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Sample records for intravenously drug application

  1. Intravenous Antiepileptic Drugs in Russia

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    P. N. Vlasov

    2014-01-01

    Full Text Available Launching four intravenous antiepileptic drugs: valproate (Depakene and Convulex, lacosamide (Vimpat, and levetiracetam (Keppra – into the Russian market has significantly broadened the possibilities of rendering care to patients in seizure emergency situations. The chemi- cal structure, mechanisms of action, indications/contraindications, clinical effectiveness and tolerability, advantages/disadvantages, and adverse events of using these drugs in urgent and elective neurology are discussed. 

  2. Intravenous drug delivery in neonates: lessons learnt.

    Science.gov (United States)

    Sherwin, Catherine M T; Medlicott, Natalie J; Reith, David M; Broadbent, Roland S

    2014-06-01

    Intravenous drug administration presents a series of challenges that relate to the pathophysiology of the neonate and intravenous infusion systems in neonates. These challenges arise from slow intravenous flow rates, small drug volume, dead space volume and limitations on the flush volume in neonates. While there is a reasonable understanding of newborn pharmacokinetics, an appreciation of the substantial delay and variability in the rate of drug delivery from the intravenous line is often lacking. This can lead to difficulties in accurately determining the pharmacokinetic and pharmacodynamic relationship of drugs in the smallest patients. The physical variables that affect the passage of drugs through neonatal lines need to be further explored in order to improve our understanding of their impact on the delivery of drugs by this route in neonates. Through careful investigation, the underlying causes of delayed drug delivery may be identified and administration protocols can then be modified to ensure predictable, appropriate drug input kinetics.

  3. INFECTIVE ENDOCARDITIS IN INTRAVENOUS DRUGS ABUSED PATIENT

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    E. Y. Ponomareva

    2011-01-01

    Full Text Available Three-year observation of acute tricuspid infective endocarditis in intravenous drug abused patient: diagnosis, clinical features, visceral lesions, the possibility of cardiac surgery and conservative treatment, outcome.

  4. Administration costs of intravenous biologic drugs for rheumatoid arthritis

    OpenAIRE

    Soini, Erkki J.; Leussu, Miina; Hallinen, Taru

    2013-01-01

    Background Cost-effectiveness studies explicitly reporting infusion times, drug-specific administration costs for infusions or real-payer intravenous drug cost are few in number. Yet, administration costs for infusions are needed in the health economic evaluations assessing intravenously-administered drugs. Objectives To estimate the drug-specific administration and total cost of biologic intravenous rheumatoid arthritis (RA) drugs in the adult population and to compare the obtained costs wit...

  5. Potential intravenous drug interactions in intensive care

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    Maiara Benevides Moreira

    Full Text Available Abstract OBJECTIVE To analyze potential intravenous drug interactions, and their level of severity associated with the administration of these drugs based on the prescriptions of an intensive care unit. METHOD Quantitative study, with aretrospective exploratory design, and descriptive statistical analysis of the ICU prescriptions of a teaching hospital from March to June 2014. RESULTS The sample consisted of 319 prescriptions and subsamples of 50 prescriptions. The mean number of drugs per patient was 9.3 records, and a higher probability of drug interaction inherent to polypharmacy was evidenced. The study identified severe drug interactions, such as concomitant administration of Tramadol with selective serotonin reuptake inhibitor drugs (e.g., Metoclopramide and Fluconazole, increasing the risk of seizures due to their epileptogenic actions, as well as the simultaneous use of Ranitidine-Fentanyl®, which can lead to respiratory depression. CONCLUSION A previous mapping of prescriptions enables the characterization of the drug therapy, contributing to prevent potential drug interactions and their clinical consequences.

  6. Lichenoid Drug Eruptionfollowing Intravenous Applicationof Orally Formulated Diamorphine, a Semisynthetic Heroin

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    I. Kolm

    2013-06-01

    Full Text Available Background: Lichen planus is a common skin disorder of unknown etiology. Most cases are idiopathic, but substances such as gold, antimalarials, penicillamine, thiazide diuretics, β-blockers, arsenic and nonsteroidal anti-inflammatory drugs have been implicated as trigger factors. Case Presentation: We report the case of a lichenoid eruption in a male drug addict who administered oral heroin (diamorphine intravenously. Diamorphine was stopped immediately. Following topical steroids, phototherapy and oral acitretin, the lesions gradually disappeared. A lymphocyte transformation test was negative for pure morphine and codeine. Discussion: A coincidental association between the intravenous application of orally formulated semisynthetic heroin and the lichenoid eruption cannot be completely ruled out. However, the diagnosis of a lichenoid drug eruption is favoured over idiopathic lichen planus because of the clear chronological correlation between drug use and appearance as well as drug withdrawal and disappearance of the skin lesions, and because of a flare-up following repeated intravenous application of diamorphine.

  7. Avoiding accidental exposure to intravenous cytotoxic drugs.

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    Meade, Elizabeth

    Many cytotoxic drugs have been shown to be mutagenic, teratogenic and carcinogenic with second malignancies known to be associated with several specific cancer drugs. Occupational exposure to cytotoxic drugs presents a signification danger to healthcare staff and unwarranted handling of these drugs should be avoided. Guidelines have been established for the safe handling of hazardous drugs but not all professionals are adhering to these recommendations. Recent environmental studies have demonstrated measurable drug contamination on surfaces even when recommended guidelines are followed. It is therefore imperative that healthcare workers are aware of the potential hazards of antineoplastic agents and employ the recommended precautions to minimise exposure. This article outlines the potential risks associated with exposure to cytotoxic drugs for healthcare staff. The safe-handling precautions required in the storage, preparation, transport, administration and waste disposal of cytotoxic drugs are presented.

  8. 静脉用药调配质量控制的应用评价%Application evaluation of the quality control of the intravenous drugs

    Institute of Scientific and Technical Information of China (English)

    邢孝玲; 张璐; 崔长然; 袁芳; 姬玉芬

    2016-01-01

    目的:探讨静脉用药调配质量控制在静脉用药调配中心(PIV AS)集中调配相关感染控制中的应用效果评价,为临床预防和控制医院感染提供参考依据。方法选择2013年3-12月 PIV AS 配制静脉药液治疗的300例患者和2014年3-12月 PIV AS 实施静脉用药调配质量控制之后治疗的300例患者,对静脉用药调配质量控制实施前后患者住院期间的医院感染情况进行观察;并对两年 PIV AS 相关物品的合格率、空气培养质量、工作人员手卫生以及使用 PIV AS 静脉用药后感染率的统计结果对比。结果2014年 PIV AS 内相关物品的卫生合格率显著优于2013年,差异均有统计学意义(P <0.05);2014年 PIV AS 内空气培养质量和工作人员手卫生合格率显著高于2013年,且差异均有统计学意义(P <0.05);通过质量控制管理后2014年内静脉用药调配和员工操作的出错率明显降低(P <0.05);2014年 PIV AS 配制的静脉药液应用于患者后住院期间出现的医院感染率明显低于2013年(P <0.05)。结论质量控制环节对于 PIV AS 控制医院感染十分关键,能优化 PIV AS 体系的管理,减少药品浪费,减少患者的医院感染现象发生。%OBJECTIVE To explore the effects of the quality control of the intravenous drugs for control of central-ized dispensing-related infection in pharmacy intravenous admixture services (PIV AS),so as to provide the basis for prevention and control of the hospital infection.METHODS A total of 300 cases treated with the intravenous drug of PIV AS from Mar.to Dec.2013,and 300 cases treated with the intravenous drug of PIV AS after the quality control from Mar.to Dec.2014 were selected.The hospital infection of the patients before and after the quality control were observed,and the statistical results of hygiene rates of related items in PIV AS,air quality, hand hygiene of the staff and infection

  9. Candida costochondritis associated with recent intravenous drug use

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    Simeon J. Crawford

    2016-01-01

    Full Text Available Candida osteoarticular infections are being reported with increasing frequency, possibly due to an expanding population at risk. However, Candida costochondritis is uncommon. We report two cases of Candida costochondritis in patients who presented with subacute-onset chest wall swelling and whose only identifiable risk factor was a history of recent intravenous drug use.

  10. The influence of intravenous solution «Neoreodez» on the course of experimental endotoxemia and evaluation of the regenerative properties of drug in the conditions of application

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    Mamchur V.I.

    2016-09-01

    Full Text Available In the experiment it was shown that experimental endotoxemia induced by introduction of carbon tetrachloride and bacterial lipopolysaccharide is characterized by activation of free radical oxidation and failure of antioxidant defense system. Intravenous injection of solution «Neoreodez» under these experimental conditions has a positive impact on the course of endogenous intoxication, which is manifested by decrease in the concentration of MDA and DC in the liver on average by 1Ѕ times (pd0.05, decrease in the level of AlAT and AsAT serum by 2 times (pd0.05 and to restore the balanced functioning of antiradical protection – increased activity of SOD by 1.6 times (p<0.05 in comparison with the performance of the active control. It is established that two-week application «Neoreodez» of solution potentiate the processes of natural reparation of damaged skin.

  11. Smart syringe pumps for drug infusion during dental intravenous sedation.

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    Seo, Kwang-Suk; Lee, Kiyoung

    2016-09-01

    Dentists often sedate patients in order to reduce their dental phobia and stress during dental treatment. Sedatives are administered through various routes such as oral, inhalation, and intravenous routes. Intravenous administration has the advantage of rapid onset of action, predictable duration of action, and easy titration. Typically, midazolam, propofol or dexmedetomidine are used as intravenous sedatives. Administration of these sedatives via infusion by using a syringe pump is more effective and successful than infusing them as a bolus. However, during intravenous infusion of sedatives or opioids using a syringe pump, fatal accidents may occur due to the clinician's carelessness. To prevent such risks, smart syringe pumps have been introduced clinically. They allow clinicians to perform effective sedation by using a computer to control the dose of the drug being infused. To ensure patient safety, various alarm features along with a drug library, which provides drug information and prevents excessive infusion by limiting the dose, have been added to smart pumps. In addition, programmed infusion systems and target-controlled infusion systems have also been developed to enable effective administration of sedatives. Patient-controlled infusion, which allows a patient to control his/her level of sedation through self-infusion, has also been developed. Safer and more successful sedation may be achieved by fully utilizing these new features of the smart pump.

  12. Infective endocarditis in intravenous drug users: a review article.

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    Colville, Thomas; Sharma, Vishal; Albouaini, Khaled

    2016-02-01

    Approximately 10% of infective endocarditis (IE) involves the right side of the heart with the majority of these cases occurring in intravenous drug users. Patients are less likely to present with classical IE signs of a new murmur and peripheral stigmata, are more frequently immunocompromised and often have significant social difficulties. These factors result in both diagnostic and therapeutic challenges in this patient group that are not often seen in other patient populations with IE.

  13. Severe Osteomalacia Related to Long-Term Intravenous Drug Abuse

    OpenAIRE

    Leslie Gamache MD; Mark R. Burge MD

    2014-01-01

    Objective. We present the clinical, biochemical, and imaging findings of a woman with vitamin D deficiency and severe osteomalacia related to intravenous heroin addiction. Results. A 54-year-old woman with a medical history significant for long-standing heroin abuse presented with complaints of bone pain, muscle cramping, and a left hip ulcer. She had been bed bound for approximately 1 year secondary to pain of uncertain etiology, and her husband was bringing her both food and drugs. She was ...

  14. Persistent staphylococcal bacteremia in an intravenous drug abuser.

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    Barg, N L; Supena, R B; Fekety, R

    1986-02-01

    A patient with methicillin-resistant Staphylococcus aureus bacteremia received vancomycin (MIC = 0.8 microgram/ml, MBC = 15 micrograms/ml) and heparin simultaneously through the same intravenous line to treat a septic deep venous thrombosis. Bacteremia persisted for 7 days. Bacteremia terminated when the simultaneous infusion of heparin and vancomycin through the same line was stopped. This suggested that an interaction between vancomycin and heparin may have occurred, which resulted in a reduction in vancomycin activity. To test for such an interaction, mixtures of heparin and vancomycin in various concentrations were made and tested for antimicrobial activity against the organisms in the patient. A precipitate formed at the concentrations achieved in the intravenous lines, and when the vancomycin concentrations were measured by bioassay, a 50 to 60% reduction in activity was noted. In contrast, when these solutions were prepared and mixed at microgram concentrations, a precipitate was no longer observed, and antimicrobial activity was not reduced. Heparin appeared to interact unfavorably with vancomycin at the concentrations in the intravenous lines when these drugs were administered simultaneously to patients. This may be the cause of poor therapeutic responses to vancomycin in some patients, especially those infected with tolerant organisms.

  15. Difficulties with interferon treatment in former intravenous drug users

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    Gábor Gazdag

    2011-04-01

    Full Text Available OBJECTIVES: Intravenous drug use accounts for most of the new hepatitis C infections worldwide. Although there is an urgent need for antiviral treatment of infected intravenous drug users (IDUs, several factors compromise their treatment including lack of treatment adherence and high dropout rate. The aim of this study was to compare antiviral treatment-related problems among former IDUs to HCV-infected patients without a history of IDU. METHODS: This was a retrospective chart review of HCV-infected IDUs who received combined antiviral therapy at the Hepatology Outpatient Clinic of Szent László Hospital between 1 January 2006 and 31 December 2008. A control group of interferon treated patients with no history of IDU matched for age and sex was selected. RESULTS: Dropout rate was significantly higher in the IDU group (p = 0.016. Treatment response at the 12th week of treatment was significantly better in the IDU group (p = 0.004. Significantly more IDUs underwent antiviral treatment while in prison (p = 0.008. CONCLUSIONS: In this study higher dropout rate was found among IDUs. IDUs had a better response rate to antiviral therapy compared to controls. More attention should be paid to factors that worsen treatment adherence of IDUs - particularly lack of abstinence - in order to increase the effectiveness of antiviral therapy.

  16. A ‘brain tumor’ in an intravenous drug abuser

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    Kathir Yoganathan

    2009-04-01

    Full Text Available Kathir YoganathanABM University Trust, Singleton Hospital, Swansea, UKAbstract: A male intravenous drug abuser who was infected with hepatitis B and C, presented with a slowly progressive hemiplegia. Contrast enhanced computerized tomography of the head showed a solitary ring-enhanced mass with surrounding edema. Clinically brain tumor was suspected but a brain biopsy confirmed cerebral toxoplasmosis. An HIV test was not considered until the result of brain biopsy. He also had lymphopenia and positive serum toxoplasma antibody. His subsequent HIV test was positive. He deteriorated after a brain biopsy. Empirical antitoxoplasma treatment is recommended in HIV-positive patients with ring-enhanced lesions with surrounding edema and with positive toxoplasma serology. Cerebral toxoplasmosis is still the commonest cerebral opportunistic infection in HIV-infected patients even though the incidence has declined with the use of antiretroviral therapy. It is often diagnosed in those patients as an initial presentation of HIV infection or in those who failed to attend for disease monitoring. Clinical features and differential diagnosis of cerebral toxoplasmosis in immunocompromised patients are discussed.Keywords: brain tumor, cerebral toxoplasmosis, intravenous drug abuser, primary brain lymphoma, HIV/AIDS

  17. Severe Osteomalacia Related to Long-Term Intravenous Drug Abuse

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    Leslie Gamache MD

    2014-09-01

    Full Text Available Objective. We present the clinical, biochemical, and imaging findings of a woman with vitamin D deficiency and severe osteomalacia related to intravenous heroin addiction. Results. A 54-year-old woman with a medical history significant for long-standing heroin abuse presented with complaints of bone pain, muscle cramping, and a left hip ulcer. She had been bed bound for approximately 1 year secondary to pain of uncertain etiology, and her husband was bringing her both food and drugs. She was admitted to the hospital for debridement of a right ischial ulcer. Further workup revealed osteomyelitis of the left hip and severe vitamin D deficiency. Radiologic evaluation demonstrated diffuse osteopenia with pseudofractures, as well as true fractures. Conclusion. This is the first case reported in the English literature of advanced osteomalacia resulting from a debilitating narcotic dependency. Vitamin D deficiency should be considered in patients with poor nutrition and prolonged sunlight deprivation from any cause.

  18. Drug policy, intravenous drug use, and heroin addiction in the UK.

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    Geraghty, Jemell

    In order to fully understand and appreciate today's drug problem in the UK, the foundations of drug legislation and the history of drug evolution require exploration. This paper critically examines the history of drug policy and the growth of heroin addiction from the perspective of a novice researcher who works closely with intravenous drug users in relation to leg ulceration and wound care in the acute setting. Today's drug policy has come a long way in understanding the problems of heroin addiction and establishing services to meet intravenous drug users' needs and the needs of society. This paper highlights the early warning signs of drug addiction and growth within the UK from an early stage with key areas such as who the early users were and how addiction grew so rapidly between 1920 and 1960. Current policy and decision makers as well as clinicians and researchers in this field must understand the impacts of past policy and embed it within their decisions surrounding drug policy today.

  19. A case of polymicrobial infective endocarditis involving Neisseria mucosa occurring in an intravenous drug abuser.

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    Giles, M W; Andrew, J H; Tellus, M M

    1988-12-01

    The incidence of polymicrobial endocarditis has increased markedly in recent years, in association with the increasing level of abuse of intravenous drugs. Neisseria mucosa, an upper respiratory tract commensal, is a rare cause of infective endocarditis. We report the first case of polymicrobial infective endocarditis involving Neisseria mucosa occurring in an intravenous drug abuser.

  20. HIV Risk in Intravenous Drug Users and Crack Cocaine Smokers: Predicting Stage of Change for Condom Use.

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    Bowen, Anne M.; Trotter, Robert, II

    1995-01-01

    Expanded the applicability of stage models to the reduction of HIV-risk behaviors. Distributed not-in-treatment crack cocaine smokers and intravenous drug users across three levels of intention to change, which revealed that benefits of change and condom assertiveness varied across the stages of change. Discusses other findings. (RJM)

  1. Long-term outcome of lung transplantation in previous intravenous drug users with talc lung granulomatosis.

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    Weinkauf, J G; Puttagunta, L; Nador, R; Jackson, K; LaBranche, K; Kapasi, A; Mullen, J; Modry, D L; Stewart, K C; Thakrar, M; Doucette, K; Lien, D C

    2013-01-01

    Talc lung granulomatosis results from the intravenous use of medication intended for oral use. Talc (magnesium silicate) acts as filler in some oral medications; when injected intravenously, it deposits in the lungs leading to airflow obstruction and impaired gas exchange. Allocation of donor lungs to previous intravenous drug users is controversial. After a careful selection process, 19 patients with talc lung granulomatosis have received lung allografts in our program. Long-term survival for these patients is excellent and our results suggest the previous use of intravenous drugs should not necessarily preclude lung transplantation.

  2. Natural killer cells in intravenous drug abusers with lymphadenopathy syndrome.

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    Poli, G; Introna, M; Zanaboni, F; Peri, G; Carbonari, M; Aiuti, F; Lazzarin, A; Moroni, M; Mantovani, A

    1985-01-01

    We have investigated 25 intravenous drug abusers with the clinical and laboratory features of lymphadenopathy syndrome (LAS) and 10 AIDS patients for the expression of NK activity. LAS and AIDS patients had low NK cytotoxicity compared to normal donors. The defective NK cytotoxicity was analysed in the eight LAS subjects with most marked depression. NK effectors were identified by morphology (large granular lymphocytes, LGL) and monoclonal antibody-defined surface markers (B73.1, N901, HNK1). LAS patients had normal percentages of LGL and B73.1+ and N901+ cells. with the exception of two subjects with very low frequency of B73.1+ and N901+ cells. The percentage of HNK1+ cells was increased in LAS, probably because of the reactivity of this reagent with a subset of conventional OKT8+ cells, relatively augmented in LAS subjects. Depletion of monocytes did not enhance NK activity consistently. LAS patients had a normal frequency of cells capable of binding K562. In-vitro exposure to interferon beta (natural) or gamma (recombinant) augmented the defective NK activity of LAS subjects. Thus, patients with LAS have defective NK activity that cannot be accounted for by a low frequency of the relevant effector cells or by monocytic suppressors. These observations suggest a functional defect of NK cells at one or more of the post-binding steps required for the completion of killing. PMID:2415279

  3. Clinical applications of intravenous immunoglobulins in neurology

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    Hughes, R A C; Dalakas, M C; Cornblath, D R; Latov, N; Weksler, M E; Relkin, N

    2009-01-01

    Intravenous immunoglobulin (IVIg) is used increasingly in the management of patients with neurological conditions. The efficacy and safety of IVIg treatment in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and Guillain–Barré syndrome (GBS) have been established clearly in randomized controlled trials and summarized in Cochrane systematic reviews. However, questions remain regarding the dose, timing and duration of IVIg treatment in both disorders. Reports about successful IVIg treatment in other neurological conditions exist, but its use remains investigational. IVIg has been shown to be efficacious as second-line therapy in patients with dermatomyositis and suggested to be of benefit in some patients with polymyositis. In patients with inclusion body myositis, IVIg was not shown to be effective. IVIg is also a treatment option in exacerbations of myasthenia gravis. Studies with IVIg in patients with Alzheimer's disease have reported increased plasma anti-Aβ antibody titres associated with decreased Aβ peptide levels in the cerebrospinal fluid following IVIg treatment. These changes at the molecular level were accompanied by improved cognitive function, and large-scale randomized trials are under way. PMID:19883422

  4. Postmarketing review of intravenous acetaminophen dosing based on Food and Drug Administration prescribing guidelines.

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    dela Cruz Ubaldo, Catherine; Hall, Natalie Semaan; Le, Brenden

    2014-12-01

    To evaluate the appropriateness of intravenous acetaminophen dosing-prescribed dose, frequency, duration, and indication-based on United States Food and Drug Administration (FDA)-approved prescribing guidelines and to evaluate the adverse effect profile of intravenous acetaminophen. Retrospective chart review. United States Navy medical center. Three hundred patients who received intravenous acetaminophen from August 1, 2011, to August 1, 2012. The indications, dose, frequency, and duration of intravenous acetaminophen were recorded for each patient. Adverse effects of intravenous acetaminophen were analyzed by thoroughly reviewing any adverse effects documented, including nausea, vomiting, headache, or any symptom specifically attributed to the drug. Baseline liver function tests, including aspartate aminotransferase and alanine aminotransferase levels, and elevations 3 times the upper limit of normal during intravenous acetaminophen therapy were recorded. The average patient weight was 78±21 kg, with 12 patients (4%) weighing less than 50 kg and 288 (96%) patients weighing 50 kg or greater. Two hundred forty-one patients (80%) were appropriately dosed, whereas 59 (20%) patients were not appropriately dosed based on the FDA-approved dosing. No patients exceeded the FDA-approved maximum daily dosing recommendations for intravenous acetaminophen (4 g). Sixty-five patients (22%) received intravenous acetaminophen for longer than 24 hours. Intravenous acetaminophen was well tolerated, without any reported adverse effects, including the commonly reported adverse effects of nausea, vomiting, headache, and insomnia. Ten patients (3%) had a documented history of liver disease and did not experience any adverse effects or increases in liver function tests after the administration of intravenous acetaminophen. Intravenous acetaminophen appeared to be a safe and effective analgesic and antipyretic agent. Dosing for patients weighing less than 50 kg needs to be appropriately

  5. [Intravenous drug use and the spread of HIV; an international perspective

    NARCIS (Netherlands)

    Meijerink, H.; Crevel, R. van; Ven, A.J.A.M. van der

    2013-01-01

    Intravenous drug use is a major international health problem. The transmission of HIV through sharing syringes or needles during drug use is an important part of this problem. Injection drug users (IDUs) also engage in high-risk sexual behaviour which facilitates the transmission between different g

  6. ECMO for Cardiac Rescue after Accidental Intravenous Mepivacaine Application

    OpenAIRE

    Michael Froehle; Haas, Nikolaus A.; Guenther Kirchner; Deniz Kececioglu; Eugen Sandica

    2012-01-01

    Mepivacaine is a potent local anaesthetic and used for infiltration and regional anaesthesia in adults and pediatric patients. Intoxications with mepivacaine affect mainly the CNS and the cardiovascular system. We present a case of accidental intravenous mepivacaine application and intoxication of an infant resulting in seizure, broad complex bradyarrhythmia, arterial hypotension and finally cardiac arrest. The patient could be rescued by prolonged resuscitations and a rapid initiation of ECM...

  7. Spontaneous kyphotic collapse followed by autostabilisation secondary to cervical osteomyelitis in an intravenous drug abuser.

    Science.gov (United States)

    Arun, Ranganathan; Kasbekar, Anand Vijay; Mehdian, S M Hossein

    2007-12-01

    There is a high risk of cervical osteomyelitis in intravenous drug abusers due to the use of jugular veins for administration of drugs. Here described is a case of rapid vertebral body destruction at two levels leading to a progressive kyphotic deformity followed by autofusion, secondary to cervical osteomyelitis. The case report goes on to hypothesise about the unique manner of progression of untreated cervical osteomyelitis with a rapid onset of kyphotic deformity and associated severe bone destruction in an intravenous drug abuser. Due to the high incidence of osteomyelitis in intravenous drug abusers, there should be a low threshold to investigate for this condition and early magnetic resonance imaging is vital. It alerts the treating spine surgeon to the fact that early immobilisation is crucial in these cases to prevent a severe impending deformity that can be surgically challenging.

  8. A continuous tri-phase transition effect for HIFU-mediated intravenous drug delivery.

    Science.gov (United States)

    Zhang, Kun; Chen, Hangrong; Li, Faqi; Wang, Qi; Zheng, Shuguang; Xu, Huixiong; Ma, Ming; Jia, Xiaoqing; Chen, Yu; Mou, Juan; Wang, Xia; Shi, Jianlin

    2014-07-01

    Aiming at substantially enhanced efficacy and biosafety of clinical HIFU therapy, a natural solid medium, L-menthol (LM), characteristic of mild and controllable "solid-liquid-gas" (SLG) tri-phase transition, was adopted, instead of those conventional explosive liquid-gas (LG) bi-phase transitional media, in constructing a multifunctional theranostic system. Owing to the continuous and controllable characteristics of SLG tri-phase transition, such a novel tri-phase transition-based theranostic system has been demonstrated of the repeatedly enhanced HIFU efficacy ex vivo and in vivo under once intravenous injection and the significantly improved treatment precision, controllability and biosafety when comparing to the traditional bi-phase transition medium, perfluorohexane (PFH), thus promising great application potential in clinical HIFU treatment. Moreover, this theranostic system has been demonstrated a long blood-circulation lifetime and continuous accumulation in tumor in 24 h, which is very beneficial for the enhanced tumor ablation in vivo along with SLG tri-phase transition. More importantly, after loading multiple model drugs and real drug, such a theranostic system presents a HIFU-mediated temperature-responsive drug release property, and depending on the versatile miscibility of LM, co-loadings with hydrophobic and hydrophilic drugs are also achieved, which provides the possibility of synergistic treatment combining HIFU therapy and chemotherapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Iris abscess a rare presentation of intravenous drug abuse associated Candida endophthalmitis

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    Jonathan Pierce

    2016-12-01

    Conclusions and importance: An iris abscess is a rare clinical presentation of intravenous drug use-associated endogenous endophthalmitis and as a result may present a diagnostic challenge as it requires a high level of clinical suspicion and a detailed social history to elicit the drug abuse. Early diagnosis and aggressive therapy is the key to better visual outcomes in these patients.

  10. Intravascular Talcosis due to Intravenous Drug Use Is an Underrecognized Cause of Pulmonary Hypertension

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    Christopher C. Griffith

    2012-01-01

    Full Text Available Intravenous injection of illegal drugs or medications meant for oral administration can cause granulomatous disease of the lung. This intravascular talcosis results in pulmonary fibrosis and pulmonary hypertension. Nine cases of histologically confirmed intravascular talcosis were reviewed with specific attention given to the clinical histories in these patients. Five autopsy cases were included in this series with detailed investigation in the anatomic features associated with intravascular talcosis and pulmonary hypertension. All nine patients showed perivascular and/or intravascular deposition of polarizable foreign material in their lungs. Intravascular talcosis as a result of previous intravenous drug use was not clinically suspected in any patient despite clinically diagnosed pulmonary hypertension in five. All patients showed dilatation of the right and left heart, but none had dilatation of the aortic valve. Congestive heart failure with hepatosplenomegaly was also common. We conclude that intravascular talcosis is an underdiagnosed cause of pulmonary hypertension in patients with known history of intravenous drug use.

  11. Hyperacute drug-induced hepatitis with intravenous amiodarone: case report and review of the literature.

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    Nasser, Mohammad; Larsen, Timothy R; Waanbah, Barryton; Sidiqi, Ibrahim; McCullough, Peter A

    2013-01-01

    Amiodarone is a benzofuran class III antiarrhythmic drug used to treat a wide spectrum of ventricular tachyarrhythmias. The parenteral formulation is prepared in polysorbate 80 diluent. We report an unusual case of acute elevation of aminotransaminase concentrations after the initiation of intravenous amiodarone. An 88-year-old Caucasian female developed acute hepatitis and renal failure after initiating intravenous amiodarone for atrial fibrillation with a rapid ventricular response in the setting of acutely decompensated heart failure and hepatic congestion. Liver transaminases returned to baseline within 7 days after discontinuing the drug. Researchers hypothesized that this type of injury is related to liver ischemia with possible superimposed direct drug toxicity. The CIOMS/RUCAM scale identifies our patient's acute hepatitis as a highly probable adverse drug reaction. Future research is needed to understand the mechanisms by which hyperacute drug toxicity occurs in the setting of impaired hepatic perfusion and venous congestion.

  12. ECMO for Cardiac Rescue after Accidental Intravenous Mepivacaine Application

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    Michael Froehle

    2012-01-01

    Full Text Available Mepivacaine is a potent local anaesthetic and used for infiltration and regional anaesthesia in adults and pediatric patients. Intoxications with mepivacaine affect mainly the CNS and the cardiovascular system. We present a case of accidental intravenous mepivacaine application and intoxication of an infant resulting in seizure, broad complex bradyarrhythmia, arterial hypotension and finally cardiac arrest. The patient could be rescued by prolonged resuscitations and a rapid initiation of ECMO and survived without neurological damage. The management strategies of this rare complication including promising other treatment options with lipid emulsions are discussed.

  13. Optimizing intravenous drug administration by applying pharmacokinetic/pharmacodynamic concepts

    NARCIS (Netherlands)

    Struys, M. M. R. F.; Sahinovic, M.; Lichtenbelt, B. J.; Vereecke, H. E. M.; Absalom, A. R.

    2011-01-01

    This review discusses the ways in which anaesthetists can optimize anaesthetic-analgesic drug administration by utilizing pharmacokinetic and pharmacodynamic information. We therefore focus on the dose-response relationship and the interactions between i.v. hypnotics and opioids. For i.v. hypnotics

  14. Treatment of early AIDS dementia in intravenous drug users : High versus low dose peptide T

    NARCIS (Netherlands)

    Kosten, TR; Rosen, MI; McMahon, TL; Bridge, TP; OMalley, SS; Pearsall, R; OConnor, PG

    1997-01-01

    This placebo-controlled, double blind, cross-over study tested the efficacy of two different doses of Peptide T in the treatment of nine intravenous drug users with early AIDS dementia who were also receiving methadone and AZT. Subjects received Peptide T doses of either 15 or 1.5 mg daily for four

  15. Hyperacute drug-induced hepatitis with intravenous amiodarone: case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Nasser M

    2013-09-01

    Full Text Available Mohammad Nasser, Timothy R Larsen, Barryton Waanbah, Ibrahim Sidiqi, Peter A McCullough Providence Hospitals and Medical Centers, Department of Medicine, Division of Cardiology, Southfield and Novi, MI, USA Abstract: Amiodarone is a benzofuran class III antiarrhythmic drug used to treat a wide spectrum of ventricular tachyarrhythmias. The parenteral formulation is prepared in polysorbate 80 diluent. We report an unusual case of acute elevation of aminotransaminase concentrations after the initiation of intravenous amiodarone. An 88-year-old Caucasian female developed acute hepatitis and renal failure after initiating intravenous amiodarone for atrial fibrillation with a rapid ventricular response in the setting of acutely decompensated heart failure and hepatic congestion. Liver transaminases returned to baseline within 7 days after discontinuing the drug. Researchers hypothesized that this type of injury is related to liver ischemia with possible superimposed direct drug toxicity. The CIOMS/RUCAM scale identifies our patient’s acute hepatitis as a highly probable adverse drug reaction. Future research is needed to understand the mechanisms by which hyperacute drug toxicity occurs in the setting of impaired hepatic perfusion and venous congestion. Keywords: intravenous amiodarone, acute hepatotoxicity, liver transaminases, drug-induced liver toxicity

  16. A comparative study of oral and intravenous drug-dependent patients on three dimensions of personality.

    Science.gov (United States)

    Gossop, M R

    1978-01-01

    In an investigation of personality differences between oral and intravenous drug addicts, 59 subjects attending a London clinic were given the Eysenck Personality Questionnaire. Both groups scored highly on the neuroticism and psychoticism dimensions, though oral users were found to have significantly higher scores on both of these scales. High P scorers have been found to be cold, unfriendly, hostile, etc., and it is suggested that the lower P scores of the intravenous users may be partly due to possible hostility-reducing effects of the narcotics used by this group. Other implications of these findings are also discussed.

  17. Stent-Graft Placement with Early Debridement and Antibiotic Treatment for Femoral Pseudoaneurysms in Intravenous Drug Addicts

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Qining, E-mail: cqmufqn@163.com; Meng, Xiyun, E-mail: 383274177@qq.com; Li, Fenghe, E-mail: lfh-cqmu@gmail.com; Wang, Xuehu, E-mail: 184037696@qq.co; Cheng, Jun, E-mail: cqdcj@163.com; Huang, Wen, E-mail: dhuangwen@hotmail.com; Ren, Wei, E-mail: renwei9771@yahoo.com.cn; Zhao, Yu, E-mail: zhaoyu-cqmu@126.com [The First Affiliated Hospital of Chongqing Medical University, Department of Vascular Surgery (China)

    2015-06-15

    PurposeExplore the application of endovascular covered stent-graft (SG) placement in femoral pseudoaneurysms in intravenous drug addicts.Materials and MethodsWe evaluated a consecutive series of pseudoaneurysm in intravenous drug addicts treated with SGs from August 2010 to December 2013.Results15 patients with 16 arterial pseudoaneurysms were enrolled in this study. All were males with a mean age of 36.9 years. Hemorrhage was the most common reason (93.8 %) for seeking medical care, and 3 of these patients were in hemorrhagic shock at admission. All patients received broad-spectrum antibiotics, and debridement and drainage were implemented after SG placement. 7 of the 13 cases which had microbiologic results showed mixed infections, while gram-negative bacteria were the major pathogens. Except for 2 patients, who were lost to follow-up, two new pseudoaneurysms formed due to delayed debridement, and one stent thrombosis occurred, none of the remaining cases had SG infection or developed claudication.ConclusionsSG placement controls massive hemorrhage rapidly, gives enough time for subsequent treatment for pseudoaneurysms due to intravenous drug abuse, and reduces the incidence of postoperative claudication. With appropriate broad-spectrum antibiotics and early debridement, the incidence of SG infection is relatively low. It is an effective alternative especially as temporary bridge measure for critical patients. However, the high cost, uncertain long-term prospects, high demand for medical adherence, and the risk of using the conduits for re-puncture call for a cautious selection of patients. More evidence is required for the application of this treatment.

  18. [Intravenous drug use and the spread of HIV; an international perspective].

    Science.gov (United States)

    Meijerink, Hinta; van Crevel, Reinout; van der Ven, André J A M

    2013-01-01

    Intravenous drug use is a major international health problem. The transmission of HIV through sharing syringes or needles during drug use is an important part of this problem. Injection drug users (IDUs) also engage in high-risk sexual behaviour which facilitates the transmission between different groups. In this article, we present a global perspective of injection drug use in relation to HIV. There are 16 million IDUs worldwide, of whom an estimated 3 million are infected with HIV. The prevalence of HIV among IDUs varies greatly between countries as well as within them. There are intervention programmes to prevent HIV transmission via drug use such as needle and syringe exchange programmes (NSPs) and opioid substitution therapy (OST). These programmes are effective for preventing HIV transmission, provided that their implementation is adequate. 80% of the countries provide NSPs, 65% also provide OST. The coverage of these services is nevertheless insufficient to have an impact on the transmission of HIV.

  19. Hepatitis C infection among intravenous drug users attending therapy programs in Cyprus.

    Science.gov (United States)

    Demetriou, Victoria L; van de Vijver, David A M C; Hezka, Johana; Kostrikis, Leondios G; Kostrikis, Leondios G

    2010-02-01

    The most high-risk population for HCV transmission worldwide today are intravenous drug users. HCV genotypes in the general population in Cyprus demonstrate a polyphyletic infection and include subtypes associated with intravenous drug users. The prevalence of HCV, HBV, and HIV infection, HCV genotypes and risk factors among intravenous drug users in Cyprus were investigated here for the first time. Blood samples and interviews were obtained from 40 consenting users in treatment centers, and were tested for HCV, HBV, and HIV antibodies. On the HCV-positive samples, viral RNA extraction, RT-PCR and sequencing were performed. Phylogenetic analysis determined subtype and any relationships with database sequences and statistical analysis determined any correlation of risk factors with HCV infection. The prevalence of HCV infection was 50%, but no HBV or HIV infections were found. Of the PCR-positive samples, eight (57%) were genotype 3a, and six (43%) were 1b. No other subtypes, recombinant strains or mixed infections were observed. The phylogenetic analysis of the injecting drug users' strains against database sequences observed no clustering, which does not allow determination of transmission route, possibly due to a limitation of sequences in the database. However, three clusters were discovered among the drug users' sequences, revealing small groups who possibly share injecting equipment. Statistical analysis showed the risk factor associated with HCV infection is drug use duration. Overall, the polyphyletic nature of HCV infection in Cyprus is confirmed, but the transmission route remains unknown. These findings highlight the need for harm-reduction strategies to reduce HCV transmission.

  20. Intravenous Drug Abuse by Patients Inside the Hospital: A Cause for Sustained Bacteremia.

    Science.gov (United States)

    Goel, Noopur; Munshi, Lubna Bashir; Thyagarajan, Braghadheeswar

    2016-01-01

    Patients with history of intravenous drug abuse are noted to be at risk of several infections including HIV, endocarditis, and other opportunistic infections. We report the case of a patient with sustained Bacillus cereus bacteremia despite use of multiple antibiotic regimens during his inpatient stay. Our case highlights the importance of high suspicion for active drug use inside the hospital in such patients. This is important in order to minimize unnecessary diagnostic workup and provide adequate treatment and safe hospital stay for these patients.

  1. Intravenous Drug Abuse by Patients Inside the Hospital: A Cause for Sustained Bacteremia

    Directory of Open Access Journals (Sweden)

    Noopur Goel

    2016-01-01

    Full Text Available Patients with history of intravenous drug abuse are noted to be at risk of several infections including HIV, endocarditis, and other opportunistic infections. We report the case of a patient with sustained Bacillus cereus bacteremia despite use of multiple antibiotic regimens during his inpatient stay. Our case highlights the importance of high suspicion for active drug use inside the hospital in such patients. This is important in order to minimize unnecessary diagnostic workup and provide adequate treatment and safe hospital stay for these patients.

  2. Intravenous drug abuse and tricuspid valve endocarditis: Growing trends in the Middle East Gulf region.

    Science.gov (United States)

    Panduranga, Prashanth; Al-Abri, Seif; Al-Lawati, Jawad

    2013-11-26

    Traditionally, tricuspid valve endocarditis is uncommon in the Middle East region. However, recent global data indicate growing trends in the use of illicit drug abuse, specifically injectable heroin, in the Middle East Gulf region. The presence of many transit port services in the Middle East Gulf States has led to smuggling of substance abuse drugs in the region. The Middle East Gulf States, currently a transit market, are also becoming a growing consumer market in view of the increased substance abuse in the youth. However, there is a paucity of data with respect to the prevalence or incidence of tricuspid valve endocarditis in the region, probably due to underdiagnosis or underreporting. A high index of suspicion of tricuspid valve endocarditis is essential in patients with a history of intravenous drug abuse. This article reviews the epidemiology of illicit drug abuse in the Middle East Gulf region, as well as the diagnosis and treatment of tricuspid valve endocarditis, and calls for all physicians in the region to be vigilant while dealing with intravenous drug abuse.

  3. Relationship between Individual Characteristics and High Risk Behavior in Intravenous Drug Addicts in Ardabil, 2012

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    Nasrin Fouladi

    2014-12-01

    Full Text Available Background & objectives: Addiction is one of the problems in world threating the social, economic and culture factors. It is essential to have an accurate knowledge about the characteristics of drug users in order to diminish the high-risk behaviors of intravenous drug addicts. This research has been done to assess relationship between individual characteristics and high risk behavior in intravenous drug addicts.   Method: In this descriptive-analytic research, 360 drug users were selected from different places in Ardabil city and interviewed by a prepared questionnaire. The data were analyzed using descriptive and analytical tests including t-test, Pearson correlation and ANOVA with SPSS statistical software.   Results: The results showed that the age, gender, material status, job position, age of addiction start, age of injection start, injection frequency, injection frequency per day, syringe supply place and the partner’s gender during recent few months had no significant difference compared to drug users with needle sharing and without needle sharing. The educational level of drug users with needle sharing was lower (P=0.037 and the number of new syringe usage per month was also lesser (P=0.001. They predicted to be more likely infected with AIDS (P=0.001 and had a less argument with their partner about using condom, also mostly have not used condom at their last sexual relationship (P=0.001. The average number of their partners during last three months was high (P=0.003 and there was a meaningful relationship between true sense of peril and using condom in drug users with needle sharing group (p=0.001.   Conclusion: There is a significant relationship between the true sense of danger and the using condom. It is necessary to have an appropriate advertising to increase using condoms among injecting drug users.

  4. Association of higher-risk alcohol consumption with injecting paraphernalia sharing behaviours in intravenous drug users.

    Science.gov (United States)

    Wang, Mei; Shen, Jiucheng; Deng, Yuan; Liu, Xianling; Li, Jianhua; Wolff, Kim; Finch, Emily

    2014-03-01

    Alcohol use is common among injecting drug users. The coexistence of alcohol consumption and injecting risk behaviour has the potential to increase harms among intravenous drug users (IDUs). This study aimed to determine whether the level of alcohol use is a risk factor for injecting paraphernalia sharing behaviours. A total of 637 treatment-seeking IDUs were assessed for injecting paraphernalia sharing behaviours and drinking risk level as defined by the National Institute for Health and Care Excellence (NICE). Multivariate analyses were performed to identify alcohol risk factors associated with injecting paraphernalia sharing behaviours. After adjusting for the effects of ethnicity, employment and drug used, the odds ratio of higher risk drinking for injecting paraphernalia sharing behaviours was 1.92 (95% CI 1.31-2.83). Higher-risk drinking in IDUs is associated with higher rates of injecting paraphernalia sharing behaviours. It is important to take alcohol use into account when evaluating these patients for treatment and designing intervention strategies.

  5. Intravenous misuse of buprenorphine: characteristics and extent among patients undergoing drug maintenance therapy.

    Science.gov (United States)

    Moratti, Enrico; Kashanpour, Hamid; Lombardelli, Tiziana; Maisto, Maria

    2010-01-01

    Sublingual buprenorphine [Subutex(R)] is used to treat opioid dependence. However, illicit intravenous (IV) injection of buprenorphine is a widespread problem. This survey investigated the IV misuse of buprenorphine among patients receiving drug replacement therapy at the Drug Addiction Centre in Udine, Italy. All patients who were receiving treatment with buprenorphine or methadone at the Drug Addiction Centre were invited to fill in a voluntary and anonymous questionnaire consisting of five questions. The questions asked if the patient had ever misused buprenorphine intravenously, when the misuse had occurred, the patient's reasons for misusing buprenorphine, the patient's perception of their experience, and the patient's perception of how widespread IV misuse of buprenorphine is. 307 patients completed the questionnaire, 93 and 214 of whom, respectively, were receiving buprenorphine and methadone. In total, 23.12% of patients admitted an IV misuse of buprenorphine, with a significantly greater prevalence among patients currently receiving buprenorphine (35.48%) than those receiving methadone (17.75%; p IV misuse was treatment of heroin addiction or withdrawal symptoms (50.71%), while only 12.67% of patients reported that their motivation was to experience pleasure or euphoria. The majority of patients who had misused buprenorphine intravenously (53.52%) had a negative experience, and methadone recipients were significantly more likely to find the experience negative than buprenorphine recipients (68.42% vs 36.36%; p = 0.007). Almost half of the patients (45.93%) thought that at least 50% of patients had taken buprenorphine by IV injection. The results of our study confirm the widespread IV misuse of buprenorphine. Misuse was most common among patients currently receiving buprenorphine treatment and younger patients. For the majority of patients, the reason for IV misuse was to treat their dependence. We believe that the prevalence of buprenorphine misuse could

  6. Successful lung transplantation for talcosis secondary to intravenous abuse of oral drug

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    Dekel Shlomi

    2008-06-01

    Full Text Available Dekel Shlomi1, David Shitrit1, Daniele Bendayan1, Gidon Sahar2, Yitshak Shechtman3, Mordechai R Kramer11Pulmonary Institute, Departments of 2Cardiothoracic Surgery and 3Pathology, Rabin Medical Center, Beilinson Campus, Petah Tiqwa, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelAbstract: Talcosis due to intravenous injection of oral drugs can cause severe pulmonary disease with progressive dyspnea even when drug use is discontinued. We describe a 54-yearold woman with severe emphysema who underwent left lung transplantation. The patient had a remote history of intravenous injection of crushed methylphenidate (Ritalin tablets. Chest computed tomography showed severe emphysematous changes, more prominent in the lower lobes. Microscopic examination of the extracted lung demonstrated multinucleated giant cells with birefringent crystals, compatible with talcosis. At follow-up, daily symptoms were completely alleviated and lung function was good. We recommend that lung transplantation be considered as a viable option in the treatment of talcosis.Keywords: methylphenidate (Ritalin, emphysema

  7. The Efficacy of Two Intravenous Sedative Drugs in Management of Uncooperative Children for Dental Treatments

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    Nasser Kaviani

    2015-03-01

    Full Text Available Statement of the Problem: Some children do not show an appropriate coopera-tion with their dentist. A number of them cannot be managed by local anesthesia and the usual techniques used to control behaviors, so further steps are required to control their pain and anxiety. Pharmaceutical control is recommended through sedation or general anesthesia. Purpose: This study was aimed to evaluate two groups of drugs in intravenous sedation method. Materials and Method: In this clinical trial intervention study, patients were randomly divided into two groups of 18 and 20 and each group received either intravenous midazolam-ketamine or midazolam-fentanyl. During the procedure, 0.25mg midazolam was administered to both groups if needed. The scores of intraoperative sedation and operation conditions were evaluated and recorded by dental sedation teacher groups (DSTG system in the 10th, 20th, 30th and 40th minutes of the operation. The results were analyzed by SPSS (version 16 using independent T-test, Wilcoxon, Mann-Whitney and Pearson Chi-Square tests as appropriated. Results: There was no significant difference between the two groups in sedation period (p= 0.55, recovery time (p= 0.18, Frankl score (p= 0.83(, score of in-traoperative sedation and operating conditions (p> 0.05, and sedation complications (p= 0.612. In addition, no complication occurred in recovery. Conclusion: There was no significant difference between the two drug groups; both were appropriate in controlling children’s behavior.

  8. The Efficacy of Two Intravenous Sedative Drugs in Management of Uncooperative Children for Dental Treatments

    Science.gov (United States)

    Kaviani, Nasser; Ashrafi, Sanaz; Jabbarifar, Seyed Ebrahim; Ghaffari, Elham

    2015-01-01

    Statement of the Problem Some children do not show an appropriate cooperation with their dentist. A number of them cannot be managed by local anesthesia and the usual techniques used to control behaviors, so further steps are required to control their pain and anxiety. Pharmaceutical control is recommended through sedation or general anesthesia. Purpose This study was aimed to evaluate two groups of drugs in intravenous sedation method. Materials and Method In this clinical trial intervention study, patients were randomly divided into two groups of 18 and 20 and each group received either intravenous midazolam-ketamine or midazolam-fentanyl. During the procedure, 0.25mg midazolam was administered to both groups if needed. The scores of intraoperative sedation and operation conditions were evaluated and recorded by dental sedation teacher groups (DSTG) system in the 10th, 20th, 30th and 40th minutes of the operation. The results were analyzed by SPSS (version 16) using independent T-test, Wilcoxon, Mann-Whitney and Pearson Chi-Square tests as appropriated. Results There was no significant difference between the two groups in sedation period (p= 0.55), recovery time (p= 0.18), Frankl score (p= 0.83(, score of intraoperative sedation and operating conditions (p> 0.05), and sedation complications (p= 0.612). In addition, no complication occurred in recovery. Conclusion There was no significant difference between the two drug groups; both were appropriate in controlling children’s behavior. PMID:26106632

  9. Docetaxel-loaded PLGA and PLGA-PEG nanoparticles for intravenous application: pharmacokinetics and biodistribution profile

    Science.gov (United States)

    Rafiei, Pedram; Haddadi, Azita

    2017-01-01

    Docetaxel is a highly potent anticancer agent being used in a wide spectrum of cancer types. There are important matters of concern regarding the drug’s pharmacokinetics related to the conventional formulation. Poly(lactide-co-glycolide) (PLGA) is a biocompatible/biodegradable polymer with variable physicochemical characteristics, and its application in human has been approved by the United States Food and Drug Administration. PLGA gives polymeric nanoparticles with unique drug delivery characteristics. The application of PLGA nanoparticles (NPs) as intravenous (IV) sustained-release delivery vehicles for docetaxel can favorably modify pharmacokinetics, biofate, and pharmacotherapy of the drug in cancer patients. Surface modification of PLGA NPs with poly(ethylene glycol) (PEG) can further enhance NPs’ long-circulating properties. Herein, an optimized fabrication approach has been used for the preparation of PLGA and PLGA–PEG NPs loaded with docetaxel for IV application. Both types of NP formulations demonstrated in vitro characteristics that were considered suitable for IV administration (with long-circulating sustained-release purposes). NP formulations were IV administered to an animal model, and docetaxel’s pharmacokinetic and biodistribution profiles were determined and compared between study groups. PLGA and PEGylated PLGA NPs were able to modify the pharmacokinetics and biodistribution of docetaxel. Accordingly, the mode of changes made to pharmacokinetics and biodistribution of docetaxel is attributed to the size and surface properties of NPs. NPs contributed to increased blood residence time of docetaxel fulfilling their role as long-circulating sustained-release drug delivery systems. Surface modification of NPs contributed to more pronounced docetaxel blood concentration, which confirms the role of PEG in conferring long-circulation properties to NPs. PMID:28184163

  10. Nanotopography applications in drug delivery

    Science.gov (United States)

    Walsh, Laura A; Allen, Jessica L; Desai, Tejal A

    2016-01-01

    Refinement of micro- and nanofabrication in the semiconductor field has led to innovations in biomedical technologies. Nanotopography, in particular, shows great potential in facilitating drug delivery. The flexibility of fabrication techniques has created a diverse array of topographies that have been developed for drug delivery applications. Nanowires and nanostraws deliver drug cytosolically for in vitro and ex vivo applications. In vivo drug delivery is limited by the barrier function of the epithelium. Nanowires on microspheres increase adhesion and residence time for oral drug delivery, while also increasing permeability of the epithelium. Low aspect ratio nanocolumns increase paracellular permeability, and in conjunction with microneedles increase transdermal drug delivery of biologics in vivo. In summary, nanotopography is a versatile tool for drug delivery. It can deliver directly to cells or be used for in vivo delivery across epithelial barriers. This editorial highlights the application of nanotopography in the field of drug delivery. PMID:26512871

  11. Intravenous Immunoglobulin: A Drug Utilization Review at Shahid Sadoughi Hospital in Yazd

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    SeyedMojtaba Sohrevardi

    2015-10-01

    Full Text Available  Background: Drug use evaluation (DUE aims at improving the patients’ care. Studying the administration pattern of intravenous immunoglobulin (IVIG is an important research topic due to its significant role in the treatment and controlling of many disorders, high prices, and limited availability of this drug.  Methods:This observational cross-sectional study was conducted at Shahid Sadoughi Hospital in Yazd, central Iran, from May to September 2014. The orders of different wards in the hospital for IVIG given to the hospital central pharmacy were surveyed. Also, a special form developed for evaluation the method of administration. The related physician and nurse were consulted on drug complications and the causes. Finally, the gleaned data were compared to the available standards on the prescription and administration of IVIG.Results:A total of 75 patients received IVIG during this study. 58.7% of the prescriptions belonged to the cases approved by Food and Drug Administration (FDA. The most frequent cause of the use of IVIG was idiopathic thrombocytopenic purpura (ITP. The rate and dose of administration was suitable in most of the patients, yet, the measurement of laboratory parameters required for IVIG were observed in only a few cases. Complications occurred in 26.7% of the patients receiving it, which was mostly related to infusion-related reactions. On the whole, 3922 g IVIG was used during this study of which 1848 g belonged to the cases approved by FDA.Conclusion:Regarding the high costs of IVIG, complications, and limited information on the quality of the effect of this drug in the treatment of many cases, physicians should be cautious enough with its appropriate use. Besides, the presence of a clinical pharmacist in the health-care team not only improves the quality of drug therapy and treatment results, but also plays an important part in decreasing the treatment costs for the patients.

  12. 76 FR 13880 - Investigational New Drug Applications and Abbreviated New Drug Applications; Technical Amendment

    Science.gov (United States)

    2011-03-15

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Parts 312 and 314 Investigational New Drug Applications and Abbreviated New Drug Applications; Technical Amendment AGENCY: Food and Drug Administration... amending its investigational new drug application (IND) regulations and abbreviated new drug...

  13. Protective KIR-HLA interactions for HCV infection in intravenous drug users

    Science.gov (United States)

    Zúñiga, Joaquin; Romero, Viviana; Azocar, José; Terreros, Daniel; Vargas-Rojas, María Inés; Torres-García, Diana; Jimenez-Alvarez, Luis; Vargas-Alarcón, Gilberto; Granados-Montiel, Julio; Husain, Zaheed; Chung, Raymond T.; Alper, Chester A.; Yunis, Edmond J.

    2009-01-01

    Intravenous drug use has become the principal route of hepatitis C virus (HCV) transmission due to the sharing of infected needles. In this study, we analyzed the distribution of HLA-KIR genotypes among 160 Puerto Rican intravenous drug users (IDUs) with HCV infection and 92 HCV-negative Puerto Rican IDUs. We found a significant association between the presence of different combinations of KIR inhibitory receptor genes (KIR2DL2 and/or KIR2DL3, pC = 0.01, OR = 0.07; KIR2DL2 and/or KIR2DL3+KIR2DS4, pC = 0.01, OR = 0.39) and HLA-C1 homozygous genotypes (HLA-C1+KIR2DS4, pC = 0.02, OR = 0.43; HLA-C1+KIR2DL2+KIR2DS4, pC = 0.02, OR = 0.40) together with the activating receptor KIR2DS4 (HLA-C1+KIR2DS4+KIR2DL3 and/or KIR2DL2, pC = 0.004, OR = 0.38) with protection from HCV infection. Our findings in HCV-infected and non-infected IDUs suggest an important role for KIRs (KIR2DL2 and KIR2DL3) with group HLA-C1 molecules, in the presence of activating KIR2DS4, in protection from HCV infection. These results support the hypothesis that activator signaling, mediated by KIR2DS4, is a determinant in the regulation of NK cell antiviral-activity. PMID:19552960

  14. Guidelines for the intravenous application of recombinant tissue-type plasminogen activator (alteplase), the second edition, October 2012: a guideline from the Japan Stroke Society.

    Science.gov (United States)

    Minematsu, Kazuo; Toyoda, Kazunori; Hirano, Teruyuki; Kimura, Kazumi; Kondo, Rei; Mori, Etsuro; Nakagawara, Jyoji; Sakai, Nobuyuki; Shiokawa, Yoshiaki; Tanahashi, Norio; Yasaka, Masahiro; Katayama, Yasuo; Miyamoto, Susumu; Ogawa, Akira; Sasaki, Makoto; Suga, Sadao; Yamaguchi, Takenori

    2013-07-01

    In Japan, intravenous alteplase, a recombinant tissue-type plasminogen activator (rt-PA), was approved for an indication of ischemic stroke in 2005 on the basis of the results of a clinical trial with a unique dose of the drug (0.6 mg/kg). The Japan Stroke Society published the guidelines for intravenous application of rt-PA and organized training sessions for proper use all over Japan in an effort to promote the safe, widespread use of intravenous alteplase. Seven years following its approval, clinical experience with intravenous alteplase has accumulated, additional evidence of intravenous alteplase has been found in Japan and overseas, and the medical environment has substantially changed, including approvals for new drugs and medical devices. Notably, the use of alteplase in the extended therapeutic time window (within 4.5 hours of symptom onset) became covered by insurance in Japan in August 2012. To address these changing situations, we have decided to prepare the revised guidelines. In preparing the second edition, we took care to make its contents more practical by emphasizing information needed in clinical practice. While the first edition was developed with emphasis on safety in light of limited clinical experience with intravenous alteplase in Japan in 2005, this second edition is a substantial revision of the first edition mainly in terms of eligibility criteria, on the basis of accumulated evidence and the clinical experience.

  15. Neuropsychological impairment among intravenous drug users in pre-AIDS stages of HIV infection.

    Science.gov (United States)

    Wellman, M C

    1992-01-01

    While much of the current literature concurs that neuropsychological decline does not occur among gay men in the early stages of HIV infection, there is no comparable body of evidence with regard to seropositive intravenous drug users (IVDU). In this study, 45 seropositive (CDC groups 2, 3, and 4a) IVDU in recovery and 55 seronegative IVDU in recovery were given a complete battery of neuropsychological tests measuring attention, language, visual-motor, memory, and conceptual skills. The groups were not significantly different in age, incidence of childhood and adult head injury, types of drugs used, length of use of cocaine, crack, amphetamines and hallucinogens, overdose history, and length of time in recovery. In addition, groups were statistically corrected for education level and length of heroin use. Results indicate that the seropositive participants scored significantly lower on measures of divided attention, visual short-term memory, graphomotor speed and accuracy, auditory language shortterm memory and abstract concept formation. Further analyses revealed that 18% of participants with Persistent Generalized Lymphadenopathy (CDC group III) and 27% of those with constitutional disease (CDC group IVa) were neuropsychologically impaired, as their performance was two standard deviations or more below the normative mean on two or more measures. These results are similar to the reported performance of gay men with full-blown AIDS in a number of studies. It is hypothesized that because of premorbid neurological insult, the toxic effects of drug abuse on brain tissue, and the immunosuppressive effects of the drugs, subcortical brain cells of IVDU are more vulnerable to the invasion of HIV, and neurological deterioration may occur at earlier stages of HIV Spectrum Disease in IVDU than in gay men.

  16. The Molecular Epidemiological Study of HCV Subtypes among Intravenous Drug Users and Non-Injection Drug Users in China.

    Directory of Open Access Journals (Sweden)

    Jun Tao

    Full Text Available More than half of intravenous drug users (IDUs in China suffer from the Hepatitis C virus (HCV. The virus is also more prevalent in non-injection drug users (NIDUs than in the general population. However, not much is known about HCV subtype distribution in these populations.Our research team conducted a cross-sectional study in four provinces in China. We sampled 825 IDUs and 244 NIDUs (1162 total, genotyped each DU's virus, and performed a phylogenetic analysis to differentiate HCV subtypes.Nucleic acid testing (NAT determined that 82% percent (952/1162 of samples were HCV positive; we subtyped 90% (859/952 of these. We found multiple HCV subtypes: 3b (249, 29.0%, 3a (225, 26.2%, 6a (156, 18.2%, 1b (137, 15.9%, 6n (50, 5.9%, 1a (27, 3.1%, and 2a (15, 1.7%. An analysis of subtype distributions adjusted for province found statistically significant differences between HCV subtypes in IDUs and NIDUs.HCV subtypes 3b, 3a, 6a, and 1b were the most common in our study, together accounting for 89% of infections. The subtype distribution differences we found between IDUs and NIDUs suggested that sharing syringes was not the most likely pathway for HCV transmission in NIDUs. However, further studies are needed to elucidate how NIDUs were infected.

  17. Hepatitis C Virus Genotype Diversity among Intravenous Drug Users in Yunnan Province, Southwestern China

    Science.gov (United States)

    Wu, Wenlong; Feng, Ruilin; Wu, Zhongxiang; Cun, Wei; Dong, Shaozhong

    2013-01-01

    Background Recently, high proportions (15.6%–98.7%) of intravenous drug users (IDUs) in China were found to be positive for hepatitis C virus (HCV). Yunnan Province is located in southwestern China and borders one of the world's most important opium-producing regions, thus it is an important drug trafficking route to other regions of China. Methodology/Principal Findings Here, we assessed 100 HCV-positive plasma samples from IDUs who were enrolled through the Kunming Center for Disease Control and Prevention in 2012. HCV C/E1 fragments were PCR-amplified and sequenced. We identified eight HCV subtypes (1a, 1b, 3a, 3b, 6a, 6n, 6u and 6v), of which genotype 6 was most predominant (frequency, 47%) followed by genotypes 3 (41%) and 1 (12%). HCV subtypes 6n (30%) and 3b (29%) were most common and were identified in 59% of the IDUs. We compared HCV genotypes among IDUs in Yunnan Province with those from other regions and found that the distribution patterns of HCV genotypes in Yunnan Province were similar to those in southern China, but different from those in eastern China. However, the distribution patterns of HCV subtypes varied among Yunnan Province and southern China, despite the shared similar genotypes. A comparison of the current data with those previously reported showed that the frequency of HCV genotype 6 increased from 25% to 47% within 5 years, especially subtypes 6a (5% to 15%) and 6n (11.2% to 30%). In contrast, the frequencies of subtypes 3b and 1b decreased by almost 50% within 5 years. Conclusion/Significance Our results provided further information to support the assertion that drug trafficking routes influence HCV transmission patterns among IDUs in Yunnan Province. The frequency of HCV genotypes and subtypes changed rapidly among IDUs in Yunnan Province and subtypes 6a and 6n may have originated in Vietnam and Myanmar, respectively. PMID:24358211

  18. Hepatitis C virus genotype diversity among intravenous drug users in Yunnan Province, Southwestern China.

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    Zhihui Zhang

    Full Text Available BACKGROUND: Recently, high proportions (15.6%-98.7% of intravenous drug users (IDUs in China were found to be positive for hepatitis C virus (HCV. Yunnan Province is located in southwestern China and borders one of the world's most important opium-producing regions, thus it is an important drug trafficking route to other regions of China. METHODOLOGY/PRINCIPAL FINDINGS: Here, we assessed 100 HCV-positive plasma samples from IDUs who were enrolled through the Kunming Center for Disease Control and Prevention in 2012. HCV C/E1 fragments were PCR-amplified and sequenced. We identified eight HCV subtypes (1a, 1b, 3a, 3b, 6a, 6n, 6u and 6v, of which genotype 6 was most predominant (frequency, 47% followed by genotypes 3 (41% and 1 (12%. HCV subtypes 6n (30% and 3b (29% were most common and were identified in 59% of the IDUs. We compared HCV genotypes among IDUs in Yunnan Province with those from other regions and found that the distribution patterns of HCV genotypes in Yunnan Province were similar to those in southern China, but different from those in eastern China. However, the distribution patterns of HCV subtypes varied among Yunnan Province and southern China, despite the shared similar genotypes. A comparison of the current data with those previously reported showed that the frequency of HCV genotype 6 increased from 25% to 47% within 5 years, especially subtypes 6a (5% to 15% and 6n (11.2% to 30%. In contrast, the frequencies of subtypes 3b and 1b decreased by almost 50% within 5 years. CONCLUSION/SIGNIFICANCE: Our results provided further information to support the assertion that drug trafficking routes influence HCV transmission patterns among IDUs in Yunnan Province. The frequency of HCV genotypes and subtypes changed rapidly among IDUs in Yunnan Province and subtypes 6a and 6n may have originated in Vietnam and Myanmar, respectively.

  19. Multicentric Castleman's Disease in a Hepatitis C-Positive Intravenous Drug User: A Case Report

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    D. Y. Talukder

    2011-01-01

    Full Text Available Introduction. We report a rare presentation of Castleman's disease in a hepatitis C-positive patient and present a short review of treatments described in other similar case reports and studies. Case Presentation. A 46-year-old male with untreated hepatitis C and a 16-year history of intravenous drug use presented with pleuritic chest pain and bony pain in the knee, hip, and lower back, on a background of unexplained weight loss of 40 kilograms, fevers, night sweats, and repeated infections over the last two years. Examination discovered tender hepatomegaly, a warm right knee effusion, and painless lymphadenopathy. The patient was reactive to Epstein Barr virus and cytomegalovirus; however, HIV and HHV-8 viral testing was negative. Osteomyelitis of vertebrae T8–T11 and septic arthritis of the knee were found on investigation. A lymph node biopsy revealed histology suggestive of plasmacytic Castleman's disease. The patient is to commence rituximab treatment. Conclusion. Castleman's disease continues to present in novel ways, which may lead to difficulties in clinicopathologic diagnosis. A growing body of evidence suggests larger studies are required to determine the best treatment for multicentric Castleman's disease, particularly in patients with a concomitant disease, including hepatitis C.

  20. [Non-transfusional and non-intravenous drug addiction related transmission of hepatitis C virus].

    Science.gov (United States)

    Serfaty, L

    1999-06-12

    PARENTERAL TRANSMISSION: Among subjects infected by the hepatitis C virus (HCV), about 40% have no history of blood transfusion or intravenous drug abuse. The highly variable presence of HCV in biological fluids other than blood would suggest that HVC transmission basically follows the parenteral route. Transmission of HCV via medical material contaminated by blood of an infected subject is a clinical reality: accidental needle prick, medical material (endoscope, physician-patient), tattooing, acupuncture, ear piercing, certain traditional practices, sharing toilet instruments (tooth brush, razor, fingernail shears). RARE SEXUAL TRANSMISSION: The prevalence of HCV infection is higher in people living with infected subjects, particularly spouses, than in the general population. However, transmission of HCV in this population probably follows a parenteral route (common risk factors, sharing toilet instruments) rather than by sexual transmission which plays a minor role except in sexually transmitted diseases with genital lesions. MOTHER-INFANT TRANSMISSION: Per- or post-partum transmission is possible though the risk is low, less than 5% of all infants are infected at the age of 1 year. The data are contradictory, but breast feeding would appear to play a role. Co-infection by the HIV virus, via high HCV viremia, clearly increases the risk of mother-infant transmission and perhaps also sexual transmission. NOSOCOMIAL TRANSMISSION: Nosocomial transmission is probably the most important factor in HCV transmission, but the risk remains to be quantified.

  1. Multicentric Castleman's Disease in a Hepatitis C-Positive Intravenous Drug User: A Case Report

    Science.gov (United States)

    Talukder, D. Y.; Delpachitra, S. N.

    2011-01-01

    Introduction. We report a rare presentation of Castleman's disease in a hepatitis C-positive patient and present a short review of treatments described in other similar case reports and studies. Case Presentation. A 46-year-old male with untreated hepatitis C and a 16-year history of intravenous drug use presented with pleuritic chest pain and bony pain in the knee, hip, and lower back, on a background of unexplained weight loss of 40 kilograms, fevers, night sweats, and repeated infections over the last two years. Examination discovered tender hepatomegaly, a warm right knee effusion, and painless lymphadenopathy. The patient was reactive to Epstein Barr virus and cytomegalovirus; however, HIV and HHV-8 viral testing was negative. Osteomyelitis of vertebrae T8–T11 and septic arthritis of the knee were found on investigation. A lymph node biopsy revealed histology suggestive of plasmacytic Castleman's disease. The patient is to commence rituximab treatment. Conclusion. Castleman's disease continues to present in novel ways, which may lead to difficulties in clinicopathologic diagnosis. A growing body of evidence suggests larger studies are required to determine the best treatment for multicentric Castleman's disease, particularly in patients with a concomitant disease, including hepatitis C. PMID:21577263

  2. Physicians' preferences for prescribing oral and intravenous anticancer drugs: a Discrete Choice Experiment.

    Science.gov (United States)

    Benjamin, Laure; Cotté, François-Emery; Philippe, Caroline; Mercier, Florence; Bachelot, Thomas; Vidal-Trécan, Gwenaëlle

    2012-04-01

    Although efficacy and tolerability are classical criteria for treatment choice, patient adherence and tariff issues related to novel oral anticancer drugs may also influence therapeutic decisions. We estimated the relative influence of efficacy, tolerability, expected adherence and route of administration of a chemotherapy treatment on 203 French physicians' preferences who participated in a Discrete Choice Experiment (DCE), a quantitative method used to elicit preferences. From a questionnaire with six scenarii, respondents had to choose between two treatments which differed with respect to these four attributes. Scenarii were first presented in a curative setting then in a palliative setting. Efficacy, tolerability and expected adherence had two modalities (good versus moderate) and route of administration had three modalities (intravenous (€286-379/session), oral with the current tariff (€28/consultation), oral with a hypothetical tariff (€114)). Efficacy was the reference criterion in choosing a treatment whatever the therapeutic goal (β: 2.114, padherence (β: 1.223, p=0.0001) were influent in curative setting while the route of administration was still predominant in palliative setting (β: 0.431, p<0.0001). Results suggest that economic considerations as well as therapeutic efficacy play a significant role in choosing a treatment. Preference for oral chemotherapy with a hypothetical tariff for a patient support programme should be considered for the development of therapeutic education and healthcare coordination, currently not taken into account in the tariff of oral chemotherapy. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. [Genetic characteristics of viral quasispecies of HIV-1 CRF07_BC among intravenous drug users].

    Science.gov (United States)

    Xin, Ruo-Lei; Ma, Ze-Qin; Cheng, Chun-Lin; Xing, Hui; Hong, Kun-Xue; Ruan, Yu-Hua; Li, Jia; Lu, Hong-Yan; Shao, Yi-Ming; He, Xiang

    2013-05-01

    To explore the genetic characteristics of viral quasispecies in HIV-1 CRF07_BC infections among intravenous drug users (IDU), the gp120 fragments of HIV-1 env gene were amplified from plasma samples collected from 6 CRF07_BC infected persons using single genome amplification and sequencing (SGA/ SGS) method, and 11 to 28 sequences were obtained from these samples, respectively, A neighbor-joining phylogenetic tree was reconstructed to describe the genetic characteristics of viral quasispecies. The Simplot, segments' phylogenetic trees and diversity plots based on average pairwise distance (APD) were used to identify the recombination events between quasispecies. The SGA sequences derived from single specimen formed a large monophyletic cluster in the neighbor-joining phylogenetic tree and showed the complex topologic structures of viral quasispecies. Of the 6 CRF07_BC infected patients, only one possessed the high genetic homogeneity, whereas the other five individuals showed high heterogeneity, with two to four subclusters inside the monophyletic cluster for each specimen. In addition, the recombinant events were identified among viral quasispecies from 3 cases. The results show SGA technique and phylogenetic analyses are useful tool to investigate the intrahost CRF07_BC gp120 complex quasispecies variation and high genetic diversity.

  4. A Model for the Application of Target-Controlled Intravenous Infusion for a Prolonged Immersive DMT Psychedelic Experience

    Science.gov (United States)

    Gallimore, Andrew R.; Strassman, Rick J.

