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Potential Therapeutic Implications (potential + therapeutic_implication)
Selected AbstractsSubtypes of major depression in substance dependenceADDICTION, Issue 10 2009Mark J. Niciu ABSTRACT Aims This study evaluated features that differentiate subtypes of major depressive episode (MDE) in the context of substance dependence (SD). Design Secondary data analysis using pooled data from family-based and case,control genetic studies of SD. Setting Community recruitment through academic medical centers. Participants A total of 1929 unrelated subjects with alcohol and/or drug dependence. Measurements Demographics, diagnostic criteria for psychiatric and substance use disorders and related clinical features were obtained using the Semi-Structured Assessment for Drug Dependence and Alcoholism. We compared four groups: no life-time MDE (no MDE), independent MDE only (I-MDE), substance-induced MDE only (SI-MDE) and both types of MDE. Findings Psychiatric measures were better predictors of MDE subtype than substance-related or socio-demographic ones. Subjects with both types of MDE reported more life-time depressive symptoms and comorbid anxiety disorders and were more likely to have attempted suicide than subjects with I-MDE or SI-MDE. Subjects with both types of MDE, like those with I-MDE, were also more likely than subjects with SI-MDE to be alcohol-dependent only than either drug-dependent only or both alcohol- and drug-dependent. Conclusions SD individuals with both types of MDE have greater psychiatric severity than those with I-MDE only or SI-MDE only. These and other features that distinguish among the MDE subtypes have important diagnostic and potential therapeutic implications. [source] Pathophysiologic role of myocardial apoptosis in post-infarction left ventricular remodelingJOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2002Antonio Abbate Left ventricular (LV) remodeling and heart failure (HF) complicate acute myocardial infarction (AMI) even weeks to months after the initial insult. Apoptosis may represent an important pathophysiologic mechanism causing progressive myocardiocyte loss and LV dilatation even late after AMI. This review will discuss the role of apoptosis according to findings in animal experimental data and observational studies in humans in order to assess clinical relevance, determinants, and mechanisms of myocardial apoptosis and potential therapeutic implications. More complete definition of the impact of myocardiocyte loss on prognosis and of the mechanisms involved may lead to improved understanding of cardiac remodeling and possibly improved patients' care. Mitochondrial damage and bcl-2 to bax balance play a central role in ischemia-dependent apoptosis while angiotensin II and ,1 -adrenergic-stimulation may be major causes of receptor-mediated apoptosis. Benefits due to treatment with ACE-inhibitors and ,-blockers appear to be in part due to reduced myocardial apoptosis. Moreover, infarct-related artery patency late after AMI may be a major determinant of myocardial apoptosis and clinical benefits deriving from an open artery late post AMI (the "open artery hypothesis") may be, at least in part, due to reduced myocardiocyte loss. © 2002 Wiley-Liss, Inc. [source] Neuroprotective effects of atorvastatin against glutamate-induced excitotoxicity in primary cortical neuronesJOURNAL OF NEUROCHEMISTRY, Issue 6 2005Julian Bösel Abstract Statins [3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors] exert cholesterol-independent pleiotropic effects that include anti-thrombotic, anti-inflammatory, and anti-oxidative properties. Here, we examined direct protective effects of atorvastatin on neurones in different cell damage models in vitro. Primary cortical neurones were pre-treated with atorvastatin and then exposed to (i) glutamate, (ii) oxygen,glucose deprivation or (iii) several apoptosis-inducing compounds. Atorvastatin significantly protected from glutamate-induced excitotoxicity as evidenced by propidium iodide staining, nuclear morphology, release of lactate dehydrogenase, and mitochondrial tetrazolium metabolism, but not from oxygen,glucose deprivation or apoptotic cell death. This anti-excitototoxic effect was evident with 2,4 days pre-treatment but not with daily administration or shorter-term pre-treatment. The protective properties occurred independently of 3-hydroxy-3-methylglutaryl-CoA reductase inhibition because co-treatment with mevalonate or other isoprenoids did not reverse or attenuate neuroprotection. Atorvastatin attenuated the glutamate-induced increase of intracellular calcium, which was associated with a modulation of NMDA receptor function. Taken together, atorvastatin exerts specific anti-excitotoxic effects independent of 3-hydroxy-3-methylglutaryl-CoA reductase inhibition, which has potential therapeutic implications. [source] Psychosocial effects of vitiligoJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 1 2006K Ongenae Abstract A limited number of studies have paid attention to the psychosocial well-being of patients affected with vitiligo. We review the psychosocial effects of vitiligo, how patients deal with them and the psychiatric morbidity in vitiligo patients. Given the appreciable comorbidity, it is important to consider these observations in the management