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Recent Clinical Trials (recent + clinical_trials)
Selected AbstractsUpdate on the Management of Hypertension: Recent Clinical Trials and the JNC 7JOURNAL OF CLINICAL HYPERTENSION, Issue 2004Marvin Moser MD Editor in Chief The following issues are highlighted: Emphasis is placed on the importance of systolic blood pressure elevations in estimating risk and in determining prognosis. A review of placebo-controlled clinical trials indicates that cardiovascular events are statistically significantly reduced with diuretic- or , blocker-based treatment regimens. The question of whether blood pressure lowering alone or specific medications make the difference in outcome is discussed. Based on the results of numerous trials, it is apparent that blood pressure lowering itself is probably of greater importance in reducing cardiovascular events than the specific medication used. Meta-analyses suggest, however, that the use of an agent that blocks the renin-angiotensin aldosterone system is probably more effective in diabetics and in patients with nephropathy than a regimen based on calcium channel blocker therapy. The Antihypertensive and Lipid-Lowering treatment to Prevent Heart Attack Trial (ALLHAT) reported no overall difference in coronary heart disease outcome among patients treated with a diuretic-based compared to a calcium channel blocker- or an angiotensin-converting enzyme inhibitor-based treatment program. However, patients in the diuretic group experienced fewer episodes of heart failure than in the calcium channel blocker group and fewer episodes of heart failure and strokes than those in the angiotensin-converting enzyme inhibitor group. Results were similar in diabetics and nondiabetics. Possible reasons for this outcome are discussed. The Australian National Blood Pressure 2 study, which was unblinded, reported a marginally significantly better outcome only in male patients receiving an angiotensin-converting enzyme inhibitor-based regimen compared to those receiving a diuretic-based program. Finally, the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) is reviewed. Highlights of this report include the new designation of prehypertension, i.e., blood pressures of 120,139 mm Hg/80,89 mm Hg. The JNC 7 suggested that diuretics should be the first-step drug of choice in most patients, but listed numerous specific reasons why other agents should be used in special situations. The report stressed that the majority of patients will require two or more medications to achieve goal blood pressure. [source] New prospects for immunotherapy at diagnosis of type 1 diabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 4 2009Paolo Pozzilli Immune intervention at diagnosis of type 1 diabetes (T1D) aims to prevent or reverse the disease by blocking autoimmunity, thereby preserving/restoring ,-cell mass and function. Recent clinical trials of non-specific and of antigen-specific immune therapies have demonstrated the feasibility of modulation of islet-specific autoimmunity in patients with partial prevention of loss of insulin secretion. In a series of review articles published in this issue of the journal, some of the most promising approaches of immune intervention in T1D are presented. Here we outline the rationale of such interventions and future prospects in this area. Copyright © 2009 John Wiley & Sons, Ltd. Insulin therapy in type 1 diabetes (T1D) rescues the patient from a certain death but not cure the disease. The goal of any therapeutic intervention in T1D is the preservation of insulin-secreting cells; this is achieved by the abrogation of pathogenic reactivity to beta cell autoantigens while preserving full capacity to generate a normal immune response against foreign antigens. Although several therapeutic candidates have been investigated in experimental models of T1D many of which showed promising results, a successful extrapolation of these findings to human T1D has proved to be difficult. In part, this failure results from the considerable disease heterogeneity associated with diverse genetic and non-genetic disease determinants and the spectrum of clinical phenotype at diagnosis. Thus, a younger age at onset is associated with stronger genetic susceptibility, more intense immune response to ,-cell antigens, shorter duration of symptoms, more severe metabolic derangement at diagnosis and a more rapid rate of ,-cell-destruction 1,3. Therefore, designing therapies that would be effective in all clinical settings is definitely challenging. In this issue five different approaches are discussed ranging from antigen-specific therapies [DiaPep277 and glutamic acid decarboxylase(GAD)], to non-antigen-specific immunoregulation (anti-CD3) and to anti-inflammatory (anti-IL1 receptor antagonist). These approaches are currently being tested in large international multicenter trials, and all of them use very similar outcome in terms of a beneficial effect (C-peptide secretion as evidence of a therapeutic effect on restoration of ,-cell function). The authors have been asked to follow a similar format in presenting their approaches so that the reader can easily compare them in terms of rationale and therapeutic goals. [source] New potential treatments for protection of pancreatic B-cell function in Type 1 