    2016-01-01

    The state of consciousness induced by N,N-dimethyltryptamine (DMT) is one of the most extraordinary of any naturally-occurring psychedelic substance. Users consistently report the complete replacement of normal subjective experience with a novel “alternate universe,” often densely populated with a variety of strange objects and other highly complex visual content, including what appear to be sentient “beings.” The phenomenology of the DMT state is of great interest to psychology and calls for rigorous academic enquiry. The extremely short duration of DMT effects—less than 20 min—militates against single dose administration as the ideal model for such enquiry. Using pharmacokinetic modeling and DMT blood sampling data, we demonstrate that the unique pharmacological characteristics of DMT, which also include a rapid onset and lack of acute tolerance to its subjective effects, make it amenable to administration by target-controlled intravenous infusion. This is a technology developed to maintain a stable brain concentration of anesthetic drugs during surgery. Simulations of our model demonstrate that this approach will allow research subjects to be induced into a stable and prolonged DMT experience, making it possible to carefully observe its psychological contents, and provide more extensive accounts for subsequent analyses. This model would also be valuable in performing functional neuroimaging, where subjects are required to remain under the influence of the drug for extended periods. Finally, target-controlled intravenous infusion of DMT may aid the development of unique psychotherapeutic applications of this psychedelic agent. PMID:27471468

  5. A Model for the Application of Target-Controlled Intravenous Infusion for a Prolonged Immersive DMT Psychedelic Experience

    Directory of Open Access Journals (Sweden)

    Andrew Robert Gallimore

    2016-07-01

    Full Text Available The state of consciousness induced by N,N-dimethyltryptamine (DMT is one of the most extraordinary of any naturally-occurring psychedelic substance. Users consistently report the complete replacement of normal subjective experience with a novel alternate universe, often densely populated with a variety of strange objects and other highly complex visual content, including what appear to be sentient beings. The phenomenology of the DMT state is of great interest to psychology and calls for rigorous academic enquiry. The extremely short duration of DMT effects—less than 20 minutes—militates against single dose administration as the ideal model for such enquiry. Using pharmacokinetic modelling and DMT blood sampling data, we demonstrate that the unique pharmacological characteristics of DMT, which also include a rapid onset and lack of acute tolerance to its subjective effects, make it amenable to administration by target-controlled intravenous infusion. This is a technology developed to maintain a stable brain concentration of anaesthetic drugs during surgery. Simulations of our model demonstrate that this approach will allow research subjects to be induced into a stable and prolonged DMT experience, making it possible to carefully observe its psychological contents, and provide more extensive accounts for subsequent analyses. This model would also be valuable in performing functional neuroimaging, where subjects are required to remain under the influence of the drug for extended periods. Finally, target-controlled intravenous infusion of DMT may aid the development of unique psychotherapeutic applications of this psychedelic agent.

  6. A Model for the Application of Target-Controlled Intravenous Infusion for a Prolonged Immersive DMT Psychedelic Experience.

    Science.gov (United States)

    Gallimore, Andrew R; Strassman, Rick J

    2016-01-01

    The state of consciousness induced by N,N-dimethyltryptamine (DMT) is one of the most extraordinary of any naturally-occurring psychedelic substance. Users consistently report the complete replacement of normal subjective experience with a novel "alternate universe," often densely populated with a variety of strange objects and other highly complex visual content, including what appear to be sentient "beings." The phenomenology of the DMT state is of great interest to psychology and calls for rigorous academic enquiry. The extremely short duration of DMT effects-less than 20 min-militates against single dose administration as the ideal model for such enquiry. Using pharmacokinetic modeling and DMT blood sampling data, we demonstrate that the unique pharmacological characteristics of DMT, which also include a rapid onset and lack of acute tolerance to its subjective effects, make it amenable to administration by target-controlled intravenous infusion. This is a technology developed to maintain a stable brain concentration of anesthetic drugs during surgery. Simulations of our model demonstrate that this approach will allow research subjects to be induced into a stable and prolonged DMT experience, making it possible to carefully observe its psychological contents, and provide more extensive accounts for subsequent analyses. This model would also be valuable in performing functional neuroimaging, where subjects are required to remain under the influence of the drug for extended periods. Finally, target-controlled intravenous infusion of DMT may aid the development of unique psychotherapeutic applications of this psychedelic agent.

  7. Preliminary research on the co-infection of human immunodeficiency virus and hepatitis virus in intravenous drug users

    Institute of Scientific and Technical Information of China (English)

    吴南屏; 李丹; 朱彪; 邹微

    2003-01-01

    Objective To confirm the close relationship of high co-infection rate between HIV and hepatitis virus in intravenous drug users (IVDUs).Methods Anti-HIV, HBV and HCV were detected by ELISA in the serum from 35 scattered and 15 massed IVDUs. PCR and RT-PCR were performed to confirm the infection of HIV, HBV, HCV, HGV and TTV among the 15 massed intravenous drug abusers.Results Among the 50 IVDUs, the positive rates of anti-HCV1 HBsAg, anti-HBe and anti-HBc were 92% (46/50), 12% (6/50), 10% (5/50) and 66% (33/50), respectively. In the samples of HBsAg positive, their HBeAg was also positive. Although the positive rate of serum markers was different in the massed IVDUs compared to the scattered IVDUs, no significant difference was shown. In the cases of massed IVDUs, the positive rates of HIV DNA, HBV-DNA, HCV-RNA, HGV-RNA, and TTV-DNA were 100% (15/15), 26.6% (4/15), 53.3% (8/15), 33.3% (5/15) and 26.6% (4/15), respectively. Among the 15 massed intravenous drug users, one was infected with HIV, HBV, HCV, HGV and TTV; two were infected with HIV, HBV, HCV and HGV; three were infected only with HIV; and the remaining had other forms of co-infection.Conclusion The co-infection rate of HIV, HBV, HCV, HGV and TTV in intravenous drug users is very high.

  8. Epidemiology of Hepatitis B, C, D and G Viruses and Cytokine Levels among Intravenous Drug Users

    Institute of Scientific and Technical Information of China (English)

    LI Jianrong; WANG Jing; TIAN Kunlun; WANG Yixin; ZHANG Lei; HUANG Hanju

    2006-01-01

    To investigate the features of various hepatitis virus infection in intravenous drug users (IVDU), we conducted an epidemiological survey of hepatitis viruses including hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV) and hepatitis G virus (HGV) in IVDU. The correlation of TH lymphocyte cytokine and hepatitis virus infection was examined. A study population of 406 IVDU consisted of 383 males and 23 females. HBV-DNA and HCV-RNA were detected by fluorescence quantitative polymerase chain reaction. HBsAg, HBeAg, anti-HBc,anti-HCV, HDV-Ag and anti-HGV were assayed by ELISA. The levels of cytokines of TH 1 and TH2 were measured by ELISA. The similar indices taken from 102 healthy persons served as controls. The infection-rate of each virus among IVDU was 36.45 % for HBV, 69. 7 % for HCV,2.22 % for HDV, and 1. 97 % for HGV, respectively. The co-infection rate of HBV and HCV was detected in 113 of 406 (27. 83%). In contrast, among controls, the infection rate was 17.65 % for HBV and 0% for the other hepatitis viruses. The levels of PHA-induced cytokines (IFN-γ and IL-4) and the level of serum IL 2 were obviously decreased in IVDU. On the other hand, the level of serum IL-4 was increased. The IFN-γ level was continuously decreased when the IVDU was infected with HBV/HCV. In conclusion, HBV and HCV infection were common in this population ofIVDU and they had led to a high incidence of impaired TH 1 cytokine levels.

  9. Drug insight: Safety of intravenous iron supplementation with sodium ferric gluconate complex.

    Science.gov (United States)

    Michael, Beckie; Fishbane, Steven; Coyne, Daniel W; Agarwal, Rajiv; Warnock, David G

    2006-02-01

    Intravenous iron is necessary for optimal management of anemia in patients receiving hemodialysis and is utilized in the majority of these patients in the US. The availability of nondextran formulations of intravenous iron has significantly improved the safety of its use. The nondextran iron formulation sodium ferric gluconate complex (SFGC) has been extensively studied in the hemodialysis population, with two large phase IV trials documenting its safety. SFGC is efficacious and, at recommended doses, is associated with a low incidence of adverse events. There have been few comparative studies of the nondextran intravenous iron preparations; however, they are known to have different pharmacokinetic characteristics. There is also evidence to indicate that these compounds differ in terms of their cytotoxic and proinflammatory properties, and their propensity to induce oxidative stress. This paper reviews the current literature on the safety of SFGC and examines the emerging safety issues surrounding the use of intravenous iron.

  10. Alarming increase in tuberculosis and hepatitis C virus (HCV among HIV infected intravenous drug users

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    Cristiana Oprea

    2014-11-01

    Full Text Available Introduction: In the last years, we observed an alarming increase in the number of newly diagnosed HIV infected intravenous drug users (IDUs co-infected with hepatitis viruses or with severe bacterial infections. The aim of our study was to assess the incidence, the demographic and clinical characteristics of IDUs diagnosed with HIV, HCV and tuberculosis (TB. Materials and Methods: Prospective study on HIV infected IDUs with HCV and TB admitted in a single centre between January 2009 and April 2014. Data were compared to a group of HIV infected IDUs without TB. Statistical analysis was performed using Graphpad Prism 4.01. Results: Out of 450 HIV infected IDUs, 134 (29.7% were diagnosed with HIV, HCV and TB. TB incidence among IDUs increases from 0% in 2009 to 30.2% in 2013. The TB coinfected patients had a mean age at diagnosis of 30 [15–56] years; were in majority males, 106 (84.4%; from urban areas, 120 (89.5%; and had significantly lower education level (85% vs 68.3%, p<0.0001 and higher rates of unemployment (80% vs 55%, p<0.0001 than those without TB. The median CD4 cell count was lower in the TB versus non TB IDUs (143 vs 472/mm3, p<0.0001. TB infected IDUs tend to be more frequently late presenters (59.7 vs 24.6, p<0.0001 and to have advanced HIV disease (47.7 vs 7.59%, p<0.0001 than those without TB. TB cultures were positive in 64 (47.7% patients, 3 (2.2% had multidrug resistant TB and 2 (1.5% had extended drug resistance. Disseminated and/or extrapulmonary TB was diagnosed in 51 patients (38%. The overall mortality rate was higher in TB compared to non TB IDUs (19.4% vs 8.2%, p=0.0007, disseminated TB being associated with the most severe immunosuppression (median CD4 cell count 42/mm3 and the highest mortality rate (27.4%. Conclusions: The incidence of TB in HIV/HCV coinfected IDUs was high and rose over the time. TB infection was more frequent in patients with severe immunosuppression and the mortality rate was higher in IDUs with

  11. Transmission of hepatitis C virus among intravenous drug users in the Uppsala region of Sweden

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    Axel Danielsson

    2014-01-01

    Full Text Available Background: Epidemiology and transmission patterns of hepatitis C virus (HCV are important subjects as we enter a new era of treatment with directly acting antivirals (DAAs. The highest prevalence of HCV in developed countries is found among intravenous drug users (IDUs, where unsafe needle sharing practices provide the main route of infection. Efforts to prohibit the continuous spread of HCV among these groups have been initiated by the community services and health care providers. Our goal was to understand how HCV was transmitted among IDUs within a limited population group. We provide a retrospective study (2005–2007 of the HCV transmission patterns in a population of IDUs in the Uppsala region of Sweden. Method: Eighty-two serum samples were collected from IDUs in Uppsala County. Our reverse transcription nested polymerase chain reaction (RT-nested PCR and sequencing method enabled a comprehensive genetic analysis for a broad spectrum of genotypes of two relatively conserved regions, NS5B and NS3, that encodes for the viral polymerase and protease, respectively. HCV RNA in serum samples was amplified and sequenced with in-house primers. Sequence similarities between individuals and subgroups were analyzed with maximum likelihood (ML phylogenetic trees. Published HCV reference sequences from other geographic regions and countries were also included for clarity. Results: Phylogenetic analysis was possible for 59 NS5B (72% and 29 NS3 (35% sequences from Uppsala patients. Additionally, we also included 15 NS3 sequences from Örebro patients, making a total of 44 NS3 sequences for the analysis. By analyzing the NS3 sequences, two transmission sets were found between the IDUs (>98% sequence identity, with one set consisting of two individuals and another set consisting of three individuals. In addition, the phylogenetic analysis done with our serum samples displayed clusters that distinguished them from the reference sequences. Conclusion: Our

  12. False-positive tests for syphilis associated with human immunodeficiency virus and hepatitis B virus infection among intravenous drug abusers. Valencian Study Group on HIV Epidemiology.

    Science.gov (United States)

    Hernández-Aguado, I; Bolumar, F; Moreno, R; Pardo, F J; Torres, N; Belda, J; Espacio, A

    1998-11-01

    The role of HIV, hepatitis C virus, and hepatitis B virus infections in the production of biological false-positive reactions for syphilis was evaluated in two large samples of intravenous drug abusers and homosexual men attending AIDS prevention centers in Spain. A significantly increased odds ratio (OR) for false-positive tests for syphilis [OR 2.23, 95% confidence intervals (CI) 1.76-2.83] was observed for HIV-seropositive intravenous drug abusers; biological false-positive reactions were also more frequent (OR 1.73, 95% CI 1.30-2.31) among intravenous drug abusers who were hepatitis B virus seropositive but not among those who were hepatitis C virus seropositive (OR 0.90; 95% CI 0.48-1.69). Among homosexuals, the association between HIV and biological false-positive reactions was restricted to subjects who were also intravenous drug abusers, indicating the crucial role of intravenous drug abuse. Only 20.5% of intravenous drug abusers with a previous biological false-positive reaction yielded a false-positive result in their subsequent visit.

  13. Monocyte function in intravenous drug abusers with lymphadenopathy syndrome and in patients with acquired immunodeficiency syndrome: selective impairment of chemotaxis.

    Science.gov (United States)

    Poli, G; Bottazzi, B; Acero, R; Bersani, L; Rossi, V; Introna, M; Lazzarin, A; Galli, M; Mantovani, A

    1985-01-01

    We have investigated monocyte function in 17 intravenous drug abusers with the clinical and laboratory features of lymphadenopathy syndrome (LAS). LAS patients had normal numbers of circulating monocytes. Monocytes from LAS patients were comparable to cells from normal donors in terms of phagocytosis of latex beads, interleukin-1 secretion, O2- release and killing of antibody-sensitized lymphoma cells or actinomycin D pretreated WEHI 164 cells. In contrast 13 out of 17 LAS subjects tested in this respect as well as six out of nine AIDS patients showed a marked defect of monocyte chemotaxis. Thus monocytes from patients with LAS or AIDS have a selective defect of monocyte chemotaxis. PMID:2998656

  14. Drug delivery applications with ethosomes.

    Science.gov (United States)

    Ainbinder, D; Paolino, D; Fresta, M; Touitou, E

    2010-10-01

    Ethosomes are specially tailored vesicular carriers able to efficiently deliver various molecules with different physicochemical properties into deep skin layers and across the skin. This paper reviews the unique characteristics of the ethosomal carriers, focusing on work carried out with drug containing ethosomal systems in animal models and in clinical studies. The paper concludes with a discussion on the safety of the ethosomal system applications.

  15. 77 FR 71802 - Guidance on Investigational New Drug Applications for Positron Emission Tomography Drugs...

    Science.gov (United States)

    2012-12-04

    ... HUMAN SERVICES Food and Drug Administration Guidance on Investigational New Drug Applications for... ``Investigational New Drug Applications for Positron Emission Tomography (PET) Drugs.'' The guidance is intended to assist manufacturers of PET drugs in submitting investigational new drug applications (INDs)....

  16. Emerging integrated nanohybrid drug delivery systems to facilitate the intravenous-to-oral switch in cancer chemotherapy.

    Science.gov (United States)

    Luo, Cong; Sun, Jin; Du, Yuqian; He, Zhonggui

    2014-02-28

    Nanohybrid drug delivery systems have presented lots of characteristic advantages as an efficient strategy to facilitate oral drug delivery. Nonetheless, oral administration of chemotherapy agents by nanoparticulate delivery technology still faces great challenges owing to the multiple biobarriers ranging from poorly physicochemical properties of drugs, to complex gastrointestinal disposition and to presystemic metabolism. This review briefly analyzes a series of biobarriers hindering oral absorption and describes the multiple aspects for facilitating the intravenous-to-oral switch in cancer therapy. Moreover, the developed nanoparticulate drug delivery strategies to overcome the above obstacles are provided, including metabolic enzyme inhibition, enteric-coated nanocarriers, bioadhesive and mucus-penetrating strategies, P-gp inhibition and active targeting. On these foundations, the emerging trends of integrated hybrid nanosystems in response to the present low-efficiency drug delivery of any single approach are summarized, such as mixed polymeric micelles and nanocomposite particulate systems. Finally, the recent advances of high-efficiency hybrid nanoparticles in oral chemotherapy are highlighted, with special attention on integrated approach to design drug delivery nanosystems.

  17. Cytoprotection by omega-3 fatty acids as a therapeutic drug vehicle when combined with nephrotoxic drugs in an intravenous emulsion: Effects on intraglomerular mesangial cells

    Directory of Open Access Journals (Sweden)

    Gabriel Alejandro Bonaterra

    2014-01-01

    Full Text Available During therapeutic interventions, blood concentrations of intravenously applied drugs are higher, and their onset of pharmacological action is faster than with other routes of drug administration. However, acute drug therapy often produces nephrotoxic side effects, as commonly seen after treatment with Ketorolac or Gentamicin leading to questions about their use, especially for patients at risk for acute renal failure. Omega-6(n-6 and omega-3(n-3 polyunsaturated fatty acids (PUFA affect eicosanoid metabolism, which plays a role in the regulation of inflammation. Eicosanoids derived from n-6 FA have proinflammatory and immunoactive functions, whereas eicosanoids derived from n-3 PUFA have anti-inflammatory and cytoprotective properties. We hypothesized that providing such injectable drugs with nephrotoxic potential in combination with n3-PUFAs from the outset, might afford rapid cytoprotection of renal cells, given the recent evidence that intravenously administered n3-PUFAs are rapidly incorporated into cell membranes. We used intraglomerular mesangial cells (MES13 that are sensitive to treatment with Ketorolac or Gentamicin instead of proximal tubular cells which do not respond to Ketorolac. We found a significant inhibition of Ketorolac (0.25, 0.5, 1 mM or Gentamicin (2.5, 5 mM induced cytotoxicity after pretreatment of MES13 cells with 0.01% of 20%w/v LipOmega-3 Emulsion 9/1, containing 90:10 wt/wt mixture of fish oil derived triglycerides to medium chain triglycerides.

  18. Hepatitis C, interferon alpha and psychiatric co-morbidity in intravenous drug users (IVDU) : guidelines for clinical practice.

    Science.gov (United States)

    De Bie, J; Robaeys, G; Buntinx, F

    2005-01-01

    The evidence regarding the co-morbidity of chronic hepatitis C, psychiatric illness and intravenous drug abuse is reviewed from the literature. Also the occurrence and the treatment of psychiatric side effects during treatment with interferon in patients with a history of drug abuse are reviewed. There is insufficient evidence for a specific hepatitis C induced depression or fatigue, but a direct link between hepatitis C and cerebral dysfunction is not excluded. Immune system activation rather than drug use may explain cerebral symptoms. In HCV positive substance users anxiety and depression are more prevalent than in HCV negative substance users. During treatment with regular or pegylated (PEG) interferon depression is a frequent side effect (ca 30%) and occurs independently from pre-existing psychiatric disorders or drug abuse. A history of drug abuse per se does not increase the risk of depression as a side effect of interferon treatment. It is extremely important to monitor symptoms of depression in the early weeks of treatment and to start antidepressant treatment as early as possible. Antidepressants should be continued throughout the interferon treatment period. There are insufficient data to assess these situations in which preventive antidepressant treatment should be started before interferon treatment. Clinical judgement can, however, lead to preventive antidepressant treatment, even at subclinical levels of depression. A cut off score of > 10 on the Beck Depression Inventory before interferon treatment is associated with a higher risk of depression during treatment. Both selective serotonin reuptake inhibitors and other classes of antidepressants can be used.

  19. Intravenous pretreatment with empty pH gradient liposomes alters the pharmacokinetics and toxicity of doxorubicin through in vivo active drug encapsulation.

    Science.gov (United States)

    Mayer, L D; Reamer, J; Bally, M B

    1999-01-01

    Liposomes have been used widely to improve the therapeutic activity of pharmaceutical agents. The traditional approach for such applications has been to formulate the pharmaceutical agent in liposomes prior to administration in vivo. In this report we demonstrate that liposomes exhibiting a transmembrane pH gradient injected intravenously (iv) can actively encapsulate doxorubicin in the circulation after iv administration of free drug. Small (110 nm) liposomes composed of phosphatidylcholine (PC)/cholesterol (Chol, 55:45 mol:mol) exhibiting a pH gradient (inside acidic) were administered iv 1 h prior to free doxorubicin, and plasma drug levels as well as toxicity and efficacy were evaluated. Predosing with egg PC/Chol pH gradient liposomes increased the plasma concentration of doxorubicin as much as 200-fold compared to free drug alone as well as to predosing with dipalmitoyl PC/Chol pH gradient liposomes or EPC/Chol liposomes without a pH gradient. The ability of the liposomes to alter the pharmacokinetics of doxorubicin was dependent on the presence of a transmembrane pH gradient and correlated with the extent of doxorubicin uptake into the liposomes at 37 degreesC in pH 7.5 buffer, indicating that doxorubicin was being actively accumulated in the circulating liposomes. This in vivo drug loading was achieved over a range of doxorubicin doses (5 mg/kg-40 mg/kg) and was dependent on the dose of EPC/Chol liposomes administered prior to free doxorubicin injection. The altered pharmacokinetic properties of doxorubicin associated with in vivo doxorubicin encapsulation were accompanied by a decrease in drug toxicity and maintained antitumor potency. These results suggest that pretreatment with empty liposomes exhibiting a pH gradient may provide a versatile and straightforward method for enhancing the pharmacological properties of many drugs that can accumulate into such vesicle systems at physiological temperatures.

  20. Inertial cavitation to non-invasively trigger and monitor intratumoral release of drug from intravenously delivered liposomes.

    Science.gov (United States)

    Graham, Susan M; Carlisle, Robert; Choi, James J; Stevenson, Mark; Shah, Apurva R; Myers, Rachel S; Fisher, Kerry; Peregrino, Miriam-Bazan; Seymour, Len; Coussios, Constantin C

    2014-03-28

    The encapsulation of cytotoxic drugs within liposomes enhances pharmacokinetics and allows passive accumulation within tumors. However, liposomes designed to achieve good stability during the delivery phase often have compromised activity at the target site. This problem of inefficient and unpredictable drug release is compounded by the present lack of low-cost, non-invasive methods to measure such release. Here we show that focused ultrasound, used at pressures similar to those applied during diagnostic ultrasound scanning, can be utilised to both trigger and monitor release of payload from liposomes. Notably, drug release was influenced by liposome composition and the presence of SonoVue® microbubbles, which provided the nuclei for the initiation of an event known as inertial cavitation. In vitro studies demonstrated that liposomes formulated with a high proportion of 1,2 distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) released up to 30% of payload following ultrasound exposure in the presence of SonoVue®, provided that the exposure created sufficient inertial cavitation events, as characterised by violent bubble collapse and the generation of broadband acoustic emissions. In contrast a 'Doxil'-like liposome formulation gave no such triggered release. In pre-clinical studies, ultrasound was used as a non-invasive, targeted stimulus to trigger a 16-fold increase in the level of payload release within tumors following intravenous delivery. The inertial cavitation events driving this release could be measured remotely in real-time and were a reliable predictor of drug release.

  1. Efficacy of Core Decompression of Femoral Head to Treat Avascular Necrosis in Intravenous Drug Users

    Directory of Open Access Journals (Sweden)

    Hossein Soleimani

    2013-04-01

    Full Text Available Core decompression (CD of the femoral head is one of the effective treatments of avascular necrosis (AVN, especially in the early stages of the disease. To investigate further the value of CD in treating the AVN, this study was performed on patients with symptomatic AVN with different etiologies who were treated with CD. This study was carried out on 25 patients (with the total number of 37 femoral head who were diagnosed AVN using X-Ray and MRI. The CD treatments for these patients were started soon after the diagnosis. The results were considered as a success if there was no progression of disease confirmed by X Ray or no subsequent operation was required. Modified Ficat staging was used to record changes before and 2 years after CD treatment. Twenty five patients were participated in this study in which 68% (n=17 were female, 32% (n=8 were male, and the average of the age of the patients were 29.58±4.58. Eight of these patients had systemic lupus erythematous (SLE (32%, 4 rheumatoid arthritis (RA (16%, 3 with kidney transplant (12%, 1 Takayasu’s vasculitis (4% and 1 Wegner vasculitis (4%. Eight of patients had a history of intravenous injection of Temgesic (32%. In patients using Temgesic the changes in Modified Ficat staging were significantly different before and after CD treatment (P=0.03 in comparison with other groups. And in all 8 Temgesic users AVN progressed to the stage 3 and 4 after CD treatment. This study demonstrated that CD treatment to prevent the changes in the femoral head has been more effective in patients with collagen vascular diseases and kidney transplant than patients using intravenous Temgesic. These patients, in spite of early operation, showed no benefit of CD to prevent the changes in the femoral head.

  2. Isolated Pulmonary Valve Endocarditis Complicated With Septic Emboli to the Lung Causing Pneumothorax, Pneumonia, and Sepsis in an Intravenous Drug Abuser

    Directory of Open Access Journals (Sweden)

    Deephak Swaminath MD

    2013-11-01

    Full Text Available Intravenous drug users are at increased risk for developing right-sided infective endocarditis involving the tricuspid and pulmonary valves. Isolated pulmonary valve endocarditis in intravenous drug users is very rare, and these patients often have more complications, such as pulmonary embolism, sepsis, and pneumonia. We report a case with pulmonary valve endocarditis and extensive pulmonary complications, including sepsis, septic emboli, pneumonia, and pneumothorax. Early identification of pulmonic valve endocarditis and treatment with appropriate antibiotics with or without surgical management should provide better outcomes, and clinicians need to think about pulmonary valve endocarditis in patients with complex respiratory presentations.

  3. Flat detector computed tomography angiography with intravenous contrast application: feasibility for visualization of cerebral arterial vasculature.

    Science.gov (United States)

    Saake, Marc; Breuer, Lorenz; Goelitz, Philipp; Ott, Sabine; Struffert, Tobias; Doerfler, Arnd

    2013-07-01

    The aim of our study was to evaluate flat detector computed tomography angiography with peripheral intravenous contrast material application (FD-CTA) for visualization of cerebral arteries in comparison with intravenous multidetector computed tomography angiography (CTA) and intraarterial digital subtraction angiography (DSA). The study was approved by the local institutional review board and informed consent was obtained by all participants. Ten patients underwent FD-CTA, CTA, and DSA of the cerebral arterial vasculature for suspected cerebrovascular disease. The image data were evaluated by two readers in consensus for the visualization of cerebral arterial segments on a 5-point scale (0 = vessel cannot be distinguished; 4 = excellent image quality). The Wilcoxon signed-rank test was used for statistical analysis. Note that P < .05 was considered to indicate a significant difference. The depiction of cerebral arterial segments with FD-CTA was significantly superior compared to CTA in most vessel segments (P < .05 in 20 of 23 anatomic regions) and was without significant difference compared with DSA in large and medium intracranial vessels. The results suggest that the cerebral arteries can be visualized by FD-CTA in high resolution, in many vessel segments comparable to DSA. Copyright © 2012 by the American Society of Neuroimaging.

  4. Analysis of Anthrax Immune Globulin Intravenous with Antimicrobial Treatment in Injection Drug Users, Scotland, 2009–2010

    Science.gov (United States)

    Cui, Xizhong; Nolen, Leisha D.; Sun, Junfeng; Booth, Malcolm; Donaldson, Lindsay; Quinn, Conrad P.; Boyer, Anne E.; Hendricks, Katherine; Shadomy, Sean; Bothma, Pieter; Judd, Owen; McConnell, Paul; Bower, William A.

    2017-01-01

    We studied anthrax immune globulin intravenous (AIG-IV) use from a 2009–2010 outbreak of Bacillus anthracis soft tissue infection in injection drug users in Scotland, UK, and we compared findings from 15 AIG-IV recipients with findings from 28 nonrecipients. Death rates did not differ significantly between recipients and nonrecipients (33% vs. 21%). However, whereas only 8 (27%) of 30 patients at low risk for death (admission sequential organ failure assessment score of 0–5) received AIG-IV, 7 (54%) of the 13 patients at high risk for death (sequential organ failure assessment score of 6–11) received treatment. AIG-IV recipients had surgery more often and, among survivors, had longer hospital stays than did nonrecipients. AIG-IV recipients were sicker than nonrecipients. This difference and the small number of higher risk patients confound assessment of AIG-IV effectiveness in this outbreak. PMID:27983504

  5. [Aorto pulmonary fistula: left-sided infective endocarditis in HIV and intravenous drugs abuser patient. Review of the literature].

    Science.gov (United States)

    Obón Azuara, B; Zalba Etayo, B; Gutiérrez Cía, I; Villanueva Anadón, B

    2007-11-01

    Infective endocarditis (IE) is the most severe complication in intravenous drug abusers (IVDAs). HIV infection increases the risk of IE in IVDAs too. IE in both population are special tendency to infect the right-sided heart, but unusual infective aortic valve. We report a case of HIV and IVDA patient admitted in hospital due to fever syndrome, with X-ray test normal and the first blood cultures negatives. CD4 count cell 90 mm3. It was impossible doing a transesophageal echocardiography (TEE) and transtoracic echocardiogramma (TTE) only showed a moderate aortic insufficiency with conserved systolic function. Despite using antibiotics, antifungals and highly active antiretroviral therapy, he developed ARDS, and mechanical ventilation should be performed. At that moment, TEE showed an aorto pulmonary fistula due to left-sided IE. Further cultures was undergone and only one blood culture was positive to Staphylococcus aureus. Cardiac surgery was not indicated. The patient died 3 weeks later.

  6. Pharmacokinetics of amoxicillin/clavulanic acid combination and of both drugs alone after intravenous administration to goats.

    Science.gov (United States)

    Escudero, E; Carceles, C M; Vicente, S

    1996-09-01

    The pharmacokinetic behaviour of an amoxicillin/clavulanic acid combination (25 mg kg-1), and both drugs alone (amoxicillin 20 mg kg-1), clavulanic acid 5 mg kg-1), was studied after intravenous (i.v.) administration of single doses of 10 goats. The objective was to determine whether there were differences in the plasma kinetics of these drugs when administered in combination or alone. The plasma concentration-time data were analysed by compartmental pharmacokinetics and non-compartmental methods. The disposition curves for both drugs alone and in combination were best described by a biexponential equation (two-compartment open model). The elimination half-lives of amoxicillin were 1.05 +/- 0.09 h alone and 1.13 +/- 0.19 h in combination, and those of clavulanic acid were 0.87 +/- 0.07 h and 0.85 +/- 0.09 h, respectively. The apparent volumes of distribution of amoxicillin and clavulanic acid were similar in the two treatments. Body clearances of amoxicillin were 0.12 +/- 0.01 l h-1.kg alone and 0.11 +/- 0.01 l h-1.kg in combination, and of clavulanic acid were 0.12 +/- 0.02 l h-1.kg alone and 0.12 +/- 0.01 l h-1.kg in combination with amoxicillin. The half-lives and body clearances of amoxicillin and clavulanic acid did not differ significantly when administered alone and in combination. It was concluded that the i.v. administration of amoxicillin and clavulanic acid as a combination product did not alter the disposition kinetics of either drug.

  7. Clinical Application of Insect Drugs

    Institute of Scientific and Technical Information of China (English)

    钟洪; 赵洁

    2003-01-01

    @@ Chinese insect drugs are drastic in nature, capable ofclearing channels and collaterals to promote a freeflow of qi and blood, and effective in someintractable and obstinate diseases due to long-termstagnation of phlegm and blood, which are hard to betreated by ordinary Chinese drugs. In clinic, properuse of insect drugs can often help raise thetherapeutic effects. Some commonly used pairs ofinsect drugs are introduced in the following.

  8. A review on phospholipids and their main applications in drug delivery systems

    Directory of Open Access Journals (Sweden)

    Jing Li

    2015-04-01

    Full Text Available Phospholipids have the characteristics of excellent biocompatibility and a especial amphiphilicity. These unique properties make phospholipids most appropriate to be employed as important pharmaceutical excipients and they have a very wide range of applications in drug delivery systems. The aim of this review is to summarize phospholipids and some of their related applications in drug delivery systems, and highlight the relationship between the properties and applications, and the effect of the species of phospholipids on the efficiency of drug delivery. We refer to some relevant literatures, starting from the structures, main sources and properties of phospholipids to introduce their applications in drug delivery systems. The present article focuses on introducing five types of carriers based on phospholipids, including liposomes, intravenous lipid emulsions, micelles, drug-phospholipids complexes and cochleates.

  9. METHYLPHENIDATE ENHANCES THE ABUSE-RELATED BEHAVIORAL EFFECTS OF NICOTINE IN RATS: INTRAVENOUS SELF-ADMINISTRATION, DRUG DISCRIMINATION AND LOCOMOTOR CROSS-SENSITIZATION

    OpenAIRE

    Wooters, Thomas E.; Neugebauer, Nichole M.; Rush, Craig R.; Bardo, Michael T.

    2007-01-01

    Stimulant drugs, including d-amphetamine, cocaine and methylphenidate, increase cigarette smoking in controlled human laboratory experiments. Although the mechanism(s) underlying this effect are unknown, it is possible that stimulants may enhance directly the abuse-related effects of nicotine. In the present study, we characterized the behavioral pharmacological interactions between methylphenidate and nicotine in the intravenous self-administration, drug discrimination and locomotor cross-se...

  10. Clinical Pharmacology of Frequently Used Intravenous Drugs During Bariatric Surgery in Adolescents.

    Science.gov (United States)

    Vaughns, Janelle D; Ziesenitz, Victoria C; van den Anker, John N

    2015-01-01

    Obesity represents one of the most important public health issues according to the World Health Organization. Additionally, in a recent National Health and Nutrition Survey of 2011-2012, approximately 17 % of children and adolescents in the United States were considered obese. The obesity rate is higher within the adolescent age group as compared to preschool children. Childhood obesity is particularly problematic, because the co-morbid disease states which accompany obesity may require frequent pharmacotherapy and/ or surgical intervention. Despite the potential for increased pharmacotherapy among obese patients, there is a paucity of dosing guidelines for this special population. Optimal drug dosing in obese pediatric patients has not been sufficiently explored as the present data available are mostly specific for obese adults. In this review, we present an overview concerning what is currently known about the pharmacokinetics and pharmacogenetics of frequently used drugs including midazolam, fentanyl and its newer derivatives, morphine, ketamine, acetaminophen, dexmedetomidine and enoxaparin in obese adolescents undergoing bariatric surgery. We will also summarize the current dosing recommendations of anesthetic drugs in bariatric anesthesia.

  11. LOCALIZATION OF PALM DORSAL VEIN PATTERN USING IMAGE PROCESSING FOR AUTOMATED INTRA-VENOUS DRUG NEEDLE INSERTION

    OpenAIRE

    Mrs. Kavitha. R,; Tripty Singh

    2011-01-01

    Vein pattern in palms is a random mesh of interconnected and inter- wining blood vessels. This project is the application of vein detection concept to automate the drug delivery process. It dealswith extracting palm dorsal vein structures, which is a key procedure for selecting the optimal drug needle insertion point. Gray scale images obtained from a low cost IR-webcam are poor in contrast, and usually noisy which make an effective vein segmentation a great challenge. Here a new vein image s...

  12. Pharmacokinetics of the antiepileptic drug levetiracetam in healthy Japanese and Caucasian volunteers following intravenous administration.

    Science.gov (United States)

    Toublanc, Nathalie; Okagaki, Takuya; Boyce, Malcolm; Chan, Robert; Mugitani, Ayumi; Watanabe, Shikiko; Yamamoto, Katsumi; Yoshida, Katsumi; Andreas, Jens-Otto

    2015-12-01

    The intravenous (iv) formulation of levetiracetam has been available in clinical practice worldwide for several years, but not in Japan. Two open-label studies were conducted: Study A evaluated the bioequivalence of iv and oral tablet formulations in healthy Japanese volunteers; and Study B subsequently compared the pharmacokinetics of iv levetiracetam in healthy Japanese and Caucasian volunteers. Study A had a randomised, two-way crossover design; a single 1,500 mg levetiracetam dose was administered as a 15-min iv infusion and as 3 × 500 mg oral tablets to Japanese volunteers. In Study B, 1,500 mg levetiracetam was administered as single and repeated 15-min iv infusions to Japanese and Caucasian volunteers. Overall, 26/27 volunteers completed Study A and 32/32 (16 Japanese; 16 Caucasian) completed Study B. In Study A, the point estimate and 90 % confidence interval (CI) for the geometric least squares mean (LSM) ratio (iv vs oral) were fully included within the acceptance range for bioequivalence (0.85-1.25) for the area under plasma concentration-time curve from 0 to last quantifiable observation (AUClast 0.97 [0.95, 0.99]), but not for the maximum plasma concentration (C max 1.64 [1.47, 1.83]). In Study B, after a single iv infusion, the point estimates (90 % CI) for the geometric LSM ratio (Japanese vs Caucasian) for body weight-normalised C max and AUClast were 1.21 (1.07, 1.36) and 0.97 (0.90, 1.04), respectively. Corresponding values after repeated iv infusions were C max,ss 1.01 (0.91, 1.12) and AUCτ,ss 0.89 (0.83, 0.96). Levetiracetam was well tolerated in both studies. Study A did not demonstrate the bioequivalence of single doses of levetiracetam 1,500 mg administered as an iv infusion and as oral tablets in healthy Japanese adults. Study B, however, showed that pharmacokinetic profiles were generally similar between Japanese and Caucasian adults after single and repeated iv infusions of levetiracetam 1,500 mg.

  13. Gender differences in HIV risk behaviours among intravenous drug users in Catalonia, Spain.

    Science.gov (United States)

    Folch, Cinta; Casabona, Jordi; Espelt, Albert; Majó, Xavier; Meroño, Mercè; Gonzalez, Victoria; Brugal, Maria Teresa

    2013-01-01

    To describe gender differences in injection and sexual risks behaviours, and human immunodeficiency virus (HIV) and hepatitis C (HCV) prevalence among injecting drug users (IDU) in Catalonia, Spain. Cross-sectional studies in 2008-2009 (n=748) and 2010-2011 (n=597) in the network of harm reduction centres. Face to face interviews were conducted and oral fluid samples were collected to estimate HIV/HCV prevalence. Female were more likely than male IDU to have had a steady sexual partner (68.2% versus 44.9%), to have had an IDU steady sexual partner (46.6% versus 15.1%) and to have exchanged sex for money or drugs in the last 6 months (25.5% versus 2.3%). There were no gender differences in injecting risk behaviours. HIV prevalence was 38.7% (91/235) in women and 31.5% (347/1103) in men (p=0.031). HIV prevalence among female IDU who reported having exchange sex for money or drugs was 53.3% (32/60). The prevalence of HCV was 67.4% (159/236) and 73.6% (810/1101) in female and male IDU, respectively (p=0.053). After adjustment by immigrant status, age and years of injection, differences among HIV/HCV prevalence by gender were not significant. This study demonstrated differences in sexual risk behaviours between male and female IDU, but failed to find gender differences in injecting risk behaviours. Apart from that, the higher prevalence of HIV among women than among men, together with a lower prevalence of HCV, provides evidence that sexual transmission of HIV is important among female IDU. Additional studies are needed to analyze in-depth these specific risk factors for women in order to develop appropriate prevention and health education programs. Copyright © 2012 SESPAS. Published by Elsevier Espana. All rights reserved.

  14. Doing Research with Vulnerable Populations: The Case of Intravenous Drug Users

    Directory of Open Access Journals (Sweden)

    Murdoch, Blake

    2016-09-01

    Full Text Available This review article considers ethical concerns when doing research on potentially vulnerable people who inject drugs (PWID in a Canadian context. The Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans broadly addresses many of the traditional ethical principles of research on vulnerable persons, but does so at the cost of clarity and precision. Vulnerability is contextual rather than absolute. When doing research with vulnerable persons, informed consent should be obtained from an independent person, and comprehension should be checked using questioning. Participants can be vulnerable due to many factors, including addiction, chronic disease, socioeconomic and racial status, and lack of education. The ability of PWID to give informed consent can be compromised by undue influence or intoxication, but existing research shows that neither the mode nor the magnitude of compensation has a significant effect on new rates of drug use. Compensation can also help dispel the therapeutic misconception. Intoxication rather than undue influence is the main concern when obtaining informed consent from PWID. The stigmatization of PWID as incapable of consent should be avoided. Paternalistic exclusion from research can harm PWID and exacerbate their vulnerability by reducing our knowledge of and ability to specifically treat them. As such, we must collect better data about the effects of research ethics policies. Studies to this effect should focus on experiences, perspectives and needs of potentially vulnerable research participants. Research ethics boards in Canada should adopt an evidence-based approach when applying discretionary power to proposals for clinical research.

  15. Effect of Intravenous Administration Center on Improving the Quality of Intravenous Drug Use%静脉用药调配中心对提高静脉用药质量的作用分析

    Institute of Scientific and Technical Information of China (English)

    曾杰

    2015-01-01

    目的 探讨静脉用药调配中心对提高静脉用药质量的作用. 方法 该院静脉用药调配中心2010年12月开始投入使用.静脉用药调配中心成立前为对照组,静脉用药调配中心成立后为观察组,统计分析医院抽检的静脉用药差错率. 并统计分析两组患者对静脉输液的满意度. 结果 两组各抽检所配的4000袋药品中,对照组发现错误578袋,差错率14.45%;观察组发现错误126袋,差错率3.15%. 观察组的差错发生率明显低于对照组,差异具有统计学意义(P<0.05).观察组对静脉输液的满意度为98%明显高于对照组的85%,差异也具有统计学意义(P<0.05).结论 静脉用药调配中心建立的配药模式有效的保证了临床医疗、护理以及药学的结合,从而达到科学、合理、安全用药的目的.%Objective To investigate the effect of intravenous administration center on improving the quality of intravenous drug use. Methods The center of intravenous drug use in our hospital began to put into use in December 2010. In the con-trol group, after the establishment of the center for intravenous drug use, for the observation group, the statistical analysis of the hospital sampling of the intravenous drug use error rate. The satisfaction of the two groups of patients with venous transfusion was analyzed. Results In the two groups, the control group was found to have an error of 578 bags, the error rate was 14.45, and the observation group was 126 bags, the error rate was 3.15. The observation group was significantly lower than that of the control group, the difference was statistically significant (P<0.05). The satisfaction of the observation group for intravenous infusion was 85, significantly higher than the control group of 98, the difference was statistically significant (P<0.05). Conclusion Intravenous drug allocation center established dispensing mode effectively ensures the clinical medi-cal treatment, nursing and pharmacy binding, so

  16. Lipid-Core Nanocapsules Act as a Drug Shuttle Through the Blood Brain Barrier and Reduce Glioblastoma After Intravenous or Oral Administration.

    Science.gov (United States)

    Rodrigues, Stephen F; Fiel, Luana A; Shimada, Ana L; Pereira, Natalia R; Guterres, Silvia S; Pohlmann, Adriana R; Farsky, Sandra H

    2016-05-01

    Lipid-core nanocapsules (LNC) are formed by an organogel surrounded by poly(epsilon-caprolactone) and stabilized by polysorbate 80. LNCs increase the concentration of drugs in the brain after oral or intravenous administration. We proposed to determine whether the drug is released from the LNC to cross the blood brain barrier (BBB) or the drug-loaded LNCs can cross the BBB to release the drug. We synthesized a Rhodamine B-polymer conjugate to prepare a fluorescent-labeled LNC formulation, and intravital microscopy was used to determine the ability of the LNCs to cross the brain barrier using different administration routes in C57BI/6 mice. A glioblastoma model was used to determine the impact of the LNC as a shuttle for treatment. After pial vessel exposure, intense fluorescence was detected inside the vessels 10 min after intravenous or 20 min after intraperitoneal injections of fluorescent-labeled LNC. The fluorescence was observed in the perivascular tissue after 30 and 60 min, respectively. Increased tissue fluorescence was detected 240 min after oral administration. The integrity of the barrier was determined during the experiments. Normal leukocyte and platelet adhesion to the vessel wall indicated that Rhodamine B-labeled LNC did not cause pial vessel alterations. After intravenous or oral administration, Rhodamine B-labeled LNC-containing co-encapsulated indomethacin and indomethacin ethyl ester exhibited similar behavior in pial vessels, being more efficient in the treatment of mice with glioblastoma than indomethacin in solution. Therefore, we demonstrated that LNCs act as drug shuttles through the BBB, delivering drugs in brain tissue with high efficiency and reducing glioblastoma after intravenous or oral administration.

  17. Efficacy of combined antiviral therapy with pegylated interferon α-2a and ribavirin for chronic hepatitis C infection in intravenous drug users

    Directory of Open Access Journals (Sweden)

    Ružić Maja

    2010-01-01

    Full Text Available Introduction. Hepatitis C Virus infection represents not just a medical, but also a socio-economic problem. It is estimated that among 170 million infected, 60% belongs to the category of intravenous drug users (IDUs. Objective. The aim of this paper was to compare the response to the combined therapy of pegylated interferon alfa 2a and ribavirin, in the group of patients with HCV infection who were intravenous drug users (IDUs and in patients who were identified in the other way of transmission of HCV. Also to identify the influence of the therapy on diseases of addiction, during the course of HCV infection and on the effects of the combined therapy of pegylated interferon alfa 2a and ribavirin. Methods. We conducted a retrospective-prospective study, on 60 patients, treated with combined antiviral therapy-pegylated interferon alfa 2a and ribavirin. 30 patients were from the group of IDUs, and 30 patients from other epidemiological groups. Results. There were significant differences between the age of the patients (30.2±7.1 vs. 39.3±11.2 years; p=0.002, but no significant difference in the duration of the HCV infection between the two groups of patients (8.9±7.4 vs. 13.1±7.0 years; p>0.05. A large number of the patients in the group of IDUs had a problem with the abstinence of the drug abuse. In this group, there was the influence of alcohol (30% and other substances with potential hepatotoxicity: marihuana (23.3% and psycho-active drugs (73.6%. Staging of the liver fibrosis was not influenced by those two parameters and was similar in both groups (p>0.05. The genotype 3a was dominant in intravenous drug users (50.0% and genotype 1b in the control group of the patients (76.6%. In both groups, SVR was achieved at a higher percentage (86% vs. 70.00%; p>0.05, but among the intravenous drug users the relapses of HCV infection were at a lower percentage (3.3% vs. 20.0%; p=0.044. Side effects were noticed in solitary cases in both of the examined

  18. LIPAEMIC report: results of clinical use of intravenous lipid emulsion in drug toxicity reported to an online lipid registry.

    Science.gov (United States)

    Cave, Grant; Harvey, Martyn; Willers, Johann; Uncles, David; Meek, Tim; Picard, John; Weinberg, Guy

    2014-06-01

    The use of intravenous lipid emulsion (ILE) as an antidote has prompted significant academic and clinical interest. Between August 2009 and August 2012, data from cases of ILE use in intoxicated patients in different hospitals on different continents were voluntarily entered into a registry based on the world wide web (www.lipidregistry.org). Here, we report data from this project. Participating centers were given access to the registry following institutional subscription. Specifically sought were details of the individual patients' presenting condition, indications for ILE use, ILE administration regimen, potential complications, and of clinical outcome. Forty-eight uses of ILE were reported from 61 participating centers. Ten cases of local anesthetic systemic toxicity were reported; all (10/10) survived. Thirty-eight cases of intoxication by other agents were reported [30 decreased conscious state, 8 cardiovascular collapse (3 deaths)]. There was an elevation in GCS (p adverse effects of ILE use were recorded in 48 reported cases (one case of bronchospastic reaction, one case of hyperamylasemia and one case of interference with laboratory testing). In this series of cases reported to the registry, improvements were seen for GCS in patients with central nervous system toxicity and in systolic blood pressure in shocked patients over a short time frame after the injection of ILE. Few adverse effects were recorded. Clinical trials and the reporting of drug concentrations after ILE use are necessary to further elucidate the role of ILE in clinical toxicology.

  19. Variation in prescribing patterns and therapeutic drug monitoring of intravenous busulfan in pediatric hematopoietic cell transplant recipients.

    Science.gov (United States)

    McCune, Jeannine S; Baker, K Scott; Blough, David K; Gamis, Alan; Bemer, Meagan J; Kelton-Rehkopf, Megan C; Winter, Laura; Barrett, Jeffrey S

    2013-03-01

    Personalizing intravenous (IV) busulfan doses in children using therapeutic drug monitoring (TDM) is an integral component of hematopoietic cell transplant. The authors sought to characterize initial dosing and TDM of IV busulfan, along with factors associated with busulfan clearance, in 729 children who underwent busulfan TDM from December 2005 to December 2008. The initial IV busulfan dose in children weighing ≤12 kg ranged 4.8-fold, with only 19% prescribed the package insert dose of 1.1 mg/kg. In those children weighing >12 kg, the initial dose ranged 5.4-fold, and 79% were prescribed the package insert dose. The initial busulfan dose achieved the target exposure in only 24.3% of children. A wide range of busulfan exposures were targeted for children with the same disease (eg, 39 target busulfan exposures for the 264 children diagnosed with acute myeloid leukemia). Considerable heterogeneity exists regarding when TDM is conducted and the number of pharmacokinetic samples obtained. Busulfan clearance varied by age and dosing frequency but not by underlying disease. The authors- group is currently evaluating how using population pharmacokinetics to optimize initial busulfan dose and TDM (eg, limited sampling schedule in conjunction with maximum a posteriori Bayesian estimation) may affect clinical outcomes in children.

  20. Spontaneous Pneumothorax as a Complication of Septic Pulmonary Embolism in an Intravenous Drug User: A Case Report

    Directory of Open Access Journals (Sweden)

    Chau-Chyun Sheu

    2006-02-01

    Full Text Available Infective endocarditis has been the major cause of morbidity and mortality among intravenous drug users (IDUs with infections, mostly involving the tricuspid valve and presenting multiple septic pulmonary embolisms. Numerous pulmonary complications of septic pulmonary embolism have been described, but only a few have reported spontaneous pneumothorax. Our patient, a 23-year-old heroin addict, was hospitalized for tricuspid endocarditis and septic pulmonary embolism. Acute onset of respiratory distress occurred on his seventh hospital day and rapidly resulted in hypoxemia. Immediate bedside chest radiograph demonstrated left pneumothorax. It was thought to be a spontaneous pneumothorax, because he had not undergone any invasive procedure before the occurrence of pneumothorax. His clinical condition improved after the insertion of an intercostal chest tube. He later underwent surgery to replace the tricuspid valve as a result of the large size of the vegetation and poor control of infection. He ultimately survived. Pneumothorax is a possible lethal complication of septic pulmonary embolism in IDUs with right-sided endocarditis and should be considered in such patients when respiratory distress occurs acutely during their hospitalization.

  1. Angiographic CT with intravenous contrast agent application for monitoring of intracranial flow diverting stents

    Energy Technology Data Exchange (ETDEWEB)

    Saake, Marc; Struffert, Tobias; Goelitz, Philipp; Ott, Sabine; Doerfler, Arnd [University of Erlangen-Nuremberg, Department of Neuroradiology, Erlangen (Germany); Seifert, Frank [University of Erlangen-Nuremberg, Department of Neurology, Erlangen (Germany); Ganslandt, Oliver [University of Erlangen-Nuremberg, Department of Neurosurgery, Erlangen (Germany)

    2012-07-15

    Intracranial flow diverting devices are increasingly used to treat cerebral aneurysms. A reliable, non-invasive follow-up modality would be desirable. Our aim was to compare intra-arterial digital subtraction angiography (ia DSA) to angiographic computed tomography with intravenous contrast agent application (iv ACT) in the visualisation of flow diverting devices and aneurysm lumina. Follow-up monitoring by iv ACT (n = 36) and ia DSA (n = 25) in 14 patients treated with flow diverting devices for intracranial aneurysms was evaluated retrospectively. Images were evaluated by two neuroradiologists in anonymous consensus reading regarding the device deployment, wall apposition, neck coverage of the aneurysm, opacification of the vessel and device lumen, as well as the degree of aneurysm occlusion. Corresponding ia DSA and iv ACT images were scored identically in all patients regarding the stent deployment, wall apposition and neck coverage, as well as the degree of aneurysm occlusion and patency status of the device and parent artery. Opacification of the parent vessel lumen and perfused parts of the aneurysm was considered slightly inferior for iv ACT in comparison with ia DSA (seven of 36 cases), without impact on diagnosis. We demonstrated the feasibility and diagnostic value of iv ACT in follow-up imaging of intracranial flow diverting devices. Due to its high spatial resolution and non-invasive character, this novel technique might become a valuable imaging modality in these patients. (orig.)

  2. Angiographic CT with intravenous contrast agent application for monitoring of intracranial flow diverting stents.

    Science.gov (United States)

    Saake, Marc; Struffert, Tobias; Goelitz, Philipp; Ott, Sabine; Seifert, Frank; Ganslandt, Oliver; Doerfler, Arnd

    2012-07-01

    Intracranial flow diverting devices are increasingly used to treat cerebral aneurysms. A reliable, non-invasive follow-up modality would be desirable. Our aim was to compare intra-arterial digital subtraction angiography (ia DSA) to angiographic computed tomography with intravenous contrast agent application (iv ACT) in the visualisation of flow diverting devices and aneurysm lumina. Follow-up monitoring by iv ACT (n = 36) and ia DSA (n = 25) in 14 patients treated with flow diverting devices for intracranial aneurysms was evaluated retrospectively. Images were evaluated by two neuroradiologists in anonymous consensus reading regarding the device deployment, wall apposition, neck coverage of the aneurysm, opacification of the vessel and device lumen, as well as the degree of aneurysm occlusion. Corresponding ia DSA and iv ACT images were scored identically in all patients regarding the stent deployment, wall apposition and neck coverage, as well as the degree of aneurysm occlusion and patency status of the device and parent artery. Opacification of the parent vessel lumen and perfused parts of the aneurysm was considered slightly inferior for iv ACT in comparison with ia DSA (seven of 36 cases), without impact on diagnosis. We demonstrated the feasibility and diagnostic value of iv ACT in follow-up imaging of intracranial flow diverting devices. Due to its high spatial resolution and non-invasive character, this novel technique might become a valuable imaging modality in these patients.

  3. New drug applications and abbreviated new drug applications; technical amendment. Final rule; technical amendment.

    Science.gov (United States)

    2009-03-06

    The Food and Drug Administration (FDA) is amending its new drug application (NDA) and abbreviated new drug application (ANDA) regulations to update agency contacts for patent information and patent notifications and to correct an inaccurate cross-reference. This action is being taken to ensure accuracy and clarity in the agency's regulations.

  4. Potential therapeutic application of intravenous autologous bone marrow infusion in patients with alcoholic liver cirrhosis.

    Science.gov (United States)

    Saito, Takafumi; Okumoto, Kazuo; Haga, Hiroaki; Nishise, Yuko; Ishii, Rika; Sato, Chikako; Watanabe, Hisayoshi; Okada, Akio; Ikeda, Motoki; Togashi, Hitoshi; Ishikawa, Tsuyoshi; Terai, Shuji; Sakaida, Isao; Kawata, Sumio

    2011-09-01

    The present study was conducted to evaluate the application and efficacy of autologous bone marrow infusion (ABMi) for improvement of liver function in patients with alcoholic liver cirrhosis (ALC). Five subjects and 5 control patients with ALC who had abstained from alcohol intake for 24 weeks before the study were enrolled. Autologous bone marrow cells were washed and injected intravenously, and the changes in serum liver function parameters, and the level of the type IV collagen 7S domain as a marker of fibrosis, were monitored for 24 weeks. The distribution of activated bone marrow was assessed by indium-111-chloride bone marrow scintigraphy. The number of cells infused was 8.0±7.3×10(9) (mean±standard error). The serum levels of albumin and total protein and the prothrombin time were significantly higher during the follow-up period after ABMi than during the observation period in treated patients, whereas no such changes were observed in the controls. In the patients who received ABMi, the Child-Pugh score decreased in all 3 who were classified as class B; the serum levels of type IV collagen 7S domain improved in 4 of the 5 patients; and bone marrow scintigraphy demonstrated an increase of indium-111-chloride uptake in 3 of the 4 patients tested. ABMi for patients with ALC helps improve liver function parameters in comparison with observation during abstinence and ameliorates the degree of fibrosis in terms of serum markers and bone marrow activation in most cases.

  5. LOCALIZATION OF PALM DORSAL VEIN PATTERN USING IMAGE PROCESSING FOR AUTOMATED INTRA-VENOUS DRUG NEEDLE INSERTION

    Directory of Open Access Journals (Sweden)

    Mrs. Kavitha. R,

    2011-06-01

    Full Text Available Vein pattern in palms is a random mesh of interconnected and inter- wining blood vessels. This project is the application of vein detection concept to automate the drug delivery process. It dealswith extracting palm dorsal vein structures, which is a key procedure for selecting the optimal drug needle insertion point. Gray scale images obtained from a low cost IR-webcam are poor in contrast, and usually noisy which make an effective vein segmentation a great challenge. Here a new vein image segmentation method is introduced, based on enhancement techniques resolves the conflict between poor contrast vein image and good quality image segmentation. Gaussian filter is used to remove the high frequency noise in the image. The ultimate goal is to identify venous bifurcations and determine the insertion point for the needle in between their branches.

  6. 78 FR 25749 - Submission of New Drug Application/Abbreviated New Drug Application Field Alert Reports: Notice...

    Science.gov (United States)

    2013-05-02

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Submission of New Drug Application/Abbreviated New Drug... submit new drug application (NDA) and abbreviated new drug application (ANDA) Field Alert Reports...

  7. Dose adjustment and application of intravenous anaesthetics in obese patients%肥胖患者静脉麻醉药应用及剂量调整

    Institute of Scientific and Technical Information of China (English)

    磨凯; 徐世元; 刘中杰; 李凤仙; 梁启波; 张庆国

    2013-01-01

    背景 肥胖患者麻醉药药代与药效动力学较体重正常人群个体差异更大,其心输出量与身体肌肉、脂肪等组织构成比的变化影响众多麻醉药物分布、消除规律,按总体重给药易致药物过量,按理想体重给药则可能剂量不足. 目的 阐述常用静脉麻醉药在肥胖患者中的药代与药效动力学特性,有助于此类患者合理用药,减少并发症. 内容 综述肥胖患者常用静脉麻醉药按总体重、理想体重、体表面积和瘦体重用药研究现状. 趋势 为避免肥胖患者肌松药术后残余作用所致并发症,非去极化肌松药按理想体重给药较合适,而大多数静脉麻醉药(包括阿片类药物)则适于按瘦体重给药.%Background Obese patients have greater inter-individual variations than the standard-size patients in the anesthetic pharmacokinetics and pharmacodynamics.In obese population,changes in cardiac output and alterations in body composition affect the distribution of numerous anaesthetics,therefore,administration of drugs based on total body weight could result in overdose,conversely,administration of drugs based on ideal body weight could result in an inadequate dose.Objective This review focuses on the pharmacokinetics and pharmacodynamics properties of intravenous anesthetic in obese patients in order to provide recommendation for rational application of intravenous anesthetic in obese patients and reduce complications.Content Discussing dosing scalars based on total body weight,ideal body weight,body surface area and lean body weight as well as its recent advances in clinical application of intravenous anaesthetics in the obese.Trend To avoid postoperative residual curarization,the ideal body weight might be appropriate for dosing scalar of the non-depolarizing neuromuscular blocking agents,whereas,lean body weight is the optimal dosing scalar for the majority of anaesthetic agents including opioids and anaesthetic-induction agents for

  8. 21 CFR 314.101 - Filing an application and receiving an abbreviated new drug application.

    Science.gov (United States)

    2010-04-01

    ... new drug application. 314.101 Section 314.101 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT... A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.101 Filing an application and receiving an abbreviated new drug application. (a)(1) Within 60 days after FDA receives...

  9. Electrical potential difference across the stomach wall and gastric morphology in anaesthetized pigs after intravenous administration of cytotoxic drugs

    DEFF Research Database (Denmark)

    Fabrin, B.; Højgaard, L.; Olesen, H.P.;

    1991-01-01

    Oncologi, cytotoxic drugs, electrical potential difference, medicin, cander, gastric, side effects, chemotherapy......Oncologi, cytotoxic drugs, electrical potential difference, medicin, cander, gastric, side effects, chemotherapy...

  10. Histamine release from basophil leukocytes in asthma patients after in vitro provocation with various neuromuscular blocking drugs and intravenous anaesthetic agents

    DEFF Research Database (Denmark)

    Guldager, H; Søndergaard, I

    1987-01-01

    Basophil histamine release is a relatively new investigation technique, which can be used in the diagnosis of anaphylactoid reactions. Our aim in this investigation was to determine reference values for asthma patients and normal subjects. Blood from eight asthmatic patients and eight normal...... subjects was tested for histamine release after in vitro provocation with various neuromuscular blocking drugs and intravenous anaesthetic agents. There was significantly higher histamine release for asthmatic patients than for normal subjects, P less than 0.001 (analysis of variance). This had no effect...

  11. Drug synergism: its detection and applications.

    Science.gov (United States)

    Tallarida, R J

    2001-09-01

    Two drugs that produce overtly similar effects will sometimes produce exaggerated or diminished effects when used concurrently. A quantitative assessment is necessary to distinguish these cases from simply additive action. This distinction is based on the classic pharmacologic definition of additivity that, briefly stated, means that each constituent contributes to the effect in accord with its own potency. Accordingly, the relative potency of the agents, not necessarily constant at all effect levels, allows a calculation using dose pairs to determine the equivalent of either agent and the effect by using the equivalent in the dose-response relation of the reference compound. The calculation is aided by a popular graph (isobologram) that provides a visual assessment of the interaction but also requires independent statistical analysis. The latter can be accomplished from calculations that use the total dose in a fixed-ratio combination along with the calculated additive total dose for the same effect. Different methods may be used, and each is applicable to experiments in which a single drug is given at two different sites. When departures from additivity are found, whether in "two-drug" or "two-site" experiments, the information is useful in designing new experiments for illuminating mechanisms. Several examples, mainly from analgesic drug studies, illustrate this application. Even when a single drug (or site) is used, its introduction places it in potential contact with a myriad of chemicals already in the system, a fact that underscores the importance of this topic in other areas of biological investigation.

  12. High Risk Drug Management Measures in the Center of Intravenous Drug use%静脉用药调配中心的高危药品管理措施

    Institute of Scientific and Technical Information of China (English)

    马德爽

    2015-01-01

    Objective To study the management of high risk drugs in the treatment of intravenous drug use. Methods To study the types of high risk drugs in the distribution center of intravenous drug use, and to analyze the harm of the high risk drugs, and to put forward the concrete management measures. Results Science placed drugs, to strengthen information man-agement, drug inventory management and drug management, while strengthening the pharmacy staff high-risk drug skills and knowledge training is the necessary measures for the management of high-risk drugs. Conclusion High attention to the management of high risk drugs can effectively improve the medical quality and management level.%目的:探讨静脉用药调配中心的高危药品管理措施。方法排查静脉用药调配中心常见的高危药品种类,分析高危药品出现差错的危害,并提出具体管理措施。结果科学放置药品,加强信息管理、药品库存管理和排药管理,同时加强药剂人员高危药品技能和知识培训是高危药品管理的必要措施。结论高度重视高危药品的管理,可以有效提高医疗质量和管理水平。

  13. Study on the blood-borne virus co-infection and T lymphocyte subset among intravenous drug users

    Institute of Scientific and Technical Information of China (English)

    Jian-Rong Li; Rui-Yu Gong; Kun-Lun Tian; Jing Wang; Yi-Xin Wang; Han-Ju Huang

    2007-01-01

    AIM: To investigate the features of various bloodborne virus infections and co-infection in intravenous drug users (IDUs), and to examine the correlation of T lymphocyte subsets with virus co-infection.METHODS: Four hundred and six IDUs without any clinical manifestation of hepatitis and 102 healthy persons were enrolled in this study. HBV-DNA and HCV-RNA were detected by fluorescence quantitative PCR. HBsAg, HBeAg, anti-HBc, anti-HCV, HDV-Ag, anti-HGV, anti-HIV, and HCMV-IgM were assayed by enzyme-linked immunosorbent assay (ELISA) and immunochromatographic tests. The levels of Th1 and Th2 cytokines were measured by ELISA and radioactive immune assay (RIA). The T lymphocyte subpopulation was detected by using fluorescence immunoassay. The similar indices taken from the healthy persons served as controls.RESULTS: The viral infection rate among IDUs was 36.45% for HBV, 69.7% for HCV, 47.3% for HIV, 2.22% for HDV, 1.97% for HGV, and 3.45% for HCMV. The co-infection rate of blood-borne virus was detected in 255 of 406 (62.81%) IDUs. More than 80% (161/192) of subjects infected with HIV were co-infected with the other viruses, such as HBV, HCV. In contrast, among the controls, the infection rate was 17.65% for HBV and 0% for the other viruses. Our investigation showed that there was a profound decrease in the proportion of CD4/CD8 and the percentage of CD3 and CD4, but not in the percentage of CD8. The levels of PHA-induced cytokines (IFN-γ and IL-4) and serum IL-2 were obviously decreased in IDUs. On the other hand, the level of serum IL-4 was increased. The level of IFN-γ and the percentage of CD4 were continuously decreased when the IDUs were infected with HIV or HIV co-infection. IDUs with HIV and HBV co-infection was 15.1% (29/192). Of those 29 IDU with HIV and HBV co-infection, 51.72% (15/29) and 37.93% (11/29) were HBV-DNA-positive and HBeAg-positive, respectively. But, among IDUs without HIV infection, only 1.68% (2/119) of cases were HBV

  14. [Drug delivery systems for intraocular applications].

    Science.gov (United States)

    Bourges, J-L; Touchard, E; Kowalczuk, L; Berdugo, M; Thomas-Doyle, A; Bochot, A; Gomez, A; Azan, F; Gurny, R; Behar-Cohen, F

    2007-12-01

    Numerous drug delivery systems (DDSs) can be used as intraocular tools to provide a sustained and calibrated release for a specific drug. Great progress has been made on the design, biocompatibility, bioavailability, and efficacy of DDSs. Although several of them are undergoing clinical trials, a few are already on the market and could be of a routine use in clinical practice. Moreover, miniaturization of the implants makes them less and less traumatic for the eye tissues and some DDSs are now able to target certain cells or tissues specifically. An overview of ocular implants with therapeutic application potentials is provided.

  15. Application of intravenous electrocardiography for insertion of central veins dialysis catheters

    Directory of Open Access Journals (Sweden)

    Beigi Ali

    2009-01-01

    Full Text Available One fifth of the inserted dialysis catheters in the internal jugular or subclavian veins may be misplaced. Appropriate positioning of the catheter tip is sometimes difficult. We attempted to use intravenous electrocardiography (ECG to guide catheter tip positioning in 30 hemodialysis patients (17 (57% were men, and the mean age was 43 ± 12 years. who required vascular accesses for dialysis by insertion of double lumen temporary catheters via the jugular veins. Before cathe-terization, standard ECG on the long lead D II was performed and P-wave height was recorded. P-wave voltage was also measured via the blue (venous and red (arterial lumens, using the guide wire as an electrical conductor. After confirmation of the appropriate position of the catheter tip at the superior vena cava (SVC-right atrial junction using chest radiography, the ECG lead corres-ponding to the right hand was connected to the guide wire lodged inside the lumen of the blue catheter. P-wave height in the long lead D II was recorded. The guide wire was withdrawn so as to bring its tip tangent to the tip of the red catheter. ECG was performed on the long lead D II in a similar manner, and the P-wave height was recorded. The mean P-wave voltage in normal ECG and intravenous ECG (red and blue catheter tips measured 1.27 ± 0.38 mm, 3.10 ± 0.95 mm, and 5.42 ± 1.76 mm, respectively. The difference between the mean P-wave voltages measured in standard and intravenous ECG (blue and red catheter tips was statistically significant (P< 0.05. We conclude that the dialysis catheter tip can be positioned appropriately via the measurement of the P-wave height by intravenous ECG and using the sinoatrial node as an accurate landmark. This method can complement the chest radiography in the appropriate placement of the central vein catheters.

  16. Prospective evaluation of a two-week course of intravenous antibiotics in intravenous drug addicts with infective endocarditis. Grupo de Estudio de Enfermedades Infecciosas de la Provincia de Cádiz.

    Science.gov (United States)

    Torres-Tortosa, M; de Cueto, M; Vergara, A; Sánchez-Porto, A; Pérez-Guzmán, E; González-Serrano, M; Canueto, J

    1994-07-01

    In a prospective study, a two-week course of antibiotics (cloxacillin 2 g/4 h plus amikacin 7.5 mg/kg/12 h) was evaluated in the therapy of right-sided infective endocarditis in intravenous drug users (IVDU). All IVDU admitted to hospital during the study period who fulfilled the strict criteria for diagnosis of infective endocarditis were analysed. A subgroup of patients with right-sided endocarditis caused by Staphylococcus aureus who had a good prognosis were selected as being eligible for the two-week course of treatment. In a total of 139 episodes of infective endocarditis in IVDU, 72 (51.8%) cases were eligible for the two-week treatment. Of this group, 67 were cured, 4 needed prolongation of treatment to cure the infection and 1 died in hospital of respiratory distress syndrome on day 10 of treatment. In patients not eligible for the two-week treatment, the mortality was higher (24.2% versus 0.7%; p = 0.00015). Drug toxicity in the treated group was low. It can be concluded that administration of cloxacillin and amikacin parenterally for 14 consecutive days was successful in the therapy of right-sided endocarditis in IVDU.

  17. Use of Physostigmine by the Intravenous, Intramuscular, and Oral Routes in the Therapy of Anticholinergic Drug Intoxication

    Science.gov (United States)

    1976-05-01

    treatment is indicated: (1) The tachycardia may produce a strain on the cardiovascular system, particularly if the patient is elderly or has preexisting...time and was given an additional 15 /ig/kg of physostigmine intravenously. Again, his delirium was markedly reversed, but the reversal lasted less...preceded by an evaluation by a physician who increased or decreased the dose or the interval of dosing. He examined the patient for signs of cholinergic

  18. [New antiepileptic drugs: characteristics and clinical applications].

    Science.gov (United States)

    Ohtsuka, Yoko

    2014-05-01

    New antiepileptic drugs (AEDs) that have been used in many other countries for more than 10 years have only recently became available for use in Japan. Gabapentin, topiramate, lamotrigine and levetiracetam were licensed for use in Japan between 2006 and 2010. Stiripentol for Dravet syndrome and rufinamide for Lennox-Gastaut syndrome were also approved in 2012 and 2013 as orphan drugs. Clinical trials of other new AEDs such as oxcarbazepine, vigabatrin, lacosamide, and perampanel are in progress. In this review, the general characteristics of the new AEDs are discussed with regards to their effectiveness, tolerability, drug interaction, safety and mechanisms of action. The effectiveness, of the new AEDs compared with established AEDs is also discussed. Clinical applications of the new AEDs, focusing on gabapentin, topiramate, lamotrigine and levetiracetam are also discussed based on our domestic experience as well as overseas reports.

