by MAPK/ERK blockade. This study showed that opioids induce endocytosis- and dynamin-dependent MAPK/ERK activation in enteric neurons and that chronic morphine treatment triggers changes at the receptor level and downstream signaling resulting in MAPK/ERK-dependent CREB activation. Blockade of this signaling pathway prevents the development of gastrointestinal
Mendorf, Alexander; Klyuchnikov, Evgeny; Langebrake, Claudia; Rohde, Holger; Ayuk, Francis; Regier, Marc; Christopeit, Maximilian; Zabelina, Tatjana; Bacher, Adelbert; Stübig, Thomas; Wolschke, Christine; Bacher, Ulrike; Kröger, Nicolaus
Toxoplasmosis and infections by other opportunistic agents such as Pneumocystis jirovecii constitute life-threatening risks for patients after allogeneic hematopoietic stem cell transplantation. Trimethoprim/sulfamethoxazole (TMP-SMX) has been well established for post-transplant toxoplasmosis and pneumocystis prophylaxis, but treatment may be limited due to toxicity. We explored atovaquone as an alternative and compared it with TMP-SMX regarding toxicity and efficacy during the first 100 days after transplantation in 155 consecutive adult stem cell recipients. Eight patients with a prior history of TMP-SMX intolerance received atovaquone as first-line prophylaxis. TMP-SMX was used for 141 patients as first-line strategy, but 13 patients (9.2%) were later switched to atovaquone due to TMP-SMX toxicity or gastrointestinal symptoms. No active toxoplasmosis or active P. jirovecii infection developed under continued prophylaxis with either TMP-SMX or atovaquone. However, for reasons of TMP-SMX and/or atovaquone toxicity, 7 patients were unable to tolerate any efficacious toxoplasmosis prophylaxis and therefore obtained inhalative pentamidine as P. jirovecii prophylaxis but no toxoplasmosis prophylaxis. Importantly, 2 of these patients developed severe toxoplasmosis. In summary, atovaquone appears as a valid alternative for at least some post-transplant patients who cannot tolerate TMP-SMX. This should be further confirmed by multicenter trials.
Vidal, José E.; Colombo, Fabio Antonio; Penalva de Oliveira, Augusto C.; Focaccia, Roberto; Pereira-Chioccola, Vera Lucia
Highly active antiretroviral therapy has decreased the incidence of opportunistic infections in the central nervous system in AIDS patients. However, neurological abnormalities still remain important causes of mortality and morbidity in developing countries. In Brazil, cerebral toxoplasmosis is the most common cerebral mass lesion in AIDS patients. For these reasons, early, inexpensive, and sensitive diagnostic tests must be evaluated. The aim of this study was to evaluate PCR, using cerebrospinal fluid (CSF) samples to detect Toxoplasma gondii DNA, and to determine if the association of PCR with immunological assays can contribute to a timely diagnosis. We studied two sample groups. First, we analyzed stored CSF samples from 29 newborns and from 39 adults with AIDS without a definitive diagnosis of toxoplasmosis. The goal of this step was to standardize the methodology with a simple and economical procedure to recover the T. gondii DNA. Next, we prospectively evaluated CSF samples from 12 AIDS patients with a first episode of cerebral toxoplasmosis and 18 AIDS patients with other neurological opportunistic diseases and without previous cerebral toxoplasmosis. In all PCR samples, an indirect immunofluorescent assay and an enzyme-linked immunosorbent assay were performed. Samples from all patients with cerebral toxoplasmosis presented positive PCR results (sensitivity, 100%), and a sample from one of the 18 AIDS patients with other neurological diseases also presented positive PCR results (specificity, 94.4%). These findings suggest the clinical utility of PCR in the diagnosis of cerebral toxoplasmosis in developing countries. PMID:15472338
Ibebuike, Kaunda; Mantanga, Leo; Emereole, Obioma; Ndolo, Patrice; Kajee, Afsana; Gopal, Rasik; Pather, Sugeshnee
Cerebellar mass lesion is an uncommon presentation of toxoplasmosis. The authors report one rare case in an 11-month-old HIV/AIDS female infant who presented with deterioration in her developmental milestones. CT scan revealed a ring-enhancing mass lesion in the right cerebellar hemisphere with secondary obstructive hydrocephalus. A ventriculoperitoneal shunt was inserted prior to posterior fossa decompression and biopsy of the lesion. The specimens obtained were divided into two. One specimen was sent for histological diagnosis immediately after surgery while the second specimen was preserved until the release of the histology report. The initial histopathology report indicated a neoplastic process. Immunohistochemical stains were attempted but interpreted with difficulty due to severe tissue necrosis. After waiting for close to 6 weeks without a definite histological diagnosis, the preserved second specimen was sent for histological analysis as a fresh specimen, and reported a diagnosis of toxoplasmosis. This case presented diagnostic challenges to the authors whose radiological impressions of either a neoplastic lesion or a tuberculoma (based on our local neuroepidemiology) were reinforced by intraoperative findings highly suggestive of tuberculoma but which contrasted with the histological report, first as a neoplastic lesion and later toxoplasmosis. Although cerebellar toxoplasmosis is a rare complication of HIV/AIDS, this case report shows that toxoplasmosis should not be overlooked as a differential diagnosis of ring-enhancing cerebellar masses in HIV/AIDS patients irrespective of the patient's age and the absence of constitutional symptoms of toxoplasmosis.
Jill R Johnson
Full Text Available Chronic allergic asthma is characterized by Th2-polarized inflammation and leads to airway remodeling and fibrosis but the mechanisms involved are not clear. To determine whether epithelial-mesenchymal transition contributes to airway remodeling in asthma, we induced allergic airway inflammation in mice by intranasal administration of house dust mite (HDM extract for up to 15 consecutive weeks. We report that respiratory exposure to HDM led to significant airway inflammation and thickening of the smooth muscle layer in the wall of the large airways. Transforming growth factor beta-1 (TGF-β1 levels increased in mouse airways while epithelial cells lost expression of E-cadherin and occludin and gained expression of the mesenchymal proteins vimentin, alpha-smooth muscle actin (α-SMA and pro-collagen I. We also observed increased expression and nuclear translocation of Snail1, a transcriptional repressor of E-cadherin and a potent inducer of EMT, in the airway epithelial cells of HDM-exposed mice. Furthermore, fate-mapping studies revealed migration of airway epithelial cells into the sub-epithelial regions of the airway wall. These results show the contribution of EMT to airway remodeling in chronic asthma-like inflammation and suggest that Th2-polarized airway inflammation can trigger invasion of epithelial cells into the subepithelial regions of the airway wall where they contribute to fibrosis, demonstrating a previously unknown plasticity of the airway epithelium in allergic airway disease.
Konturek, S J; Drozdowicz, D; Pytko-Polonczyk, J; Brzozowski, T; Bielański, W
Solcoseryl, a deproteinized extract of calf blood, protects the gastric mucosa against various topical irritants and enhances the healing of chronic gastric ulcerations but the mechanisms of these effects have been little studied. This study was designed to elucidate the active principle in Solcoseryl and to determine the role of prostaglandins (PG) and polyamines in the antiulcer properties of this agent. Using both, the radioimmunoassay and radioreceptor assay, EGF-like material was detected in Solcoseryl preparation. Solcoseryl given s.c. prevented the formation of stress-induced gastric lesions and this was accompanied by an increase in the generation of PGE2 in the gastric mucosa. Similar effects were obtained with EGF. Pretreatment with indomethacin, to suppress mucosal generation of prostaglandins (PG), greatly augmented stress-induced gastric ulcerations and antagonized the protection exerted by both Solcoseryl and EGF. Solcoseryl, like EGF, enhanced the healing of chronic gastro-duodenal ulcerations. This effect was abolished by the pretreatment with difluoromethylornithine, an inhibitor of ornithine decarboxylase, the key enzyme in the biosynthesis of polyamines. The healing effects of Solcoseryl and EGF was also reduced by prednisolone which decreased the angiogenesis in the granulation tissue in the ulcer area. These results indicate that Solcoseryl 1. contains EGF-like material, 2. displays the protective and ulcer healing effects similar to those of EGF and involving both PG and polyamines and 3. acts via similar mechanism as does EGF.
Larguinho, Miguel; Cordeiro, Ana; Diniz, Mário S; Costa, Pedro M; Baptista, Pedro V
Although the neurotoxic and genotoxic potential of acrylamide has been established in freshwater fish, the full breadth of the toxicological consequences induced by this xenobiotic has not yet been disclosed, particularly in aquatic invertebrates. To assess the effects of acrylamide on a bivalve model, the Mediterranean mussel (Mytilus galloprovincialis), two different setups were accomplished: 1) acute exposure to several concentrations of waterborne acrylamide to determine lethality thresholds of the substance and 2) chronic exposure to more reduced acrylamide concentrations to survey phases I and II metabolic endpoints and to perform a whole-body screening for histopathological alterations. Acute toxicity was low (LC50≈400mg/L). However, mussels were responsive to prolonged exposure to chronic concentrations of waterborne acrylamide (1-10mg/L), yielding a significant increase in lipid peroxidation plus EROD and GST activities. Still, total anti-oxidant capacity was not exceeded. In addition, no neurotoxic effects could be determined through acetylcholine esterase (AChE) activity. The findings suggest aryl-hydrocarbon receptor (Ahr)-dependent responses in mussels exposed to acrylamide, although reduced comparatively to vertebrates. No significant histological damage was found in digestive gland or gills but female gonads endured severe necrosis and oocyte atresia. Altogether, the results indicate that acrylamide may induce gonadotoxicity in mussels, although the subject should benefit from further research. Altogether, the findings suggest that the risk of acrylamide to aquatic animals, especially molluscs, may be underestimated. Copyright © 2014 Elsevier Inc. All rights reserved.
Nurulain, Syed M; Petroianu, Georg; Shafiullah, Mohamed; Kalász, Huba; Oz, Murat; Saeed, Tariq; Adem, Abdu; Adeghate, Ernest
There is an increasing belief that organophosphorus compounds (OPCs) impair glucose homeostasis and cause hyperglycemia and diabetes mellitus. The present study was undertaken to investigate the putative diabetogenic effect of sub-lethal and sub-chronic exposure to paraoxon (POX), an extremely hazardous OPC used in pesticides. The effect of paraoxon on streptozotocin-induced diabetic rats was also examined. Each rat was injected with 100 nmol of POX 5 days per week for 6 weeks. Blood glucose levels and red blood cell acetylcholinesterase activity were measured weekly. Biochemical analysis and morphological studies were performed at the end of the experiment. The results revealed that POX neither induces nor exacerbates diabetes mellitus in experimental rats. Liver and kidney/body weight ratios revealed statistically insignificant differences when compared with controls. Biochemical analysis of urine samples showed a small but not significant increase in protein level in all groups. Urine bilirubin was significantly higher in the diabetes + POX group when compared with the control group. The number of blood cells in urine was significantly higher in the POX-treated group compared with the control group. Hyperglycemia was noted in the diabetes and diabetes + POX groups, but neither in the saline control nor in POX-treated normal rats. Electron microscopy of POX-treated pancreas did not show any morphological changes in beta cells. These results suggest that POX does not cause diabetes mellitus at sub-lethal sub-chronic exposure. Copyright © 2012 John Wiley & Sons, Ltd.
Sura Wanessa Santos Rocha
Full Text Available This study investigated the anti-inflammatory effects of DEC on the CCl4-induced hepatotoxicity in C57BL/6 mice. Chronic inflammation was induced by i.p. administration of CCl4 0.5 μL/g of body weight through two injections a week for 6 weeks. DEC (50 mg/kg was administered by gavage for 12 days before finishing the CCl4 induction. Histological analyses of the DEC-treated group exhibited reduced inflammatory process and prevented liver necrosis and fibrosis. Immunohistochemical and immunofluorescence analyses of the DEC-treated group showed reduced COX-2, IL1β, MDA, TGF-β, and αSMA immunopositivity, besides exhibiting decreased IL1β, COX-2, NFκB, IFNγ, and TGFβ expressions in the western blot analysis. The DEC group enhanced significantly the IL-10 expression. The reduction of hepatic injury in the DEC-treated group was confirmed by the COX-2 and iNOS mRNA expression levels. Based on the results of the present study, DEC can be used as a potential anti-inflammatory drug for chronic hepatic inflammation.
Weng, Lianjin; Guo, Xiaohua; Li, Yang; Yang, Xin; Han, Yuanyuan
Previous researches found that apigenin exerted antidepressant-like effects in rodents. However, it is unclear whether the neurotrophic system is involved in the antidepressant-like effects of apigenin. Our present study aimed to explore the neurotrophic related mechanism of apigenin in depressive-like mice induced by chronic corticosterone treatment. Mice were repeatedly injected with corticosterone (40 mg/kg) subcutaneously (s.c) once daily for consecutive 21 days. Apigenin (20 and 40 mg/kg) and fluoxetine (20 mg/kg) were administered 30 min prior to the corticosterone injection. The behavioral tests indicated that apigenin reversed the reduction of sucrose preference and the elevation of immobility time in mice induced by chronic corticosterone treatment. In addition, the increase in serum corticosterone levels and the decrease in hippocampal brain-derived neurotrophic factor (BDNF) levels in corticosterone-treated mice were also ameliorated by apigenin administration. Taken together, our findings intensively confirmed the antidepressant-like effects of apigenin and indicated that the antidepressant-like mechanism of apigenin was mediated, at least partly by up-regulation of BDNF levels in the hippocampus.
刘慎微; 石黎明; 刘晓城
Summary: The role of HO 1 inducer, hemin, in chronic renal failure (CRF) rats and its possible mechanism of action was studied. 5/6 subtotal nephrectomy was performed to establish chronic renal failure model. Rats were randomly assigned to 4 groups: sham-operated group, CRF group,ferrous gluconate group and hemin group. At the 10th week after operation, serum creatinine,BUN, RBC, HGB and HCT were measured. Renal pathologic changes were observed. RT-PCR and immunohistochemistry were used to detect the expression and distribution of HO-1. RT-PCR and radioimmunoassay was used to determine the expression of ET-1 in the kidney and plasma. The results showed that as compared with CRF group, serum creatinine and BUN in hemin group were reduced significantly and nephrogenic anemia was improved markedly. Glomerular mesangial proliferation and interstitial lesion were also ameliorated significantly. Hemin not only increased the expression of HO-1 but also reduced the expression of ET-1 in the kidney. The level of ET-1 protein in the plasma was also reduced after hemin treatment. Most of these indexes were not obviously changed in ferrous gluconate group. It was suggested that through inducing the expression of HO-1 and reducing the level of ET-1 in the kidney and plasma, hemin plays an important protective role in 5/6 subtotal nephrectomized rats.