diabetesDIABETIC MEDICINE, Issue 11 2008S. Cernea Abstract Type 1 diabetes mellitus results from the progressive and specific autoimmune destruction of insulin-secreting pancreatic B-cells, which develops over a period of years and continues after the initial clinical presentation. The ultimate goal of therapeutic intervention is prevention or reversal of the disease by the arrest of autoimmunity and by preservation/restoration of B-cell mass and function. Recent clinical trials of antigen-specific or non-specific immune therapies have proved that modulation of islet specific autoimmunity in humans and prevention of insulin secretion loss in the short term after the onset of disease is achievable. The identification of suitable candidates for therapy, appropriate dosage and timing, specificity of intervention and the side-effect profile are crucial for the success of any approach. Considering the complexity of the disease, it is likely that a rationally designed approach of combined immune-based therapies that target suppression of B-cell specific autoreactivity and maintenance of immune tolerance, coupled with islet regeneration or replacement of the destroyed B-cell mass, will prove to be most effective in causing remission/reversal of disease in a durable fashion. [source] The therapeutic potential of NO-NSAIDsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 1 2003John L. Wallace Abstract NSAIDs, including those that are selective for cyclooxygenase-2, are among the most widely used drugs. However, these drugs produce significant side effects in the gastrointestinal and cardiorenal systems, which greatly limit their utility. In recent years, a new type of anti-inflammatory agent has been developed that appears to offer significant advantages over conventional and Cox-2-selective NSAIDs. No-NSAIDs are derivatives of conventional NSAIDs, which are able to release nitric oxide over prolonged periods of time. The combination of balanced inhibition of the two main isoforms of COX with controlled release of nitric oxide yields a series of drugs that exert anti-inflammatory and analgesic activities in a wide range of settings, and have markedly reduced gastrointestinal and cardiorenal toxicity. Recent clinical trials of NO-NSAIDs have provided a ,proof of concept' that is completely consistent with pre-clinical characterization of these compounds. [source] What is the impact of PRIME on real-life diabetic nephropathy?INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 3 2004L. M. Ruilope Summary Type 2 diabetes is increasing globally and is a major cause of conditions such as cardiovascular disease, retinopathy and nephropathy. The Diabetes Control and Complications Trial and the UK Prospective Diabetes Study demonstrated that the progression of renal disease could be slowed by tight glycaemic control and treating any associated hypertension with angiotensin-converting enzyme inhibition. Recent clinical trials have supported the use of angiotensin II receptor antagonists in the treatment of diabetic nephropathy, resulting in the approval of new therapeutic indications in the United States and Europe. The objective of this review is to demonstrate how results from the Program for Irbesartan Mortality and morbidity Evaluation studies apply to clinical practice, and to show how the benefits of irbesartan therapy can be realised at any stage of renal disease in patients with diabetes. [source] Metabolic syndrome and mitochondrial function: Molecular replacement and antioxidant supplements to prevent membrane peroxidation and restore mitochondrial function,JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2007Garth L. Nicolson Abstract Metabolic syndrome consists of a cluster of metabolic conditions, such as hypertriglyeridemia, hyper-low-density lipoproteins, hypo-high-density lipoproteins, insulin resistance, abnormal glucose tolerance and hypertension, that,in combination with genetic susceptibility and abdominal obesity,are risk factors for type 2 diabetes, vascular inflammation, atherosclerosis, and renal, liver and heart disease. One of the defects in metabolic syndrome and its associated diseases is excess cellular oxidative stress (mediated by reactive oxygen and nitrogen species, ROS/RNS) and oxidative damage to mitochondrial components, resulting in reduced efficiency of the electron transport chain. Recent evidence indicates that reduced mitochondrial function caused by ROS/RNS membrane oxidation is related to fatigue, a common complaint of MS patients. Lipid replacement therapy (LRT) administered as a nutritional supplement with antioxidants can prevent excess oxidative membrane damage, restore mitochondrial and other cellular membrane functions and reduce fatigue. Recent clinical trials have shown the benefit of LRT plus antioxidants in restoring mitochondrial electron transport function and reducing moderate to severe chronic fatigue. Thus LRT plus antioxidant supplements should be considered for metabolic syndrome patients who suffer to various degrees from fatigue. J. Cell. Biochem. 