  19. An intravenous clarithromycin lipid emulsion with a high drug loading, H-bonding and a hydrogen-bonded ion pair complex exhibiting excellent antibacterial activity

    Directory of Open Access Journals (Sweden)

    Haoyu Gong

    2016-10-01

    Full Text Available The aim of this study was to develop an intravenous clarithromycin lipid emulsion (CLE with good stability and excellent antibacterial activity. The CLE was prepared by the thin-film dispersed homogenization method. The interaction between clarithromycin (CLA and cholesteryl hemisuccinate (CHEMS was confirmed by DSC, FT-IR and 1H NMR analysis. The interfacial drug loading, thermal sterilization, freeze–thaw stability, and in vitro and in vivo antibacterial activity were investigated systematically. DSC, FT-IR and 1H NMR spectra showed that CHEMS (CLA: CHEMS, M ratio 1:2 could interact with CLA through H-bonding and a hydrogen-bonded ion pair. The CHEMS was found necessary to maintain the stability of CLE. Ultracentrifugation showed that almost 88% CLA could be loaded into the interfacial layer. The optimized CLE formulation could withstand autoclaving at 121 °C for 10 min and remain stable after three freeze–thaw cycles. The in vitro susceptibility test revealed that the CLA–CHEMS ion-pair and CLE have similar activity to the parent drug against many different bacterial strains. The in vivo antibacterial activity showed that the ED50 of intravenous CLE was markedly lower than that of CLA solution administrated orally. CLE exhibited pronounced antibacterial activity and might be a candidate for a new nanocarrier for CLA with potential advantages over the current commercial formulation.

  20. An outbreak in intravenous drug users due to USA300 Latin-American variant community-acquired methicillin-resistant Staphylococcus aureus in France as early as 2007.

    Science.gov (United States)

    Sassi, M; Felden, B; Revest, M; Tattevin, P; Augagneur, Y; Donnio, P-Y

    2017-09-02

    Intravenous drug users are at increased risk of Staphylococcus aureus infections. Most cases are related to clones prevalent in the community. We report an outbreak of community-acquired methicillin-resistant Staphylococcus aureus infections that occurred from 2007 to 2009 in intravenous drug users and their close contacts in Northwestern France. Clinical and molecular investigations suggested that the clones were more similar than those usually isolated in the American continent although none of the patients traveled abroad or had contact with individuals who had traveled to the Americas. Then, a retrospective whole genome sequencing and phylogenetic analyses demonstrated that the strains isolated from the first case belong to the USA300 Latin-American variant clone, based on the absence of arginine catabolic mobile element (ACME), and the presence of copper and mercury resistance mobile element (COMER), a distinctive feature of the South American variant. Our study shows genetic evidence for introduction of this clone as early as 2007 in France. This report also illustrates the importance of genome sequencing to finely characterize and monitor the emergence of unexpected S. aureus clones among high-risk populations, especially when living in promiscuity.

  1. Pharmacokinetics of enrofloxacin and flunixin meglumine and interactions between both drugs after intravenous co-administration in healthy and endotoxaemic rabbits.

    Science.gov (United States)

    Elmas, Muammer; Yazar, Enver; Uney, Kamil; Er Karabacak, Ayşe; Traş, Bünyamin

    2008-09-01

    The purpose of this study was to determine the pharmacokinetics and possible interactions of enrofloxacin (ENR) and flunixin meglumine (FM) in healthy rabbits and in rabbits where endotoxaemia had been induced by administering Escherichia coli lipopolysaccharide (LPS). Six male adult New Zealand White rabbits were used for the study. In Phase I, FM (2.2 mg/kg) and ENR (5 mg/kg) were given simultaneously as a bolus intravenous (IV) injection to each healthy rabbit. After a washout period, Phase II consisted of purified LPS administered as an IV bolus injection, then FM and ENR. LPS produced statistically significant increases in some serum biochemical concentrations. After the drugs were co-administered, the kinetic parameters of FM were not significantly different in healthy compared to endotoxaemic rabbits. It is concluded that ENR and FM could be co-administered to rabbits to treat endotoxaemia as no negative interaction was observed between the pharmacokinetics of both drugs.

  2. Use of an intravenous microdose of 14C-labeled drug and accelerator mass spectrometry to measure absolute oral bioavailability in dogs; cross-comparison of assay methods by accelerator mass spectrometry and liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Miyaji, Yoshihiro; Ishizuka, Tomoko; Kawai, Kenji; Hamabe, Yoshimi; Miyaoka, Teiji; Oh-hara, Toshinari; Ikeda, Toshihiko; Kurihara, Atsushi

    2009-01-01

    A technique utilizing simultaneous intravenous microdosing of (14)C-labeled drug with oral dosing of non-labeled drug for measurement of absolute bioavailability was evaluated using R-142086 in male dogs. Plasma concentrations of R-142086 were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and those of (14)C-R-142086 were measured by accelerator mass spectrometry (AMS). The absence of metabolites in the plasma and urine was confirmed by a single radioactive peak of the parent compound in the chromatogram after intravenous microdosing of (14)C-R-142086 (1.5 microg/kg). Although plasma concentrations of R-142086 determined by LC-MS/MS were approximately 20% higher than those of (14)C-R-142086 as determined by AMS, there was excellent correlation (r=0.994) between both concentrations after intravenous dosing of (14)C-R-142086 (0.3 mg/kg). The oral bioavailability of R-142086 at 1 mg/kg obtained by simultaneous intravenous microdosing of (14)C-R-142086 was 16.1%, this being slightly higher than the value (12.5%) obtained by separate intravenous dosing of R-142086 (0.3 mg/kg). In conclusion, on utilizing simultaneous intravenous microdosing of (14)C-labeled drug in conjunction with AMS analysis, absolute bioavailability could be approximately measured in dogs, but without total accuracy. Bioavailability in humans may possibly be approximately measured at an earlier stage and at a lower cost.

  3. 77 FR 8262 - Draft Guidance on Investigational New Drug Applications for Positron Emission Tomography Drugs...

    Science.gov (United States)

    2012-02-14

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance on Investigational New Drug Applications for Positron Emission Tomography Drugs; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of a draft...

  4. 75 FR 32482 - Investigational New Drug Applications; Co-development of Investigational Drugs

    Science.gov (United States)

    2010-06-08

    ... HUMAN SERVICES Food and Drug Administration Investigational New Drug Applications; Co-development of Investigational Drugs AGENCY: Food and Drug Administration, HHS. ACTION: Notice; establishment of docket; request for comments. SUMMARY: The Food and Drug Administration (FDA) is establishing a public docket...

  5. 75 FR 55334 - Schmid Laboratories, Inc. et al.; Withdrawal of Approval of Five New Drug Applications

    Science.gov (United States)

    2010-09-10

    ... Five New Drug Applications AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is withdrawing approval of five new drug applications (NDAs)...

  6. A new multiple-drug applicator with minimal drug cross-talk, leakage, and consumption.

    Science.gov (United States)

    Fujita, Yosuke; Shimomura, Takeshi; Hosoguchi, Masafumi; Kano, Masanobu; Fukurotani, Kenkichi; Tabata, Toshihide

    2010-04-01

    The relative effects of multiple drugs give an important clue to dissect a neuronal mechanism and to seek for a candidate neurotherapeutical agent. Here we have devised a "flute" applicator which can deliver several drugs to a neural cell preparation. The applicator stands by, cleaning itself with bath perfusate and delivers drugs only during test applications. This minimizes drug cross-talk in and leakage from the applicator and drug consumption. Using the applicator, we successfully compared the relative effects of widely different doses of an agonist in single neurons. The flute applicator would be a useful tool for pharmacological analyses.

  7. 10 CFR 707.8 - Applicant drug testing.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Applicant drug testing. 707.8 Section 707.8 Energy... testing. An applicant for a testing designated position will be tested for the use of illegal drugs before... contractors from conducting drug testing on applicants for employment in any position. ...

  8. Nanodiamond and its application to drug delivery

    Directory of Open Access Journals (Sweden)

    Eiji Osawa

    2012-08-01

    Full Text Available Quasi-spherical diamond crystals having an average diameter of 3.7±0.6 nm are attracting much attention as an ideal material in carbon nanotechnology. In contrast to the other popular nanocarbons including fullerenes, carbon nanotubes and graphenes, our single-nanodiamond can be produced in uniform shape/size on industrial scale. Thus, the most serious problem in nanocarbon industry that persisted in the past 25 years, namely the technical failure to produce highly crystalline nanocarbons in narrow shape/size range does not exist in our diamond from the beginning. Among potential applications of the single-nanodiamond under development, this review concentrates on its highly promising role as a drug carrier, especially for therapeutic-resistant cancer. An interesting possibility of intercalation is proposed as the mechanism of drug transport through blood, which takes into accounts of the spontaneous formation of nanographene layer on the [111] facets, which is then extensively oxidized during oxidative soot removal process to give nanographene oxide partial surface, capable of intercalating drug molecules to prevent them from leaking and causing undesirable side effects during transportation to target malignant cells. A perspective of quantifying the drug delivery process by anticipating orders of magnitude in the number of administered detonation nanodiamond (DND particles is suggested.

  9. Intravenous application of an anticalin dramatically lowers plasma digoxin levels and reduces its toxic effects in rats

    Energy Technology Data Exchange (ETDEWEB)

    Eyer, Florian, E-mail: Florian.Eyer@mac.com [Department of Toxicology, Klinikum rechts der Isar, Munich (Germany); Steimer, Werner [Institute of Clinical Chemistry and Pathobiochemistry, Klinikum rechts der Isar, Munich (Germany); Nitzsche, Thomas [Munich Center for Integrated Protein Science (CIPS-M), Freising-Weihenstephan (Germany); Lehrstuhl für Biologische Chemie, Technische Universität München, Freising-Weihenstephan (Germany); Jung, Nicole; Neuberger, Heidi [Department of Toxicology, Klinikum rechts der Isar, Munich (Germany); Müller, Christine [Institute of Clinical Chemistry and Pathobiochemistry, Klinikum rechts der Isar, Munich (Germany); Schlapschy, Martin [Munich Center for Integrated Protein Science (CIPS-M), Freising-Weihenstephan (Germany); Lehrstuhl für Biologische Chemie, Technische Universität München, Freising-Weihenstephan (Germany); Zilker, Thomas [Department of Toxicology, Klinikum rechts der Isar, Munich (Germany); Skerra, Arne [Munich Center for Integrated Protein Science (CIPS-M), Freising-Weihenstephan (Germany); Lehrstuhl für Biologische Chemie, Technische Universität München, Freising-Weihenstephan (Germany)

    2012-09-15

    Lipocalins tailored with high affinity for prescribed ligands, so-called anticalins, constitute promising candidates as antidotes. Here, we present an animal study to investigate both pharmacokinetic and clinical effects of an anticalin specific for the digitalis compound digoxin. Intravenous digoxin (2.5–50 μg/kg/min) was administered to rats until first changes in the ECG occurred (dose finding study) or a priori for 30 min (kinetic study). The anticalin DigA16(H86N), dubbed DigiCal, was administered intravenously at absolute doses of 1, 5, 10 and 20 mg, while the control group received isotonic saline. Hemodynamic changes, several ECG parameters and digoxin concentration in plasma were monitored at given time intervals. After DigiCal administration free digoxin concentration in plasma ultrafiltrate declined dramatically within 1 min to the presumably non-toxic range. There was also a significant and DigiCal dose-dependent effect on longer survival, less ECG alterations, arrhythmia, and improved hemodynamics. Infusion of a lower digoxin dose (2.5 μg/kg/min) resulted in a more sustained reduction of free digoxin in plasma after DigiCal administration compared to a higher digoxin dose (25 μg/kg/min), whereas ECG and hemodynamic parameters did not markedly differ, reflecting the known relative insensitivity of rats towards digoxin toxicity. Notably, we observed a re-increase of free digoxin in plasma some time after bolus administration of DigiCal, which was presumably due to toxin redistribution from tissue in combination with the relatively fast renal clearance of the rather small protein antidote. We conclude that anticalins with appropriately engineered drug-binding activities and, possibly, prolonged plasma half-life offer prospects for next-generation antidotal therapy. -- Highlights: ► We provide an advanced model of digoxin toxicity in rats. ► We report on binding of digoxin to a novel designed anticalin. ► We report on pharmacokinetics of digoxin

  10. 76 FR 64951 - Apothecon et al.; Withdrawal of Approval of 103 New Drug Applications and 35 Abbreviated New Drug...

    Science.gov (United States)

    2011-10-19

    ... HUMAN SERVICES Food and Drug Administration Apothecon et al.; Withdrawal of Approval of 103 New Drug Applications and 35 Abbreviated New Drug Applications; Correction AGENCY: Food and Drug Administration, HHS... new drug applications (NDAs) and 35 abbreviated new drug applications (ANDAs) from multiple...

  11. HIV-1 A1 Subtype Epidemic in Italy Originated from Africa and Eastern Europe and Shows a High Frequency of Transmission Chains Involving Intravenous Drug Users.

    Directory of Open Access Journals (Sweden)

    Alessia Lai

    Full Text Available Subtype A accounts for only 12% of HIV-1 infections worldwide but predominates in Russia and Former Soviet Union countries of Eastern Europe. After an early propagation via heterosexual contacts, this variant spread explosively among intravenous drug users. A distinct A1 variant predominates in Greece and Albania, which penetrated directly from Africa. Clade A1 accounts for 12.5% of non-B subtypes in Italy, being the most frequent after F1 subtype.Aim of this study was to investigate the circulation of A1 subtype in Italy and trace its origin and diffusion through phylogenetic and phylodynamic approaches.The phylogenetic analysis of 113 A1 pol sequences included in the Italian ARCA database, indicated that 71 patients (62.8% clustered within 5 clades. A higher probability to be detected in clusters was found for patients from Eastern Europe and Italy (88.9% and 60.4%, respectively compared to those from Africa (20% (p < .001. Higher proportions of clustering sequences were found in intravenous drug users with respect to heterosexuals (85.7% vs. 59.3%, p = .056 and in women with respect to men (81.4% vs. 53.2%, p < .006. Subtype A1 dated phylogeny indicated an East African origin around 1961. Phylogeographical reconstruction highlighted 3 significant groups. One involved East European and some Italian variants, the second encompassed some Italian and African strains, the latter included the majority of viruses carried by African and Italian subjects and all viral sequences from Albania and Greece.Subtype A1 originated in Central Africa and spread among East European countries in 1982. It entered Italy through three introduction events: directly from East Africa, from Albania and Greece, and from the area encompassing Moldavia and Ukraine. As in previously documented A1 epidemics of East European countries, HIV-1 A1 subtype spread in Italy in part through intravenous drug users. However, Eastern European women contributed to the penetration of

  12. 护理人员在静脉用药调配中心的作用%The Role of Nursing Staff in the Deployment of Intravenous Drug Use

    Institute of Scientific and Technical Information of China (English)

    谭冉

    2015-01-01

    目的:探讨护理人员在静脉用药调配中心的作用。方法选取一直参与该院静脉用药调配中心工作的40例护理人员作为研究对象,随即分为两组,分别为实验组和对照组,每组各20例。对照组只是进行常规护理工作,而实验组则在常规护理工作的基础上,实施护理干预措施。结果试验组药物使用量626270例,出错1056例,错误率0.169%;对照组药物使用量626419例,出错775例,错误率0.124%。实验组出错率远远低于对照组,两组之间差异具有统计学意义(P<0.05)。结论护理人员在静脉用药调配中心中发挥着非常重要的作用,可以显著降低配药出错率,减少医患纠纷。%Objective To investigate the effect of nursing staff in the treatment of intravenous drug use. Methods 40 cases of nursing staff who have been involved in the deployment of intravenous drug use in our hospital were randomly divided in-to two groups: experimental group and control group, 20 cases in each group. The control group only carries on a series of routine nursing work, while the experimental group is on the basis of routine nursing work, the implementation of nursing intervention measures. Results In the experimental group, 626270 cases were used in medicine, 1056 cases were in error, the error rate was 0.169, the control group was used in 626419 cases, 775 cases were in error, the error rate was 0.124. The error rate in the experimental group was much lower than that in the control group, and there was significant difference be-tween the two groups (P<0.05). Conclusion Nursing staff in intravenous drug allocation center plays a very important role, can significantly reduce the dispensing error rate, reduce medical disputes.

  13. Subcutaneous versus intravenous immunoglobulin in drug-naïve patients with chronic inflammatory demyelinating polyneuropathy (CIDP)

    DEFF Research Database (Denmark)

    Markvardsen, L H; Sindrup, S H; Christiansen, I;

    2016-01-01

    BACKGROUND AND PURPOSE: Subcutaneous immunoglobulin (SCIG) is superior to placebo treatment for maintenance of muscle strength during 12 weeks in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). The present study evaluated whether SCIG preserves muscle strength for 1 year...... in an open-label follow-up study. METHODS: Seventeen responders to intravenous immunoglobulin (IVIG) who had participated in the previous study of SCIG versus placebo in CIDP were included. After one IVIG infusion 2 weeks prior to baseline, all continued on SCIG treatment at weekly equal dosage and were...... remained unchanged. CONCLUSION: SCIG preserves muscle strength and functional ability in patients with CIDP who previously responded to IVIG. SCIG should be considered as an alternative in long-term treatment of CIDP patients....

  14. Histopathological confirmation of similar intramucosal distribution of fluorescein in both intravenous administration and local mucosal application for probe-based confocal laser endomicroscopy of the normal stomach.

    Science.gov (United States)

    Nonaka, Kouichi; Ohata, Ken; Ban, Shinichi; Ichihara, Shin; Takasugi, Rumi; Minato, Yohei; Tashima, Tomoaki; Matsuyama, Yasushi; Takita, Maiko; Matsuhashi, Nobuyuki; Neumann, Helmut

    2015-12-16

    Probe-based confocal laser endomicroscopy (pCLE) is capable of acquiring in vivo magnified cross-section images of the gastric mucosa. Intravenous injection of fluorescein sodium is used for confocal imaging. However, it is still under debate if local administration of the dye to the mucosa is also effective for confocal imaging as it is not yet clear if topical application also reveals the intramucosal distribution of fluorescein. The objective of this study was to evaluate the intramucosal distribution of fluorescein sodium after topical application and to compare the distribution to the conventional intravenous injection used for confocal imaging. pCLE of the stomach uninfected with Helicobacter pylori was performed in a healthy male employing intravenous administration and local mucosal application of fluorescein. The mucosa of the lower gastric body was biopsied 1 min and 5 min after intravenous administration or local mucosal application of fluorescein, and the distribution of fluorescein in the biopsy samples was examined histologically. Green fluorescence was already observed in the cytoplasm of fundic glandular cells in the biopsied deep mucosa 1 min after local mucosal application of fluorescein. It was also observed in the foveolar lumen and inter-foveolar lamina propria, although it was noted at only a few sites. In the tissue biopsied 5 min after the local mucosal application of fluorescein, green fluorescence was more frequently noted in the cytoplasm of fundic glandular cells than in that 1 min after the local mucosal application of fluorescein, although obvious green fluorescence was not identified in the foveolar lumen or inter-foveolar lamina propria. The distribution of intravenously administered fluorescein in the cytoplasm of fundic glandular cells was also clearly observed similarly to that after local mucosal application of fluorescein. Green fluorescence in more cells was observed in many cells 5 min after intravenous administration compared

  15. Antimicrobial Peptides: Multifunctional Drugs for Different Applications

    Directory of Open Access Journals (Sweden)

    Lea-Jessica Albrecht

    2012-02-01

    Full Text Available Antimicrobial peptides (APs are an important part of the innate immune system in epithelial and non-epithelial surfaces. So far, many different antimicrobial peptides from various families have been discovered in non-vertebrates and vertebrates. They are characterized by antibiotic, antifungal and antiviral activities against a variety of microorganisms. In addition to their role as endogenous antimicrobials, APs participate in multiple aspects of immunity. They are involved in septic and non-septic inflammation, wound repair, angiogenesis, regulation of the adaptive immune system and in maintaining homeostasis. Due to those characteristics AP could play an important role in many practical applications. Limited therapeutic efficiency of current antimicrobial agents and the emerging resistance of pathogens require alternate antimicrobial drugs. The purpose of this review is to highlight recent literature on functions and mechanisms of APs. It also shows their current practical applications as peptide therapeutics and bioactive polymers and discusses the possibilities of future clinical developments.

  16. Intravenous contrast media application using cone-beam computed tomography in a rabbit model

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Min Sung; Kim, Bok Yeol; Choi, Hwa Young [Dept. of Oral and Maxillofacial Radiology, School of Dentistry, Kyung Hee University, Seoul (Korea, Republic of); and others

    2015-03-15

    This study was performed to evaluate the feasibility of visualizing soft tissue lesions and vascular structures using contrast-enhanced cone-beam computed tomography (CE-CBCT) after the intravenous administration of a contrast medium in an animal model. CBCT was performed on six rabbits after a contrast medium was administered using an injection dose of 2 mL/kg body weight and an injection rate of 1 mL/s via the ear vein or femoral vein under general anesthesia. Artificial soft tissue lesions were created through the transplantation of autologous fatty tissue into the salivary gland. Volume rendering reconstruction, maximum intensity projection, and multiplanar reconstruction images were reconstructed and evaluated in order to visualize soft tissue contrast and vascular structures. The contrast enhancement of soft tissue was possible using all contrast medium injection parameters. An adequate contrast medium injection parameter for facilitating effective CE-CBCT was a 5-mL injection before exposure combined with a continuous 5-mL injection during scanning. Artificial soft tissue lesions were successfully created in the animals. The CE-CBCT images demonstrated adequate opacification of the soft tissues and vascular structures. Despite limited soft tissue resolution, the opacification of vascular structures was observed and artificial soft tissue lesions were visualized with sufficient contrast to the surrounding structures. The vascular structures and soft tissue lesions appeared well delineated in the CE-CBCT images, which was probably due to the superior spatial resolution of CE-CBCT compared to other techniques, such as multislice computed tomography.

  17. Successful Anti-HCV Therapy of a Former Intravenous Drug User with Sofosbuvir and Daclatasvir in a Peritranspant Setting: A Case Report

    Science.gov (United States)

    Seifert, Leon Louis; Heinzow, Hauke; Kabar, Iyad; Christensen, Stefan; Hüsing, Anna; Schmidt, Hartmut H.-J.

    2016-01-01

    Patient: Male, 37 Final Diagnosis: Chronic HCV-infection • hepatic decompensation Symptoms: Esophageal varices • portal-hypertensive gastropathy • splenomegaly • recurrent ascitic decompensation • hepatorenal syndrome • hepatic encephalopathy Medication: — Clinical Procedure: Liver transplantation • antiviral therapy Specialty: Gastroenterology and Hepatology Objective: Unusual setting of medical care Background: Direct-acting antivirals (DAAs) represent a new hallmark in antiviral therapy of hepatitis C virus (HCV). DAAs have been shown to be safe and effective after liver transplantation (LT), but there is little information about their use in peritransplant settings. Former intravenous drug users represent an increasing group seeking HCV treatment. This case report demonstrates the successful peritransplant antiviral treatment of a former intravenous drug user who had been treated in a methadone maintenance program. Case Report: The patient was diagnosed with Child B cirrhosis for the first time in 2009. He had a Model for End-stage Liver Disease (MELD) score of 21 and started antiviral therapy with sofosbuvir (SOF) and daclatasvir (DCV) in March 2014. Due to hepatic decompensation, he received a LT in April 2014. Immunosuppression was performed with tacrolimus (TAC) and mycophenolate-mofetil (MMF), and boosted with prednisolone in the initial stage. Four weeks after his LT, the patient presented with an acute renal injury. The patient was discharged one week later after sufficient hydration, discontinuation of non-steroidal anti-phlogistics therapy, and adjustments to his immunosuppressive regimen. At the beginning of his therapy, the number of RNA copies was 13,000 IU/mL. He received 24 weeks of anti-HCV treatment with SOF and DCV; the antiviral treatment was successful and his LT was well tolerated. Conclusions: Treatment of HCV is feasible in a peritransplant setting. The antiviral regimen we used did not seem to have any relevant

  18. Methylphenidate enhances the abuse-related behavioral effects of nicotine in rats: intravenous self-administration, drug discrimination, and locomotor cross-sensitization.

    Science.gov (United States)

    Wooters, Thomas E; Neugebauer, Nichole M; Rush, Craig R; Bardo, Michael T

    2008-04-01

    Stimulant drugs, including D-amphetamine, cocaine, and methylphenidate, increase cigarette smoking in controlled human laboratory experiments. Although the mechanism(s) underlying this effect are unknown, it is possible that stimulants may enhance directly the abuse-related effects of nicotine. In the present study, we characterized the behavioral pharmacological interactions between methylphenidate and nicotine in the intravenous self-administration, drug discrimination, and locomotor cross-sensitization procedures. Adult male Sprague-Dawley rats were trained to respond for intravenous nicotine (0.01 or 0.03 mg/kg/infusion) or sucrose, and the acute effects of methylphenidate (1.25-10 mg/kg) were determined; in addition, separate groups of rats were treated with methylphenidate (2.5 mg/kg) or saline before 12 consecutive nicotine (0.03 mg/kg/infusion) self-administration sessions. Next, the discriminative stimulus effects of nicotine (0.03-0.3 mg/kg) and methylphenidate (1.25-10 mg/kg), alone and in combination with a low nicotine dose (0.056 mg/kg), were tested in nicotine-trained rats. Finally, the locomotor effect of repeated methylphenidate (2.5 mg/kg) was tested in rats previously treated with nicotine (0.2-0.8 mg/kg). Results indicated that acute methylphenidate increased the rate of nicotine self-administration at doses that reduced sucrose-maintained responding; furthermore, tolerance to this effect was not apparent following repeated methylphenidate. Methylphenidate, while not substituting for nicotine alone, dose-dependently enhanced the discriminative stimulus effect of a low nicotine dose. In addition, repeated nicotine exposure promoted the development of locomotor sensitization to methylphenidate. Taken together with recent clinical findings, these results suggest that methylphenidate may enhance the abuse-related behavioral effects of nicotine, perhaps increasing vulnerability to tobacco dependence.

  19. 紫杉醇蛋白结合型药物静脉滴注的护理%Protein drug taxol intravenous drip of care

    Institute of Scientific and Technical Information of China (English)

    黄妹兰

    2016-01-01

    Objective To study the protein drug taxol intravenous drip of care;The nursing points Strict with the preparation of the drugs and infusion method, told before medication, medication during ecg monitoring, blood pressure monitor;Results Through the specification of the static drop time and the observation of the adverse drug reaction and nursing, patients with no serious adverse reaction, chemotherapy is completed on schedule.%目的:研究紫杉醇蛋白结合型药物的静脉滴注的护理。其护理要点:严格要求药物的配制与输注方法,用药前的告知,用药期间予心电监护、血压监测。结果:通过规范的静滴时间安排及对药物不良反应的观察与护理,患者无一例发生严重不良反应,按期顺利完成化疗。

  20. 静脉吸毒人员共用针具行为调查%Needle sharing and its influential factors among intravenous drugs users

    Institute of Scientific and Technical Information of China (English)

    汪慧; 卢次勇; 何源; 吴杰; 洪令瑶; 高雪; 邓雪清

    2012-01-01

    目的 了解静脉吸毒人群的针具共用情况并探索可能的影响因素.方法 采用横断面研究方法于2011年5-6月对广东省某戒毒所内静脉吸毒人员进行一对一的问卷调查,调查内容包括一般人口学信息、吸毒相关行为、性行为及艾滋病综合防治知识.结果 调查的267名男性静脉吸毒人员的平均年龄为(38±6.1)岁,首次注射吸毒的平均年龄为(28土6.9)岁.30.71%的被调查者曾有过共用针具行为,被调查者使用的毒品种类主要是海洛因.Logistic回归分析表明,与别人一起吸毒(0R=3.62,95%CI=1.77-7.37)以及共用过辅助器具者(0R=13.48,95%CI=6.66-27.27)是共用针具的危险因素.结论 共用针具行为普遍存在于静脉吸毒人群中,相关部门应采取有效管理措施,以减少该人群中高危行为的发生.%Objective To understand the status and explore influential factors for needle sharing among intravenous drug users. Methods A cross-sectional survey among intravenous drug users in a rehabilitation center in Guangdong province was carried out during May and June 2011. Questionnaire-based interviews were conducted to collect information including socio-demographics, drug use patterns, sexual behaviors and HlV-related knowledge. Results Of 267 eligible participants, the mean age was(38±6.1).The mean initial age of injecting drug was (28±6.9). 30.71% of them reported having shared needles and heroin was the most widely used drug among them. The Logistic regression showed that not injecting alone(OR=3.62,95%CI=1.77-7.37) and sharing injection paraphernalia (OR= 13.48,95%CI=6.66-27.27) were the risk factors for needle sharing. Conclusions Needle sharing is not rare among intravenous drug users. Targeted effective measures should be carried out to reduce those risky behaviors.

  1. 24 CFR 960.205 - Drug use by applicants: Obtaining information from drug treatment facility.

    Science.gov (United States)

    2010-04-01

    ... information from drug treatment facility. 960.205 Section 960.205 Housing and Urban Development Regulations... Admission § 960.205 Drug use by applicants: Obtaining information from drug treatment facility. (a) Purpose. This section addresses a PHA's authority to request and obtain information from drug abuse...

  2. 75 FR 73108 - Guidance for Industry on Abbreviated New Drug Applications: Impurities in Drug Products...

    Science.gov (United States)

    2010-11-29

    ... HUMAN SERVICES Food and Drug Administration Guidance for Industry on Abbreviated New Drug Applications...: The Food and Drug Administration (FDA) is announcing the availability of a guidance for industry...) guidance for industry ``Q3B(R) Impurities in New Drug Products,'' which was announced in August 2006....

  3. Flat-detector computed tomography with intravenous contrast material application in experimental aneurysms: comparison with multislice CT and conventional angiography.

    Science.gov (United States)

    Struffert, Tobias; Doelken, Marc; Adamek, Edyta; Schwarz, Marc; Engelhorn, Tobias; Kloska, Stephan; Ott, Sabine; Doerfler, Arnd

    2010-05-01

    Despite limited soft tissue resolution flat-detector computed tomography (FD-CT) provides substantial superior spatial resolution in comparison with multislice computed tomography (MS-CT). This may add value in the visualization of small vascular structures if intravenous contrast application leads to substantial opacification and visibility of intracranial vessels or aneurysms. To evaluate the feasibility of visualization of vascular structures by FD-CT angiography (FD-CTA) after intravenous contrast injection compared with MS-CTA and intra-arterial digital subtracted angiography (IADSA) in an animal model. Aneurysms were created in the right common carotid artery in six New Zealand White Rabbits using the elastase technique. Imaging was performed using FD-CTA, MS-CTA (injection of 1 ml/kg body weight) and IADSA. Anonymized volume rendering reconstruction (VRT), maximum intensity projection (MIP), and multiplanar reconstruction (MPR) images were reconstructed and evaluated by two experienced reviewers for aneurysm geometry and vascular structure anatomy using standard tools of a dedicated workstation. Aneurysms could be successfully created in all animals. Measurements of aneurysm geometry (aneurysm height, width, neck width) and vascular structures (brachiocephalic trunk, carotid artery diameter and plane) were nearly identical in all three modalities. Intra- and inter-observer correlations of the different parameters showed high r values between 0.83 and 0.99. Our results show the feasibility of FD-CTA in comparison with MS-CTA and IADSA in an animal model. Despite limited soft tissue resolution, opacification of vascular structures with sufficient contrast to the surrounding structures was possible in all animals. Vascular structures appeared better delineated in FD-CTA than in MS-CTA, probably due to the superior spatial resolution.

  4. Pharmacokinetics of difloxacin in pigs and broilers following intravenous, intramuscular, and oral single-dose applications.

    Science.gov (United States)

    Ding, H Z; Yang, G X; Huang, X H; Chen, Z L; Zeng, Z L

    2008-06-01

    Pharmacokinetics of difloxacin, a fluoroquinolone antibiotic, was determined in pigs and broilers after intravenous (i.v.), intramuscular (i.m.), or oral (p.o.) administration at a single dose of five (pigs) or 10 mg/kg (broilers). Plasma concentration profiles were analyzed by a compartmental pharmacokinetic method. Following i.v., i.m. and p.o. doses, the elimination half-lives (t(1/2beta)) were 17.14 +/- 4.14, 25.79 +/- 8.10, 16.67 +/- 4.04 (pigs) and 6.11 +/- 1.50, 5.64 +/- 0.74, 8.20 +/- 3.12 h (broilers), respectively. After single i.m. and p.o. administration, difloxacin was rapidly absorbed, with peak plasma concentrations (C(max)) of 1.77 +/- 0.66, 2.29 +/- 0.85 (pigs) and 2.51 +/- 0.36, 1.00 +/- 0.21 microg/mL (broilers) attained at t(max) of 1.29 +/- 0.26, 1.41 +/- 0.88 (pigs) and 0.86 +/- 0.4, 4.34 +/- 2.40 h (broilers), respectively. Bioavailabilities (F) were (95.3 +/- 28.9)% and (105.7 +/- 37.1)% (pigs) and (77.0 +/- 11.8)% and (54.2 +/- 12.6)% (broilers) after i.m. and p.o. doses, respectively. Apparent distribution volumes(V(d(area))) of 4.91 +/- 1.88 and 3.10 +/- 0.67 L/kg and total body clearances(Cl(B)) of 0.20 +/- 0.06 and 0.37 +/- 0.10 L/kg/h were determined in pigs and broilers, respectively. Areas under the curve (AUC), the half-lives of both absorption and distribution(t(1/2ka), t(1/2alpha)) were also determined. Based on the single-dose pharmacokinetic parameters determined, multiple dosage regimens were recommended as: a dosage of 5 mg/kg given intramuscularly every 24 h in pigs, or administered orally every 24 h at the dosage of 10 mg/kg in broilers, can maintain effective plasma concentrations with bacteria infections, in which MIC(90) are <0.25 microg/mL and <0.1 microg/mL respectively.

  5. ENHANCED LIVER DELIVERY AND SUSTAINED RELEASE OF CURCUMIN WITH DRUG LOADED NANOPARTICLES AFTER INTRAVENOUS ADMINISTRATION IN RATS

    Directory of Open Access Journals (Sweden)

    SURESH K, BONEPALLY REDDY, JITHAN A

    2013-09-01

    Full Text Available Liver targeting drug delivery systems can improve thedelivery of several drugs useful in the treatment of liverdisorders such as cirrhosis and liver cancer. Theobjective of this study was to prepare the biodegradablenanoparticles containing curcumin, a well-knownhepatoprotective agent and further to evaluate the livertargetability and sustained release of curcumin with thedeveloped nanoformulation. Curcumin nanoparticleswere prepared by double emulsion (w/o/w solventevaporation method using different drug polymer ratios.Poly-ε-caprolactone was used in the preparation. Theprepared formulations were evaluated for particles size,surface potential, entrapment efficiency, in vitro release,drug polymer interaction. Four different formulationsCNP1, CNP2, CNP3 and CNP4 were prepared.Optimized formulation (CNP3 was evaluated forpharmacokinetics and hepatoprotective activity in CCl4induced liver toxicity model after i.v. administration.Optimized formulation was selected based on the size,entrapment efficiency and release characteristics.Curcumin i.v. solution and oral suspension form wereused as the reference. Particle size of all formulationswas in the range of 300-470 nm and the entrapmentefficiencies were in the range of 75-85 %. Drug releasefrom the nanoparticles was sustained both in vitro and invivo. Nanoparticle formulation tested in vivodemonstrated better pharmacokinetics andpharmacodynamics compared to the reference. Druglevels in the liver were significantly higher withnanoparticular formulation. Thus, this studysuccessfully prepared a nanoparticular formulationcontaining curcumin with polycaprolactone as thepolymer. With the developed formulation better livertargetability was achieved.

  6. Therapeutic drug monitoring for either oral or intravenous busulfan when combined with pre- and post-transplantation cyclophosphamide.

    Science.gov (United States)

    Lombardi, Lindsey R; Kanakry, Christopher G; Zahurak, Marianna; Durakovic, Nadira; Bolaños-Meade, Javier; Kasamon, Yvette L; Gladstone, Douglas E; Matsui, William; Borrello, Ivan; Huff, Carol Ann; Swinnen, Lode J; Brodsky, Robert A; Ambinder, Richard F; Fuchs, Ephraim J; Rosner, Gary L; Jones, Richard J; Luznik, Leo

    2016-01-01

    Busulfan (Bu)/cyclophosphamide (Cy) is a standard conditioning platform for allogeneic transplantation. We developed a strategy separating the Cy into two pre/post-transplantation doses (PTCy), providing myeloablative conditioning and single-agent graft-versus-host disease (GVHD) prophylaxis. We investigated the impact of Bu route on treatment-related toxicity for 131 consecutive adult patients. Busulfan was administered in four daily divided doses either orally (n = 72) or intravenously (n = 59) with pharmacokinetics on the first-dose and as necessary on subsequent doses to achieve a target area-under-the-concentration-curve (AUC) of 800-1400 μmol*min/L per dose. BuCy/PTCy with pharmacokinetics is well-tolerated with low treatment-related toxicity. Hepatic veno-occlusive disease incidence was 6% with two fatal events. Bu administration route in the context of BuCy/PTCy did not statistically impact hepatotoxicity, GVHD, relapse, disease-free survival, or overall survival. The BuCy/PTCy platform has a low incidence of treatment-related toxicity, including hepatotoxicity, in hematologic malignancies when using pharmacokinetics for a target AUC of 800-1400 μmol*min/L, irrespective of Bu administration route.

  7. Partial intravenous anesthesia in cats and dogs.

    Science.gov (United States)

    Duke, Tanya

    2013-03-01

    The partial intravenous anesthesia technique (PIVA) is used to lower the inspired concentration of an inhalational anesthetic by concurrent use of injectable drugs. This technique reduces the incidence of undesirable side-effects and provides superior quality of anesthesia and analgesia. Drugs commonly used for PIVA include opioids, alpha-2 adrenergic agonists, injectable anesthetic agents, and lidocaine. Most are administered by intravenous infusion.

  8. Therapeutic drug monitoring, a practical application

    NARCIS (Netherlands)

    Kees Neef, C.; Touw, D.J.

    2010-01-01

    Therapeutic Drug Monitoring (TDM) is an indispensable tool in therapeutic handling and medication safety. A definition of TDM is: Therapeutic drug monitoring is a system of quality assurance of a drug management system, aiming that the right drug is given tot the right patient in the right dose in o

  9. 静脉药物配制护理差错分析与解决对策研究%Analysis Nursing Error of Intravenous Drug Preparation and Research Countermeasures

    Institute of Scientific and Technical Information of China (English)

    孙艳梅

    2015-01-01

    Objective Analyzes the reasons of nursing errors in intravenous drug allocation, and discussed countermeasures.MethodsSelected nursing error in intravenous drug allocation data from 2012 September to 2014 September in our hospital, analyzed it retrospectively, discussed speciifc reasons of nursing errors in conifguration of intravenous drugs, and proposes the corresponding solution.ResultsAnalyzed a total intravenous drugs configuration nursing error data retrospectively, mainly intravenous drug configuration nursing error is the doctor's advice, nursing staff into the doctor's advice, medicine medicine and configuration, and finished product checked.Conclusion Through the study found, only to strengthen the responsibility of medical staff, in strict accordance with the rules and regulations of intravenous drugs conifguration, reduce the intravenous drugs allocation nursing error that can promote patients recover.%目的:分析静脉药物配制护理差错的原因,并对其解决对策进行探讨。方法选取我院于2012年9月~2014年9月的静脉药物配制护理差错资料,对其进行回顾性分析,探讨静脉药物配制护理差错的具体原因,并对其提出相应的解决办法。结果通过对我院静脉药物配制护理差错资料进行回顾性分析发现,静脉药物配制护理差错主要是医嘱审核、护理人员医嘱确认、药护排药和配制以及成品核对等方面。结论通过研究发现,必须增强医护人员工作责任感,严格按照规章制度进行静脉药物配制,才能减少静脉药物配制护理差错,促进患者康复。

  10. 静脉药物配置中心药物配置过程中的质量管理%Quality management in the process of drug disposition in intravenous drug allocation center

    Institute of Scientific and Technical Information of China (English)

    吴芳

    2015-01-01

    Objective:To explore the quality management in the process of drug disposition in intravenous drug allocation center. Methods:We summarized the operation experience of quality management in the process of drug disposition,and analyzed the rational and operational errors in the process of drug disposition,to correct errors in a timely manner.800 cases of intravenous infusion configuration orders were selected from March 2011 to August 2011 as the control group,and 1 000 cases of medical advice were selected from June 2013 to June 2014 as the observation group.We compared two groups of irrational medication. Results:In the observation group,the proportion of incompatibility,improper combination of drugs,improper medication frequency, repeated administration,concentrations of misconduct were significantly lower than the control group,and the difference was statistically significant(P<0.05).Conclusion:In PIVAS,we should pay attention to drug reaction,dispensing order,incompatibility, dissolved standard in the process of drug disposition,which was an important role of drug quality management.%目的:探讨静脉药物配置中心药物配置过程中的质量管理.方法:总结在药物配置过程中对质量管理的操作经验,分析配置过程中出现的不合理与错误操作,及时纠正错误.2011年3月-2011年8月系统提供的静脉输液配置医嘱单800例为对照组,2013年6月-2014年6月1 000例医嘱单为观察组,比较两组不合理医嘱发生情况.结果:观察组的配伍禁忌、联合用药不当、给药频次不当、重复给药、给药浓度不当发生比例均显著低于对照组,差异有统计学意义(P<0.05).结论:静脉药物配置中心药物配置过程中应注意药物间反应、配药顺序、配伍禁忌、溶解标准,对药物质量管理起重要作用.

  11. Improving Drug Administration to Reduce Drug Use Error Rare of Pharmacy Intravenous Admixture Service%完善药品管理降低静脉用药调配中心药品使用差错率

    Institute of Scientific and Technical Information of China (English)

    周璐; 陈海燕

    2015-01-01

    Objective To reduce drug using error rare of pharmacy intravenous admixture service (PIVAS) by improving drug administration. Methods Drug using errors in PIVAS from March 2014 to August in 2014 were analyzed retrospective-ly, and during this time some measures about drug administration were taken. Results Drug using errors were decreased from 162 cases in March to 39 cases in August in 2014,and the drug using error rate was reduced from 2.04‰to 0.48‰(P<0.05). Conclusion Drug administration played a vital operation in PIVAS, and improving drug management can not only reduce the error rate in PIVAS but also reduce medical risks.%目的 完善药品管理,降低儿童医院静脉用药调配中心(PIVAS)药品使用差错率.方法 回顾该院PIVAS2014年3月-2014年8月,分析完善药品管理前后,药品使用差错的变化情况. 结果 药品使用差错由2014年3月的162例减少为8月的39例,药品使用差错率由2.04‰降为0.48‰(P<0.05). 结论 药品管理在PIVAS运行中起着至关重要的作用,做好药品管理,可降低PIVAS差错率,减少医疗隐患.

  12. Intra-articular versus intravenous tranexamic acid application in total knee arthroplasty: a meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Mi, Bobin; Liu, Guohui; Zhou, Wu; Lv, Huijuan; Liu, Yi; Zha, Kun; Wu, Qipeng; Liu, Jing

    2017-07-01

    The purpose of this meta-analysis was to compare the blood loss and complications of intra-articular (IA) with intravenous (IV) tranexamic acid (TXA) for total knee arthroplasty (TKA). A comprehensive search of studies was conducted to identify related articles in Pubmed, Embase, Cochrane central Register of Controlled Trials, springerLink, OVID and the Research published from January 1980 to September 2016. All studies that compared IA TXA with IV TXA application on TKA were included. Main outcomes of the two methods were collected and analyzed by using Review Manager 5.3. There were 16 randomized controlled trials with 1308 cases met the criteria. Compared with IV TXA, IA TXA had similar blood volume of drainage, hidden blood loss, transfusion rate and complications (P > 0.05). IA TXA had lower total blood loss than IV TXA, and there was significant difference (P  0.05) when compared with IA TXA. Both IA TXA and single dose of IV TXA are effective in reducing total blood loss and postoperative hemoglobin drop without increasing complications of DVT or PE. The current meta-analysis suggests that 1.5 g TXA by IA administration or 1 g TXA by IV administration 10 min before tourniquet deflation is effective and safe in patients undergoing TKA.

  13. Laryngotracheal application of lidocaine spray increases the incidence of postoperative sore throat after total intravenous anesthesia.

    Science.gov (United States)

    Maruyama, Koichi; Sakai, Hironori; Miyazawa, Hideki; Iijima, Kyou; Toda, Naoyuki; Kawahara, Shuji; Hara, Katsumi

    2004-01-01

    To determine the effect of laryngotracheal application of different doses of lidocaine spray on postoperative sore throat and hoarseness, we evaluated the incidence and severity of these complications in 168 ASA I-III patients aged 15-92 years in a placebo-controlled study. After induction of anesthesia with propofol, ketamine, fentanyl, and vecuronium, the laryngotracheal area was sprayed immediately before intubation with lidocaine spray either 5 times (L5 group, n = 47) or 10 times (L10 group, n = 48) or with normal saline 1 ml (placebo group, n = 51). Postoperative sore throat and hoarseness were evaluated immediately after surgery and on the day after surgery. The incidence of sore throat was significantly higher in the L10 group than in the placebo group on both the day of and the day after surgery. The severity of sore throat was significantly higher in the L5 and L10 groups than in the placebo group on the day of surgery. On the day after surgery, the severity of sore throat remained significantly higher in the L10 group than in the placebo group. Although the incidence and severity of sore throat increased in a dose-dependent manner, these were not significantly different between the L5 and L10 groups. In addition, the incidence and severity of hoarseness did not differ at all among the three groups. We recommend that applications of lidocaine spray to the laryngotracheal area should be avoided to help eliminate unnecessary postoperative sore throat, thereby leading to improvement in patient satisfaction.

  14. 78 FR 52931 - Draft Guidance for Industry on Abbreviated New Drug Applications: Stability Testing of Drug...

    Science.gov (United States)

    2013-08-27

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Abbreviated New Drug Applications: Stability Testing of Drug Substances and Products, Questions and Answers; Availability AGENCY... announcing the availability of a draft guidance for industry entitled ``ANDAs: Stability Testing of...

  15. 21 CFR 320.31 - Applicability of requirements regarding an “Investigational New Drug Application.”

    Science.gov (United States)

    2010-04-01

    ...Investigational New Drug Application.â 320.31 Section 320.31 Food and Drugs FOOD AND DRUG ADMINISTRATION... Applicability of requirements regarding an “Investigational New Drug Application.” (a) Any person planning to... drug product that is the subject of an approved new drug application or abbreviated new...

  16. The application of drug dose equivalence in the quantitative analysis of receptor occupation and drug combinations

    OpenAIRE

    Tallarida, Ronald J.; Raffa, Robert B.

    2010-01-01

    In this review we show that the concept of dose equivalence for two drugs, the theoretical basis of the isobologram, has a wider use in the analysis of pharmacological data derived from single and combination drug use. In both its application to drug combination analysis with isoboles and certain other actions, listed below, the determination of doses, or receptor occupancies, that yield equal effects provide useful metrics that can be used to obtain quantitative information on drug actions w...

  17. Comparison of HIV-, HBV-, HCV- and co-infection prevalence between Chinese and Burmese intravenous drug users of the China-Myanmar border region.

    Science.gov (United States)

    Zhou, Yan-Heng; Liu, Feng-Liang; Yao, Zhi-Hong; Duo, Lin; Li, Hong; Sun, Yi; Zheng, Yong-Tang

    2011-01-21

    Co-infection with HIV and HCV and/or HBV is highly prevalent in intravenous drug users (IDUs). Because of the proximity to the "Golden Triangle", HIV prevalence among the IDUs is very high in the China-Myanmar border region. However, there are few studies about co-infection with HIV and HCV and/or HBV, especially in the region that belongs to Myanmar. 721 IDUs, including 403 Chinese and 318 Burmese, were investigated for their HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV) serological status. Statistical analysis was performed to evaluate the differences of the epidemic situation between the Chinese IDUs and the Burmese IDUs. Among the Chinese IDUs and the Burmese IDUs, HCV infection was the most prevalent (69.0% vs 48.1%, P0.05). Besides, there were more HIV-HBV co-infected IDUs (20.1% vs 11.3%, Ptriple infection (19.1% vs 10.4%, Pborder region. The HIV epidemic appears to be in a downward trend, compared with previous reports. However, all infections were more prevalent among the Chinese IDUs than among the Burmese.

  18. Inaccuracy of transthoracic echocardiography for the identification of right-sided vegetation in patients with no history of intravenous drug abuse or cardiac device insertion.

    Science.gov (United States)

    Xie, Jiang; Liu, Shuang; Yang, Jinghua; Xu, Jie; Zhu, Guangfa

    2014-06-01

    The use of transthoracic echocardiography (TTE) to identify right-sided infective endocarditis (RSIE) vegetation is controversial. Data are scarce for patients with no history of intravenous drug abuse (IVDA) or cardiac device insertion. This study analysed the consistency of presurgical echocardiographic results with surgical findings for vegetation identification, and the factors that influence accuracy of echocardiography. This retrospective trial divided infective endocarditis (IE) patients into three subgroups according to the results of their presurgical TTE: left-sided native IE (LSNIE), left-sided prosthetic valve IE (LSPIE) and RSIE. The accuracy of TTE was tested by comparing vegetation (number and location), detected presurgery by TTE, with actual findings during surgery. In total, 416 patients were analysed, 322 with LSNIE, 31 with LSPIE and 63 with RSIE. Consistency between TTE findings and surgical results was lower in the RSIE group compared with the LSPIE and LSNIE groups. Consistency was lowered by the presence of vegetation in multiple locations and atypical distribution--both of which were increased in the RSIE group. The chance of vegetation in both sides of the heart rose with increased numbers of vegetation locations in RSIE patients. A high proportion of RSIE patients had congenital heart defects, mostly ventricular septal defects. TTE may be unsuitable for RSIE patients with no history of IVDA or cardiac device insertion, because multifocal and atypically distributed vegetation may influence detection accuracy. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  19. 21 CFR 314.152 - Notice of withdrawal of approval of an application or abbreviated application for a new drug.

    Science.gov (United States)

    2010-04-01

    ... or abbreviated application for a new drug. 314.152 Section 314.152 Food and Drugs FOOD AND DRUG... APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.152 Notice of withdrawal of approval of an application or abbreviated application for a new drug. If the Food and...

  20. Phylodynamic analysis reveals CRF01_AE dissemination between Japan and neighboring Asian countries and the role of intravenous drug use in transmission.

    Directory of Open Access Journals (Sweden)

    Teiichiro Shiino

    Full Text Available BACKGROUND: One major circulating HIV-1 subtype in Southeast Asian countries is CRF01_AE, but little is known about its epidemiology in Japan. We conducted a molecular phylodynamic study of patients newly diagnosed with CRF01_AE from 2003 to 2010. METHODS: Plasma samples from patients registered in Japanese Drug Resistance HIV-1 Surveillance Network were analyzed for protease-reverse transcriptase sequences; all sequences undergo subtyping and phylogenetic analysis using distance-matrix-based, maximum likelihood and Bayesian coalescent Markov Chain Monte Carlo (MCMC phylogenetic inferences. Transmission clusters were identified using interior branch test and depth-first searches for sub-tree partitions. Times of most recent common ancestor (tMRCAs of significant clusters were estimated using Bayesian MCMC analysis. RESULTS: Among 3618 patient registered in our network, 243 were infected with CRF01_AE. The majority of individuals with CRF01_AE were Japanese, predominantly male, and reported heterosexual contact as their risk factor. We found 5 large clusters with ≥5 members and 25 small clusters consisting of pairs of individuals with highly related CRF01_AE strains. The earliest cluster showed a tMRCA of 1996, and consisted of individuals with their known risk as heterosexual contacts. The other four large clusters showed later tMRCAs between 2000 and 2002 with members including intravenous drug users (IVDU and non-Japanese, but not men who have sex with men (MSM. In contrast, small clusters included a high frequency of individuals reporting MSM risk factors. Phylogenetic analysis also showed that some individuals infected with HIV strains spread in East and South-eastern Asian countries. CONCLUSIONS: Introduction of CRF01_AE viruses into Japan is estimated to have occurred in the 1990s. CFR01_AE spread via heterosexual behavior, then among persons connected with non-Japanese, IVDU, and MSM. Phylogenetic analysis demonstrated that some viral

  1. Modification by dopaminergic drugs of choice behavior under concurrent schedules of intravenous saline and food delivery in monkeys.

    Science.gov (United States)

    Gasior, Maciej; Paronis, Carol A; Bergman, Jack

    2004-01-01

    The allocation of "choice" behavior provides a measure that may be useful in developing experimental models of clinical relapse. In the present experiments, indirect monoaminergic agonists [cocaine, 1-(2-[bis(4-fluorophenyl)methoxy]ethyl)-4-(3-phenylpropyl)piperazine (GBR 12909), desipramine, and citalopram], and dopaminergic D1 family agonists [(+/-)-6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF 82958), R-(+)-6-bromo-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (R-(+)-6-BrAPB), and 6-chloro-7,8-dihydroxy-3-methyl-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF 83959)] and D2 family agonists [quinelorane, R-(-)-10,11-dihydroxy-N-n-propylnorapomorphine (R-NPA), (+)-N-propyl-hydroxynaphoxazine [(+)-PHNO], and S-(+)-(4aR,10bR)-3,4,4a,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano-[4,3-b]-1,4-oxazin-9-ol (PD 128907)] were evaluated for their capacity to alter the distribution of choice behavior in cocaine-experienced monkeys. Rhesus monkeys responded on two levers (injection-lever and food-lever) under concurrent fixed ratio 30; fixed ratio 30 schedules of i.v. cocaine and food delivery. Under training conditions, the distribution of behavior was related to the unit dose of i.v. cocaine: when saline was available, responding occurred predominantly on the food-lever and when reinforcing doses of cocaine were available, responding occurred predominantly on the injection-lever. Drugs were studied by administering i.m. pretreatment doses before components in sessions of i.v. saline availability. Cocaine produced dose-related increases in injection-lever responding in all monkeys, whereas desipramine failed to alter the distribution of behavior in any monkey. The dopamine transport blocker GBR 12909 and each dopamine D1 family agonist markedly increased injection-lever responding in three of four monkeys; the serotonin transport blocker citalopram and D2 family agonists were comparably effective in only one

  2. Analysis of intravenous glucose tolerance test data using parametric and nonparametric modeling: application to a population at risk for diabetes.

    Science.gov (United States)

    Marmarelis, Vasilis Z; Shin, Dae C; Zhang, Yaping; Kautzky-Willer, Alexandra; Pacini, Giovanni; D'Argenio, David Z

    2013-07-01

    Modeling studies of the insulin-glucose relationship have mainly utilized parametric models, most notably the minimal model (MM) of glucose disappearance. This article presents results from the comparative analysis of the parametric MM and a nonparametric Laguerre based Volterra Model (LVM) applied to the analysis of insulin modified (IM) intravenous glucose tolerance test (IVGTT) data from a clinical study of gestational diabetes mellitus (GDM). An IM IVGTT study was performed 8 to 10 weeks postpartum in 125 women who were diagnosed with GDM during their pregnancy [population at risk of developing diabetes (PRD)] and in 39 control women with normal pregnancies (control subjects). The measured plasma glucose and insulin from the IM IVGTT in each group were analyzed via a population analysis approach to estimate the insulin sensitivity parameter of the parametric MM. In the nonparametric LVM analysis, the glucose and insulin data were used to calculate the first-order kernel, from which a diagnostic scalar index representing the integrated effect of insulin on glucose was derived. Both the parametric MM and nonparametric LVM describe the glucose concentration data in each group with good fidelity, with an improved measured versus predicted r² value for the LVM of 0.99 versus 0.97 for the MM analysis in the PRD. However, application of the respective diagnostic indices of the two methods does result in a different classification of 20% of the individuals in the PRD. It was found that the data based nonparametric LVM revealed additional insights about the manner in which infused insulin affects blood glucose concentration. © 2013 Diabetes Technology Society.

  3. Multifunctional Nanoparticles for Drug Delivery Applications Imaging, Targeting, and Delivery

    CERN Document Server

    Prud'homme, Robert

    2012-01-01

    This book clearly demonstrates the progression of nanoparticle therapeutics from basic research to applications. Unlike other books covering nanoparticles used in medical applications, Multifunctional Nanoparticles for Drug Delivery Applications presents the medical challenges that can be reduced or even overcome by recent advances in nanoscale drug delivery. Each chapter highlights recent progress in the design and engineering of select multifunctional nanoparticles with topics covering targeting, imaging, delivery, diagnostics, and therapy.

  4. The Design and Application of the Transfusion Warning Card in the Intra-venous Administration Center%静脉用药调配中心输液警示卡的设计与应用研究

    Institute of Scientific and Technical Information of China (English)

    付梦丽

    2015-01-01

    目的:探讨静脉用药调配中心输液警示卡的设计与应用。方法该院静脉用药调配中心根据静脉用药需求制订了警示卡,在审方过程中,药师将医院采购新药物的使用方法和注意事项,以及输液使用时的注意事项及时地填写到PIVAS临床输液警示卡上。结果警示卡的使用保证了患者的输液质量,提高了患者对医护工作的满意度。结论警示卡将用药过程中的一些注意事项标出,变事后管理为预见性管理,对于临床输液的注意事项起到了积极的宣教作用,这样不仅提高了护士的药物知识,还可以提高护理的工作效率,降低不良反应的发生,从而有效提高输液过程中的安全控制,保证输液安全。%Objective To study the design and application of the venous transfusion warning card in the center of intra-venous drug use. Methods In our hospital, the intravenous drug allocation center according to the demand of intravenous medication developed a caution card, in the process of the trial, the pharmacist will purchase new drug use method and matters needing attention, and matters needing attention when used by infusion in time to fill out the PIVAS infusion warn-ing card. Results The use of the warning card to ensure the quality of the patient's transfusion, improve the patient's satis-faction with health care work. Conclusion Warning card will be course of medication in some note mark, after the change of management is the preview of management, for clinical transfusion note to the positive role in education. This will not only improve the nurses knowledge of drugs, but also can improve the efficiency of nursing work, reduced the occurrence of low adverse reaction, so as to effectively improve the safety in the process of transfusion control to ensure safe transfusion.

  5. The Effects of a Normal Rate versus a Slow Intervalled Rate of Oral Nutrient Intake and Intravenous Low Rate Macronutrient Application on Psychophysical Function – Two Pilot Studies

    Science.gov (United States)

    Denzer-Lippmann, Melanie Y.; Bachlechner, Stephan; Wielopolski, Jan; Fischer, Marie; Buettner, Andrea; Doerfler, Arndt; Schöfl, Christof; Münch, Gerald; Kornhuber, Johannes; Thürauf, Norbert

    2017-01-01

    Stomach distension and energy per time are factors influencing satiety. Moreover, different rates of nutrient intake induce different stomach distension. The goal of our studies was to elucidate the influence of different oral rates of nutrient intake (normal rate versus slow intervalled rate; study I) and intravenous low rate macronutrient application (protein, carbohydrate, fat) or placebo (study II) on psychophysical function. The pilot studies investigated the effects of 1) study I: a mixed nutrient solution (1/3 protein, 1/3 fat, 1/3 carbohydrates) 2) study II: intravenous macronutrient infusions (protein, carbohydrate, fat) or placebo on psychophysical function (mood, hunger, food craving, alertness, smell intensity ratings and hedonic ratings) in human subjects. In study I 10 male subjects (age range: 21–30 years) completed the study protocol participating in both test conditions and in study II 20 male subjects (age range: 19–41 years) completed the study protocol participating in all test conditions. Additionally, metabolic function was analyzed and cognitive and olfactory tests were conducted twice starting 100 min before the beginning of the intervention and 240 min after. Psychophysical (mood, hunger, fat-, protein-, carbohydrate-, sweets- and vegetable-craving), alertness and metabolic function tests were performed seven times on each examination day. Greater effects on hunger and food cravings were observed for normal rate of intake compared to slow intervalled rate of intake and intravenous low rate macronutrient application. Our findings potentially confirm that volume of the food ingested and a higher rate of energy per time contribute to satiety during normal rate of food intake, while slow intervalled rate of food intake and intravenous low rate macronutrient application showed no effects on satiation. Our results motivate the view that a certain amount of volume of the food ingested and a certain energy per time ratio are necessary to reduce

  6. The Effects of a Normal Rate versus a Slow Intervalled Rate of Oral Nutrient Intake and Intravenous Low Rate Macronutrient Application on Psychophysical Function – Two Pilot Studies

    Directory of Open Access Journals (Sweden)

    Melanie Y. Denzer-Lippmann

    2017-06-01

    Full Text Available Stomach distension and energy per time are factors influencing satiety. Moreover, different rates of nutrient intake induce different stomach distension. The goal of our studies was to elucidate the influence of different oral rates of nutrient intake (normal rate versus slow intervalled rate; study I and intravenous low rate macronutrient application (protein, carbohydrate, fat or placebo (study II on psychophysical function. The pilot studies investigated the effects of 1 study I: a mixed nutrient solution (1/3 protein, 1/3 fat, 1/3 carbohydrates 2 study II: intravenous macronutrient infusions (protein, carbohydrate, fat or placebo on psychophysical function (mood, hunger, food craving, alertness, smell intensity ratings and hedonic ratings in human subjects. In study I 10 male subjects (age range: 21–30 years completed the study protocol participating in both test conditions and in study II 20 male subjects (age range: 19–41 years completed the study protocol participating in all test conditions. Additionally, metabolic function was analyzed and cognitive and olfactory tests were conducted twice starting 100 min before the beginning of the intervention and 240 min after. Psychophysical (mood, hunger, fat-, protein-, carbohydrate-, sweets- and vegetable-craving, alertness and metabolic function tests were performed seven times on each examination day. Greater effects on hunger and food cravings were observed for normal rate of intake compared to slow intervalled rate of intake and intravenous low rate macronutrient application. Our findings potentially confirm that volume of the food ingested and a higher rate of energy per time contribute to satiety during normal rate of food intake, while slow intervalled rate of food intake and intravenous low rate macronutrient application showed no effects on satiation. Our results motivate the view that a certain amount of volume of the food ingested and a certain energy per time ratio are necessary

  7. Nanobiotechnology and its applications in drug delivery system: a review.

    Science.gov (United States)

    Khan, Imran; Khan, Momin; Umar, Muhammad Naveed; Oh, Deog-Hwan

    2015-12-01

    Nanobiotechnology holds great potential in various regimes of life sciences. In this review, the potential applications of nanobiotechnology in various sectors of nanotechnologies, including nanomedicine and nanobiopharmaceuticals, are highlighted. To overcome the problems associated with drug delivery, nanotechnology has gained increasing interest in recent years. Nanosystems with different biological properties and compositions have been extensively investigated for drug delivery applications. Nanoparticles fabricated through various techniques have elevated therapeutic efficacy, provided stability to the drugs and proved capable of targeting the cells and controlled release inside the cell. Polymeric nanoparticles have shown increased development and usage in drug delivery as well as in diagnostics in recent decades.

  8. Application of supercritical antisolvent method in drug encapsulation: a review

    Directory of Open Access Journals (Sweden)

    Kalani M

    2011-07-01

    Full Text Available Mahshid Kalani, Robiah YunusChemical and Environmental Engineering, Faculty of Engineering, University Putra Malaysia, Selangor Darul Ehsan, MalaysiaAbstract: The review focuses on the application of supercritical fluids as antisolvents in the pharmaceutical field and demonstrates the supercritical antisolvent method in the use of drug encapsulation. The main factors for choosing the solvent and biodegradable polymer to produce fine particles to ensure effective drug delivery are emphasized and the effect of polymer structure on drug encapsulation is illustrated. The review also demonstrates the drug release mechanism and polymeric controlled release system, and discusses the effects of the various conditions in the process, such as pressure, temperature, concentration, chemical compositions (organic solvents, drug, and biodegradable polymer, nozzle geometry, CO2 flow rate, and the liquid phase flow rate on particle size and its distribution.Keywords: supercritical antisolvent method, drug encapsulation, particle size, drug release mechanisms, drug delivery

  9. Immediate haemodynamic effects of a novel partial agonist, beta 1-adrenoceptor blocking drug ICI 141,292 after intravenous administration to healthy young volunteers and patients with ischaemic heart disease

    DEFF Research Database (Denmark)

    Bonde, J; Svendsen, T L; Lyngborg, K;

    1987-01-01

    ICI 141,292 is a new beta 1-adrenoceptor blocking drug. The beta 1-adrenoceptor antagonistic effect of ICI 141,292 was examined in a double-blind, randomised crossover study in eight healthy young volunteers and compared with atenolol. Three doses of ICI 141,292 (1, 2 and 4 mg) and atenolol 5 mg...... were administered intravenously. The attenuation in exercise induced tachycardia varied between 16.0 and 21.2% (P less than 0.01). A significant reduction in blood pressure could be demonstrated following all three doses of ICI 141,292 and atenolol during exercise. At rest in the sitting position HR...... decreased approximately 8% following all three doses of ICI 141,292 and 14.9% after atenolol 5 mg. No changes in blood pressure were observed under resting conditions after any of the drugs. In six patients with ischaemic heart disease the intrinsic sympathomimetic activity following intravenous...

  10. 76 FR 79701 - Bristol-Myers Squibb Co. et al.; Withdrawal of Approval of 70 New Drug Applications and 97...

    Science.gov (United States)

    2011-12-22

    ... 70 New Drug Applications and 97 Abbreviated New Drug Applications; Correction AGENCY: Food and Drug... withdrawal of approval of 70 new drug applications (NDAs) and 97 abbreviated new drug applications...

  11. Drug interaction studies on new drug applications: current situations and regulatory views in Japan.

    Science.gov (United States)

    Nagai, Naomi

    2010-01-01

    Drug interaction studies on new drug applications (NDAs) for new molecular entities (NMEs) approved in Japan between 1997 and 2008 are examined in the Pharmaceuticals and Medical Devices Agency (PMDA). The situations of drug interaction studies in NDAs have changed over the past 12 years, especially in metabolizing enzyme and transporter-based drug interactions. Materials and approaches to study drug-metabolizing enzyme-based drug interactions have improved, and become more rational based on mechanistic theory and new technologies. On the basis of incremental evidence of transporter roles in human pharmacokinetics, transporter-based drug interactions have been increasingly studied during drug development and submitted in recent NDAs. Some recently approved NMEs include transporter-based drug interaction information in their package inserts (PIs). The regulatory document "Methods of Drug Interaction Studies," in addition to recent advances in science and technology, has also contributed to plan and evaluation of drug interaction studies in recent new drug development. This review summarizes current situations and further discussion points on drug interaction studies in NDAs in Japan.

  12. Nanosuspension technology and its applications in drug delivery

    Directory of Open Access Journals (Sweden)

    Arunkumar N

    2009-01-01

    Full Text Available Solubility is an essential factor for drug effectiveness, independent of the route of administration. Poorly soluble drugs are often a challenging task for formulators in the industry. Conventional approaches for enhancement of solubility have limited applicability, especially when the drugs are poorly soluble simultaneously in aqueous and in non-aqueous media. Nanosuspension technology can be used to improve the stability as well as the bioavailability of poorly soluble drugs. Nanosuspensions are biphasic systems consisting of pure drug particles dispersed in an aqueous vehicle, stabilized by surfactants. These are simple to prepare and are more advantageous than other approaches. Techniques such as wet milling, high-pressure homogenization, emulsification-solvent evaporation and super critical fluid have been used in the preparation of nanosuspensions. It has the advantage of delivery by various routes, including oral, parenteral, pulmonary and ocular routes. The present article reviews the current methods used to prepare nanosuspensions and their application in drug delivery.

  13. The impact of IL-6 and IL-28B gene polymorphisms on treatment outcome of chronic hepatitis C infection among intravenous drug users in Croatia

    Science.gov (United States)

    Bradarić, Nikola; Forempoher, Gea; Polašek, Ozren; Anđelinović, Šimun

    2016-01-01

    Background Several genes and their single nucleotide polymorphisms (SNPs) are associated with either spontaneous resolution of hepatitis C infection or better treatment-induced viral clearance. We tested a cohort of intravenous drug users (IVDU) diagnosed with chronic hepatitis C virus (HCV) for treatment response and its association with the SNPs in the interleukin-6 (rs1800795-IL6) and the interleukin-28B (rs12979860-IL28B) genes. Methods The study included 110 Croatian IVDU positive for anti-HCV antibody. Genotyping was performed by polymerase chain reaction (PCR) based approach. Patients were treated by standard pegylated-interferon/ribavirin and followed throughout a period of four years, during which sustained virological response (SVR) was determined. All data were analysed with statistical package SPSS 19.0 (IBM Corp, Armonk, NY, USA) and PLINK v1.07 software. Results Patients showed a significantly better response to treatment according to the number of copies of the C allele carried at rs1800795-IL6 (P = 0.034). All but one of the patients with CC genotype achieved SVR (93%), whereas the response rate of patients with GG genotype was 64%. The association of rs1800795-IL6 with SVR status remained significant after further adjustment for patients’ age, fibrosis staging, and viral genotype (OR 2.15, 95% CI 1.16–4.68, P = 0.019). Distributions of allele frequencies at the locus rs12979860-IL28B among the study cohort and the underlying general population were suggestive of a protective effect of CC genotype in acquiring chronic hepatitis C in the Croatian IVDU population. Discussion The rs1800795-IL6 polymorphism is associated with positive response to treatment in IVDU patients positive for HCV infection. A protective role of rs12979860-IL28B CC genotype in acquiring chronic hepatitis C is suggested for Croatian IVDU population.

  14. The impact of IL-6 and IL-28B gene polymorphisms on treatment outcome of chronic hepatitis C infection among intravenous drug users in Croatia

    Directory of Open Access Journals (Sweden)

    Zoran Bogdanović

    2016-10-01

    Full Text Available Background Several genes and their single nucleotide polymorphisms (SNPs are associated with either spontaneous resolution of hepatitis C infection or better treatment-induced viral clearance. We tested a cohort of intravenous drug users (IVDU diagnosed with chronic hepatitis C virus (HCV for treatment response and its association with the SNPs in the interleukin-6 (rs1800795-IL6 and the interleukin-28B (rs12979860-IL28B genes. Methods The study included 110 Croatian IVDU positive for anti-HCV antibody. Genotyping was performed by polymerase chain reaction (PCR based approach. Patients were treated by standard pegylated-interferon/ribavirin and followed throughout a period of four years, during which sustained virological response (SVR was determined. All data were analysed with statistical package SPSS 19.0 (IBM Corp, Armonk, NY, USA and PLINK v1.07 software. Results Patients showed a significantly better response to treatment according to the number of copies of the C allele carried at rs1800795-IL6 (P = 0.034. All but one of the patients with CC genotype achieved SVR (93%, whereas the response rate of patients with GG genotype was 64%. The association of rs1800795-IL6 with SVR status remained significant after further adjustment for patients’ age, fibrosis staging, and viral genotype (OR 2.15, 95% CI 1.16–4.68, P = 0.019. Distributions of allele frequencies at the locus rs12979860-IL28B among the study cohort and the underlying general population were suggestive of a protective effect of CC genotype in acquiring chronic hepatitis C in the Croatian IVDU population. Discussion The rs1800795-IL6 polymorphism is associated with positive response to treatment in IVDU patients positive for HCV infection. A protective role of rs12979860-IL28B CC genotype in acquiring chronic hepatitis C is suggested for Croatian IVDU population.

  15. Comparison of HIV-, HBV-, HCV- and co-infection prevalence between Chinese and Burmese intravenous drug users of the China-Myanmar border region.

    Directory of Open Access Journals (Sweden)

    Yan-Heng Zhou

    Full Text Available BACKGROUND: Co-infection with HIV and HCV and/or HBV is highly prevalent in intravenous drug users (IDUs. Because of the proximity to the "Golden Triangle", HIV prevalence among the IDUs is very high in the China-Myanmar border region. However, there are few studies about co-infection with HIV and HCV and/or HBV, especially in the region that belongs to Myanmar. METHODS: 721 IDUs, including 403 Chinese and 318 Burmese, were investigated for their HIV, hepatitis B virus (HBV, and hepatitis C virus (HCV serological status. Statistical analysis was performed to evaluate the differences of the epidemic situation between the Chinese IDUs and the Burmese IDUs. RESULTS: Among the Chinese IDUs and the Burmese IDUs, HCV infection was the most prevalent (69.0% vs 48.1%, P0.05. Besides, there were more HIV-HBV co-infected IDUs (20.1% vs 11.3%, P<0.005, and HIV-HCV co-infected IDUs (31.8% vs 23.9%, P<0.05 in China than in Myanmar, as well as HIV-HBV-HCV triple infection (19.1% vs 10.4%, P<0.005. CONCLUSION: Co-infection with HIV and HCV and/or HBV is highly prevalent among the IDUs in the China-Myanmar border region. The HIV epidemic appears to be in a downward trend, compared with previous reports. However, all infections were more prevalent among the Chinese IDUs than among the Burmese.