Full Text Available INTRODUCTION: Chronic exposure to high levels of ozone induces emphysema and chronic inflammation in mice. We determined the recovery from ozone-induced injury and whether an antioxidant, N-acetylcysteine (NAC, could prevent or reverse the lung damage. METHODS: Mice were exposed to ozone (2.5 ppm, 3 hours/12 exposures, over 6 weeks and studied 24 hours (24h or 6 weeks (6W later. Nac (100 mg/kg, intraperitoneally was administered either before each exposure (preventive or after completion of exposure (therapeutic for 6 weeks. RESULTS: After ozone exposure, there was an increase in functional residual capacity, total lung volume, and lung compliance, and a reduction in the ratio of forced expiratory volume at 25 and 50 milliseconds to forced vital capacity (FEV25/FVC, FEV50/FVC. Mean linear intercept (Lm and airway hyperresponsiveness (AHR to acetylcholine increased, and remained unchanged at 6W after cessation of exposure. Preventive NAC reduced the number of BAL macrophages and airway smooth muscle (ASM mass. Therapeutic NAC reversed AHR, and reduced ASM mass and apoptotic cells. CONCLUSION: Emphysema and lung function changes were irreversible up to 6W after cessation of ozone exposure, and were not reversed by NAC. The beneficial effects of therapeutic NAC may be restricted to the ASM.
Radahmadi, Maryam; Alaei, Hojjatallah; Sharifi, Mohammad Reza; Hosseini, Nasrin
Previous results indicated that stress impairs learning and memory. In this research, the effects of preventive, therapeutic and regular continually running activity on chronic stress-induced memory deficit in rats were investigated. 70 male rats were randomly divided into seven groups as follows: Control, Sham, Stress-Rest, Rest-Stress, Stress-Exercise, Exercise-Stress and Exercise-Stress & Exercise groups. Chronic restraint stress was applied 6 h/day for 21days and treadmill running 1 h/day. Memory function was evaluated by the passive avoidance test. The results revealed that running activities had therapeutic effect on mid and long-term memory deficit and preventive effects on short and mid-term memory deficit in stressed rats. Regular continually running activity improved mid and long-term memory compared to Exercise-Stress group. The beneficial effects of exercise were time-dependent in stress conditions. Finally, data corresponded to the possibility that treadmill running had a more important role on treatment rather than on prevention on memory impairment induced by stress.
Milkiewicz, Malgorzata; Klak, Marta; Kempinska-Podhorodecka, Agnieszka; Wiechowska-Kozlowska, Anna; Urasinska, Elzbieta; Blatkiewicz, Malgorzata; Wunsch, Ewa; Elias, Elwyn; Milkiewicz, Piotr
Pathogenesis of primary sclerosing cholangitis (PSC) may involve impaired bile acid (BA) homeostasis. We analyzed expressions of factors mediating enterohepatic circulation of BA using ileal and colonic (ascending and sigmoid) biopsies obtained from patients with PSC with and without ulcerative colitis (UC) and explanted PSC livers. Two-fold increase of BA-activated farnesoid X receptor (FXR) protein levels were seen in ascending and sigmoid colon of PSC patients with correspondingly decreased apical sodium-dependent BA transporter (ASBT) gene expression. This was associated with increased OSTβ protein levels in each part of analyzed gut. An intestinal fibroblast growth factor (FGF19) protein expression was significantly enhanced in ascending colon. Despite increased hepatic nuclear receptors (FXR, CAR, SHP), and FGF19, neither CYP7A1 suppression nor CYP3A4 induction were observed. The lack of negative regulation of BA synthesis may be accountable for lower levels of cholesterol observed in PSC in comparison to primary biliary cholangitis (PBC). In conclusion, chronic cholestasis in PSC induces adaptive changes in expression of BA transporters and FXR in the intestine. However hepatic impairment of expected in chronic cholestasis downregulation of CYP7A1 and upregulation of CYP3A4 may promote BA-induced liver injury in PSC. PMID:28008998
Prakash, Chandra; Kumar, Vijay
The present study was executed to study the effect of chronic arsenic exposure on generation of mitochondrial oxidative stress and biogenesis in rat liver. Chronic sodium arsenite treatment (25 ppm for 12 weeks) decreased mitochondrial complexes activity in rat liver. There was a decrease in mitochondrial superoxide dismutase (MnSOD) activity in arsenic-treated rats that might be responsible for increased protein and lipid oxidation as observed in our study. The messenger RNA (mRNA) expression of mitochondrial and nuclear-encoded subunits of complexes I (ND1 and ND2) and IV (COX I and COX IV) was downregulated in arsenic-treated rats only. The protein and mRNA expression of MnSOD was reduced suggesting increased mitochondrial oxidative damage after arsenic treatment. There was activation of Bax and caspase-3 followed by release of cytochrome c from mitochondria suggesting induction of apoptotic pathway under oxidative stress. The entire phenomenon was associated with decrease in mitochondrial biogenesis as evident by decreased protein and mRNA expression of nuclear respiratory factor 1 (NRF-1), nuclear respiratory factor 2 (NRF-2), peroxisome proliferator activator receptor gamma-coactivator 1α (PGC-1α), and mitochondrial transcription factor A (Tfam) in arsenic-treated rat liver. The results of the present study indicate that arsenic-induced mitochondrial oxidative stress is associated with decreased mitochondrial biogenesis in rat liver that may present one of the mechanisms for arsenic-induced hepatotoxicity.
Synhaeve, Nicholas; Musilli, Stefania; Stefani, Johanna; Nicolas, Nour; Delissen, Olivia; Dublineau, Isabelle; Bertho, Jean-Marc
Strontium 90 ((90)Sr) remains in the environment long after a major nuclear disaster occurs. As a result, populations living on contaminated land are potentially exposed to daily ingesting of low quantities of (90)Sr. The potential long-term health effects of such chronic contamination are unknown. In this study, we used a mouse model to evaluate the effects of (90)Sr ingestion on the immune system, the animals were chronically exposed to (90)Sr in drinking water at a concentration of 20 kBq/l, for a daily ingestion of 80-100 Bq/day. This resulted in a reduced number of CD19(+) B lymphocytes in the bone marrow and spleen in steady-state conditions. In contrast, the results from a vaccine experiment performed as a functional test of the immune system showed that in response to T-dependent antigens, there was a reduction in IgG specific to tetanus toxin (TT), a balanced Th1/Th2 response inducer antigen, but not to keyhole limpet hemocyanin (KLH), a strong Th2 response inducer antigen. This was accompanied by a reduction in Th1 cells in the spleen, consistent with the observed reduction in specific IgG concentration. The precise mechanisms by which (90)Sr acts on the immune system remain to be elucidated. However, our results suggest that (90)Sr ingestion may be responsible for some of the reported effects of internal contamination on the immune system in civilian populations exposed to the Chernobyl fallout.
DU Jian-hang; WU Gui-fu; ZHENG Zhen-sheng; DAI Gang; FENG Ming-zhe
To make clear the precise hemodynamic mechanism underlying the anti-atherogenesis benefit of enhanced external couterpulsation(EECP) treatment, and to investigate the proper role of some important hemodynamic factors during the atherosclerotic progress, a comprehensive study combining long-term animal experiment and numerical solving was conducted in this paper. An experimentally induced hypercholesterolemic porcine model was developed and the chronic EECP intervention was subjected. Basic hemodynamic measurement was performed in vivo, as well as the arterial endothelial samples were extracted for physiological examination. Meanwhile, a numerical model was introduced to solve the complex hemodynamic factors such as WSS and OSI. The results show that EECP treatment resulted in significant increase of the instant levels of arterial WSS, blood pressure, and OSI. During EECP treatment, the instant OSI level of the common carotid arteries over cardiac cycles raised to a mean value of 8.58 ×10-2 ±2.13 ×10-2. Meanwhile, the chronic intervention of EECP treatment significantly reduced the atherosclerotic lesions in abdominal aortas and the endothelial cellular adherence. The present study suggests that the unique blood flow pattern induced by EECP treatment and the augmentation of WSS level in cardiac cycles may be the most important hemodynamic mechanism that contribute to its anti-atherogenesis effect. And as one of the indices that cause great concern in current hemodynamic study, OSI may not play a key role during the initiation of atherosclerosis.
Paruthikunnan, Samir; Shankar, Balasubramanyam; Kadavigere, Rajagopal; Prabhu, Mukhyaprana; Narayanan, Ramakrishna; Jain, Harshwardhan
Toxoplasmosis is a ubiquitous protozoal infection that during pregnancy commonly affects the fetus severely, with maternal infection usually being mild self-limiting. Disseminated toxoplasmosis in a healthy pregnant woman has, to the best of our knowledge, not been reported before. We present a case of disseminated toxoplasmosis involving pulmonary, central nervous system, and lymph nodes in a pregnant woman and imaging findings on radiography, computed tomography, and magnetic resonance imaging.
Mueller-Mang, C.; Mang, T.G.; Thurnher, M.M. [University Hospital Vienna, Department of Radiology, Vienna (Austria); Kalhs, P. [University Hospital Vienna, Department of Internal Medicine, Vienna (Austria)
Toxoplasmosis encephalitis is a severe, but often misdiagnosed complication in patients after bone marrow transplantation (BMT). We describe the unique computed tomography (CT) and magnetic resonance (MR) imaging features of cerebral toxoplasmosis in two bone marrow recipients and compare them to the cases in the literature. To our knowledge, this is the first report analyzing the appearance of cerebral toxoplasmosis on diffusion-weighted MR imaging (DWI). (orig.)
Zhao, Yuanting; Qin, Yue; Liu, Tuanjiang; Hao, Dingjun
Neuropathic pain, which is characterized by hyperalgesia, allodynia and spontaneous pain, is one of the most painful symptoms that can be experienced in the clinic. It often occurs as a result of injury to the peripheral nerves, dorsal root ganglion (DRG), spinal cord or brain. The renin-angiotensin system (RAS) plays an important role in nociception. As an essential component of the RAS, the angiotensin (Ang)-(1-7)/Mas axis may be involved in antinociception. The aim of the present study was to explore the expression pattern of Mas in DRG neurons following chronic nerve injury and examine the effects of Mas inhibition and activation on neuropathic pain in a chronic constriction injury (CCI) rat model. The results showed, that compared with the sham group, CCI caused a time-dependent induction of Mas expression at both the mRNA and the protein levels in DRG neurons. Consistent with the results, isolated DRG neurons showed a time-dependent increase in Ang-(1-7) binding on the cell membrane following the CCI surgery, but not the sham surgery. Compared with the sham control groups, CCI significantly decreased the paw withdrawal latency and threshold, and this was markedly improved and aggravated by intrathecal injection of the selective Mas agonist Ang-(1-7) and the selective Mas inhibitor D-Pro7-Ang-(1-7), respectively. In conclusion, this study has provided the first evidence, to the best of our knowledge, that the Mas expression in DRG neurons is time-dependently induced by chronic nerve injury and that the intrathecal activation and inhibition of Mas can improve and aggravate CCI-induced neuropathic pain, respectively. This study has provided novel insights into the pathophysiological process of neuropathic pain and suggests that the Ang-(1-7)/Mas axis could be an effective therapeutic target for neuropathic pain, warranting further study.
Rho, Sang-Gyun; Kim, Yong Sung; Choi, Suck Chei; Lee, Moon Young
To investigate whether palatable sweet foods have a beneficial effect on chronic stress-induced colonic motility and inflammatory cytokines. Adult male rats were divided into 3 groups: control (CON, n = 5), chronic variable stress with chow (CVS-A, n = 6), and chronic variable stress with chow and sweet food (CVS-B, n = 6). The rats were fed standard rodent chow as the chow food and/or AIN-76A as the sweet food. A food preference test for AIN-76A was performed in another group of normal rats (n = 10) for twelve days. Fecal pellet output (FPO) was measured for 6 wk during water bedding stress in the CVS groups. The weight of the adrenal glands, adrenocorticotropic hormone (ACTH) and corticosterone levels in plasma were measured. The expression levels of transforming growth factor-β, interleukin (IL)-2, and interferon-gamma (IFN-γ) were measured in the distal part of colonic tissues and plasma using Western blot analysis. In sweet preference test, all rats initially preferred sweet food to chow food. However, the consumption rate of sweet food gradually decreased and reduced to below 50% of total intake eight days after sweet food feeding. Accumulated FPO was higher in the CVS-A group compared with the CVS-B group over time. All stress groups showed significant increases in the adrenal to body weight ratio (CVS-A, 0.14 ± 0.01; CVS-B, 0.14 ± 0.01) compared with the control group (0.12 ± 0.01, P colon compared to the control group, whereas this effect was significantly attenuated in the CVS-B group. These results suggest that concurrent sweet food ingestion during CVS might have an effect on the reduction of stress-induced colonic hyper-motility and pro-inflammatory cytokine production in rats.
Chun-Sheng Hou; Gui-Qiang Wang; Shu-Lan Lu; Bei Yue; Ming-Rong Li; Xiao-Yan Wang; Jian-Wu Yu
AIM: To study and compare the difference of activationinduced cell death (AICD) in peripheral blood T-lymphocytes (PBL-Ts) from patients with chronic hepatitis B (CHB) and the normal people in vitro, and to explore the role of AICD in chronic hepatitis B virus (HBV) infection and the pathogenesis of CHB.METHODS: Twenty-five patients and fourteen healthy people were selected for isolation of PBL-Ts. During cultivation, antiCD3 mAb, PMA and ionomycin were used for AICD of PBL-Ts.AICD ratio of PBL-Ts was detected with TdT-mediated dUTP nick end labeling and assessed by flow cytometry.RESULTS: When induced with anti-CD3, PMA and ionomycin in vitro, AICD ratio of PBL-Ts from CHB patients was significantly higher than that from healthy control (17.24±1.21VS. 6.63±1.00, P＜0.01) and that from CHB patients without induction (17.24±1.21 VS. 9.88±1.36, P＜0.0L). There was a similar AICD ratio of PBL-Ts between induction group and without induction group, but no difference was found before and after induction in healthy control. The density of INF-γ in culture media of induction groups of CHB was lower than that of other groups (P＜0.01). There was no difference between these groups in density of IL-10 (P＞0.05).CONCLUSION: When induced during cultivation in vitro,PBL-Ts from CHB have AICD very commonly. This phenomenon has a potentially important relation with pathogenesis of CHB and chronicity of HBV infection.
Lyons, D N; Kniffin, T C; Zhang, L P; Danaher, R J; Miller, C S; Bocanegra, J L; Carlson, C R; Westlund, K N
Our laboratory previously developed a novel neuropathic and inflammatory facial pain model for mice referred to as the Trigeminal Inflammatory Compression (TIC) model. Rather than inducing whole nerve ischemia and neuronal loss, this injury induces only slight peripheral nerve demyelination triggering long-term mechanical allodynia and cold hypersensitivity on the ipsilateral whisker pad. The aim of the present study is to further characterize the phenotype of the TIC injury model using specific behavioral assays (i.e. light-dark box, open field exploratory activity, and elevated plus maze) to explore pain- and anxiety-like behaviors associated with this model. Our findings determined that the TIC injury produces hypersensitivity 100% of the time after surgery that persists at least 21 weeks post injury (until the animals are euthanized). Three receptive field sensitivity pattern variations in mice with TIC injury are specified. Animals with TIC injury begin displaying anxiety-like behavior in the light-dark box preference and open field exploratory tests at week eight post injury as compared to sham and naïve animals. Panic anxiety-like behavior was shown in the elevated plus maze in mice with TIC injury if the test was preceded with acoustic startle. Thus, in addition to mechanical and cold hypersensitivity, the present study identified significant anxiety-like behaviors in mice with TIC injury resembling the clinical symptomatology and psychosocial impairments of patients with chronic facial pain. Overall, the TIC injury model's chronicity, reproducibility, and reliability in producing pain- and anxiety-like behaviors demonstrate its usefulness as a chronic neuropathic facial pain model.
