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Pharmaceutical Intervention (pharmaceutical + intervention)
Selected AbstractsCXCL10-induced cell death in neurons: role of calcium dysregulationEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2006Yongjun Sui Abstract Chemokines play a key role in the regulation of central nervous system disease. CXCL10 over-expression has been observed in several neurodegenerative diseases, including multiple sclerosis, Alzheimer's disease and HIV-associated dementia. More recent studies by others and us have shown that CXCL10 elicits apoptosis in fetal neurons. The mechanism of CXCL10-mediated neurotoxicity, however, remains unclear. In this study, we provide evidence for the direct role of Ca2+ dysregulation in CXCL10-mediated apoptosis. We demonstrate that treatment of fetal neuronal cultures with exogenous CXCL10 produced elevations in intracellular Ca2+ and that this effect was modulated via the binding of CXCL10 to its cognate receptor, CXCR3. We further explored the association of intracellular Ca2+ elevations with the caspases that are involved in CXC10-induced neuronal apoptosis. Our data showed that increased Ca2+, which is available for uptake by the mitochondria, is associated with membrane permeabilization and cytochrome c release from this compartment. The released cytochrome c then activates the initiator active caspase-9. This initiator caspase sequentially activates the effector caspase-3, ultimately leading to apoptosis. This study identifies the temporal signaling cascade involved in CXCL10-mediated neuronal apoptosis and provides putative targets for pharmaceutical intervention of neurological disorders associated with CXCL10 up-regulation. [source] Metabolic side effects of antipsychotic medicationINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 8 2007A. Tschoner Summary The use of second-generation antipsychotics (SGAs) is associated with metabolic side effects including weight gain, diabetes mellitus and an atherogenic lipid profile. These adverse effects are not only the risk factors for cardiovascular disease, insulin resistance and diabetes mellitus leading to increased morbidity and mortality but may also impair the patient's adherence to treatment. SGAs in particular are associated with significant weight gain with clozapine and olanzapine carrying the highest risk, whereas newer agents, such as risperidone and aripiprazole, are considered to be less prone to cause weight gain. Consequently, a consensus development conference convened issuing recommendations on patient monitoring when treated with SGAs. The metabolic effects of antipsychotic drugs should be of concern when planning a patient's treatment strategy. Baseline screening and regular follow-up monitoring whose intervals should depend on the individual predisposition are advised. Possible therapeutical strategies for the management of drug-induced obesity include therapeutic approaches, such as life style change and pharmaceutical intervention. Drugs with a weight reducing effect become more important because of the lack of compliance with behavioural intervention. Topiramate, histamine-antagonists, dopaminergic- and serotoninergic agents have shown positive results in the management of psychotropic medication induced weight gain. However, further trials are required to support a specific therapeutical approach as well as studies to investigate the underlying mechanisms for future drug development. [source] Diagnostic criteria in patients with complex regional pain syndrome assessed in an out-patient clinicACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 7 2010E. A. M. VAN BODEGRAVEN HOF Background: Specific criteria have been described and accepted worldwide for diagnosing patients with complex regional pain syndrome (CRPS). Nevertheless, a clear-cut diagnosis cannot be confirmed in a number of cases. Aim: The objective of this study was to investigate the effectiveness of the described diagnostic criteria used by several clinical disciplines. Methods: We included 195 patients who were referred to our pain clinic within a period of 1 year. Data were collected on patient characteristics, signs, symptoms, disease-related medication, and the background of the referring clinicians. Results: The Harden and Bruehl criteria were confirmed in 95 patients (49%). These patients used a higher than average number of analgesics, opiates, and anti-oxidants, and frequently received prescriptions for benzodiazepines instead of anti-depressants. The mean disease duration was 29 ± 4.6 months and the mean visual analogue score for pain was 8.1 ± 0.19. A subgroup of patients had a colder temperature in the affected extremity compared with the unaffected extremity. This subgroup showed a longer disease duration and higher visual analogue scale pain. Conclusion: The diagnostic criteria used to determine CRPS should be further improved. A large number of referred patients experienced substantial pain, without receiving adequate medication. Disease-related medication is unrelated to CRPS-specific disease activity. Knowledge of underlying mechanisms is warranted before an adequate pharmaceutical intervention can be considered. [source] Pharmacological approaches towards rationalizing the use of endoparasitic drugs in small animalsJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2006S. F. SANCHEZ BRUNI Parasitic diseases are an important health concern to small animal veterinarians worldwide, and their zoonotic potential is also of relevance to human medicine. The treatment and control of such conditions relies heavily on pharmaceutical intervention using a range of antiparasitic drugs and/or their biologically active metabolites. Broad spectrum agents have been produced, although narrow and even monospecific drugs are used in some situations. Their efficacy may depend on dosage, the target pathogen(s), the host species and/or the site of infection. Optimal use of antiparasitics requires a detailed consideration of the pharmacokinetic and pharmacodynamic properties of the drugs in specific clinical contexts. This review summarizes the present status of knowledge on the metabolism, and physicochemical and pharmacological properties of the major antiparasitic drugs currently used in small animal veterinary practice. In addition, data relevant to therapeutic dosage, efficacy and clinical indication/contraindication, particularly in relation to