  16. The human experience with intravenous levodopa

    Directory of Open Access Journals (Sweden)

    Shan H Siddiqi

    2016-01-01

    Full Text Available Objective: To compile a comprehensive summary of published human experience with levodopa given intravenously, with a focus on information required by regulatory agencies.Background: While safe intravenous (IV use of levodopa has been documented for over 50 years, regulatory supervision for pharmaceuticals given by a route other than that approved by the U.S. Food and Drug Administration (FDA has become increasingly cautious. If delivering a drug by an alternate route raises the risk of adverse events, an investigational new drug (IND application is required, including a comprehensive review of toxicity data.Methods: Over 200 articles referring to IV levodopa were examined for details of administration, pharmacokinetics, benefit and side effects.Results: We identified 142 original reports describing IVLD use in humans, beginning with psychiatric research in 1959-1960 before the development of peripheral decarboxylase inhibitors. Over 2750 subjects have received IV levodopa, and reported outcomes include parkinsonian signs, sleep variables, hormone levels, hemodynamics, CSF amino acid composition, regional cerebral blood flow, cognition, perception and complex behavior. Mean pharmacokinetic variables were summarized for 49 healthy subjects and 190 with Parkinson’s disease. Side effects were those expected from clinical experience with oral levodopa and dopamine agonists. No articles reported deaths or induction of psychosis.Conclusion: Over 2750 patients have received IV levodopa with a safety profile comparable to that seen with oral administration.

  17. The Human Experience with Intravenous Levodopa.

    Science.gov (United States)

    Siddiqi, Shan H; Abraham, Natalia K; Geiger, Christopher L; Karimi, Morvarid; Perlmutter, Joel S; Black, Kevin J

    2015-01-01

    To compile a comprehensive summary of published human experience with levodopa given intravenously, with a focus on information required by regulatory agencies. While safe intravenous (IV) use of levodopa has been documented for over 50 years, regulatory supervision for pharmaceuticals given by a route other than that approved by the U.S. Food and Drug Administration (FDA) has become increasingly cautious. If delivering a drug by an alternate route raises the risk of adverse events, an investigational new drug (IND) application is required, including a comprehensive review of toxicity data. Over 200 articles referring to IV levodopa were examined for details of administration, pharmacokinetics, benefit, and side effects. We identified 142 original reports describing IVLD use in humans, beginning with psychiatric research in 1959-1960 before the development of peripheral decarboxylase inhibitors. At least 2760 subjects have received IV levodopa, and reported outcomes include parkinsonian signs, sleep variables, hormone levels, hemodynamics, CSF amino acid composition, regional cerebral blood flow, cognition, perception and complex behavior. Mean pharmacokinetic variables were summarized for 49 healthy subjects and 190 with Parkinson's disease. Side effects were those expected from clinical experience with oral levodopa and dopamine agonists. No articles reported deaths or induction of psychosis. At least 2760 patients have received IV levodopa with a safety profile comparable to that seen with oral administration.

  18. Liposomal drug delivery systems--clinical applications.

    Science.gov (United States)

    Goyal, Parveen; Goyal, Kumud; Vijaya Kumar, Sengodan Gurusamy; Singh, Ajit; Katare, Om Prakash; Mishra, Dina Nath

    2005-03-01

    Liposomes have been widely investigated since 1970 as drug carriers for improving the delivery of therapeutic agents to specific sites in the body. As a result, numerous improvements have been made, thus making this technology potentially useful for the treatment of certain diseases in the clinics. The success of liposomes as drug carriers has been reflected in a number of liposome-based formulations, which are commercially available or are currently undergoing clinical trials. The current pharmaceutical preparations of liposome-based therapeutic systems mainly result from our understanding of lipid-drug interactions and liposome disposition mechanisms. The insight gained from clinical use of liposome drug delivery systems can now be integrated to design liposomes that can be targeted on tissues, cells or intracellular compartments with or without expression of target recognition molecules on liposome membranes. This review is mainly focused on the diseases that have attracted most attention with respect to liposomal drug delivery and have therefore yielded most progress, namely cancer, antibacterial and antifungal disorders. In addition, increased gene transfer efficiencies could be obtained by appropriate selection of the gene transfer vector and mode of delivery.

  19. Transdermal microneedles for drug delivery applications

    Energy Technology Data Exchange (ETDEWEB)

    Teo, Ai Ling [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117510 (Singapore); Shearwood, Christopher [School of Mechanical and Aerospace Engineering, 50 Nanyang Avenue, Singapore 639798 (Singapore); Ng, Kian Chye [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117510 (Singapore); Lu Jia [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117510 (Singapore); Moochhala, Shabbir [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117510 (Singapore)]. E-mail: mshabbir@dso.org.sg

    2006-07-25

    Transdermal drug delivery (TDD) has many advantages, the main one being the ability to maintain the prolonged release of drugs to attain optimal blood concentrations. Unfortunately, nature has provided a very effective protective barrier, the stratum corneum (sc), which limits TDD to certain types of drugs with specific properties. In order to enhance TDD, the idea of using microneedles to painlessly penetrate the sc barrier has previously been proposed. In this paper, we will review the different microneedles that are currently being developed as well as our own efforts in this area. Based on our experiences, we will offer our view on the key parameters for effective transdermal microneedle design as well as future directions in this area.

  20. 78 FR 36194 - Draft Guidance for Industry and FDA Staff: Investigational New Drug Applications for Minimally...

    Science.gov (United States)

    2013-06-17

    ... New Drug Applications for Minimally Manipulated, Unrelated Allogeneic Placental/Umbilical Cord Blood... for Industry and FDA Staff: ] Investigational New Drug Applications for Minimally Manipulated... Investigational New Drug Application (IND) for certain hematopoietic progenitor cells from...

  1. Applications of electrospinning/electrospraying in drug delivery.

    Science.gov (United States)

    Jahangiri, Azin; Adibkia, Khosro

    2016-01-01

    During recent years, nanoscaled materials have gained much attention because of their applications in the field of pharmaceutical and biomedical sciences. Electrospinning/electrospraying, as simple, effective and single-step methods, are used in the preparation of nanostructured materials (nanofibers and nanobeads). They offer an opportunity for direct encapsulation of the different types of drug molecules. The generated nanomaterials possess high surface area with porous characteristics, and the liberation of the loaded drugs follows a controlled-release pattern. Because of their wide applications in medical/pharmaceutical researches, the aim of this editorial is to highlight the importance of electrospinning/electrospraying technologies in drug delivery.

  2. Study on the lymphocyte immunity function in intravenous drug users with HIV infection in certain area%某省HIV阳性的静脉吸毒人群淋巴细胞免疫功能研究

    Institute of Scientific and Technical Information of China (English)

    朱红艳; 欧阳红梅; 宋建新; 甸自金; 张芹; 蒋雅先

    2011-01-01

    目的 探讨人类免疫缺陷病毒(HIV)阳性的静脉吸毒者细胞免疫功能的变化.方法 对静脉吸毒人员组成的HIV阳性组和HIV阴性组与健康对照组检测丙型肝炎病毒(HCV)感染率及淋巴细胞绝对值.结果 HIV阳性组和HIV阴性组HCV感染率分别是94.59%和82.93%;HIV阳性组T淋巴细胞亚群及自然杀伤(NK)细胞群均有不同程度的变化.结论 HIV阳性的静脉吸毒人群淋巴细胞免疫功能发生了不同程度的变化.%Objective To explore the lymphocyte immunity function in intravenous drug users with HIV infection. Methods HCV infection and absolute counts of T lymphocyte subsets were analyzed for intravenous drug users with or without HIV infec tion and healthy controls. Results The infection rates of HCV were 82.9% and 94.59% in HIV negative and HIV positive drug users respectively. There were changes of T lymphocyte subsets and natural killer cells for different degree in HIV positive drug us ers. Conclusion There could be certain alternations of lymphocyte immunity function in HIV positive intravenous drug users.

  3. 76 FR 78530 - Applications for Food and Drug Administration Approval To Market a New Drug; Revision of...

    Science.gov (United States)

    2011-12-19

    ... Administration Approval To Market a New Drug; Revision of Postmarketing Reporting Requirements-- Discontinuance... concern that, although the Orange Book lists all drug products with approved new drug applications (NDA) and abbreviated new drug applications (ANDA), it is not possible to determine whether the...

  4. Applications for oncologic drugs: a descriptive analysis of the oncologic drugs advisory committee reviews.

    Science.gov (United States)

    Chan, John K; Kiet, Tuyen K; Monk, Bradley J; Young-Lin, Nichole; Blansit, Kevin; Kapp, Daniel S; Amanam, Idoroenyi

    2014-03-01

    Despite advances in cancer research, the majority of drug applications submitted to the U.S. Food and Drug Administration (FDA) are not approved. It is important to identify the concerns of the Oncologic Drugs Advisory Committee (ODAC) from rejected applications. All applications referred to the ODAC from 2001 to 2012 were reviewed. Of 46 applications, 31 (67%) were for full and 15 (33%) were for supplemental approval, 34 (74%) were for solid and 12 (26%) were for hematologic tumors. In all, 22 (48%) were not approved. ODAC comments addressed missing or inadequate data (65%), excessive toxicity (55%), inappropriate study endpoints (45%), poor study design (40%), and insufficient sample size (30%). To define efficacy, 19 applications used response rates (RR) (median = 38%), and 19 applications used hazard ratios (HR) (median = 0.67). For all organ systems combined, the median cumulative grade 3 or 4 toxicity was 64%. Drugs with higher RR, lower HR, and lower toxicity were more likely to be approved versus other drugs (89% vs. 45%; p = .02). Over time (2001-2004, 2005-2008, 2009-2012), there was an increase in the following: number of applications submitted for review (from 11 to 12 to 23, respectively), number of approvals (from 6 to 6 to 12, respectively), and proportion of trials using progression-free survival as a primary endpoint (from 0% to 50% to 70%, respectively; p = .01). Of all applications, common ODAC concerns included inadequate data, excessive toxicity, and inappropriate study endpoints. Over time, there was an approximate doubling of FDA application submissions and approved oncology drugs.

  5. Applications for Oncologic Drugs: A Descriptive Analysis of the Oncologic Drugs Advisory Committee Reviews

    Science.gov (United States)

    Kiet, Tuyen K.; Monk, Bradley J.; Young-Lin, Nichole; Blansit, Kevin; Kapp, Daniel S.; Amanam, Idoroenyi

    2014-01-01

    Background Despite advances in cancer research, the majority of drug applications submitted to the U.S. Food and Drug Administration (FDA) are not approved. It is important to identify the concerns of the Oncologic Drugs Advisory Committee (ODAC) from rejected applications. Methods All applications referred to the ODAC from 2001 to 2012 were reviewed. Results Of 46 applications, 31 (67%) were for full and 15 (33%) were for supplemental approval, 34 (74%) were for solid and 12 (26%) were for hematologic tumors. In all, 22 (48%) were not approved. ODAC comments addressed missing or inadequate data (65%), excessive toxicity (55%), inappropriate study endpoints (45%), poor study design (40%), and insufficient sample size (30%). To define efficacy, 19 applications used response rates (RR) (median = 38%), and 19 applications used hazard ratios (HR) (median = 0.67). For all organ systems combined, the median cumulative grade 3 or 4 toxicity was 64%. Drugs with higher RR, lower HR, and lower toxicity were more likely to be approved versus other drugs (89% vs. 45%; p = .02). Over time (2001–2004, 2005–2008, 2009–2012), there was an increase in the following: number of applications submitted for review (from 11 to 12 to 23, respectively), number of approvals (from 6 to 6 to 12, respectively), and proportion of trials using progression-free survival as a primary endpoint (from 0% to 50% to 70%, respectively; p = .01). Conclusion. Of all applications, common ODAC concerns included inadequate data, excessive toxicity, and inappropriate study endpoints. Over time, there was an approximate doubling of FDA application submissions and approved oncology drugs. PMID:24599479

  6. 76 FR 6143 - Draft Guidance on Positron Emission Tomography Drug Applications-Content and Format for New Drug...

    Science.gov (United States)

    2011-02-03

    ...] [FR Doc No: 2011-2314] DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No... Commissioner for Policy. [FR Doc. 2011-2314 Filed 2-2-11; 8:45 am] BILLING CODE 4160-01-P ... Applications--Content and Format for New Drug Applications and Abbreviated New Drug Applications; Availability...

  7. Intravenous drug use combined with severe tetanus infection:an analysis of 17 cases%静脉吸毒合并重症破伤风感染17例病例分析

    Institute of Scientific and Technical Information of China (English)

    梁茂裕; 莫燕燕; 陈跃华

    2016-01-01

    目的:探讨静脉吸毒合并重症破伤风感染病例的特点及治疗措施对预后情况的影响。方法:回顾性分析2009-2014年收治的17例静脉吸毒合并重症破伤风感染病例的临床资料。结果:17例患者,治愈16例,死亡1例。患者平均住院时间为25 d。结论:(1)静脉吸毒合并重症破伤风感染者病情进展迅速,吸毒因素使病情变得更危重和复杂。(2)超常强度使用镇静剂、肌松剂控制痉挛,尽早行气管插管及气管切开术能有效提高破伤风患者抢救成功率。%Objective:To investigate the characteristics and treatment of intravenous drug use combined with severe tetanus infection and the effect on the prognosis conditions.Methods:Clinical data of 17 cases of intravenous drug use combined with severe tetanus in-fection treated in our hospital during 2009-2014 were retrospectively analyzed.Results:16 cases were cured and 1 died.The average length of stay was 25 days.Conclusion:①Intravenous drug use combined with severe tetanus infection makes the disease progress rap-idly.Factors of drugs make the disease more critical and complex;②Large doses of sedatives and muscle relaxants to control spasms, early endotracheal intubation and tracheostomy can improve the survival rate of patients with tetanus.

  8. Engineering of drug nanoparticles by HGCP for pharmaceutical applications

    Institute of Scientific and Technical Information of China (English)

    TingTing Hu; JieXin Wang; ZhiGang Shen; JianFeng Chen

    2008-01-01

    This paper reviews our work on the fundamental principles of high gravity controlled precipitation (HGCP) technology, and its applications in the production of drug nenoparticles, which was carded out in a rotating packed bed (RPB). Several kinds of drug nanoparticles with narrow particle size distributions (PSDs) were successfully prepared via HGCP, including the 300-nm Cefuroxirne Axetil (CFA) particles, 200-400-nm cephradine particles, 500-nm salbutamol sulfate (SS) particles (100 nm in width), end 850-nm beclomethasone dipropionate (BDP) particles, etc. Compared to drugs available in the current market, all the drug nanoparticles produced by HGCP exhibited advantages in both formulation end drug delivery, thus improving the bioavailability of drugs. HGCP is essentially a platform technology for the preparation of poorly water-soluble drug nanoparticles for oral and injection delivery, and of inhalable drugs for pulmonary delivery. Consequently, HGCP offers potential applications in the pharmaceutical industry due to its cost-effectiveness, efficient processing end the ease of scaling-up.

  9. Organically modified titania nanoparticles for sustained drug release applications.

    Science.gov (United States)

    Sethi, Komal; Roy, Indrajit

    2015-10-15

    In this paper, we report the synthesis, characterization of drug-doped organically modified titania nanoparticles, and their applications in sustained drug release. The drug-doped nanoparticles were synthesized in the hydrophobic core of oil-in-water microemulsion medium. Structural aspects obtained through TEM and FESEM depicted that organically modified titania nanoparticles are monodispersed with spherical morphology, with an average size of around 200 nm. Their polymorphic forms and porosity were determined using powder XRD and BET, respectively, which showed that they are present in the anatase form, with a surface area of 136.5 m(2)/g and pore-diameter of 5.23 nm. After synthesis and basic structural characterizations, optical properties were studied for both fluorophore and drug encapsulated nanoparticles. The results showed that though the optical properties of the fluorophore are partially diminished upon nanoencapsulation, it became more stable against chemical quenching. The nanoparticles showed pH-dependent drug release pattern. In vitro studies showed that the nanoparticles were efficiently uptaken by cells. Cell viability assay results showed that though the placebo nanoparticles are non-cytotoxic, the drug-doped nanoparticles show drug-induced toxicity. Therefore, such porous nanoparticles can be used in non-toxic drug delivery applications.

  10. Coaxial electrospun fibers: applications in drug delivery and tissue engineering.

    Science.gov (United States)

    Lu, Yang; Huang, Jiangnan; Yu, Guoqiang; Cardenas, Romel; Wei, Suying; Wujcik, Evan K; Guo, Zhanhu

    2016-09-01

    Coelectrospinning and emulsion electrospinning are two main methods for preparing core-sheath electrospun nanofibers in a cost-effective and efficient manner. Here, physical phenomena and the effects of solution and processing parameters on the coaxial fibers are introduced. Coaxial fibers with specific drugs encapsulated in the core can exhibit a sustained and controlled release. Their exhibited high surface area and three-dimensional nanofibrous network allows the electrospun fibers to resemble native extracellular matrices. These features of the nanofibers show that they have great potential in drug delivery and tissue engineering applications. Proteins, growth factors, antibiotics, and many other agents have been successfully encapsulated into coaxial fibers for drug delivery. A main advantage of the core-sheath design is that after the process of electrospinning and release, these drugs remain bioactive due to the protection of the sheath. Applications of coaxial fibers as scaffolds for tissue engineering include bone, cartilage, cardiac tissue, skin, blood vessels and nervous tissue, among others. A synopsis of novel coaxial electrospun fibers, discussing their applications in drug delivery and tissue engineering, is covered pertaining to proteins, growth factors, antibiotics, and other drugs and applications in the fields of bone, cartilage, cardiac, skin, blood vessel, and nervous tissue engineering, respectively. WIREs Nanomed Nanobiotechnol 2016, 8:654-677. doi: 10.1002/wnan.1391 For further resources related to this article, please visit the WIREs website.

  11. Multifaceted Applications of Chitosan in Cancer Drug Delivery and Therapy.

    Science.gov (United States)

    Babu, Anish; Ramesh, Rajagopal

    2017-03-27

    Chitosan is a versatile polysaccharide of biological origin. Due to the biocompatible and biodegradable nature of chitosan, it is intensively utilized in biomedical applications in scaffold engineering as an absorption enhancer, and for bioactive and controlled drug release. In cancer therapy, chitosan has multifaceted applications, such as assisting in gene delivery and chemotherapeutic delivery, and as an immunoadjuvant for vaccines. The present review highlights the recent applications of chitosan and chitosan derivatives in cancer therapy.

  12. Multifaceted Applications of Chitosan in Cancer Drug Delivery and Therapy

    Directory of Open Access Journals (Sweden)

    Anish Babu

    2017-03-01

    Full Text Available Chitosan is a versatile polysaccharide of biological origin. Due to the biocompatible and biodegradable nature of chitosan, it is intensively utilized in biomedical applications in scaffold engineering as an absorption enhancer, and for bioactive and controlled drug release. In cancer therapy, chitosan has multifaceted applications, such as assisting in gene delivery and chemotherapeutic delivery, and as an immunoadjuvant for vaccines. The present review highlights the recent applications of chitosan and chitosan derivatives in cancer therapy.

  13. 21 CFR 314.153 - Suspension of approval of an abbreviated new drug application.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Suspension of approval of an abbreviated new drug... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA... new drug application. (a) Suspension of approval. The approval of an abbreviated new drug...

  14. 77 FR 50702 - Ranbaxy Laboratories Limited; Withdrawal of Approval of 27 Abbreviated New Drug Applications

    Science.gov (United States)

    2012-08-22

    ... Abbreviated New Drug Applications AGENCY: Food and Drug Administration, HHS. ACTION: Notice. ] SUMMARY: The Food and Drug Administration (FDA) is withdrawing approval of 27 abbreviated new drug applications... introduction into interstate commerce of products without approved new drug applications violates section...

  15. Asymmetrical Polymer Vesicles for Drug delivery and Other Applications

    Directory of Open Access Journals (Sweden)

    Yi Zhao

    2017-06-01

    Full Text Available Scientists have been attracted by polymersomes as versatile drug delivery systems since the last two decades. Polymersomes have the potential to be versatile drug delivery systems because of their tunable membrane formulations, stabilities in vivo, various physicochemical properties, controlled release mechanisms, targeting abilities, and capacities to encapsulate a wide range of drugs and other molecules. Asymmetrical polymersomes are nano- to micro-sized polymeric capsules with asymmetrical membranes, which means, they have different outer and inner coronas so that they can exhibit better endocytosis rate and endosomal escape ability than other polymeric systems with symmetrical membranes. Hence, asymmetrical polymersomes are highly promising as self-assembled nano-delivery systems in the future for in vivo therapeutics delivery and diagnostic imaging applications. In this review, we prepared a summary about recent research progresses of asymmetrical polymersomes in the following aspects: synthesis, preparation, applications in drug delivery and others.

  16. Application of supercritical antisolvent method in drug encapsulation: a review.

    Science.gov (United States)

    Kalani, Mahshid; Yunus, Robiah

    2011-01-01

    The review focuses on the application of supercritical fluids as antisolvents in the pharmaceutical field and demonstrates the supercritical antisolvent method in the use of drug encapsulation. The main factors for choosing the solvent and biodegradable polymer to produce fine particles to ensure effective drug delivery are emphasized and the effect of polymer structure on drug encapsulation is illustrated. The review also demonstrates the drug release mechanism and polymeric controlled release system, and discusses the effects of the various conditions in the process, such as pressure, temperature, concentration, chemical compositions (organic solvents, drug, and biodegradable polymer), nozzle geometry, CO(2) flow rate, and the liquid phase flow rate on particle size and its distribution.

  17. 75 FR 63189 - Draft Guidance for Industry on Investigational New Drug Applications-Determining Whether Human...

    Science.gov (United States)

    2010-10-14

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Investigational New Drug... Drug Administration (FDA) is announcing the availability of a draft guidance for industry entitled... draft guidance for industry entitled ``Investigational New Drug Applications (INDs)--Determining...

  18. Ceramic Nanoparticles: Fabrication Methods and Applications in Drug Delivery.

    Science.gov (United States)

    Thomas, Shindu C; Harshita; Mishra, Pawan Kumar; Talegaonkar, Sushama

    2015-01-01

    Ceramic nanoparticles are primarily made up of oxides, carbides, phosphates and carbonates of metals and metalloids such as calcium, titanium, silicon, etc. They have a wide range of applications due to a number of favourable properties, such as high heat resistance and chemical inertness. Out of all the areas of ceramic nanoparticles applications, biomedical field is the most explored one. In the biomedical field, ceramic nanoparticles are considered to be excellent carriers for drugs, genes, proteins, imaging agents etc. To be able to act as a good and successful drug delivery agent, various characteristics of nanoparticles need to be controlled, such as size range, surface properties, porosity, surface area to volume ratio, etc. In achieving these properties on the favourable side, the method of preparation and a good control over process variables play a key role. Choosing a suitable method to prepare nanoparticles, along with loading of significant amount of drug(s) leads to development of effective drug delivery systems which are being explored to a great extent. Ceramic nanoparticles have been successfully used as drug delivery systems against a number of diseases, such as bacterial infections, glaucoma, etc., and most widely, against cancer. This review gives a detailed account of commonly used methods for synthesising nanoparticles of various ceramic materials, along with an overview of their recent research status in the field of drug delivery.

  19. Dendrimeric Systems and Their Applications in Ocular Drug Delivery

    Directory of Open Access Journals (Sweden)

    Burçin Yavuz

    2013-01-01

    Full Text Available Ophthalmic drug delivery is one of the most attractive and challenging research area for pharmaceutical scientists and ophthalmologists. Absorption of an ophthalmic drug in conventional dosage forms is seriously limited by physiological conditions. The use of nonionic or ionic biodegradable polymers in aqueous solutions and colloidal dosage forms such as liposomes, nanoparticles, nanocapsules, microspheres, microcapsules, microemulsions, and dendrimers has been studied to overcome the problems mentioned above. Dendrimers are a new class of polymeric materials. The unique nanostructured architecture of dendrimers has been studied to examine their role in delivery of therapeutics and imaging agents. Dendrimers can enhance drug’s water solubility, bioavailability, and biocompatibility and can be applied for different routes of drug administration successfully. Permeability enhancer properties of dendrimers were also reported. The use of dendrimers can also reduce toxicity versus activity and following an appropriate application route they allow the delivery of the drug to the targeted site and provide desired pharmacokinetic parameters. Therefore, dendrimeric drug delivery systems are of interest in ocular drug delivery. In this review, the limitations related to eye’s unique structure, the advantages of dendrimers, and the potential applications of dendrimeric systems to ophthalmology including imaging, drug, peptide, and gene delivery will be discussed.

  20. Treatment of post-operative pain in old oncology patients with intravenous application of 50% glucose solution

    Directory of Open Access Journals (Sweden)

    Jovanović Nikola Č.

    2003-01-01

    Full Text Available Postoperative pain is the most important factor od so called "tumor promotive effect of surgery" ie. of endocrine-metabolic changes having the consequence drop in immune, antiinfective and antitumor defense. Due to presence of organic involutive changes, old people (≥ 65 years, often have serious side effects during application of usual analgetics. Since hypertonic glucose (33% given i.v. or per os, works analgesically in small children there is assumption that it can be used in treatment of postoperative pain in old oncology patients. We tested the hypothesis that postoperative pain in old oncology patients can be treated with i.v. application of 50% of glucose solution. 37 oncology patients over 65 years, 26 females and 11 males, operated for breast cancer and soft tissue cancer, werw investigated. Average age of the patients was 72±4 years. 50% Glucose solution was given in two boluses of 20 ml each: the first bolus was given to all patients at the end of anesthesia and the other bolus was given individually after appearance of post-operative pain. Pain intensity (in coefficients of the visual analogue scale VAK = 1-100 and its characteristics were tested by oral testing of operated patients: after weaking from anesthesia, after the first appearance of the pain and 15 minutes after giving of the second glucose bolus. None patient had pain weaking from anesthesia. All tested patients experienced pain during the first 70 minutes and it could be categorized as very strong pain (=82 VAK. The pain was decreased with another glucose bolus by approximately (=56% VAK so it was classifies in category of bearable pains (=36 VAK. In 9 patients (24,3% the pain had neuropatic component (filing of "burning" which could not be eliminated by hypertonic glucose but only with application of tramadol. Activation of the central cholinergic transmission is the most significant mechanism of analgesic glucose effect, but, probably there is another one

  1. Peripheral intravenous line (image)

    Science.gov (United States)

    A peripheral intravenous line is a small, short plastic catheter that is placed through the skin into a vein, ... or foot, but occasionally in the head. A peripheral intravenous line is used to give fluids and ...

  2. Recent Applications of Mesoscale Modeling to Nanotechnology and Drug Delivery

    Energy Technology Data Exchange (ETDEWEB)

    Maiti, A; Wescott, J; Kung, P; Goldbeck-Wood, G

    2005-02-11

    Mesoscale simulations have traditionally been used to investigate structural morphology of polymer in solution, melts and blends. Recently we have been pushing such modeling methods to important areas of Nanotechnology and Drug delivery that are well out of reach of classical molecular dynamics. This paper summarizes our efforts in three important emerging areas: (1) polymer-nanotube composites; (2) drug diffusivity through cell membranes; and (3) solvent exchange in nanoporous membranes. The first two applications are based on a bead-spring-based approach as encoded in the Dissipative Particle Dynamics (DPD) module. The last application used density-based Mesoscale modeling as implemented in the Mesodyn module.

  3. Clinical applications of biomedical microdevices for controlled drug delivery.

    Science.gov (United States)

    Gurman, Pablo; Miranda, Oscar R; Clayton, Kevin; Rosen, Yitzhak; Elman, Noel M

    2015-01-01

    Miniaturization of devices to micrometer and nanometer scales, combined with the use of biocompatible and functional materials, has created new opportunities for the implementation of drug delivery systems. Advances in biomedical microdevices for controlled drug delivery platforms promise a new generation of capabilities for the treatment of acute conditions and chronic illnesses, which require high adherence to treatment, in which temporal control over the pharmacokinetic profiles is critical. In addition, clinical conditions that require a combination of drugs with specific pharmacodynamic profiles and local delivery will benefit from drug delivery microdevices. This review provides a summary of various clinical applications for state-of-the-art controlled drug delivery microdevices, including cancer, endocrine and ocular disorders, and acute conditions such as hemorrhagic shock. Regulatory considerations for clinical translation of drug delivery microdevices are also discussed. Drug delivery microdevices promise a remarkable gain in clinical outcomes and a substantial social impact. A review of articles covering the field of microdevices for drug delivery was performed between January 1, 1990, and January 1, 2014, using PubMed as a search engine.

  4. 静脉药物配置中心药师对细胞毒药品静脉给药的药学监护%Pharmaceutical Care for Intravenous Administration of Cytotoxic Drugs by PIVAS Pharmacists

    Institute of Scientific and Technical Information of China (English)

    余红玲

    2012-01-01

    OBJECTIVE: To reduce medication error of cytotoxic drugs, and to guide clinical rational drug use. METHODS: Pharmaceutical care for intravenous administration of cytotoxic drugs was interpreted in terms of rationality of drug use, ADR prevention, drug configuration process and drug storage. RESULTS&CONCLUSION: PIVAS pharmacists provide pharmaceutical care in terms of concentration of cytotoxic drugs, dosage, dripping speed, medication time and orders, drug interaction, ADR prevention, drug configuration process and drug storage. It plays positive role on preventing medication error, improving clinical efficacy, reducing the incidence and severity of ADR and promoting the safety and reasonability of clinical drug use.%目的:减少细胞毒药品给药差错,指导临床合理用药.方法:从用药合理性、不良反应预防、药物配置过程、药品储存等4个方面阐述细胞毒药品静脉给药的药学监护内容.结果与结论:静脉药物配置中心药师通过对细胞毒药品静脉给药浓度、剂量、滴注速度、给药时序、药物相互作用、不良反应预防、药物的配置过程以及药品的储存等方面进行监护,可对预防给药差错、提高临床疗效、降低不良反应的发生率和严重程度起到积极作用,提高临床用药安全性和合理性.

  5. Does the application of X-ray contrast agents impair the clinical effect of intravenous recombinant tissue-type plasminogen activator in acute ischemic stroke patients?

    Science.gov (United States)

    Dzialowski, Imanuel; Puetz, Volker; Buchan, Alastair M; Demchuk, Andrew M; Hill, Michael D

    2012-06-01

    Experimental data suggest a negative interaction between x-ray contrast agents and fibrinolytic efficacy of recombinant tissue-type plasminogen activator (rtPA). We hypothesized that the application of a contrast agent before intravenous thrombolysis with rtPA reduces its clinical efficacy in acute ischemic stroke. We retrospectively studied consecutive ischemic stroke patients receiving contrast agents for computed tomography angiography before intravenous treatment with rtPA. We compared functional outcomes with an historical control group from the Canadian Alteplase for Stroke Effectiveness Study who did not receive contrast agents before thrombolysis with rtPA. Primary end point was favorable functional outcome at 90 days defined as modified Rankin Scale scores 0 to 2. We performed logistic regression analysis and a propensity score matching analysis to estimate the effect size of contrast agent use as a negative predictor of outcome. We identified 111 patients for the computed tomography angiography and 1119 patients for the control group. Proportions of favorable functional outcome were 47.7% (53/111 patients) for the computed tomography angiography group and 49.5% (542/1094 patients) for the control group (P=0.77). Adjusted probabilities for favorable outcome were 0.48 (95% CI, 0.37-0.58) and 0.51 (95% CI, 0.47-0.54), respectively. Contrast use was associated with reduced odds of favorable outcome (OR, 0.62(;) 95% CI, 0.38-0.99). Propensity score matching suggested a larger effect size (OR, 10.0%; 95% CI, 0.5%-19.3%). Our study did not show a significant negative clinical effect of x-ray contrast agents applied before intravenous thrombolysis with rtPA. However, to confirm a possible small negative interaction between contrast agents and rtPA, additional experimental and prospective clinical studies are needed.

  6. Applications of Pattern Recognition in Drug Discovery

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    This is a brief account of the plenary talk given to the meeting of the Chinese Society of Chemical Science and Technology held in Oxford on 6 October 2001. The talk covered the application of pattern recognition techniques to discover molecules which will bind to the binding sites of proteins. Three situations were considered: the structure of the protein being unknown; the structure known but the binding site unknown; and finally, and this is the most important case for the future, both the structure and nature of the target site available in atomic detail. For this case we have developed a massively distributed computer program using a screensaver which now involves over one million personal computers, including over a thousand in China. The project will involve the screening of 3.5 billion small molecules against 16 protein targets, all of which are implicated in the process of cancer.

  7. Subcutaneous bortezomib in multiple myeloma patients induces similar therapeutic response rates as intravenous application but it does not reduce the incidence of peripheral neuropathy.

    Directory of Open Access Journals (Sweden)

    Jiri Minarik

    Full Text Available Subcutaneous (SC application of bortezomib has been recently introduced as a new application route in multiple myeloma (MM patients. We performed an analysis to compare the outcomes of bortezomib-based therapy in multiple myeloma (MM patients treated using either intravenous (IV or subcutaneous (SC route of administration.During January 2012 through December 2013, we performed a retrospective analysis of 446 patients with MM treated with bortezomib-based regimens (either once weekly - 63% or twice weekly - 27% in both, the first line setting, and in relapse, with separate analysis of patients undergoing autologous stem cell transplantation. We assessed the response rates and toxicity profiles in both, IV and SC route of bortezomib administration.The response rates in both IV and SC arm were similar with overall response rate 71.7% vs 70.7%, complete remissions in 13.9% vs 8.6%, very good partial remissions in 30.8% vs 34.5% and partial remissions in 27% vs 27.6%. The most frequent grade ≥ 3 toxicities were anemia, thrombocytopenia and neutropenia, with no significant differences between IV and SC group. There were no significant differences in the rate of peripheral neuropathy (PN. PN of any grade was present in 48% in the IV arm and in 41% in the SC arm. PN grade ≥ 2 was present in 20% vs 18% and PN grade ≥ 3 was present in 6% vs 4%.We conclude that subcutaneous application of bortezomib has similar therapeutic outcomes and toxicity profile as intravenous route of application. In our cohort there was no difference in the incidence of PN, suggesting that PN is dose dependent and might be reduced by lower intensity schemes rather than by the route of administration.

  8. Anaphylactic reaction to intravenous diclofenac

    Directory of Open Access Journals (Sweden)

    Ranju Singh

    2011-01-01

    Full Text Available Diclofenac sodium is a non-steroidal anti-inflammatory drug widely used as an opioid sparing agent for postoperative analgesia. Anaphylaxis due to intravenous diclofenac sodium is very rare. We report a case of anaphylactic reaction to IV diclofenac sodium, occurring postoperatively in a 25-year-old primigravida, the clinical features of which mimicked pulmonary embolism. The rarity, clinical importance and the diagnostic dilemma associated prompted us to report this case.

  9. 76 FR 54473 - Guidance on Positron Emission Tomography Drug Applications-Content and Format for New Drug...

    Science.gov (United States)

    2011-09-01

    ..., 2011 (76 FR 6143), and Docket No. FDA- 2000-D-1542 was open for comments until April 4, 2011. The... Emission Tomography Drug Products,'' issued on March 10, 2000 (65 FR 13010). The February 3, 2011, revised...-- Content and Format for New Drug Applications and Abbreviated New Drug Applications; Availability AGENCY...

  10. What´s cheapest, intravenous iron sucrose- or intravenous iron carboxymaltose treatment in IBD patients?

    DEFF Research Database (Denmark)

    Bager, Palle; Dahlerup, Jens Frederik

    for a total of iron-dose was to 233€ to reduce the numbers of infusion from 7 till 2.    Conclusion: The cost of choosing iron carboxymaltose rather than iron sucrose in treatment of iron deficiency in IBD differs depending of the economic perspective chosen. Only the Budget Impact Analysis showed iron......  What´s cheapest, intravenous iron sucrose- or intravenous iron carboxymaltose treatment in IBD patients? It dependent on the economic evaluation perspective!   Aim: To evaluate the health care cost for intravenous iron sucrose (Venofer®, Vifor) and intravenous iron carboxymaltose (Ferinject......®, Vifor) treatment to IBD patients in an outpatient setting.   Background: Intravenous iron sucrose can be given as a maximum of 200 mg Fe++ per infusion vs. intravenous iron carboxymaltose that can be given as a maximum of 1000 mg Fe++ in a single infusion leading to fewer infusions and visits. The drug...

  11. Effect of Intravenous Acetaminophen on Post-Anesthesia Care Unit Length of Stay, Opioid Consumption, Pain, and Analgesic Drug Costs After Ambulatory Surgery

    Science.gov (United States)

    Khobrani, Moteb A.; Camamo, James M.; Patanwala, Asad E.

    2017-01-01

    Objectives The primary objective was to assess whether the use of intravenous acetaminophen (APAP) in the ambulatory surgery setting is associated with a decreased length of stay in the post-anesthesia care unit (PACU). The secondary outcomes evaluated were pain scores, opioid consumption, and total cost of analgesics used in the PACU. Methods This was a retrospective cohort study conducted in adult patients (18 years of age or older) who received an eye, ear, nose, or throat (EENT) procedure at an outpatient surgery center between January 2014 and January 2015. Patients were consecutively included until the desired sample was reached during two six-month time periods: 1) intravenous APAP available on the formulary (APAP group) and 2) intravenous APAP not available on the formulary (non-APAP group). Results The cohort included 174 patients who received an EENT procedure (87 patients in the APAP group and 87 patients in the non-APAP group). The median PACU length of stay was 66 minutes (interquartile range [IQR], 48–92) in the APAP group and 71 minutes (IQR, 52–89) in the non-APAP group (P = 0.269). Mean pain score categories in the APAP versus non-APAP group were mild (85% versus 53%, respectively; P < 0.001), moderate (13% versus 33%, respectively; P = 0.002), and severe (2% versus 14%, respectively; P = 0.005). The median opioid consumption in morphine equivalents was 9 mg (IQR, 5–13) in the APAP group and 8 mg (IQR, 5–12) in the non-APAP group (P = 0.081). The total cost of analgesics used in the PACU was significantly greater in the APAP group ($15 versus $1; P < 0.001). Conclusions Intravenous APAP use in EENT ambulatory surgery is not associated with decreased PACU length of stay. However, it may decrease postoperative pain following EENT procedures. PMID:28163558

  12. Drug delivery application of extracellular vesicles; insight into production, drug loading, targeting, and pharmacokinetics

    Directory of Open Access Journals (Sweden)

    Masaharu Somiya

    2017-01-01

    Full Text Available Extracellular vesicles (EVs are secreted from any types of cells and shuttle between donor cells and recipient cells. Since EVs deliver their cargos such as proteins, nucleic acids, and other molecules for intercellular communication, they are considered as novel mode of drug delivery vesicles. EVs possess advantages such as inherent targeting ability and non-toxicity over conventional nanocarriers. Much efforts have so far been made for the application of EVs as a drug delivery carrier, however, basic techniques, such as mass-scale production, drug loading, and engineering of EVs are still limited. In this review, we summarize following four points. First, recent progress on the production method for EVs is described. Second, current techniques of drug loading methods are summarized. Third, targeting approach to specifically deliver cargo molecules for diseased sites by engineered EVs is discussed. Lastly, strategies to control pharmacokinetics and improve biodistribution are discussed.

  13. Sulfated Seaweed Polysaccharides as Multifunctional Materials in Drug Delivery Applications

    Science.gov (United States)

    Cunha, Ludmylla; Grenha, Ana

    2016-01-01

    In the last decades, the discovery of metabolites from marine resources showing biological activity has increased significantly. Among marine resources, seaweed is a valuable source of structurally diverse bioactive compounds. The cell walls of marine algae are rich in sulfated polysaccharides, including carrageenan in red algae, ulvan in green algae and fucoidan in brown algae. Sulfated polysaccharides have been increasingly studied over the years in the pharmaceutical field, given their potential usefulness in applications such as the design of drug delivery systems. The purpose of this review is to discuss potential applications of these polymers in drug delivery systems, with a focus on carrageenan, ulvan and fucoidan. General information regarding structure, extraction process and physicochemical properties is presented, along with a brief reference to reported biological activities. For each material, specific applications under the scope of drug delivery are described, addressing in privileged manner particulate carriers, as well as hydrogels and beads. A final section approaches the application of sulfated polysaccharides in targeted drug delivery, focusing with particular interest the capacity for macrophage targeting. PMID:26927134

  14. 75 FR 80061 - Abbott Laboratories, Inc.; Withdrawal of Approval of a New Drug Application for MERIDIA

    Science.gov (United States)

    2010-12-21

    ... HUMAN SERVICES Food and Drug Administration Abbott Laboratories, Inc.; Withdrawal of Approval of a New Drug Application for MERIDIA AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is withdrawing approval of a new drug application (NDA) for...

  15. 21 CFR 314.127 - Refusal to approve an abbreviated new drug application.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Refusal to approve an abbreviated new drug... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications and Abbreviated Applications § 314.127 Refusal to approve an abbreviated new...

  16. Microencapsulation of protein drugs for drug delivery: strategy, preparation, and applications.

    Science.gov (United States)

    Ma, Guanghui

    2014-11-10

    Bio-degradable poly(lactide) (PLA)/poly(lactide-glycolide) (PLGA) and chitosan microspheres (or microcapsules) have important applications in Drug Delivery Systems (DDS) of protein/peptide drugs. By encapsulating protein/peptide drugs in the microspheres, the serum drug concentration can be maintained at a higher constant value for a prolonged time, or injection formulation can be changed to orally or mucosally administered formulation. PLA/PLGA and chitosan are most often used in injection formulation and oral formulation. However, in the preparation and applications of PLA/PLGA and chitosan microspheres containing protein/peptide drugs, the problems of broad size distribution and poor reproducibility of microspheres, and deactivation of protein during the preparation, storage and release, are still big challenges. In this article, the techniques for control of the diameter of microspheres and microcapsules will be introduced at first, then the strategies about how to maintain the bioactivity of protein drugs during preparation and drug release will be reviewed and developed in our research group. The membrane emulsification techniques including direct membrane emulsification and rapid membrane emulsification processes were developed to prepare uniform-sized microspheres, the diameter of microspheres can be controlled from submicron to 100μm by these two processes, and the reproducibility of products can be guaranteed. Furthermore, compared with conventional stirring method, the big advantages of membrane emulsification process were that the uniform microspheres with much higher encapsulation efficiency can be obtained, and the release behavior can be adjusted by selecting microsphere size. Mild membrane emulsification condition also can prevent the deactivation of proteins, which frequently occurred under high shear force in mechanical stirring, sonification, and homogenization methods. The strategies for maintaining the bioactivity of protein drug were

  17. Potential applications of boron nitride nanotubes as drug delivery systems.

    Science.gov (United States)

    Ciofani, Gianni

    2010-08-01

    In recent years, there has been an explosion of research in the 'bio-nano' field, with the discovery and introduction of ever more fascinating materials for applications as drug delivery systems, sensors, transducers, and so on. The author's group, for the first time in the literature, proposed boron nitride nanotubes as a valid alternative to carbon nanotubes and other kinds of inorganic materials, because of their improved chemical properties that theoretically guarantee better stability and compatibility in a biological context. In this paper, the bio-applications of boron nitride nanotubes that have emerged in the literature are summarized, with special attention given to their exploitation as safe drug delivery and targeting carriers. Finally, the possibility of combining their physical and chemical properties is approached, highlighting the features that render these innovative nanovectors unique and exceptional candidates for many bio-applications.

  18. Biocompatibility of Chitosan Carriers with Application in Drug Delivery

    Directory of Open Access Journals (Sweden)

    Ana Grenha

    2012-09-01

    Full Text Available Chitosan is one of the most used polysaccharides in the design of drug delivery strategies for administration of either biomacromolecules or low molecular weight drugs. For these purposes, it is frequently used as matrix forming material in both nano and micron-sized particles. In addition to its interesting physicochemical and biopharmaceutical properties, which include high mucoadhesion and a great capacity to produce drug delivery systems, ensuring the biocompatibility of the drug delivery vehicles is a highly relevant issue. Nevertheless, this subject is not addressed as frequently as desired and even though the application of chitosan carriers has been widely explored, the demonstration of systems biocompatibility is still in its infancy. In this review, addressing the biocompatibility of chitosan carriers with application in drug delivery is discussed and the methods used in vitro and in vivo, exploring the effect of different variables, are described. We further provide a discussion on the pros and cons of used methodologies, as well as on the difficulties arising from the absence of standardization of procedures.

  19. Inhibition of brain tumor growth by intravenous poly (β-L-malic acid) nanobioconjugate with pH-dependent drug release

    National Research Council Canada - National Science Library

    Hui Ding; Satoshi Inoue; Alexander V. Ljubimov; Rameshwar Patil; Jose Portilla-Arias; Jinwei Hu; Bindu Konda; Kolja A. Wawrowsky; Manabu Fujita; Natalya Karabalin; Takako Sasaki; Keith L. Black; Eggehard Holler; Julia Y. Ljubimova; Alexander M. Klibanov

    2010-01-01

    .... A polymeric nanobioconjugate drug based on biodegradable, nontoxic, and nonimmunogenic polymalic acid as a universal delivery nanoplatform was used for design and synthesis of nanomedicine drug for i.v...

  20. Abbreviated New Drug Applications and 505(b)(2) Applications. Final rule.

    Science.gov (United States)

    2016-10-06

    The Food and Drug Administration (FDA, the Agency, or we) is issuing a final rule to implement Title XI of the Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA), which amended provisions of the Federal Food, Drug, and Cosmetic Act (the FD&C Act) that govern the approval of 505(b)(2) applications and abbreviated new drug applications (ANDAs). This final rule implements portions of Title XI of the MMA that pertain to provision of notice to each patent owner and the new drug application (NDA) holder of certain patent certifications made by applicants submitting 505(b)(2) applications or ANDAs; the availability of 30-month stays of approval on 505(b)(2) applications and ANDAs that are otherwise ready to be approved; submission of amendments and supplements to 505(b)(2) applications and ANDAs; and the types of bioavailability and bioequivalence data that can be used to support these applications. This final rule also amends certain regulations regarding 505(b)(2) applications and ANDAs to facilitate compliance with and efficient enforcement of the FD&C Act.

  1. Drug delivery to the nail following topical application.

    Science.gov (United States)

    Murdan, Sudaxshina

    2002-04-02

    The absorption of drugs into the nail unit, following topical application to the nail plate, is highly desirable to treat nail disorders, such as onychomycosis (fungal infections of the nail). Nail permeability is however quite low and limits topical therapy to early/mild disease states. In this paper, the recent research into ungual drug delivery is reviewed. The nail unit and the two most common diseases affecting the nail--onychomycosis and nail psoriasis--are briefly described to set the scene and to give an overview of the nature and scope of the problem. The factors, which affect drug uptake and permeation through the nail plate such as solute molecular size, hydrophilicity/hydrophobicity, charge, and the nature of the vehicle, are then discussed, followed by ways of enhancing drug transport into and through the nail plate. Finally, drug-containing nail lacquers which, like cosmetic varnish, are brushed onto the nail plates to form a film, and from which drug is released and penetrates into the nail, are reviewed.

  2. Third Generation Sequencing Techniques and Applications to Drug Discovery

    Science.gov (United States)

    Ozsolak, Fatih

    2012-01-01

    Introduction There is an immediate need for functional and molecular studies to decipher differences between disease and “normal” settings to identify large quantities of validated targets with the highest therapeutic utilities. Furthermore, drug mechanism of action and biomarkers to predict drug efficacy and safety need to be identified for effective design of clinical trials, decreasing attrition rates, regulatory agency approval process and drug repositioning. By expanding the power of genetics and pharmacogenetics studies, next generation nucleic acid sequencing technologies have started to play an important role in all stages of drug discovery. Areas covered This article reviews the first and second generation sequencing technologies (SGSTs) and challenges they pose to biomedicine. The article then focuses on the emerging third generation sequencing technologies (TGSTs), their technological foundations and potential contributions to drug discovery. Expert Opinion Despite the scientific and commercial success of SGSTs, the goal of rapid, comprehensive and unbiased sequencing of nucleic acids has not been achieved. TGSTs promise to increase sequencing throughput and read lengths, decrease costs, run times and error rates, eliminate biases inherent in SGSTs, and offer capabilities beyond nucleic acid sequencing. Such changes will have positive impact in all sequencing applications to drug discovery. PMID:22468954

  3. Carbon nanotubes: a potential concept for drug delivery applications.

    Science.gov (United States)

    Kumar, Rakesh; Dhanawat, Meenakshi; Kumar, Sudhir; Singh, Brahma N; Pandit, Jayant K; Sinha, Vivek R

    2014-04-01

    The unique properties of carbon nanotubes (CNTs) make them a highly interesting and demandable nanocarrier in the field of nanoscience. CNTs facilitate efficient delivery of therapeutics like drugs, proteins, genes, nucleic acids, vitamins and lot more. Even though highly beneficial, the biocompatibility of CNTs is a major issue in their questioning their potential application in targeting drug delivery. Studies confirmed subdued toxicity of CNTs following slight modifications like functionalization, controlled dimensions, purification etc. A well-established mechanism for cellular internalization is an insistent need to attain a more efficient and targeted delivery. Recent patents have been thoroughly discussed in the text below.

  4. Metabolism and disposition of [(14)C]dimethylamine borane in male Harlan Sprague Dawley rats following gavage administration, intravenous administration and dermal application.

    Science.gov (United States)

    Mathews, James M; Watson, Scott L; Patel, Purvi R; Black, Sherry R; Hong, Yan; Levine, Keith E; Ross, Glenn; Germolec, Dori R; Thakur, Sheetal A; Waidyanatha, Suramya

    2014-01-01

    1. Dimethylamine borane (DMAB) is used as a reducing agent in the manufacturing of a variety of products and in chemical synthesis. National Toxicology Program is evaluating the toxicity of DMAB in rodents following dermal application. The objective of this study was to evaluate the metabolism and disposition of DMAB in male Harlan Sprague Dawley (HSD) rats. 2. Disposition of radioactivity was similar between gavage and intravenous administration of 1.5 mg/kg [(14)C] DMAB, with nearly 84%-89% of the administered radioactivity recovered in urine 24 h post dosing. At 72 h, only 1% or less was recovered in feces, 0.3% as CO2, and 0.5%-1.4% as volatiles and 0.3%-0.4 % in tissues. 3. The absorption of [(14)C]DMAB following dermal application was moderate; percent dose absorbed increased with the dose, with 23%, 32% and 46% of dose absorbed at 0.15, 1.5 and 15 mg/kg, respectively. Urinary and fecal excretion ranged from 18%-37% and 2%-4% of dose, respectively, and 0.1%-0.2% as CO2, and 1%-3% as volatiles. Tissue retention of the radiolabel was low ∼1%, but was higher than following the gavage or intravenous administration. 4. Following co-adminsitration of DMAB and sodium nitrite by gavage, N-nitrosodimethylamine was not detected in blood or urine above the limit of quantitation of the analytical method of 10 ng/mL. 5. Absorption of DMAB in fresh human skin in vitro was ∼41% of the applied dose: the analysis of the receptor fluid shows that the intact DMAB complex can be absorbed through the skin.

  5. Applications of polymers in intraocular drug delivery systems

    Science.gov (United States)

    Alhalafi, Ali Mohammed

    2017-01-01

    We are entering a new era of ophthalmic pharmacology where new drugs are rapidly being developed for the treatment of anterior and posterior segment of the eye disease. The pharmacokinetics of drug delivery to the eye remains a very active area of ophthalmic research. Intraocular drug delivery systems allow the release of the drug, bypassing the blood-ocular barrier. The main advantage of these preparations is that they can release the drug over a long time with one single administration. These pharmaceutical systems are of great important in the treatment of the posterior segment diseases, and they can be prepared from biodegradable or nonbiodegradable polymers. Biodegradable polymers have the advantage of disappearing from the site of action after releasing the drug. The majority of intraocular devices are prepared from nonbiodegradable polymers, and they can release controlled amounts of drugs for months. Nonbiodegradable polymers include silicone, polyvinyl alcohol, and ethylene-vinyl acetate. The polymers usually employed to prepare nanoparticles for the topical ophthalmic route are poly (acrylic acid) derivatives (polyalquilcyanocrylates), albumin, poly-ε-caprolactone, and chitosan. Dendrimers are a recent class of polymeric materials with unique nanostructure which has been studied to discover their role in the delivery of therapeutics and imaging agents. Hydrogels are polymers that can swell in aqueous solvent system, and they hold the solvents in a swollen cross-linked gel for delivery. This review exhibits the current literature regarding applications of polymers in ophthalmic drug delivery systems including pharmacokinetics, advantages, disadvantages, and indications aimed to obtain successful eye therapy. Method of Literature Search: A systematic literature review was performed using PubMed databases into two steps. The first step was oriented to classification of intraocular polymers implants focusing on their advantages and disadvantages. The second

  6. Applications of polymers in intraocular drug delivery systems

    Directory of Open Access Journals (Sweden)

    Ali Mohammed Alhalafi

    2017-01-01

    Full Text Available We are entering a new era of ophthalmic pharmacology where new drugs are rapidly being developed for the treatment of anterior and posterior segment of the eye disease. The pharmacokinetics of drug delivery to the eye remains a very active area of ophthalmic research. Intraocular drug delivery systems allow the release of the drug, bypassing the blood–ocular barrier. The main advantage of these preparations is that they can release the drug over a long time with one single administration. These pharmaceutical systems are of great important in the treatment of the posterior segment diseases, and they can be prepared from biodegradable or nonbiodegradable polymers. Biodegradable polymers have the advantage of disappearing from the site of action after releasing the drug. The majority of intraocular devices are prepared from nonbiodegradable polymers, and they can release controlled amounts of drugs for months. Nonbiodegradable polymers include silicone, polyvinyl alcohol, and ethylene-vinyl acetate. The polymers usually employed to prepare nanoparticles for the topical ophthalmic route are poly (acrylic acid derivatives (polyalquilcyanocrylates, albumin, poly-μ-caprolactone, and chitosan. Dendrimers are a recent class of polymeric materials with unique nanostructure which has been studied to discover their role in the delivery of therapeutics and imaging agents. Hydrogels are polymers that can swell in aqueous solvent system, and they hold the solvents in a swollen cross-linked gel for delivery. This review exhibits the current literature regarding applications of polymers in ophthalmic drug delivery systems including pharmacokinetics, advantages, disadvantages, and indications aimed to obtain successful eye therapy. Method of Literature Search: A systematic literature review was performed using PubMed databases into two steps. The first step was oriented to classification of intraocular polymers implants focusing on their advantages and

  7. 75 FR 37295 - Change of Address; Abbreviated New Drug Applications; Technical Amendment

    Science.gov (United States)

    2010-06-29

    ...The Food and Drug Administration (FDA) is amending its regulations to update the address for applicants to submit abbreviated new drug applications (ANDAs) and ANDA amendments, supplements, and resubmissions. FDA is also updating the address for ANDA applicants to submit investigational new drug applications (INDs) for in vivo bioavailability and bioequivalence studies in humans that are......

  8. Applications of chemogenomic library screening in drug discovery.

    Science.gov (United States)

    Jones, Lyn H; Bunnage, Mark E

    2017-01-20

    The allure of phenotypic screening, combined with the industry preference for target-based approaches, has prompted the development of innovative chemical biology technologies that facilitate the identification of new therapeutic targets for accelerated drug discovery. A chemogenomic library is a collection of selective small-molecule pharmacological agents, and a hit from such a set in a phenotypic screen suggests that the annotated target or targets of that pharmacological agent may be involved in perturbing the observable phenotype. In this Review, we describe opportunities for chemogenomic screening to considerably expedite the conversion of phenotypic screening projects into target-based drug discovery approaches. Other applications are explored, including drug repositioning, predictive toxicology and the discovery of novel pharmacological modalities.

  9. [Intravenous remifentanyl for labor analgesia].

    Science.gov (United States)

    Arnal, D; Serrano, M L; Corral, E M; García del Valle, S

    2009-04-01

    Intravenous remifentanil may be the preferred analgesic when regional techniques are contraindicated. To perform a systematic review on the use of remifentanil for analgesia in labor. We searched MEDLINE (January 1995-August 2007) for studies on obstetric analgesia with remifentanil. We found 32 references representing the use of remifentanil in 257 women in labor. In most cases, patients reported relief of pain and a high level of satisfaction, with no severe side effects in mothers or neonates. When compared with meperidine and nitrous oxide in clinical trials, remifentanil provided better analgesia with fewer adverse effects. Analgesia with intravenous remifentanil is more effective and safer than other alternatives to regional analgesic techniques in obstetrics. Nevertheless, the optimum system for infusing the drug must b e established and further studies of maternal and fetal safety should be carried out.

  10. 76 FR 22713 - Withdrawal of Approval of New Animal Drug Applications; Phenylbutazone; Pyrantel; Tylosin...

    Science.gov (United States)

    2011-04-22

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Withdrawal of Approval of New Animal Drug Applications; Phenylbutazone; Pyrantel; Tylosin; Sulfamethazine; Correction AGENCY: Food and Drug Administration, HHS. ACTION...

  11. Application of quality by design in the current drug development

    Directory of Open Access Journals (Sweden)

    Lan Zhang

    2017-01-01

    Full Text Available Quality by Test was the only way to guarantee quality of drug products before FDA launched current Good Manufacturing Practice. To clearly understand the manufacture processes, FDA generalized Quality by Design (QbD in the field of pharmacy, which is based on the thorough understanding of how materials and process parameters affect the quality profile of final products. The application of QbD in drug formulation and process design is based on a good understanding of the sources of variability and the manufacture process. In this paper, the basic knowledge of QbD, the elements of QbD, steps and tools for QbD implementation in pharmaceutics field, including risk assessment, design of experiment, and process analytical technology (PAT, are introduced briefly. Moreover, the concrete applications of QbD in various pharmaceutical related unit operations are summarized and presented.

  12. 评判性思维在静脉输液中应用的效果评价%Application effect of critical thinking in the intravenous infusion

    Institute of Scientific and Technical Information of China (English)

    谢春雷; 李春霞; 李爱文

    2013-01-01

    目的 探讨评判性思维在静脉输液中的应用效果.方法 选择2012年1~4月在神经外科工作的护士进行评判性思维能力的培养,运用评判性思维在静脉输液过程中进行分析、判断、制定与落实相应护理措施,观察实施评判性思维培训后患者的静脉输液穿刺成功率及患者对护理工作的满意度.结果 对护理人员进行静脉输液评判性思维的培训后,患者的静脉穿刺成功率及患者对护理工作的满意度较培训前明显提高.结论 对护士在静脉输液过程中实施评判性思维培训可有效提高护士的穿刺技能,减少输液肿胀及并发症的发生,提高临床护理质量及患者对护理工作的满意度.%Objective To explore the application effect of critical thinking applied in the intravenous infusion.Methods To give nurses who worked in the Neurosurgery Department from January to April 2012 training lessons of critical thinking so that they could analyze,judge,formulate and implement corresponding nursing measures during the intravenous infusion process through their critical thinking.Then the successful rate of venepuncture for patients and the patients' satisfaction degree with nursing before and after the critical thinking training lessons were observed.Results The successful rate of venepuncture for patients and the patients' satisfaction degree of nursing were apparently improved after the nurses received critical thinking training.The difference was of statistical significance.Conclusions After the implementation of critical thinking training during the intravenous infusion process for nurses,nurses puncture skills is enhanced,infusion swelling and complications are reduced,and the quality of clinical nursing care and patients' satisfaction degree of nursing is improved.

  13. Comparison of self-administration behavior and responsiveness to drug-paired cues in rats running an alley for intravenous heroin and cocaine

    OpenAIRE

    Su, Zu-In; Wenzel, Jennifer; Baird, Rebeccah; Ettenberg, Aaron

    2010-01-01

    Rationale Evidence suggests that responsiveness to a drug-paired cue is predicted by the reinforcing magnitude of the drug during prior self-administration. It remains unclear, however, if this principle holds true when comparisons are made across drug reinforcers. Objective The current study was therefore devised to test the hypothesis that differences in the animals’ responsiveness to a cocaine- or heroin-paired cue presented during extinction would reflect differences in the patterns of pr...

  14. Inhibition of brain tumor growth by intravenous poly(β-l-malic acid) nanobioconjugate with pH-dependent drug release

    OpenAIRE

    Ding, Hui; Inoue, Satoshi; Ljubimov, Alexander V.; Patil, Rameshwar; Portilla-Arias, Jose; Hu, Jinwei; Konda, Bindu; Wawrowsky, Kolja A; Fujita, Manabu; Karabalin, Natalya; Sasaki, Takako; Black, Keith L.; Holler, Eggehard; Ljubimova, Julia Y

    2010-01-01

    Effective treatment of brain neurological disorders such as Alzheimer's disease, multiple sclerosis, or tumors should be possible with drug delivery through blood–brain barrier (BBB) or blood–brain tumor barrier (BTB) and targeting specific types of brain cells with drug release into the cell cytoplasm. A polymeric nanobioconjugate drug based on biodegradable, nontoxic, and nonimmunogenic polymalic acid as a universal delivery nanoplatform was used for design and synthesis of nanomedicine dru...

  15. Liposomal drug delivery systems: from concept to clinical applications.

    Science.gov (United States)

    Allen, Theresa M; Cullis, Pieter R

    2013-01-01

    The first closed bilayer phospholipid systems, called liposomes, were described in 1965 and soon were proposed as drug delivery systems. The pioneering work of countless liposome researchers over almost 5 decades led to the development of important technical advances such as remote drug loading, extrusion for homogeneous size, long-circulating (PEGylated) liposomes, triggered release liposomes, liposomes containing nucleic acid polymers, ligand-targeted liposomes and liposomes containing combinations of drugs. These advances have led to numerous clinical trials in such diverse areas as the delivery of anti-cancer, anti-fungal and antibiotic drugs, the delivery of gene medicines, and the delivery of anesthetics and anti-inflammatory drugs. A number of liposomes (lipidic nanoparticles) are on the market, and many more are in the pipeline. Lipidic nanoparticles are the first nanomedicine delivery system to make the transition from concept to clinical application, and they are now an established technology platform with considerable clinical acceptance. We can look forward to many more clinical products in the future.

  16. Injectable biopolymer based hydrogels for drug delivery applications.

    Science.gov (United States)

    Atta, Sadia; Khaliq, Shaista; Islam, Atif; Javeria, Irtaza; Jamil, Tahir; Athar, Muhammad Makshoof; Shafiq, Muhammad Imtiaz; Ghaffar, Abdul

    2015-09-01

    Biopolymer based pH-sensitive hydrogels were prepared using chitosan (CS) with polyethylene glycol (PEG) of different molecular weights in the presence of silane crosslinker. The incorporated components remain undissolved in different swelling media as they are connected by siloxane linkage which was confirmed by Fourier transform infrared spectroscopy. The swelling in water was enhanced by the addition of higher molecular weight PEG. The swelling behaviour of the hydrogels against pH showed high swelling in acidic and basic pH, whereas, low swelling was examined at pH 6 and 7. This characteristic pH responsive behaviour at neutral pH made them suitable for injectable controlled drug delivery. The controlled release analysis of Cefixime (CFX) (model drug) loaded CS/PEG hydrogel exhibited that the entire drug was released in 30 min in simulated gastric fluid (SGF) while in simulated intestinal fluid (SIF), 85% of drug was released in controlled manner within 80 min. This inferred that the developed hydrogels can be an attractive biomaterial for injectable drug delivery with physiological pH and other biomedical applications.

  17. The application of drug dose equivalence in the quantitative analysis of receptor occupation and drug combinations.

    Science.gov (United States)

    Tallarida, Ronald J; Raffa, Robert B

    2010-08-01

    In this review we show that the concept of dose equivalence for two drugs, the theoretical basis of the isobologram, has a wider use in the analysis of pharmacological data derived from single and combination drug use. In both its application to drug combination analysis with isoboles and certain other actions, listed below, the determination of doses, or receptor occupancies, that yield equal effects provide useful metrics that can be used to obtain quantitative information on drug actions without postulating any intimate mechanism of action. These other drug actions discussed here include (1) combinations of agonists that produce opposite effects, (2) analysis of inverted U-shaped dose-effect curves of single agents, (3) analysis on the effect scale as an alternative to isoboles and (4) the use of occupation isoboles to examine competitive antagonism in the dual receptor case. New formulas derived to assess the statistical variance for additive combinations are included, and the more detailed mathematical topics are included in the Appendix.

  18. Molecularly imprinted polymers based drug delivery devices: a way to application in modern pharmacotherapy. A review.

    Science.gov (United States)

    Luliński, Piotr

    2017-07-01

    This review presents the current status of molecularly imprinted polymers (MIPs) for drug delivery, in particular the studies that focus on biocompatibility, cytotoxicity, and in vitro or in vivo behavior of MIPs. It also shows the limitations that hamper the introduction of MIPs to pharmacotherapy and prevent this class of polymers from commercialization. MIPs are promising materials in the construction of drug delivery devices because they can provide improved delivery profiles or longer release times and deliver the drugs in the feedback regulated way, which is extremely important in modern pharmacotherapy. Here, a brief overview of the imprinting process and a concise description of drug release mechanisms from the imprinted materials will be presented followed by the discussion of potential MIP drug delivery devices for ocular, dermal, intravenous and oral routes of administration. Finally, future prospects for imprinted drug delivery forms will be outlined. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. 75 FR 71135 - Hoffmann-La Roche Inc.; Withdrawal of Approval of a New Drug Application

    Science.gov (United States)

    2010-11-22

    ... HUMAN SERVICES Food and Drug Administration Hoffmann-La Roche Inc.; Withdrawal of Approval of a New Drug... Administration (FDA) is withdrawing approval of a new drug application (NDA) for ACCUTANE (isotretinoin) Capsules... be marketed under approved abbreviated new drug applications (ANDAs). The holders of ANDAs...

  20. Immunocompatibility and toxicity studies of poly-L-lysine nanocapsules in sprague-dawley rats for drug-delivery applications.

    Science.gov (United States)

    Ayyappan, Janeesh Plakkal; Sami, Haider; Rajalekshmi, Dhanya Chandrasekharan; Sivakumar, Sri; Abraham, Annie

    2014-09-01

    Poly-L-Lysine (PLL) nanocapsules are the emerging drug-delivery vehicle for the therapeutics of targeted diseases. The study was designed for the synthesis and characterization of PLL nanocapsules and to know its immunocompatibility and toxicity behavior for in vivo drug-delivery applications. Alteration in hematologic parameters, immunomodulatory gene expression by RT-PCR studies, toxicity markers status, immunoblotting of major inflammatory marker proteins, and histopathologic studies from major tissues of rat after intravenous administration of PLL nanocapsules after 30 days were assessed. In vivo toxicity markers activity, hematologic parameters alteration, and RT-PCR analysis of important immunomodulatory genes such as monocyte chemotactic protein-1(MCP 1), tumor necrosis factor-alpha (TNF-α), Intercellular adhesion molecule-1 (ICAM-1), and interleukin-6 (IL-6) showed least changes when compared with control. The immunoblotting of major inflammatory markers such as cyclooxygenase-2 (COX-2), lipo-oxygenase-15 (LOX-15), and nitric oxide synthase (NOS) found have least expression showing the immunocompatibility of PLL nanocapsules. Histopathologic studies of important tissues showed almost normal architecture after treatment using different concentration of PLL nanocapsules after the experimental period. The results showed a promising outcome and further confirmed the immunocompatibility and non-toxicity of PLL nanocapsules in vivo for drug-delivery applications.

  1. 77 FR 24723 - AstraZeneca Pharmaceuticals LP; Withdrawal of Approval of a New Drug Application for IRESSA

    Science.gov (United States)

    2012-04-25

    ... New Drug Application for IRESSA AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is withdrawing approval of a new drug application (NDA)...

  2. Intravenous paracetamol (acetaminophen).

    Science.gov (United States)

    Duggan, Sean T; Scott, Lesley J

    2009-01-01

    Intravenous paracetamol (rINN)/intravenous acetaminophen (USAN) is an analgesic and antipyretic agent, recommended worldwide as a first-line agent for the treatment of pain and fever in adults and children. In double-blind clinical trials, single or multiple doses of intravenous paracetamol 1 g generally provided significantly better analgesic efficacy than placebo treatment (as determined by primary efficacy endpoints) in adult patients who had undergone dental, orthopaedic or gynaecological surgery. Furthermore, where evaluated, intravenous paracetamol 1 g generally showed similar analgesic efficacy to a bioequivalent dose of propacetamol, and a reduced need for opioid rescue medication. In paediatric surgical patients, recommended doses of intravenous paracetamol 15 mg/kg were not significantly different from propacetamol 30 mg/kg for the treatment of pain, and showed equivocal analgesic efficacy compared with intramuscular pethidine 1 mg/kg in several randomized, active comparator-controlled studies. In a randomized, noninferiority study in paediatric patients with an infection-induced fever, intravenous paracetamol 15 mg/kg treatment was shown to be no less effective than propacetamol 30 mg/kg in terms of antipyretic efficacy. Intravenous paracetamol was well tolerated in clinical trials, having a tolerability profile similar to placebo. Additionally, adverse reactions emerging from the use of the intravenous formulation of paracetamol are extremely rare (<1/10 000). [table: see text].

  3. Pharmacokinetics of meropenem during intermittent and continuous intravenous application in patients treated by continuous renal replacement therapy.

    Science.gov (United States)

    Langgartner, Julia; Vasold, Antje; Glück, Thomas; Reng, Michel; Kees, Frieder

    2008-06-01

    The clinical effect of beta-lactam antibiotics depends on the time of drug concentration above the minimal inhibitory concentration (MIC) for a susceptible bacterium. Continuous infusion (CI) of beta-lactams such as meropenem may therefore be a more rational approach than intermittent bolus injections (IB). The aim of this study was to test whether CI of meropenem achieves effective drug concentrations comparable to IB in patients treated by continuous renal replacement therapy (CRRT). Prospective, randomised cross-over study. Twelve-bed medical intensive care unit (ICU). Six ICU patients were randomised to receive either meropenem 1 g IB every 12 h or a 0.5 g i.v. loading dose followed by 2 g i.v. CI over 24 h. After 2 days, regimens were crossed over. Meropenem pharmacokinetics were determined on days 2 and 4. Peak serum concentration [median (25% and 75% quartiles)] after short infusion of 1 g meropenem were 62.8 (51.4; 85.0) mg/l, trough levels at 12 h were 8.1 (4.5; 18.7) mg/l, and serum half-life was 5.3 (5.1; 7.0) h. Steady-state concentrations during CI were 18.6 (13.3; 24.5) mg/l. The AUCs during either treatment were comparable and determined as 233 (202; 254) mg/l*h (IB) and 227 (182; 283) mg/l*h (CI), respectively. Four hours after IB, drug concentrations dropped below CI steady-state concentrations. Appropriate antibacterial concentrations of meropenem in patients with CRRT are easily achievable with CI. CI may be an effective alternative dosing regimen to IB. A prospective comparison of the clinical efficacy of the two dosage regimens is warranted.

  4. Packaged peristaltic micropump for controlled drug delivery application

    Science.gov (United States)

    Vinayakumar, K. B.; Nadiger, Girish; R. Shetty, Vikas; Dinesh, N. S.; Nayak, M. M.; Rajanna, K.