Full Text Available Objectives: The stomach is a sensitive digestive organ that is susceptible to exogenous pathogens from the diet. In response to such pathogens, the stomach induces oxidative stress, which might be related to the development of both gastric organic disorders such as gastritis, gastric ulcers, and gastric cancer, and functional disorders such as functional dyspepsia. This study was accomplished to investigate the effect of Ganoderma lucidum pharmacopuncture (GLP on chronic gastric ulcers in rats. Methods: The rats were divided into 4 groups of 8 animals each: the normal, the control, the normal saline (NP and the GLP groups. In this study, the modified ethanol gastritis model was used. The rats were administrated 56% ethanol orally every other day. The dose of ethanol was 8 g/kg body weight. The normal group received the same amount of normal saline instead of ethanol. The NP and the GLP groups were treated with injection of saline and GLP respectively. The control group received no treatment. Two local acupoints CV12 (中脘 and ST36 (足三里 were used. All laboratory rats underwent treatment for 15 days. On last day, the rats were sacrificed and their stomachs were immediately excised. Results: Ulcers of the gastric mucosa appeared as elongated bands of hemorrhagic lesions parallel to the long axis of the stomach. In the NP and GLP groups, the injuries to the gastric mucosal injuries were not as severe as they were in the control group. Wound healings of the chronic gastric ulcers was promoted by using GLP and significant alterations of the indices in the gastric mucosa were observed. Such protection was demonstrated by gross appearance, histology and immunehistochemistry staining for Bcl-2-associated X (BAX, B-cell lymphoma 2 (Bcl-2 and Transforming growth factor-beta 1 (TGF-β1. Conclusion: These results suggest that GLP at CV12 and ST36 can provide significant protection to the gastric mucosa against an ethanol induced chronic gastric ulcer.
Lin, Li; Zhu, Bao-Ping; Cai, Liang
The present study was aimed to establish a model of chronic prostatitis in rat with the use of intraprostatic injection of Complete Freund's Adjuvant, and to examine the anti-inflammatory and analgesic effects of melittin on the newly-developed chronic prostatic pain model. Adult male Sprague-Dawley rats were injected with Complete Freund's Adjuvant (CFA) into the prostate. Twelve days after model rats of the treatment group were injected melittin into the prostate, while those of the control group received sterile saline injection. The nociceptive effects of CFA were evaluated by using a behavior approach (i.e. mechanical pain threshold measurement) on the day of CFA injection and 6, 12, and 18days after CFA injection. After the in-live study was done, the prostate was collected for histological examination of inflammatory cell infiltration. Levels of cyclooxygenase (COX)-2 in prostate and glial fibrillary acidic protein (GFAP) in spinal cord were determined using immunohistochemistry. Rats of the sham control group received intraprostatic injection of sterile saline and were studied using the same methods RESULTS: Intraprostatic CFA injection induced local allodynia that lasted over at least 2 weeks. The pain behavior of rat was associated with increases in inflammatory cell infiltration into the prostate. Levels of COX-2 in prostate and GFAP in spinal cord were also elevated. Treatment with melittin significantly raised pain threshold, decreased inflammatory infiltrates, and suppressed COX-2 and GFAP expression. Intraprostatic injection of CFA induced neurogenic prostatitis and prostatic pain. The established model will be useful to the study of CP/CPPS pathogenesis. Melittin demonstrated profound anti-inflammatory and analgesic effects on the chronic prostatic pain model, suggesting melittin may hold promise as a novel therapeutic for treatment of CP/CPPS. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
Full Text Available Previous studies reported the oral administration of Naja naja atra venom (NNAV reduced adriamycin-induced chronic kidney damage. This study investigated the effects of intragastric administrated cardiotoxin from Naja naja atra venom on chronic kidney disease in rats. Wistar rats were injected with adriamycin (ADR; 6 mg/kg body weight via the tail vein to induce chronic kidney disease. The cardiotoxin was administrated daily by intragastric injection at doses of 45, 90, and 180 μg/kg body weight until the end of the protocol. The rats were placed in metabolic cages for 24 hours to collect urine, for determination of proteinuria, once a week. After 6 weeks, the rats were sacrificed to determine serum profiles relevant to chronic kidney disease, including albumin, total cholesterol, phosphorus, blood urea nitrogen, and serum creatinine. Kidney histology was examined with hematoxylin and eosin, periodic acid-Schiff, and Masson’s trichrome staining. The levels of kidney podocin were analyzed by Western blot analysis and immunofluorescence. We found that cardiotoxin reduced proteinuria and can improve biological parameters in the adriamycin-induced kidney disease model. Cardiotoxin also reduced adriamycin-induced kidney pathology, suggesting that cardiotoxin is an active component of NNAV for ameliorating adriamycin-induced kidney damage and may have a potential therapeutic value on chronic kidney disease.
Ding, Zhi-Hui; Xu, Li-Min; Wang, Shu-Zhi; Kou, Jian-Qun; Xu, Yin-Li; Chen, Cao-Xin; Yu, Hong-Pei; Qin, Zheng-Hong; Xie, Yan
Previous studies reported the oral administration of Naja naja atra venom (NNAV) reduced adriamycin-induced chronic kidney damage. This study investigated the effects of intragastric administrated cardiotoxin from Naja naja atra venom on chronic kidney disease in rats. Wistar rats were injected with adriamycin (ADR; 6 mg/kg body weight) via the tail vein to induce chronic kidney disease. The cardiotoxin was administrated daily by intragastric injection at doses of 45, 90, and 180 μ g/kg body weight until the end of the protocol. The rats were placed in metabolic cages for 24 hours to collect urine, for determination of proteinuria, once a week. After 6 weeks, the rats were sacrificed to determine serum profiles relevant to chronic kidney disease, including albumin, total cholesterol, phosphorus, blood urea nitrogen, and serum creatinine. Kidney histology was examined with hematoxylin and eosin, periodic acid-Schiff, and Masson's trichrome staining. The levels of kidney podocin were analyzed by Western blot analysis and immunofluorescence. We found that cardiotoxin reduced proteinuria and can improve biological parameters in the adriamycin-induced kidney disease model. Cardiotoxin also reduced adriamycin-induced kidney pathology, suggesting that cardiotoxin is an active component of NNAV for ameliorating adriamycin-induced kidney damage and may have a potential therapeutic value on chronic kidney disease.
Leles, Daniela; Lobo, Amanda; Rhodes, Taís; Millar, Patrícia Riddell; Amendoeira, Maria Regina Reis; Araújo, Adauto
Paleoparasitology studies parasite infections by finding the parasites' remains in preserved organic remains such as natural or artificial mummy tissues, skeletons, teeth, and coprolites, among others. However, some currently important infections like toxoplasmosis have not been studied by paleoparasitology. The reasons include this parasite's complex life cycle, the resulting difficulties in locating this protozoan in the intermediate host tissues, and the limitation of coprolite studies to felines, the protozoan's definitive host. The current study thus aimed to produce an experimental model for molecular diagnosis of toxoplasmosis, prioritizing its study in bones and skin, the most abundant materials in archeological collections and sites. The study demonstrated the feasibility of recovering Toxoplasma gondii DNA from desiccated material, including bones and skin, in experimental models both with circulating tachyzoites (RH strain), characteristic of acute infection, and with cysts (ME49 cystogenic strain), characteristic of chronic infection. At present, most individuals with T. gondii infection are in the chronic phase, and the same was probably true in the past. The current study thus expands the odds of finding the parasite in archeological material, enhanced by the nature of the material in which the diagnosis was made. Finding the parasite may help answer questions that are widely debated in the literature on this protozoan's origin (Old World versus New World). In addition, when conditions do not allow ideal storage of samples for molecular tests, the methodology creates the possibility of testing oven-dried samples transported at room temperature.
De Wilde, Maarten; Speeckaert, Marijn; Callens, Rutger; Van Biesen, Wim
'Chronic Lyme disease' is a controversial condition. As any hard evidence is lacking that unresolved systemic symptoms, following an appropriately diagnosed and treated Lyme disease, are related to a chronic infection with the tick-borne spirochaetes of the Borrelia genus, the term 'chronic Lyme disease' should be avoided and replaced by the term 'post-treatment Lyme disease syndrome.' The improper prescription of prolonged antibiotic treatments for these patients can have an impact on the community antimicrobial resistance and on the consumption of health care resources. Moreover, these treatments can be accompanied by severe complications. In this case report, we describe a life-threatening ceftriaxone-induced immune hemolytic anemia with an acute kidney injury (RIFLE-stadium F) due to a pigment-induced nephropathy in a 76-year-old woman, who was diagnosed with a so-called 'chronic Lyme disease.'
Full Text Available Toxoplamosis is a parasitic zoonosis which occurs worldwide, but is prevalent in Europe, South America and Africa. When infection occurs for the first time during pregnancy, mother to child transmission of the parasite can cause congenital toxoplasmosis. Rate of congenital infection ranges from less than 0.1 to approximately 1 per 1,000 live births. The risk of transmission depends on the gestational age at the time of maternal infection. A diagnosis of congenital toxoplasmosis is usually considered in infants who present: hydrocephalus, chorioretinitis, and intracranial calcifications, but this triade is very rare. Approximately 85% of the infants with congenital toxoplasmosis are clinically normal at birth; however, sequelae of infection may become apparent only months or even years later. Chorioretinitis is the main complication of congenital toxoplasmosis, late onset retinal lesions and relapse can appear many years after birth, but the overall ocular prognosis is satisfactory when infection is identified and treated accordingly. Fortunately, serious neonatal forms and severe neurological impairment have become rare, but prompt treatment of children with convulsions, abnormal muscle tone, hydrocephalus, may improve the prognosis and result in almost normal outcome. For infants who have congenital toxoplasmosis, treatment soon after birth for 1 year with pyrimetamine, sulfadiazine and leukoverin led to remarkable resolution of serious, active disease. A long follow-up is necessary to assess the long-term outcome of children and young adults with congenital toxoplasmosis, that is favourable for the majority of cases. Epidemiological surveillance needs to be improved in order to determine the effectiveness of prevention programs.Articoli Selezionati del “3° Convegno Pediatrico del Medio Campidano” · Guspini · 25 Maggio 2013Guest Editor: Roberto Antonucci
Constantin, Farah; Denislam, Dogan
Two thirds of the congenital toxoplasmosis cases describe minimal or inapparent symptoms present at birth, being diagnosed from a psychomotor retard. The forms of chorioretinitis may be described by repeated outbursts in the first years of life. Chorioretinitis or focal necrotizing retinitis usually develops in a bilateral way, being progressive and leading to blindness. Usually there is only one focal inflammatory beginning at the edge of a pigmented scar and the local inflammatory process may extend through successive spikes in other regions of the retina. Active chorioretinitis is expressed clinically by a blurred misty eyesight, with the advent of scotomas, photophobia, and if the macula is involved, the loss of the central eyesight may occur. In this paper I present the patient R.A., 6 years old from Constanta who is hospitalized in the Clinic of Infectious Diseases for investigations and treatment continuity because positive IgG Toxoplasma was previously found. The child has spastic quadriplegia and profound mental retardation.
Zhang, Wei; Xu, Li; Cho, Si-Young; Min, Kyung-Jin; Oda, Tatsuya; Zhang, LiJun; Yu, Qing; Jin, Jun-O
This study investigates the in vivo functions of ginseng berry extract (GB) as a therapy for dextran sodium sulfate (DSS)-induced colitis. C57BL/6 mice were given drinking water containing DSS (3%) for eight days to induce acute colitis. At the same time, the mice received an oral dose of GB (50 mg/kg) once daily. The GB-treated mice were less susceptible to the development of acute colitis than were control mice treated with saline, as determined by weight loss, disease activity, and colon histology. The administration of GB to DSS-treated mice also reduced the numbers and inhibited the activation of colon-infiltrating T cells, neutrophils, intestinal CD103(-)CD11c⁺ dendritic cells (cDCs), and macrophages. In addition, GB treatment promoted the migration of CD103⁺CD11c⁺ cDCs and expansion of Foxp3⁺ regulatory T cells in the colons of DSS-treated mice. Similarly, in the DSS-induced chronic colitis model, GB treatment improved the macroscopic and histological appearance of the colon wall when compared to untreated control mice, as indicated by longer colon length and lower histological scores. This is the first report to show that oral administration of GB suppresses immune activation and protects against experimentally induced colitis.
Full Text Available Xiaoyaosan (XYS decoction is a famous prescription which can protect nervous system from stress and treat liver stagnation and spleen deficiency syndrome (LSSDS. In this experiment, we observed the effect of XYS decoction on chronic immobilization stress (CIS induced learning and memory deficit in rats from behaviors and changes of proteins in hippocampus. We used XYS decoction to treat CIS induced learning and memory deficit in rats with rolipram as positive control, used change of body weight and behavioral tests to determine whether the rats have LSSDS and have learning and memory deficit or not. We used Western blotting to determine the content of postsynaptic density protein 95 (PSD-95 and synaptophysin (SYP in hippocampus. Results showed that XYS could improve the situation of slow weight gain induced by CIS, improve the ability of learning and memory, reverse the symptom of liver stagnation and spleen deficiency syndrome (LSSDS in rats, and increase the levels of PSD-95 and SYP on the hippocampal nerve synapses. These findings suggested that XYS decoction may be helpful in reversing CIS induced learning and memory deficit by increasing the levels of PSD-95 and SYP on the hippocampal nerve synapses and improving synaptic plasticity.
Full Text Available This study investigates the in vivo functions of ginseng berry extract (GB as a therapy for dextran sodium sulfate (DSS-induced colitis. C57BL/6 mice were given drinking water containing DSS (3% for eight days to induce acute colitis. At the same time, the mice received an oral dose of GB (50 mg/kg once daily. The GB-treated mice were less susceptible to the development of acute colitis than were control mice treated with saline, as determined by weight loss, disease activity, and colon histology. The administration of GB to DSS-treated mice also reduced the numbers and inhibited the activation of colon-infiltrating T cells, neutrophils, intestinal CD103−CD11c+ dendritic cells (cDCs, and macrophages. In addition, GB treatment promoted the migration of CD103+CD11c+ cDCs and expansion of Foxp3+ regulatory T cells in the colons of DSS-treated mice. Similarly, in the DSS-induced chronic colitis model, GB treatment improved the macroscopic and histological appearance of the colon wall when compared to untreated control mice, as indicated by longer colon length and lower histological scores. This is the first report to show that oral administration of GB suppresses immune activation and protects against experimentally induced colitis.