100: 1352,1369, 2007. © 2007 Wiley-Liss, Inc. [source] Clinical and experimental aspects of Adreno-muscarinic synergy in the bladder base and prostate,,NEUROUROLOGY AND URODYNAMICS, Issue 8 2009Alexander Roosen Abstract Recent clinical trials have shown that combination therapy using an alpha-receptor antagonist and an antimuscarinic is more effective than either agent alone in improving quality of life and objective urodynamic variables in men with bladder outflow obstruction. There appear to be no negative effects on bladder function. The mode of action of this combination is unknown but presumed to be an antimuscarinic reduction in detrusor overactivity and the alpha-receptor antagonist reduced outflow tract resistance. We have shown with in vitro experiments that in smooth muscles influencing outflow tract resistance (prostate, trigone) there is a profound contractile synergy between adrenergic and muscarinic pathways. We propose the hypothesis that both arms of the combination therapy reduce contractile tone of the outflow tract and that their simultaneous attenuation has a disproportionately large effect on outflow tract resistance. Our data from trigone muscle suggest that adrenergic and muscarinic receptor activation increase the intracellular [Ca2+] but the adrenergic pathway also operates through Ca2+ -sensitisation of the contractile apparatus, primarily through a PKC-dependent pathway. Neurourol. Urodynam. 28:938,943, 2009. © 2009 Wiley-Liss, Inc. [source] Who's afraid of the big bad wolf?AUSTRALIAN OCCUPATIONAL THERAPY JOURNAL, Issue 4 2007Making sense of results from randomised controlled trials Background:, Reading and interpreting results from research can be challenging. Many therapists read the abstract and discussion but confess to bypassing the results section of journal articles. Methods:, This paper discusses necessary steps to reading the results section of a published randomised controlled trial. Recent clinical trials are used as examples. Results:, An ability to read and interpret the results section of a paper requires the therapist to consider whether the tests conducted are appropriate, the results reported are accurate and the conclusions drawn by the authors are appropriate. Estimates of treatment effect sizes can be calculated by the therapist and used to determine if the effect of treatment is likely to be large enough to be "clinically worthwhile". Conclusions:, The ability to extract meaningful statistical information from clinical trials is a fundamental skill that will enhance therapists' knowledge and understanding of evidence-based practice. [source] Inhibition of angiogenesis in the treatment of non-small cell lung cancerCANCER SCIENCE, Issue 12 2007Vicki L. Keedy Angiogenesis and its role in the growth and development of metastases has become a topic of increasing importance. In non-small cell lung cancer (NSCLC), vascular endothelial growth factor (VEGF) plays an important role in angiogenesis, growth of the primary tumor, and development of metastases. In addition, elevated expression in tissue samples is a negative prognostic feature. For these reasons, VEGF is a worthy target for novel therapies. Recent clinical trials have shown that the anti-VEGF monoclonal antibody bevacizumab adds to the effect of chemotherapy in the metastatic setting. Hypertension and proteinuria are, as expected, commonly seen in this patient population, but the unexpected toxicity of life-threatening hemoptysis has also been observed. This makes careful patient selection especially important for this class of drugs. Our understanding of the VEGF pathway is increasing, as are the number of available targeted agents. In addition to the monoclonal antibody, bevacizumab, VEGF receptor tyrosine kinase inhibitors, multitargeted kinase inhibitors, and combination VEGF and epidermal growth factor receptor (EGFR) inhibition, are all being evaluated in NSCLC. Small phase I and II trials have suggested modest benefit when used alone; however, we now know that the anti-angiogenic therapies work best in combination with chemotherapy. The results of ongoing trials using these agents in combination with standard therapy will provide more insight into their potential benefit. As it is known that small tumors require angiogenesis to grow and metastasize, the use of anti-angiogenic therapies in the adjuvant setting may provide even greater benefit, and increase the potential cure rate in this population of patients. The results of well-designed phase III trials will be required to truly understand how to best use this class of targeted therapies in resectable and metastatic NSCLC. (Cancer Sci 2007; 98: 1825,1830) [source] Immune responses to gene therapy vectors in the context of corneal transplantationACTA OPHTHALMOLOGICA, Issue 2009T RITTER Purpose The genetic engineering of grafts or cells prior to transplantation is an attractive approach to protect the graft from allogeneic rejection. Virus vector-based gene therapy is a promising method for successful ex-vivo gene transfer however, the induction of an immune response against gene-modified tissues raises concern. Methods Different virus families (Adenovirus, Retrovirus, Adeno-associated virus, Herpesvirus) have been studied as gene therapy vehicles for the delivery of therapeutic molecules. Moreover, different serotypes or envelope proteins have been used to modulate transduction efficiencies of target cells or to evade pre-existing immunity. Results Here we review gene therapeutic applications using viral vectors in the context of cornea transplantation. Both