    2017-01-01

    Micropump technology has evolved significantly in the last two decades and is finding a variety of applications ranging from μTAS (micro Total Analysis System) to drug delivery. However, the application area of the micropump is limited owing to: simple pumping mechanism, ease of handling, controlled (microliter to milliliter) delivery, continuous delivery, and accuracy in flow rate. Here, the author presents the design, development, characterization, and precision flow controlling of a DC-motor driven peristaltic pump for controlled drug delivery application. All the micropump components were fabricated using the conventional fabrication technique. The volume flow variation of the pump has been characterized for different viscous fluids. The change in volume flow due to change in back pressure has been presented in detail. The fail-safe mode operation of the pump has been tested and leak rate was measured (˜0.14% leak for an inlet pressure of 140 kPa) for different inlet pressures. The precision volume flow of the pump has been achieved by measuring the pinch cam position and load current. The accuracy in the volume flow has been measured after 300 rotations. Finally, the complete system has been integrated with the necessary electronics and an android application has been developed for the self-administration of bolus and basal delivery of insulin.

  5. Inhibition of brain tumor growth by intravenous poly (β-L-malic acid) nanobioconjugate with pH-dependent drug release [corrected].

    Science.gov (United States)

    Ding, Hui; Inoue, Satoshi; Ljubimov, Alexander V; Patil, Rameshwar; Portilla-Arias, Jose; Hu, Jinwei; Konda, Bindu; Wawrowsky, Kolja A; Fujita, Manabu; Karabalin, Natalya; Sasaki, Takako; Black, Keith L; Holler, Eggehard; Ljubimova, Julia Y

    2010-10-19

    Effective treatment of brain neurological disorders such as Alzheimer's disease, multiple sclerosis, or tumors should be possible with drug delivery through blood-brain barrier (BBB) or blood-brain tumor barrier (BTB) and targeting specific types of brain cells with drug release into the cell cytoplasm. A polymeric nanobioconjugate drug based on biodegradable, nontoxic, and nonimmunogenic polymalic acid as a universal delivery nanoplatform was used for design and synthesis of nanomedicine drug for i.v. treatment of brain tumors. The polymeric drug passes through the BTB and tumor cell membrane using tandem monoclonal antibodies targeting the BTB and tumor cells. The next step for polymeric drug action was inhibition of tumor angiogenesis by specifically blocking the synthesis of a tumor neovascular trimer protein, laminin-411, by attached antisense oligonucleotides (AONs). The AONs were released into the target cell cytoplasm via pH-activated trileucine, an endosomal escape moiety. Drug delivery to the brain tumor and the release mechanism were both studied for this nanobiopolymer. Introduction of a trileucine endosome escape unit resulted in significantly increased AON delivery to tumor cells, inhibition of laminin-411 synthesis in vitro and in vivo, specific accumulation in brain tumors, and suppression of intracranial glioma growth compared with pH-independent leucine ester. The availability of a systemically active polymeric drug delivery system that passes through the BTB, targets tumor cells, and inhibits glioma growth gives hope for a successful strategy of glioma treatment. This delivery system with drug release into the brain-specific cell type could be useful for treatment of various brain pathologies.

  6. To investigate the impact facots of dose of drug in intravenous infusion for decision-making%浅析静脉用药过程中影响药物剂量的护理因素及对策

    Institute of Scientific and Technical Information of China (English)

    卢桂华

    2012-01-01

    Objective To investigate the impact facots of dose of drug in intravenous infusion for decision-making. Methods 80 cases used of piperacillin tazobactam were randomly divided into control and experimental groups, using double-blind study, collection residual liquid of the original bottles and infusion tube, calculating drug dose, with daily infusion process in the control group, while strict intervention infusion process in experimental group. Average of drug residues between two groups with t-test. Results In control group, piperacillin tazobactam sodium content of the residual liquid average was(0. 9256 ± 0. 1189) g; experimental group ( 0. 2654 ± 0. 0398 ) g, P = 0. 000, the difference was statistically significant. Conclusion In intravenous drug preparation and the infusion process, strict rules of the nurses to reduce the residual liquid of drug.%目的 探讨静脉治疗过程中影响药物剂量的护理因素及对策.方法 80例输注哌拉西林钠他唑巴坦钠患者随机分为对照组和实验组,并采用双盲研究,收集原药瓶和输液器中的残留液计算残留药物剂量,对照组为护士日常输液流程,实验组为研究人员严格干预下输液流程.两组残留药物平均数进行t检验.结果 对照组残余药液平均含量为(0.9256±0.1189)g;实验组为(0.2654±0.0398)g(P=0.000),差异有统计学意义.结论 静脉药物配制及输液过程中,护理人员严格操作规程,可减少药液的残留.

  7. Time Course of Pupil Center Location after Ocular Drug Application.

    Science.gov (United States)

    Hoang, Tony A; Macdonnell, Jacqueline E; Mangan, Michelle C; Monsour, Cindy S; Polwattage, Buddhika L; Wilson, Sarah F; Suheimat, Marwan; Atchison, David A

    2016-06-01

    To investigate the time course of pupil centration after application of common topical ocular drugs. Single drops of 2.5% phenylephrine hydrochloride, 1% tropicamide, and 2% pilocarpine hydrochloride were applied on different days to the right eyes of 12 participants. Anterior eye images were captured, at 5-min intervals for an hour, using an infrared-sensitive camera. The images were analyzed to determine pupil diameter and pupil center, the latter with respect to the limbal center. As a control, natural pupil size and pupil center were determined under different illuminances. Pupil centers of natural pupils shifted temporally as pupils dilated. At common pupil sizes, drug-induced pupil centers were different from natural pupil centers. Phenylephrine produced a center shift in the nasal and inferior directions that peaked after a mean of 30 min, whereas dilation was continuing up to 60 min. Tropicamide produced transient center shifts in the nasal and inferior directions that peaked at about 10 min before reducing toward baseline values, whereas dilation reached a peak at about 25 min. Pilocarpine produced a small sustained superior shift that, like constriction, reached a peak after about 25 min. Application of topical ophthalmic drugs cause shifts in pupil center that do not match those produced by natural changes in pupil size and that, in the cases of phenylephrine and tropicamide, follow a different time course than the pupil size changes.

  8. IMMUNOREGULATORY EFFECTS OF INTRAVENOUS IMMUNOGLOBULINS

    Directory of Open Access Journals (Sweden)

    S. A. Sel'kov

    2013-01-01

    Full Text Available Treatment with intravenous immunoglobulins (IVIG is widely used in modern clinical practice inorder to cure different clinical disorders, including obstetric conditions. Currently, IVIGs have become drugs of  choice  for  treatment of  anti-phospholipid  syndrome  in pregnant women,  like  as  in  cases of  intrauterine cytomegalovirus infection.

  9. Pharmacokinetics and pharmacodynamics of intravenous inotropic agents.

    Science.gov (United States)

    Lehtonen, Lasse A; Antila, Saila; Pentikäinen, Pertti J

    2004-01-01

    Positive inotropic drugs have various mechanisms of action. Long-term use of cyclic adenosine monophosphate (cAMP)-dependent drugs has adverse effects on the prognosis of heart failure patients, whereas digoxin has neutral effect on mortality. There are, however, little data on the effects of intravenous inotropic drugs on the outcome of patients. Intravenous inotropic agents are used to treat cardiac emergencies and refractory heart failure. beta-Adrenergic agonists are rapid acting and easy to titrate, with short elimination half-life. However, they increase myocardial oxygen consumption and are thus hazardous during myocardial ischaemia. Furthermore they may promote myocyte apoptosis. Phosphodiesterase (PDE) III inhibiting drugs (amrinone, milrinone and enoximone) increase contractility by reducing the degradation of cAMP. In addition, they reduce both preload and afterload via vasodilation. Short-term use of intravenous milrinone is not associated with increased mortality, and some symptomatic benefit may be obtained when it is used in refractory heart failure. Furthermore, PDE III inhibitors facilitate weaning from the cardiopulmonary bypass machine after cardiac surgery. Levosimendan belongs to a new group of positive inotropic drugs, the calcium sensitisers. It has complex pharmacokinetics and long-lasting haemodynamic effects as a result of its active metabolites. In comparative trials, it has been better tolerated than the most widely used beta-agonist inotropic drug, dobutamine. The pharmacokinetics of the intravenous inotropic drugs might sometimes greatly modify and prolong the response to the therapy, for example because of long-acting active metabolites. These drugs display considerable differences in their pharmacokinetics and pharmacodynamics, and the selection of the most appropriate inotropic drug for each patient should be based on careful consideration of the clinical status of the patient and on the pharmacology of the drug.

  10. Applications and limitations of in silico models in drug discovery.

    Science.gov (United States)

    Sacan, Ahmet; Ekins, Sean; Kortagere, Sandhya

    2012-01-01

    Drug discovery in the late twentieth and early twenty-first century has witnessed a myriad of changes that were adopted to predict whether a compound is likely to be successful, or conversely enable identification of molecules with liabilities as early as possible. These changes include integration of in silico strategies for lead design and optimization that perform complementary roles to that of the traditional in vitro and in vivo approaches. The in silico models are facilitated by the availability of large datasets associated with high-throughput screening, bioinformatics algorithms to mine and annotate the data from a target perspective, and chemoinformatics methods to integrate chemistry methods into lead design process. This chapter highlights the applications of some of these methods and their limitations. We hope this serves as an introduction to in silico drug discovery.

  11. Assessing acute systemic effects of an inhaled drug with serial echocardiography: a placebo-controlled comparison of inhaled and intravenous dihydroergotamine

    Directory of Open Access Journals (Sweden)

    Noveck RJ

    2013-07-01

    Full Text Available Robert J Noveck,1 Pamela S Douglas,2 Shein-Chung Chow,3 Barry Mangum,4 Shashidhar Kori,5 Donald J Kellerman51Duke Clinical Research Unit, Division of Clinical Pharmacology, Duke University School of Medicine, Durham, NC, USA; 2Imaging Program, Duke Clinical Research Institute, Durham, NC, USA; 3Department of Biostatistics and Bioinformatics, Duke-NUS Graduate Medical School, Durham, NC, USA; 4Clinical Pharmacology, Duke Clinical Research Unit, Duke University School of Medicine, Durham, NC, USA; 5MAP Pharmaceuticals, Inc, Mountain View, CA, USAObjective: MAP0004 is an investigational product which delivers dihydroergotamine (DHE through the lung via a breath-synchronized metered dose inhaler. The objective of this study was to compare the acute effects of orally inhaled and intravenous (IV DHE to placebo on maximum change and area under the curve for pulmonary arterial systolic pressure (PASP.Research design and methods: A randomized, double-blind, placebo-controlled, 3-period, crossover study of 24 health adults. Trial registration NCT01089062. Study assessments included pharmacokinetics, electrocardiograms (ECG, and validated echocardiographic (Doppler-derived measures of PASP by echocardiogram. The primary endpoint was the absolute change in calculated PASP using area under the curve, 0 to 2 hours (AUC0–2h.Results: The change in PASP with IV DHE was significantly different than MAP0004 and placebo (AUC0–2h2857, 2624, and 2453 mmHg*min, respectively. After a second dose of MAP0004, AUC0–4h remained lower with MAP0004 than with a single dose of IV DHE. Adverse events were more common with IV DHE than with MAP0004 or placebo. None of the treatments produced clinically significant changes in PASP or other cardiac parameters. Changes in PASP were significantly smaller with MAP0004 compared with IV DHE.Conclusion: These results indicate the effects 1 mg of orally inhaled DHE on the cardiovascular system are less than with 1 mg of IV DHE, and

  12. Application of aptamers in diagnostics, drug-delivery and imaging

    Indian Academy of Sciences (India)

    CHETAN CHANDOLA; SHEETAL KALME; MARCO G CASTELEIJN; ARTO URTTI; MUNIASAMY NEERATHILINGAM

    2016-09-01

    Aptamers are small, single-stranded oligonucleotides (DNA or RNA) that bind to their target with high specificity andaffinity. Although aptamers are analogous to antibodies for a wide range of target recognition and variety ofapplications, they have significant advantages over antibodies. Since aptamers have recently emerged as a class ofbiomolecules with an application in a wide array of fields, we need to summarize the latest developments herein. Inthis review we will discuss about the latest developments in using aptamers in diagnostics, drug delivery and imaging.We begin with diagnostics, discussing the application of aptamers for the detection of infective agents itself, antigens/toxins (bacteria), biomarkers (cancer), or a combination. The ease of conjugation and labelling of aptamers makesthem a potential tool for diagnostics. Also, due to the reduced off-target effects of aptamers, their use as a potentialdrug delivery tool is emerging rapidly. Hence, we discuss their use in targeted delivery in conjugation with siRNAs,nanoparticles, liposomes, drugs and antibodies. Finally, we discuss about the conjugation strategies applicable forRNA and DNA aptamers for imaging. Their stability and self-assembly after heating makes them superior overprotein-based binding molecules in terms of labelling and conjugation strategies.

  13. Enzyme kinetics in drug metabolism: fundamentals and applications.

    Science.gov (United States)

    Nagar, Swati; Argikar, Upendra A; Tweedie, Donald J

    2014-01-01

    Enzymes are protein catalysts that lower the energy barrier for a reaction and speed the rate of a chemical change. The kinetics of reactions catalyzed by enzymes, as well as several mechanisms underlying the kinetics, have been comprehensively studied and written in textbooks (1, 2). The importance of quantitative evaluation of enzymatic processes has been recognized in many fields of study, including biochemistry, molecular biology, and pharmaceutical sciences to name a few. In pharmaceutical sciences, the applications of enzyme kinetics range from hit finding efforts for new chemical entities on a pharmacological target to concentration effect relationships to large-scale biosynthesis. The study of the science of drug metabolism has two principal concepts-rate and extent. While understanding disposition pathways and identification of metabolites provides an insight into the extent of metabolism, kinetics of depletion of substrates (endogenous or exogenous) and formation of metabolites deals with the rate of metabolism. The current textbook specifically focuses on kinetics of drug-metabolizing enzymes, detailing specific enzyme classes, and discusses kinetics as they apply to drug transporters. This textbook also outlines additional factors that contribute to the kinetics of reactions catalyzed by these proteins such as variability in isoforms (pharmacogenomics) and experimental factors including key concepts such as alterations of substrate concentrations due to binding. Applications of these approaches in predicting kinetic parameters and alternative approaches for enzymes (systems biology) and transporters are also discussed. The final section focuses on real-life examples (case studies) to try and exemplify the applications of enzyme kinetic principles. This chapter provides a brief overview outlining some key concepts within each of the sections and the chapters within this textbook.

  14. Proteomics and Its Application in Biomarker Discovery and Drug Development

    Institute of Scientific and Technical Information of China (English)

    He Qing-Yu; Chiu Jen-Fu

    2004-01-01

    Proteomics is a research field aiming to characterize molecular and cellular dynamics in protein expression and function on a global level. The introduction of proteomics has been greatly broadening our view and accelerating our path in various medical researches. The most significant advantage of proteomics is its ability to examine a whole proteome or sub-proteome in a single experiment so that the protein alterations corresponding to a pathological or biochemical condition at a given time can be considered in an integrated way. Proteomic technology has been extensively used to tackle a wide variety of medical subjects including biomarker discovery and drug development. By complement with other new technique advance in genomics and bioinformatics,proteomics has a great potential to make considerable contribution to biomarker identification and revolutionize drug development process. A brief overview of the proteomic technologies will be provided and the application of proteomics in biomarker discovery and drug development will be discussed using our current research projects as examples.

  15. Chemical functionalization of hyaluronic acid for drug delivery applications

    Energy Technology Data Exchange (ETDEWEB)

    Vasi, Ana-Maria [“Gheorghe Asachi” Technical University of Iasi, Faculty of Chemical Engineering and Environmental Protection, 73 Prof. dr. docent Dimitrie Mangeron Street, 700050 Iasi (Romania); Popa, Marcel Ionel, E-mail: mipopa@ch.tuiasi.ro [“Gheorghe Asachi” Technical University of Iasi, Faculty of Chemical Engineering and Environmental Protection, 73 Prof. dr. docent Dimitrie Mangeron Street, 700050 Iasi (Romania); Butnaru, Maria [“Grigore T. Popa” University of Medicine Pharmacy, Faculty of Medical Bioengineering, 9-13 Kogalniceanu Street, 700454 Iasi (Romania); Dodi, Gianina [“Gheorghe Asachi” Technical University of Iasi, Faculty of Chemical Engineering and Environmental Protection, 73 Prof. dr. docent Dimitrie Mangeron Street, 700050 Iasi (Romania); SCIENT — Research Center for Instrumental Analysis, S.C. CROMATEC PLUS, 18 Sos. Cotroceni, 060114 Bucharest (Romania); Verestiuc, Liliana [“Grigore T. Popa” University of Medicine Pharmacy, Faculty of Medical Bioengineering, 9-13 Kogalniceanu Street, 700454 Iasi (Romania)

    2014-05-01

    Functionalized hyaluronic acid (HA) derivatives were obtained by ring opening mechanism of maleic anhydride (MA). FTIR and H{sup 1} NMR spectroscopy were used to confirm the chemical linkage of MA on the hyaluronic acid chains. Thermal analysis (TG-DTG and DSC) and GPC data for the new products revealed the formation of new functional groups, without significant changes in molecular weight and thermal stability. New gels based on hyaluronic acid modified derivatives were obtained by acrylic acid copolymerization in the presence of a redox initiation system. The resulted circular and interconnected pores of the gels were visualized by SEM. The release profiles of an ophthalmic model drug, pilocarpine from tested gels were studied in simulated media. Evaluation of the cytotoxicity and cell proliferation properties indicates the potential of the new systems to be used in contact with biological media in drug delivery applications. - Highlights: • New functionalized hyaluronic acid was prepared by ring opening of maleic anhydride. • Gels with circular pores based on acrylic acid copolymerization were formulated. • In vitro drug loading/release profile was evaluated in simulated ophthalmic media. • The cytotoxicity indicates the potential of derivatives to be used in vivo.

  16. Once-daily intravenous busulfan with therapeutic drug monitoring compared to conventional oral busulfan improves survival and engraftment in children undergoing allogeneic stem cell transplantation

    NARCIS (Netherlands)

    Bartelink, Imke H.; Bredius, Robbert G. M.; Ververs, Tessa T.; Raphael, Martine F.; van Kesteren, Charlotte; Bierings, Marc; Rademaker, Carin M. A.; den Hartigh, J.; Uiterwaal, Cuno S. P. M.; Zwaveling, Juliette; Boelens, Jaap J.

    2008-01-01

    Because of intra- and interindividual variability, bioavailability, and pharmacokinetics of busulfan (Bu) in children, oral busulfan without therapeutic drug monitoring (TDM) is assumed to be associated with higher graft failure rates as well as higher toxicity (eg, veno-occlusive disease [VOD]). Th

  17. [Comparison of the action of Cordemcura on selected cardiovascular parameters following intraduodenal and intravenous application in beagles].

    Science.gov (United States)

    Hübler, D; Mudhaffar, A A; Schilling, G; Elze, M; Chemnitius, K H

    1986-03-01

    The novel cardiotonic Cordemcura was tested for its cardiovascular effects after intraduodenal application to anaesthetized dogs. For this purpose, beagles received Cordemcura intraduodenally as a Tylose suspension, with 4 bolus injections (10(-5), 3 X 10(-5), 6 X 10(-5), and 10(-4) mol/kg) given at 30-min intervals. The test parameters used to analyze the onset of action and its course include: heart frequency (HFR), maximum rate of pressure rise (dp/dtmax) and decline (dp/dtmin) in the left ventricle, cardiac output (CO), stroke volume (SV), total peripheral resistance (TPR) and peripheral arterial blood pressure, systolic (Ps) and diastolic (Pd), and dose-effect curves determined for the individual test parameters. There was a dose-dependent increase of dp/dtmax up to a maximum of 130%, which 3 h afterwards was still about 60% above the initial value. The heart frequency, too, rose dose-dependently by a maximum of 80%, though not being significantly different from the initial value any longer 3 h after the last bolus injection. The Ps was slightly, but significantly decreased with the higher dose levels used. The influence on dp/dtmin and Pd was insignificant. A significant rise was found in the cardiac output, whereas the peripheral resistance showed a slight decline. After 3 h, a significant rise was still seen in the contractility (dp/dtmax), whereas the other parameters were no longer significantly different from the initial values. Moreover, selected dose levels of Cordemcura were tested after i. v. application, and a comparison was made of their effect on heart frequency, peripheral blood pressure, and inotropism. The importance of the findings was discussed.

  18. Fluorescence detection of Zabofloxacin, a novel fluoroquinolone antibiotic, in plasma, bile, and urine by HPLC: the first oral and intravenous applications in a pharmacokinetic study in rats.

    Science.gov (United States)

    Jin, Hyo Eon; Kang, In Hyul; Shim, Chang Koo

    2011-01-01

    To develop an HPLC method using fluorescence detection for the pharmacokinetic evaluation of levels of zabofloxacin, a novel broad spectrum fluoroquinolone antibiotic, in the plasma, bile and urine of rats. A simple reversed-phase HPLC method using a C18 column with fluorescence detection was developed and validated for the simultaneous determination of zabofloxain and enrofloxacin as an internal standard. The plasma sample was treated with methanol for protein precipitation, and treatment of the bile and urine samples included deproteinization and extraction using chloroform. The applicability of the developed assay method to pharmacokinetic studies of zabofloxacin in rats was examined. Zabofloxacin was intravenously and orally administered to rats at a dose of 20 mg/kg. The limits of quantification (LOQ) was determined to be 50 ng/mL for the plasma with acceptable linearity ranging from 50 to 25,000 ng/mL (R>0.999), and 0.5 μg/mL for the bile and urine samples with acceptable linearity ranging from 0.5 to 100 μg/mL (R>0.999). The validation parameters for zabofloxacin were found to be acceptable according to FDA assay validation (2001). While zabofloxacin in plasma and urine has been stable in all tested handling conditions, it has been unstable in bile during freeze-thaw cycles for 24 h at room temperature. Following intravenous and oral administration of zabofloxacin to rats at a dose of 20 mg/kg, concentration was quantifiable in plasma for up to 8 h. The bioavailability of zabofloxacin was 27.7%, and it was excreted into bile and urine at about 8% each per oral administration. These observations suggest that a validated assay can be used in pharmacokinetic studies of zabofloxacin in small animals. Due to the limited stability of zabofloxcin in rat bile, freeze-thaw cycles or prolonged handling at room temperature is not recommended. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on

  19. Administration and monitoring of intravenous anesthetics

    NARCIS (Netherlands)

    Sahinovic, Marko M.; Absalom, Anthony R.; Struys, Michel M. R. F.

    2010-01-01

    Purpose of review The importance of accuracy in controlling the dose-response relation for intravenous anesthetics is directly related to the importance of optimizing the efficacy and quality of anesthesia while minimizing adverse drug effects. Therefore, it is important to measure and control all

  20. Effects of intravenous administration of perzinfotel, fentanyl, and a combination of both drugs on the minimum alveolar concentration of isoflurane in dogs.

    Science.gov (United States)

    Ueyama, Yukie; Lerche, Phillip; Eppler, C Mark; Muir, William W

    2009-12-01

    OBJECTIVE-To determine the effects of IV administration of perzinfotel and a perzinfotel-fentanyl combination on the minimum alveolar concentration (MAC) of isoflurane in dogs. ANIMALS-6 healthy sexually intact Beagles (3 males and 3 females). PROCEDURES-All dogs were instrumented with a telemetry device for continuous monitoring of heart rate, arterial blood pressure, and core body temperature (at a femoral artery). Dogs were anesthetized with propofol (6 mg/kg, IV) and isoflurane. Isoflurane MAC values were determined in 3 experiments in each dog, separated by at least 7 days, before (baseline) and after the following treatments: no treatment (anesthetic only), perzinfotel (20 mg/kg, IV), fentanyl (5 microg/kg bolus, IV, followed by a continuous IV infusion at 0.15 microg/kg/min), and a fentanyl-perzinfotel combination (20 mg of perzinfotel/kg, IV, plus the fentanyl infusion). Bispectral index and oxygen saturation as measured by pulse oximetry were also monitored throughout anesthesia. RESULTS-Without treatment, the mean +/- SD isoflurane MAC for all 6 dogs was 1.41 +/- 0.10%. Baseline MAC was 1.42 +/- 0.08%. Intravenous administration of perzinfotel, fentanyl, and the perzinfotel-fentanyl combination significantly decreased the MAC by 39%, 35%, and 66%, respectively. Perzinfotel and perzinfotel-fentanyl administration yielded significant increases in the bispectral index. Mean, systolic, and diastolic arterial blood pressures significantly increased from baseline values when perzinfotel was administered. Systolic arterial blood pressure significantly increased from the baseline value when perzinfotel-fentanyl was administered. No adverse effects were detected. CONCLUSIONS AND CLINICAL RELEVANCE-IV administration of perzinfotel, fentanyl, or a perzinfotel-fentanyl combination reduced isoflurane MAC in dogs and increased arterial blood pressure.

  1. Applications of Fiberoptics-Based Nanosensors to Drug Discovery

    Science.gov (United States)

    Vo-Dinh, Tuan; Scaffidi, Jonathan; Gregas, Molly; Zhang, Yan; Seewaldt, Victoria

    2013-01-01

    Background Fiber-optic nanosensors are fabricated by heating and pulling optical fibers to yield sub-micron diameter tips, and have been used for in vitro analysis of individual living mammalian cells. Immobilization of bioreceptors (e.g., antibodies, peptides, DNA, etc) selective to target analyte molecules of interest provides molecular specificity. Excitation light can be launched into the fiber, and the resulting evanescent field at the tip of the nanofiber can be used to excite target molecules bound to the bioreceptor molecules. The fluorescence or surface-enhanced Raman scattering produced by the analyte molecules is detected using an ultra-sensitive photodetector. Objective This article provides an overview of the development and application of fiber-optic nanosensors for drug discovery. Conclusions The nanosensors provide minimally invasive tools to probe sub-cellular compartments inside single living cells for health effect studies (e.g., detection of benzopyrene adducts) and medical applications (e.g., monitoring of apoptosis in cells treated with anti-cancer drugs). PMID:23496274

  2. Development of a Computerized Intravenous Insulin Application (AutoCal) at Kaiser Permanente Northwest, Integrated into Kaiser Permanente HealthConnect: Impact on Safety and Nursing Workload

    OpenAIRE

    Olinghouse, Christine

    2012-01-01

    Context: The electronic medical record, HealthConnect, at the Kaiser Sunnyside Medical Center in the Northwest used scanned paper protocols for intravenous insulin administration. A chart review of 15 patients on intravenous insulin therapy using state-of-the-art paper-based column protocols revealed 40% deviation from the protocol. A time study of experienced nurses computing the insulin dose revealed an average of 2 minutes per calculation per hour to complete.

  3. 76 FR 46820 - Proposal To Refuse To Approve a Supplemental New Drug Application for Bromday (Bromfenac...

    Science.gov (United States)

    2011-08-03

    ... HUMAN SERVICES Food and Drug Administration Proposal To Refuse To Approve a Supplemental New Drug Application for Bromday (Bromfenac Ophthalmic Solution), 0.09%; Opportunity for a Hearing AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA), the...

  4. 78 FR 67985 - Supplemental Applications Proposing Labeling Changes for Approved Drugs and Biological Products

    Science.gov (United States)

    2013-11-13

    ... RLD throughout the lifecycle of the generic drug product (see Sec. 314.150(b)(10) (21 CFR 314.150(b... Applications Proposing Labeling Changes for Approved Drugs and Biological Products AGENCY: Food and Drug... drug or biological product to change the product labeling to reflect certain types of newly acquired...

  5. 77 FR 50121 - Hospira, Inc.; Withdrawal of Approval of a New Drug Application for DEXTRAN 70

    Science.gov (United States)

    2012-08-20

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Hospira, Inc.; Withdrawal of Approval of a New Drug... Drug Administration (FDA) is withdrawing approval of a new drug application (NDA) for DEXTRAN 70...

  6. 76 FR 43689 - Draft Guidance for Industry and Food and Drug Administration Staff; Mobile Medical Applications...

    Science.gov (United States)

    2011-07-21

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry and Food and Drug Administration Staff; Mobile Medical Applications; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of the...

  7. 78 FR 59038 - Mobile Medical Applications; Guidance for Industry and Food and Drug Administration Staff...

    Science.gov (United States)

    2013-09-25

    ... HUMAN SERVICES Food and Drug Administration Mobile Medical Applications; Guidance for Industry and Food and Drug Administration Staff; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of the guidance...

  8. MRI Based Localisation and Quantification of Abscesses following Experimental S. aureus Intravenous Challenge: Application to Vaccine Evaluation.

    Directory of Open Access Journals (Sweden)

    Elizabeth R Allen

    Full Text Available To develop and validate a sensitive and specific method of abscess enumeration and quantification in a preclinical model of Staphylococcus aureus infection.S. aureus infected murine kidneys were fixed in paraformaldehyde, impregnated with gadolinium, and embedded in agar blocks, which were subjected to 3D magnetic resonance microscopy on a 9.4T MRI scanner. Image analysis techniques were developed, which could identify and quantify abscesses. The result of this imaging was compared with histological examination. The impact of a S. aureus Sortase A vaccination regime was assessed using the technique.Up to 32 murine kidneys could be imaged in a single MRI run, yielding images with voxels of about 25 μm3. S. aureus abscesses could be readily identified in blinded analyses of the kidneys after 3 days of infection, with low inter-observer variability. Comparison with histological sections shows a striking correlation between the two techniques: all presumptive abscesses identified by MRI were confirmed histologically, and histology identified no abscesses not evident on MRI. In view of this, simulations were performed assuming that both MRI reconstruction, and histology examining all sections of the tissue, were fully sensitive and specific at abscess detection. This simulation showed that MRI provided more sensitive and precise estimates of abscess numbers and volume than histology, unless at least 5 histological sections are taken through the long axis of the kidney. We used the MRI technique described to investigate the impact of a S. aureus Sortase A vaccine.Post mortem MRI scanning of large batches of fixed organs has application in the preclinical assessment of S. aureus vaccines.

  9. Image-guided drug delivery: preclinical applications and clinical translation

    NARCIS (Netherlands)

    Ojha, Tarun; Rizzo, Larissa; Storm, Gert; Kiessling, Fabian; Lammers, Twan

    2015-01-01

    Image-guided drug delivery refers to the combination of drug targeting and imaging. Preclinically, image-guided drug delivery can be used for several different purposes, including for monitoring biodistribution, target site accumulation, off-target localization, drug release and drug efficacy. Clini

  10. Image-guided drug delivery : Preclinical applications and clinical translation

    NARCIS (Netherlands)

    Ojha, Tarun; Rizzo, Larissa; Storm, G; Kiessling, Fabian; Lammers, Twan

    2015-01-01

    Image-guided drug delivery refers to the combination of drug targeting and imaging. Preclinically, image-guided drug delivery can be used for several different purposes, including for monitoring biodistribution, target site accumulation, off-target localization, drug release and drug efficacy. Clini

  11. 78 FR 37231 - Guidance for Industry; Guidance on Abbreviated New Drug Applications: Stability Testing of Drug...

    Science.gov (United States)

    2013-06-20

    ... HUMAN SERVICES Food and Drug Administration Guidance for Industry; Guidance on Abbreviated New Drug... the availability of a guidance for industry entitled ``ANDAs: Stability Testing of Drug Substances and... generic drug review, FDA is recommending that the generic drug industry follow the approach in...

  12. Titanium MEMS Technology Development for Drug Delivery and Microfluidic Applications

    Science.gov (United States)

    Khandan, Omid

    The use of microelectromechanical systems (MEMS) technology in medical and biological applications has increased dramatically in the past decade due to the potential for enhanced sensitivity, functionality, and performance associated with the miniaturization of devices, as well as the market potential for low-cost, personalized medicine. However, the utility of such devices in clinical medicine is ultimately limited due to factors associated with prevailing micromachined materials such as silicon, as it poses concerns of safety and reliability due to its intrinsically brittle properties, making it prone to catastrophic failure. Recent advances in titanium (Ti) micromachining provides an opportunity to create devices with enhanced safety and performance due to its proven biocompatibility and high fracture toughness, which causes it to fail by means of graceful, plasticity-based deformation. Motivated by this opportunity, we discuss our efforts to advance Ti MEMS technology in two ways: 1) Through the development of titanium-based microneedles (MNs) that seek to provide a safer, simpler, and more efficacious means of ocular drug delivery, and 2) Through the advancement of Ti anodic bonding for future realization of robust microfluidic devices for photocatalysis applications. As for the first of these thrusts, we show that MN devices with in-plane geometry and through-thickness fenestrations that serve as drug reservoirs for passive delivery via diffusive transport from fast-dissolving coatings can be fabricated utilizing Ti deep reactive ion etching (Ti DRIE). Our mechanical testing and finite element analysis (FEA) results suggest that these devices possess sufficient stiffness for reliable corneal insertion. Our MN coating studies show that, relative to solid MNs of identical shank dimension, fenestrated devices can increase drug carrying capacity by 5-fold. Furthermore, we demonstrate that through-etched fenestrations provide a protective cavity for delivering

  13. Nanotechnology for delivery of drugs and biomedical applications.

    Science.gov (United States)

    Leucuta, Sorin Emilian

    2010-11-01

    Nanotechnology is a multidisciplinary scientific field that deals with the formulation, preparation, characterization and application of structures, devices and systems at nanometric scale. Area of concern is interdisciplinary, but with peculiarities, among others, medicine, pharmacy, biophysics, electronics, bioengineering, and molecular biology. Interest for modern nanotechnology lies in the creation and use of structures which have new properties because of their small size as well as the possibility of using these systems to control or manipulate biological structures at nanometric or atomic level. It will open the way to diagnosis and medical treatment to molecular level. This paper covers various fundamental and applied aspects of nanotechnology, in its chapters: introduction; nanoparticles (therapeutic polymers, polymeric nanoparticles, non-polymeric nanoparticles, liposomes, nanodevices) nanopharmaceutical systems used in diagnosis and therapy, in tissue engineering; pharmacokinetics and toxicity of nanoparticulate systems. Nanoparticulate systems have the potential to constitute a new generation of drug delivery systems. By their nature, nanodevices can be used as innovative diagnostic tool for detecting and monitoring disease, also for its treatment and use in developing new drugs.

  14. Screening applications in drug discovery based on microfluidic technology.

    Science.gov (United States)

    Eribol, P; Uguz, A K; Ulgen, K O

    2016-01-01

    Microfluidics has been the focus of interest for the last two decades for all the advantages such as low chemical consumption, reduced analysis time, high throughput, better control of mass and heat transfer, downsizing a bench-top laboratory to a chip, i.e., lab-on-a-chip, and many others it has offered. Microfluidic technology quickly found applications in the pharmaceutical industry, which demands working with leading edge scientific and technological breakthroughs, as drug screening and commercialization are very long and expensive processes and require many tests due to unpredictable results. This review paper is on drug candidate screening methods with microfluidic technology and focuses specifically on fabrication techniques and materials for the microchip, types of flow such as continuous or discrete and their advantages, determination of kinetic parameters and their comparison with conventional systems, assessment of toxicities and cytotoxicities, concentration generations for high throughput, and the computational methods that were employed. An important conclusion of this review is that even though microfluidic technology has been in this field for around 20 years there is still room for research and development, as this cutting edge technology requires ingenuity to design and find solutions for each individual case. Recent extensions of these microsystems are microengineered organs-on-chips and organ arrays.

  15. Injection Molding and its application to drug delivery.

    Science.gov (United States)

    Zema, Lucia; Loreti, Giulia; Melocchi, Alice; Maroni, Alessandra; Gazzaniga, Andrea

    2012-05-10

    Injection Molding (IM) consists in the injection, under high pressure conditions, of heat-induced softened materials into a mold cavity where they are shaped. The advantages the technique may offer in the development of drug products concern both production costs (no need for water or other solvents, continuous manufacturing, scalability, patentability) and technological/biopharmaceutical characteristics of the molded items (versatility of the design and composition, possibility of obtaining solid molecular dispersions/solutions of the active ingredient). In this article, process steps and formulation aspects relevant to IM are discussed, with emphasis on the issues and advantages connected with the transfer of this technique from the plastics industry to the production of conventional and controlled-release dosage forms. Moreover, its pharmaceutical applications thus far proposed in the primary literature, intended as either alternative manufacturing strategies for existing products or innovative systems with improved design and performance characteristics, are critically reviewed.

  16. Legal Responsibility of Doctor Regarding off-label Drug Applications

    Directory of Open Access Journals (Sweden)

    Erdal Yüzbaşıoğlu

    2012-03-01

    Full Text Available The use of off-label medication, which has been frequently applied in oncology, also started to be used in ophthalmology recently; thus, the legal problems that the doctors can encounter more often come up to be a topic of discussion. According to the drug administration guidelines released by the Ministry of Health, off-label medication depends on certain conditions, and applications other than these will be accepted as an experiment on humans according to the law No 5237 of the Turkish Criminal Code (TCC. The aim of this study was to clarify this issue in accordance with the justification of TCC/90. (Turk J Ophthalmol 2012; 42: 135-8

  17. Clinical trial with intravenous clonidine in treatment of severe hypertension

    Directory of Open Access Journals (Sweden)

    Gadgil U

    1977-01-01

    Full Text Available Thirty six patients with severe hypertension were treated with intravenous clonidine. In 67% of cases maximum response was obtained within 11 hours of administration of the drug. Aver-age reduction in mean arterial pressure was 29%. Paradoxical rise in blood pressure was observed in some patients, immediately after clonidine administration. This could be prevented with prior administration of phentolamine intravenously. Clonidine (I.V. sup-plied by two drug firms gave identical results.

  18. 77 FR 58999 - Draft Guidance for Industry on Abbreviated New Drug Applications: Stability Testing of Drug...

    Science.gov (United States)

    2012-09-25

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Abbreviated New Drug... availability of a draft guidance for industry entitled ``ANDAs: Stability Testing of Drug Substances and... of a draft guidance for industry entitled ``ANDAs: Stability Testing of Drug Substances and...

  19. Post-marketing safety evaluation of the intravenous anti-influenza neuraminidase inhibitor peramivir: A drug-use investigation in patients with high risk factors.

    Science.gov (United States)

    Komeda, Takuji; Ishii, Shingo; Itoh, Yumiko; Sanekata, Masaki; Yoshikawa, Takayoshi; Shimada, Jingoro

    2016-10-01

    Peramivir, the only injectable anti-influenza neuraminidase inhibitor medically available in Japan at present, is considered first-line treatment in patients with high risk factors for influenza exacerbation. We conducted a drug-use investigation of peramivir in inpatients with high risk factors (old age, pregnancy, and underlying disease such as chronic respiratory disease) from January 2010 to March 2013. Data of 772 patients from 124 facilities across Japan were collected; peramivir's safety in 770 patients and effectiveness in 688 patients were examined. In total, 412 adverse events were observed in 219 patients (28.4%). Of these, 155 events were adverse drug reactions (ADRs) observed in 98 patients (12.7%). Major ADRs (≥2%) were increased aspartate aminotransferase (5.1%), increased alanine aminotransferase (3.8%) and decreased white blood cell count (2.5%). Fourteen serious ADRs were observed in 12 patients (1.6%). All serious ADRs were resolved or improved except for two events for which outcomes were unknown. Multivariate analyses revealed that ADR incidences were significantly associated with these four backgrounds of patients: medical history, no influenza vaccination, renal impairment and other infection(s). With regard to its effectiveness, the median time to alleviation of both influenza symptoms and fever was 3 days, including the first day of administration, which was the same as in other previous surveillance studies. This surveillance study indicated the safety of peramivir in the treatment of influenza inpatients with high risk factors under routine clinical settings. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. [Anaesthesia and vasomotor tone during CPB: intravenous anaesthetics].

    Science.gov (United States)

    Durand, M

    2012-05-01

    Anaesthesia during CBP is frequently provided using intravenous anaesthetic drugs, particularly propofol. The effects of the different drugs have been studied during CPB. These drugs have an arterial and venous vasodilator effect during CPB which is dose dependent and is more pronounced for propofol. High doses of propofol or thiopental reduce cerebral blood flow but provide no additional neurological protection.

  1. Intravenous lipid emulsion and dexmedetomidine for treatment of feline permethrin intoxication: a report from 4 cases

    Directory of Open Access Journals (Sweden)

    G. Ceccherini

    2015-08-01

    Full Text Available Four cases of feline permethrin intoxication are described. The cause of intoxication is the application of canine permethrin spot-on product (Advantix®, Bayer by the owners. Principal clinical guidelines recommends the use of anticonvulsant drugs to treat seizures or neurological symptoms after initial stabilization and dermal decontamination. The use of lipid emulsion had an increasing interest in the last decade for treatment of toxicosis caused by lipophilic drugs as reported in human and in veterinary medical practices. All cats presented in this study, were treated with intravenous lipid emulsion (ILE at variable dosages, and dexmedetomidine was also administered by intravenous way. No adverse reaction such as thrombophlebitis, overload circulation or others was noticed during and after administration of ILE. Dexmedetomidine was proved to be helpful in tranquillizing the cats. All cats were discharged in good condition faster than other cases treated without their use.

  2. Application of SHEL model in safety management of intravenous medication nursing in emergency department%SHEL模式在急诊静脉用药护理安全管理中的应用分析

    Institute of Scientific and Technical Information of China (English)

    林喜爱

    2012-01-01

    目的 评价SHEL模式在急诊静脉用药护理安全管理中的应用效果.方法 对比分析SHEL模式实施前后静脉用药护理安全缺陷、急诊科护士用药安全知识的变化.结果 除皮试阳性结果判断标准外,SHEL模式实施后的其余四个主题的得分均显著优于SHEL模式实施前;SHEL模式实施后静脉用药缺陷率为35.7%,显著低于SHEL模式实施前的60.0%(X2=5.893,P=0.015).结论 SHEL模式能够显著降低急诊科静脉用药缺陷,是一种有效的护理安全管理工作方法.%Objective To assess the effect of the SHEL model in safety management of intravenous medication nursing in emergency department.Methods The changes of intravenous medication errors and knowledge of medication nursing safety in emergency nurses were compared after application of the SHEL model.Results Medication nursing safety knowledge,except judgement of skin test results.was significantly improved after application of the SHEL model The rate of intravenous medication errors was 35.7% after application of the SHEL model,which was decreased significantly as compared with the baseline ( X2 =5.893,P=0.015 ).Conclusions The SHEL model can markedly reduce intravenous medication errors in emergency department and is a management method for nursing safety.

  3. 78 FR 58318 - Clinical Trial Design for Intravenous Fat Emulsion Products; Public Workshop

    Science.gov (United States)

    2013-09-23

    ... HUMAN SERVICES Food and Drug Administration Clinical Trial Design for Intravenous Fat Emulsion Products... ``Clinical Trial Design for Intravenous Fat Emulsion Products.'' This workshop will provide a forum to discuss trial design of clinical trials intended to support registration of intravenous fat...

  4. PEGylation of superparamagnetic iron oxide nanoparticle for drug delivery applications with decreased toxicity: an in vivo study

    Energy Technology Data Exchange (ETDEWEB)

    Prabhu, Suma [Manipal University, Department of Radiation Biology & Toxicology, School of Life Sciences (India); Mutalik, Srinivas [Manipal University, Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences (India); Rai, Sharada [Manipal University, Department of Pathology, Kasturba Medical College (India); Udupa, Nayanabhirama [Manipal University, Director - Research (Health Sciences) (India); Rao, Bola Sadashiva Satish, E-mail: satishraomlsc@gmail.com, E-mail: rao.satish@manipal.edu [Manipal University, Department of Radiation Biology & Toxicology, School of Life Sciences (India)

    2015-10-15

    Superparamagnetic iron oxide nanoparticles (SPIONs) are evolving as a mainstay across various applications in the field of Science and Technology. SPIONs have enticed attention on the grounds of their unique physicochemical properties as well as potential applications in magnetic hyperthermia, immunoassays, as a contrast agent in magnetic resonance imaging and targeted drug delivery among others. Toward this goal, we synthesized SPIONs by chemical co-precipitation and PEGylated it. PEGylated SPIONs (PS) were studied for its detailed in vivo toxicity profile, in view of further surface engineering for its clinical applications. The intravenous LD{sub 50(14)} of the PS was ascertained as 508.16 ± 41.52 mg/kg b wt. Histopathology of the vital organs of the animals injected with acute toxic doses showed pathological changes in spleen, lung, liver, and kidney. Accumulation of SPION was found in the aforementioned organs as confirmed by Prussian blue staining. Further, 1/10th dose of LD{sub 50(14)} of PS and the Bare SPION (BS) was used to analyze a detailed toxicity profile, including genotoxicity (micronuclei formation and chromosomal aberration assays), organ-specific toxicity (a detailed serum biochemical analysis), and also determination of oxidative stress. The results of toxicity profile indicated no significant toxicity due to systemic exposure of PS. Atomic absorption spectroscopy (AAS) analysis confirmed the accumulation of SPION majorly in lungs, liver spleen, and kidneys. The present study thus indicated an optimal dose of PS which could be used for surface modification for targeted drug delivery applications with least toxicity.

  5. PEGylation of superparamagnetic iron oxide nanoparticle for drug delivery applications with decreased toxicity: an in vivo study

    Science.gov (United States)

    Prabhu, Suma; Mutalik, Srinivas; Rai, Sharada; Udupa, Nayanabhirama; Rao, Bola Sadashiva Satish

    2015-10-01

    Superparamagnetic iron oxide nanoparticles (SPIONs) are evolving as a mainstay across various applications in the field of Science and Technology. SPIONs have enticed attention on the grounds of their unique physicochemical properties as well as potential applications in magnetic hyperthermia, immunoassays, as a contrast agent in magnetic resonance imaging and targeted drug delivery among others. Toward this goal, we synthesized SPIONs by chemical co-precipitation and PEGylated it. PEGylated SPIONs (PS) were studied for its detailed in vivo toxicity profile, in view of further surface engineering for its clinical applications. The intravenous LD50(14) of the PS was ascertained as 508.16 ± 41.52 mg/kg b wt. Histopathology of the vital organs of the animals injected with acute toxic doses showed pathological changes in spleen, lung, liver, and kidney. Accumulation of SPION was found in the aforementioned organs as confirmed by Prussian blue staining. Further, 1/10th dose of LD50(14) of PS and the Bare SPION (BS) was used to analyze a detailed toxicity profile, including genotoxicity (micronuclei formation and chromosomal aberration assays), organ-specific toxicity (a detailed serum biochemical analysis), and also determination of oxidative stress. The results of toxicity profile indicated no significant toxicity due to systemic exposure of PS. Atomic absorption spectroscopy (AAS) analysis confirmed the accumulation of SPION majorly in lungs, liver spleen, and kidneys. The present study thus indicated an optimal dose of PS which could be used for surface modification for targeted drug delivery applications with least toxicity.

  6. Natural Polymers and their Application in Drug Delivery and Biomedical Field

    Directory of Open Access Journals (Sweden)

    Jana S*,1

    2011-01-01

    Full Text Available Biodegradable polymers are widely being studied as a potential carrier material for site specific drug delivery because of its non-toxic,biocompatible in nature. Natural polysaccharides have been investigated for drug delivery applications as well as in biomedical fields. Modified polymer has found its application as a support material for gene delivery, cell culture, and tissue engineering. Now a day, the polymer is being modified to obtain novel biomaterial for controlled drug delivery applications. This review provides an overview of the different modified polymer derivatives and their applications with special attention being put on controlled drug delivery and biomedical engineering.

  7. Pain management in emergency department: intravenous morphine vs. intravenous acetaminophen

    Directory of Open Access Journals (Sweden)

    Morteza Talebi Doluee

    2015-01-01

    Full Text Available Pain is the most common complaint in emergency department and there are several methods for its control. Among them, pharmaceutical methods are the most effective. Although intravenous morphine has been the most common choice for several years, it has some adverse effects. There are many researches about intravenous acetaminophen as an analgesic agent and it appears that it has good analgesic effects for various types of pain. We searched some electronic resources for clinical trials comparing analgesic effects of intravenous acetaminophen vs. intravenous morphine for acute pain treatment in emergency setting.In two clinical trials, the analgesic effect of intravenous acetaminophen has been compared with intravenous morphine for renal colic. The results revealed no significant difference between analgesic effects of two medications. Another clinical trial revealed that intravenous acetaminophen has acceptable analgesic effects on the post-cesarean section pain when combined with other analgesic medications. One study revealed that administration of intravenous acetaminophen compared to placebo before hysterectomy decreased consumption of morphine via patient-controlled analgesia pump and decreased the side effects. Similarly, another study revealed that the infusion of intravenous acetaminophen vs. placebo after orthopedic surgery decreased the consumption of morphine after the surgery. A clinical trial revealed intravenous acetaminophen provided a level of analgesia comparable to intravenous morphine in isolated limb trauma, while causing less side effects than morphine.It appears that intravenous acetaminophen has good analgesic effects for visceral, traumatic and postoperative pains compare with intravenous morphine.

  8. Use of intravenous immunoglobulin in pediatric practice

    Science.gov (United States)

    Zülfikar, Bülent; Koç, Başak

    2014-01-01

    In recent years, human-driven intravenous immunoglobulins (IVIG) administered intravenously have been widely used in treatment of many diseases. Intravenous immunoglobulin is obtained from human-driven plasma pools as in other plasma-driven products and IVIG preperations contain structurally and functionally intact immunoglobulin. Intravenous immunoglobulin was approved by FDA (Food and Drug Administration) in USA in 1981 for the first time and was started to be primarily used in patients with immune deficiency with hypogammaglobulinemia. The effects of intravenous immunoglobulin include complex mechanisms, but it exerts its essential action by eliminating the non-specific Fc receptors found in the mononuclear phagocytic system or by inhibiting binding of immune complexes to Fc receptors in the cells. Their areas of usage include conditions where their anti-inflammatory and immunomudulator effects are utilized in addition to replacement of deficient immunoglobulin. Although the definite indications are limited, it has been shown that it is useful in many diseases in clinical practice. Its side effects include fever, sweating, nausea, tachycardia, eczematous reactions, aseptic meningitis, renal failure and hematological-thromboembolic events. In this article, use of IVIG, its mechanisms of action, indications and side effects were discussed. PMID:26078679

  9. 静脉留置针在深部游离组织瓣移植中监测血供的临床应用%Clinical application of intravenous catheter in monitoring blood supply of deep free flap graft

    Institute of Scientific and Technical Information of China (English)

    胡广伟; 廖天安; 王鸿; 邱勋永

    2012-01-01

    目的:评价静脉留置针在深部游离组织瓣移植中监测血供的临床应用价值.方法:应用腓骨肌(皮)瓣、髂骨肌骨瓣、前臂皮瓣等游离移植修复组织缺损的病例共26例,年龄22~ 70岁,在深部游离组织瓣静脉远心端留置静脉针,术后通过静脉留置针输注低分子右旋糖酐,20ml/h,持续7天,并给予罂粟碱30mg肌肉注射,1次/8h,抗凝及扩血管处理.结果:7天内现测25例静脉留置针滴注通畅,有1例患者在术后48h内出现静脉留置针滴速变慢,给予灌注稀释肝素生理盐水后阻力恢复正常.26例深部组织瓣全部存活,未出现血管危象.结论:静脉留置针在深部游离组织瓣移植应用能持续监测组织瓣血管通畅状况,有效预防静脉血栓形成,提高组织瓣的成活率.%Objective To assess the clinical application value of intravenous catheter in monitoring blood supply of deep free flap graft. Methods 26 cases of tissue defects which were reconstructed by free radical fibular osteocutaneous flap,iliac osteomusculocutaneous flap,forearm flaps,the age from 22 to 70,were treated with intravenous catheter from distal vein of deep free flap by which intravenous drip dextran-40 were given,average 20 milliliter each hour and last 7 days.The patients were given narceine 30mg, intramuscular injection every 8 hour anticoagulation and vasodilator therapy by routine. Results Distal intravenous catheter of 25 cases kept fluent, and intravenous catheter of 1 case appeared slow,became normal after repeated infusion of dilute heparin saline.26 cases'deep free flaps were all survived without occurring vascular crisis. Conclusion Application of intravenous catheter in deep free flap graft can monitor blood supply of free flap continuously, prevent venous thrombosis effectively and improve flap survival.

  10. Correlação anátomo-clínica: granulomatose sistêmica por talco em drogadicto hiv negativo Systemic talc granulomatosis in a HIV-negative intravenous drug addict

    Directory of Open Access Journals (Sweden)

    D.F. da Cunha

    1999-07-01

    Full Text Available É descrita a correlação anatomopatológica de um paciente usuário de drogas injetáveis com talcose sistêmica acometendo pulmões, pleuras, fígado, baço e linfonodos e que desenvolveu hipertensão arterial pulmonar e cor pulmonale. Destaca-se o fato de que apesar do uso crônico de drogas injetáveis e outros comportamentos de alto risco para infecção pelo retrovírus, o paciente era HIV negativo, não apresentava linfocitopenia, nem alterações histopatológicas compatíveis com AIDS à necropsia.Anatomo-pathological correlation in a case of systemic talc granulomatosis affecting lungs, pleura, liver, spleen and mesenteric lymph nodes resulting in pulmonary arterial hypertension and cor pulmonale is described. The patient, a 26-year-old male HIV-negative intravenous drug addict had no lymphopenia or any histopathologic findings at necroscopy compatible with AIDS, despite of a chronic high-risk behavior favoring this illness.

  11. Modelling Framework and Assistive Device for Peripheral Intravenous Injections

    Science.gov (United States)

    Kam, Kin F.; Robinson, Martin P.; Gilbert, Mathew A.; Pelah, Adar

    2016-02-01

    Intravenous access for blood sampling or drug administration that requires peripheral venepuncture is perhaps the most common invasive procedure practiced in hospitals, clinics and general practice surgeries.We describe an idealised mathematical framework for modelling the dynamics of the peripheral venepuncture process. Basic assumptions of the model are confirmed through motion analysis of needle trajectories during venepuncture, taken from video recordings of a skilled practitioner injecting into a practice kit. The framework is also applied to the design and construction of a proposed device for accurate needle guidance during venepuncture administration, assessed as consistent and repeatable in application and does not lead to over puncture. The study provides insights into the ubiquitous peripheral venepuncture process and may contribute to applications in training and in the design of new devices, including for use in robotic automation.

  12. Recent HIV-1 Outbreak Among Intravenous Drug Users in Romania: Evidence for Cocirculation of CRF14_BG and Subtype F1 Strains.

    Science.gov (United States)

    Niculescu, Iulia; Paraschiv, Simona; Paraskevis, Dimitrios; Abagiu, Adrian; Batan, Ionelia; Banica, Leontina; Otelea, Dan

    2015-05-01

    Since 2011, Romania has faced an HIV outbreak among injecting drug users (IDUs). Our aim was to identify and describe clinical and epidemiological patterns of this outbreak. A cross-sectional study enrolled 138 IDUs diagnosed with HIV infection between 2011 and 2013 with 58 sexually infected individuals included as the control group. The IDUs had a long history of heroin abuse (10 years) and a recent history of new psychostimulant injection (3-4 years). Classical epidemiological data and molecular techniques were used to describe the transmission dynamics. A high prevalence of hepatitis C virus (HCV) coinfection was noted (98.6%) compared to the control group (10.3%) (p<0.001). IDUs had initially been infected with HCV. HIV infection was more recent, linked to starting injecting stimulants. HIV subtype analysis showed a predominance of the local F1 strain in both IDUs and sexually infected patients; in IDUs it also identified 28 CRF14_BG recombinants and six unique recombinant forms (URFs) between F1 and CRF14_BG. A few patients from both risk groups were infected with subtype B. Among IDUs, CRF14_BG was associated with a lower CD4 cell count and more advanced stages of disease, which correlated with CXCR4 tropism. Phylogenetic analysis revealed the spread of HIV through three major IDU clusters of recent date. Among IDUs with CRF14_BG, some reported travel abroad (Spain, Greece). By identifying clusters of IDUs with related viruses, molecular epidemiologic methods provide valuable information on patterns of HIV transmission that can be useful in planning appropriate harm reduction interventions.

  13. Risk Factors Associated with Unsafe Injection Practices at the First Injection Episode among Intravenous Drug Users in France: Results from PrimInject, an Internet Survey

    Directory of Open Access Journals (Sweden)

    Anne Guichard

    2015-01-01

    Full Text Available Background. New drug use patterns may increase the risk of human immunodeficiency virus and hepatitis infections. In France, new injection patterns among youths with diverse social backgrounds have emerged, which may explain the persistently high rates of hepatitis C virus infection. This study explores factors associated with injection risk behaviours at first injection among users who began injecting in the post-2000 era. Methods. A cross-sectional study was conducted on the Internet from October 2010 to March 2011, through an online questionnaire. Multivariate logistic regression identified the independent correlates of needle sharing and equipment (cooker/cotton filter sharing. Results. Among the 262 respondents (mean age 25 years, 65% were male. Both risk behaviours were positively associated with initiation before 18 years of age (aOR 3.7 CI 95% 1.3–10.6 and aOR 3.0 CI 95% 1.3–7.0 and being injected by another person (aOR 3.1 CI 95% 1.0–9.9 and aOR 3.0 CI 95% 1.3–7.1. Initiation at a party was an independent correlate of equipment sharing (aOR 2.6 95% CI 1.0–6.8. Conclusions. Results suggest a need for innovative harm reduction programmes targeting a variety of settings and populations, including youths and diverse party scenes. Education of current injectors to protect both themselves and those they might initiate into injection is critically important.

  14. Antiparasitic peptides from arthropods and their application in drug therapy

    Directory of Open Access Journals (Sweden)

    Ariane Ferreira Lacerda

    2016-02-01

    Full Text Available Africa, Asia and Latin America are regions highly affected by endemic diseases, such as Leishmaniasis, Malaria and Chagas’ disease. They are responsible for the death of thousands of patients every year, as there is not yet a cure for them and the drugs used are inefficient against the pathogenic parasites. During the life cycle of some parasitic protozoa, insects become the most important host and disseminator of the diseases triggered by these microorganisms. As infected insects do not develop nocive symptoms, they can carry the parasites for long time inside their body, enabling their multiplication and life cycle completion. Eventually, parasites infect human beings after insects transmission through their saliva and/or feces. Hence, host insects and general arthropods, which developed a way to coexist with such parasites, are a promising source for the prospection of antiparasitic compounds, as alternative methods for the treatment of protozoa-related diseases. Among the molecules already isolated and investigated, there are proteins and peptides with high activity against parasites, able to inhibit parasite activity in different stages of development. Although studies are still taking their first steps, initial results show new perspectives on the treatment of parasitic diseases. Therefore, in this report, we describe about peptides from host insect sources with activity against the three most endemic parasites: Leishmania sp, Plasmodium sp. and Trypanosomes. Moreover, we discuss the future application insect peptides as anti-parasitic drugs and the use of non-hosts insect transcriptomes on the prospection of novel molecules for the treatment of parasitic neglected diseases.

  15. Application of gold nanoparticles for improved drug efficiency

    Science.gov (United States)

    Shittu, K. O.; Bankole, M. T.; Abdulkareem, A. S.; Abubakre, O. K.; Ubaka, A. U.

    2017-09-01

    Due to increasing resistance of microorganisms towards current antibiotics, there is a need for new or enhanced antibiotics. Nanotechnology is a technology that enhances the use of gold nanoparticles (AuNP) in area of medical applications, especially as a drug carrier for targeted drug delivery. In this research, AuNPs was synthesized using biological method via bioreduction of Piper guineense aqueous leaf extract on tetra gold chloride, characterized using UV-Vis spectrophometer, DLS, TEM/EDS and FTIR. The synthesized AuNPs was covalently functionalized with polyethylene glycol and encapsulated with Lincomycin and in vitro dissolution methods was used to evaluate the potential performance of the formulated nanodrug. The nanodrug has highest release efficiency at the 9th minutes (23.4 mg ml-1 for 40 °C) and (29.5 mg ml-1 for 60 °C) compared with the non-nanodrug. The antibacterial potential of the nanodrug was seen on the gram-positive bacteria of Staphylococcus aureus and Streptococcus pyogenes with highest inhibitions of 18 mm (at 40 °C) and 16 mm (at 60 °C) for S. aureus, and 16 mm for S. pyogenes (both at 40 °C and 60 °C). The bacteria growth inhibition continued and lasted for 15 min, while that of non-nanodrug lasted for 9 min with lesser growth inhibition compared to the formulated nanodrug. This work shows that the presence of the AuNPs increased the release efficiency of lincomycin even at a lower concentration and also bacteria growth inhibition thereby suggesting the effectiveness of the nanodrug formulation.

  16. Template synthesized chitosan nano test tubes for drug delivery applications

    Science.gov (United States)

    Perry, Jillian L. Moulton

    (glutathione) found within cells. Therefore, once the nano test tubes reach their target site and are taken into a cell, the tubes can be degraded and release their payload. This chitosan nano test tube delivery stystem shows great potential for applications in targeted drug delivery. (Full text of this dissertation may be available via the University of Florida Libraries web site. Please check http://www.uflib.ufl.edu/etd.html)

  17. Drug: D04516 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D04516 Drug Immune globulin intravenous pentetate (USAN); Macroscint (TN) Diagnosti...c aid USP drug classification [BR:br08302] Immunological Agents Immunizing Agents, Passive Immune Globulin I...ntravenous (Human) D04516 Immune globulin intravenous pentetate (USAN) CAS: 145464-27-3 PubChem: 47206363 ...

  18. 77 FR 24724 - Sanofi-aventis, U.S., LLC; Withdrawal of Approval of a New Drug Application for OFORTA

    Science.gov (United States)

    2012-04-25

    ... HUMAN SERVICES Food and Drug Administration Sanofi-aventis, U.S., LLC; Withdrawal of Approval of a New Drug Application for OFORTA AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is withdrawing approval of a new drug application (NDA) for...

  19. The safety of a loading dose of intravenous antiepileptic drugs%静脉应用负荷剂量抗癫痫药物的安全性

    Institute of Scientific and Technical Information of China (English)

    宿英英; 田飞; 陈卫碧; 高冉; 张运周; 张艳; 叶红; 高岱俭; 刘芳

    2013-01-01

    和骨髓抑制分别为3、2、5和1例.地西泮组不良反应发生率明显低于地西泮后续苯巴比妥组(P =0.033).上述不良反应经停药与对症治疗后均可消除. 结论 静脉给予负荷剂量地西泮或丙戊酸或苯巴比妥治疗成人GCSE均安全有效.用药过程中应密切监测患者的不良反应,特别是对地西泮与苯巴比妥联用的患者.一旦出现不良反应,应及时停药并予以对症治疗.%Objective To investigate the safety of a loading dose of Ⅳ antiepileptic drugs (AED)in the treatment of adult patients with generalized convulsive status epilepticus (GCSE).Methods A method for the analysis of pooled data was adopted.The results from the two prospective randomized controlled trials (RCTs) performed by Xuanwu Hospital from January 2007 to January 2010 and from June 2010 to May 2012 were collected.The clinical data were analyzed and compared among the patients in the diazepam group,the diazepam and subsequent valproate group,and the diazepam and subsequent phenobarbital group.A loading dose of Ⅳ diazepam (0.2 mg/kg,5 mg/min) was as first-line AED treatment for all patients in the 3 groups.Second-line AED treatment were as follows:in the diazepam group,a loading dose of Ⅳ diazepam (0.2 mg/kg,5mg/min) was given,then a maintenance dose of Ⅳ diazepam (4.0 mg/h,increase by 1.0 μg/kg every 3 minutes) was given via a pump.In the diazepam subsequent valproate group,a loading dose of Ⅳ diazepam [30 mg/kg,6 mg/(kg · min)] was given,then a maintenance dose of Ⅳ valproate 1-2 mg/(kg · h) was given via a pump.In the diazepam subsequent phenobarbital group,a loading dose of Ⅳ phenobarbital (20 mg/kg,50 mg/min) was given,then a maintenance dose of Ⅳ phenobarbital (100 mg/6 h,50 mg/min) was given.The second-line AED treatment should be continued until 24 hours after epileptic seizure stopped,then the dosage was gradually reduced.The patients should be closely monitored for reactions after drug administration.Results A total of

  20. Model-based drug development: strengths, weaknesses, opportunities, and threats for broad application of pharmacometrics in drug development.

    Science.gov (United States)

    Wetherington, Jeffrey D; Pfister, Marc; Banfield, Christopher; Stone, Julie A; Krishna, Rajesh; Allerheiligen, Sandy; Grasela, Dennis M

    2010-09-01

    Systematic implementation of model-based drug development (MBDD) to drug discovery and development has the potential to significantly increase the rate of medical breakthroughs and make available new and better treatments to patients. An analysis of the strengths, weaknesses, opportunities, and threats (ie, SWOT) was conducted through focus group discussions that included 24 members representing 8 pharmaceutical companies to systematically assess the challenges to implementing MBDD into the drug development decision-making process. The application of the SWOT analysis to the successful implementation of MBDD yielded 19 strengths, 27 weaknesses, 34 opportunities, and 22 threats, which support the following conclusions. The shift from empirical drug development to MBDD requires a question-based mentality; early, proactive planning; dynamic access to multisource data; quantitative knowledge integration; multidisciplinary collaboration; effective communication and leadership skills; and innovative, impactful application of pharmacometrics focused on enhancing quantitative decision making. The ultimate goal of MBDD is to streamline discovery and development of innovative medicines to benefit patients.

  1. 75 FR 65642 - Withdrawal of Approval of New Animal Drug Applications; Aklomide; Levamisole Hydrochloride...

    Science.gov (United States)

    2010-10-26

    ...The Food and Drug Administration (FDA) is withdrawing approval of eight new animal drug applications (NADAs). In a final rule published elsewhere in this issue of the Federal Register, FDA is amending the animal drug regulations to remove portions reflecting approval of these...

  2. 78 FR 70062 - Withdrawal of Approval of New Animal Drug Applications; Carbarsone; Roxarsone

    Science.gov (United States)

    2013-11-22

    ...; Carbarsone; Roxarsone AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is withdrawing approval of three new animal drug applications (NADAs) for roxarsone or... longer manufactured or marketed: NADA 007-891 for 3-NITRO (roxarsone) Type A medicated article, NADA...

  3. 78 FR 46984 - Pfizer, Inc.; Withdrawal of Approval of a New Drug Application for BEXTRA

    Science.gov (United States)

    2013-08-02

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Pfizer, Inc.; Withdrawal of Approval of a New Drug... Administration (FDA) is withdrawing approval of a new drug application (NDA) for BEXTRA (valdecoxib) 10...

  4. 76 FR 60504 - Guidance for Industry on Time and Extent Applications for Nonprescription Drug Products...

    Science.gov (United States)

    2011-09-29

    ... HUMAN SERVICES Food and Drug Administration (Formerly 2004D-0027) Guidance for Industry on Time and... a guidance for industry entitled ``Time and Extent Applications for Nonprescription Drug Products... in 21 CFR part 25 and the guidance for industry entitled ``Environmental Assessment of Human Drug...

  5. The effect size, study design, and development experience in commercially sponsored studies for new drug applications in approved drugs

    OpenAIRE

    Fukunaga, Satoshi; Kusama, Makiko; Ono, Shunsuke

    2014-01-01

    Pharmaceutical companies incorporate different features into the trials for new drug applications (NDAs) to render them efficient, making use of their experience. The objective of this analysis was to examine the associations between outcome and features related to study design and clinical development experience in commercially sponsored clinical trials. We collected data of phase 2 and phase 3 trials of all the drugs that obtained approval for depression, schizophrenia, asthma, hypertension...

  6. Proteomics profile of cellular response to chiral drugs: prospects for pharmaceutical applications.

    Science.gov (United States)

    Bun Ching, Chi; Zhang, Jianhua; Sui, Jianjun; Ning Chen, Wei

    2010-02-01

    Chiral drugs account for a large proportion of drugs available in the market. There is increasing awareness of the importance of drug chirality and the role it plays in explaining the oftentimes dramatic differences in biological activities in the current drug development portfolio. Using recently developed chiral drugs-cell interaction system, several examples of protein profiles induced by chiral drugs were illustrated in detail on the platform of 2-D LC interfaced with MS/MS system. In addition, the background of chiral drug investigation from which contemporary drug chirality research has emerged, the techniques involved in proteomics technology, the application of proteomics in this exciting area, and the perspectives in future applications are also discussed.

  7. QCC活动在儿科病房静脉输液穿刺中的推广应用%The application of Quality Control Circle on intravenous in the pediatric ward

    Institute of Scientific and Technical Information of China (English)

    戴可蓉; 冯佳俊

    2014-01-01

    Objective: To explore the effect of quality control circle i on intravenous in the pediatric ward. Methods: The quality control circle team reviewed 240 hospitalized patients in the pediatric ward from March 2012 to September 2012,analyzed intravenous causes, set the goals, develop counter measures, put them into effect, and confirmed the intravenous success rate of hospitalized patients after the application of quality control circle from March 2012 to September 2012. Result: The intravenous success rate of hospitalized patients increased from 79.58% to 96.67% after the application of quality control circle and the difference was significant (P<0.05). Conclusions: The application of the quality improvement tool of"quality control circle" could increase the intravenous success rate of hospitalized patients and improve the ability of the circle members.%目的:探讨QCC在儿科病房静脉输液穿刺中的应用效果。方法:成立品管圈,在儿科病房静脉输液穿刺管理中融入品管圈的手法和技巧,对儿科病房静脉输液穿刺中存在的问题进行改进,并将改进前后状况进行比较。结果:儿科病房静脉输液穿刺一次成功率由79.58%升至96.67%。护士专业知识得到加强,沟通协调能力提高,工作幸福感、积极性及科室团队凝聚力大幅上升,圈员运用QCC的能力从0分上升到5分。结论:运用QCC对注射室进行管理,不仅降低了差错率,节省了医院开支,还提高了护理队伍的整体素质。

  8. Mining unexpected temporal associations: applications in detecting adverse drug reactions.

    Science.gov (United States)

    Jin, Huidong Warren; Chen, Jie; He, Hongxing; Williams, Graham J; Kelman, Chris; O'Keefe, Christine M

    2008-07-01

    In various real-world applications, it is very useful mining unanticipated episodes where certain event patterns unexpectedly lead to outcomes, e.g., taking two medicines together sometimes causing an adverse reaction. These unanticipated episodes are usually unexpected and infrequent, which makes existing data mining techniques, mainly designed to find frequent patterns, ineffective. In this paper, we propose unexpected temporal association rules (UTARs) to describe them. To handle the unexpectedness, we introduce a new interestingness measure, residual-leverage, and develop a novel case-based exclusion technique for its calculation. Combining it with an event-oriented data preparation technique to handle the infrequency, we develop a new algorithm MUTARC to find pairwise UTARs. The MUTARC is applied to generate adverse drug reaction (ADR) signals from real-world healthcare administrative databases. It reliably shortlists not only six known ADRs, but also another ADR, flucloxacillin possibly causing hepatitis, which our algorithm designers and experiment runners have not known before the experiments. The MUTARC performs much more effectively than existing techniques. This paper clearly illustrates the great potential along the new direction of ADR signal generation from healthcare administrative databases.

  9. Optimized shapes of magnetic arrays for drug targeting applications

    Science.gov (United States)

    Barnsley, Lester C.; Carugo, Dario; Stride, Eleanor

    2016-06-01

    Arrays of permanent magnet elements have been utilized as light-weight, inexpensive sources for applying external magnetic fields in magnetic drug targeting applications, but they are extremely limited in the range of depths over which they can apply useful magnetic forces. In this paper, designs for optimized magnet arrays are presented, which were generated using an optimization routine to maximize the magnetic force available from an arbitrary arrangement of magnetized elements, depending on a set of design parameters including the depth of targeting (up to 50 mm from the magnet) and direction of force required. A method for assembling arrays in practice is considered, quantifying the difficulty of assembly and suggesting a means for easing this difficulty without a significant compromise to the applied field or force. Finite element simulations of in vitro magnetic retention experiments were run to demonstrate the capability of a subset of arrays to retain magnetic microparticles against flow. The results suggest that, depending on the choice of array, a useful proportion of particles (more than 10% ) could be retained at flow velocities up to 100 mm s-1 or to depths as far as 50 mm from the magnet. Finally, the optimization routine was used to generate a design for a Halbach array optimized to deliver magnetic force to a depth of 50 mm inside the brain.