Tripathi, Sunil Jamuna; Chakraborty, Suwarna; Srikumar, B N; Raju, T R; Shankaranarayana Rao, B S
Chronic stress causes detrimental effects on various forms of learning and memory. The basolateral amygdala (BLA) not only plays a crucial role in mediating certain forms of memory, but also in the modulation of the effects of stress. Chronic immobilization stress (CIS) results in hypertrophy of the BLA, which is believed to be one of the underlying causes for stress' effects on learning. Thus, it is plausible that preventing the effects of CIS on amygdala would preclude its deleterious cognitive effects. Accordingly, in the first part, we evaluated the effect of excitotoxic lesion of the BLA on chronic stress-induced hippocampal-dependent spatial learning using a partially baited radial arm maze task. The BLA was ablated bilaterally using ibotenic acid prior to CIS. Chronically stressed rats showed impairment in spatial learning with decreased percentage correct choice and increased reference memory errors. Excitotoxic lesion of the BLA prevented the impairment in spatial learning and reference memory. In the retention test, lesion of the BLA was able to rescue the chronic stress-induced impairment. Interestingly, stress-induced enhanced plasma corticosterone levels were partially prevented by the lesion of BLA. These results motivated us to evaluate if the same effects can be observed with temporary inactivation of BLA, only during stress. We found that chronic stress-induced spatial learning deficits were also prevented by temporary inactivation of the BLA. Additionally, temporary inactivation of BLA partially precluded the stress-induced increase in plasma corticosterone levels. Thus, inactivation of BLA precludes stress-induced spatial learning deficits, and enhanced plasma corticosterone levels. It is speculated that BLA inactivation-induced reduction in corticosterone levels during stress, might be crucial in restoring spatial learning impairments. Our study provides evidence that amygdalar modulation during stress might be beneficial for strategic
Full Text Available Autophagy is an intracellular pathway by which lysosomes degrade and recycle long-lived proteins and cellular organelles. The effects of ethanol on autophagy are complex but recent studies have shown that autophagy serves a protective function against ethanol-induced liver injury. Autophagy was found to also be protective against CYP2E1-dependent toxicity in vitro in HepG2 cells which express CYP2E1 and in vivo in an acute alcohol/CYPE1-dependent liver injury model. The goal of the current report was to extend the previous in vitro and acute in vivo experiments to a chronic ethanol model to evaluate whether autophagy is also protective against CYP2E1-dependent liver injury in a chronic ethanol-fed mouse model. Wild type (WT, CYP2E1 knockout (KO or CYP2E1 humanized transgenic knockin (KI, mice were fed an ethanol liquid diet or control dextrose diet for four weeks. In the last week, some mice received either saline or 3-methyladenine (3-MA, an inhibitor of autophagy, or rapamycin, which stimulates autophagy. Inhibition of autophagy by 3-MA potentiated the ethanol-induced increases in serum transaminase and triglyceride levels in the WT and KI mice but not KO mice, while rapamycin prevented the ethanol liver injury. Treatment with 3-MA enhanced the ethanol-induced fat accumulation in WT mice and caused necrosis in the KI mice; little or no effect was found in the ethanol-fed KO mice or any of the dextrose-fed mice. 3-MA treatment further lowered the ethanol-decrease in hepatic GSH levels and further increased formation of TBARS in WT and KI mice, whereas rapamycin blunted these effects of ethanol. Neither 3-MA nor rapamycin treatment affected CYP2E1 catalytic activity or content or the induction CYP2E1 by ethanol. The 3-MA treatment decreased levels of Beclin-1 and Atg 7 but increased levels of p62 in the ethanol-fed WT and KI mice whereas rapamycin had the opposite effects, validating inhibition and stimulation of autophagy, respectively. These
Martín, Víctor; Vale, Carmen; Rubiolo, Juan A; Roel, Maria; Hirama, Masahiro; Yamashita, Shuji; Vieytes, Mercedes R; Botana, Luís M
Ciguatoxins are sodium channels activators that cause ciguatera, one of the most widespread nonbacterial forms of food poisoning, which presents with long-term neurological alterations. In central neurons, chronic perturbations in activity induce homeostatic synaptic mechanisms that adjust the strength of excitatory synapses and modulate glutamate receptor expression in order to stabilize the overall activity. Immediate early genes, such as Arc and Egr1, are induced in response to activity changes and underlie the trafficking of glutamate receptors during neuronal homeostasis. To better understand the long lasting neurological consequences of ciguatera, it is important to establish the role that chronic changes in activity produced by ciguatoxins represent to central neurons. Here, the effect of a 30 min exposure of 10-13 days in vitro (DIV) cortical neurons to the synthetic ciguatoxin CTX 3C on Arc and Egr1 expression was evaluated using real-time polymerase chain reaction approaches. Since the toxin increased the mRNA levels of both Arc and Egr1, the effect of CTX 3C in NaV channels, membrane potential, firing activity, miniature excitatory postsynaptic currents (mEPSCs), and glutamate receptors expression in cortical neurons after a 24 h exposure was evaluated using electrophysiological and western blot approaches. The data presented here show that CTX 3C induced an upregulation of Arc and Egr1 that was prevented by previous coincubation of the neurons with the NaV channel blocker tetrodotoxin. In addition, chronic CTX 3C caused a concentration-dependent shift in the activation voltage of NaV channels to more negative potentials and produced membrane potential depolarization. Moreover, 24 h treatment of cortical neurons with 5 nM CTX 3C decreased neuronal firing and induced synaptic scaling mechanisms, as evidenced by a decrease in the amplitude of mEPSCs and downregulation in the protein level of glutamate receptors that was also prevented by tetrodotoxin
Assenmacher, I.; Mekaouche, M.; Maurel, D.; Barbanel, G.; Givalois, L.; Boissin, J.; Malaval, F.; Ixart, G.
The tail-cast suspension rat model has been developed in ground laboratories interested in space physiology for extensive study of mechanisms causing the pathophysiological syndrome associated with space flights. We used individually-caged male rats to explore the effects of acute and chronic (7d) orthostatic restraint (OR) and head-down anti-orthostatic restraint (AOR) on a series of physiological variables. The acute restraint study showed that (1) the installation of the OR device induced an acute reaction for 2 days, with a substantial rise in ACTH (x2) and CORT (x6), and that (2) the head-down tilt from OR to AOR induced (i) within 10 min and lasting 60 min a 2-fold rise in the intra-cerebro-ventricular pressure (Picv) monitored with an icv telemetric recording system, which receded to normal between 60 and 120 min; and (ii) within 30 min a short-lived 4-fold rise in plasma ACTH and CORT levels. Chronic OR induced (1) the suppression of the diurnal ACTH/CORT rhythm, with increased mean levels, especially for ACTH, (2) a degraded circadian locomotor activity rhythm manifested by a significant reduction in the spectral power of the 24h periodicity and a concomitant emergence of shorter (ultradian) periodicities, (3) an associated, but less pronounced alteration of the diurnal rhythm in body temperature; and (4) a marked increase in baseline plasma levels of IL-1β and an increased reactivity in cytokine release following an E. coli endotoxin (LPS) challenge. AOR induced (1) a similar obliteration of the circadian ACTH/CORT rhythm, (2) the loss of close correlation between ACTH and CORT, (3) a generalized increase in baseline plasma IL-1β levels and (4) more extensive degradation of the arcadian periodicity for both locomotor activity and, to a lesser extent, body temperature, replaced by dominant spectral powers for ultradian periodicities (3 to 10h). In conclusion, both experimental paradigms — but AOR more than OR — caused a blockade of the arcadian
Kazuo Nakamoto; Takashi Nishinaka; Naoya Sato; Mitsumasa Mankura; Yutaka Koyama; Fumiyo Kasuya; Shogo Tokuyama
GPR40 has been reported to be activated by long-chain fatty acids, such as docosahexaenoic acid (DHA). However, reports studying functional role of GPR40 in the brain are lacking. The present study focused on the relationship between pain regulation and GPR40, investigating the functional roles of hypothalamic GPR40 during chronic pain caused using a complete Freund's adjuvant (CFA)-induced inflammatory chronic pain mouse model. GPR40 protein expression in the hypothalamus was transiently inc...
Mady, Rasha F; El-Hadidy, Wessam; Elachy, Samar
Toxoplasmosis is a parasitic infection caused by Toxoplasma gondii protozoon. It is most commonly treated by pyrimethamine (PYR); however, this was intolerable by many patients. The aim of this study was to assess therapeutic effects of Nigella sativa oil (NSO) alone and combined with pyrimethamine (PYR) compared to a previous combination of clindamycin (CLN) and (PYR). One hundred Albino mice were used in the current study and were equally divided into five groups: normal (I), infected untreated control (II); infected, treated with NSO-only (III); infected, treated with NSO + PYR (IV); and infected, treated with CLN + PYR (V). The virulent RH Toxoplasma strain was used in infection survival rates estimation, impression smears from liver and spleen, and histopathological and ultrastructural studies were done. Liver malondialdehyde (MDA) level and total antioxidant capacity (TAC) were determined. Interferon-γ and specific IgM were also measured in sera by ELISA. Results showed that NSO alone has no direct anti-Toxoplasma effect, whereas its combination with PYR produced potent effect that is comparable to CLN + PYR. It significantly increased the survival rate and decreased the parasite density and pathological insult in both liver and spleen. Also, significant increase in interferon-γ level denotes stimulation of cellular immunity. NSO + PYR combination markedly improved the antioxidant capacity of Toxoplasma infected mice compared to the infected untreated ones and to CLN/PYR. In conclusion, although NSO, if administered alone, has significant immunostimulant and antioxidant properties, it failed to decrease tachyzoite counts. Combination of NSO and PYR had synergistic effect in treatment of toxoplasmosis.
Full Text Available Abstract Background Mechanisms underlying pain in chronic pancreatitis (CP are incompletely understood. Our previous data showed that astrocytes were actively involved. However, it was unclear how astrocytic activation was induced in CP conditions. In the present study, we hypothesized that toll-like receptors (TLRs were involved in astrocytic activation and pain behavior in CP-induced pain. Results To test our hypothesis, we first investigated the changes of TLR2-4 in the rat CP model induced by intrapancreatic infusion of trinitrobenzene sulfonic acid (TNBS. Western blot showed that after TNBS infusion, TLR3, but not TLR2 or TLR4, was increased gradually and maintained at a very high level for up to 5 w, which correlated with the changing course of mechanical allodynia. Double immunostaining suggested that TLR3 was highly expressed on astrocytes. Infusion with TLR3 antisense oligodeoxynucleotide (ASO dose-dependently attenuated CP-induced allodynia. CP-induced astrocytic activation in the spinal cord was also significantly suppressed by TLR3 ASO. Furthermore, real-time PCR showed that IL-1β, TNF-α, IL-6 and monocyte chemotactic protein-1 (MCP-1 were significantly increased in spinal cord of pancreatic rats. In addition, TLR3 ASO significantly attenuated CP-induced up-regulation of IL-1β and MCP-1. Conclusions These results suggest a probable "TLR3-astrocytes-IL-1β/MCP-1" pathway as a positive feedback loop in the spinal dorsal horn in CP conditions. TLR3-mediated neuroimmune interactions could be new targets for treating persistent pain in CP patients.
Alzoubi, K H; Abdul-Razzak, K K; Khabour, O F; Al-Tuweiq, G M; Alzubi, M A; Alkadhi, K A
Caffeine alleviates cognitive impairment associated with a variety of health conditions. In this study, we examined the effect of caffeine treatment on chronic stress- and/or high fat-high carbohydrate Western diet (WD)-induced impairment of learning and memory in rats. Chronic psychosocial stress, WD and caffeine (0.3 g/L in drinking water) were simultaneously administered for 3 months to adult male Wistar rats. At the conclusion of the 3 months, and while the previous treatments continued, rats were tested in the radial arm water maze (RAWM) for learning, short-term and long-term memory. This procedure was applied on a daily basis to all animals for 5 consecutive days or until the animal reaches days to criterion (DTC) in the 12th learning trial and memory tests. DTC is the number of days that the animal takes to make zero error in two consecutive days. Chronic stress and/or WD groups caused impaired learning, which was prevented by chronic caffeine administration. In the memory tests, chronic caffeine administration also prevented memory impairment during chronic stress conditions and/or WD. Furthermore, DTC value for caffeine treated stress, WD, and stress/WD groups indicated that caffeine normalizes memory impairment in these groups. These results showed that chronic caffeine administration prevented stress and/or WD-induced impairment of spatial learning and memory.
Angelini Daniel J
Full Text Available Abstract Background Both chronic hypoxia and allergic inflammation induce vascular remodeling in the lung, but only chronic hypoxia appears to cause PH. We investigate the nature of the vascular remodeling and the expression and role of hypoxia-induced mitogenic factor (HIMF/FIZZ1/RELMα in explaining this differential response. Methods We induced pulmonary vascular remodeling through either chronic hypoxia or antigen sensitization and challenge. Mice were evaluated for markers of PH and pulmonary vascular remodeling throughout the lung vascular bed as well as HIMF expression and genomic analysis of whole lung. Results Chronic hypoxia increased both mean pulmonary artery pressure (mPAP and right ventricular (RV hypertrophy; these changes were associated with increased muscularization and thickening of small pulmonary vessels throughout the lung vascular bed. Allergic inflammation, by contrast, had minimal effect on mPAP and produced no RV hypertrophy. Only peribronchial vessels were significantly thickened, and vessels within the lung periphery did not become muscularized. Genomic analysis revealed that HIMF was the most consistently upregulated gene in the lungs following both chronic hypoxia and antigen challenge. HIMF was upregulated in the airway epithelial and inflammatory cells in both models, but only chronic hypoxia induced HIMF upregulation in vascular tissue. Conclusions The results show that pulmonary vascular remodeling in mice induced by chronic hypoxia or antigen challenge is associated with marked increases in HIMF expression. The lack of HIMF expression in the vasculature of the lung and no vascular remodeling in the peripheral resistance vessels of the lung is likely to account for the failure to develop PH in the allergic inflammation model.
Marsha L Quick
Full Text Available The etiology of chronic prostatitis/chronic pelvic pain syndrome in men is unknown but may involve microbes and autoimmune mechanisms. We developed an infection model of chronic pelvic pain in NOD/ShiLtJ (NOD mice with a clinical Escherichia coli isolate (CP-1 from a patient with chronic pelvic pain. We investigated pain mechanisms in NOD mice and compared it to C57BL/6 (B6 mice, a strain resistant to CP-1-induced pain. Adoptive transfer of CD4+ T cells, but not serum, from CP-1-infected NOD mice was sufficient to induce chronic pelvic pain. CD4+ T cells in CP-1-infected NOD mice expressed IFN-γ and IL-17A but not IL-4, consistent with a Th1/Th17 immune signature. Adoptive transfer of ex-vivo expanded IFN-γ or IL-17A-expressing cells was sufficient to induce pelvic pain in naïve NOD recipients. Pelvic pain was not abolished in NOD-IFN-γ-KO mice but was associated with an enhanced IL-17A immune response to CP1 infection. These findings demonstrate a novel role for Th1 and Th17-mediated adaptive immune mechanisms in chronic pelvic pain.