local and systemic expression of immunomodulatory molecules have led to the prevention of corneal graft rejection. However, different results have been obtained with regard to the induction of immune responses after local or systemic expression of the gene therapy vector. Not surprisingly over-expression of anti-inflammatory molecules not only modulated allograft rejection but also influenced the immune response against the viral vector and virally transduced cells. Conclusion Recent clinical trials indicate that the application of viral vectors in ophthalmology is promising however, the generation of immune responses against the viral vector or virally transduced cells are still a serious obstacle for a broader application of gene therapy. Supported by Deutsche Forschungsgemeinschaft (DFG Pl 150/14-1 and Ri 764/10-1) and Science Foundation of Ireland (SFI 06/RFP/BIC056 and SFI 07/IN.1/B925) [source] Stroke in patients with diabetes mellitusDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 4 2004Boris N. Mankovsky Abstract The article's objective is to review the key advances in the scientific literature related to the association of stroke with diabetes mellitus and to summarize the current approaches to stroke prevention in diabetic patients. The key findings from the literature regarding stroke incidence in patients with diabetes, specific and nonspecific risk factors of stroke in the diabetic population, such as arterial hypertension, dyslipidemia, hyperglycemia, diabetes duration, diabetic complications, insulin resistance/hyperinsulinemia, course and outcome of stroke in subjects with diabetes and/or hyperglycemia, and the peculiarities of type, site and size of stroke in diabetic patients are discussed. The results of recent clinical trials aimed at correcting hyperglycemia, hypertension, and dyslipidemia, to prevent stroke in people with diabetes, are reviewed. The medical database Medline along with original articles from peer-reviewed journals were used for analysis. There is convincing evidence suggesting that diabetes mellitus represents a strong independent risk factor of stroke. The contribution of hyperglycemia to increased stroke risk is not proven. Data suggest an association of the full cluster of the insulin resistance syndrome and stroke. Diabetes is a risk factor mainly for ischemic stroke, while its association with hemorrhagic stroke remains controversial. Hyperglycemia is common in stroke patients, but it is not known whether it independently influences the course and outcome of stroke or merely reflects stroke severity and location. Aggressive control of arterial hypertension and dyslipidemia allows to decrease the risk of stroke in diabetic patients substantially, while the importance of glucose control for stroke prevention remains unproven. Copyright © 2004 John Wiley & Sons, Ltd. [source] The renin,angiotensin system and the long-term complications of diabetes: pathophysiological and therapeutic considerationsDIABETIC MEDICINE, Issue 8 2003R. E. Gilbert Abstract The relationship between the renin,angiotensin system (RAS) and the progression of diabetic renal disease has been a major focus of investigation over the past 20 years. More recently, experimental and clinical studies have also suggested that the RAS may have a pathogenetic role at other sites of micro- and macrovascular injury in diabetes. Complementing major advances into the understanding of the local, as distinct from the systemic RAS, a number of large clinical trials have examined whether blockade of the RAS might provide protection from the long-term complications of diabetes, beyond that due to blood pressure reduction alone. While some controversy remains, these studies have, in general, suggested that angiotensin converting enzyme (ACE) inhibition and more recently, angiotensin receptor blockade reduce the development and progression of diabetic nephropathy, cardiovascular disease and possibly retinopathy. This review will focus on recent developments in our understanding of the tissue-based RAS and its role in end-organ injury in diabetes, the results of recent clinical trials and newer strategies for the pharmacological manipulation of the RAS. [source] Treatment options for hydroxyurea-refractory disease complications in myeloproliferative neoplasms: JAK2 inhibitors, radiotherapy, splenectomy and transjugular intrahepatic portosystemic shuntEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2010Elena Mishchenko Abstract Clinical care of patients with polycythemia vera, essential thrombocythemia and myelofibrosis (MF) requires not only a broad understanding of general treatment principles but also familiarity with the management of hydroxyurea-refractory disease complications. The latter include progressive splenomegaly, symptomatic portal hypertension (e.g. ascites, variceal bleeding), pulmonary hypertension, bone pain, intractable pruritus, constitutional symptoms (e.g. fatigue, night sweats) and cachexia (i.e. loss of lean body mass, general ill health, poor appetite). Some of these symptoms are directly or indirectly related to extramedullary hematopoiesis (EMH) and others to proinflammatory cytokine excess. Results from recent clinical trials of JAK inhibitors suggest remarkable activity in MF-associated constitutional symptoms, cachexia, pruritus