  10. Microencapsulation of indocyanine green for potential applications in image-guided drug delivery.

    Science.gov (United States)

    Zhu, Zhiqiang; Si, Ting; Xu, Ronald X

    2015-02-07

    We present a novel process to encapsulate indocyanine green (ICG) in liposomal droplets at high concentration for potential applications in image-guided drug delivery. The microencapsulation process follows two consecutive steps of droplet formation by liquid-driven coaxial flow focusing (LDCFF) and solvent removal by oil phase dewetting. These biocompatible lipid vesicles may have important applications in drug delivery and fluorescence imaging.

  11. 78 FR 78716 - Withdrawal of Approval of New Animal Drug Applications; Roxarsone

    Science.gov (United States)

    2013-12-27

    ... Applications; Roxarsone AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and... five new animal drug applications (NADAs) for roxarsone oral dosage form products at the sponsor's... requested that FDA withdraw approval of the following five NADAs for roxarsone oral dosage form...

  12. [Thought and application of traditional Chinese medicine multiple drug delivery system based on material basis component].

    Science.gov (United States)

    Sun, E; Jia, Xiaobin; Huang, Yang; Chen, Bin; Hu, Qin; Xiao, Wei

    2012-07-01

    To aim directly at the research status of Chinese drugs pharmaceutics, this study provides a new research idea "traditional Chinese medicine multiple drug delivery system based on material basis component". This thought according to whole concept, syndrome, and Chinese medicine characteristics of multi-component, multi-target, multi-effect. The premise of designing traditional Chinese medicine multiple drug delivery system is material basis component, and the purpose is to improve bioavailability. The example of multi-drug delivery system of tongmai micro-pellets is expounded for application. This new research model of Chinese drugs pharmaceutics provides new strategies and methods for the development of modern Chinese drug delivery systems.

  13. [Application analysis of adverse drug reaction terminology WHOART and MedDRA].

    Science.gov (United States)

    Liu, Jing; Xie, Yan-ming; Gai, Guo-zhong; Liao, Xing

    2015-12-01

    Drug safety has always been a global focus. Discovery and accurate information acquisition of adverse drug reaction have been the most crucial concern. Terminology of adverse drug reaction makes adverse reaction medical report meaningful, standardized and accurate. This paper discussed the domestic use of the terminology WHOART and MedDRA in terms of content, structure, and application situation. It also analysed the differences between the two terminologies and discusses the future trend of application in our country

  14. Natural Polymers and their Application in Drug Delivery and Biomedical Field

    OpenAIRE

    Jana S; Gandhi A; Sen KK; Basu SK

    2011-01-01

    Biodegradable polymers are widely being studied as a potential carrier material for site specific drug delivery because of its non-toxic,biocompatible in nature. Natural polysaccharides have been investigated for drug delivery applications as well as in biomedical fields. Modified polymer has found its application as a support material for gene delivery, cell culture, and tissue engineering. Now a day, the polymer is being modified to obtain novel biomaterial for controlled drug delivery appl...

  15. Natural Polymers and their Application in Drug Delivery and Biomedical Field

    OpenAIRE

    Jana S; Gandhi A; Sen KK; Basu SK

    2011-01-01

    Biodegradable polymers are widely being studied as a potential carrier material for site specific drug delivery because of its non-toxic,biocompatible in nature. Natural polysaccharides have been investigated for drug delivery applications as well as in biomedical fields. Modified polymer has found its application as a support material for gene delivery, cell culture, and tissue engineering. Now a day, the polymer is being modified to obtain novel biomaterial for controlled drug delivery appl...

  16. In Vitro Drug Transfer Due to Drug Retention in Human Epidermis Pretreated with Application of Marketed Estradiol Transdermal Systems.

    Science.gov (United States)

    Krishnaiah, Yellela S R; Pavurala, Naresh; Yang, Yang; Manda, Prashanth; Katragadda, Usha; Yang, Yongsheng; Shah, Rakhi; Fang, Guodong; Khan, Mansoor A

    2016-12-27

    Study objective was to assess skin-to-skin drug transfer potential that may occur due to drug retention in human epidermis (DRE) pretreated with application of estradiol transdermal drug delivery systems (TDDS) and other estradiol transdermal dosage forms (gels and sprays). TDDS (products-A, B, and C) with varying formulation design and composition, and other estradiol transdermal products (gel and spray) were applied to heat separated human epidermis (HSE) and subjected to in vitro drug permeation study. Amounts of DRE were quantified after 24 h. The DRE with product-B was significantly (P  0.05) amounts of DRE. A separate in vitro permeation study was carried out to determine amounts of drug transferred from drug-retaining epidermis to untreated HSE. The amounts of drug transferred, due to DRE after 8 h, with product-C were significantly (P drug transfer due to the DRE after labeled period of using estradiol TDDS, though the clinical relevance of these findings is yet to be determined.

  17. 78 FR 46977 - Generic Drug User Fee-Abbreviated New Drug Application, Prior Approval Supplement, Drug Master...

    Science.gov (United States)

    2013-08-02

    ..., Prior Approval Supplement, Drug Master File, Final Dosage Form Facility, and Active Pharmaceutical... active pharmaceutical ingredient (API), and finished dosage form (FDF) facilities user fees related to... one or more finished dosage forms of a human generic drug or an active pharmaceutical ingredient...

  18. Intravenous injections in neonatal mice.

    Science.gov (United States)

    Gombash Lampe, Sara E; Kaspar, Brian K; Foust, Kevin D

    2014-11-11

    Intravenous injection is a clinically applicable manner to deliver therapeutics. For adult rodents and larger animals, intravenous injections are technically feasible and routine. However, some mouse models can have early onset of disease with a rapid progression that makes administration of potential therapies difficult. The temporal (or facial) vein is just anterior to the ear bud in mice and is clearly visible for the first two days after birth on either side of the head using a dissecting microscope. During this window, the temporal vein can be injected with volumes up to 50 μl. The injection is safe and well tolerated by both the pups and the dams. A typical injection procedure is completed within 1-2 min, after which the pup is returned to the home cage. By the third postnatal day the vein is difficult to visualize and the injection procedure becomes technically unreliable. This technique has been used for delivery of adeno-associated virus (AAV) vectors, which in turn can provide almost body-wide, stable transgene expression for the life of the animal depending on the viral serotype chosen.

  19. Microcosting Study of Rituximab Subcutaneous Injection Versus Intravenous Infusion.

    Science.gov (United States)

    Mihajlović, Jovan; Bax, Pieter; van Breugel, Erwin; Blommestein, Hedwig M; Hoogendoorn, Mels; Hospes, Wobbe; Postma, Maarten J

    2017-06-01

    The goal of this study is to identify and compare all direct costs of intravenous and subcutaneous rituximab given to patients with diffuse large B-cell lymphoma in the Netherlands. Using a prospective, observational, bottom-up microcosting study, we collected primary data on the direct medical costs of the preparation, administration, and acquisition of rituximab. Drug costs and costs of drug wastage, labor costs, material costs, and outpatient costs were identified using standardized forms, structured using prices from official pricelists, and compared for the intravenous and subcutaneous forms of rituximab. Measurements were taken on 53 rituximab administrations (33 intravenous and 20 subcutaneous) and on 13 rituximab preparation (7 intravenous and 6 subcutaneous). The mean total costs were €2176.77 for the intravenous infusion and €1911.09 for the subcutaneous injection. The estimated difference of €265.17 (95% CI, €231.99-`€298.35) per administration was mainly attributable to differences in time spent in the chemotherapy unit, related outpatient costs, drug wastage, and drug costs. Rituximab administered in the form of subcutaneous injection is less costly than its intravenous form. With their equal effectiveness taken into account, subcutaneous rituximab administration can result in significant savings when transferred to the total diffuse large B-cell lymphoma population in the Netherlands. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

  20. SOLID LIPID NANOPARTICLES: AN ADVANCED DRUG DELIVERY SYSTEM

    OpenAIRE

    Raghu Nandan Reddy* and Arshia Shariff

    2013-01-01

    Solid lipid nanoparticles are at the forefront of the rapidly developing field of nanotechnology with several potential applications in drug delivery, research and clinical medicine, as well as in other varied sciences. Solid lipid nanoparticle (SLN) dispersions have been proposed as a new type of colloidal drug carrier system suitable for intravenous administration. Solid lipid nanoparticles (SLNs) technology represents a promising new approach to lipophilic drug delivery. Solid lipid nanopa...

  1. Intravenous lipid emulsions combine extracorporeal blood purification: a novel therapeutic strategy for severe organophosphate poisoning.

    Science.gov (United States)

    Zhou, Yaguang; Zhan, Chengye; Li, Yongsheng; Zhong, Qiang; Pan, Hao; Yang, Guangtian

    2010-02-01

    Organophosphorus (OP) pesticide self-poisoning is a major clinical problem in rural Asia and it results in the death of 200,000 people every year. At present, it is lack of effective methods to treat severe organophosphate poisoning. The high mortality rate lies on the amount of toxic absorption. Intravenous lipid emulsions can be used as an antidote in fat-soluble drug poisoning. The detoxification mechanism of intravenous lipid emulsions is "lipid sink", which lipid emulsions can dissolve the fat-soluble drugs and separate poison away from the sites of toxicity. Most of organophosphorus pesticides are highly fat-soluble. So, intravenous lipid emulsions have the potentially clinical applications in treatment of OP poisoning. Extracorporeal blood purification especially charcoal hemoperfusion is an efficient way to eliminate the poison contents from the blood. We hypothesize that the combination of intravenous lipid emulsions and charcoal hemoperfusion can be used to cure severe organophosphate poisoning. This novel protocol of therapy comprises two steps: one is obtained intravenous access to infuse lipid emulsions as soon as possible; another is that charcoal hemoperfusion will be used to clear the OP substances before the distribution of OP compounds in tissue is not complete. The advantages of this strategy lie in three points. Firstly, it will alleviate the toxic effect of OP pesticide in the patients by isolation and removal the toxic contents. Secondly, the dosage of antidotes can be reduced and its side-effects will be eased. Thirdly, a large bolus of fatty acids provide energy substrate for the patients who are nil by mouth. We consider that it would become a feasible, safe and efficient detoxification intervention in the alleviation of severe organophosphate poisoning, which would also improve the outcome of the patients.

  2. [Application of direct electric current and intravenous ozone therapy in the complex treatment of destructive forms of acute pancreatitis in experiment].

    Science.gov (United States)

    Zhakiev, B S; Zhumabaeva, A N; Kaliev, A A; Kazbekova, G A

    2013-01-01

    The results of experimental study which have carried out on 40 outbread dogs were analyzed in this thesis. Modeling of destructive pancreatitis in animals has been achieved via canalicular-hypertensive model by S.A. Shalimov. 4 series of experimental study were made to achieve the targeted goal. The first series 10 dogs without treatment, the second series 10 dogs in which conventional conservative therapy was used for the treatment of acute experimental destructive pancreatitis in animals, the third series 10 dogs that underwent intravenous ozone therapy in the complex together with medication therapy, the forth series the effectiveness of combined administration of intravenous ozone therapy and small doses of direct current in 10 dogs was evaluated. Combined administration of small doses of DC and intravenous ozone therapy in the complex treatment of destructive pancreatitis shows antiphlogistic action, favors accelerated rejection of necrotic tissue, remits inflammatory process as well as encourages regeneration process in pancreas whereby allows to decrease the mortality in experimental animals from 60% to 20%.

  3. Molecular Epidemiology of Methicillin-Resistant Staphylococcus aureus in Zürich, Switzerland (2003): Prevalence of Type IV SCCmec and a New SCCmec Element Associated with Isolates from Intravenous Drug Users

    Science.gov (United States)

    Qi, Wei; Ender, Miriam; O'Brien, Frances; Imhof, Alexander; Ruef, Christian; McCallum, Nadine; Berger-Bächi, Brigitte

    2005-01-01

    The majority of methicillin-resistant Staphylococcus aureus (MRSA) isolates, recovered in 2003 at the Department of Medical Microbiology in Zürich, Switzerland, belonged to major clones that are circulating worldwide. Staphylococcal cassette chromosome mec type IV (SCCmec-IV), harbored by half of the isolates, was found in sequence type 217 (ST217), which is an allelic variant of epidemic MRSA-15 (designated EMRSA-15), in a new local ST617 descending from clonal complex CC8 and in low-level oxacillin-resistant strains of multiple genetic lineages characteristic of community-onset MRSA. SCCmec-I, SCCmec-II, and SCCmec-III were in the minority, and four MRSA isolates had complex, rearranged SCCmec elements. A novel SCCmec-N1 of approximately 30 kb, associated with a dfrA gene and a ccr4-related recombinase complex, was identified in a large number of low-level oxacillin-resistant isolates, which descended from the successful clonal complex CC45 and are spreading among intraveneous drug users. In contrast, the SCCmec types of oxacillin-resistant coagulase-negative staphylococci (MRCNS) were of completely different composition. SCCmec type I (SCCmec-I) and SCCmec-II were more frequent than in the MRSA, while fewer contained SCCmec-IV. The other MRCNS displayed 11 different, complex patterns, suggesting frequent recombination between different SCCmec elements. With one ccr-negative exception, these strains amplified between one and three different ccr products, indicating either new varied complexes or multiple ccr loci. This suggests the presence of novel SCCmec types in MRCNS and no extensive interspecies SCCmec transfer between MRSA and MRCNS. PMID:16207979

  4. Genetic Characterization of a Novel HIV-1 Circulating Recombinant Form (CRF74_01B) Identified among Intravenous Drug Users in Malaysia: Recombination History and Phylogenetic Linkage with Previously Defined Recombinant Lineages.

    Science.gov (United States)

    Cheong, Hui Ting; Chow, Wei Zhen; Takebe, Yutaka; Chook, Jack Bee; Chan, Kok Gan; Al-Darraji, Haider Abdulrazzaq Abed; Koh, Clayton; Kamarulzaman, Adeeba; Tee, Kok Keng

    2015-01-01

    In many parts of Southeast Asia, the HIV-1 epidemic has been driven by the sharing of needles and equipment among intravenous drug users (IDUs). Over the last few decades, many studies have proven time and again that the diversity of HIV-1 epidemics can often be linked to the route of infection transmission. That said, the diversity and complexity of HIV-1 molecular epidemics in the region have been increasing at an alarming rate, due in part to the high tendency of the viral RNA to recombine. This scenario was exemplified by the discovery of numerous circulating recombinant forms (CRFs), especially in Thailand and Malaysia. In this study, we characterized a novel CRF designated CRF74_01B, which was identified in six epidemiologically unlinked IDUs in Kuala Lumpur, Malaysia. The near-full length genomes were composed of CRF01_AE and subtype B', with eight breakpoints dispersed in the gag-pol and nef regions. Remarkably, this CRF shared four and two recombination hotspots with the previously described CRF33_01B and the less prevalent CRF53_01B, respectively. Genealogy-based Bayesian phylogenetic analysis of CRF74_01B genomic regions showed that it is closely related to both CRF33_01B and CRF53_01B. This observation suggests that CRF74_01B was probably a direct descendent from specific lineages of CRF33_01B, CRF53_01B and subtype B' that could have emerged in the mid-1990s. Additionally, it illustrated the active recombination processes between prevalent HIV-1 subtypes and recombinants in Malaysia. In summary, we report a novel HIV-1 genotype designated CRF74_01B among IDUs in Kuala Lumpur, Malaysia. The characterization of the novel CRF74_01B is of considerable significance towards the understanding of the genetic diversity and population dynamics of HIV-1 circulating in the region.

  5. 可拆卸静脉输液摆药分置盒的研制与应用%Development and Application of Detachable Split Boxes for Intravenous Medication Dispensing

    Institute of Scientific and Technical Information of China (English)

    胡校云; 吴明慧; 魏天华; 刘迪娜

    2016-01-01

    本文阐述了一种可拆卸静脉输液摆药分置盒的研制及应用过程。该摆药分置盒主要由输液牌、撑杆、定位销、活动隔板、药盒、分置盒体、号码牌等结构组成。使用该摆药分置盒进行摆药,可规范药物的摆放操作,改进相应的工作流程,控制静脉输液过程中易出现差错的环节,从而保障用药安全,减轻护士工作量,提高护士的工作效率。实际应用效果表明,该摆药分置盒实用性强,达到了设计目的,值得临床推广。%This paper describes the development and application of the detachable split box for intravenous medication dispensing, which is mainly composed of transfusion card, supporting pole, positioning pin, movable partition board, medication container, the body of the split box and number card. The application of the detachable split box to dispense medication can standardize medication administration, improve clinical processes, monitor the errors during intravenous infusion, ensure nursing safety management, reduce nurses’ workloads, and improve efifciency during nursing process. The detachable split box for intravenous medication dispensing is practical and is worthy of clinical application.

  6. A review on phospholipids and their main applications in drug delivery systems

    OpenAIRE

    Jing Li; Xuling Wang; Ting Zhang; Chunling Wang; Zhenjun Huang; Xiang Luo; Yihui Deng

    2015-01-01

    Phospholipids have the characteristics of excellent biocompatibility and a especial amphiphilicity. These unique properties make phospholipids most appropriate to be employed as important pharmaceutical excipients and they have a very wide range of applications in drug delivery systems. The aim of this review is to summarize phospholipids and some of their related applications in drug delivery systems, and highlight the relationship between the properties and applications, and the effect of t...

  7. Dendrimers: General Aspects, Applications and Structural Exploitations as Prodrug/ Drug-delivery Vehicles in Current Medicine.

    Science.gov (United States)

    Mariyam, Merina; Ghosal, Kajal; George, Anne; Thomas, Sabu; Kalarikkal, Nandakumar; S Latha, Mahima

    2017-05-11

    Dendrimers are hyper branched macro molecules with well-defined structure and high degree of functionality on the surface. The dendrimer architecture allows control over properties such as shape, size, density, polarity, reactivity, solubility etc. This can be manipulated to design molecules with desired properties in biomedical applications. Recent advancement in correlating structure to biodegradability and invivo performance opens up new avenue for these molecules in biological applications like drug delivery and tissue engineering. The unique structure of dendrimers provides enough attachment sites for drugs in drug delivery applications. It is possible to tune the molecule in such a way as to encapsulate drug molecule outside target area and release in the local environment of targets. This review presents the general aspects of dendrimers and how these properties are exploited for drug delivery applications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Analysis on Application of Intravenous Infusion for 53 Diseases in Outpatient and Emergency Department of Suzhou Municipal Hospital Before and After Comprehensive InterventionΔ%综合干预前后宿州市立医院门、急诊53种疾病静脉输液应用分析Δ

    Institute of Scientific and Technical Information of China (English)

    刘洪峰; 范秀英; 孟现奇; 代玉琦

    2016-01-01

    OBJECTIVE:To probe into the effects of comprehensive intervention on application of intravenous infusion in outpatient and emergency department of Suzhou Municipal Hospital ( hereinafter referred to as “our hospital”) , so as to establish long-term mechanism of intravenous infusion of supervision by comprehensive intervention measures.METHODS:Statistical analysis was conducted on the intravenous infusion rate in outpatient and emergency department, intravenous infusion rate of antibiotics, intravenous infusion rate of 53 diseases and rational rate of prescriptions with intravenous infusion in our hospital from Jul.to Dec.2014 ( before intervention) and from Jul.to Dec.2015 ( after intervention).RESULTS: The average intravenous infusion rate in outpatient department decreased from 24.03%before intervention to 16.49%after intervention, the decreasing range was 7.54%; and in emergency department, it decreased from 65.19% before intervention to 54.64% after intervention, the decreasing range was 10.55%.Meanwhile, the average intravenous infusion rate for 53 diseases in outpatient department decreased from 22.40%before intervention to 12.66%after intervention, the decreasing range was 9.74%; and in emergency department, it decreased from 63.74% before intervention to 55.68% after intervention, the decreasing range was 8.06%.The rational rate of prescriptions with intravenous infusion in outpatient and emergency department increased from 83.00% before intervention to 95.50% after intervention, the increasing range was 12.50%.After intervention, the related indicators were significantly better than before intervention, the differences were statistically significant(P<0.05).CONCLUSIONS:Comprehensive intervention can effectively decrease intravenous infusion rate in outpatient and emergency department and improve the level of rational application of drugs.%目的:探讨综合干预对宿州市立医院(以下简称“我院”)门、急诊静脉输液使用情况

  9. Classification of chronic orofacial pain using an intravenous diagnostic test

    OpenAIRE

    Tjakkes, G. -H. E.; de Bont, L. G. M.; Wijhe, M. van; Stegenga, B.

    2009-01-01

    The aim of this study was to evaluate the ability of a preliminary intravenous diagnostic test to classify chronic orofacial pain patients into different subgroups. Patients with chronic orofacial pain conditions that could not be unambiguously diagnosed. A retrospective evaluation of series of conducted pharmacodiagnostic tests, consisting of the consecutive intravenous administration of drugs. Visual analogue scale scores were retrieved from all patients, based on which they were classified...

  10. Preparation and application of functionalized nano drug carriers

    Directory of Open Access Journals (Sweden)

    Rudong Gong

    2016-05-01

    Full Text Available Objective: Targeting at category memory characteristics and preparation methods of functionalized nano drugs, preparation technology of functionalized nano drug carriers is studied, and then important role of functionalized nano drug carrier in preparation of medicine is studied. Methods: Carry out the relevant literature search with computer, change limited language in the paper to Chinese and necessarily remove repetitive studies. Results: After first review of 1260 retrieved literature, it can be found that nano drug is with accurate quantity, relatively good targeting, specificity and absorbency. Necessary research of nano drug carriers can prevent and treat disease to a certain extent. Conclusion: Preparation of functionalized nanocarrier is simple and convenient, which can improve frequency of use of nano preparation technology and provide better development space for medical use. Therefore, nanocarriers should be combined with drugs with relatively strong specificity in clinics, in order to be able to conduct effective research on nanometer intelligent drug, effectively promote long-term development of nano biotechnology, and then provide favorable, reliable basis for clinical diagnosis and treatment.

  11. Advances in the Applications of Polyhydroxyalkanoate Nanoparticles for Novel Drug Delivery System

    Directory of Open Access Journals (Sweden)

    Anupama Shrivastav

    2013-01-01

    Full Text Available Drug delivery technology is emerging as an interdisciplinary science aimed at improving human health. The controlled delivery of pharmacologically active agents to the specific site of action at the therapeutically optimal rate and dose regimen has been a major goal in designing drug delivery systems. Over the past few decades, there has been considerable interest in developing biodegradable drug carriers as effective drug delivery systems. Polymeric materials from natural sources play an important role in controlled release of drug at a particular site. Polyhydroxyalkanoates, due to their origin from natural sources, are given attention as candidates for drug delivery materials. Biodegradable and biocompatible polyhydroxyalkanoates are linear polyesters produced by microorganisms under unbalanced growth conditions, which have emerged as potential polymers for use as biomedical materials for drug delivery due to their unique physiochemical and mechanical properties. This review summarizes many of the key findings in the applications of polyhydroxyalkanoates and polyhydroxyalkanoate nanoparticles for drug delivery system.

  12. [Application of thermoplastic elastomer in hot-melt pressure sensitive adhesives for transtermal drug delivery].

    Science.gov (United States)

    Yan, Xiaoping; Zheng, Rui; Guan, Shijie; Yi, Bowen

    2009-06-01

    Development of drug dosage forms to a great extent depends on the development of drug auxiliary materials. The development of a new type of polymeric drug auxiliary materials will bring on the developing of a novel dosage forms technology and a flood of new drug dosage forms. Thermoplastic elastomer is a new type of drug polymeric auxiliary materials, at present, which has a broad application in the field of hot-melt pressure sensitive adhesives. This review mainly discussed a new transtermal Chinese drug delivery system, including matrix composition of the formula, modified thermoplastic elastomer for hot-melt pressure sensitive adhesives and their development prospects in the traditional Chinese drug delivery system. It suggested that thermoplastic elastomer of hot-melt pressure sensitive adhesives has broad development prospects in the field of the transtermal drug delivery system for traditional Chinese medicine.

  13. Rescue Thrombectomy in Large Vessel Occlusion Strokes Leads to Better Outcomes than Intravenous Thrombolysis Alone: A ‘Real World’ Applicability of the Recent Trials

    Science.gov (United States)

    Nogueira, Raul G.; Zaidat, Osama O.; Castonguay, Alicia C.; Haussen, Diogo C.; Martin, Coleman O.; Holloway, William E.; Mueller-Kronast, Nils; English, Joey; Linfante, Italo; Dabus, Guilherme; Malisch, Tim W.; Marden, Franklin A.; Bozorgchami, Hormozd; Xavier, Andrew; Rai, Ansaar T.; Froehler, Michael T.; Badruddin, Aamir; Nguyen, Thanh N.; Taqi, M. Asif; Abraham, Michael G.; Janardhan, Vallabh; Yoo, Albert J.; Shaltoni, Hashem; Abou-Chebl, Alex; Chen, Peng R.; Britz, Gavin W.; Novakovic, Roberta; Nanda, Ashish; Kaushal, Ritesh; Issa, Mohammad A.; Frankel, Michael R.; Gupta, Rishi

    2016-01-01

    Background The Interventional Management of Stroke III (IMS-III) trial demonstrated no benefit for intravenous recombinant tissue plasminogen activator (IV rt-PA) followed by endovascular therapy versus IV rt-PA alone. However, IMS-III mostly included earlier generation devices. The recent thrombectomy trials have incorporated the stent-retriever technology, but their generalizability remains unknown. Methods The North American Solitaire Acute Stroke (NASA) registry recruited patients treated with the Solitaire FR™ device between March 2012 and February 2013. The NASA-IMS-III-Like Group (NILG baseline NIHSS score ≥10 who received IV rt-PA) was compared to the IV rt-PA and IV + intra-arterial (IA)-IMS-III groups and the MR CLEAN, ESCAPE, SWIFT Prime, and REVASCAT trial controls to assess the stent-retriever treatment in the ‘real-world’ setting. The NILG was also compared to non-IV rt-PA NASA patients to evaluate the impact of IV rt-PA on thrombectomy. Results A total of 136 of the 354 NASA patients fulfilled criteria for the NILG. Baseline characteristics were well balanced across groups. Time from onset to puncture was higher in NILG than IV+IA-IMS-III patients (274 ± 112 vs. 208 ± 47 min, p < 0.0001). Occlusions involving the intracranial ICA, MCA-M1, or basilar arteries were more common in NILG than IV+IA-IMS-III patients (91.2 vs. 47.2%, p < 0.00001). Modified thrombolysis in cerebral infarction ≥2b reperfusion was higher in NILG than IV+IA-IMS-III patients (74.3 vs. 39.6%, p < 0.00001). A 90-day modified Rankin Scale score ≤2 was more frequent in the NILG than IV+IA-IMS-III patients (51.9 vs. 40.8%, p = 0.03) and MR CLEAN (51.9 vs. 19.1%, p < 0.00001), ESCAPE (51.9 vs. 29.3%, p = 0.0002), SWIFT Prime (51.9 vs. 35.5%, p = 0.02), and REVASCAT (51.9 vs. 28.2%, p = 0.0003) controls. Symptomatic intracranial hemorrhage definitions varied across the different studies with rates ranging from 2.7% (ESCAPE) to 11.9% (NILG). The NILG 90-day mortality (24

  14. Application of Various Types of Liposomes in Drug Delivery Systems

    Directory of Open Access Journals (Sweden)

    Mehran Alavi

    2017-04-01

    Full Text Available Liposomes, due to their various forms, require further exploration. These structures can deliver both hydrophilic and hydrophobic drugs for cancer, antibacterial, antifungal, immunomodulation, diagnostics, ophtalmica, vaccines, enzymes and genetic elements. Preparation of liposomes results in different properties for these systems. In addition, based on preparation methods, liposomes types can be unilamellar, multilamellar and giant unilamellar; however, there are many factors and difficulties that affect the development of liposome drug delivery structure. In the present review, we discuss some problems that impact drug delivery by liposomes. In addition, we discuss a new generation of liposomes, which is utilized for decreasing the limitation of the conventional liposomes.

  15. Application of Various Types of Liposomes in Drug Delivery Systems.

    Science.gov (United States)

    Alavi, Mehran; Karimi, Naser; Safaei, Mohsen

    2017-04-01

    Liposomes, due to their various forms, require further exploration. These structures can deliver both hydrophilic and hydrophobic drugs for cancer, antibacterial, antifungal, immunomodulation, diagnostics, ophtalmica, vaccines, enzymes and genetic elements. Preparation of liposomes results in different properties for these systems. In addition, based on preparation methods, liposomes types can be unilamellar, multilamellar and giant unilamellar; however, there are many factors and difficulties that affect the development of liposome drug delivery structure. In the present review, we discuss some problems that impact drug delivery by liposomes. In addition, we discuss a new generation of liposomes, which is utilized for decreasing the limitation of the conventional liposomes.

  16. [Application of phosphates and phosphonates prodrugs in drug research and development].

    Science.gov (United States)

    Ji, Xun; Wang, Jiang; Zhang, Lei; Zhao, Lin-Xiang; Jiang, Hua-Liang; Liu, Hong

    2013-05-01

    Based on the character of the molecular structure, the prodrugs of phosphates and phosphonates were divided into two categories. The first is the drug which contained the phosphate group, introducing protected groups to increase lipophilicity and improve bioavailability. The other one is the drug which had no phosphate group, introducing the phosphate group into molecules to enhance the solubility, regulate the distribution coefficient and enhance the drug-like property. This review focuses on the application of phosphates and phosphonates in drug research and development based on improvement of physico-chemical property, drug safety and the pharmacokinetics.

  17. Initial pharmacology and toxicology of intravenous desmethylmisonidazole

    Energy Technology Data Exchange (ETDEWEB)

    Coleman, C.N. (Stanford Univ., CA); Wasserman, T.H.; Phillips, T.L.; Strong, J.M.; Urtasun, R.C.; Schwade, J.G.; Johnson, R.J.; Zagars, G.

    1982-03-01

    Since January 1981, 52 patients have entered the Radiaton Therapy Oncology Group Phase I trial with intravenous (i.v.) desmethylmisonidazole (DMM). DMM is less lipophilic than misonidazole (MISO) and theoretically will be less neurotoxic due to lower penetration into neural tissue and more rapid elimination. The drug is administered intravenously to achieve the maximum drug concentration in tumor for a given dose. The protocol slowly escalates the total dose of drug administered. At this time the planned dose on the three week schedule is 1 g/m/sup 2/ twice weekly to a total dose of 17.5g/m/sup 2/. The preliminary plasma pharmacokinetic data demonstrates high peak plasma levels within five minutes of the end of the drug infusion. Compared to MISO the percent of DMM excreted in the urine is increased, 63% vs 10%, and the elimination half-life is decreased: DMM, i.v. 5.3h; MISO, i.v. 9.3h; MISO, oral 10 to 13h. Neurotoxicity has been observed in approximately 30% of patients given a cumulative dose of >11g/m/sup 2/. This is in comparison to a 50% incidence in RTOG Phase 1 study with oral MISO at doses of 12g/m/sup 2/. There is not sufficient data to evaluate the relationship between neurotoxicity and drug exposure. Further patient accrual on this study is required to better define the properties of DMN.

  18. What Can Be Learned from Recent New Drug Applications? A Systematic Review of Drug Interaction Data for Drugs Approved by the US FDA in 2015.

    Science.gov (United States)

    Yu, Jingjing; Zhou, Zhu; Owens, Katie H; Ritchie, Tasha K; Ragueneau-Majlessi, Isabelle

    2017-01-01

    As a follow up to previous reviews, the aim of the present analysis was to systematically examine all drug metabolism, transport, pharmacokinetics (PK), and drug-drug interaction (DDI) data available in the 33 new drug applications (NDAs) approved by the Food and Drug Administration (FDA) in 2015, using the University of Washington Drug Interaction Database, and to highlight the significant findings. In vitro, a majority of the new molecular entities (NMEs) were found to be substrates or inhibitors/inducers of at least one drug metabolizing enzyme or transporter. In vivo, 95 clinical DDI studies displayed positive PK interactions, with an area under the curve (AUC) ratio ≥ 1.25 for inhibition or ≤ 0.8 for induction. When NMEs were considered as victim drugs, 21 NMEs had at least one positive clinical DDI, with three NMEs shown to be sensitive substrates of CYP3A (AUC ratio ≥ 5 when coadministered with strong inhibitors): cobimetinib, isavuconazole (the active metabolite of prodrug isavuconazonium sulfate), and ivabradine. As perpetrators, nine NMEs showed positive inhibition and three NMEs showed positive induction, with some of these interactions involving both enzymes and transporters. The most significant changes for inhibition and induction were observed with rolapitant, a moderate inhibitor of CYP2D6 and lumacaftor, a strong inducer of CYP3A. Physiologically based pharmacokinetics simulations and pharmacogenetics studies were used for six and eight NMEs, respectively, to inform dosing recommendations. The effects of hepatic or renal impairment on the drugs' PK were also evaluated to support drug administration in these specific populations.

  19. Curative Effect of Intravenous Immune Globulin Drug on Severe Adenovirus Pneumonia in Children%静脉用丙种球蛋白佐治重症腺病毒肺炎84例疗效评价

    Institute of Scientific and Technical Information of China (English)

    崔艳杰; 程军; 孙雯

    2015-01-01

    Objective To investigate the curative effect of intravenous immune-enhancing drug on the severe adenovirus pneumonia (SAP)in children. Methods 168 children cases of SAP in the hospital from April 2009 to May 2014 were selected and randomly di-vided into the observation group and control group,84 cases in each group. The control group adopted the traditional routine therapy mode,while on this basis the observation group was given the intravenous immune-enhancing drug immunoglobulin(IG). Results The average fever time and average length of hospital stay were (5. 17 ± 2. 58) d and (11. 17 ± 5. 11) d in the observation group and (6. 78 ± 4. 02) d and (12. 71 ± 5. 75) d in the control group,the differences between the two groups were statistically significant( t=2. 281,2. 181,P < 0. 05). 21 cases (25. 00%) in the two groups used the breathing machine,including 11 cases in the observation group with the average use time of(4. 58+1. 39)d and 10 cases in the control group with the average use time of(5. 96+3. 39)d,the differences between the two groups showed statistical significance ( t=1. 992,P=0. 047);68 cases in the observation group appeared complications,while all the cases in the control group suffered from complications,in which the occurrence rates of atelectasis,pleural effusion,myocarditis,tozic encephalopathy and diarrhea in the observation group were significantly lower than those in the control group;the effective rate in the observation group was 22. 62%,which was significantly higher than 10. 71% in the control group(χ2=7. 872, P=0. 002 ),and the ineffective rate in the control group was significantly higher than that in the observation group(χ2=4. 421 , P=0. 037). Conclusion The assisted therapy of intravenous immune globulin in the treatment of children SAP can reduce the occur-rence of some complications,improve the curative effect and prognosis,shorten the hospitalization time,breathing machine using time and persistent fever time.%目的:探

  20. Applications of structure-based design to antibacterial drug discovery.

    Science.gov (United States)

    Cain, Ricky; Narramore, Sarah; McPhillie, Martin; Simmons, Katie; Fishwick, Colin W G

    2014-08-01

    In recent years bacterial resistance has been observed against many of our current antibiotics, for instance most worryingly against the cephalosporins which are typically the last line of defence against many bacterial infections. Additionally the failure of high throughput screening in the discovery of new antibacterial drug leads has led to a decline in the number of antibacterial agents reaching the market. Alternative methods of drug discovery including structure based drug design are needed to meet the threats caused by the emergence of resistance. In this review we explore the latest advancements in the identification of new antibacterial agents through the use of a number of structure based drug design programs. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Deep Learning Applications for Predicting Pharmacological Properties of Drugs and Drug Repurposing Using Transcriptomic Data.

    Science.gov (United States)

    Aliper, Alexander; Plis, Sergey; Artemov, Artem; Ulloa, Alvaro; Mamoshina, Polina; Zhavoronkov, Alex

    2016-07-05

    Deep learning is rapidly advancing many areas of science and technology with multiple success stories in image, text, voice and video recognition, robotics, and autonomous driving. In this paper we demonstrate how deep neural networks (DNN) trained on large transcriptional response data sets can classify various drugs to therapeutic categories solely based on their transcriptional profiles. We used the perturbation samples of 678 drugs across A549, MCF-7, and PC-3 cell lines from the LINCS Project and linked those to 12 therapeutic use categories derived from MeSH. To train the DNN, we utilized both gene level transcriptomic data and transcriptomic data processed using a pathway activation scoring algorithm, for a pooled data set of samples perturbed with different concentrations of the drug for 6 and 24 hours. In both pathway and gene level classification, DNN achieved high classification accuracy and convincingly outperformed the support vector machine (SVM) model on every multiclass classification problem, however, models based on pathway level data performed significantly better. For the first time we demonstrate a deep learning neural net trained on transcriptomic data to recognize pharmacological properties of multiple drugs across different biological systems and conditions. We also propose using deep neural net confusion matrices for drug repositioning. This work is a proof of principle for applying deep learning to drug discovery and development.

  2. The effect size, study design, and development experience in commercially sponsored studies for new drug applications in approved drugs.

    Science.gov (United States)

    Fukunaga, Satoshi; Kusama, Makiko; Ono, Shunsuke

    2014-01-01

    Pharmaceutical companies incorporate different features into the trials for new drug applications (NDAs) to render them efficient, making use of their experience. The objective of this analysis was to examine the associations between outcome and features related to study design and clinical development experience in commercially sponsored clinical trials. We collected data of phase 2 and phase 3 trials of all the drugs that obtained approval for depression, schizophrenia, asthma, hypertension, and diabetes in Japan from 1970 to 2011. In total, 145 trials from 90 test drugs were eligible for our study. We calculated the effect size, the standard mean of differences between test drug and comparator therapeutic effects, as the objective variable for use in our analysis. A linear mixed effect model with nested and crossed random effects was used in the analysis including variety of therapeutic area, test drugs and clinical trials. The analysis showed that trial features including sample size, subjective endpoints and active comparator of the same mode of action were negatively associated with effect size. In addition, sponsors' domestic clinical development experience with similar drugs seemed to have a positive association, but prior development experience in foreign countries did not. The accumulation of skills and knowledge within sponsors, and accumulated experience in domestic professionals who implement clinical trials under study contracts with sponsors would be of great importance for yielding clear outcomes. This study provides additional evidence with respect to possible sizes and directions of the influence of study design features that must be considered when planning and implementing trials for new drug applications, and when retrospectively comparing outcomes from trials with different designs and environments.

  3. Dialdehyde starch nanoparticles: Preparation and application in drug carrier

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Dialdehyde starch nanoparticles (DASNP) were prepared by the redox reaction of NaIO4 and starch in water-in-oil microemulsion. IR spectrum showed that DASNP had aldehyde groups, and quantitative alkali consumption showed that its dialdehyde content was about (50±5)%. The average diameter of DASNP determined by SEM was about 100 nm. TGA-DTA showed that its thermal stability was better than starch nanoparticle (StNP) and dialdehyde starch (DAS). Its low biological toxicity was detected by cell experiment. Also the best mass ratio of doxorubicin (DOX) to combined DASNP detected by UV-VIS was 15 : 1, and the product was effective for controlled release of DOX. The cell experiment showed that the drug-carrier particle (DOX-DASNP) can release DOX for a long time and strengthened the effect of the anticancer drug. This work demonstrates that the DASNP, which has good thermal stability, small particle size, low biological toxicity, and slowly anticancer drug-releasing to strengthen drug effect, is a potentially useful carrier for anticancer drug.

  4. HPLC determination of five polyphenols in rat plasma after intravenous administration of hawthorn leaves extract and its application to pharmacokinetic study.

    Science.gov (United States)

    Wang, Si-Yuan; Chai, Ji-Yan; Zhang, Wen-Jie; Liu, Xun; DU, Yang; Cheng, Zhong-Zhe; Ying, Xi-Xiang; Kang, Ting-Guo

    2010-11-01

    A simple and specific HPLC-UV method was developed to simultaneously determine five active compounds including vitexin-4"-O-glucoside (VG), vitexin-2"-O-rhamnoside (VR), vitexin (VIT), rutin (RUT) and hyperoside (HP) in rat plasma after intravenous administrating the hawthorn leaves extract (HLE). With baicalin as internal standard (I.S.), sample pretreatment involved a one-step extraction with methanol of 0.2 ml plasma. The HPLC assay was carried out using a Phenomsil C18 analytical column with UV detection at 332 nm. The mobile phase consisted of methanol-acetonitrile-tetrahydrofuran-1% glacial acetic acid (6:1.5:18.5:74, v/v/v/v). The calibration curves were liner over the range of 2.030-500.5, 0.1513-75.64, 0.2507-12.54, 0.5128-25.64 and 0.4032-20.16 µg/ml for VG, VR, VIT, RUT and HP, respectively. The relative standard deviations (RSD) of the intra- and inter-day precisions for the analysis of the five analytes were between 1.0 and 8.9% with accuracies (relative error) below 8.2% for the analysis of the five analytes. The average extraction recoveries of five analytes were more than 82.67 ± 4.74%. The HPLC method herein described was fully validated and successfully applied to the pharmacokinetic studies after intravenous administration of HLE solution to rats over three doses.

  5. Urinalysis and hair analysis for illicit drugs of driver applicants and drivers in the trucking industry.

    Science.gov (United States)

    Mieczkowski, Tom

    2010-07-01

    The purpose of this article is to compare the differential rate of detection of illicit drugs when using two distinct sample types, hair and urine specimens. The specimens were collected from persons who applied for employment as a truck driver, or were collected from randomly selected currently employed truck drivers. The data is examined for job applicants and employees to determine if any differences in outcomes are associated with employment status or specimen type. The data is also assessed for specific patterns associated with particular drugs and their assay outcomes. Overall, it was determined that drug positive cases are relatively rare. Job applicants are more likely to test positive for an illicit drug than a currently employed driver. Applicants are more frequently positive for a drug by a factor of 3 for both urinalysis and hair analysis when compared to currently employed drivers. Approximately 2% of applicants were urine positive and 9% hair positive for an illegal drug. Considering employed truck drivers 0.6% were drug positive by urinalysis and 3% when using hair analysis. It is concluded that hair assays detect more drug use than urinalysis. It is also concluded that when urine and hair assay outcomes are non-concordant the typical case is a positive hair analysis with a negative urinalysis.

  6. 78 FR 78796 - Supplemental Applications Proposing Labeling Changes for Approved Drugs and Biological Products...

    Science.gov (United States)

    2013-12-27

    ... Applications Proposing Labeling Changes for Approved Drugs and Biological Products; Correction and Extension of... holders of an approved drug or biological product to change the product labeling to reflect certain types... biological product to change the product labeling to reflect certain types of newly acquired information...

  7. Applications of nanodiamonds in drug delivery and catalysis

    KAUST Repository

    Moosa, Basem

    2014-01-01

    The interest of researchers in utilizing nanomaterials as carriers for a wide spectrum of molecules has exploded in the last two decades. Nanodiamonds are one class of carbon-based nanomaterials that have emerged as promising drug delivery vehicles and imaging probes. Their ease of functionalization also led to the generation of stimuli-responsive nanodiamonds that deliver drugs on demand in a controlled manner. The ample surface area of NDs allowed for a higher loading of not only small molecules but also macromolecules like genes and proteins. Recently, the unique surface of NDs has attracted more attention as catalyst support in a huge range of organic modification and C-C bond formation reactions. Herein, recent advances in the utilization of nanodiamonds as a drug delivery vehicle and catalytical support are highlighted and summarized to illustrate the potential and versatility of this cheap and commercially available nanomaterial. Copyright © 2014 American Scientific Publishers All rights reserved.

  8. Applications of nanodiamonds in drug delivery and catalysis.

    Science.gov (United States)

    Moosa, Basem; Fhayli, Karim; Li, Song; Julfakyan, Khatchatur; Ezzeddine, Alaa; Khashab, Niveen M

    2014-01-01

    The interest of researchers in utilizing nanomaterials as carriers for a wide spectrum of molecules has exploded in the last two decades. Nanodiamonds are one class of carbon-based nanomaterials that have emerged as promising drug delivery vehicles and imaging probes. Their ease of functionalization also led to the generation of stimuli-responsive nanodiamonds that deliver drugs on demand in a controlled manner. The ample surface area of NDs allowed for a higher loading of not only small molecules but also macromolecules like genes and proteins. Recently, the unique surface of NDs has attracted more attention as catalyst support in a huge range of organic modification and C-C bond formation reactions. Herein, recent advances in the utilization of nanodiamonds as a drug delivery vehicle and catalytical support are highlighted and summarized to illustrate the potential and versatility of this cheap and commercially available nanomaterial.

  9. Computational modeling of drug response with applications to neuroscience.

    Science.gov (United States)

    Herwig, Ralf

    2014-12-01

    The development of novel high-throughput technologies has opened up the opportunity to deeply characterize patient tissues at various molecular levels and has given rise to a paradigm shift in medicine towards personalized therapies. Computational analysis plays a pivotal role in integrating the various genome data and understanding the cellular response to a drug. Based on that data, molecular models can be constructed that incorporate the known downstream effects of drug-targeted receptor molecules and that predict optimal therapy decisions. In this article, we describe the different steps in the conceptual framework of computational modeling. We review resources that hold information on molecular pathways that build the basis for constructing the model interaction maps, highlight network analysis concepts that have been helpful in identifying predictive disease patterns, and introduce the basic concepts of kinetic modeling. Finally, we illustrate this framework with selected studies related to the modeling of important target pathways affected by drugs.

  10. Application of the design of experiments in optimization of drug layering of pellets with an insight into drug polymer interactions.

    Science.gov (United States)

    Kovacevic, Jovana; Ibric, Svetlana; Djuris, Jelena; Kleinebudde, Peter

    2016-06-15

    This study consists of two experimental designs. Within the first one, suitable technique for application of model drug onto inactive pellets was evaluated and formulation and process parameters with greatest impact to process efficency and useful yield were determined. Results of experiments showed that formulation characteristics were the ones with the greatest impact on coating efficiency and that suspension layering technique was significantly better for drug application onto inactive pellets in comparison to solution layering during which pronounced agglomeration of pellets occurred. Analysis of drug-polymer interactions by differential scanning calorimetry was performed to explain the results of experiments. The reason for agglomeration of pellets during solution layering was formation of low Tg amorphous form of model drug. The second set of experiments was performed according to central composite design experimental plan in order to optimize level of binder and concentration of solids in the coating liquid which were found to have greatest positive impact on process efficiency and useful yield in the screening study. Statistically significant models were obtained by response surface methodology and it was possible to use them to define optimal levels of excipients in the formulation.

  11. Positron Emission Tomography Application to Drug Development and Research

    Science.gov (United States)

    Salvadori, Piero A.

    The research for the identification and development of new drugs represents a very complex process implying long times and massive investments. This process was not able to parallel the rate of discoveries made in the field of genomic and molecular biology and a gap created between demand of new drugs and the ability of pharmaceutical companies to select good candidates. Positron Emission Tomography, among the different Molecular Imaging modalities, could represent a new tool for the early assessment and screening of new drug candidates and, due to its physical performances and the characteristics of positron-labeled tracers, gain the role of "Biomarker" accepted by the Companies and the Regulatory Bodies of Drug Agencies. To fulfil this task PET has to exploit all of its special features such as data absolute quantification and modelling, high spatial resolution and dynamic imaging. Relevant efforts need to be directed to the careful design and validation of experimental protocols with the main goal of achieving consistency in multi- centric trials.

  12. 78 FR 52429 - New Animal Drugs; Withdrawal of Approval of New Animal Drug Applications; Diethylcarbamazine...

    Science.gov (United States)

    2013-08-23

    ... of NADA 098-371 for use of nicarbazin, penicillin, and roxarsone in 3-way, combination drug Type C... ``Penicillin 2.4 to 50 and roxarsone 22.7 to 45.4''. Sec. 558.460 0 7. In Sec. 558.460, remove and...

  13. On resource survey of natural mineral drugs in eastern Jilin and their sustaining application

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    There are rich natural resources of natural mineral drugs in eastern Jilin Province. Systematic resource investigation can elevate fractional conversion of this area' s mineral drugs resources superiority. Research on natural mineral drugs of this area can upgrade the translation rate of resource superiority and accelerate the development of local medical industry, especially, it can provide scientific data for founding the strategic design of Chinese traditional medicine's trademark of Jilin Changbai Mountain. Since the resource of mineral drugs can not be regenerated, it must be exploited scientifically, utilized reasonably and protected effectively its sustaining application.

  14. Polymers and formulation strategies of nanofibrous systems for drug delivery application and tissue engineering.

    Science.gov (United States)

    Sebe, I; Kállai-Szabó, B; Zelkó, R; Szabó, D

    2015-01-01

    During the last decade, the formulation of nanofibrous materials loaded with different drugs for biomedical applications has evoked considerable interest. The large specific surface area, the special micro- and macrostructure of fiber mats, the possibility for gradual release and site-specific local delivery of the active compounds lead to cytotoxicity decrease and enhancement of the therapeutic effect of drugs and implants. The present review details the different spinning techniques applied for the design of micro- and nanofibrous drug delivery systems. It furthermore deals with the use of various polymers that are capable for the formation of fiber scaffolds of various biomedical applications.

  15. SynergyFinder: a web application for analyzing drug combination dose-response matrix data.

    Science.gov (United States)

    Ianevski, Aleksandr; He, Liye; Aittokallio, Tero; Tang, Jing

    2017-08-01

    Rational design of drug combinations has become a promising strategy to tackle the drug sensitivity and resistance problem in cancer treatment. To systematically evaluate the pre-clinical significance of pairwise drug combinations, functional screening assays that probe combination effects in a dose-response matrix assay are commonly used. To facilitate the analysis of such drug combination experiments, we implemented a web application that uses key functions of R-package SynergyFinder, and provides not only the flexibility of using multiple synergy scoring models, but also a user-friendly interface for visualizing the drug combination landscapes in an interactive manner. The SynergyFinder web application is freely accessible at https://synergyfinder.fimm.fi ; The R-package and its source-code are freely available at http://bioconductor.org/packages/release/bioc/html/synergyfinder.html . jing.tang@helsinki.fi.

  16. Pharmacogenomic information in FDA-approved drug labels: Application to pediatric patients.

    Science.gov (United States)

    Green, D J; Mummaneni, P; Kim, I W; Oh, J M; Pacanowski, M; Burckart, G J

    2016-06-01

    Pharmacogenomic (PGx) information is increasingly being incorporated into US Food and Drug Administration-approved drug labels. We reviewed the data source (adults vs. pediatrics) of PGx information in approved drug labels and assessed the suitability of applying adult-derived PGx information and related prescribing recommendations to the care of pediatric patients. We identified 65 drugs with labels containing PGx information and that have also been evaluated in children and found that in the majority of cases (56/65, 86%), the PGx information described was derived from adult studies. The application of PGx information from adults to pediatrics was deemed suitable for 71.4% (n = 40) of the drugs and unclear for 28.6% (n = 16). An ontogeny effect, limited or conflicting data regarding ontogeny of the genetic biomarker, or a difference in the pathophysiology or progression of the adult vs. pediatric disease were the primary reasons for deeming direct application from adults to pediatrics unclear.

  17. The application of nanomaterials in controlled drug delivery for bone regeneration.

    Science.gov (United States)

    Shi, Shuo; Jiang, Wenbao; Zhao, Tianxiao; Aifantis, Katerina E; Wang, Hui; Lin, Lei; Fan, Yubo; Feng, Qingling; Cui, Fu-zhai; Li, Xiaoming

    2015-12-01

    Bone regeneration is a complicated process that involves a series of biological events, such as cellular recruitment, proliferation and differentiation, and so forth, which have been found to be significantly affected by controlled drug delivery. Recently, a lot of research studies have been launched on the application of nanomaterials in controlled drug delivery for bone regeneration. In this article, the latest research progress in this area regarding the use of bioceramics-based, polymer-based, metallic oxide-based and other types of nanomaterials in controlled drug delivery for bone regeneration are reviewed and discussed, which indicates that the controlling drug delivery with nanomaterials should be a very promising treatment in orthopedics. Furthermore, some new challenges about the future research on the application of nanomaterials in controlled drug delivery for bone regeneration are described in the conclusion and perspectives part.

  18. [Review process of new oncology drug application in Japan--role of MD reviewer].

    Science.gov (United States)

    Fujiwara, Y

    1999-01-01

    On the basis of discussion by the Committee for Drug Safety Ensuring Measures, the Japanese Ministry of Health and Welfare (MHW) has amended the Pharmaceutical Affairs Law and related laws, and is reforming its review system for approving new drugs. One of the most important changes in the review system is the establishment of Pharmaceuticals and Medical Devices Evaluation Center (PMDEC) in July, 1997 under the National Institute of Health Sciences, a research institute under MHW. PMDEC, the Evaluation and Licensing Division at MHW and the Organization for Drug ADR Relief, R&D Promotion and Product Review (the Drug Organization) are in charge of drug approval, and reexamination and reevaluation applications. Before the reform new drug application reviews had been conducted mainly by the Central Pharmaceutical Affairs Council (CPAC). After the reform PMDEC, employing technical officials who have expertise in pharmacology, toxicology, biostatistics, clinical medicine, or other scientific fields, jointly review the applications with CPAC. The Evaluation and Licensing Division takes charge of administrative matters, such as final decisions on approvals, developing guidelines concerning the review process, international affairs, and regulatory instructions. During the early part of review the Drug Organization conducts a compliance review on the documents, which a sponsor submits with the approval application, and GCP inspection.

  19. Graphene-oxide stabilization in electrolyte solutions using hydroxyethyl cellulose for drug delivery application.

    Science.gov (United States)

    Mianehrow, Hanieh; Moghadam, Mohamad Hasan Mohamadzadeh; Sharif, Farhad; Mazinani, Saeedeh

    2015-04-30

    Stabilization of graphene oxide (GO) in physiological solution is performed using hydroxyethyl cellulose (HEC) to make the resultant nanohybrid suitable for targeted drug delivery purposes. Short and long term stability of GO suspensions with different ionic strengths were assessed using ultraviolet-visible spectroscopy (UV-vis), atomic force microscopy (AFM) and zeta potential measurements. Results depicted that HEC effectively stabilized GO in electrolyte solutions and the mechanism of stabilization appeares to be depended on HEC content. Drug loading and release behavior of folic acid (FA) as a model drug, from GO-HEC nanohybrid were studied to assess its application in drug delivery systems. Results showed the nanohybrid could be highly loaded by folic acid. Moreover, HEC content in the nanohybrid played an important role in final application to make it applicable either as a carrier for controllable drug release or as a folate-targeted drug carrier. In addition, according to cytotoxicity results, the nanohybrid showed good biocompatibility which indeed confirms its potential application as a drug carrier.

  20. High-content analysis for drug delivery and nanoparticle applications.

    Science.gov (United States)

    Brayden, David J; Cryan, Sally-Ann; Dawson, Kenneth A; O'Brien, Peter J; Simpson, Jeremy C

    2015-08-01

    High-content analysis (HCA) provides quantitative multiparametric cellular fluorescence data. From its origins in discovery toxicology, it is now addressing fundamental questions in drug delivery. Nanoparticles (NPs), polymers, and intestinal permeation enhancers are being harnessed in drug delivery systems to modulate plasma membrane properties and the intracellular environment. Identifying comparative mechanistic cytotoxicity on sublethal events is crucial to expedite the development of such systems. NP uptake and intracellular routing pathways are also being dissected using chemical and genetic perturbations, with the potential to assess the intracellular fate of targeted and untargeted particles in vitro. As we discuss here, HCA is set to make a major impact in preclinical delivery research by elucidating the intracellular pathways of NPs and the in vitro mechanistic-based toxicology of formulation constituents.

  1. Telephone surveying for drug abuse: methodological issues and an application.

    Science.gov (United States)

    Frank, B

    1985-01-01

    In light of New York State's experience, it is probable that future household drug use surveys will use telephone administration. Drug use questions are not as sensitive as had been thought, and are easily administered by telephone. In addition, the lower costs, the computer-assisted capabilities, and the saving in time are some of the advantages in comparison to face-to-face surveying. In order to address the nontelephone segments of the household population--despite their declining proportion--and to improve response rates, mixed-mode interviewing may have to be considered. Given a better understanding of telephone-associated behavior and the increasing popularity of technological advances, such as the portability and mobility of phones, telephone surveying may become even more attractive in the future.

  2. Application of Fused Deposition Modelling (FDM) Method of 3D Printing in Drug Delivery.

    Science.gov (United States)

    Long, Jingjunjiao; Gholizadeh, Hamideh; Lu, Jun; Bunt, Craig; Seyfoddin, Ali

    2017-01-01

    Three-dimensional (3D) printing is an emerging manufacturing technology for biomedical and pharmaceutical applications. Fused deposition modelling (FDM) is a low cost extrusion-based 3D printing technique that can deposit materials layer-by-layer to create solid geometries. This review article aims to provide an overview of FDM based 3D printing application in developing new drug delivery systems. The principle methodology, suitable polymers and important parameters in FDM technology and its applications in fabrication of personalised tablets and drug delivery devices are discussed in this review. FDM based 3D printing is a novel and versatile manufacturing technique for creating customised drug delivery devices that contain accurate dose of medicine( s) and provide controlled drug released profiles. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. Raman spectroscopy towards clinical application: drug monitoring and pathogen identification.

    Science.gov (United States)

    Neugebauer, Ute; Rösch, Petra; Popp, Jürgen

    2015-12-01

    Raman spectroscopy is a label-free method that measures quickly and contactlessly, providing detailed information from the sample, and has proved to be an ideal tool for medical and life science research. In this review, recent advances of the technique towards drug monitoring and pathogen identification by the Jena Research Groups are reviewed. Surface-enhanced Raman spectroscopy (SERS) and ultraviolet resonance Raman spectroscopy in hollow-core optical fibres enable the detection of drugs at low concentrations as shown for the metabolites of the immunosuppressive drug 6-mercaptopurine as well as antimalarial agents. Furthermore, Raman spectroscopy can be used to characterise pathogenic bacteria in infectious diseases directly from body fluids, making time-consuming cultivation processes dispensable. Using the example of urinary tract infection, it is shown how bacteria can be identified from patients' urine samples within <1 h. The methods cover both single-cell analysis and dielectrophoretic capturing of bacteria in suspension. The latter method could also be used for fast (<3.5 h) identification of antibiotic resistance as shown exemplarily for vancomycin-resistant enterococci. Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  4. Central Nervous System Multiparameter Optimization Desirability: Application in Drug Discovery.

    Science.gov (United States)

    Wager, Travis T; Hou, Xinjun; Verhoest, Patrick R; Villalobos, Anabella

    2016-06-15

    Significant progress has been made in prospectively designing molecules using the central nervous system multiparameter optimization (CNS MPO) desirability tool, as evidenced by the analysis reported herein of a second wave of drug candidates that originated after the development and implementation of this tool. This simple-to-use design algorithm has expanded design space for CNS candidates and has further demonstrated the advantages of utilizing a flexible, multiparameter approach in drug discovery rather than individual parameters and hard cutoffs of physicochemical properties. The CNS MPO tool has helped to increase the percentage of compounds nominated for clinical development that exhibit alignment of ADME attributes, cross the blood-brain barrier, and reside in lower-risk safety space (low ClogP and high TPSA). The use of this tool has played a role in reducing the number of compounds submitted to exploratory toxicity studies and increasing the survival of our drug candidates through regulatory toxicology into First in Human studies. Overall, the CNS MPO algorithm has helped to improve the prioritization of design ideas and the quality of the compounds nominated for clinical development.

  5. Application of drug testing using exhaled breath for compliance monitoring of drug addicts in treatment.

    Science.gov (United States)

    Carlsson, Sten; Olsson, Robert; Lindkvist, Irene; Beck, Olof

    2015-04-01

    Exhaled breath has recently been identified as a possible matrix for drug testing. This study explored the potential of this new method for compliance monitoring of patients being treated for dependence disorders. Outpatients in treatment programs were recruited for this study. Urine was collected as part of clinical routine and a breath sample was collected in parallel together with a questionnaire about their views of the testing procedure. Urine was analyzed for amphetamines, benzodiazepines, cannabis, cocaine, buprenorphine, methadone and opiates using CEDIA immunochemical screening and mass spectrometry confirmation. The exhaled breath was collected using the SensAbues device and analyzed by mass spectrometry for amphetamine, methamphetamine, diazepam, oxazepam, tetrahydrocannabinol, cocaine, benzoylecgonine, buprenorphine, methadone, morphine, codeine and 6-acetylmorphine. A total of 122 cases with parallel urine and breath samples were collected; 34 of these were negative both in urine and breath. Out of 88 cases with positive urine samples 51 (58%) were also positive in breath. Among the patients on methadone treatment, all were positive for methadone in urine and 83% were positive in breath. Among patients in treatment with buprenorphine, 92% were positive in urine and among those 80% were also positive in breath. The questionnaire response documented that in general, patients accepted drug testing well and that the breath sampling procedure was preferred. Compliance testing for the intake of prescribed and unprescribed drugs among patients in treatment for dependence disorders using the exhaled breath sampling technique is a viable method and deserves future attention.

  6. Synthesis, characterization and bioevaluation of drug-collagen hybrid materials for biomedical applications.

    Science.gov (United States)

    Voicu, Georgeta; Geanaliu-Nicolae, Ruxandra-Elena; Pîrvan, Adrian-Alexandru; Andronescu, Ecaterina; Iordache, Florin

    2016-08-30

    This work presents a study based on the preparation and characterization of drug-collagen hybrid materials. Materials used for obtaining drug-collagen hybrids were collagen type I (Coll) as matrix and fludarabine (F) and epirubicin (E) as hydrophilic active substances. After incorporation of drugs into Coll in different ratios, the obtained hybrid materials (Coll/F and Coll/E) could be used according to our results as potential drug delivery systems in medicine for the topical (local) treatment of cancerous tissues (e.g. the treatment of breast, stomach, lung, colorectal or advanced ovarian cancer). The materials were characterized considering their composition (by XRD, FT-IR and DTA-TG) and their morphology (by SEM). The delivery of drug was assessed by UV-vis. The in vitro citotoxicity demonstrates an antitumoral activity of the obtained hybrid materials and their potential use for biomedical applications as drug delivery systems in tumoral treatments.

  7. Application of RNAi to Genomic Drug Target Validation in Schistosomes.

    Directory of Open Access Journals (Sweden)

    Alessandra Guidi

    2015-05-01

    Full Text Available Concerns over the possibility of resistance developing to praziquantel (PZQ, has stimulated efforts to develop new drugs for schistosomiasis. In addition to the development of improved whole organism screens, the success of RNA interference (RNAi in schistosomes offers great promise for the identification of potential drug targets to initiate drug discovery. In this study we set out to contribute to RNAi based validation of putative drug targets. Initially a list of 24 target candidates was compiled based on the identification of putative essential genes in schistosomes orthologous of C. elegans essential genes. Knockdown of Calmodulin (Smp_026560.2 (Sm-Calm, that topped this list, produced a phenotype characterised by waves of contraction in adult worms but no phenotype in schistosomula. Knockdown of the atypical Protein Kinase C (Smp_096310 (Sm-aPKC resulted in loss of viability in both schistosomula and adults and led us to focus our attention on other kinase genes that were identified in the above list and through whole organism screening of known kinase inhibitor sets followed by chemogenomic evaluation. RNAi knockdown of these kinase genes failed to affect adult worm viability but, like Sm-aPKC, knockdown of Polo-like kinase 1, Sm-PLK1 (Smp_009600 and p38-MAPK, Sm-MAPK p38 (Smp_133020 resulted in an increased mortality of schistosomula after 2-3 weeks, an effect more marked in the presence of human red blood cells (hRBC. For Sm-PLK-1 the same effects were seen with the specific inhibitor, BI2536, which also affected viable egg production in adult worms. For Sm-PLK-1 and Sm-aPKC the in vitro effects were reflected in lower recoveries in vivo. We conclude that the use of RNAi combined with culture with hRBC is a reliable method for evaluating genes important for larval development. However, in view of the slow manifestation of the effects of Sm-aPKC knockdown in adults and the lack of effects of Sm-PLK-1 and Sm-MAPK p38 on adult viability

  8. Application Effect of Nursing Risk Management Measures in Pediatric Scalp Intravenous Infusion%护理风险管理措施在儿童头皮静脉输液中的应用效果分析

    Institute of Scientific and Technical Information of China (English)

    孙连红

    2016-01-01

    目的:探讨护理风险管理措施在儿童头皮静脉输液中的应用效果。方法选择2015年4月~2016年4月我院收治的头皮静脉输液患儿304例,将其平均分为研究组与对照组,各152例。对照组采取常规输液护理干预,研究组在此基础上应用护理风险管理干预。结果研究组反复穿刺率、液体渗出率及针头脱落率分别为3.29%、1.97%、1.97%,均低于对照组的9.87%、7.89%、8.55%(P<0.05)。结论护理风险管理措施在儿童头皮静脉输液中具有显著的应用效果,适于推广。%Objective To study the nursing risk management measures in pediatric scalp intravenous infusion in application effect. Methods 304 cases of scalp intravenous infusion were selected from April 2015 to April 2016 in our hospital, they average were divided into the research group and the control group (n=152). The control group was given regular transfusion nursing intervention, the research group on the basis of the application was given nursing risk management intervention. Results The repeated puncture rate, liquid leakage rate and needle loss rate of the research group were 3.29%, 1.97% and 1.97% respectively, were lower than the control group(9.87%, 7.89%, 8.55%) (P<0.05). Conclusion Nursing risk management measures in the children's scalp intravenous fluids has obvious application effect, suitable for promotion.

  9. Alginate drug delivery systems: application in context of pharmaceutical and biomedical research.

    Science.gov (United States)

    Jain, Dharmendra; Bar-Shalom, Daniel

    2014-12-01

    Alginates are natural polymers widely used in the food industry because of their biocompatible, biodegradable character, nontoxicity and easy availability. The bioadhesive character of alginates makes them useful in the pharmaceutical industry as well. The application areas of sodium alginate-based drug delivery systems are many and these systems can be formulated as gels, matrices, membranes, nanospheres, microspheres, etc. Worldwide researchers are exploring possible applications of alginates as coating material, preparation of controlled-release drug delivery systems such as microspheres, beads, pellets, gels, fibers, membranes, etc. In the present review, such applications of alginates are discussed.

  10. 77 FR 65198 - Generic Drug User Fee-Abbreviated New Drug Application, Prior Approval Supplement, and Drug...

    Science.gov (United States)

    2012-10-25

    ... applications in the backlog as of October 1, 2012, on finished dosage form (FDF) and active pharmaceutical ingredient (API) facilities, and on type II active pharmaceutical ingredient DMFs to be made available for... pharmaceutical ingredients other than by reference to a DMF will pay an additional fee that is based on...

  11. 78 FR 60292 - Draft Guidance for Industry on Abbreviated New Drug Application Submissions-Refuse-to-Receive...

    Science.gov (United States)

    2013-10-01

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Abbreviated New Drug Application Submissions--Refuse-to-Receive Standards; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of a...

  12. Biotech injectable drugs: clinical applications and financial effects.

    Science.gov (United States)

    Vogenberg, F Randy; Young, Coleen

    2004-07-01

    Biotechnology-derived injectable medications raise complex issues with respect to access and administration for both manufacturers and payers. In addition, biotech injectables rarely fit within traditional prescription drug benefit design structures, thereby creating inequities in reimbursement and access that can undermine a health benefit plan's goals.Benefit-design changes focusing on short-term solutions can exacerbate such situations. Employers, insurers, and managed care organizations need to consider innovative benefit-plan designs to effectively address issues that are associated with biotech medications.Actuarial models, such as the Reimbursement model described in this article, can help to provide the options analyses and decision-making support that are required.

  13. The Influence of Drug Testing Attributes, Participation, and Personality on Potential Applicant's Attitudes and Job Pursuit Intentions.

    Science.gov (United States)

    Stoffey, Ronald W.

    Researchers are increasingly aware of the importance of job applicants' reactions to the personnel selection process. This study examines three variables in connection with drug testing policies: (1) the potential applicant's reactions to two different drug testing policies which varied in terms of drug policy characteristics and their impact on…

  14. 76 FR 59144 - Novartis Pharmaceuticals Corp. et al.; Withdrawal of Approval of 27 New Drug Applications and 58...

    Science.gov (United States)

    2011-09-23

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Novartis Pharmaceuticals Corp. et al.; Withdrawal of Approval of 27 New Drug Applications and 58 Abbreviated New Drug Applications; Correction AGENCY: Food...

  15. [Intravenous monoanesthesia and antianesthetics in emergency surgery].

    Science.gov (United States)

    D'iachenko, P K; Kostiuchenko, A L

    1984-04-01

    Profiles of using the intravenous mononarcosis (sodium hydroxybutyrate, viadryl , ketamin , sombrevin, seduxen) in urgent surgery and traumatology are analyzed. Choice of certain narcotics is motivated for patients with blood loss and shock, intoxication, insufficiency of kidneys, adrenals and liver, cardio-vascular and respiratory disorders. The problem of antinarcotics is considered with reference to the efficiency of specific (bemegride, gutimine , amtizol , cytochrome "C") and nonspecific ( osmodiuretics , infusion media containing thawing water) antinarcotics . A preliminary assessment of the efficiency of different drugs of antinarcotic action is given.

  16. THROMBOTIC MICROANGIOPATHY ASSOCIATED WITH OPANA ER INTRAVENOUS ABUSE A Case Report.

    Science.gov (United States)

    Jabr, Fadi I; Yu, Ling

    2016-01-01

    Thrombotic microangiopathy is characterized by endothelial changes and microvascular stenosis. Several entities such as pregnancy, infection, connective tissue diseases, and drugs are associated with secondary thrombotic microangiopathy. Recently, new reformulation of Opana ER had been associated with thrombotic microangiopathy when injected intravenously. Here, we report the case of a 37-year-old man who developed renal failure and hemolytic anemia secondary to Opana ER intravenous abuse. Renal biopsy pathology was consistent with thrombotic microangiopathy likely caused by Opana ER intravenous abuse.

  17. Multiple sclerosis: Therapeutic applications of advancing drug delivery systems.

    Science.gov (United States)

    Dolati, Sanam; Babaloo, Zohreh; Jadidi-Niaragh, Farhad; Ayromlou, Hormoz; Sadreddini, Sanam; Yousefi, Mehdi

    2017-02-01

    Multiple sclerosis (MS) is an inflammatory autoimmune disease of the central nervous system, which is accompanying with demyelination, neurodegeneration and sensibility to oxidative stress. In MS, auto-reactive lymphocytes cross the blood-brain barrier (BBB) and reside in the perivenous demyelinating lesions which create various distinct inflammatory demyelinated plaques situated predominantly in the white matter. The current MS-related therapeutic approaches can be classified into disease-modifying therapies (DMTs) and symptomatic therapy. DMTs suppress circulating immune cells, inhibit passing the BBB and decrease the inflammatory responses. Recent advances have remarkably delayed disease development and improved the quality of life for numerous patients. In spite of major improvements in therapeutic options, there are some limitations regarding the routes of administration and the necessity for repeated and long-term dosing in which cause to systemic disadvantageous consequences and patient non-compliance. Nanotechnology presents promising approaches to improve autoimmune disease treatment with the capability to overcome many of the limitations common to the current immunosuppressive and biological therapies. Here we emphasis on nanomedicine-based drug delivery approaches of biological immunomodulatory mediators for the treatment of multiple sclerosis. This comprehensive review details the most successful drugs in MS therapy and also focuses on conceptions and clinical potential of novel nanomedicine attitudes for inducing immunosuppression and immunological tolerance in MS to modulate abnormal and pathologic immune responses.