Bonaventura, Paola; Lamboux, Aline; Albarède, Francis; Miossec, Pierre
Zinc (Zn) has major effects on immune system activation while Cadmium (Cd) has anti-inflammatory and anti-proliferative effects in several chronic inflammatory contexts. The aim of this work was to investigate by which mechanisms Zn could compete with Cd and eventually counteract its deleterious effects. Rheumatoid arthritis (RA) synoviocytes exposed to cytokines were used as a model of chronic inflammation; osteoarthritis (OA) synoviocytes were used as control. Cell/medium fractionation constants were analyzed for different metals by inductively-coupled-plasma mass-spectrometry by comparison to the 70Zn spike. Interleukin-17 (IL-17) and tumor necrosis factor-alpha (TNF-α) were used to mimic inflammation. Gene expression of ZIP-8 importer, metallothioneins-1 (MT-1s) and the ratio between metalloprotease-3 and the tissue inhibitor of metalloproteinases (MMP-3)/TIMP-1) were evaluated after pre-exposure to cytokines and Cd, with or without the addition of exogenous Zn (0.9 ppm). Cell viability was measured by neutral red assay and IL-6 production by ELISA. Synoviocytes selectively absorbed and retained Cd in comparison to Zn. Metal import increased with IL-17/TNF-α exposure, through the enhanced ZIP-8 expression. Zn did not modify ZIP-8 expression, while Cd reduced it (p<0.05). Zn induced a reduction of Cd-induced MT-1s expression, in particular of MT-1X (3-fold), and subsequently the final intra-cellular content of Cd. By reducing Cd accumulation in cells, Zn reversed Cd anti-proliferative and anti-inflammatory effects but preserved the low MMP-3/TIMP-1 ratio induced by Cd, which was enhanced by inflammatory conditions. Zinc counteracts the deleterious effect of Cd by reducing its import and accumulation in the cell, without the reactivation of destructive pathways such as MMPs.
Schneider, Johanna; Lother, Achim; Hein, Lutz; Gilsbach, Ralf
Increased activity of the sympathetic system is an important feature contributing to the pathogenesis and progression of chronic heart failure. While the mechanisms and consequences of enhanced norepinephrine release from sympathetic nerves have been intensely studied, the role of the adrenal gland in the development of cardiac hypertrophy and progression of heart failure is less well known. Thus, the aim of the present study was to determine the effect of chronic cardiac pressure overload in mice on adrenal medulla structure and function. Cardiac hypertrophy was induced in wild-type mice by transverse aortic constriction (TAC) for 8 weeks. After TAC, the degree of cardiac hypertrophy correlated significantly with adrenal weight and adrenal catecholamine storage. In the medulla, TAC caused an increase in chromaffin cell size but did not result in chromaffin cell proliferation. Ablation of chromaffin α(2C)-adrenoceptors did not affect adrenal weight or epinephrine synthesis. However, unilateral denervation of the adrenal gland completely prevented adrenal hypertrophy and increased catecholamine synthesis. Transcriptome analysis of microdissected adrenal medulla identified 483 up- and 231 downregulated, well-annotated genes after TAC. Among these genes, G protein-coupled receptor kinases 2 (Grk2) and 6 and phenylethanolamine N-methyltransferase (Pnmt) were significantly upregulated by TAC. In vitro, acetylcholine-induced Pnmt and Grk2 expression as well as enhanced epinephrine content was prevented by inhibition of nicotinic acetylcholine receptors and Ca(2+)/calmodulin-dependent signaling. Thus, activation of preganglionic sympathetic nerves innervating the adrenal medulla plays an essential role in inducing adrenal hypertrophy, enhanced catecholamine synthesis and induction of Grk2 expression after cardiac pressure overload.
María F Ferrer
Full Text Available Leptospirosis is a global zoonosis caused by pathogenic Leptospira, which can colonize the proximal renal tubules and persist for long periods in the kidneys of infected hosts. Here, we characterized the infection of C57BL/6J wild-type and Daf1-/- mice, which have an enhanced host response, with a virulent Leptospira interrogans strain at 14 days post-infection, its persistence in the kidney, and its link to kidney fibrosis at 90 days post-infection. We found that Leptospira interrogans can induce acute moderate nephritis in wild-type mice and is able to persist in some animals, inducing fibrosis in the absence of mortality. In contrast, Daf1-/- mice showed acute mortality, with a higher bacterial burden. At the chronic stage, Daf1-/- mice showed greater inflammation and fibrosis than at 14 days post-infection and higher levels at all times than the wild-type counterpart. Compared with uninfected mice, infected wild-type mice showed higher levels of IL-4, IL-10 and IL-13, with similar levels of α-smooth muscle actin, galectin-3, TGF-β1, IL-17, IFN-γ, and lower IL-12 levels at 90 days post-infection. In contrast, fibrosis in Daf1-/- mice was accompanied by high expression of α-smooth muscle actin, galectin-3, IL-10, IL-13, and IFN-γ, similar levels of TGF-β1, IL-12, and IL-17 and lower IL-4 levels. This study demonstrates the link between Leptospira-induced murine chronic nephritis with renal fibrosis and shows a protective role of Daf1.
Ferrer, María F; Scharrig, Emilia; Alberdi, Lucrecia; Cedola, Maia; Pretre, Gabriela; Drut, Ricardo; Song, Wen-Chao; Gomez, Ricardo M
Leptospirosis is a global zoonosis caused by pathogenic Leptospira, which can colonize the proximal renal tubules and persist for long periods in the kidneys of infected hosts. Here, we characterized the infection of C57BL/6J wild-type and Daf1-/- mice, which have an enhanced host response, with a virulent Leptospira interrogans strain at 14 days post-infection, its persistence in the kidney, and its link to kidney fibrosis at 90 days post-infection. We found that Leptospira interrogans can induce acute moderate nephritis in wild-type mice and is able to persist in some animals, inducing fibrosis in the absence of mortality. In contrast, Daf1-/- mice showed acute mortality, with a higher bacterial burden. At the chronic stage, Daf1-/- mice showed greater inflammation and fibrosis than at 14 days post-infection and higher levels at all times than the wild-type counterpart. Compared with uninfected mice, infected wild-type mice showed higher levels of IL-4, IL-10 and IL-13, with similar levels of α-smooth muscle actin, galectin-3, TGF-β1, IL-17, IFN-γ, and lower IL-12 levels at 90 days post-infection. In contrast, fibrosis in Daf1-/- mice was accompanied by high expression of α-smooth muscle actin, galectin-3, IL-10, IL-13, and IFN-γ, similar levels of TGF-β1, IL-12, and IL-17 and lower IL-4 levels. This study demonstrates the link between Leptospira-induced murine chronic nephritis with renal fibrosis and shows a protective role of Daf1.
Full Text Available Toxoplasma gondii is the causative agent for toxoplasmosis. The rhoptry protein 1 (ROP1 is secreted by rhoptry, an apical secretory organelle of the parasite. ROP1 plays an important role in host cell invasion. In this study, the efficacy of ROP1 as a vaccine candidate against toxoplasmosis was evaluated through intramuscular or subcutaneous injection of BALB/c mice followed by immunological characterization (humoral- and cellular-mediated and lethal challenge against virulent T. gondii RH strain in BALB/c mice. Briefly, a recombinant DNA plasmid (pVAX1-GFP-ROP1 was expressed in CHO cells while expression of recombinant ROP1 protein (rROP1 was carried out in Escherichia coli expression system. Immunization study involved injection of the recombinant pVAX1-ROP1 and purified rROP1 into different group of mice. Empty vector and PBS served as two different types of negative controls. Results obtained demonstrated that ROP1 is an immunogenic antigen that induced humoral immune response whereby detection of a protein band with expected size of 43 kDa was observed against vaccinated mice sera through western blot analysis. ROP1 antigen was shown to elicit cellular-mediated immunity as well whereby stimulated splenocytes with total lysate antigen (TLA and rROP1 from pVAX1-ROP1 and rROP1-immunized mice respectively readily proliferated and secreted large amount of IFN-γ (712±28.1 pg/ml and 1457±31.19 pg/ml respectively and relatively low IL-4 level (94±14.5 pg/ml and 186±14.17 pg/ml respectively. These phenomena suggested that Th1-favored immunity was being induced. Vaccination with ROP1 antigen was able to provide partial protection in the vaccinated mice against lethal challenge with virulent RH strain of tachyzoites. These findings proposed that the ROP1 antigen is a potential candidate for the development of vaccine against toxoplasmosis.
Bojovic, Ognjen; Bramham, Clive R; Tjølsen, Arne
Synaptic plasticity is a property of neurons that can be induced by conditioning electrical stimulation (CS) of afferent fibers in the spinal cord. This is a widely studied property of spinal cord and hippocampal neurons. CS has been shown to trigger enhanced expression of immediate early gene proteins (IEGPs), with peak increases observed 2 hour post stimulation. Chronic morphine treatment has been shown to promoteinduce opioid-induced hyperalgesia, and also to increase CS-induced central sensitization in the dorsal horn. As IEGP expression may contribute to development of chronic pain states, we aimed to determine whether chronic morphine treatment affects the expression of IEGPs following sciatic nerve CS. Changes in expression of the IEGPs Arc, c-Fos or Zif268 were determined in cells of the lumbar dorsal horn of the spinal cord. Chronic Morphine pretreatment over 7 days led to a significant increase in the number of IEGP positive cells observed at both 2 h and 6 h after CS. The same pattern of immunoreactivity was obtained for all IEGPs, with peak increases occurring at 2 h post CS. In contrast, morphine treatment alone in sham operated animals had no effect on IEGP expression. We conclude that chronic morphine treatment enhances stimulus-induced expression of IEGPs in the lumbar dorsal horn. These data support the notion that morphine alters gene expression responses linked to nociceptive stimulation and plasticity.
Morella Bouchard Pereira
Full Text Available El objetivo de este estudio fue evaluar en muestras de suero y humor acuoso los niveles de anticuerpos anti-toxoplasma a través del Coeficiente de Goldmann y Witmer (CGW y el patrón de reconocimiento antigénico a través del immunoblotting (IB, en pacientes con serología positiva con y sin lesiones de toxoplasmosis ocular. Se recogieron simultáneamente muestras de suero y humor acuoso de 26 pacientes: un grupo de casos que poseían lesiones retinales de toxoplasmosis ocular en fase activa e inactiva (n=17 y un grupo control que requería cirugía ocular por presencia de cataratas (n=9. Las determinación de IgM e IgG específicas se realizó por ELISA de inmunocaptura e indirecto, respectivamente. Se utilizó la inmunodifusión radial para la cuantificación de la IgG total. El CGW resultó >2, indicativo de producción local de anticuerpos específicos en 12/17 de los casos, mientras que en los controles no se observó, esto evidenció una sensibilidad del 71% y una especificidad de 100%. En IB, la aparición de bandas diferentes en humor acuoso, indicativo de producción local de anticuerpos específicos se observaron en 11/17 de los casos y 1/9 de los controles, reflejando una sensibilidad de 65% y una especificidad de 89%. Al considerar las dos pruebas la sensibilidad se incrementó a un 73%, pero la especificidad disminuyó a 89%. En conclusión el IB es útil como prueba confirmatoria para diagnóstico de toxoplasmosis ocular, pero sólo como un complemento del coeficiente de GW especialmente en pacientes con lesiones atípicas donde el diagnóstico clínico es difícil. Aqueous humor and serum immunoblotting profiles and anti–toxoplasma gondii antibodies in patients with toxoplasmosis-induced retinal lesions Abstract The purpose of this study was to analize the anti-Toxoplasma gondii antibodies levels in serum and aqueous humor samples in patients with ocular toxoplasmosis by using Goldman and Witmer Coefficient (GWC and the
Full Text Available AbstractBackground and Purpose: According to the previous studies, Toxoplasma gondii excreted / secreted antigens (E/SA appear to be suitable marker for serodiagnosis of toxoplasmosis. Most of the previous studies used whole E/SA. The present study, was carried out to evaluate the ELISA method using E/SA components from Toxoplasma gondii for the diagnosis of toxoplasmosis.Materials and Methods: Components obtained by incubation of tachiziotes at RPMI-1640 culture medium were purified by Ion exchange chromatogeraphy and fractions were analyzed by native-PAGE electrophoresis. Forty noninfected rats were injected as IP with 4×106 Toxoplasma tachyzoites and their serum samples were collected at 8, 15, 22 and 60 days after infection then were tested by dye-test. Based on these results the sera of 15 and 60 days were selected and tested by ELISA using E/SA.Results: Second fraction of chromatography was selected as antigens. The cut-off point of ELISA with 99% confidence was found to be 0.41. Optical density of all sera samples of 15 and 3 of 60 days after infection and 2 negative sera were over the test cut-off. Therefore sensitivity and specificity of the method were determined to be 100% and 91% respectively.Conclusion: These results indicated that the second fraction of Ion exchange chromatography of Toxoplasma E/SA under these conditions may be useful tool for the serediagnosis and differentiation of acute and chronic phases of toxoplasmosis. J Mazand Univ Med Sci 2008; 18(65:42-51 (Persian
Falkencronec, Sidsel; Poulsen, Lars; Maurer, Marcus; Bindslev-Jensen, Carsten; Skov, Per Stahl
Background Previous studies from our group have demonstrated that IgE-mediated basophil activation leads to release of TNFα that in turn can induce matrix metallo-proteinase-9 (MMP-9) release from monocytes. We wished to investigate if serum from chronic spontaneous urticaria-patients with auto-antibodies against IgE/IgE-receptor could induce TNFα and MMP-9 release from donor PBMCs, and if release levels could be used to assess severity and activity of chronic spontaneous urticaria (CSU). Met...
El-Zawawy, Lobna A; El-Said, Doaa; Mossallam, Shereen F; Ramadan, Heba S; Younis, Salwa S
Efficacy of triclosan (TS) and TS-loaded liposomes against the virulent strain of Toxoplasma gondii (T. gondii) was evaluated. Swiss albino mice were intraperitoneally infected with 10(4) tachyzoites of RH HXGPRT(-) strain of T. gondii, then were orally treated with 150 mg/kg TS or 100 mg/kg TS liposomes twice daily for 4 days. Mice mortality, peritoneal and liver parasite burdens, viability, infectivity and ultrastructural changes of peritoneal tachyzoites of infected treated mice were studied, in comparison with those of infected non-treated controls. Drug safety was biochemically assessed by measuring liver enzymes and thyroxin. Both TS and TS liposomes induced significant reduction in mice mortality, parasite burden, viability and infectivity of tachyzoites harvested from infected treated mice. Scanning electron microscopy of treated tachyzoites showed distorted shapes, reduced sizes, irregularities, surface protrusions, erosions and peeling besides apical region distortion. Transmission electron microscopy showed that treated tachyzoites were intracellularly distorted, had cytoplasmic vacuolation, discontinuous plasma membranes, nuclear abnormalities and disrupted internal structures. Besides, in TS liposomes-treated subgroup, most tachyzoites were seen intracellularly with complete disintegration of the parasite plasma and nuclear membranes, with complete destruction of the internal structures. Biochemical safety of TS and TS liposomes was proven. Accordingly, TS can be considered as a promising alternative to the standard therapy for treating acute murine toxoplasmosis. Liposomal formulation of TS enhanced its efficacy and allowed its use in a lower dose.