and hydroxyurea-refractory splenomegaly. Involved-field radiotherapy is best utilized in the setting of EMH-associated symptoms, including ascites, bone (extremity) pain and pulmonary hypertension. Splenectomy is indicated in the presence of drug-refractory splenomegaly and frequent red cell transfusion requirement. Transjugular intrahepatic portosystemic shunt is used to alleviate symptoms of portal hypertension. [source] Clinical pharmacology and therapeutic use of antioxidant vitaminsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 2 2007Ramón Rodrigo Abstract The clinical use of antioxidants has gained considerable interest during the last decade. It was suggested from epidemiological studies that diets high in fruits and vegetables might help decrease the risk of cardiovascular disease. Therefore, supplements of vitamins C and E were applied through protocols aimed to prevent diseases such as atherosclerosis, preeclampsia or hypertension, thought to be mediated by oxidative stress. Despite the biological properties of these vitamins could account for an effective protection, as shown by several clinical and experimental studies, their efficacy remains controversial in the light of some recent clinical trials and meta-analyses. However, the methodology of these studies, criteria for selection of patients, the uncertain extent of progression of the disease when initiating supplementation, the lack of mechanistic studies containing basic scientific aspects, such as the bioavailability, pharmacokinetic properties, and the nature of the antioxidant sources of vitamins, could account for the inconsistency of the various clinical trials and meta-analyses assessing the efficacy of these vitamins to prevent human diseases. This review presents a survey of the clinical use of antioxidant vitamins E and C, proposing study models based on the biological effects of these compounds likely to counteract the pathophysiological mechanisms able to explain the structural and functional organ damage. [source] Rationale, design and methods of the OSCAR study: observational study on cognitive function and systolic blood pressure reduction in hypertensive patientsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 2 2007Atul Pathak Abstract Data from several recent clinical trials have suggested a beneficial effect of antihypertensive medications on preservation of cognitive function. Eprosartan, an angiotensin type-1 receptor antagonist (ARA) with dual action on both pre- and postsynaptic angiotensin type 1 receptors, may be effective in the control of SBP and the prevention of cognitive decline. The OSCAR (Observational Study on Cognitive function And SBP Reduction) study is an international longitudinal observational study with a duration of 6 months intended to examine the impact of the ARA eprosartan on cognitive function (assessed using the Mini-Mental State Examination [MMSE]) and control of systolic blood pressure (SBP) in a large international population of hypertensive patients managed in a standard primary care setting. A total of 100 000 hypertensive patients, aged ,50 years and with SBP of >140 mmHg will be recruited by more than 20 000 primary care physicians in 27 countries. These patients will receive eprosartan 600 mg once a day for 6 months. The MMSE, a globally validated cognitive screening test, will be performed at baseline, and after 6 months of treatment. After the first month of monotherapy, eprosartan treatment may, at the absolute discretion of individual investigators, be supplemented with other antihypertensive medications for the remainder of the study. The primary outcome indices are the mean relative change in MMSE score and the absolute change from baseline in SBP in the study population as a whole and in subsets of patients according to various factors among them: ethnicity, comorbidities (i.e. target organ damage, diabetes), baseline cognitive level and baseline blood pressure level. The secondary objectives are to identify factors influencing SBP and MMSE changes. The OSCAR trial is the first international observational study focusing on MMSE in a wide international cohort of hypertensive patients. The results are expected in 2007. [source] A pilot study evaluating the safety and microbiologic efficacy of an economically viable antimicrobial lozenge in patients with head and neck cancer receiving radiation therapyHEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 1 2002FRCPC, Samy El-Sayed MD Abstract Background Mucositis occurs in almost all radiotherapy-treated head and neck cancer patients, in approximately 75% of patients receiving hematopoietic marrow transplantation, and in approximately 40% of all patients who receive chemotherapy. Mucositis is painful, may affect all oral functions, and is a dose- and rate-limiting toxicity of therapy for cancer. Radiation-associated mucositis (onset, intensity, and duration) has been shown in recent clinical trials to be modified by the use of antibacterial/antifungal lozenges. Purpose The aim of this collaborative two-center phase II study was to assess the toxicity and microbiologic efficacy of an economically viable antimicrobial lozenge in the management of patients receiving radiation therapy for head and neck cancer. Materials and Methods Seventeen patients scheduled to receive