of patients, for example in patient,physician interaction but also in treatment strategies and evaluation of treatments. The effects of the psychological state on the disease itself together with the potential therapeutic implications are reviewed. Based on these data, we suggest how to further improve patient's management. [source] Intraepidermal nerve fiber density as a marker of early diabetic neuropathyMUSCLE AND NERVE, Issue 5 2007T. Umapathi MB Abstract The purpose of the study was to reliably identify an early stage of diabetic polyneuropathy (DPN) by measuring injury to epidermal nerve fibers. We compared intraepidermal nerve fiber density (IENFD) at the ankle and thigh of 29 diabetic subjects who had no clinical or electrophysiological evidence of small- or large-fiber neuropathy to that of 84 healthy controls. The mean ankle IENFD of diabetic subjects was 9.1 ± 5.0 mm and that of controls, 13.0 ± 4.8 mm (P < 0.001). The thigh IENFD did not differ significantly. The IENFD ratio (thigh IENFD divided by ankle IENFD) was 2.39 ± 1.30 in diabetic subjects and 1.77 ± 0.58 in controls (P < 0.001), indicating a length-dependent reduction of IENFD in diabetics. Ankle IENFD remained significantly lower and the IENFD ratio higher in diabetic subjects after adjusting for age. Two subjects had parasympathetic dysfunction, two had retinopathy, and two early nephropathy. Age, height, weight, duration of diabetes, and average HbA1c did not influence IENFD among diabetic subjects. We used receiver operating characteristic (ROC) curves to describe and compare the utility of various threshold values of ankle IENFD and IENFD ratio for the diagnosis of early DPN. The sensitivity and specificity of diagnosing DPN using ankle IENFD of less than 10 mm were 72.4% and 76.2%, respectively. Thus, asymptomatic diabetics have a measurable, length-dependent reduction of distal epidermal nerves. Analogous to microalbuminuria in diabetic nephropathy, reliable identification and quantitation of nascent diabetic neuropathy may have potential therapeutic implications. Muscle Nerve, 2007 [source] Leptin and Insulin Action in the Central Nervous SystemNUTRITION REVIEWS, Issue 2002Daniel Porte Jr M.D. Body adiposity is known to be carefully regulated and to remain relatively stable for long periods of time in most mammalian species. This review summarizes old and recent data implicating insulin and leptin as key circulating signals to the central nervous system, particularly the ventral hypothalamus, in communicating thesizeand thedistribution of body fat stores. This input ultimately alters food intake and energy expenditure to maintain constancy of the adipose depot. The key primary neurons in the arcuate nucleus containing NPY/AgRP and POMC/CART appear be critical constituents of the CNS regulating system, and are shown to contribute to anabolic and catabolic signaling systems to complete the feedback loop. New data to indicate shared intracellular signaling from leptin and insulin is provided. The satiety system for meals, consisting of neural afferents to the hind-brain from the gastrointestinal tract, is described and its effectiveness is shown to vary with the strength of the insulin and leptin signals. This provides anefferent mechanism that plays a key role in a complex feedback system that allows intermittent meals to vary from day to day, but provides appropriate long-term adjustment to need. Recently described contributions of this system to obesity are described and potential therapeutic implications are discussed. [source] Inflammation and Sleep Disordered Breathing in Children: A State-of-the-Art Review,PEDIATRIC PULMONOLOGY, Issue 12 2008Aviv D. Goldbart MD Abstract Sleep disordered breathing (SDB) represents a spectrum of breathing disorders, ranging from snoring to obstructive sleep apnea syndrome (OSAS), that disrupt nocturnal respiration and sleep architecture. OSAS is a common disorder in children, with a prevalence of 2,3%. It is associated with neurobehavioral, cognitive, and cardiovascular morbidities. In children, adenotonsillectomy is the first choice for treatment and is reserved for moderate to severe OSAS, as defined by an overnight polysomnography. In adults, OSAS is the result of mechanical dysfunction of the upper airway, manifesting as severity-dependent nasal, oropharyngeal, and systemic inflammation that decrease after continuous positive airway pressure therapy. Inflammatory changes have been reported in upper airway samples from children with OSAS, and systemic inflammation, as indicated by high-sensitivity C-reactive protein (hsCRP) levels, has been shown to decrease in children with OSAS after adenotonsillectomy. Anti-inflammatory treatments for children with mild OSAS are associated with major improvements in symptoms, polysomnographic respiratory values, and radiologic measures of adenoid size. Inflammation is correlated to some extent with OSAS-related neurocognitive morbidity, but the role of inflammatory markers in the diagnosis and management of OSAS, and the role of anti-inflammatory treatments, remains to be clarified. This review examines the role of inflammation in the pathophysiology of sleep-disordered breathing in pediatric patients and the potential therapeutic implications. Pediatr. Pulmonol. 2008; 43:1151,1160. © 2008 Wiley-Liss, Inc. [source] | |||||||||||||