Full Text Available BACKGROUND: Chronic obstructive pulmonary disease (COPD is a progressive lung disease characterized by abnormal cellular responses to cigarette smoke, resulting in tissue destruction and airflow limitation. Autophagy is a degradative process involving lysosomal turnover of cellular components, though its role in human diseases remains unclear. METHODOLOGY AND PRINCIPAL FINDINGS: Increased autophagy was observed in lung tissue from COPD patients, as indicated by electron microscopic analysis, as well as by increased activation of autophagic proteins (microtubule-associated protein-1 light chain-3B, LC3B, Atg4, Atg5/12, Atg7. Cigarette smoke extract (CSE is an established model for studying the effects of cigarette smoke exposure in vitro. In human pulmonary epithelial cells, exposure to CSE or histone deacetylase (HDAC inhibitor rapidly induced autophagy. CSE decreased HDAC activity, resulting in increased binding of early growth response-1 (Egr-1 and E2F factors to the autophagy gene LC3B promoter, and increased LC3B expression. Knockdown of E2F-4 or Egr-1 inhibited CSE-induced LC3B expression. Knockdown of Egr-1 also inhibited the expression of Atg4B, a critical factor for LC3B conversion. Inhibition of autophagy by LC3B-knockdown protected epithelial cells from CSE-induced apoptosis. Egr-1(-/- mice, which displayed basal airspace enlargement, resisted cigarette-smoke induced autophagy, apoptosis, and emphysema. CONCLUSIONS: We demonstrate a critical role for Egr-1 in promoting autophagy and apoptosis in response to cigarette smoke exposure in vitro and in vivo. The induction of autophagy at early stages of COPD progression suggests novel therapeutic targets for the treatment of cigarette smoke induced lung injury.
Ali, Badreldin H; Alza'abi, Mohamed; Ramkumar, Aishwarya; Al-Lawati, Intisar; Waly, Mostafa I; Beegam, Sumaya; Nemmar, Abderrahim; Brand, Susanne; Schupp, Nicole
Activated charcoal (AC) is a sorbent that has been shown to remove urinary toxins like urea and indoxyl sulfate. Here, the influence of AC on kidney function of rats with experimental chronic renal failure (CRF) is investigated. CRF was induced in rats by feeding adenine (0.75%) for four weeks. As an intervention, AC was added to the feed at concentrations of 10%, 15% or 20%. Adenine treatment impaired kidney function: it lowered creatinine clearance and increased plasma concentrations of creatinine, urea, neutrophil gelatinase-associated lipocalin and vanin-1. Furthermore, it raised plasma concentrations of the uremic toxins indoxyl sulfate, phosphate and uric acid. Renal morphology was severely damaged and histopathological markers of inflammation and fibrosis were especially increased. In renal homogenates, antioxidant indices, including superoxide dismutase and catalase activity, total antioxidant capacity and reduced glutathione were adversely affected. Most of these changes were significantly ameliorated by dietary administration of AC at a concentration of 20%, while effects induced by lower doses of dietary AC on adenine nephrotoxicity were not statistically significant. The results suggest that charcoal is a useful sorbent agent in dietary adenine-induced CRF in rats and that its usability as a nephroprotective agent in human kidney disease should be studied.
Carbon tetrachloride (CCl(4)) is a well-known hepatotoxicant, and its exposure induces hepatorenal injury via oxidative stress and biochemical alterations. This study had been conducted to confirm the protective role of propolis extract on CCl(4)-induced hepatorenal oxidative stress and resultant injury. Propolis extracts collected from Gwalior district and 24 female Sprague Dawley rats were used for experiment. Animals were exposed to CCl(4) (0.15 mL/kg, i.p.) for 12 weeks (5 days/week) followed by treatment with propolis extract (200 mg/kg, p.o.) for consecutive 2 weeks. CCl(4) exposure significantly depleted blood sugar and hemoglobin level and raised the level of transaminases, alkaline phosphatase, lactate dehydrogenase, protein, urea, albumin, bilirubin, creatinine, triglycerides, and cholesterol in serum. Lipid peroxidation was enhanced, whereas GSH was decreased significantly in liver and kidney in CCl(4)-intoxicated group. Ethanolic extract of propolis successfully prevented these alterations in experimental animals. Activities of catalase, adenosine triphosphatase, glucose-6-phosphatase, acid, and alkaline phosphatase were also maintained towards normal with propolis therapy. Light microscopical studies showed considerable protection in liver and kidney with propolis treatment, thus, substantiated biochemical observations. This study confirmed hepatoprotective potential of propolis extract against chronic injury induced by CCl(4) by regulating antioxidative defense activities.
Full Text Available Carbon tetrachloride (CCl4 is a well-known hepatotoxicant, and its exposure induces hepatorenal injury via oxidative stress and biochemical alterations. This study had been conducted to confirm the protective role of propolis extract on CCl4-induced hepatorenal oxidative stress and resultant injury. Propolis extracts collected from Gwalior district and 24 female Sprague Dawley rats were used for experiment. Animals were exposed to CCl4 (0.15 mL/kg, i.p. for 12 weeks (5 days/week followed by treatment with propolis extract (200 mg/kg, p.o. for consecutive 2 weeks. CCl4 exposure significantly depleted blood sugar and hemoglobin level and raised the level of transaminases, alkaline phosphatase, lactate dehydrogenase, protein, urea, albumin, bilirubin, creatinine, triglycerides, and cholesterol in serum. Lipid peroxidation was enhanced, whereas GSH was decreased significantly in liver and kidney in CCl4-intoxicated group. Ethanolic extract of propolis successfully prevented these alterations in experimental animals. Activities of catalase, adenosine triphosphatase, glucose-6-phosphatase, acid, and alkaline phosphatase were also maintained towards normal with propolis therapy. Light microscopical studies showed considerable protection in liver and kidney with propolis treatment, thus, substantiated biochemical observations. This study confirmed hepatoprotective potential of propolis extract against chronic injury induced by CCl4 by regulating antioxidative defense activities.
Nikolaos P. Karidis
Full Text Available Chronic hepatitis C virus (HCV infection may eventually lead to progressive liver fibrosis and cirrhosis through a complex, multistep process involving hepatocyte death and regeneration. Despite common pathogenetic pathways present in all forms of liver cirrhosis irrespective of etiology, hepatocyte turnover and related molecular events in HCV-induced cirrhosis are increasingly being distinguished from even “similar” causes, such as hepatitis B virus- (HBV- related cirrhosis. New insights in HCV-induced hepatocellular injury, differential gene expression, and regenerative pathways have recently revealed a different pattern of progression to irreversible parenchymal liver damage. A shift to the significant role of the host immune response rather than the direct effect of HCV on hepatocytes and the imbalance between antiapoptotic and proapoptotic signals have been investigated in several studies but need to be further elucidated. The present review aims to comprehensively summarize the current evidence on HCV-induced hepatocellular turnover with a view to outline the significant trends of ongoing research.
Saskia A Overbeek
Full Text Available BACKGROUND: Cigarette smoking induces inflammatory responses in all smokers and is the major risk factor for lung disease such as chronic obstructive pulmonary disease (COPD. In this progressive disease, chronic inflammation in the lung contributes to lung tissue destruction leading to the formation of chemotactic collagen fragments such as N-acetylated Proline-Glycine-Proline (N-ac-PGP. The generation of this tripeptide is mediated by a multistep pathway involving matrix metalloproteases (MMPs 8 and 9 and prolyl endopeptidase (PE. Here we investigated whether cigarette smoke extract (CSE stimulates human PMNs to breakdown whole matrix collagen leading to the generation of the chemotactic collagen fragment N-ac-PGP. METHODOLOGY/PRINCIPAL FINDINGS: Incubating PMNs with CSE led to the release of chemo-attractant CXCL8 and proteases MMP8 and MMP9. PMNs constitutively expressed PE activity as well as PE protein. Incubating CSE-primed PMNs with collagen resulted in collagen breakdown and in N-ac-PGP generation. Incubation of PMNs with the tripeptide N-ac-PGP resulted in the release of CXCL8, MMP8 and MMP9. Moreover, we tested whether PMNs from COPD patients are different from PMNs from healthy donors. Here we show that the intracellular basal PE activity of PMNs from COPD patients increased 25-fold compared to PMNs from healthy donors. Immunohistological staining of human lung tissue for PE showed that besides neutrophils, macrophages and epithelial cells express PE. CONCLUSIONS: This study indicates that neutrophils activated by cigarette smoke extract can breakdown collagen into N-ac-PGP and that this collagen fragment itself can activate neutrophils, which may lead in vivo to a self-propagating cycle of neutrophil infiltration, chronic inflammation and lung emphysema. MMP-, PE- or PGP-inhibitors can serve as an attractive therapeutic target and may open new avenues towards effective treatment of COPD.
Ibrahim, Marwa K.; Salum, Ghada Maher; Bader El Din, Noha G.; Dawood, Reham M.; Barakat, Ahmed; Khairy, Ahmed; El Awady, Mostafa K.
IFN orchestrates the expression of various genes to halt hepatitis C virus (HCV) replication with the possibility of either reduced or increased liver fibrosis; due to controlled viral replication or overproduction of inflammatory mediators, repectively. In this study, we examined the transcriptional profiling of type I IFN related genes in HCV-chronically infected patients with varying degrees of liver fibrosis. PCR array was used to examine the expression of 84 type I IFN related genes in peripheral blood mononuclear cells (PBMCs) RNA from 12 treatment-naïve chronic HCV patients (5 F0-F1 and 7 F2-F4) and 5 healthy subjects. We further validated our results by quantitative real time PCR (qRT-PCR) in 103 treatment-naïve chronic HCV patients (43 F0-F1 and 60 F2-F4) and 15 controls. PCR array data revealed dysregulation in TLR7 pathway. The expression of TLR7 was decreased by 4 folds and MyD88 was increased by 3 folds in PBMCs of F2-F4 patients when compared to the healthy volunteers (p = 0.03 and 0.002, respectively). In addition, IRF7 and TLR7 showed dramatic downregulation (6 and 8 folds, respectively) in F2-F4 patients when compared to F0-F1 ones. qRT-PCR confirmed the altered expression patterns of TLR7 and MyD88 in F2-F4 patients when compared to either controls or F0-F1 patients. However, by qRT-PCR, IRF7 and NF-κB1 (TLR7 pathway transcription factors) exhibited similar mRNA abundance among F2-F4 and F0-F1 patients. These results suggest that TLR7 and MyD88 are possible candidates as biomarkers for the progression of HCV-induced liver fibrosis and/ or targets for therapeutic intervention. PMID:27135246
Ibrahim, Marwa K; Salum, Ghada Maher; Bader El Din, Noha G; Dawood, Reham M; Barakat, Ahmed; Khairy, Ahmed; El Awady, Mostafa K
IFN orchestrates the expression of various genes to halt hepatitis C virus (HCV) replication with the possibility of either reduced or increased liver fibrosis; due to controlled viral replication or overproduction of inflammatory mediators, repectively. In this study, we examined the transcriptional profiling of type I IFN related genes in HCV-chronically infected patients with varying degrees of liver fibrosis. PCR array was used to examine the expression of 84 type I IFN related genes in peripheral blood mononuclear cells (PBMCs) RNA from 12 treatment-naïve chronic HCV patients (5 F0-F1 and 7 F2-F4) and 5 healthy subjects. We further validated our results by quantitative real time PCR (qRT-PCR) in 103 treatment-naïve chronic HCV patients (43 F0-F1 and 60 F2-F4) and 15 controls. PCR array data revealed dysregulation in TLR7 pathway. The expression of TLR7 was decreased by 4 folds and MyD88 was increased by 3 folds in PBMCs of F2-F4 patients when compared to the healthy volunteers (p = 0.03 and 0.002, respectively). In addition, IRF7 and TLR7 showed dramatic downregulation (6 and 8 folds, respectively) in F2-F4 patients when compared to F0-F1 ones. qRT-PCR confirmed the altered expression patterns of TLR7 and MyD88 in F2-F4 patients when compared to either controls or F0-F1 patients. However, by qRT-PCR, IRF7 and NF-κB1 (TLR7 pathway transcription factors) exhibited similar mRNA abundance among F2-F4 and F0-F1 patients. These results suggest that TLR7 and MyD88 are possible candidates as biomarkers for the progression of HCV-induced liver fibrosis and/ or targets for therapeutic intervention.
SHANG Ming-hua; YUAN Wei-jie; ZHANG Shujian; FAN Yu; ZHANG Zheng
Background The relationship between cyclosporine-induced chronic nephrotoxicity (CAN) and renin-angiotenein Ⅱ in humans is still contradictory. This study was conducted to detect the levels of renin and angiotensin Ⅱ (ANGII) both in renal tissue and plasma from kidney transplantation patients suffering from CAN.Methods Twenty-six patients with allograft biopsy-proven CsA-related chronic nephrotoxicity (CAN group) and chronic rejection (control group) were enrolled in this study. Renal tissues were subjected to immunohistochemical staining with renin and ANGII antibodies. Renin and ANGII plasma levels were measured when the biopsy was performed. The relationship between expression of renin or ANGII and clinicopathological manifestations were also investigated. The cyclosporine plasma level was obtained 2 hours after morning dose (C2). In vitro, human umbilical vein endothelial cells (HUVEC) and rat mesangial cells (MC) were incubated with different concentrations of CsA (0, 250, 500, 1000 μg/L) for 24 hours. Secretion and expression of renin and ANGII was measured by radioimmunoassay or immunohistochemical staining.Results Renal pathological scores for renin and ANGII expression were significantly higher in specimens of CAN than in controls (P＜0.05). The plasma levels of renin, ANGII and C2 in the CAN group were higher than the control group, but no significant difference was found ((0.37±0.12) ng.ml-1·h-1 vs (0.20±0.10) ng.ml-1·h-1, P=0.076; (122.69±26.73) pg/ml vs(121.88±36.35) pg/ml, P=0.977; (719.04±55.89) ng/ml vs (658.80±90.78) ng/ml, P=0.196, respectively). In vitro, renin as well as ANGII expression increased significantly in both HUVEC and MC after the cells were incubated with CsA for 24 hours (P ＜0.05). CsA also stimulated the secretion of ANGII in HUVEC and MC in a dose-dependent manner.Conclusions Renal allograft biopsy is important to differentiate chronic CsA-related nephropathy from chronic rejection. The intrarenal renin angiotensin
Yuxi Liu; Weicheng Hao; Xiaoming Yang; Yimin Wang; Yu Su
The present study analyzed a patient with epilepsy due to chronic inflammation on the cerebral surface underwent sudden cardiac arrest. Paradoxical brain discharge, which occurred prior to epileptic seizures, induced a sudden cardiac arrest. However, when the focal brain pressure was relieved, cardiac arrest disappeared. A 27-year-old male patient underwent pre-surgical video-electroencephalogram monitoring for 160 hours. During monitoring, secondary tonic-clonic seizures occurred five times. A burst of paradoxical brain discharges occurred at 2-19 seconds (mean 8 seconds) prior to epileptic seizures. After 2-3 seconds, sudden cardiac arrest occurred and lasted for 12-22 seconds (average 16 seconds). The heart rate subsequently returned to a normal rate. Results revealed arachnoid pachymenia and adhesions, as well as mucus on the focal cerebral surface, combined with poor circulation and increased pressure. Intracranial electrodes were placed using surgical methods. Following removal of the arachnoid adhesions and mucus on the local cerebral surface, paradoxical brain discharge and epileptic seizures occurred three times, but sudden cardiac arrest was not recorded during 150-hour monitoring. Post-surgical histological examination indicated meningitis. Experimental findings suggested that paradoxical brain discharge led to cardiac arrest instead of epileptic seizures; the insult was associated with chronic inflammation on the cerebral surface, which subsequently led to hypertension and poor blood circulation in focal cerebral areas.