  18. Quinoline based polymeric drug for biological applications: synthesis, characterization, antimicrobial, and drug releasing studies.

    Science.gov (United States)

    Uma, P; Suresh, J; Selvaraj, Revathy; Karthik, S; Arun, A

    2015-01-01

    Novel acrylate monomer of quinoline-based chalcone 1-(4-(7-chloroquinolin-4-ylamino)phenyl) acrylate (CPA) was synthesized using (4-(2-chloroquinolin-5-ylamino)phenyl)-3-(4-hydroxyphenyl)prop-2-en-1-one (CPE) and acryloyl chloride. CPA is characterized by different techniques like IR, (1)H NMR and UV-visible spectrometry techniques. Poly(CPA), poly(CPA-co-AA) and poly(CPA-co-HEA) are prepared by solution polymerization technique using CPA, acrylic acid (AA) and hydroxyethylacrylate (HEA), respectively. The antimicrobial activities of the compounds are tested using four different micro-organisms. In vitro cumulative drug release studies are done using UV visible spectroscopic technique. The molecular weights of these polymers are found to be around 5000 g/mol. The synthesized polymers showed two stages of thermal decomposition temperature centred around 220 and 350 °C, respectively. The antimicrobial activity of the polymer sample is found to be very high and especially for gram-negative bacteria with a minimum value of 3.91 μg/mL. The in vitro drug-releasing rate is dependent on the comonomer, pH and temperature of the medium.

  19. Applications of alcohol clamping in early drug development

    NARCIS (Netherlands)

    Zoethout, Remco Wiebe Martijn

    2012-01-01

    This thesis describes the development of a novel alcohol clamp, a new method to obtain stable plasma levels of alcohol and its application in CNS-research. The method might have several advantages that were explored in subsequent studies described in this thesis. The stability of the alcohol clamp w

  20. Applicability of the SPAN-100 index in a prospective and contemporary cohort of patients treated with intravenous rtPA in Catalonia.

    Science.gov (United States)

    Abilleira, S; Ribera, A; Quesada, H; Rubiera, M; Castellanos, M; Vargas, M; Gomis, M; Krupinski, J; Delgado-Mederos, R; Gómez-Choco, M; Giralt-Steinhauer, E; Garcia, M C; Pellisé, A; Purroy, F; Garcés, M; Gallofré, M

    Prognostic scales can be helpful for selecting patients for reperfusion treatment. This study aims to assess the prognostic ability of the recently published SPAN-100 index in a large cohort of stroke patients treated with intravenous thrombolysis (IV rtPA). Using data from the prospective registery of all reperfusion treatments administered in Catalonia, we selected patients treated with IV rtPA alone between 2011 and 2012. The SPAN-100 index was calculated as the sum of age (years) and NIHSS score, and patients in the cohort were classified as SPAN-100 positive [≥ 100] or SPAN-100 negative [independence (mRS 0-2) at 3 months was nearly 8 times higher in the SPAN-100 negative group than in the positive group. Furthermore, the 3-month mortality rate was 5 times higher in the SPAN-100 positive group. ROC curve analysis showed high specificities for predicting both functional independence and 3-month mortality for a cut-off point of 100. The SPAN-100 index is a simple and straightforward method that may be useful for selecting candidates for rtPA treatment in doubtful cases, and for informing patients and their relatives about likely outcomes. Copyright © 2013 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. In Vitro Transcription Assays and Their Application in Drug Discovery.

    Science.gov (United States)

    Yang, Xiao; Ma, Cong

    2016-09-20

    In vitro transcription assays have been developed and widely used for many years to study the molecular mechanisms involved in transcription. This process requires multi-subunit DNA-dependent RNA polymerase (RNAP) and a series of transcription factors that act to modulate the activity of RNAP during gene expression. Sequencing gel electrophoresis of radiolabeled transcripts is used to provide detailed mechanistic information on how transcription proceeds and what parameters can affect it. In this paper we describe the protocol to study how the essential elongation factor NusA regulates transcriptional pausing, as well as a method to identify an antibacterial agent targeting transcription initiation through inhibition of RNAP holoenzyme formation. These methods can be used a as platform for the development of additional approaches to explore the mechanism of action of the transcription factors which still remain unclear, as well as new antibacterial agents targeting transcription which is an underutilized drug target in antibiotic research and development.

  2. Nano Sponges for Drug Delivery and Medicinal Applications

    Science.gov (United States)

    Tour, James M.; Lucente-Schultz, Rebecca; Leonard, Ashley; Kosynkin, Dimitry V.; Price, Brandi Katherine; Hudson, Jared L.; Conyers, Jodie L., Jr.; Moore, Valerie C.; Casscells, S. Ward; Myers, Jeffrey N.; Milas, Zvonimir L.; Milas, Luka; Mason, Kathy A.

    2012-01-01

    This invention is a means of delivering a drug, or payload, to cells using non-covalent associations of the payload with nano-engineered scaffolds; specifically, functionalized single-walled carbon nanotubes (SWNTs) and their derivatives where the payload is effectively sequestered by the nanotube's addends and then delivered to the site (often interior of a cell) of interest. Polyethylene glycol (PEG) and other water-soluble organic molecules have been shown to greatly enhance the solubility of SWNTs in water. PEG groups and other water-solubilizing addends can act to sequester (sponge) molecules and deliver them into cells. Using PEG that, when attached to the SWNTs, the SWNT/PEG matrix will enter cells has been demonstrated. This was visualized by the addition of fluorescein isothiocyanate (FITC) to the SWNT/PEG matrix. Control studies showed that both FITC alone and FITC/PEG did not enter the cells. These observations suggest that the FITC is highly associated with the SWNT/PEG matrix that brings the FITC into the cells, allowing visualization of SWNTs in cells. The FITC is not covalently attached, because extended dialysis in hot DMF will remove all fluorescence quickly (one week). However, prolonged dialysis in water (1-2 months) will only slowly diminish the fluorescence. This demonstrates that the SWNT/PEG matrix solubilizes the FITC by sequestering it from the surrounding water and into the more solubilizing organic environment of the SWNT/PEG matrix of this type. This can be extended for the sequestering of other molecules such as drugs with PEG and other surfactants.

  3. Application of lean manufacturing concepts to drug discovery: rapid analogue library synthesis.

    Science.gov (United States)

    Weller, Harold N; Nirschl, David S; Petrillo, Edward W; Poss, Michael A; Andres, Charles J; Cavallaro, Cullen L; Echols, Martin M; Grant-Young, Katherine A; Houston, John G; Miller, Arthur V; Swann, R Thomas

    2006-01-01

    The application of parallel synthesis to lead optimization programs in drug discovery has been an ongoing challenge since the first reports of library synthesis. A number of approaches to the application of parallel array synthesis to lead optimization have been attempted over the years, ranging from widespread deployment by (and support of) individual medicinal chemists to centralization as a service by an expert core team. This manuscript describes our experience with the latter approach, which was undertaken as part of a larger initiative to optimize drug discovery. In particular, we highlight how concepts taken from the manufacturing sector can be applied to drug discovery and parallel synthesis to improve the timeliness and thus the impact of arrays on drug discovery.

  4. Application of imaging mass spectrometry approaches to facilitate metal-based anticancer drug research.

    Science.gov (United States)

    Lee, Ronald F S; Theiner, Sarah; Meibom, Anders; Koellensperger, Gunda; Keppler, Bernhard K; Dyson, Paul J

    2017-02-03

    Mass spectrometry imaging is being increasingly used in metal-based anticancer drug development to study elemental and/or molecular drug distributions in different biological systems. The main analytical tools employed are SIMS (especially nanoSIMS), LA-ICP-MSI and MALDI-MSI as well as a combination of complementary imaging techniques. Main challenges are appropriate sample preparation methods, reliable and validated quantification strategies and a trade-off between sensitivity and spatial resolution. So far, research has mostly focused on the development of analytical methods for imaging with the long term goal to study drug uptake into tumor tissue and toxicity affected organs and to identify cellular targets of metal-based drugs. In this review we cover the technological features of the mass spectrometry imaging methods used and give an overview of the applications in metal-based anticancer drug research as well as some future perspectives.

  5. Clinical applications of drug desensitization in the Asia-Pacific region.

    Science.gov (United States)

    Thong, Bernard Yu-Hor

    2011-04-01

    Drug desensitization is the induction, within hours to days, of a temporary state of tolerance to a drug which the patient has developed a hypersensitivity reaction to. It may be used for IgE and non-IgE mediated allergic reactions, and certain non-allergic reactions. The indication for desensitization is where no alternative medications are available for the treatment of that condition, and where the benefits of desensitization outweigh the risks. Desensitization is a therapeutic modality for drug allergy (similar to allergen specific immunotherapy for allergic rhinitis and insect venom anaphylaxis). In contrast, the drug provocation test is a diagnostic modality used to confirm or refute the diagnosis of drug allergy. This review discusses the clinical applications of desensitization for the treatment of common infectious, metabolic and cardiovascular diseases, and oncological conditions in the Asia-Pacific region.

  6. Applications of nanosystems to anticancer drug therapy (Part I. Nanogels, nanospheres, nanocapsules).

    Science.gov (United States)

    Talevi, Alan; Gantner, Melisa E; Ruiz, María E

    2014-01-01

    One of the greatest challenges in cancer drug therapy is to maximize the effectiveness of the active agent while reducing its systemic adverse effects. To add more, many widely-used chemoterapeutic agents present unfavorable physicochemical properties (e.g. low solubility, lack of chemical or biological stability) that hamper or limit their therapeutic applications. All these issues may be overcome by designing adequate drug delivery systems; nanocarriers are particularly suitable for this purpose. Nanosystems can be used for targeted-drug release, treatment, diagnostic imaging and therapy monitoring. They allow the formulation of drug delivery systems with user-defined characteristics regarding solubility, biodegradability, particle size, release kinetics and active targeting, among others. This review (Part I) focuses on recent patents published between 2008 and the present day, related to nanospheres, nanocapsules and nanogels applied to anticancer drug therapy. Other nanosystems is covered in a second article (Part II).

  7. Possible Penalties Alternative to Imprisonment Applicable to Drug Consumers

    Directory of Open Access Journals (Sweden)

    Corina Nicolae

    2009-10-01

    Full Text Available Alternative criminal penalties to imprisonment represent a remedy for eliminating the negative consequences of detention and a consequence of the evolution and humanization of penalties. The economic and social advantages of the alternative criminal penalties explain to a great extent the necessity of their application, together with the diversification of these penalties in order to respond more effectively to individualization according to the offender as well as to the necessity to protect the society.

  8. Biodegradable PLGA-b-PEG polymeric nanoparticles: synthesis, properties, and nanomedical applications as drug delivery system

    Energy Technology Data Exchange (ETDEWEB)

    Locatelli, Erica; Comes Franchini, Mauro, E-mail: mauro.comesfranchini@unibo.it [University of Bologna, Dipartimento di Chimica Industriale Toso Montanari (Italy)

    2012-12-15

    During the past decades many synthetic polymers have been studied for nanomedicine applications and in particular as drug delivery systems. For this purpose, polymers must be non-toxic, biodegradable, and biocompatible. Polylactic-co-glycolic acid (PLGA) is one of the most studied polymers due to its complete biodegradability and ability to self-assemble into nanometric micelles that are able to entrap small molecules like drugs and to release them into body in a time-dependent manner. Despite fine qualities, using PLGA polymeric nanoparticles for in vivo applications still remains an open challenge due to many factors such as poor stability in water, big diameter (150-200 nm), and the removal of these nanocarriers from the blood stream by the liver and spleen thus reducing the concentration of drugs drastically in tumor tissue. Polyethylene glycol (PEG) is the most used polymers for drug delivery applications and the first PEGylated product is already on the market for over 20 years. This is due to its stealth behavior that inhibits the fast recognition by the immune system (opsonization) and generally leads to a reduced blood clearance of nanocarriers increasing blood circulation time. Furthermore, PEG is hydrophilic and able to stabilize nanoparticles by steric and not ionic effects especially in water. PLGA-PEG block copolymer is an emergent system because it can be easily synthesized and it possesses all good qualities of PLGA and also PEG capability so in the last decade it arose as one of the most promising systems for nanoparticles formation, drug loading, and in vivo drug delivery applications. This review will discuss briefly on PLGA-b-PEG synthesis and physicochemical properties, together with its improved qualities with respect to the single PLGA and PEG polymers. Moreover, we will focus on but in particular will treat nanoparticles formation and uses as new drug delivery system for nanomedical applications.

  9. Fabrication of biodegradable polymer (PLGA) microstructures and applications in controlled drug delivery

    Science.gov (United States)

    Yang, Ren; Chen, Tianning; Chen, Hualing; Wang, Wanjun

    2004-01-01

    Using biodegradable polymers for implantable drug delivery purposes has been a very important research area and industry for many years. Polymers, such as PLGA, have been the most attractive one because it does not require removal after the drug has been released. We report a research effort to microfabricate high aspect ratio microstructures of PLGA and its potential applications in implantable drug delivery. The prototypes of packaged cells with dyes have also been made and currently under test for linear release of sample dyes.

  10. The application of antitumor drug-targeting models on liver cancer.

    Science.gov (United States)

    Yan, Yan; Chen, Ningbo; Wang, Yunbing; Wang, Ke

    2016-06-01

    Hepatocarcinoma animal models, such as the induced tumor model, transplanted tumor model, gene animal model, are significant experimental tools for the evaluation of targeting drug delivery system as well as the pre-clinical studies of liver cancer. The application of antitumor drug-targeting models not only furnishes similar biological characteristics to human liver cancer but also offers guarantee of pharmacokinetic indicators of the liver-targeting preparations. In this article, we have reviewed some kinds of antitumor drug-targeting models of hepatoma and speculated that the research on this field would be capable of attaining a deeper level and expecting a superior achievement in the future.

  11. An Analysis of Therapeutic Effect of Drug Acupoint Application in 209 Cases of Allergic Asthma

    Institute of Scientific and Technical Information of China (English)

    赖新生; 李月梅; 范兆金; 张家维; 刘炳权

    2001-01-01

    Both therapies of traditional crude herb moxibustion and drug acupoint application were used in 209 cases of allergic asthma to compare their long-term and short-term therapeutic effects and to analyze the relationship between clinic therapeutic effects of both therapies and differential types of the disease. The results showed that the short-term total effective rate in the group of drug acupoint application was higher than that in the group of traditional crude herb moxibustion, the therapeutic effects of drug acupoint application being closely related to differential types. Analysis also shows the best short-term therapeutic effect was in the type of heat in the lung while the poorest effect in the type of deficiency of the kidney-yang.

  12. Systematic Evaluation of Drug-Loaded Hydrogels for Application in Osteosarcoma Treatment.

    Science.gov (United States)

    Ali Gumustas, Seyit; Isyar, Mehmet; Topuk, Savas; Yilmaz, Ibrahim; Oznam, Kadir; Onay, Tolga; Ofluoglu, Onder; Mahirogullari, Mahir

    This is a literature review of studies focusing on the preparation of hydrogels for use as oncological drug delivery systems in the treatment of osteosarcoma (OS). The databases of the US National Library of Medicine National Institutes of Health, Embase, OVID, and Cochrane Library, and the references of retrieved studies, were traced from 1843 to December 21, 2015, without language restrictions. The obtained data were evaluated by complementary statistical methods. Potentially relevant studies were found and included in the analysis. OS-specific chemotherapeutic agents can be successfully embedded within the hydrogels and these drug-loaded hydrogels can be applied locally, rather than systemically, without organ tissue toxicity. Further, OS-specific drug-loaded hydrogels significantly increased tumor inhibition and decreased osteolysis and lung metastases. Drug-loaded hydrogels could be useful in the treatment of OS, although their development remains at the experimental phase. Following evaluation of their application in surgery and the completion of drug release kinetics studies, drug-loaded hydrogels could be tested on living mammals in large samples with the aim of applying these in clinical settings. In the future, development of such drug delivery systems and application of targeted approaches against osteosarcoma and other malignancies may render surgery, radiotherapy and chemotherapy unnecessary.

  13. Vesiculobullous eruption of the right arm after intravenous clarithromycin

    Directory of Open Access Journals (Sweden)

    Abdulkadir Kuçukbayrak

    2011-01-01

    Full Text Available Clarithromycin is a macrolide antibiotic. In clinical trials, adverse drug reactions of clarithromycin are usually mild and transient. Only 1% of the adverse reactions are severe. Herein, we present a case with vesiculobullous skin reaction and vein thrombosis caused by administration of intravenous clarithromycin.

  14. 21 CFR 314.107 - Effective date of approval of a 505(b)(2) application or abbreviated new drug application under...

    Science.gov (United States)

    2010-04-01

    ... introduction into interstate commerce when approval of the application or abbreviated application for the drug... for 5 years of exclusive marketing under § 314.108(b)(2) and the patent owner or its representative or... application first commences commercial marketing of its drug product; or (ii) The date of a decision of...

  15. Packaging protein drugs as bacterial inclusion bodies for therapeutic applications

    Directory of Open Access Journals (Sweden)

    Villaverde Antonio

    2012-06-01

    Full Text Available Abstract A growing number of insights on the biology of bacterial inclusion bodies (IBs have revealed intriguing utilities of these protein particles. Since they combine mechanical stability and protein functionality, IBs have been already exploited in biocatalysis and explored for bottom-up topographical modification in tissue engineering. Being fully biocompatible and with tuneable bio-physical properties, IBs are currently emerging as agents for protein delivery into mammalian cells in protein-replacement cell therapies. So far, IBs formed by chaperones (heat shock protein 70, Hsp70, enzymes (catalase and dihydrofolate reductase, grow factors (leukemia inhibitory factor, LIF and structural proteins (the cytoskeleton keratin 14 have been shown to rescue exposed cells from a spectrum of stresses and restore cell functions in absence of cytotoxicity. The natural penetrability of IBs into mammalian cells (reaching both cytoplasm and nucleus empowers them as an unexpected platform for the controlled delivery of essentially any therapeutic polypeptide. Production of protein drugs by biopharma has been traditionally challenged by IB formation. However, a time might have arrived in which recombinant bacteria are to be engineered for the controlled packaging of therapeutic proteins as nanoparticulate materials (nanopills, for their extra- or intra-cellular release in medicine and cosmetics.

  16. Application of Caco-2 Cell Line in Herb-Drug Interaction Studies: Current Approaches and Challenges

    Science.gov (United States)

    Awortwe, C.; Fasinu, P.S.; Rosenkranz, B.

    2015-01-01

    The Caco-2 model is employed in pre-clinical investigations to predict the likely gastrointestinal permeability of drugs because it expresses cytochrome P450 enzymes, transporters, microvilli and enterocytes of identical characteristics to the human small intestine. The FDA recommends this model as integral component of the Biopharmaceutics Classification System (BCS). Most dedicated laboratories use the Caco-2 cell line to screen new chemical entities through prediction of its solubility, bioavailability and the possibility of drug-drug or herb-drug interactions in the gut lumen. However, challenges in the inherent characteristics of Caco-2 cell and inter-laboratory protocol variations have resulted to generation of irreproducible data. These limitations affect the extrapolation of data from pre-clinical research to clinical studies involving drug-drug and herb-drug interactions. This review addresses some of these caveats and enumerates the plausible current and future approaches to reduce the anomalies associated with Caco-2 cell line investigations focusing on its application in herb-drug interactions. PMID:24735758

  17. Rational drug design approach for overcoming drug resistance: application to pyrimethamine resistance in malaria.

    Science.gov (United States)

    McKie, J H; Douglas, K T; Chan, C; Roser, S A; Yates, R; Read, M; Hyde, J E; Dascombe, M J; Yuthavong, Y; Sirawaraporn, W

    1998-04-23

    Pyrimethamine acts by selectively inhibiting malarial dihydrofolate reductase-thymidylate synthase (DHFR-TS). Resistance in the most important human parasite, Plasmodium falciparum, initially results from an S108N mutation in the DHFR domain, with additional mutation (most commonly C59R or N51I or both) imparting much greater resistance. From a homology model of the 3-D structure of DHFR-TS, rational drug design techniques have been used to design and subsequently synthesize inhibitors able to overcome malarial pyrimethamine resistance. Compared to pyrimethamine (Ki 1.5 nM) with purified recombinant DHFR fromP. falciparum, the Ki value of the m-methoxy analogue of pyrimethamine was 1.07 nM, but against the DHFR bearing the double mutation (C59R + S108N), the Ki values for pyrimethamine and the m-methoxy analogue were 71.7 and 14.0 nM, respectively. The m-chloro analogue of pyrimethamine was a stronger inhibitor of both wild-type DHFR (with Ki 0.30 nM) and the doubly mutant (C59R +S108N) purified enzyme (with Ki 2.40 nM). Growth of parasite cultures of P. falciparum in vitro was also strongly inhibited by these compounds with 50% inhibition of growth occurring at 3.7 microM for the m-methoxy and 0.6 microM for the m-chloro compounds with the K1 parasite line bearing the double mutation (S108N + C59R), compared to 10.2 microM for pyrimethamine. These inhibitors were also found in preliminary studies to retain antimalarial activity in vivo in P. berghei-infected mice.

  18. Advances in the use of intravenous techniques in ambulatory anesthesia

    Directory of Open Access Journals (Sweden)

    Eng MR

    2015-07-01

    Full Text Available Matthew R Eng,1 Paul F White1,2 1Department of Anesthesiology, Cedars-Sinai Medical Center, Los Angeles, CA, USA; 2White Mountain Institute, The Sea Ranch, CA, USA Summary statement: Advances in the use of intravenous techniques in ambulatory anesthesia has become important for the anesthesiologist as the key perioperative physician in outpatient surgery. Key techniques and choices of anesthetics are important in accomplishing fast track goals of ambulatory surgery. Purpose of review: The anesthesiologist in the outpatient environment must focus on improving perioperative efficiency and reducing recovery times while accounting for patients' well-being and safety. This review article focuses on recent intravenous anesthetic techniques to accomplish these goals. Recent findings: This review is an overview of techniques in intravenous anesthesia for ambulatory anesthesia. Intravenous techniques may be tailored to accomplish outpatient surgery goals for the type of surgical procedure and individual patient needs. Careful anesthetic planning and the application of the plans are critical to an anesthesiologist's success with fast-track ambulatory surgery. Conclusion: Careful planning and application of intravenous techniques are critical to an anesthesiologist's success with fast-track ambulatory surgery. Keywords: intravenous anesthesia, outpatient anesthesia, fast-track surgery

  19. A review of intravenous minocycline for treatment of multidrug-resistant Acinetobacter infections.

    Science.gov (United States)

    Ritchie, David J; Garavaglia-Wilson, Alexandria

    2014-12-01

    Options for treatment of multidrug-resistant (MDR) Acinetobacter baumannii infections are extremely limited. Minocycline intravenous is active against many MDR strains of Acinetobacter, and Clinical and Laboratory Standards Institute breakpoints exist to guide interpretation of minocycline susceptibility results with Acinetobacter. In addition, minocycline intravenous holds a US Food and Drug Administration indication for treatment of infections caused by Acinetobacter. There is an accumulating amount of literature reporting successful use of minocycline intravenous for treatment of serious MDR Acinetobacter infections, particularly for nosocomial pneumonia. These results, coupled with the generally favorable tolerability of minocycline intravenous, support its use as a viable therapeutic option for treatment of MDR Acinetobacter infections.

  20. 78 FR 52430 - Withdrawal of Approval of New Animal Drug Applications; Quali-Tech Products, Inc.; Bambermycins...

    Science.gov (United States)

    2013-08-23

    ... Animal Drug Applications; Quali- Tech Products, Inc.; Bambermycins; Pyrantel; Tylosin; Virginiamycin... (pyrantel tartrate), NADA 132-705 for FLAVOMYCIN (bambermycins), and NADA 133-335 for STAFAC...

  1. Cognitive status of junior pediatric nurses on intravenous infusion of high risk drugs and analysis of its influencing factors%低年资儿科护士对静脉输注高危药物的认知现状与影响因素分析

    Institute of Scientific and Technical Information of China (English)

    杨卫红; 赵丽; 吴月丽

    2015-01-01

    Objective:To probe into the cognitive status quo of junior pediatric nurses on intravenous infusion of high risk drugs and analysis of its influencing factors .Methods:A total of 539 cases of junior pediatric nurses in many hospitals in the region were surveyed by using general questionnaire and intravenous infusion of high risk drugs cognitive questionnaire ,and analyzing the influencing factors .Results:the total cognition score of nurses on intravenous infusion of high risk drugs was 85 .20 ± 6 .33 .Single factor analysis showed that sex ,marital sta‐tus ,educational background ,title ,gender ,age ,working years ,employment way had the influences on total cognition score of nurses on intravenous infusion of high risk drugs (P<0 .05) .Conclusion:The junior pediatric nurses had cognition deficiency on intravenous infusion of high risk drugs ,and it was related to employment way ,marital status ,working years and title .The hospital should take the targeted management training posi‐tively and improve the cognition level of junior pediatric nurses .%[目的]探讨低年资儿科护士对静脉输注高危药物的认知现状与影响因素。[方法]采用一般情况调查表和静脉输注高危药物认知调查表对选取的本地区多家医院儿科低年资护士539人进行调查,并分析其影响因素。[结果]护士对于静脉输注高危药物的认知总分为85.20分±6.33分。单因素分析显示,性别、婚姻状况、学历、职称、性别、聘用形式、年龄、工作年限都对静脉输注高危药物认知总分有影响(P<0.05);多因素逐步回归分析结果显示,聘用形式、婚姻状况、工作年限与职称对护士的静脉输注高危药物认知有影响(P<0.05)。[结论]低年资儿科护士静脉输注高危药物的认知存在不足,与护士的聘用形式、婚姻状况、工作年限与职称有关,医院应积极进行有针对性的管理培训,提高低年资护士的认知水平。

  2. Intravenous lipid emulsion in clinical toxicology

    Directory of Open Access Journals (Sweden)

    Oswald Sarah

    2010-10-01

    Full Text Available Abstract Intravenous lipid emulsion is an established, effective treatment for local anesthetic-induced cardiovascular collapse. The predominant theory for its mechanism of action is that by creating an expanded, intravascular lipid phase, equilibria are established that drive the offending drug from target tissues into the newly formed 'lipid sink'. Based on this hypothesis, lipid emulsion has been considered a candidate for generic reversal of toxicity caused by overdose of any lipophilic drug. Recent case reports of successful resuscitation suggest the efficacy of lipid emulsion infusion for treating non-local anesthetic overdoses across a wide spectrum of drugs: beta blockers, calcium channel blockers, parasiticides, herbicides and several varieties of psychotropic agents. Lipid emulsion therapy is gaining acceptance in emergency rooms and other critical care settings as a possible treatment for lipophilic drug toxicity. While protocols exist for administration of lipid emulsion in the setting of local anesthetic toxicity, no optimal regimen has been established for treatment of acute non-local anesthetic poisonings. Future studies will shape the evolving recommendations for lipid emulsion in the setting of non-local anesthetic drug overdose.

  3. 语言暗示在儿科静脉注射中的应用研究%The application of hinted language in children with intravenous injection

    Institute of Scientific and Technical Information of China (English)

    程艳; 汤华军; 张杨

    2015-01-01

    Objective To discussed the effect of different hinted language in reaction to pain for children with intra﹣venous injection(IV). Methods A total of 180 patients were chosen from January 2013 to December 2013 were randomly divid﹣ed into the positive hinted language group and the negative hinted language group ,separately used positive language or negative language to hint,then the two groups of patients were compared with pain feelings and related indicators. Results Positive lan﹣guage hinted group was better than negative language hinted group on the anxiety levels,the blood pressure changes,the pulse changes,the pain levels. There were statistically significant in difference (P<0.05);the negative hinted language group was better than the positive hinted language group in the satisfaction,there were statistically significant in differnce(P<0.05). Conclusion The positive hinted language can ease the pain of children in the intravenous injection.%目的:探讨不同语言暗示在儿科静脉注射时对疼痛反应的影响。方法选择2013年1~12月收治的180例患儿,随机分为正性语言暗示组、负性语言暗示组,各90例。在静脉注射前相应给予正性语言暗示和负性语言暗示,比较两组患儿焦虑值、疼痛分级及相关指标差异。结果正性语言暗示组在焦虑程度、血压变化、脉搏变化、疼痛程度优于负性语言暗示组,差异均有统计学意义(P<0.05),但满意度低于负性语言暗示组,差异有统计学意义(P<0.05)。结论正性语言暗示可减轻儿童静脉注射的疼痛反应。

  4. Seaweed Polysaccharide-Based Nanoparticles: Preparation and Applications for Drug Delivery

    Directory of Open Access Journals (Sweden)

    Jayachandran Venkatesan

    2016-01-01

    Full Text Available In recent years, there have been major advances and increasing amounts of research on the utilization of natural polymeric materials as drug delivery vehicles due to their biocompatibility and biodegradability. Seaweed polysaccharides are abundant resources and have been extensively studied for several biological, biomedical, and functional food applications. The exploration of seaweed polysaccharides for drug delivery applications is still in its infancy. Alginate, carrageenan, fucoidan, ulvan, and laminarin are polysaccharides commonly isolated from seaweed. These natural polymers can be converted into nanoparticles (NPs by different types of methods, such as ionic gelation, emulsion, and polyelectrolyte complexing. Ionic gelation and polyelectrolyte complexing are commonly employed by adding cationic molecules to these anionic polymers to produce NPs of a desired shape, size, and charge. In the present review, we have discussed the preparation of seaweed polysaccharide-based NPs using different types of methods as well as their usage as carriers for the delivery of various therapeutic molecules (e.g., proteins, peptides, anti-cancer drugs, and antibiotics. Seaweed polysaccharide-based NPs exhibit suitable particle size, high drug encapsulation, and sustained drug release with high biocompatibility, thereby demonstrating their high potential for safe and efficient drug delivery.

  5. Hydrolyzed polyacrylamide grafted maize starch based microbeads: application in pH responsive drug delivery.

    Science.gov (United States)

    Setty, C Mallikarjuna; Deshmukh, Anand S; Badiger, Aravind M

    2014-09-01

    The present study details the synthesis, characterization and pharmaceutical application of hydrolysed polyacrylamide grafted maize starch (HPam-g-MS) as promising polymeric material for the development of pH responsive microbeads. Different grades of graft copolymer were synthesized by changing the net microwave irradiation time, while keeping all other factors constant. Acute oral toxicity study performed in rodents ensured the bio-safety of graft copolymer for clinical application. Various batches of aceclofenac loaded microbeads were prepared by ionic gelation method using synthesized graft copolymers and evaluated for formulation parameters. FTIR spectroscopy confirmed the chemical compatibility between drug and graft copolymer. Results of in vitro release study (USP type-II) carried out in two different pH media (pH 1.2 acid buffer and pH 7.4 phosphate buffer) showed that release rate of drug from developed microbeads was a function of both: (a) surrounding pH and (b) the matrix composition. The drug release was relatively higher at alkaline pH as compared to acidic pH and this feature is desirable from viewpoint of site specific drug delivery. A direct correlation was observed between percentage grafting and microbeads performance and it presents a scope for further research on application and optimization of HPam-g-MS based microbeads as drug delivery carriers.

  6. [Threshold of Application of Antidepressant Drugs for Treatment of Depressive Disorder].

    Science.gov (United States)

    Kuroki, Toshihide; Tanaka, Teppei

    2015-01-01

    In recent years, along with the expansion of medical care for depressive disorder, there has been much controversy regarding the application of antidepressant drugs for its treatment. The aim of this paper is to consider critical issues concerning the threshold of application of antidepressant drugs for the treatment of depression. It was formerly important to diagnose the 'quality' of depression (melancholia or non-melancholia) in order to choose antidepressant treatment, whereas an assessment of the 'quantity' of depression (severity of symptoms) is crucial today to decide on the threshold. Recent guidelines for the treatment of major depressive disorder do not positively recommend the use of medication for the treatment of mild depression. The guidelines published by the Japanese Society of Mood Disorders also state that doctors have to give priority to treatments avoiding medication, although the effectiveness of antidepressant drugs for mild depression is controversial. Actually, in a clinical setting, doctors have to understand the conditions of individual cases and cope with many issues, such as a risk of suicide, comorbidity of other psychiatric disorders, target symptoms of pharmacotherapy, and choices of classes and doses of antidepressant drugs. The threshold of application of antidepressant drugs for the treatment of depression may vary according to the doctor-patient relationship and surrounding conditions. Doctors are required to provide treatment options other than pharmacotherapy.

  7. The application of carbon nanotubes in target drug delivery systems for cancer therapies

    Directory of Open Access Journals (Sweden)

    Zhang Zhenzhong

    2011-01-01

    Full Text Available Abstract Among all cancer treatment options, chemotherapy continues to play a major role in killing free cancer cells and removing undetectable tumor micro-focuses. Although chemotherapies are successful in some cases, systemic toxicity may develop at the same time due to lack of selectivity of the drugs for cancer tissues and cells, which often leads to the failure of chemotherapies. Obviously, the therapeutic effects will be revolutionarily improved if human can deliver the anticancer drugs with high selectivity to cancer cells or cancer tissues. This selective delivery of the drugs has been called target treatment. To realize target treatment, the first step of the strategies is to build up effective target drug delivery systems. Generally speaking, such a system is often made up of the carriers and drugs, of which the carriers play the roles of target delivery. An ideal carrier for target drug delivery systems should have three pre-requisites for their functions: (1 they themselves have target effects; (2 they have sufficiently strong adsorptive effects for anticancer drugs to ensure they can transport the drugs to the effect-relevant sites; and (3 they can release the drugs from them in the effect-relevant sites, and only in this way can the treatment effects develop. The transporting capabilities of carbon nanotubes combined with appropriate surface modifications and their unique physicochemical properties show great promise to meet the three pre-requisites. Here, we review the progress in the study on the application of carbon nanotubes as target carriers in drug delivery systems for cancer therapies.

  8. Cutaneous ulceration: an unusual complication of intravenous pentamidine therapy.

    Science.gov (United States)

    Bolognia, J L

    1991-01-01

    Pentamidine is one of two agents currently used to treat infections with Pneumocystis carinii. The intramuscular route of administration is associated with cutaneous side effects such as dermal necrosis, sterile abscesses and ulcer formation at the injection site, while urticaria may develop near the site of intravenous drug infusion. This is a report of a renal transplant patient with Pneumocystis pneumonia who developed chemical cellulitis and ulceration following the extravasation of intravenous pentamidine into the soft tissues of the left hand and forearm. The area healed slowly over 7 weeks, but there was a residual loss of cutaneous sensation. In a review of the literature no report of a similar case was found.

  9. Recurrence of Intravenous Talc Granulomatosis following Single Lung Transplantation

    Directory of Open Access Journals (Sweden)

    Richard C Cook

    1998-01-01

    Full Text Available Advanced pulmonary disease is an unusual consequence of the intravenous injection of oral medications, usually developing over a period of several years. A number of patients with this condition have undergone lung transplantation for respiratory failure. However, a history of drug abuse is often considered to be a contraindication to transplantation in the context of limited donor resources. A patient with pulmonary talc granulomatosis secondary to intravenous methylphenidate injection who underwent successful lung transplantation and subsequently presented with recurrence of the underlying disease in the transplanted lung 18 months after transplantation is reported.

  10. Magnetic nanoparticles: an update of application for drug delivery and possible toxic effects.

    Science.gov (United States)

    Kim, Ji-Eun; Shin, Ji-Young; Cho, Myung-Haing

    2012-05-01

    Magnetic nanoparticles (MNPs) represent a subclass within the overall category of nanomaterials and are widely used in many applications, particularly in the biomedical sciences such as targeted delivery of drugs or genes, in magnetic resonance imaging, and in hyperthermia (treating tumors with heat). Although the potential benefits of MNPs are considerable, there is a distinct need to identify any potential toxicity associated with these MNPs. The potential of MNPs in drug delivery stems from the intrinsic properties of the magnetic core combined with their drug loading capability and the biomedical properties of MNPs generated by different surface coatings. These surface modifications alter the particokinetics and toxicity of MNPs by changing protein-MNP or cell-MNP interactions. This review contains current advances in MNPs for drug delivery and their possible organ toxicities associated with disturbance in body iron homeostasis. The importance of protein-MNP interactions and various safety considerations relating to MNP exposure are also addressed.

  11. Influence of cochleostomy and cochlear implant insertion on drug gradients following intratympanic application in guinea pigs

    Science.gov (United States)

    King, EB; Hartsock, JJ; O'Leary, SJ; Salt, AN

    2013-01-01

    Locally-applied drugs can protect residual hearing following cochlear implantation. The influence of cochlear implantation on drug levels in scala tympani (ST) after round window application was investigated in guinea pigs using the marker trimethylphenlyammonium (TMPA) measured in real-time with TMPA-selective microelectrodes. TMPA concentration in the upper basal turn of ST rapidly increased during implantation and then declined due to cerebrospinal fluid entering ST at the cochlear aqueduct and exiting at the cochleostomy. The TMPA increase was found to be caused by the cochleostomy drilling, if the burr tip partially entered ST. TMPA distribution in the second turn was less affected by implantation procedures. These findings show that basal turn drug levels may be changed during implantation and the changes may need to be considered in the interpretation of therapeutic effects of drugs in conjunction with implantation. PMID:24008355

  12. Energy-triggered drug release from polymer nanoparticles for orthopedic applications.

    Science.gov (United States)

    Pullan, Jessica E; Pullan, Austin T; Taylor, V Bryce; Brooks, Benjamin D; Ewert, Daniel; Brooks, Amanda E

    2017-01-01

    Sequestra, present in many cancers and orthopedic infections, provide a safe harbor for the development of drug resistance. In the face of burgeoning drug resistance, the importance of nanoscale, microenvironment-triggered drug delivery cannot be overestimated. Such strategies may preserve pharmaceutical efficacy and significantly alter the etiology of many orthopedic diseases. Although temperature-, pH- and redox-responsive nanoparticle-based systems have been extensively studied, local drug delivery from polymeric nanoparticles can be triggered by a variety of energy forms. This review offers an overview of the state of the field as well as a perspective on the safety and efficacy of ultrasound, hyperthermia and radio frequency-triggered internal delivery systems in a variety of applications.

  13. Emerging technologies, recent developments, and novel applications for drug metabolite identification.

    Science.gov (United States)

    Lu, Wenjie; Xu, Youzhi; Zhao, Yinglan; Cen, Xiaobo

    2014-01-01

    Drug metabolite identification and metabolic characteristics analysis play a crucial role in new drug research and development, because they can lead to varied efficacy, severe adverse reactions, and even toxicity. Classical methodologies for metabolite identification have mainly been based on mass spectrometry (MS) coupled with gas chromatography (GC) or liquid chromatography (LC), and some other techniques are used as complementary approaches, such as nuclear magnetic resonance (NMR). Over the past decade, more and more newly emerging techniques or technologies have been applied to metabolite identification, and are making the procedure easier and more robust, such as LC-NMR-MS, ion mobility MS, ambient ionization techniques, and imaging MS. A novel application of drug metabolite identification based on "omics" known as pharmacometabonomics is discussed, which is an interdisciplinary field that combines pre-dose metabolite profiling and chemometrics methods for data analysis and modeling, aiming to predict the responses of individuals to drugs.

  14. Application of electron paramagnetic resonance (EPR) spectroscopy and imaging in drug delivery research - chances and challenges.

    Science.gov (United States)

    Kempe, Sabine; Metz, Hendrik; Mäder, Karsten

    2010-01-01

    Electron Paramagnetic Resonance (EPR) spectroscopy is a powerful technique to study chemical species with unpaired electrons. Since its discovery in 1944, it has been widely used in a number of research fields such as physics, chemistry, biology and material and food science. This review is focused on its application in drug delivery research. EPR permits the direct measurement of microviscosity and micropolarity inside drug delivery systems (DDS), the detection of microacidity, phase transitions and the characterization of colloidal drug carriers. Additional information about the spatial distribution can be obtained by EPR imaging. The chances and also the challenges of in vitro and in vivo EPR spectroscopy and imaging in the field of drug delivery are discussed.

  15. Synthesis of an amphiphilic dendrimer-like block copolymer and its application on drug delivery

    KAUST Repository

    Wang, Shuaipeng

    2014-10-27

    Dendrimer-like amphiphilic copolymer is a kind of three-dimensional spherical structure polymer. An amphiphilic dendrimer-like diblock copolymer, PEEGE-G2-b-PEO(OH)12, constituted of a hydrophobic poly(ethoxyethyl glycidol ether) inner core and a hydrophilic poly(ethylene oxide) outer layer, has been successfully synthesized by the living anionic ring-opening polymerization method. The intermediates and targeted products were characterized with 1H NMR spectroscopy and gel permeation chromatography. The application on drug delivery of dendrimer-like diblock copolymer PEEGE-G2-b-PEO(OH)12 using DOX as a model drug was also studied. The drug loading content and encapsulation efficiency were found at 13.07% and 45.75%, respectively. In vitro release experiment results indicated that the drug-loaded micelles exhibited a sustained release behavior under acidic media.

  16. Guidance on preparing an investigational new drug application for fecal microbiota transplantation studies.

    Science.gov (United States)

    Kelly, Colleen R; Kunde, Sachin S; Khoruts, Alexander

    2014-02-01

    Fecal microbiota transplantation (FMT) is an effective treatment for Clostridium difficile infections that are refractory to antibiotic therapy. Because of the important roles of the microbiota in the function of the gastrointestinal tract and other aspects of human physiology, there is a growing interest in studying FMT for other clinical indications. The US Food and Drug Administration regulates clinical studies to evaluate the safety and efficacy of FMT. Studies of FMT for recurrent Clostridium difficile infection or other indications could require submission of an investigational new drug application. Most academic physicians and investigators do not have the regulatory experience necessary to undertake this process. We provide guidance to researchers on the preparation and submission of investigational new drug applications to study FMT. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  17. Modified chitosan hydrogels as drug delivery and tissue engineering systems: present status and applications

    Directory of Open Access Journals (Sweden)

    Tapan Kumar Giri

    2012-10-01

    Full Text Available Chitosan, a natural cationic polysaccharide, is prepared industrially by the hydrolysis of the aminoacetyl groups of chitin, a naturally available marine polymer. Chitosan is a non-toxic, biocompatible and biodegradable polymer and has attracted considerable interest in a wide range of biomedical and pharmaceutical applications including drug delivery, cosmetics, and tissue engineering. The primary hydroxyl and amine groups located on the backbone of chitosan are responsible for the reactivity of the polymer and also act as sites for chemical modification. However, chitosan has certain limitations for use in controlled drug delivery and tissue engineering. These limitations can be overcome by chemical modification. Thus, modified chitosan hydrogels have gained importance in current research on drug delivery and tissue engineering systems. This paper reviews the general properties of chitosan, various methods of modification, and applications of modified chitosan hydrogels.

  18. Investigation of Diffusion Characteristics through Microfluidic Channels for Passive Drug Delivery Applications

    Directory of Open Access Journals (Sweden)

    Marcus J. Goudie

    2016-01-01

    Full Text Available Microfluidics has many drug delivery applications due to the ability to easily create complex device designs with feature sizes reaching down to the 10s of microns. In this work, three different microchannel designs for an implantable device are investigated for treatment of ocular diseases such as glaucoma, age-related macular degeneration (AMD, and diabetic retinopathy. Devices were fabricated using polydimethylsiloxane (PDMS and soft lithography techniques, where surface chemistry of the channels was altered using 2-[methoxy(polyethyleneoxypropyl]trimethoxysilane (PEG-silane. An estimated delivery rate for a number of common drugs was approximated for each device through the ratio of the diffusion coefficients for the dye and the respective drug. The delivery rate of the model drugs was maintained at a physiological condition and the effects of channel design and surface chemistry on the delivery rate of the model drugs were recorded over a two-week period. Results showed that the surface chemistry of the device had no significant effect on the delivery rate of the model drugs. All designs were successful in delivering a constant daily dose for each model drug.

  19. Investigation of Diffusion Characteristics through Microfluidic Channels for Passive Drug Delivery Applications.

    Science.gov (United States)

    Goudie, Marcus J; Ghuman, Alyssa P; Collins, Stephanie B; Pidaparti, Ramana M; Handa, Hitesh

    2016-01-01

    Microfluidics has many drug delivery applications due to the ability to easily create complex device designs with feature sizes reaching down to the 10s of microns. In this work, three different microchannel designs for an implantable device are investigated for treatment of ocular diseases such as glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy. Devices were fabricated using polydimethylsiloxane (PDMS) and soft lithography techniques, where surface chemistry of the channels was altered using 2-[methoxy(polyethyleneoxy)propyl]trimethoxysilane (PEG-silane). An estimated delivery rate for a number of common drugs was approximated for each device through the ratio of the diffusion coefficients for the dye and the respective drug. The delivery rate of the model drugs was maintained at a physiological condition and the effects of channel design and surface chemistry on the delivery rate of the model drugs were recorded over a two-week period. Results showed that the surface chemistry of the device had no significant effect on the delivery rate of the model drugs. All designs were successful in delivering a constant daily dose for each model drug.

  20. Two-photon absorption-induced drug delivery from polymers for medical applications

    Science.gov (United States)

    Kim, Hee-Cheol; Kreiling, Stefan; Haertner, Sebastian; Hesse, Lutz; Greiner, Andreas; Hampp, Norbert A.

    2004-06-01

    Novel polymeric materials carrying a drug depot have been developed which are suitable for fabrication of photochemically modulated drug delivery devices. In order to avoid uncontrolled drug release the drug is covalently attached to the polymer backbone using a photo-active linker. Controlled drug release from the polymer can be accomplished either via single-photon excitation or by two-photon absorption (TPA). In particular the second possibility is of interest for applications where exposure to day light or UV light may not be omitted. One example are polymeric intraocular lenses (IOL), which are implanted instead of the opaque natural lens during cataract surgery. Secondary cataract formation is quite often observed after implantation of polymeric IOLs. In this study the well known cell toxic agent 5-fluorouracil (5FU) attached to a methylmethacrylate-based polymer was investigated as an IOL which can upon photochemical excitation release 5FU in order to treat or to prevent secondary cataract formation. The photochemical cleavage of the linker molecule was analyzed with single- and two-photon excitation. UV/VIS spectroscopy and HPLC analysis confirmed the release of 5FU form the polymer backbone. The diffusion of the drug precursor out from the polymer as well as the hydrolysis of the drug precursor which leads to 5FU formation were investigated in vitro.

  1. Biodegradable gelatin-ciprofloxacin-montmorillonite composite hydrogels for controlled drug release and wound dressing application.

    Science.gov (United States)

    Kevadiya, Bhavesh D; Rajkumar, Shalini; Bajaj, Hari C; Chettiar, Shiva Shankaran; Gosai, Kalpeshgiri; Brahmbhatt, Harshad; Bhatt, Adarsh S; Barvaliya, Yogesh K; Dave, Gaurav S; Kothari, Ramesh K

    2014-10-01

    This work reports intercalation of a sparingly soluble antibiotic (ciprofloxacin) into layered nanostructure silicate, montmorillonite (MMT) and its reaction with bone derived polypeptide, gelatin that yields three-dimensional composite hydrogel. Drug intercalation results in changes in MMT layered space and drug loaded MMT and gelatin creates 3D morphology with biodegradable composite hydrogels. These changes can be correlated with electrostatic interactions between the drug, MMT and the gelatin polypeptides as confirmed by X-ray diffraction patterns, thermal, spectroscopic analyses, computational modeling and 3D morphology revealed by SEM and TEM analysis. No significant changes in structural and functional properties of drug was found after intercalation in MMT layers and composite hydrogels. In vitro drug release profiles showed controlled release up to 150h. The drug loaded composite hydrogels were tested on lung cancer cells (A549) by MTT assay. The results of in vitro cell migration and proliferation assay were promising as composite hydrogels induced wound healing progression. In vitro biodegradation was studied using proteolytic enzymes (lysozyme and protease K) at physiological conditions. This new approach of drug intercalation into the layered nanostructure silicate by ion-exchange may have significant applications in cost-effective wound dressing biomaterial with antimicrobial property.

  2. A review of integrating electroactive polymers as responsive systems for specialized drug delivery applications.

    Science.gov (United States)

    Pillay, Viness; Tsai, Tong-Sheng; Choonara, Yahya E; du Toit, Lisa C; Kumar, Pradeep; Modi, Girish; Naidoo, Dinesh; Tomar, Lomas K; Tyagi, Charu; Ndesendo, Valence M K

    2014-06-01

    Electroactive polymers (EAPs) are promising candidate materials for the design of drug delivery technologies, especially in conditions where an "on-off" drug release mechanism is required. To achieve this, EAPs such as polyaniline, polypyrrole, polythiophene, ethylene vinyl acetate, and polyethylene may be blended into responsive hydrogels in conjunction with the desired drug to obtain a patient-controlled drug release system. The "on-off" drug release mechanism can be achieved through the environmental-responsive nature of the interpenetrating hydrogel-EAP complex via (i) charged ions initiated diffusion of drug molecules; (ii) conformational changes that occur during redox switching of EAPs; or (iii) electroerosion. These release mechanisms are not exhaustive and new release mechanisms are still under investigation. Therefore, this review seeks to provide a concise incursion and critical overview of EAPs and responsive hydrogels as a strategy for advanced drug delivery, for example, controlled release of neurotransmitters, sulfosalicyclic acid from cross-linked hydrogel, and vaccine delivery. The review further discusses techniques such as linear sweep voltammetry, cyclic voltammetry, impedance spectroscopy, and chronoamperometry for the determination of the redox capability of EAPs. The future implications of the hydrogel-EAP composites include, but not limited to, application toward biosensors, DNA hybridizations, microsurgical tools, and miniature bioreactors and may be utilized to their full potential in the form of injectable devices as nanorobots or nanobiosensors.

  3. Nanotechnology in Drug Delivery and Tissue Engineering: From Discovery to Applications

    Science.gov (United States)

    Shi, Jinjun; Votruba, Alexander R.; Farokhzad, Omid C.; Langer, Robert

    2010-01-01

    The application of nanotechnology in medicine, referred to as nanomedicine, is offering numerous exciting possibilities in healthcare. Herein, we discuss two important aspects of nanomedicine—drug delivery and tissue engineering—highlighting the advances we have recently experienced, the challenges we are currently facing, and what we are likely to witness in the near future. PMID:20726522

  4. 77 FR 60442 - Withdrawal of Approval of New Animal Drug Applications; Butorphanol; Doxapram; Triamcinolone...

    Science.gov (United States)

    2012-10-03

    ... (NADA) and three abbreviated new animal drug applications (ANADAs) at the sponsors' request because the... approval of the NADA and ANADAs listed in table 1 of this document because the products are no longer manufactured or marketed. Table 1--NADA and ANADAs for Which Withdrawal of Approval Has Been Requested NADA...

  5. Medical applications of membranes: Drug delivery, artificial organs and tissue engineering

    NARCIS (Netherlands)

    Stamatialis, Dimitrios F.; Papenburg, Bernke J.; Gironès, Miriam; Saiful, Saiful; Bettahalli, Srivatsa N.M.; Schmitmeier, Stephanie; Wessling, Matthias

    2008-01-01

    This paper covers the main medical applications of artificial membranes. Specific attention is given to drug delivery systems, artificial organs and tissue engineering which seem to dominate the interest of the membrane community this period. In all cases, the materials, methods and the current stat

  6. Medical applications of membranes: Drug delivery, artificial organs and tissue engineering

    NARCIS (Netherlands)

    Stamatialis, Dimitrios; Papenburg, B.J.; Girones nogue, Miriam; Saiful, S.; Bettahalli Narasimha, M.S.; Schmitmeier, Stephanie; Wessling, Matthias

    2008-01-01

    This paper covers the main medical applications of artificial membranes. Specific attention is given to drug delivery systems, artificial organs and tissue engineering which seem to dominate the interest of the membrane community this period. In all cases, the materials, methods and the current

  7. A new soy-based hydrogels: development, viscoelastic properties, and application for controlled drug release

    Science.gov (United States)

    Hydrogels have been widely studied due to their potential application in drug delivery systems as they are capable of forming aggregates in aqueous solutions. Hydrogels formed from biopolymers or natural sources have special advantages because of their biodegradable and biocompatible properties. I...

  8. 78 FR 70566 - Withdrawal of Approval of New Animal Drug Applications; Arsanilic Acid

    Science.gov (United States)

    2013-11-26

    ... withdrawing approval of a new animal drug application (NADA) for an arsanilic acid Type A medicated article at... 34384, Charlotte, NC 28234 has requested that FDA withdraw approval of NADA 008-019 for PRO-GEN... approval of NADA 008-019, and all supplements and amendments thereto, is hereby withdrawn. Elsewhere...

  9. 78 FR 70496 - Withdrawal of Approval of New Animal Drug Applications; Arsanilic Acid

    Science.gov (United States)

    2013-11-26

    ... approval of a new animal drug application (NADA) for an arsanilic acid Type A medicated article at the.... Box 34384, Charlotte, NC 28234 has requested that FDA withdraw approval of NADA 008-019 for PRO-GEN... gave notice that approval of NADA 008-019, and all supplements and amendments thereto, is...

  10. Pharmacokinetics of a florfenicol-tylosin combination after intravenous and intramuscular administration to beagle dogs.

    Science.gov (United States)

    Kim, Eun-Young; Gebru, Elias; Lee, Joong-Su; Kim, Jong-Choon; Park, Seung-Chun

    2011-04-01

    A pharmacokinetic study of a commercial florfenicol-tylosin (2:1) combination product was conducted in six beagle dogs after intravenous (IV) and intramuscular (IM) administration at doses of 10 mg/kg (florfenicol) and 5 mg/kg (tylosin). Serum drug concentrations were determined by a validated high performance liquid chromatography (HPLC) using UV detection. A rapid and nearly complete absorption of both drugs with a mean IM bioavailability of 103.9% (florfenicol) and 92.6% (tylosin), prolonged elimination half-life, and high tissue penetration with steady state volume of distribution of 2.63 l/kg (florfenicol) and 1.98 l/kg (tylosin) were observed. Additional studies, including pharmacodynamic and toxicological evaluation are required before recommendations can be made regarding the clinical application of the product in dogs.

  11. [Stabilizing the social and health status of drug dependent patients with methadone. Long-term maintainance therapy--Vienna results].

    Science.gov (United States)

    Loimer, N; Werner, E; Hollerer, E; Pfersmann, V; Schmid-Siegel, B; Presslich, O

    1991-01-01

    On September 25th, 1987 methadone was legalized in Austria for therapeutic use in drug addiction treatment in case of: 1. Long-term drug addiction with intravenous application of the drug, and several unsuccessful withdrawal therapies and/or 2. opiate addiction through intravenous application of the drug along with an existing HIV-1 infection. Since than, 291 patients were treated with methadone at the drug-dependency outpatient clinic of the Psychiatric Clinic of the University of Vienna. In 1990, 96 patients treated for more than one year were investigated using a standardized questionnaire. The image in which crime, prostitution, poverty, ill health all merge was broken by this decriminalization. Methadone treatment offers a first step toward social rehabilitation for drug addicts who have been living as criminals on the fringe of society.

  12. The Research and Applications of Quantum Dots as Nano-Carriers for Targeted Drug Delivery and Cancer Therapy.

    Science.gov (United States)

    Zhao, Mei-Xia; Zhu, Bing-Jie

    2016-12-01

    Quantum dots (QDs), nano-carriers for drugs, can help realize the targeting of drugs, and improve the bioavailability of drugs in biological fields. And, a QD nano-carrier system for drugs has the potential to realize early detection, monitoring, and localized treatments of specific disease sites. In addition, QD nano-carrier systems for drugs can improve stability of drugs, lengthen circulation time in vivo, enhance targeted absorption, and improve the distribution and metabolism process of drugs in organization. So, the development of QD nano-carriers for drugs has become a hotspot in the fields of nano-drug research in recent years. In this paper, we review the advantages and applications of the QD nano-carriers for drugs in biological fields.

  13. The Research and Applications of Quantum Dots as Nano-Carriers for Targeted Drug Delivery and Cancer Therapy

    Science.gov (United States)

    Zhao, Mei-Xia; Zhu, Bing-Jie

    2016-04-01

    Quantum dots (QDs), nano-carriers for drugs, can help realize the targeting of drugs, and improve the bioavailability of drugs in biological fields. And, a QD nano-carrier system for drugs has the potential to realize early detection, monitoring, and localized treatments of specific disease sites. In addition, QD nano-carrier systems for drugs can improve stability of drugs, lengthen circulation time in vivo, enhance targeted absorption, and improve the distribution and metabolism process of drugs in organization. So, the development of QD nano-carriers for drugs has become a hotspot in the fields of nano-drug research in recent years. In this paper, we review the advantages and applications of the QD nano-carriers for drugs in biological fields.

  14. 78 FR 33426 - Eli Lilly and Co.; Withdrawal of Approval of a New Drug Application for ORAFLEX

    Science.gov (United States)

    2013-06-04

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Eli Lilly and Co.; Withdrawal of Approval of a New Drug... Administration (FDA) is withdrawing approval of a new drug application (NDA) for ORAFLEX (benoxaprofen)...

  15. Systematic review: intravenous Ibuprofen in preterm newborns.

    Science.gov (United States)

    Aranda, J V; Thomas, Ronald

    2006-06-01

    Ibuprofen, a nonsteroidal antiinflammatory drug, widely used as antipyretic, antiinflammatory, and analgesic agent and for therapy of arthritis, exerts a dose-dependent constriction of the ductus arteriosus in newborn lambs. Two intravenous preparations, namely ibuprofen lysine and ibuprofen-THAM, have been studied in preterm newborns with patent ductus arteriosus. Clinical trials have compared IV ibuprofen to placebo, or to indomethacin. Pharmacodynamic effects of this drug before and after its administration have also been evaluated. Compared with placebo, IV ibuprofen effectively closed PDA with minimal effect on renal function. One study using intravenous ibuprofen-THAM showed decreased renal function and increased risk of NEC and PPHN. Compared with indomethacin, IV ibuprofen lysine exerted similar efficacy (75% to 93% closure). However, indomethacin increased abnormal renal function and decreased mesenteric and cerebral blood flow and bio-energetics. Two clinical trials showed that ibuprofen did not reduce the incidence of intraventricular hemorrhage compared with placebo. The drug has prolonged elimination (plasma half-life = ca 23 hours), suggesting that once daily dosing is appropriate. Dose finding studies indicate that a starting dose of 10 mg/kg followed by 5 mg/kg/d for 2 more days provides optimal efficacy with the least adverse effects. Neonatal data on ibuprofen and indomethacin indicate that, on the first day of life when IVH prevention is desired, indomethacin and not ibuprofen should be used since ibuprofen has no effect on IVH risk. On or after the second day of postnatal life, when early or therapeutic PDA closure is needed, ibuprofen and not indomethacin is probably the first choice due to its better adverse event profile.

  16. Nanodiamonds as novel nanomaterials for biomedical applications: drug delivery and imaging systems

    Directory of Open Access Journals (Sweden)

    Kaur R

    2013-01-01

    Full Text Available Randeep Kaur, Ildiko BadeaDrug Design and Discovery Research Group, College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, Saskatchewan, CanadaAbstract: Detonation nanodiamonds (NDs are emerging as delivery vehicles for small chemical drugs and macromolecular biotechnology products due to their primary particle size of 4 to 5 nm, stable inert core, reactive surface, and ability to form hydrogels. Nanoprobe technology capitalizes on the intrinsic fluorescence, high refractive index, and unique Raman signal of the NDs, rendering them attractive for in vitro and in vivo imaging applications. This review provides a brief introduction of the various types of NDs and describes the development of procedures that have led to stable single-digit-sized ND dispersions, a crucial feature for drug delivery systems and nanoprobes. Various approaches used for functionalizing the surface of NDs are highlighted, along with a discussion of their biocompatibility status. The utilization of NDs to provide sustained release and improve the dispersion of hydrophobic molecules, of which chemotherapeutic drugs are the most investigated, is described. The prospects of improving the intracellular delivery of nucleic acids by using NDs as a platform are exemplified. The photoluminescent and optical scattering properties of NDs, together with their applications in cellular labeling, are also reviewed. Considering the progress that has been made in understanding the properties of NDs, they can be envisioned as highly efficient drug delivery and imaging biomaterials for use in animals and humans.Keywords: dispersion, surface functionalization, toxicity, carriers, fluorescence, light scattering

  17. Live cell in vitro and in vivo imaging applications: accelerating drug discovery.

    Science.gov (United States)

    Isherwood, Beverley; Timpson, Paul; McGhee, Ewan J; Anderson, Kurt I; Canel, Marta; Serrels, Alan; Brunton, Valerie G; Carragher, Neil O

    2011-04-04

    Dynamic regulation of specific molecular processes and cellular phenotypes in live cell systems reveal unique insights into cell fate and drug pharmacology that are not gained from traditional fixed endpoint assays. Recent advances in microscopic imaging platform technology combined with the development of novel optical biosensors and sophisticated image analysis solutions have increased the scope of live cell imaging applications in drug discovery. We highlight recent literature examples where live cell imaging has uncovered novel insight into biological mechanism or drug mode-of-action. We survey distinct types of optical biosensors and associated analytical methods for monitoring molecular dynamics, in vitro and in vivo. We describe the recent expansion of live cell imaging into automated target validation and drug screening activities through the development of dedicated brightfield and fluorescence kinetic imaging platforms. We provide specific examples of how temporal profiling of phenotypic response signatures using such kinetic imaging platforms can increase the value of in vitro high-content screening. Finally, we offer a prospective view of how further application and development of live cell imaging technology and reagents can accelerate preclinical lead optimization cycles and enhance the in vitro to in vivo translation of drug candidates.

  18. 静脉用蔗糖铁注射液改善产科贫血的临床疗效观察%Application of intravenous iron sucrose in treatment of anemia in pregnancy

    Institute of Scientific and Technical Information of China (English)

    王任晓

    2013-01-01

    Objective To compare the efficacy and safety of intravenous iron sucrose and oral iron therapy for pregnancy with anemia,the new method was explored.Methods All of 40 patients with cervical cancer were randomly divided into experiment group (20 cases) and the control group (20 cases).The experiment group is received 200 mg intravenous iron sucrose plus 100 mL 0.9% sodium chloride injection,while the control group is provided with compound ferrous sulfate and folic acid tablets,with 4 pills one time and 3 times a day for 4 weeks.The level of hemoglobin (Hb),hematokrit (Hct),serum ferritin (SF) and transferrin saturation (TSAT) of two groups were compared before and after therapy.Results The levels of Hb,Hct,SF and TSAT of patients significantly increased at 4 weeks after drug therapy (P < 0.05),the levels of Hb,Hct,SF and TSAT of experiment group were significantly higher than those of control group (P < 0.05).No adverse event was found in experiment group,while there were 3 cases with adverse gastrointestinal effects in control group.Conclusion Intravenous iron sucrose is effective and safe in improving iron deficiency anemia in pregnancy.%目的 比较静脉用蔗糖铁注射液与口服铁剂对产科贫血的疗效与安全性,研究改善产科贫血的新途径.方法 选取产科晚期妊娠中度贫血患者40例,随机分为实验组和对照组,各20例.实验组:每周2次静脉注射200 mg蔗糖铁注射液加0.9%氯化钠注射液100 mL,直至完成总补铁量;对照组:给予复方硫酸亚铁叶酸片口服,每日3次,每次4片,共4周.比较治疗前后患者的血红蛋白(Hb)、红细胞压积(Hct)、血清铁蛋白(SF)、血清转铁蛋白饱和度(TSAT).结果 用药4周后,两组患者Hb、Hct、SF、TSAT均较治疗前明显升高(P<0.05);治疗1、2、3、4周后,实验组Hb、Hct、SF、TSAT升高幅度明显优于对照组,差异有统计学意义(P<0.05);实验组在用药过程中无不良反应发生,对照组出现3

  19. New development and application of ultrasound targeted microbubble destruction in gene therapy and drug delivery.

    Science.gov (United States)

    Chen, Zhi-Yi; Yang, Feng; Lin, Yan; Zhang, Jin-Shan; Qiu, Ri-Xiang; Jiang, Lan; Zhou, Xing-Xing; Yu, Jiang-Xiu

    2013-08-01

    Ultrasound is a common used technique for clinical imaging. In recent years, with the advances in preparation technology of microbubbles and the innovations in ultrasound imaging, ultrasound is no longer confined to detection of tissue perfusion, but extends to specific ultrasound molecular imaging and target therapy gradually. With the development of research, ultrasound molecular imaging and target therapy have made great progresses. Targeted microbubbles for molecular imaging are achieved by binding target molecules, specific antibody or ligand to the surface of microbubbles to obtain specific imaging by attaching to target tissues. Meanwhile, it can also achieve targeting gene therapy or drug delivery by ultrasound targeted microbubble destruction (UTMD) mediating genes or drugs to specific target sites. UTMD has a number of advantages, such as target-specific, highly effective, non-invasivity, relatively low-cost and no radiation, and has broad application prospects, which is regarded as one hot spot in medical studies. We reviewed the new development and application of UTMD in gene therapy and drug delivery in this paper. With further development of technology and research, the gene or drug delivery system and related methods will be widely used in application and researches.

  20. [Impact factors analysis of standardized perioperative antibiotic application on nosocomial infection and drug-resistance bacteria].

    Science.gov (United States)

    Li, Yan; Xu, Yan-shan; Xu, Jing; Liu, Xue-yi; Li, Ya-jun

    2013-11-01

    To investigate the impact factors and clinical significance of standardized perioperative antibiotic application on nosocomial infection and drug-resistant bacteria strains in eye hospital. It was a retrospective series case study. The inpatients underwent ophthalmologic operation of one year before standardized application (from Sep. 2009 to Aug. 2010) and one year after standardized application (from Sep. 2010 to Aug. 2011) in Tianjin Eye Hospital were selected and the incidence rate of nosocomial infection and types of drug-resistant strains in these two years were analyzed. From Sep. 2009 to Aug. 2010, the prophylactic antibiotics application rate for type I incisional surgeries was 80.29% (12937/16 111), the nosocomial infection rate was 0.011% (2/17 563). From Sep. 2010 to Aug. 2011, the same values were 44.50% (7968/17 905) and 0.005% (1/19 441). There was a significant decrease of prophylactic antibiotics application comparing these two years (χ(2) = 4587.78, P nosocomial infection rate (χ(2) = 0.44, P > 0.05). Average antibiotics application rate for inpatient (type I-IV incisional surgeries) was 76.69% (13 469/17 563) from Sep. 2009 to Aug. 2010, and 49.40% (9604/19 441) from Sep. 2010 to Aug. 2011. There was a significant decrease over these two years (χ(2) = 2927.19, P resistance rate of staphylococcus was 42.86% (33/77) from Sep. 2009 to Aug. 2010 and 39.19% (39/74) from Sep. 2010 to Aug. 2011. Drug resistance rate of pseudomonas aeruginosa was 2/11 from Sep. 2009 to Aug. 2010 and 2/13 from Sep. 2010 to Aug. 2011. There were no significant differences in drug resistance rate of staphylococcus and pseudomonas aeruginosa between these two years (χ(2) = 0.09, P > 0.05, χ(2) = 0.03, P > 0.05). By standardizing the perioperative antibiotics application in eye hospital, the rate of systemic administration of antibiotics declined gradually. The Choices and the administrative mode of antibiotics were more rational than before. In the meanwhile, the rate

  1. Magnetic Properties of Polyvinyl Alcohol and Doxorubicine Loaded Iron Oxide Nanoparticles for Anticancer Drug Delivery Applications.

    Directory of Open Access Journals (Sweden)

    Muhammad Nadeem

    Full Text Available The current study emphasizes the synthesis of iron oxide nanoparticles (IONPs and impact of hydrophilic polymer polyvinyl alcohol (PVA coating concentration as well as anticancer drug doxorubicin (DOX loading on saturation magnetization for target drug delivery applications. Iron oxide nanoparticles particles were synthesized by a reformed version of the co-precipitation method. The coating of polyvinyl alcohol along with doxorubicin loading was carried out by the physical immobilization method. X-ray diffraction confirmed the magnetite (Fe3O4 structure of particles that remained unchanged before and after polyvinyl alcohol coating and drug loading. Microstructure and morphological analysis was carried out by transmission electron microscopy revealing the formation of nanoparticles with an average size of 10 nm with slight variation after coating and drug loading. Transmission electron microscopy, energy dispersive, and Fourier transform infrared spectra further confirmed the conjugation of polymer and doxorubicin with iron oxide nanoparticles. The room temperature superparamagnetic behavior of polymer-coated and drug-loaded magnetite nanoparticles were studied by vibrating sample magnetometer. The variation in saturation magnetization after coating evaluated that a sufficient amount of polyvinyl alcohol would be 3 wt. % regarding the externally controlled movement of IONPs in blood under the influence of applied magnetic field for in-vivo target drug delivery.

  2. One-step bulk preparation of calcium carbonate nanotubes and its application in anticancer drug delivery.

    Science.gov (United States)

    Tang, Jing; Sun, Dong-Mei; Qian, Wen-Yu; Zhu, Rong-Rong; Sun, Xiao-Yu; Wang, Wen-Rui; Li, Kun; Wang, Shi-Long

    2012-06-01

    Bulk fabrication of ordered hollow structural particles (HSPs) with large surface area and high biocompatibility simultaneously is critical for the practical application of HSPs in biosensing and drug delivery. In this article, we describe a smart approach for batch synthesis of calcium carbonate nanotubes (CCNTs) based on supported liquid membrane (SLM) with large surface area, excellent structural stability, prominent biocompatibility, and acid degradability. The products were characterized by transmission electron micrograph, X-ray diffraction, Fourier transform infrared spectra, UV-vis spectroscopy, zeta potential, and particle size distribution. The results showed that the tube-like structure facilitated podophyllotoxin (PPT) diffusion into the cavity of hollow structure, and the drug loading and encapsulation efficiency of CCNTs for PPT are as high as 38.5 and 64.4 wt.%, respectively. In vitro drug release study showed that PPT was released from the CCNTs in a pH-controlled and time-dependent manner. The treatment of HEK 293T and SGC 7901 cells demonstrated that PPT-loaded CCNTs were less toxic to normal cells and more effective in antitumor potency compared with free drugs. In addition, PPT-loaded CCNTs also enhanced the apoptotic process on tumor cells compared with the free drugs. This study not only provides a new kind of biocompatible and pH-sensitive nanomaterial as the feasible drug container and carrier but more importantly establishes a facile approach to synthesize novel hollow structural particles on a large scale based on SLM technology.

  3. Common characteristics of open source software development and applicability for drug discovery: a systematic review.

    Science.gov (United States)

    Ardal, Christine; Alstadsæter, Annette; Røttingen, John-Arne

    2011-09-28

    Innovation through an open source model has proven to be successful for software development. This success has led many to speculate if open source can be applied to other industries with similar success. We attempt to provide an understanding of open source software development characteristics for researchers, business leaders and government officials who may be interested in utilizing open source innovation in other contexts and with an emphasis on drug discovery. A systematic review was performed by searching relevant, multidisciplinary databases to extract empirical research regarding the common characteristics and barriers of initiating and maintaining an open source software development project. Common characteristics to open source software development pertinent to open source drug discovery were extracted. The characteristics were then grouped into the areas of participant attraction, management of volunteers, control mechanisms, legal framework and physical constraints. Lastly, their applicability to drug discovery was examined. We believe that the open source model is viable for drug discovery, although it is unlikely that it will exactly follow the form used in software development. Hybrids will likely develop that suit the unique characteristics of drug discovery. We suggest potential motivations for organizations to join an open source drug discovery project. We also examine specific differences between software and medicines, specifically how the need for laboratories and physical goods will impact the model as well as the effect of patents.