radical or postoperative radiotherapy were provided with bacitracin, clotrimazole, and gentamicin (BCoG) lozenges (one lozenge dissolved in the mouth qid from day 1 of radiotherapy until completion). Ease of use and palatability of the lozenges, patients' symptoms (swallowing and pain), and quantitative and qualitative microbiologic evaluation of an oral rinse collection was conducted at least once weekly during radiation therapy. Results No significant side effects were reported from the use of the lozenges. The lozenges were well tolerated at the beginning of treatment by all patients, with some minor difficulty associated with oral discomfort toward the end of the treatment. Microbiologic evaluation showed consistent elimination of yeast organisms in all patients. In four patients there was no growth of gram-negative bacilli on culture, whereas in two patients, fluctuating counts were seen, and one patient had increased counts. The remaining patients had significant reduction in the gram-negative bacilli counts. Conclusions This study demonstrated that the BCoG lozenge is tolerable and microbiologically efficacious, achieving elimination of Candida in all patients and reduction in gram-negative flora in most patients. A phase III study is underway to evaluate the clinical efficacy of this lozenge. © 2002 John Wiley & Sons, Inc. Head Neck 24: 6,15, 2002. [source] ,1 -Adrenoceptor subtypes and lower urinary tract symptomsINTERNATIONAL JOURNAL OF UROLOGY, Issue 3 2008Debra A Schwinn Abstract: Benign prostatic hyperplasia (BPH) is a common cause of urinary outflow obstruction in aging men leading to lower urinary tract symptoms (LUTS). ,1 -Adrenoceptors (,1ARs) antagonists (blockers) have become a mainstay of LUTS treatment because they relax prostate smooth muscle and decrease urethral resistance, as well as relieving bladder LUTS symptoms. A review of key recent clinical trials suggests new insights into the role of specific ,1AR subtypes in the treatment of LUTS. [source] Citicoline: neuroprotective mechanisms in cerebral ischemiaJOURNAL OF NEUROCHEMISTRY, Issue 1 2002Rao Muralikrishna Adibhatla Abstract Cytidine-5,-diphosphocholine (citicoline or CDP-choline), an intermediate in the biosynthesis of phosphatidylcholine (PtdCho), has shown beneficial effects in a number of CNS injury models and pathological conditions of the brain. Citicoline improved the outcome in several phase-III clinical trials of stroke, but provided inconclusive results in recent clinical trials. The therapeutic action of citicoline is thought to be caused by stimulation of PtdCho synthesis in the injured brain, although the experimental evidence for this is limited. This review attempts to shed some light on the properties of,citicoline that are responsible for its effectiveness. Our studies in transient cerebral ischemia suggest that citicoline might enhance reconstruction (synthesis) of PtdCho and sphingomyelin, but could act by inhibiting the destructive processes (activation of phospholipases). Citicoline neuroprotection may,include: (i) preserving cardiolipin (an exclusive inner mitochondrial membrane component) and sphingomyelin; (ii),preserving the arachidonic acid content of PtdCho and phosphatidylethanolamine; (iii) partially restoring PtdCho levels; (iv) stimulating glutathione synthesis and glutathione reductase activity; (v) attenuating lipid peroxidation; and (vi),restoring Na+/K+ -ATPase activity. These observed effects,of citicoline could be explained by the attenuation of,phospholipase A2 activation. Based on these findings, a singular unifying,mechanism has been hypothesized. Citicoline also provides choline for synthesis of neurotransmitter acetylcholine, stimulation of tyrosine hydroxylase activity and dopamine release. [source] Quality of different chondroitin sulfate preparations in relation to their therapeutic activityJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 10 2009Prof. Nicola Volpi Abstract Objectives Chondroitin sulfate is currently recommended by the European League Against Rheumatism (EULAR) as a SYSADOA (symptomatic slow acting drug for osteoarthritis) in Europe in the treatment of knee and hand osteoarthritis based on research evidence and meta-analysis of numerous clinical studies. Furthermore, recent clinical trials demonstrated its possible structure-modifying effects. Chondroitin sulfate, alone or in combination with glucosamine or other ingredients, is also utilized as a nutraceutical in dietary supplements in Europe and the USA. However, it is derived from animal sources by extraction and purification processes. As a consequence, source material, manufacturing processes, the presence of contaminants and many other factors contribute to the overall biological and pharmacological actions of these agents. We aim to review the quality control of chondroitin sulfate in pharmaceutical-grade preparations and nutraceuticals. Key findings Pharmaceutical-grade formulations of chondroitin sulfate are of high and standardized quality, purity and properties, due to the stricter regulations to which this drug is subjected by local national health institutes as regards production and characteristics. On the contrary, as several published studies available in literature indicate, the chondroitin sulfate quality of several nutraceuticals is