combination drug therapy, are included. [source] Chemokines and their receptors in asthma and chronic obstructive pulmonary diseaseCLINICAL & EXPERIMENTAL ALLERGY REVIEWS, Issue 2004F. Sinigaglia Summary T-cell trafficking into pulmonary tissue is a critical component of the host defense response. Migration of T cells into the lung also appears to orchestrate inflammation, tissue injury and remodelling of tissue architecture. Accumulating evidence suggest that chemokines and their receptors constitute essential cues for the recruitment and localization of T cells into sites of inflammation. Because of the clinical importance of chemokines and the potential benefit of pharmaceutical intervention in the chemokine pathway, there have been many recent advances in the chemokine field. This review focuses on recent data either from clinical observations or animal models that have highlighted the role chemokine biology in asthma and COPD. [source] The economic consequences of noncompliance in cardiovascular disease and related conditions: a literature reviewINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 2 2008N. Muszbek Summary Objectives:, To review studies on the cost consequences of compliance and/or persistence in cardiovascular disease (CVD) and related conditions (hypertension, dyslipidaemia, diabetes and heart failure) published since 1995, and to evaluate the effects of noncompliance on healthcare expenditure and the cost-effectiveness of pharmaceutical interventions. Methods:, English language papers published between January 1995 and February 2007 that examined compliance/persistence with medication for CVD or related conditions, provided an economic evaluation of pharmacological interventions or cost analysis, and quantified the cost consequences of noncompliance, were identified through database searches. The cost consequences of noncompliance were compared across studies descriptively. Results:, Of the 23 studies identified, 10 focused on hypertension, seven on diabetes, one on dyslipidaemia, one on coronary heart disease, one on heart failure and three covered multiple diseases. In studies assessing drug costs only, increased compliance/persistence led to increased drug costs. However, increased compliance/persistence increased the effectiveness of treatment, leading to a decrease in medical events and non-drug costs. This offset the higher drug costs, leading to savings in overall treatment costs. In studies evaluating the effect of compliance/persistence on the cost-effectiveness of pharmacological interventions, increased compliance/persistence appeared to reduce cost-effectiveness ratios, but the extent of this effect was not quantified. Conclusions:, Noncompliance with cardiovascular and antidiabetic medication is a significant problem. Increased compliance/persistence leads to increased drug costs, but these are offset by reduced non-drug costs, leading to overall cost savings. The effect of noncompliance on the cost-effectiveness of pharmacological interventions is inconclusive and further research is needed to resolve the issue. [source] Advances in vertebrate aging research 2007AGING CELL, Issue 2 2008Steven Austad Summary Among this year's highlights in vertebrate aging research, we find a study in which, contrary to the oxidative stress hypothesis of aging, reduced expression of a major cellular antioxidant, glutathione peroxidase 4, led to a small increase in mouse lifespan. By contrast, a large comparative proteomic analysis discovered a remarkably robust and previous unsuspected inverse association between species lifespan and relative frequency of cysteine residues in mitochondrially encoded respiratory chain proteins only, which the authors attribute to cysteine's ease of oxidation. Another study evaluated more cleanly than any previous work the hypothesis that blood glucose concentration is a key mediator of aging, and concluded that it wasn't. Several new mouse longevity mutants were also reported this year, some (PAPP-A, IRS-1, and IRS-2 knockouts) supporting previous work on the importance of insulin/insulin-like growth factor-1 signaling and aging. However, there were inconsistencies between laboratories in some of the results, which merit further investigation. Also, somewhat inconsistent with these findings, over-expression of insulin-like growth factor-1 in heart only lengthened life. From a completely new direction, type 5 adenylyl cyclase knockout mice were observed to live more than 30% longer than controls. Finally, a new program for evaluating potential pharmaceutical interventions in aging and longevity made its appearance, and is notable at this point chiefly for the excellence of its experimental design. A similar program for the disinterested evaluation of reported longevity mutations in mice would be a service to the community of vertebrate aging researchers. [source] Therapeutic Plasma Exchange in Patients With Severe Hypertriglyceridemia: A Multicenter StudyARTIFICIAL ORGANS, Issue 12 2009Claudia Stefanutti Abstract Extremely high plasma triglyceride (TG) concentration is a recognized risk factor for acute pancreatitis (AP). In order to evaluate the therapeutic efficacy of plasma-exchange plasmapheresis in treating patients with severe hypertriglyceridemia (sHTG), 17 patients who had not responded to conventional medical therapy (fat-free diet plus pharmaceutical interventions) were referred for therapeutic plasma exchange (TPE) in a multicenter frame case series study. Two hundred seventeen TPE sessions were performed, and therapy is ongoing for five (30%) of the patients. After treatment, the mean plasma TG and total cholesterol concentrations were significantly reduced from 1929 and 510 mg/dL, to 762 and 227 mg/dL, respectively (P , 0.001 in both cases). In most cases, the interval between treatments was related to the clinical presentation and individual circumstances. The removal of TG-rich lipoproteins prevented relapses of AP. In this case series, TPE is confirmed as a safe and reliable method for treating patients with refractory sHTG when a severe complication, such as AP, is clinically demonstrated or can be actively prevented. Therefore, in cases where standard medical approaches fail to promote the clearance of TGs from plasma and a high risk of first or second hypertriglyceridemic pancreatitis persists, TPE provides a therapeutic option for preventing life-threatening sHTG. [source] | |||||||||||||