  4. Biocompatible fluorescent zein nanoparticles for simultaneous bioimaging and drug delivery application

    Science.gov (United States)

    Girija Aswathy, Ravindran; Sivakumar, Balasubramanian; Brahatheeswaran, Dhandayudhapani; Fukuda, Takahiro; Yoshida, Yasuhiko; Maekawa, Toru; Sakthi Kumar, D.

    2012-06-01

    We report the synthesis of 5-fluorouracil (5-FU) loaded biocompatible fluorescent zein nanoparticles. Zein is the storage protein in corn kernels that has a variety of unique characteristics and functionalities that makes zein valuable in various commercial applications. It is classified as generally recognized as safe (GRAS) by the Food and Drug Administration (FDA). We synthesized zein nanoparticles of around 800 nm in size and conjugated with quantum dot ZnS:Mn. The nanoparticle was in turn encapsulated with the drug 5-FU. The luminescent properties of these nanoparticles were studied by using fluorescence microscopy. The nanoparticles were characterized and the drug release profile was studied. The biocompatibility of zein nanoparticle and the cytotoxicity with drug-loaded nanoparticle was studied in L929 and MCF-7 cell lines. The nanoparticles were successfully employed for cellular imaging. In vitro drug release studies were also performed. The biocompatibility of the nanoparticle showed that nanoparticles at higher concentrations are compatible for cells and are expected to be promising agents for the targeted delivery of drugs in the near future.

  5. Functional hydrogel contact lens for drug delivery in the application of oculopathy therapy.

    Science.gov (United States)

    Hu, Xiaohong; Tan, Huaping; Hao, Lingyun

    2016-12-01

    Although hydrogel contact lens has attracted increasingly concerns as delivery carriers in the field of oculopathy therapy, traditional hydrogel does not show excellent drug encapsulated and controlled properties due to simple hydrophilic polymer chain lacking extra interaction with drug molecule. Herein, functional hydrogels were synthesized in this research to delivery ophthalmic drug for oculopathy therapy. Functional monomer of mono-GMA-β-CD and functional crosslinker of MA-β-CD were incorporated into hydrogel by copolymerization. For hydrogels, equilibrium swelling ratio and contact angle was influenced by mono-GMA-β-CD ratio and MA-β-CD ratio, respectively. All hydrogels exhibited similar water loss behavior and good transparency. Hydrogels had rheological characteristic of typical elastomer. Viscoelasticity and surface morphology of hydrogel were also affected by mono-GMA-β-CD ratio and MA-β-CD ratio. In the aspect of properties, functional hydrogel containing β-CD domain exhibited better protein resistance capacity and significantly higher equilibrium encapsulated drug amount than traditional hydrogel. Besides the performance, drug release behavior of drug encapsulated hydrogel was adjusted by both mono-GMA-β-CD ratio and MA-β-CD ratio. Preliminary in vivo evaluation revealed that functional hydrogel contact lens had better effect and efficacy on lowering intraocular tension than commercial eye drop. It is inferred from all results that functional contact lens has a bright prospect in the application of oculopathy therapy.

  6. Sulfur Containing Scaffolds in Drugs: Synthesis and Application in Medicinal Chemistry.

    Science.gov (United States)

    Feng, Minghao; Tang, Bingqing; Liang, Steven H; Jiang, Xuefeng

    2016-01-01

    The impact of the development of sulfur therapeutics is instrumental to the evolution of the pharmaceutical industry. Sulfur-derived functional groups can be found in a broad range of pharmaceuticals and natural products. For centuries, sulfur continues to maintain its status as the dominating heteroatom integrated into a set of 362 sulfur-containing FDA approved drugs (besides oxygen or nitrogen) through the present. Sulfonamides, thioethers, sulfones and Penicillin are the most common scaffolds in sulfur containing drugs, which are well studied both on synthesis and application during the past decades. In this review, these four moieties in pharmaceuticals and recent advances in the synthesis of the corresponding core scaffolds are presented.

  7. Application and effect of ISO9001 quality certification in quality management of intravenous infusion%ISO9001质量认证在静脉输液质量管理中的应用及效果

    Institute of Scientific and Technical Information of China (English)

    蒋梅; 易东

    2013-01-01

    目的 探讨ISO9001质量管理在静脉输液患者中的应用及效果.方法 选择2010年9月~2012年10月在重庆市红十字会医院(江北区人民医院)住院治疗的200例静脉输液患者为研究对象,根据有无实施ISO9001质量管理分为A组和B组,A组患者仅给予常规管理,而B组患者则接受ISO9001质量管理模式指导下的干预措施,比较两组患者静脉输液不良事件发生率、基础护理合格率和患者对护理服务的满意度.结果 B组患者不良事件发生率明显低于A组,差异均有统计学意义(均P < 0.05);B组患者的护理质量和患者对护理服务的满意度均明显高于A组,差异均有统计学意义(均P < 0.05).结论 ISO9001质量管理能减少静脉输液不良事件的发生,有效提高静脉输液护理质量和患者对静脉输液护理服务的满意度,值得推广应用.%Objective To investigate the application and effect of ISO9001 quality certification in patients with intravenous infusion. Methods 200 patients treated with intravenous infusion in red cross hospital in Chongqing City (People's Hospital of Jiangbei District) from September 2010 to October 2012 were collected. Then the patients were divided into group A and group B according to providing ISO9001 quality management or not. Patients in group A were given routine management, patients in group B were given specific intervention measures under the theory of ISO9001 quality management. The incidence of adverse events, basic nursing qualified rate and patients' satisfaction for the nursing service were evaluated. Results The incidence of adverse events in group B was all lower than that in group A (all P < 0.05); but the basic nursing qualified rate and the patients' satisfaction for nursing service in group B were all higher than those in group A (all P < 0.05). Conclusion ISO9001 quality management can obviously reduce the adverse events of intravenous infusion in patients, and improve the basic nursing

  8. Panlobular emphysema in young intravenous Ritalin abusers

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, R.A.; Glenny, R.W.; Godwin, J.D.; Hampson, N.B.; Cantino, M.E.; Reichenbach, D.D. (Univ. of Washington, Seattle (USA))

    1991-03-01

    We studied a distinctive group of young intravenous Ritalin abusers with profound obstructive lung disease. Clinically, they seemed to have severe emphysema, but the pathologic basis of their symptoms had not been investigated previously. Seven patients have died and been autopsied: in four, the lungs were fixed, inflated, dried, and examined in detail radiologically, grossly, microscopically, and by electron probe X-ray microanalysis. All seven patients had severe panlobular (panacinar) emphysema that tended to be more severe in the lower lung zones and that was associated with microscopic talc granulomas. Vascular involvement by talc granulomas was variable, but significant interstitial fibrosis was not present. Five patients were tested for alpha-1-antitrypsin deficiency and found to be normal, as were six similar living patients. These findings indicate that some intravenous drug abusers develop emphysema that clinically, radiologically, and pathologically resembles that caused by alpha-1-antitrypsin deficiency but which must have a different pathogenesis. Talc from the Ritalin tablets may be important, but the mechanism remains to be elucidated.

  9. Inductively coupled plasma-MS in drug development: bioanalytical aspects and applications.

    Science.gov (United States)

    van Heuveln, Fred; Meijering, Henri; Wieling, Jaap

    2012-08-01

    The vast majority of today's modern bioanalytical methods for pharmacokinetic, pharmacodynamic and immunogenicity purposes are based on LC-MS/MS and immunoanalytical approaches. Indeed, these methodologies are suitable for a wide range of molecules from small to large. For a smaller but not insignificant group of compounds, LC-MS/MS is not suitable - or in some cases much less suitable - as a reliable bioanalytical methodology, and inductively coupled plasma (ICP)-MS is a more appropriate methodology. ICP-MS is one of these less widely used techniques in drug development. This methodology is predominantly used for elemental bioanalysis for pharmacokinetics, for imaging purposes, for mass-balance, food-effect and biomarker studies. In addition, in the last couple of years an increasing number of applications has been published, where ICP-MS and its various hyphenations (LC-ICP-MS, CE-ICP-MS) have been used for speciation/metabolism and proteomics studies. Here, the analytical potential, the quantitative bioanalytical aspects, the various modes of operation and the challenges of the application of ICP-MS in life sciences applications are given. This includes an overview of recent applications in this area in scientific literature, the various hyphenation possibilities and their application areas and the analysis of the various sample matrices applicable to these fields. It also provides a brief outlook of where the potential of this technique lies in the future of regulated bioanalysis and drug development.

  10. A vision for cyclodextrin nanoparticles in drug delivery systems and pharmaceutical applications.

    Science.gov (United States)

    Lakkakula, Jaya Raju; Maçedo Krause, Rui Werner

    2014-05-01

    Cyclodextrins (CDs) have brought a revolution in the pharmaceutical field over the last decade. Natural and modified CDs (α-CD and β-CD) have been studied and some have gained US FDA approval or achieved 'Generally Regarded as Safe' (GRAS) status. Another characteristic of CDs is the ease with which they can be induced to form supramolecular structures for its use in drug delivery. CDs, grafted or crosslinked with polymers, are now being developed into 'smart' systems for efficient targeted drug delivery, especially for hydrophobic drugs. Amphiphilic CDs have the ability to form nanospheres or nanocapsules via a simple nanoprecipitation technique. This review deals with different types of CDs, and their efficacy, physicochemical properties and transformation into nanoparticles with interesting in vitro and in vivo applications.

  11. Multi-target drug design approaches for multifactorial diseases: from neurodegenerative to cardiovascular applications.

    Science.gov (United States)

    Katselou, M G; Matralis, A N; Kourounakis, A P

    2014-01-01

    In multi-target drug design (MTD) medicinal chemistry aims to integrate multiple pharmacophores into a single drug molecule in order to make it active on several molecular biological mechanisms simultaneously. Given the fact that most diseases are multifactorial in nature, MTD is being pursued with increasing intensity, which has resulted in improved outcomes in disease models and several compounds have entered clinical trials. In a wide range of examples we illustrate how various functionalities have been combined within single structures and how this has affected their (pre)clinical outcome. This review describes the successful application of MTD for disorders such as neurodegenerative, cardiovascular, diabetes, metabolic and inflammatory diseases, especially focusing on the field of atherosclerosis where multi-target strategies are a promising alternative to the classical "one target-one drug" design approach.

  12. Polymeric formulations for drug release prepared by hot melt extrusion: application and characterization.

    Science.gov (United States)

    Stanković, Milica; Frijlink, Henderik W; Hinrichs, Wouter L J

    2015-07-01

    Over the past few decades hot melt extrusion (HME) has emerged as a powerful processing technology for the production of pharmaceutical solid dosage forms in which an active pharmaceutical ingredient (API) is dispersed into polymer matrices. It has been shown that formulations using HME can provide time-controlled, sustained and targeted drug delivery, and improved bioavailability of poorly soluble drugs. In this review, the basic principles of the HME process are described together with an overview of some of the most common biodegradable and nonbiodegradable polymers used for the preparation of different formulations using this method. Further, the applications of HME in drug delivery and analytical techniques employed to characterize HME products are addressed.

  13. Design, Synthesis, and Characterization of Novel Zwitterionic Lipids for Drug and siRNA Delivery Applications

    Science.gov (United States)

    Walsh, Colin L.

    Lipid-based nanoparticles have long been used to deliver biologically active molecules such as drugs, proteins, peptides, DNA, and siRNA in vivo. Liposomes and lipoplexes alter the biodistribution, pharmacokinetics, and cellular uptake of their encapsulated or associated cargo. This can increase drug efficacy while reducing toxicity, resulting in an increased therapeutic index and better clinical outcomes. Unlike small molecule drugs, which passively diffuse through lipid membranes, nucleic acids and proteins require an active, carrier mediated escape mechanism to reach their site of action. As such, the therapeutic application and drug properties dictate the required biophysical characteristics of the lipid nanoparticle. These carrier properties depend on the structure and biophysical characteristics of the lipids and other components used to formulate them. This dissertation presents a series of studies related to the development of novel synthetic lipids for use in drug delivery systems. First, we developed a novel class of zwitterionic lipids with head groups containing a cationic amine and anionic carboxylate and ester-linked oleic acid tails. These lipids exhibit structure-dependent, pH-responsive biophysical properties, and may be useful components for next-generation drug delivery systems. Second, we extended the idea of amine/carboxylate containing zwitterionic head groups and synthesized a series of acetate terminated diacyl lipids containing a quaternary amine. These lipids have an inverted headgroup orientation compared to naturally occurring zwitterionic lipids, and show interesting salt-dependent biophysical properties. Third, we synthesized and characterized a focused library of ionizable lysine-based lipids, which contain a lysine head group linked to a long-chain dialkylamine. A focused library was synthesized to determine the impact of hydrophobic fluidity, lipid net charge, and lipid pKa on the biophysical and siRNA transfection characteristics

  14. [Efficacy of intravenous phenobarbital treatment for status epilepticus].

    Science.gov (United States)

    Muramoto, Emiko; Mizobuchi, Masahiro; Sumi, Yoshihiro; Sako, Kazuya; Nihira, Atsuko; Takeuchi, Akiko; Nakamura, Hirohiko

    2013-08-01

    Intravenous phenobarbital (IV-PB) therapy was launched in Japan in October 2008. We retrospectively investigated its efficacy and tolerability in patients with status epilepticus. Forty-three consecutive patients received IV-PB for status epilepticus between June 2009 and April 2011. Among them, 39 patients had underlying diseases, which included acute diseases in 19 patients and chronic conditions in 20 patients. Although 18 patients had been taking antiepileptic drugs (AEDs) before the occurrence of status epilepticus, the blood AED concentrations in 8 patients was below the therapeutic levels. Before the administration of IV-PB, 39 patients were treated with intravenous benzodiazepine, 17 patients were treated with intravenous phenytoin, and 15 patients with intravenous infusion of lidocaine. The initial doses of IV-PB ranged from 125 to 1,250 mg (1.9-20.0 mg/kg). Additional doses of IV-PB were required in 12 patients. Seizures were controlled in 35 patients (81%) after IV-PB administration. Cessation of status epilepticus was attained in 24 patients after the initial dose and in 11 patients after additional doses. There were no serious adverse effects, although respiratory suppression was observed in 3 patients and drug eruption was observed in 1 patient. IV-PB is relatively safe and effective for controlling status epilepticus. If the first dose is not effective, additional doses are required up to the recommended maximum dose.

  15. LC-UV Determination of Baicalin in Rabbit Plasma and Tissues for Application in Pharmacokinetics and Tissue Distribution Studies of Baicalin after Intravenous Administration of Liposomal and Injectable Formulations.

    Science.gov (United States)

    Wei, Yumeng; Pi, Chao; Yang, Gang; Xiong, Xiaoming; Lan, Yongshu; Yang, Hongru; Zhou, Yang; Ye, Yun; Zou, Yonggen; Zheng, Wenwu; Zhao, Ling

    2016-04-19

    A simple and sensitive LC-UV method to investigate the pharmacokinetics and biodistribution pattern of baicalin in rabbits was established and validated. Baicalin and the internal standard, rutin, were extracted from biosamples using acetonitrile as protein precipitation after pretreated with ammonium acetate buffer (pH 3.5; 1 M) to obtain a pure chromatographic peak and high extraction recovery. Chromatographic separation was achieved on a reverse-phase C18 column with a gradient elution at flow rate of 1.0 mL/min. UV absorption was set at 278 nm. Chromatographic response was linear over the ranges of 0.05-10.00 μg/mL in plasma and 0.05-300.00 μg/g in tissues with the limits of quantification of 50.0 ng/mL in plasma and tissues, and the limit of detection of baicalin in bio-samples of 15 ng/mL. The RSD of intra-and inter-day for the biosamples were from 4.19% to 10.84% and from 4.37% to 10.93%, respectively. The accuracy of plasma and tissue samples ranged from 81.6% to 95.2% and 80.8% to 98.4%, respectively. The extraction recoveries ranged from 81.5% to 88.3% for plasma, from 73.1% to 93.2% for tissues, respectively. Baicalin was stable in rabbit biosamples. The validated method was successfully applied to the study of the pharmacokinetics and tissue distribution of baicalin after intravenous administration of liposomal and injectable formulations to rabbits. Compared to baicalin injection, the pharmacokinetics and biodistribution behavior of baicalin was altered significantly in rabbits treated with its liposomes and drug concentration in the lungs was greatly increased.

  16. Application value of multifunctional dynamic fiat panel X-ray detector in intravenous pyelography%多功能动态平板X线机在静脉肾盂造影检查中的价值

    Institute of Scientific and Technical Information of China (English)

    胡辉军; 陈娇霞; 陈玥瑶; 谭志; 云丹丹

    2014-01-01

    Objective To investigate the application value of multifunctional dynamic flat panel X-ray detector in intravenous pyelography.Methods Total 540 patients with intravenous pyelography were divided into multifunctional dynamic flat panel X-ray detector group (300 cases) and conventional flat panel X-ray detector group (240 cases) by random digits table method.Image quality,radiation dosage and examination time were analyzed and compared between the two groups.Results There was no statistical difference between the two groups in image quality (P > 0.05).The examination time and radiation dosage was (25.5 ± 8.2) min and (12.5 ± 6.8) mAs respectively in multifunctional dynamic flat panel X-ray detector group and (39.2 ± 12.1) min and (23.6 ± 7.6) mAs in conventional flat panel X-ray detector group.The differences had statistical significance (P < 0.01).Conclusions Multifunctional dynamic flat panel X-ray detector in intravenous pyelography can provide lower radiation dose,shorter examination time and higher image quality.It has obvious advantages in urography.%目的 探讨多功能动态平板X线机在静脉肾盂造影检查中的应用价值.方法 将540例进行静脉肾盂造影患者按随机数字表法分成多功能动态平板X线机组(300例)及普通平板X线机组(240例),并对两组图像质量、辐射剂量和检查时间进行比较分析.结果 两组静脉肾盂造影图像质量比较差异无统计学意义(P> 0.05),多功能动态平板X线机组检查时间为(25.5±8.2)min,辐射剂量为(12.5±6.8) mAs,普通平板X线机组检查时间为(39.2±12.1) min,辐射剂量为(23.6±7.6) mAs,两组比较差异有统计学意义(P<0.01).结论 多功能动态平板X线机在静脉肾盂造影检查中能明显有效地降低辐射剂量和缩短检查时间,并能提高影像质量,在泌尿系造影中具有明显优势.

  17. Applications and limitations of lipid nanoparticles in dermal and transdermal drug delivery via the follicular route.

    Science.gov (United States)

    Lauterbach, Andreas; Müller-Goymann, Christel C

    2015-11-01

    Lipid nanoparticles (LN) such as solid lipid nanoparticles (SLN) and nanolipid carriers (NLC) feature several claimed benefits for topical drug therapy including biocompatible ingredients, drug release modification, adhesion to the skin, and film formation with subsequent hydration of the superficial skin layers. However, penetration and permeation into and across deeper skin layers are restricted due to the barrier function of the stratum corneum (SC). As different kinds of nanoparticles provide the potential for penetration into hair follicles (HF) LN are applicable drug delivery systems (DDS) for this route in order to enhance the dermal and transdermal bioavailability of active pharmaceutical ingredients (API). Therefore, this review addresses the HF as application site, published formulations of LN which showed follicular penetration (FP), and characterization methods in order to identify and quantify the accumulation of API delivered by the LN in the HF. Since LN are based on lipids that appear in human sebum which is the predominant medium in HF an increased localization of the colloidal carriers as well as a promoted drug release may be assumed. Therefore, sebum-like lipid material and a size of less or equal 640 nm are appropriate specifications for FP of particulate formulations.

  18. Nanodiamonds as novel nanomaterials for biomedical applications: drug delivery and imaging systems.

    Science.gov (United States)

    Kaur, Randeep; Badea, Ildiko

    2013-01-01

    Detonation nanodiamonds (NDs) are emerging as delivery vehicles for small chemical drugs and macromolecular biotechnology products due to their primary particle size of 4 to 5 nm, stable inert core, reactive surface, and ability to form hydrogels. Nanoprobe technology capitalizes on the intrinsic fluorescence, high refractive index, and unique Raman signal of the NDs, rendering them attractive for in vitro and in vivo imaging applications. This review provides a brief introduction of the various types of NDs and describes the development of procedures that have led to stable single-digit-sized ND dispersions, a crucial feature for drug delivery systems and nanoprobes. Various approaches used for functionalizing the surface of NDs are highlighted, along with a discussion of their biocompatibility status. The utilization of NDs to provide sustained release and improve the dispersion of hydrophobic molecules, of which chemotherapeutic drugs are the most investigated, is described. The prospects of improving the intracellular delivery of nucleic acids by using NDs as a platform are exemplified. The photoluminescent and optical scattering properties of NDs, together with their applications in cellular labeling, are also reviewed. Considering the progress that has been made in understanding the properties of NDs, they can be envisioned as highly efficient drug delivery and imaging biomaterials for use in animals and humans.

  19. Application of Multivariate Linear and Nonlinear Calibration and Classification Methods in Drug Design.

    Science.gov (United States)

    Abdolmaleki, Azizeh; Ghasemi, Jahan B; Shiri, Fereshteh; Pirhadi, Somayeh

    2015-01-01

    Data manipulation and maximum efficient extraction of useful information need a range of searching, modeling, mathematical, and statistical approaches. Hence, an adequate multivariate characterization is the first necessary step in investigation and the results are interpreted after multivariate analysis. Multivariate data analysis is capable of not only large dataset management but also interpret them surely and rapidly. Application of chemometrics and cheminformatics methods may be useful for design and discovery of new drug compounds. In this review, we present a variety of information sources on chemometrics, which we consider useful in different fields of drug design. This review describes exploratory analysis (PCA), classification and multivariate calibration (PCR, PLS) methods to data analysis. It summarizes the main facts of linear and nonlinear multivariate data analysis in drug discovery and provides an introduction to manipulation of data in this field. It handles the fundamental aspects of basic concepts of multivariate methods, principles of projections (PCA and PLS) and introduces the popular modeling and classification techniques. Enough theory behind these methods, more particularly concerning the chemometrics tools is included for those with little experience in multivariate data analysis techniques such as PCA, PLS, SIMCA, etc. We describe each method by avoiding unnecessary equations, and details of calculation algorithms. It provides a synopsis of the method followed by cases of applications in drug design (i.e., QSAR) and some of the features for each method.

  20. Drug discovery applications for KNIME: an open source data mining platform.

    Science.gov (United States)

    Mazanetz, Michael P; Marmon, Robert J; Reisser, Catherine B T; Morao, Inaki

    2012-01-01

    Technological advances in high-throughput screening methods, combinatorial chemistry and the design of virtual libraries have evolved in the pursuit of challenging drug targets. Over the last two decades a vast amount of data has been generated within these fields and as a consequence data mining methods have been developed to extract key pieces of information from these large data pools. Much of this data is now available in the public domain. This has been helpful in the arena of drug discovery for both academic groups and for small to medium sized enterprises which previously would not have had access to such data resources. Commercial data mining software is sometimes prohibitively expensive and the alternate open source data mining software is gaining momentum in both academia and in industrial applications as the costs of research and development continue to rise. KNIME, the Konstanz Information Miner, has emerged as a leader in open source data mining tools. KNIME provides an integrated solution for the data mining requirements across the drug discovery pipeline through a visual assembly of data workflows drawing from an extensive repository of tools. This review will examine KNIME as an open source data mining tool and its applications in drug discovery.

  1. Requirements for Foreign and Domestic Establishment Registration and Listing for Human Drugs, Including Drugs That Are Regulated Under a Biologics License Application, and Animal Drugs. Final rule.

    Science.gov (United States)

    2016-08-31

    The Food and Drug Administration (FDA) is amending its regulations governing drug establishment registration and drug listing. These amendments reorganize, modify, and clarify current regulations concerning who must register establishments and list human drugs, human drugs that are also biological products, and animal drugs. The final rule requires electronic submission, unless waived in certain circumstances, of registration and listing information. This rulemaking pertains to finished drug products and to active pharmaceutical ingredients (APIs) alone or together with one or more other ingredients. The final rule describes how and when owners or operators of establishments at which drugs are manufactured or processed must register their establishments with FDA and list the drugs they manufacture or process. In addition, the rule makes certain changes to the National Drug Code (NDC) system. We are taking this action to improve management of drug establishment registration and drug listing requirements and make these processes more efficient and effective for industry and for us. This action also supports implementation of the electronic prescribing provisions of the Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA) and the availability of current drug labeling information through DailyMed, a computerized repository of drug information maintained by the National Library of Medicine.

  2. Challenges and Opportunities for the Application of Boron Clusters in Drug Design.

    Science.gov (United States)

    Leśnikowski, Zbigniew J

    2016-09-08

    There are two branches in boron medicinal chemistry: the first focuses on single boron atom compounds, and the second utilizes boron clusters. Boron clusters and their heteroatom counterparts belong to the family of cage compounds. A subset of this extensive class of compounds includes dicarbadodecaboranes, which have the general formula C2B10H12, and their metal biscarboranyl complexes, metallacarboranes, with the formula [M(C2B10H12)2(-2)]. The unique properties of boron clusters have resulted in their utilization in applications such as in pharmacophores, as scaffolds in molecular construction, and as modulators of bioactive compounds. This Perspective presents an overview of the properties of boron clusters that are pertinent for drug discovery, recent applications in the design of various classes of drugs, and the potential use of boron clusters in the construction of new pharmaceuticals.

  3. Nanoporous metal organic frameworks as hybrid polymer-metal composites for drug delivery and biomedical applications.

    Science.gov (United States)

    Beg, Sarwar; Rahman, Mahfoozur; Jain, Atul; Saini, Sumant; Midoux, Patrick; Pichon, Chantal; Ahmad, Farhan Jalees; Akhter, Sohail

    2017-04-01

    Metal organic frameworks (MOFs), porous hybrid polymer-metal composites at the nanoscale, are recent innovations in the field of chemistry; they are novel polymeric materials with diverse biomedical applications. MOFs are nanoporous materials, consisting of metal ions linked together by organic bridging ligands. The unique physical and chemical characteristics of MOFs have attracted wider attention from the scientific community, exploring their utility in the field of material science, biology, nanotechnology and drug delivery. The practical feasibility of MOFs is possible owing to their abilities for biodegradability, excellent porosity, high loading capacity, ease of surface modification, among others. In this regard, this review provides an account of various types of MOFs, their physiochemical characteristics and use in diverse disciplines of biomedical sciences - with special emphasis on drug delivery and theranostics. Moreover, this review also highlights the stability and toxicity issues of MOFs, along with their market potential for biomedical applications. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Sonochemically synthesized biocompatible zirconium phosphate nanoparticles for pH sensitive drug delivery application.

    Science.gov (United States)

    Kalita, Himani; Prashanth Kumar, B N; Konar, Suraj; Tantubay, Sangeeta; Kr Mahto, Madhusudan; Mandal, Mahitosh; Pathak, Amita

    2016-03-01

    The present work reports the synthesis of biocompatible zirconium phosphate (ZP) nanoparticles as nanocarrier for drug delivery application. The ZP nanoparticles were synthesized via a simple sonochemical method in the presence of cetyltrimethylammonium bromide and their efficacy for the delivery of drugs has been tested through various in-vitro experiments. The particle size and BET surface area of the nanoparticles were found to be ~48 nm and 206.51 m(2)/g respectively. The conventional MTT assay and cellular localization studies of the particles, performed on MDA-MB-231 cell lines, demonstrate their excellent biocompatibility and cellular internalization behavior. The loading of curcumin, an antitumor drug, onto the ZP nanoparticles shows the rapid drug uptake ability of the particles, while the drug release study, performed at two different pH values (at 7.4 and 5) depicts pH sensitive release-profile. The MTT assay and cellular localization studies revealed higher cellular inhibition and better bioavailability of the nanoformulated curcumin compared to free curcumin.

  5. Isoniazid loaded gelatin-cellulose whiskers nanoparticles for controlled drug delivery applications

    Indian Academy of Sciences (India)

    MANDIP SARMAH; ANOWAR HUSSAIN; ANAND RAMTEKE; TARUN K MAJI

    2016-08-01

    Natural polymers like gelatin have been used as a potential drug carrier for controlled delivery applications due to their various advantages over synthetic polymers. Cellulose Whiskers (CWs) have the capacity to form strong hydrogen bonds which help in controlling the release of drug and also provide goodstrength to the drug carrier. In this report, CWs were prepared from filter paper cellulose by acid hydrolysis. Also, attempt was made to prepare gelatin-CWs nanoparticles by desolvation method using an anti-tuberculosis drug, isoniazid and a crosslinker glutaraldehyde (GA). The CWs and gelatin-CWs nanoparticles were characterized by X-ray diffractometry (XRD), Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM). The effect of CWs on gelatin nanoparticlesover 8-hour period was measured in swelling studies. Efficiency of drug loading and subsequent release of isoniazid in buffer solutions at pH 1.2 (0.1N HCl) and pH 7.4 (phosphate buffer) were studied. Cytotoxicity study showed less toxicity for gelatin-CWs nanoparticles.

  6. Current advances in Phi29 pRNA biology and its application in drug delivery.

    Science.gov (United States)

    Ye, Xin; Hemida, Maged; Zhang, Huifang M; Hanson, Paul; Ye, Qiu; Yang, Decheng

    2012-01-01

    Bacteriophage 29 (Phi29) packaging RNA (pRNA) is one of the key components in the viral DNA-packaging motor. It contains two functional domains facilitating the translocation of DNA into the viral capsid by interacting with other elements in the motor and promoting adenosine triphosphates hydrolysis. Through the connection between interlocking loops in adjacent pRNA monomers, pRNA functions in the form of multimer ring in the motor. Previous studies have addressed the unique structure and conformation of pRNA. However, there are different DNA-packaging models proposed for the viral genome transportation mechanism. The DNA-packaging ability and the unique features of pRNA have been attracting efforts to study its potential applications in nanotechnology. The pRNA has been proved to be a promising tool for delivering nucleic acid-based therapeutic molecules by covalent linkage with ribozymes, small interfering RNAs, aptamers, and artificial microRNAs. The flexibility in constructing dimers, trimers, and hexamers enables the assembly of polyvalent nanoparticles to carry drug molecules for therapeutic purposes, cell ligands for target delivery, image detector for drug entry monitoring, and endosome disrupter for drug release. Besides these fascinating pharmacological advantages, pRNA-based drug delivery has also been demonstrated to prolong the drug half life with minimal induction of immune response and toxicity.

  7. Application of Personal Drug (P-Drug) Seminar to Clinical Pharmacy Education in the Graduate School of Pharmaceutical Sciences

    OpenAIRE

    2002-01-01

    The P-drug seminar, a novel method of teaching the process of rational pharmacotherapy, was introduced in 2000 into the practice program of the clinical pharmacy course in the Graduate School of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University (TMPU). The P-drug concept is evidence-based drug selection according to criteria (i.e., efficacy, safety, suitability and cost) deter mined in advance and rational prescribing by each physician. The P-drug seminar originated from e...

  8. Strategies of bringing drug product marketing applications to meet current regulatory standards.

    Science.gov (United States)

    Wu, Yan; Freed, Anita; Lavrich, David; Raghavachari, Ramesh; Huynh-Ba, Kim; Shah, Ketan; Alasandro, Mark

    2015-08-01

    In the past decade, many guidance documents have been issued through collaboration of global organizations and regulatory authorities. Most of these are applicable to new products, but there is a risk that currently marketed products will not meet the new compliance standards during audits and inspections while companies continue to make changes through the product life cycle for continuous improvement or market demands. This discussion presents different strategies to bringing drug product marketing applications to meet current and emerging standards. It also discusses stability and method designs to meet process validation and global development efforts.

  9. Poly(amidoamine) (PAMAM) dendrimers: from biomimicry to drug delivery and biomedical applications.

    Science.gov (United States)

    Esfand, R; Tomalia, D A.

    2001-04-01

    Poly(amidoamine) (PAMAM) dendrimers are the first complete dendrimer family to be synthesized, characterized and commercialized. Based on this extensive activity, they are recognized as a unique new class of synthetic nanostructures. Dendrimers allow the precise control of size, shape and placement of functional groups that is desirable for many life science applications. From this perspective, this review focuses on crucial properties of biomimetic dendrimers that will broaden the potential for their use as macromolecular vectors in novel drug delivery and biomedical applications.

  10. A Performance/Cost Evaluation for a GPU-Based Drug Discovery Application on Volunteer Computing

    Directory of Open Access Journals (Sweden)

    Ginés D. Guerrero

    2014-01-01

    Full Text Available Bioinformatics is an interdisciplinary research field that develops tools for the analysis of large biological databases, and, thus, the use of high performance computing (HPC platforms is mandatory for the generation of useful biological knowledge. The latest generation of graphics processing units (GPUs has democratized the use of HPC as they push desktop computers to cluster-level performance. Many applications within this field have been developed to leverage these powerful and low-cost architectures. However, these applications still need to scale to larger GPU-based systems to enable remarkable advances in the fields of healthcare, drug discovery, genome research, etc. The inclusion of GPUs in HPC systems exacerbates power and temperature issues, increasing the total cost of ownership (TCO. This paper explores the benefits of volunteer computing to scale bioinformatics applications as an alternative to own large GPU-based local infrastructures. We use as a benchmark a GPU-based drug discovery application called BINDSURF that their computational requirements go beyond a single desktop machine. Volunteer computing is presented as a cheap and valid HPC system for those bioinformatics applications that need to process huge amounts of data and where the response time is not a critical factor.

  11. Analysis on Irrational Drug Use in Pharmacy Intravenous Admixture Service of Guangdong Panyu Maternal and Child Health Hospital%广东省妇幼保健院番禺院区静脉用药调配中心不合理用药分析

    Institute of Scientific and Technical Information of China (English)

    赵晶晶; 盛飞凤; 杨亮; 陈小葵

    2016-01-01

    OBJECTIVE:To investigate the irrational prescriptions and medical orders in Pharmacy Intravenous Admixture Service of Guangdong Panyu Maternal and Child Health Hospital ( hereinafter referred to as “our hospital”) . METHODS: Retrospective analysis was conducted on the irrational prescriptions and medical orders found in the process of intravenous medicine prescriptions audit during Jun .to Nov.2014 in our hospital , and then modification suggestions were put forward .RESULTS:A total of 123 368 prescriptions was reviewed , and 240 pieces of irrational prescriptions were found , accounting for 0.20%.The problems included irrational selection of solvent ( 35.83%) , improper dosage and usage ( 32.08%) , irrational selection of medicine ( 14.58%) , repeated drug use ( 4.17%) and medicine incompatibility ( 3.75%) , etc.CONCLUSIONS: The review of intravenous medicine prescriptions and medical orders by clinical pharmacists can timely find and correct the irrational phenomenon in clinic , and improve the safety and effectiveness of drug treatment .%目的:了解广东省妇幼保健院(以下简称“我院”)番禺院区静脉用药调配中心不合理处方和医嘱情况。方法:对我院番禺院区2014年6—11月静脉药物审方过程中发现的不合理处方和医嘱进行回顾性统计、分析,对其中不合理处方和医嘱提出修改意见和建议。结果:共审核处方和医嘱123368条,其中不合理处方和医嘱240条,占总数的0.20%。不合理处方和医嘱类型包括溶剂不适宜(35.83%)、用法和用量不适宜(32.08%)、遴选药物不适宜(14.58%)、重复给药(4.17%)、配伍禁忌(3.75%)等。结论:临床药师对静脉用药处方和医嘱进行审核,可及时发现并纠正临床的不合理用药现象,提高药物治疗的安全性和有效性。

  12. Polydioxanone-based bio-materials for tissue engineering and drug/gene delivery applications.

    Science.gov (United States)

    Goonoo, Nowsheen; Jeetah, Roubeena; Bhaw-Luximon, Archana; Jhurry, Dhanjay

    2015-11-01

    Since the commercialization of polydioxanone (PDX) as a biodegradable monofilament suture by Ethicon in 1981, the polymer has received only limited interest until recently. The limitations of polylactide-co-glycolide (PLGA) coupled with the growing need for materials with enhanced features and the advent of new fabrication techniques such as electrospinning have revived interest for PDX in medical devices, tissue engineering and drug delivery applications. Electrospun PDX mats show comparable mechanical properties as the major structural components of native vascular extracellular matrix (ECM) i.e. collagen and elastin. In addition, PDX's unique shape memory property provides rebound and kink resistance when fabricated into vascular conduits. The synthesis of methyl dioxanone (MeDX) monomer and copolymers of dioxanone (DX) and MeDX have opened up new perspectives for poly(ester-ether)s, enabling the design of the next generation of tissue engineering scaffolds for application in regenerating such tissues as arteries, peripheral nerve and bone. Tailoring of polymer properties and their formulation as nanoparticles, nanomicelles or nanofibers have brought along important developments in the area of controlled drug or gene delivery. This paper reviews the synthesis of PDX and its copolymers and provides for the first time an exhaustive account of its applications in the (bio)medical field with focus on tissue engineering and drug/gene delivery.

  13. Delays in new drug applications in Japan and industrial R&D strategies.

    Science.gov (United States)

    Hirai, Y; Kinoshita, H; Kusama, M; Yasuda, K; Sugiyama, Y; Ono, S

    2010-02-01

    The gap between Japan and both the United States (US) and the European Union (EU) with regard to access to new drugs is becoming a major issue in Japan. We analyzed the time lags involved in new drug application (NDA) and biological license application submissions in Japan, the US, and the EU in order to identify the causes of delayed access. The time lag related to submission of applications ("submission lag") was longer for in-licensed products and for non-Japanese companies. Factors related to costs of clinical studies and potential volumes of sales were not associated with the submission lag. A bridging strategy (extrapolative use of foreign clinical data in the clinical data package based on International Conference on Harmonisation guideline E5) seemed to reduce submission lag, but the association between the two diminished when the cause-and-effect relationship was specifically investigated. These results suggest that multinational companies are likely to place more emphasis on the choice of development strategies that successfully lead to their goal rather than on direct costs and expected sales when deciding to introduce their pharmaceutical products in Japan. Our findings indicate that the clinical development guidances that helps pharmaceutical companies decide on investment and strategies are also the key to narrowing the gap in access to new drugs.

  14. Methods for Elucidation of DNA-Anticancer Drug Interactions and their Applications in the Development of New Drugs.

    Science.gov (United States)

    Misiak, Majus; Mantegazza, Francesco; Beretta, Giovanni L

    2016-01-01

    DNA damaging agents including anthracyclines, camptothecins and platinum drugs are among most frequently used drugs in the chemotherapeutic routine. Due to their relatively low selectivity for cancer cells, administration of these drugs is associated with adverse side effects, inherent genotoxicity with risk of developing secondary cancers. Development of new drugs, which could be spared of these drawbacks and characterize by improved antitumor efficacy, remains challenging yet vitally important task. These properties are in large part dictated by the selectivity of interaction between the drug and DNA and in this way the studies aimed at elucidating the complex interactions between ligand and DNA represent a key step in the drug development. Studies of the drug-DNA interactions encompass determination of DNA sequence specificity and mode of DNA binding as well as kinetic, dynamic and structural parameters of binding. Here, we consider the types of interactions between small molecule ligands and polynucleotides, how they are affected by DNA sequence and structure, and what is their significance for the antitumor activity. Based on this knowledge, we discuss the wide array of experimental techniques available to researchers for studying drug-DNA interactions, which include absorption and emission spectroscopies, NMR, magnetic and optical tweezers or atomic force microscopy. We show, using the clinical and experimental anticancer drugs as examples, how these methods provide various types of information and at the same time complement each other to provide full picture of drug- DNA interaction and aid in the development of new drugs.

  15. HDL as a drug and nucleic acid delivery vehicle

    Directory of Open Access Journals (Sweden)

    Andras G Lacko

    2015-10-01

    Full Text Available This review is intended to evaluate the research findings and potential clinical applications of drug transport systems, developed based on the concepts of the structure/function and physiological role(s of high density lipoprotein=type nanoparticles. These macromolecules provide targeted transport of cholesteryl esters (a highly lipophilic payload in their natural/physiological environment. The property of accommodating highly water insoluble constituents in their core region enables HDL type nanoparticles to effectively transport hydrophobic drugs upon intravenous administration. Even though the application of reconstituted HDL in the treatment of a number of diseases is reviewed, the primary focus is on the application of HDL type drug delivery agents in cancer chemotherapy. The use of both native and synthetic HDL as drug delivery agents are compared to evaluate their respective potentials for commercial and clinical development. The current status and future perspectives for HDL type nanoparticles are discussed, including current obstacles and future applications in therapeutics.

  16. Mesoporous Silica Nanomaterials for Applications in Catalysis, Sensing, Drug Delivery and Gene Transfection

    Energy Technology Data Exchange (ETDEWEB)

    Radu, Daniela Rodica [Iowa State Univ., Ames, IA (United States)

    2004-01-01

    The central theme of this dissertation is represented by the versatility of mesoporous silica nanomaterials in various applications such as catalysis and bio-applications, with main focus on biological applications of Mesoporous Silica Nanospheres (MSN). The metamorphosis that we impose to these materials from catalysis to sensing and to drug and gene delivery is detailed in this dissertation. First, we developed a synthetic method that can fine tune the amount of chemically accessible organic functional groups on the pores surface of MSN by exploiting electrostatic and size matching between the cationic alkylammonium head group of the cetyltrimethylammonium bromide (CTAB) surfactant and various anionic organoalkoxysilane precursors at the micelle-water interface in a base-catalyzed condensation reaction of silicate. Aiming nature imitation, we demonstrated the catalytic abilities of the MSNs, We utilized an ethylenediamine functional group for chelating Cu2+ as a catalytic functional group anchored inside the mesopores. Thus, a polyalkynylene-based conducting polymer (molecular wire) was synthesized within the Cu-functionalized MSNs silica catalyst. For sensing applications, we have synthesized a poly(lactic acid) coated mesoporous silica nanosphere (PLA-MSN) material that serves as a fluorescence sensor system for detection of amino-containing neurotransmitters in neutral aqueous buffer. We exploited the mesoporosity of MSNs for encapsulating pharmaceutical drugs. We examined bio-friendly capping molecules such as polyamidoamine dendrimers of generations G2 to G4, to prevent the drug leaching. Next, the drug delivery system employed MSNs loaded with Doxorubicin, an anticancer drug. The results demonstrated that these nano-Trojan horses have ability to deliver Doxorubicin to cancer cells and induce their death. Finally, to demonstrate the potential of MSN as an universal cellular transmembrane nanovehicle, we anchored positively charged dendrimers on

  17. Mesoporous Silica Nanomaterials for Applications in Catalysis, Sensing, Drug Delivery and Gene Transfection

    Energy Technology Data Exchange (ETDEWEB)

    Daniela Rodica Radu

    2005-12-19

    The central theme of this dissertation is represented by the versatility of mesoporous silica nanomaterials in various applications such as catalysis and bio-applications, with main focus on biological applications of Mesoporous Silica Nanospheres (MSN). The metamorphosis that we impose to these materials from catalysis to sensing and to drug and gene delivery is detailed in this dissertation. First, we developed a synthetic method that can fine tune the amount of chemically accessible organic functional groups on the pores surface of MSN by exploiting electrostatic and size matching between the cationic alkylammonium head group of the cetyltrimethylammonium bromide (CTAB) surfactant and various anionic organoalkoxysilane precursors at the micelle-water interface in a base-catalyzed condensation reaction of silicate. Aiming nature imitation, we demonstrated the catalytic abilities of the MSNs, We utilized an ethylenediamine functional group for chelating Cu{sup 2+} as a catalytic functional group anchored inside the mesopores. Thus, a polyalkynylene-based conducting polymer (molecular wire) was synthesized within the Cu-functionalized MSNs silica catalyst. For sensing applications, we have synthesized a poly(lactic acid) coated mesoporous silica nanosphere (PLA-MSN) material that serves as a fluorescence sensor system for detection of amino-containing neurotransmitters in neutral aqueous buffer. We exploited the mesoporosity of MSNs for encapsulating pharmaceutical drugs. We examined bio-friendly capping molecules such as polyamidoamine dendrimers of generations G2 to G4, to prevent the drug leaching. Next, the drug delivery system employed MSNs loaded with Doxorubicin, an anticancer drug. The results demonstrated that these nano-Trojan horses have ability to deliver Doxorubicin to cancer cells and induce their death. Finally, to demonstrate the potential of MSN as an universal cellular transmembrane nanovehicle, we anchored positively charged dendrimers on the

  18. Anisotropic noble metal nanoparticles: Synthesis, surface functionalization and applications in biosensing, bioimaging, drug delivery and theranostics.

    Science.gov (United States)

    Paramasivam, Gokul; Kayambu, Namitharan; Rabel, Arul Maximus; Sundramoorthy, Ashok K; Sundaramurthy, Anandhakumar

    2017-02-01

    Anisotropic nanoparticles have fascinated scientists and engineering communities for over a century because of their unique physical and chemical properties. In recent years, continuous advances in design and fabrication of anisotropic nanoparticles have opened new avenues for application in various areas of biology, chemistry and physics. Anisotropic nanoparticles have the plasmon absorption in the visible as well as near-infrared (NIR) region, which enables them to be used for crucial applications such as biological imaging, medical diagnostics and therapy ("theranostics"). Here, we describe the progress in anisotropic nanoparticles achieved since the millennium in the area of preparation including various shapes and modification of the particle surface, and in areas of application by providing examples of applications in biosensing, bio-imaging, drug delivery and theranostics. Furthermore, we also explain various mechanisms involved in cellular uptake of anisotropic nanoparticles, and conclude with our opinion on various obstacles that limit their applications in biomedical field. Anisotropy at the molecular level has always fascinated scientists and engineering communities for over a century, however, the research on novel methods through which shape and size of nanoparticles can be precisely controlled has opened new avenues for anisotropic nanoparticles in various areas of biology, chemistry and physics. In this manuscript, we describe progress achieved since the millennium in the areas of preparation of various shapes of anisotropic nanoparticles, investigate various methods involved in modifying the surface of these NPs, and provide examples of applications in biosensing and bio-imaging, drug delivery and theranostics. We also present mechanisms involved in cellular uptake of nanoparticles, describe different methods of preparation of anisotropic nanoparticles including biomimetic and photochemical synthesis, and conclude with our opinion on various

  19. Efficacy of Intravenous Immunoglobulin in Neurological Diseases.

    Science.gov (United States)

    Lünemann, Jan D; Quast, Isaak; Dalakas, Marinos C

    2016-01-01

    Owing to its anti-inflammatory efficacy in various autoimmune disease conditions, intravenous immunoglobulin (IVIG)-pooled IgG obtained from the plasma of several thousands individuals-has been used for nearly three decades and is proving to be efficient in a growing number of neurological diseases. IVIG therapy has been firmly established for the treatment of Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, and multifocal motor neuropathy, either as first-line therapy or adjunctive treatment. IVIG is also recommended as rescue therapy in patients with worsening myasthenia gravis and is beneficial as a second-line therapy for dermatomyositis and stiff-person syndrome. Subcutaneous rather than intravenous administration of IgG is gaining momentum because of its effectiveness in patients with primary immunodeficiency and the ease with which it can be administered independently from hospital-based infusions. The demand for IVIG therapy is growing, resulting in rising costs and supply shortages. Strategies to replace IVIG with recombinant products have been developed based on proposed mechanisms that confer the anti-inflammatory activity of IVIG, but their efficacy has not been tested in clinical trials. This review covers new developments in the immunobiology and clinical applications of IVIG in neurological diseases.

  20. Mathematical Model to Predict Skin Concentration after Topical Application of Drugs

    Directory of Open Access Journals (Sweden)

    Hiroaki Todo

    2013-12-01

    Full Text Available Skin permeation experiments have been broadly done since 1970s to 1980s as an evaluation method for transdermal drug delivery systems. In topically applied drug and cosmetic formulations, skin concentration of chemical compounds is more important than their skin permeations, because primary target site of the chemical compounds is skin surface or skin tissues. Furthermore, the direct pharmacological reaction of a metabolically stable drug that binds with specific receptors of known expression levels in an organ can be determined by Hill’s equation. Nevertheless, little investigation was carried out on the test method of skin concentration after topically application of chemical compounds. Recently we investigated an estimating method of skin concentration of the chemical compounds from their skin permeation profiles. In the study, we took care of “3Rs” issues for animal experiments. We have proposed an equation which was capable to estimate animal skin concentration from permeation profile through the artificial membrane (silicone membrane and animal skin. This new approach may allow the skin concentration of a drug to be predicted using Fick’s second law of diffusion. The silicone membrane was found to be useful as an alternative membrane to animal skin for predicting skin concentration of chemical compounds, because an extremely excellent extrapolation to animal skin concentration was attained by calculation using the silicone membrane permeation data. In this chapter, we aimed to establish an accurate and convenient method for predicting the concentration profiles of drugs in the skin based on the skin permeation parameters of topically active drugs derived from steady-state skin permeation experiments.

  1. The application of EDTA in drug delivery systems: doxorubicin liposomes loaded via NH4EDTA gradient

    Directory of Open Access Journals (Sweden)

    Song YZ

    2014-08-01

    Full Text Available Yanzhi Song,1 Zhenjun Huang,1 Yang Song,2 Qingjing Tian,1 Xinrong Liu,1 Zhennan She,1 Jiao Jiao,1 Eliza Lu,3 Yihui Deng11College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China; 2Jiangsu Hansoh Pharmaceutical Co., Ltd., Lianyungang, People’s Republic of China; 3Livzon Mabpharm Inc., Zhuhai, People’s Republic of ChinaAbstract: The applications of ethylenediaminetetraacetic acid (EDTA have been expanded from the treatment of heavy metal poisoning to chelation therapies for atherosclerosis, heart disease, and cancers, in which EDTA reduces morbidity and mortality by chelating toxic metal ions. In this study, EDTA was used in a drug delivery system by adopting an NH4EDTA gradient method to load doxorubicin into liposomes with the goal of increasing therapeutic effects and decreasing drug-related cytotoxicity. The particle size of the optimum NH4EDTA gradient liposomes was 79.4±1.87 nm, and the entrapment efficiency was 95.54%±0.59%. In vitro studies revealed that liposomes prepared using an NH4EDTA gradient possessed long-term stability and delayed drug release. The in vivo studies also showed the superiority of the new doxorubicin formulation. Compared with an equivalent drug dose (5 mg/kg prepared by (NH42SO4 gradient, NH4EDTA gradient liposomes showed no significant differences in tumor inhibition ratio, but cardiotoxicity and liposome-related immune organ damage were lower, and no drug-related deaths were observed. These results show that use of the NH4EDTA gradient method to load doxorubicin into liposomes could significantly reduce drug toxicity without influencing antitumor activity.Keywords: NH4EDTA, liposome, doxorubicin, ion gradient, antitumor activity, toxicity

  2. Biological applications of LbL multilayer capsules: from drug delivery to sensing.

    Science.gov (United States)

    del Mercato, Loretta Laureana; Ferraro, Marzia Maria; Baldassarre, Francesca; Mancarella, Serena; Greco, Valentina; Rinaldi, Ross; Leporatti, Stefano

    2014-05-01

    Polyelectrolyte multilayer (PEM) capsules engineered with active elements for targeting, labeling, sensing and delivery hold great promise for the controlled delivery of drugs and the development of new sensing platforms. PEM capsules composed of biodegradable polyelectrolytes are fabricated for intracellular delivery of encapsulated cargo (for example peptides, enzymes, DNA, and drugs) through gradual biodegradation of the shell components. PEM capsules with shells responsive to environmental or physical stimuli are exploited to control drug release. In the presence of appropriate triggers (e.g., pH variation or light irradiation) the pores of the multilayer shell are unlocked, leading to the controlled release of encapsulated cargos. By loading sensing elements in the capsules interior, PEM capsules sensitive to biological analytes, such as ions and metabolites, are assembled and used to detect analyte concentration changes in the surrounding environment. This Review aims to evaluate the current state of PEM capsules for drug delivery and sensing applications. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Microfabricated engineered particle systems for respiratory drug delivery and other pharmaceutical applications.

    Science.gov (United States)

    Garcia, Andres; Mack, Peter; Williams, Stuart; Fromen, Catherine; Shen, Tammy; Tully, Janet; Pillai, Jonathan; Kuehl, Philip; Napier, Mary; Desimone, Joseph M; Maynor, Benjamin W

    2012-01-01

    Particle Replication in Non-Wetting Templates (PRINT(®)) is a platform particle drug delivery technology that coopts the precision and nanoscale spatial resolution inherently afforded by lithographic techniques derived from the microelectronics industry to produce precisely engineered particles. We describe the utility of PRINT technology as a strategy for formulation and delivery of small molecule and biologic therapeutics, highlighting previous studies where particle size, shape, and chemistry have been used to enhance systemic particle distribution properties. In addition, we introduce the application of PRINT technology towards respiratory drug delivery, a particular interest due to the pharmaceutical need for increased control over dry powder characteristics to improve drug delivery and therapeutic indices. To this end, we have produced dry powder particles with micro- and nanoscale geometric features and composed of small molecule and protein therapeutics. Aerosols generated from these particles show attractive properties for efficient pulmonary delivery and differential respiratory deposition characteristics based on particle geometry. This work highlights the advantages of adopting proven microfabrication techniques in achieving unprecedented control over particle geometric design for drug delivery.

  4. Promote potential applications of nanoparticles as respiratory drug carrier: insights from molecular dynamics simulations.

    Science.gov (United States)

    Lin, Xubo; Bai, Tingting; Zuo, Yi Y; Gu, Ning

    2014-03-07

    Nanoparticles (NPs) show great promises in biomedical applications as the respiratory drug carrier system. Once reaching the alveolar region, NPs first interact with the pulmonary surfactant (PS) film, which serves as the first biological barrier and plays an important role in maintaining the normal respiratory mechanics. Therefore, understanding the interactions between NPs and PS can help promote the NP-based respiratory drug carrier systems. Using coarse-grained molecular dynamics simulations, we studied the effect of rigid spherical NPs with different hydrophobicity and sizes on a dipalmitoylphosphatidylcholine (DPPC) monolayer at the air-water interface. Four different NPs were considered, including hydrophilic and hydrophobic NPs, each with two diameters of 3 nm and 5 nm (the sizes are comparable to that of generation 3 and 5 PAMAM dendrimers, which have been widely used for nanoscale drug carrier systems). Our simulations showed that hydrophilic NPs can readily penetrate into the aqueous phase with little or no disturbance on the DPPC monolayer. However, hydrophobic NPs tend to induce large structural disruptions, thus inhibiting the normal phase transition of the DPPC monolayer upon film compression. Our simulations also showed that this inhibitory effect of hydrophobic NPs can be mitigated through PEGylation. Our results provide useful guidelines for molecular design of NPs as carrier systems for pulmonary drug delivery.

  5. Application of PK/PD Modeling in Veterinary Field: Dose Optimization and Drug Resistance Prediction

    Directory of Open Access Journals (Sweden)

    Ijaz Ahmad

    2016-01-01

    Full Text Available Among veterinary drugs, antibiotics are frequently used. The true mean of antibiotic treatment is to administer dose of drug that will have enough high possibility of attaining the preferred curative effect, with adequately low chance of concentration associated toxicity. Rising of antibacterial resistance and lack of novel antibiotic is a global crisis; therefore there is an urgent need to overcome this problem. Inappropriate antibiotic selection, group treatment, and suboptimal dosing are mostly responsible for the mentioned problem. One approach to minimizing the antibacterial resistance is to optimize the dosage regimen. PK/PD model is important realm to be used for that purpose from several years. PK/PD model describes the relationship between drug potency, microorganism exposed to drug, and the effect observed. Proper use of the most modern PK/PD modeling approaches in veterinary medicine can optimize the dosage for patient, which in turn reduce toxicity and reduce the emergence of resistance. The aim of this review is to look at the existing state and application of PK/PD in veterinary medicine based on in vitro, in vivo, healthy, and disease model.

  6. The application of 3D cell models to support drug safety assessment: opportunities & challenges.

    Science.gov (United States)

    Roth, Adrian; Singer, Thomas

    2014-04-01

    The selection of drug candidates early in development has become increasingly important to minimize the use of animals and to avoid costly failures of drugs later in development. In vitro systems to predict and assess organ toxicity have so far been of limited value due to difficulties in demonstrating in vivo-relevant toxicity at a cell culture level. To overcome the limitations of single-cell type monolayer cultures and short-lived primary cell preparations, researchers have created novel 3-dimensional culture systems which appear to more closely resemble in vivo biology. These could become a key for the pharmaceutical industry in the evaluation of drug candidates. However, the value and acceptance of those new models in standard drug safety applications have yet to be demonstrated. This review aims to provide an overview of the different approaches undertaken in the field of pre-clinical safety assessment, organ toxicity, in particular, with an emphasis on examples and technical challenges. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Thermosensitive hydrogel for periodontal application: in vitro drug release, antibacterial activity and toxicity evaluation.

    Science.gov (United States)

    Pakzad, Yousef; Ganji, Fariba

    2016-02-01

    Injectable thermosensitive chitosan hydrogel is an attractive temperature-induced sol-gel solution that is widely used in drug delivery and biomedical applications. In this study, an injectable antimicrobial delivery system for periodontal treatment based on chitosan/gelatin/β-glycerolphosphate solution has been developed. The result of thermal and mechanical evaluations of chitosan/gelatin/β-glycerolphosphate hydrogel showed that adding gelatin to chitosan/β-glycerolphosphate solution significantly decreased gelling time and increased gel strength at 37℃. The antimicrobial agents chosen for release studies were metronidazole with a low molecular weight and vancomycin hydrochloride with a high molecular weight. The initial burst and total in vitro drug release for metronidazole was 13% and 67%, respectively. The initial burst and total drug release for vancomycin hydrochloride was relatively low at 3% and 23%, respectively. The momentary and total percentage of metronidazole accumulated in the phosphate buffer revealed that chitosan/gelatin/β-glycerolphosphate can develop and maintain sustained release of metronidazole in concentrations that are effective for eliminating pathogenic bacteria over time. Cytotoxicity evaluations show that chitosan/gelatin/β-glycerolphosphate thermosensitive hydrogel is a drug carrier with no cytotoxic effects.

  8. Microfabricated Engineered Particle Systems for Respiratory Drug Delivery and Other Pharmaceutical Applications

    Directory of Open Access Journals (Sweden)

    Andres Garcia

    2012-01-01

    Full Text Available Particle Replication in Non-Wetting Templates (PRINT® is a platform particle drug delivery technology that coopts the precision and nanoscale spatial resolution inherently afforded by lithographic techniques derived from the microelectronics industry to produce precisely engineered particles. We describe the utility of PRINT technology as a strategy for formulation and delivery of small molecule and biologic therapeutics, highlighting previous studies where particle size, shape, and chemistry have been used to enhance systemic particle distribution properties. In addition, we introduce the application of PRINT technology towards respiratory drug delivery, a particular interest due to the pharmaceutical need for increased control over dry powder characteristics to improve drug delivery and therapeutic indices. To this end, we have produced dry powder particles with micro- and nanoscale geometric features and composed of small molecule and protein therapeutics. Aerosols generated from these particles show attractive properties for efficient pulmonary delivery and differential respiratory deposition characteristics based on particle geometry. This work highlights the advantages of adopting proven microfabrication techniques in achieving unprecedented control over particle geometric design for drug delivery.

  9. Integrating biomarkers to predict renal and cardiovascular drug efficacy: PRE score applications from drug registration to personalized medicine

    OpenAIRE

    Schievink, Bauke

    2016-01-01

    The prevalence of chronic kidney disease is increasing worldwide, and forecasts for 2030 indicate that the number of patients requiring renal replacement therapies will more than double. The increase in requirement of renal replacement therapies and the availability of only few proven effective therapies highlight the need to develop new drugs and intervention strategies. In the current drug development and registration process a single renal risk marker is selected and a drug is targeted tow...

  10. High intensity focused ultrasound technology, its scope and applications in therapy and drug delivery.

    Science.gov (United States)

    Phenix, Christopher Peter; Togtema, Melissa; Pichardo, Samuel; Zehbe, Ingeborg; Curiel, Laura

    2014-01-01

    Ultrasonography is a safe, inexpensive and wide-spread diagnostic tool capable of producing real-time non-invasive images without significant biological effects. However, the propagation of higher energy, intensity and frequency ultrasound waves through living tissues can induce thermal, mechanical and chemical effects useful for a variety of therapeutic applications. With the recent development of clinically approved High Intensity Focused Ultrasound (HIFU) systems, therapeutic ultrasound is now a medical reality. Indeed, HIFU has been used for the thermal ablation of pathological lesions; localized, minimally invasive ultrasound-mediated drug delivery through the transient formation of pores on cell membranes; the temporary disruption of skin and the blood brain barrier; the ultrasound induced break-down of blood clots; and the targeted release of drugs using ultrasound and temperature sensitive drug carriers. This review seeks to engage the pharmaceutical research community by providing an overview on the biological effects of ultrasound as well as highlighting important therapeutic applications, current deficiencies and future directions.

  11. Application of Absorption Modeling in Rational Design of Drug Product Under Quality-by-Design Paradigm.

    Science.gov (United States)

    Kesisoglou, Filippos; Mitra, Amitava

    2015-09-01

    Physiologically based absorption models can be an important tool in understanding product performance and hence implementation of Quality by Design (QbD) in drug product development. In this report, we show several case studies to demonstrate the potential application of absorption modeling in rational design of drug product under the QbD paradigm. The examples include application of absorption modeling—(1) prior to first-in-human studies to guide development of a formulation with minimal sensitivity to higher gastric pH and hence reduced interaction when co-administered with PPIs and/or H2RAs, (2) design of a controlled release formulation with optimal release rate to meet trough plasma concentrations and enable QD dosing, (3) understanding the impact of API particle size distribution on tablet bioavailability and guide formulation design in late-stage development, (4) assess impact of API phase change on product performance to guide specification setting, and (5) investigate the effect of dissolution rate changes on formulation bioperformance and enable appropriate specification setting. These case studies are meant to highlight the utility of physiologically based absorption modeling in gaining a thorough understanding of the product performance and the critical factors impacting performance to drive design of a robust drug product that would deliver the optimal benefit to the patients.

  12. Advances and applications of binding affinity prediction methods in drug discovery.

    Science.gov (United States)

    Parenti, Marco Daniele; Rastelli, Giulio

    2012-01-01

    Nowadays, the improvement of R&D productivity is the primary commitment in pharmaceutical research, both in big pharma and smaller biotech companies. To reduce costs, to speed up the discovery process and to increase the chance of success, advanced methods of rational drug design are very helpful, as demonstrated by several successful applications. Among these, computational methods able to predict the binding affinity of small molecules to specific biological targets are of special interest because they can accelerate the discovery of new hit compounds. Here we provide an overview of the most widely used methods in the field of binding affinity prediction, as well as of our own work in developing BEAR, an innovative methodology specifically devised to overtake some limitations in existing approaches. The BEAR method was successfully validated against different biological targets, and proved its efficacy in retrieving active compounds from virtual screening campaigns. The results obtained so far indicate that BEAR may become a leading tool in the drug discovery pipeline. We primarily discuss advantages and drawbacks of each technique and show relevant examples and applications in drug discovery.

  13. Upgrading HepG2 cells with adenoviral vectors that encode drug-metabolizing enzymes: application for drug hepatotoxicity testing.

    Science.gov (United States)

    Gómez-Lechón, M José; Tolosa, Laia; Donato, M Teresa

    2017-02-01

    Drug attrition rates due to hepatotoxicity are an important safety issue considered in drug development. The HepG2 hepatoma cell line is currently being used for drug-induced hepatotoxicity evaluations, but its expression of drug-metabolizing enzymes is poor compared with hepatocytes. Different approaches have been proposed to upgrade HepG2 cells for more reliable drug-induced liver injury predictions. Areas covered: We describe the advantages and limitations of HepG2 cells transduced with adenoviral vectors that encode drug-metabolizing enzymes for safety risk assessments of bioactivable compounds. Adenoviral transduction facilitates efficient and controlled delivery of multiple drug-metabolizing activities to HepG2 cells at comparable levels to primary human hepatocytes by generating an 'artificial hepatocyte'. Furthermore, adenoviral transduction enables the design of tailored cells expressing particular metabolic capacities. Expert opinion: Upgraded HepG2 cells that recreate known inter-individual variations in hepatic CYP and conjugating activities due to both genetic (e.g., polymorphisms) or environmental (e.g., induction, inhibition) factors seems a suitable model to identify bioactivable drug and conduct hepatotoxicity risk assessments. This strategy should enable the generation of customized cells by reproducing human pheno- and genotypic CYP variability to represent a valuable human hepatic cell model to develop new safer drugs and to improve existing predictive toxicity assays.

  14. Evaluation of blood-brain barrier transport and CNS drug metabolism in diseased and control brain after intravenous L-DOPA in a unilateral rat model of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Ravenstijn Paulien GM

    2012-02-01

    Full Text Available Abstract Background Changes in blood-brain barrier (BBB functionality have been implicated in Parkinson's disease. This study aimed to investigate BBB transport of L-DOPA transport in conjunction with its intra-brain conversion, in both control and diseased cerebral hemispheres in the unilateral rat rotenone model of Parkinson's disease. Methods In Lewis rats, at 14 days after unilateral infusion of rotenone into the medial forebrain bundle, L-DOPA was administered intravenously (10, 25 or 50 mg/kg. Serial blood samples and brain striatal microdialysates were analysed for L-DOPA, and the dopamine metabolites DOPAC and HVA. Ex-vivo brain tissue was analyzed for changes in tyrosine hydroxylase staining as a biomarker for Parkinson's disease severity. Data were analysed by population pharmacokinetic analysis (NONMEM to compare BBB transport of L-DOPA in conjunction with the conversion of L-DOPA into DOPAC and HVA, in control and diseased cerebral hemisphere. Results Plasma pharmacokinetics of L-DOPA could be described by a 3-compartmental model. In rotenone responders (71%, no difference in L-DOPA BBB transport was found between diseased and control cerebral hemisphere. However, in the diseased compared with the control side, basal microdialysate levels of DOPAC and HVA were substantially lower, whereas following L-DOPA administration their elimination rates were higher. Conclusions Parkinson's disease-like pathology, indicated by a huge reduction of tyrosine hydroxylase as well as by substantially reduced levels and higher elimination rates of DOPAC and HVA, does not result in changes in BBB transport of L-DOPA. Taking the results of this study and that of previous ones, it can be concluded that changes in BBB functionality are not a specific characteristic of Parkinson's disease, and cannot account for the decreased benefit of L-DOPA at later stages of Parkinson's disease.

  15. 77 FR 40367 - Wyeth Pharmaceuticals, Inc.; Withdrawal of Approval of a New Drug Application for DURACT Capsules

    Science.gov (United States)

    2012-07-09

    ... Drug Application for DURACT Capsules AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY... DURACT (bromfenac sodium) Capsules, held by Wyeth Pharmaceuticals, Inc. (Wyeth), P.O. Box 8299.... SUPPLEMENTARY INFORMATION: In June 1998, Wyeth voluntarily withdrew DURACT (bromfenac sodium) Capsules from the...

  16. Main Reasons for Registration Application Refusal of Generic and Similar Pharmaceutical Drug Products by the Brazilian Health Regulatory Agency (ANVISA)

    Science.gov (United States)

    do Carmo, Ana Cerúlia Moraes; Piras, Stefânia Schimaneski; Rocha, Nayrton Flávio Moura

    2017-01-01

    Objective. The marketing authorization of generic and similar pharmaceutical drug products involves the analysis of proposing company's administrative aspects as well as drug product technical description and scientific evaluations. This study evaluated the main reasons for registration refusal of generic and similar pharmaceutical drug products in Brazil. The aim is to help future applicants to better organize the proposal. Methods. A retrospective search of drug products registration processes was performed on the Brazilian Government Official Gazette from January 1, 2015, and December 31, 2015. Results. Drug product quality control, drug product stability study, deadline accomplishment, API quality control made by drug manufacturer, active pharmaceutical ingredient (API), and production report were the main reasons for marketing authorization application refusal of generic and similar pharmaceutical drug products in 2015. Conclusion. Disclosure of the reasons behind failed applications is a step forward on regulatory transparency. Sharing of experiences is essential to international regulatory authorities and organizations to improve legislation requirements for the marketing authorization of generic and similar pharmaceutical drug products. PMID:28280742

  17. Main Reasons for Registration Application Refusal of Generic and Similar Pharmaceutical Drug Products by the Brazilian Health Regulatory Agency (ANVISA).

    Science.gov (United States)

    do Carmo, Ana Cerúlia Moraes; Piras, Stefânia Schimaneski; Rocha, Nayrton Flávio Moura; Gratieri, Tais

    2017-01-01

    Objective. The marketing authorization of generic and similar pharmaceutical drug products involves the analysis of proposing company's administrative aspects as well as drug product technical description and scientific evaluations. This study evaluated the main reasons for registration refusal of generic and similar pharmaceutical drug products in Brazil. The aim is to help future applicants to better organize the proposal. Methods. A retrospective search of drug products registration processes was performed on the Brazilian Government Official Gazette from January 1, 2015, and December 31, 2015. Results. Drug product quality control, drug product stability study, deadline accomplishment, API quality control made by drug manufacturer, active pharmaceutical ingredient (API), and production report were the main reasons for marketing authorization application refusal of generic and similar pharmaceutical drug products in 2015. Conclusion. Disclosure of the reasons behind failed applications is a step forward on regulatory transparency. Sharing of experiences is essential to international regulatory authorities and organizations to improve legislation requirements for the marketing authorization of generic and similar pharmaceutical drug products.

  18. 78 FR 48177 - Purdue Pharma L.P.; Withdrawal of Approval of a New Drug Application for Oxycontin

    Science.gov (United States)

    2013-08-07

    .... FDA-2013-N-0883] Purdue Pharma L.P.; Withdrawal of Approval of a New Drug Application for Oxycontin...) Extended-Release Tablets, held by Purdue Pharma L.P. (Purdue), One Stamford Forum, Stamford, CT...

  19. Are postoperative intravenous antibiotics necessary after bimaxillary orthognathic surgery? A prospective, randomized, double-blind, placebo-controlled clinical trial.

    Science.gov (United States)

    Tan, S K; Lo, J; Zwahlen, R A

    2011-12-01

    Postoperative antibiotic prophylaxis is often administered intravenously, despite an increased morbidity rate compared with oral application. This study investigates whether a postoperative oral antibiotic regimen is as effective as incorporation of intravenous antibiotics after bimaxillary orthognathic surgery. 42 patients who underwent bimaxillary orthognathic surgery between December 2008 and May 2010 were randomly allocated to 2 placebo-controlled postoperative antibiotic prophylaxis groups. Group 1 received oral amoxicillin 500mg three times daily; group 2 received intravenous ampicillin 1g four times daily, during the first two postoperative days. Both groups subsequently took oral amoxicillin for three more days. Clinically, the infection rate was assessed in both study groups for a period of 6 weeks after the surgery. 9 patients (21.4%) developed infection. No adverse drug event was detected. No significant difference (p=0.45) was detected in the infection rate between group 1 (3/21) and group 2 (6/21). Age, type of surgical procedures, duration of the operative procedure, surgical procedure-related events, blood loss, and blood transfusion were all found not related to infection (p>0.05). Administration of more cost-effective oral antibiotic prophylaxis, which causes less comorbidity, can be considered to be safe in bimaxillary orthognathic surgery with segmentalizations. Copyright © 2011 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  20. [Lethal intravenous infusion of a wound antiseptic containing polyhexanide].

    Science.gov (United States)

    Wehner, Frank; Wehner, Heinz-Dieter; Schulz, Martin Manfred

    2009-01-01

    Polyhexamethylene biguanide (PHMB) is considered to be highly histocompatible and is one of the most frequently used wound antiseptics. Only one case of intoxication has been reported so far. The present case of a lethal intoxication is the first fatal incident described where causality is substantiated by a temporal coincidence between application and ascertainable organ damage. The laboratory-chemical and histological investigations verified the toxicity of this substance after intravenous application with the main findings being severe hepatic and pancreatic damage.