Full Text Available Abstract Hypersecretion and chronic phlegm are major symptoms of chronic obstructive pulmonary disease (COPD but animal models of COPD with a defined functional hypersecretion have not been established so far. To identify an animal model of combined morphological signs of airway inflammation and functional hypersecretion, rats were continuously exposed to different levels of sulfur dioxide (SO2, 5 ppm, 10 ppm, 20 ppm, 40 ppm, 80 ppm for 3 (short-term or 20–25 (long-term days. Histology revealed a dose-dependent increase in edema formation and inflammatory cell infiltration in short-term-exposed animals. The submucosal edema was replaced by fibrosis after long-term-exposure. The basal secretory activity was only significantly increased in the 20 ppm group. Also, stimulated secretion was significantly increased only after exposure to 20 ppm. BrdU-assays and AgNOR-analysis demonstrated cellular metaplasia and glandular hypertrophy rather than hyperplasia as the underlying morphological correlate of the hypersecretion. In summary, SO2-exposure can lead to characteristic airway remodeling and changes in mucus secretion in rats. As only long-term exposure to 20 ppm leads to a combination of hypersecretion and airway inflammation, only this mode of exposure should be used to mimic human COPD. Concentrations less or higher than 20 ppm or short term exposure do not induce the respiratory symptom of hypersecretion. The present model may be used to characterize the effects of new compounds on mucus secretion in the background of experimental COPD.
Umashankar, P R; Arun, T; Kumary, T V
Decellularised tissue produces a variety of host responses ranging from constructive remodeling to scarring on account of its differences in the source of tissue, processing or sterilization methods. In this study, in vivo regeneration induced by decellularised bovine pericardium with or without mild glutaraldehyde crosslinking was studied in relation to its immune and inflammatory response using rat abdominal regeneration model. Mild glutaraldehyde crosslinking was done to subdue inflammatory and immune response without compromising host cell incorporation and graft remodeling. Evaluations were done at both 21 and 90 days. Un-crosslinked decellularised bovine pericardium showed more intense macrophage response predominantly of M2 phenotype at 90 days indicating chronic inflammatory response compared to mildly crosslinked group. This group also showed significant increase in plasma cell and lymphocyte count indicating immune stimulation. Lymphocyte transformation test detected presence of bovine pericardial antigen sensitized lymphocytes at both periods in un-crosslinked group. Lymphocytes from mildly crosslinked group failed to respond in this test at both periods. Significantly higher antibody response was also noted at both periods in un-crosslinked group. However, abdominal wall regeneration was observed only in animals implanted with un-crosslinked decellularised bovine pericardium at 90 days. From the above findings, it is inferred that un-crosslinked decellularised bovine pericardium produced significant chronic inflammatory response at 90 days and stimulated both humoral and cell mediated immune response in comparison to mildly crosslinked decellularised bovine pericardium. Yet this group produced skeletal muscle formation within graft at 90 days. Copyright © 2012 Wiley Periodicals, Inc.
Wang, Yuchan; Kan, Hongwei; Yin, Yanyan; Wu, Wangyang; Hu, Wen; Wang, Mingming; Li, Weiping; Li, Weizu
Alzheimer's disease (AD) is one of the major neurological diseases of the elderly. Chronic stress, which can induce atrophy and functional impairments in several key brain areas such as the frontal cortex and hippocampus, plays an important role in the generation and progression of AD. Currently, there are no effective drug treatment options for preventing chronic stress induced learning and memory impairments and neuronal damage. Ginsenoside Rg1 (Rg1) is a steroidal saponin abundantly contained in ginseng. This study explored the neuroprotective effects of Rg1 on chronic restraint stress (CRS) induced learning and memory impairments in a mouse model. Our results showed that Rg1 (5mg/kg) significantly protected against learning and memory impairments induced by CRS in a Morris water maze. Besides, Rg1 (2, 5mg/kg) was able to decrease ROS generation and attenuate the neuronal oxidative damage in the frontal cortex and hippocampus CA1 in mice. Additionally, the inhibition of NOX2, p47phox and RAC1 expression is also involved in the action mechanisms of Rg1 in this experimental model. This study provided an experimental basis for the clinical application of Rg1 in chronic stress induced neuronal oxidative damage.
Chen, Mayun; Cai, Hui; Yu, Chang; Wu, Peiliang; Fu, Yangyang; Xu, Xiaomei; Fan, Rong; Xu, Cunlai; Chen, Yanfan; Wang, Liangxing; Huang, Xiaoying
Salidroside, an active ingredient isolated from Rhodiola rosea, has shown to exert protective effects against chronic hypoxia-induced pulmonary arterial hypertension (PAH). However, the underlying mechanisms were not well known. Based on our recent reports, we predicted the involvement of adenosine monophosphate-activated protein kinase (AMPK) mediated effects in salidroside regulation of PAH. Firstly, to prove the hypothesis, rats were exposed to chronic hypoxia and treated with increasing concentrations of salidroside or a selective AMPK activator-5'-aminoimidazole-4-carboxamide ribonucleoside (AICAR) for 4 weeks. After salidroside or AICAR treatment, the chronic hypoxia-induced right ventricular hypertrophy and pulmonary artery remodeling were attenuated. Then the effects of salidroside or AICAR on hypoxia-induced excess cellular proliferation and apoptosis resistance of pulmonary arterial smooth muscle cells (PASMCs), which contributed to pulmonary arterial remodeling, were investigated. Our results suggested salidroside, as well as AICAR, reversed hypoxia-induced PASMCs proliferation and apoptosis resistance while AMPK inhibitor Compound C enhanced the effects of hypoxia. To reveal the potential cellular mechanisms, activation of AMPKα1 and expression of the genes related to proliferation and apoptosis were analyzed in PASMCs after salidroside treatment under hypoxia conditions. The results demonstrated salidroside as well as AICAR might inhibit chronic hypoxia-induced PASMCs proliferation via AMPKα1-P53-P27/P21 pathway and reverse apoptosis resistance via AMPKα1-P53-Bax/Bcl-2-caspase 9-caspase 3 pathway.
Full Text Available Nilotinib, a second-generation tyrosine kinase inhibitor, is used for treatment of chronic myeloid leukemia (CML; it has been widely used especially for imatinib-resistant CML. Despite being a novel drug in this therapeutic class, it has the potential to be harmful. We present the case of an elderly woman who developed life-threatening acute pancreatitis as an adverse event after having started the drug. There is only one reported case in the literature of nilotinib-induced acute pancreatitis. The purpose of this case report is to educate physicians who prescribe this medication to be aware of potential life-threatening adverse events. As more and more therapies are available, physicians should be aware of potential effects of cancer treatment that could be life-threatening to patients.
Ali, Badreldin H; Al Balushi, Khalid A; Ashique, Mohammed; Shalaby, Asem; Al Kindi, Mohammed A; Adham, Sirin A; Karaca, Turan; Beegam, Sumaya; Yuvaraju, Priya; Nemmar, Abderrahim
There is a global increase in the popularity of water-pipe tobacco smoking including in Europe and North America. Nevertheless, little is known about the male reproductive effects of water-pipe smoke (WPS), especially after long-term exposure. Here, we assessed effects of WPS exposure (30 min/day) in male mice for 6 months. Control mice were exposed to air-only for the same period of time. Twenty-four hours after the last exposure, testicular histopathology, and markers of inflammation and oxidative stress, and the tyrosine-protein kinase vascular endothelial growth factor receptor 1 (VEGFR1) were assessed in testicular homogenates. Moreover, plasma testosterone, estradiol, and luteinizing hormone (LH) concentrations were also measured. Chronic WPS exposure induced a significant decrease of testosterone and estradiol, and a slight but significant increase of LH. Glutathione reductase, catalase, and ascorbic acid were significantly decreased following WPS exposure. Plasma concentration of leptin was significantly decreased by WPS exposure, whereas that of tumor necrosis factor α and interleukin 6 was significantly increased. Histopathological analysis of the testes revealed the presence of a marked reduction in the diameter of the seminiferous tubules with reduced spermatogenesis. Transmission electron microscopy examination showed irregular thickening and wrinkling of the basement membranes with abnormal shapes and structures of the spermatozoa. VEGFR1 was overexpressed in the testis of the mice exposed to WPS and was not detected in the control. The urine concentration of cotinine, the predominant metabolite of nicotine, was significantly increased in the WPS-exposed group compared with the control group. We conclude that chronic exposure to WPS induces damaging effects to the reproductive system in male mice. If this can be confirmed in humans, it would be an additional concern to an already serious public health problem, especially with the increased use of WPS
Full Text Available We report a case of severe toxoplasmosis in an immunocompetent patient, characterized by pneumonia, retinochoroiditis, hepatitis and myositis. Diagnosis was confirmed by serology, T. gondii in thick blood smear and presence of bradyzoites in muscle biopsy. Treatment with pyrimethamine plus sulfadoxine was successful but visual acuity and hip extension were partially recovered. This is the first case report of severe toxoplasmosis in an immunocompetent patient from Peru.Reportamos un caso de toxoplasmosis severa en un paciente inmunocompetente caracterizado por neumonía, retinocoroiditis, hepatitis y miositis. El diagnóstico fue confirmado por serología, el hallazgo de T. gondii en gota gruesa y la presencia de bradizoitos en biopsia muscular. El tratamiento con pirimetamina mas sulfadoxina fue exitoso pero solo hubo una parcial recuperación de la agudeza visual y de la capacidad de extensión de la cadera. Este es el primer reporte de un caso de toxoplasmosis severa en el Perú.
LI Ru-jun; FANG Wei; ZHU Hua-jiang; ZHANG Feng-xia; XU Ou-fang; XU Li-juan; ZHANG Zhen-gang; GONG Kai-zheng
Emerging evidence has indicated that BRCC 36-mediated K63-linked ubiquitination modification was involved in diverse cellular functions , including endocytosis , apoptosis and DNA damage repair .We previously showed that activation of cGMP/PKG pathway con-tributed to the binding of BRCC36 and the pro-fibrotic factor Smad3.The current study tested the hypothesis that BRCC 36 functions as a negative regulator of transforming growth factor-beta ( TGF-β)/Smad3 pathway and participates in cardiac remodeling .In isolated adult mouse cardiac fibroblasts , we have demonstrated that TGF-β1 treatment significantly increased the expression of BRCC 36.Over-expression BRCC36 suppressed TGF-β1-induced Smad3 phosphorylation, nuclear translocation, extracellular matrix molecular expres-sion and cell proliferation .On the contrary, silencing BRCC36 by transfection of adenovirus-carrying BRCC36 shRNA potentiated to enhance the pro-fibrotic effect of TGF-β.In vivo, under chronic pressure overload condition-induced by transverse aortic constriction , myocardial pro-survival protein Bcl-2 and Mcl-1 expression were significantly decreased and the pro-apoptosis protein Puma was in-creased.However, the cardiac-specific over-expression of BRCC36 significantly increased myocardial Bcl-2 and Mcl-1 and inhibited Puma expression .Interestingly , we also found that sustained pressure overload resulted in a significant myocardial DNA injury in wild type mice, which was characterized by the increase of γH2AX level.However, cardiac-specific BRCC36 over-expression significantly decreased the level of γH2AX in the pressure overloaded heart in the transgenic mice , while effectively enhanced myocardial RAD 51 expression, a marker of DNA damage repair.Furthermore, BRCC36 over-expression effectively attenuated TAC-induced cardiac fibro-sis and remodeling in the transgenic mice , compared with the wild type mice .Collectively , the results have suggested that BRCC 36 ef-fectively protected heart
Tran, L; Chaloner, A; Sawalha, A H; Greenwood Van-Meerveld, B
Epigenetic molecular mechanisms, which include DNA methylation and histone deacetylation, are implicated in the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. Previously, we demonstrated that repeated water avoidance stress (WAS), a validated model of chronic psychological stress, induces heightened visceral pain behaviors in rodents that resemble irritable bowel syndrome (IBS) sequelae. However, the involvement of epigenetic molecular mechanisms in the pathophysiology of stress-induced visceral pain has not been explored. Our hypothesis is that epigenetic mechanisms within the central nervous system (CNS) are important to chronic stress-induced visceral hypersensitivity. Adult male F-344 rats with intracerebroventricular (i.c.v.) cannulae were exposed to 7 days of repeated WAS. Controls received a SHAM stress. Following the daily 1h stressor, trichostatin A (TSA; 100 ng/ml), a potent histone deacetylase inhibitor, or vehicle (VEH; 0.1% DMSO/saline,) as control was administered via the i.c.v. cannula. Visceral sensitivity was assessed 24h after the final WAS and quantified the visceromotor response (VMR) by recording the number of abdominal contractions in response to graded pressures (20-60 mmHg) of colorectal distensions (CRD). From a separate group of rats that were exposed to repeated WAS or SHAM stress, the amygdala was isolated to assess the methylation status of glucocorticoid receptor (GR) and corticotropin releasing-factor (CRF) genes via bisulfite sequencing and verified by pyrosequencing. GR and CRF gene expression was quantified via qRT-PCR. Stressed rats exhibited visceral hypersensitivity that was significantly attenuated by TSA. Compared to SHAM controls, methylation of the GR gene was increased following WAS while expression of the GR gene was decreased. Methylation of the CRF promoter was decreased with WAS with a concomitant increase in CRF expression. This study demonstrates the involvement of central epigenetic mechanisms in
animals that drank water.Conclusions: Ethanol-induced structural liver injury was qualitatively and quantitatively milder in rats which chronically imbibed alcohol then afterward drank NCP beverage in place of water. The antioxidant and anti-inflammatory properties of polyphenols in NCP are postulated in mitigating the damage of rat liver due to chronic ethanol consumption. Thus, it is suggested from these findings that regular drinking of NCP beverage may slow progression of alcoholic liver disease in dipsomaniacs.
Maria Clecia P. Sena
Full Text Available OBJECTIVE: Chronic ethanol consumption is a major public health problem throughout the world. We investigated the anxiolytic-like effects and the possible ever injury induced by the chronic consumption of ethanol or sugarcane spirit in mice. METHOD: Adult mice were exposed to a two-bottle free-choice paradigm for 6 weeks. The mice in Group A (n = 16 had access to sugarcane spirit + distilled water, the mice in Group B (n = 15 had access to ethanol + distilled water, and the mice in Group C (control, n = 14 had access to distilled water + distilled water. The ethanol content in the beverages offered to Groups A and B was 2% for the first week, 5% for the second week and 10% for the remaining four weeks. At the end of the experimental period, the mice were evaluated using the elevated-plus maze and the hole-board test to assess their anxiety-related behaviors. We also determined the serum aspartate aminotransferase and alanine aminotransferase levels. RESULTS: In the elevated-plus maze, the time spent in the open arms was increased in the mice exposed to chronic ethanol (32 + 8 vs. 7 + 2 s, n = 9 or sugarcane spirit (36 + 9 vs. 7 + 2 s, n = 9 compared to the controls. In the hole-board test, the mice exposed to ethanol or sugarcane spirit displayed increases in their head-dipping frequency (16 + 1 for the control group, 27 + 2 for the ethanol group, and 31 + 3 for the sugarcane-spirit group; n = 9 for each group. In addition, the mice exposed to sugarcane spirit displayed an increase in the aspartate aminotransferase / alanine aminotransferase ratio compared to the ethanol group (1.29 + 0.17 for the control group and 2.67 + 0.17 for the sugarcane spirit group; n = 8 for each group. CONCLUSION: The chronic consumption of sugarcane-spirit produces liver injury and anxiolytic-like effects and the possible liver injury in mice.