poor. Additionally, there are no definite regulations governing the origin of the ingredients in these nutraceuticals and the origin of the ingredients in natural products is the most important factor ensuring quality, and thus safety and efficacy, in particular for chondroitin sulfate, due to its extraction from different sources. Conclusions Due to the poor chondroitin sulfate quality of some nutraceuticals, we conclude that stricter regulations regarding their quality control should be introduced to guarantee the manufacture of high quality products for nutraceutical utilization and to protect customers from low-quality, ineffective and potentially dangerous products. There is a need for specific and accurate analytical procedures, which should be enforced to confirm purity and label claims both for raw materials and finished chondroitin sulfate products, and also to govern the origin of ingredients. Until these stricter regulations are in place, then it is strongly recommended that pharmaceutical-grade chondroitin sulfate is used rather than food supplements. [source] Efficacy of Cognitive Nursing Intervention for Voice HearingPERSPECTIVES IN PSYCHIATRIC CARE, Issue 2 2007Margaret England PhD PROBLEM.,Many individuals who hear negative voices are troubled by their voices even when they adhere to prescribed neuroleptic medication regimens. At the same time, recent clinical trials provide evidence that structured, cognitive intervention can reduce distress tied to refractory auditory hallucinations and other psychiatric symptoms. PURPOSE.,The purpose of this randomized controlled trial was to determine whether usual care (UC), or usual care plus 12, 90-min episodes of cognitive nursing intervention (UC + CNI) led to sustained improvement in the psychiatric symptoms and self-esteem of 65 voice hearers assigned a diagnosis of schizophrenia or schizoaffective disorder. ANALYSIS AND FINDINGS.,Analysis of covariance with repeated measures procedures indicate that the 44 participants exposed to UC + CNI, were significantly more likely than the 21 participants exposed to UC only, to sustain significant improvement in psychiatric symptoms and self-esteem 1 year following treatment. IMPLICATIONS.,These findings provide encouragement for nurses to further develop and investigate cognitive strategies to treat psychiatric symptoms of voice hearers. [source] DNA vaccination against tumorsTHE JOURNAL OF GENE MEDICINE, Issue 1 2005Gérald J. Prud'homme Abstract DNA vaccines have been used to generate protective immunity against tumors in a variety of experimental models. The favorite target antigens have been those that are frequently expressed by human tumors, such as carcinoembryonic antigen (CEA), ErbB2/neu, and melanoma-associated antigens. DNA vaccines have the advantage of being simple to construct, produce and deliver. They can activate all arms of the immune system, and allow substantial flexibility in modifying the type of immune response generated through codelivery of cytokine genes. DNA vaccines can be applied by intramuscular, dermal/epidermal, oral, respiratory and other routes, and pose relatively few safety concerns. Compared to other nucleic acid vectors, they are usually devoid of viral or bacterial antigens and can be designed to deliver only the target tumor antigen(s). This is likely to be important when priming a response against weak tumor antigens. DNA vaccines have been more effective in rodents than in larger mammals or humans. However, a large number of methods that might be applied clinically have been shown to ameliorate these vaccines. This includes in vivo electroporation, and/or inclusion of various immunostimulatory molecules, xenoantigens (or their epitopes), antigen-cytokine fusion genes, agents that improve antigen uptake or presentation, and molecules that activate innate immunity mechanisms. In addition, CpG motifs carried by plasmids can overcome the negative effects of regulatory T cells. There have been few studies in humans, but recent clinical trials suggest that plasmid/virus, or plasmid/antigen-adjuvant, prime-boost strategies generate strong immune responses, and confirm the usefulness of plasmid-based vaccination. Copyright © 2004 John Wiley & Sons, Ltd. [source] A study examining inter-rater and intrarater reliability of a novel instrument for assessment of psoriasis: the Copenhagen Psoriasis Severity IndexBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2008J. Berth-Jones Summary Background, There is a perceived need for a better method for clinical assessment of the severity of psoriasis vulgaris. The most frequently used system is the Psoriasis Area and Severity Index (PASI), which has significant disadvantages, including the requirement for assessment of the percentage of skin affected, an inability to separate milder cases, and a lack of linearity. The Copenhagen Psoriasis Severity Index (CoPSI) is a novel approach which comprises assessment of three signs: erythema, plaque thickness and scaling, each on a four-point scale (0, none; 1, mild; 2, moderate; 3, severe), at each of 10 sites: face, scalp, upper limbs (excluding hands and wrists), hands and wrists, chest and abdomen, back, buttocks and sacral area, genitalia, lower limbs (excluding feet and ankles), feet and ankles. Objectives, To evaluate the inter-rater and