Jaquenod De Giusti, Carolina; Ure, Agustín E; Rivadeneyra, Leonardo; Schattner, Mirta; Gomez, Ricardo M
Macrophage influx and galectin 3 production have been suggested as major players driving acute inflammation and chronic fibrosis in many diseases. However, their involvement in the pathogenesis of viral myocarditis and subsequent cardiomyopathy are unknown. Our aim was to characterise the role of macrophages and galectin 3 on survival, clinical course, viral burden, acute pathology, and chronic fibrosis in coxsackievirus B3 (CVB3)-induced myocarditis. Our results showed that C3H/HeJ mice infected with CVB3 and depleted of macrophages by liposome-encapsulated clodronate treatment compared with infected untreated mice presented higher viral titres but reduced acute myocarditis and chronic fibrosis, compared with untreated infected mice. Increased galectin 3 transcriptional and translational expression levels correlated with CVB3 infection in macrophages and in non-depleted mice. Disruption of the galectin 3 gene did not affect viral titres but reduced acute myocarditis and chronic fibrosis compared with C57BL/6J wild-type mice. Similar results were observed after pharmacological inhibition of galectin 3 with N-acetyl-d-lactosamine in C3H/HeJ mice. Our results showed a critical role of macrophages and their galectin 3 in controlling acute viral-induced cardiac injury and the subsequent fibrosis. Moreover, the fact that pharmacological inhibition of galectin 3 induced similar results to macrophage depletion regarding the degree of acute cardiac inflammation and chronic fibrosis opens up the possibility of new pharmacological strategies for viral myocarditis.
Dardou, D; Reyrolle, L; Chassain, C; Durif, F
Dopamine replacement therapy (DRT) reduces motor symptoms in Parkinson's disease (PD), but also induces impulsive-compulsive behavior (ICB) in up to 25% of PD patients. These non-motor side effects of DRT generally follow a gradual transition from impulsive to compulsive-like-i.e. repetitive, compelled, and non-pleasurable-behavior. Here, we investigated the effect of chronic pramipexole (PPX) treatment on the onset of compulsive-like behavior, measured via the post-training signal attenuation (PTSA) procedure, in rats with dopaminergic lesions. Accordingly, we aimed to mimic chronic DRT in a PD context, and obtain data on the brain regions that potentially sustain this type of compulsive behavior pattern in rats. We observed that the lesion or treatment alone did not induce compulsive lever pressing in rats. However, rats with lesions of the substantia nigra and ventral tegmental area as well as with chronic PPX treatment developed strong compulsive lever-pressing behavior, as measured via PTSA. Furthermore, when chronic PPX treatment was discontinued before the PTSA test, the lesioned rats showed the same level of compulsive behavior as sham-operated rats. In fact, lesioned, treated, and compulsive-like rats showed significantly higher Fos expression in the orbitofrontal cortex and dorsal striatum. Thus, chronic PPX treatment in PD rats induced a strong compulsive-like behavior. Furthermore, Fos expression mapping suggests that the behavior was sustained via the activation of the orbitofrontal cortex and dorsal striatum. Copyright © 2017 Elsevier B.V. All rights reserved.
Full Text Available Abstract AIM Sleep disturbances induce proinflammatory immune responses, which might increase cardiovascular disease risk. So far the effects of acute sleep deprivation and chronic sleep illnesses on the immune system have been investigated. The particular impact of shift work induced chronic circadian disruption on specific immune responses has not been addressed so far. Methods Pittsburgh-Sleep-Quality-Index (PSQI questionnaire and blood sampling was performed by 225 shift workers and 137 daytime workers. As possible markers the proinflammatory cytokines IL-6 and TNF-α and lymphocyte cell count were investigated. A medical examination was performed and biometrical data including age, gender, height, weight, waist and hip circumference and smoking habits were collected by a structured interview. Results Shift workers had a significantly higher mean PSQI score than day workers (6.73 vs. 4.66; p Conclusion Shift work induces chronic sleep debt. Our data reveals that chronic sleep debt might not always lead to an activation of the immune system, as we did not observe differences in lymphocyte count or level of IL-6 or TNF-α serum concentration between shift workers and day workers. Therefore chronic sleep restriction might be eased by a long-term compensating immune regulation which (in healthy protects against an overstimulation of proinflammatory immune mechanisms and moderates metabolic changes, as they are known from short-term sleep deprivation or sleep related breathing disorders.
Ghiassy, Bentolhoda; Rahimi, Nastaran; Javadi-Paydar, Mehrak; Gharedaghi, Mohammad Hadi; Norouzi-Javidan, Abbas; Dehpour, Ahmad R
Recent studies suggest endogenous opioids and nitric oxide (NO) are involved in the pathophysiology of hepatic encephalopathy (HE). In this study, the interaction between the opioid receptor antagonist and NO was investigated on lipopolysaccharide (LPS)-induced HE in cirrhotic rats. Male rats were divided in the sham- and bile duct ligation (BDL)-operated groups. Animals were treated with saline; naltrexone (10 mg/kg, i.p.); or L-NAME (3 mg/kg, i.p.), alone or in combination with naltrexone. To induce HE, LPS (1 mg/kg, i.p.) was injected 1 h after the final drug treatment. HE scoring, hepatic histology, and plasma NO metabolites levels and mortality rate were recorded. Deteriorated level of consciousness and mortality after LPS administration significantly ameliorated following both acute and chronic treatment with naltrexone in cirrhotic rats. However, acute and chronic administration of L-NAME did not change HE scores in cirrhotic rats. The effects of acute but not chronic treatment of naltrexone on HE parameters were reversed by L-NAME. Plasma NOx concentrations elevated in BDL rats, which were decreased after acute and chronic treatment by naltrexone or L-NAME, significantly. We suggest both acute and chronic treatment with naltrexone improved LPS-induced HE. But, only acute treatment with naltrexone may affect through NO pathway.
Villegas, Isabel; La Casa, Carmen; Orjales, Aurelio; Alarcón de la Lastra, Catalina
Activated neutrophils and proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) are clearly involved in the pathogenesis of bowel disease. Increased expression of epidermal growth factor-receptor (EGF receptor) has been reported for the colon mucosa surrounding areas of ulceration, suggesting a pivotal role in mucosal defence and repair. In this study, we examined the effects of dosmalfate, a new flavonoid derivative compound (diosmin heptakis) with antioxidant and cytoprotective properties, on acute and chronic experimental trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats. The inflammation response was assessed by neutrophil infiltration as evaluated by histology and myeloperoxidase activity. Mucosal TNF-alpha production and histological analysis of the lesions was also carried out. In addition, we studied the expression of the EGF receptor inmunohistochemically during the healing of TNBS-induced chronic colitis. A 2-day treatment with 400 or 800 mg/kg of dosmalfate ameliorated the colon damage score and the incidence of adhesions. It also significantly (P<0.05) decreased myeloperoxidase activity and colonic mucosal production of TNF-alpha. Chronic treatment (14 days) with 800 mg/kg/day of dosmalfate also had significant protective effects on TNBS-induced colitis which were reflected by significant attenuation (P<0.05) of the damage score while the inflammatory indicators were not improved. The chronic beneficial effect of dosmalfate was apparently related to the enhancement of EGF receptor expression. These findings confirm the protective effects of dosmalfate in acute and chronic experimental colitis.
Wimalawansa, Shehani A; Wimalawansa, Sunil J
Environmentally induced, occupational diseases are increasing worldwide, especially in rural agricultural communities. Poverty-associated malnutrition, environmental hazards and pollution, and lack of access to clean water, safe sanitation, and modern healthcare facilities are often associated with these chronic illnesses. The authors systematically reviewed occupational public health issues that have been related to the environment. General interpretations of results were included as per the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Pertinent publications from research databases were reviewed on (A) the risk-benefits, (B) the prevalence of risk factors for various diseases, (C) the benefits of not ignoring the risk factors (i.e., broader evidence), and (D) the risks, effects, and outcomes of different types of interventions. The authors used chronic kidney disease of multifactorial origin (CKDmfo) as an example to explore the theme. Emphasis was given to the regions with emerging economies and developing countries located in the vicinity of the equator. Geographical, socio-economic and aetiological similarities exist for many chronic non-communicable diseases that are affecting tropical countries around the equator. The authors identified manufacturing, mining, and agriculture as the biggest polluters of the environment. In addition, deforestation and associated soil erosion, overuse of agrochemicals, and irresponsible factory discharge (e.g., chemicals and paint, from rubber and textile factories, etc.), all contribute to pollution. To decrease the escalating incidences of environmentally induced diseases, governments should work proactively to protect the environment, especially watersheds, and take steps to minimise harmful occupational exposures and strictly enforce environmental regulations. Creating public awareness of environmental issues and their relationship to public health is essential. This includes
To study the contribution of T cell subsets in the pathogenesis of Murine hepatitis virus Type3 (MHV-3) induced chronic viral hepatitis in C3H/Hej mice, ninety C3H/Hej mice were chosen to individually receive 10 plaque forming units (PFU) of MHV-3 intraperitoneally. The changes of virus titer and pathology in liver tissue were examined by standard plaque assay and by the hematoxylin/eosin (HE) staining method from 2 days post MHV-3 infection. The ratios of T cell subsets including CD3+CD4+CD8-, CD3+CD4-CD8+, CD3+CD4-CD8-, CD3+CD4+CD25+, CD3+CD4+CD25- and CD3+CD4-CD25+ T lymphocyte of total T lymphocytes in blood, spleen and liver were examined at 0, 2, 4, 6,8, 10, 12, 15, 20, 25, 30, 40 days post MHV-3 infection by flow cytosorting. We observed that the virus titer raised and showed persistent virus duplications and inflammatory changes in the livers of C3H/Hej mice from 2 days post MHV-3 infection. The double negative T cell (DN Treg cell) and CD4+CD25+ T cell ratios increased significantly from 2 days post MHV-3 infection in C3H/Hej mice, and CD3+CD4+CD8-, CD3+CD4-CD8+, CD3+CD4+CD25- and CD3+CD4-CD25+ T cell ratios decreased accordingly. In conclusion, the changes of virus titer and pathology in the livers of C3H/Hej mice post MHV-3 suggest their contribution to viral persistence. Further characterizations of DN Treg cells are that infection indicates that MHV-3 could induce the chronic inflammation in livers of C3H/Hej mice.The increase of the DN Treg cell and CD4+CD25+ T cell ratios in C3H/Hej mice post MHV-3 infection suggests that DN Treg cells and CD4+CD25+ T cells may both have important suppressive immunomodulation functions in the development of chronic viral hepatitis and have important roles in the virus persistent infection. Further characterizations of DNT cell and CD4+CD25+ T cell are under investigation.
Matthew J Campen
Full Text Available Exposure to chronic hypoxia (CH induces elevated pulmonary artery pressure/resistance, leading to an eventual maladaptive right ventricular hypertrophy (RVH. Muscle RING finger-1 (MuRF1 is a muscle-specific ubiquitin ligase that mediates myocyte atrophy and has been shown to play a role in left ventricular hypertrophy and altered cardiac bioenergetics in pressure overloaded hearts. However, little is known about the contribution of MuRF1 impacting RVH in the setting of CH. Therefore, we hypothesized that MuRF1 deletion would enhance RVH compared to their wild-type littermates, while cardiac-specific overexpression would reduce hypertrophy following CH-induced pulmonary hypertension. We assessed right ventricular systolic pressure (RVSP, right ventricle to left ventricle plus septal weight ratio (RV/LV+S and hematocrit (Hct following a 3-wk isobaric CH exposure. Additionally, we conducted dual-isotope SPECT/CT imaging with cardiac function agent 201Tl-chloride and cell death agent 99mTc-annexin V. Predictably, CH induced pulmonary hypertension, measured by increased RVSP, RV/LV+S and Hct in WT mice compared to normoxic WT mice. Normoxic WT and MuRF1-null mice exhibited no significant differences in RVSP, RV/LV+S or Hct. CH-induced increases in RVSP were also similar between WT and MuRF1-null mice; however, RV/LV+S and Hct were significantly elevated in CH-exposed MuRF1-null mice compared to WT. In cardiac-specific MuRF1 overexpressing mice, RV/LV+S increased significantly due to CH exposure, even greater than in WT mice. This remodeling appeared eccentric, maladaptive and led to reduced systemic perfusion. In conclusion, these results are consistent with an atrophic role for MuRF1 regulating the magnitude of right ventricular hypertrophy following CH-induction of pulmonary hypertension.
Drapała, Dorota; Holec-Gąsior, Lucyna; Kur, Józef; Ferra, Bartłomiej; Hiszczyńska-Sawicka, Elżbieta; Lautenbach, Dariusz
The preliminary diagnostic utility of two mixtures of Toxoplasma gondii recombinant antigens (rROP1+rSAG2 and rROP1+rGRA6) in IgG ELISA and IgG avidity test has been evaluated. A total of 173 serum samples from patients with toxoplasmosis and seronegative people were examined. The sensitivity of IgG ELISA for rROP1+rSAG2 and rROP1+rGRA6 was 91.1% and 76.7%, respectively, while the reactivity for sera from patients where acute toxoplasmosis was suspected was higher, at 100% and 95.4%, respectively, than for people with chronic infection, at 88.2% and 70.6%. In this study a different trend in avidity maturation of IgG antibodies for two mixtures of proteins in comparison with native antigen was observed. The results suggest that a new IgG avidity test using the mixtures of recombinant antigens may be useful for the diagnosis of difficult-to-identify phases of toxoplasmosis. For this reason, selected mixtures after the additional tests on groups of sera with well-defined dates of infection could be used as a better alternative to the native antigens of the parasite in the serodiagnosis of human T. gondii infection.
Hui XIE; Wing-ho YUNG
Obstructive sleep apnea (OSA) is well known for its metabolic as well as neurobehavioral consequences.Chronic intermittent hypoxia (IH) is a major component of OSA.In recent years,substantial advances have been made in elucidating the cellular and molecular mechanisms underlying the effect of chronic IH on neurocognitive functions,many of which are based on studies in animal models.A number of hypotheses have been put forward to explain chronic IH-induced neurological dysfunctions.Among these,the roles of oxidative stress and apoptosis-related neural injury are widely accepted.Here,focusing on results derived from animal studies,we highlight a possible role of reduced expression of brain-derived neurotrophic factor (BDNF) in causing impairment in long-term synaptic plasticity and neurocognitive functions during chronic IH.The possible relationship between BDNF and previous findings on this subject will be elucidated.