intrarater reliability of the CoPSI and to provide comparative data from the PASI and a Physician's Global Assessment (PGA) used in recent clinical trials on psoriasis vulgaris. Methods, On the day before the study, 14 dermatologists (raters) with an interest in psoriasis participated in a detailed training session and discussion (2·5 h) on use of the scales. On the study day, each rater evaluated 16 adults with chronic plaque psoriasis in the morning and again in the afternoon. Raters were randomly assigned to assess subjects using the scales in a specific sequence, either PGA, CoPSI, PASI or PGA, PASI, CoPSI. Each rater used one sequence in the morning and the other in the afternoon. The primary endpoint was the inter-rater and intrarater reliability as determined by intraclass correlation coefficients (ICCs). Results, All three scales demonstrated ,substantial' (a priori defined as ICC > 80%) intrarater reliability. The inter-rater reliability for each of the CoPSI and PASI was also ,substantial' and for the PGA was ,moderate' (ICC 61%). The CoPSI was better at distinguishing between milder cases. Conclusions, The CoPSI and the PASI both provided reproducible psoriasis severity assessments. In terms of both intrarater and inter-rater reliability values, the CoPSI and the PASI are superior to the PGA. The CoPSI may overcome several of the problems associated with the PASI. In particular, the CoPSI avoids the need to estimate a percentage of skin involved, is able to separate milder cases where the PASI lacks sensitivity, and is also more linear and simpler. The CoPSI also incorporates more meaningful weighting of different anatomical areas. [source] Antiplatelet Therapy in Cerebrovascular Disease: Implications of MATCH and CHARISMA Results for CardiologistsCLINICAL CARDIOLOGY, Issue 12 2007Dan James Fintel M.D. Abstract Cardiovascular disease is prevalent among patients with stroke; thus, cardiologists frequently treat patients at high risk for stroke. Results from recent clinical trials of antiplatelet medications, given alone or in combination, may be of special interest to cardiologists. The MATCH study demonstrated no significant difference between clopidogrel alone and clopidogrel plus aspirin in reducing risk of vascular events after stroke or transient ischemic attack. A 1.3% increased risk of major bleeding was associated with clopidogrel plus aspirin. In CHARISMA, clopidogrel plus aspirin did not reach statistical significance vs. placebo plus aspirin in reducing incidence of myocardial infarction (MI), stroke, or death from cardiovascular causes in patients with stable atherothrombotic disease; clopidogrel was associated with an increase in moderate bleeding. These results suggest that clopidogrel plus aspirin may be inappropriate as first-line therapy for secondary stroke prevention. In patients with established cardiovascular disease at risk for MI or other vascular events, physicians must weigh the benefits and risks before choosing this therapy. Selection of an antiplatelet agent must be based on patient history, including previous MI and stroke, susceptibility to bleeding, and other high-risk factors (e.g. advanced age and diabetes). Aspirin plus extended-release dipyridamole may be more effective than clopidogrel for preventing stroke in high-risk patients. This article strives to put MATCH and CHARISMA results into context by providing an overview of antiplatelet therapy, including relevant clinical trial results, a review of current practice guidelines, and a summary of an ongoing study that will improve clinical decision making. Copyright © 2007 Wiley Periodicals, Inc. [source] Clinical trial experience around the globe: Focus on calcium-channel blockersCLINICAL CARDIOLOGY, Issue S2 2003William B. White M.D. Abstract Although certain classes of drugs appear to possess benefits apart from their blood-pressure lowering capability, reduction of blood pressure remains the single most important action of antihypertensive therapy. Calcium-channel blockers (CCBs) have long been recognized as potent agents for hypertension therapy. This is especially true for the prevention of stroke in hypertensive patients as evidenced from the Systolic Hypertension in Europe (Syst-Eur) and Systolic Hypertension in China (Syst-China) trials with a long acting dihydropyridine CCB. The same can be said for beta blockers in patients post myocardial infarction. However, most recent clinical trials have underscored the necessity of multiple drug therapy to achieve the goals of blood pressure reduction coupled with outcomes reduction. For example, the many recent large-scale clinical trials have required an average of three or more agents to achieve goal. Thus, the paradigm for hypertension management has been altered to determine the best treatment regimen rather than the best initial agent. While response rates to individual agents across a wide spectrum of patients vary little, not all drugs are equally suited as companion products. In this article, we discuss the most recent outcome trials with the long acting CCBs alone or in combination with other drugs. The evidence shows that calcium antagonists remain an important part of hypertension management, including in those individuals at risk of cardiac and cerebrovascular events. [source] | ||||||||||||||||||||||||||||