Current Issue : April - June Volume : 2012 Issue Number : 2 Articles : 9 Articles
Obesity has been considered a risk factor for osteoarthritis and it is usually accepted that obesity contributes to the development\r\nand progression of osteoarthritis by increasing mechanical load of the joints. Nevertheless, recent advances in the physiology\r\nof white adipose tissue evidenced that fat cells produce a plethora of factors, called adipokines, which have a critical role in the\r\ndevelopment of ostearthritis, besides to mechanical effects. In this paper, we review the role of adipokines and highlight the cellular\r\nand molecular mechanisms at play in osteoarthritis elicited by adipokines.We also emphasize how defining the role of adipokines\r\nhas broadned our understanding of the diversity of factors involved in the genesis and progression of osteoarthritis in the hope of\r\nmodifying it to prevent and treat diseases....
Chronobiology is a field of science that examines periodic (cyclic) phenomena in living organisms and their adaptation to solar and lunar related rhythms. These cycles are known as biological rhythms. The present review is on basic concept of chronopharmacology and Chronobiological studies include but are not limited to comparative anatomy, physiology, genetics, molecular biology and behavior of organisms within biological rhythms mechanics. Other aspects include development, reproduction, ecology and evolution. Chronobiology is an interdisciplinary field of investigation. It interacts with medical and other research fields such as jetlag, sleep disorders, endocrinology, geriatrics, sports medicine, space medicine and photoperiodism. This also includes biological rhythms, biological clock- SCN, implications in drug therapy....
Pancreatic cancer is one of the most malignant tumors that responded poorly to currently available\r\nchemotherapy. Casticin, a flavonoid compound, has been reported to induce apoptosis in various\r\ncancer cell lines. However, there is no report on the anti-pancreatic cancer potential of casticin. In the\r\npresent study, we showed for the first time that casticin strongly inhibits the growth of PANC-1\r\npancreatic carcinoma cells. The anti-proliferative effect assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-\r\nDiphenyltetrazolium Bromide (MTT) assay demonstrated that casticin inhibited the growth of PANC-1\r\ncells in a dose-dependent manner. Further analysis using flow cytometry and immunoblot showed that\r\nthe growth inhibitory effect of casticin was associated with cell cycle arrest at G2/M phase and\r\ninduction of apoptosis. Mechanistic studies indicated that the induction of apoptosis was associated\r\nwith up-regulation of pro-apoptotic protein Bax, down-regulation of anti-apoptotice protein Bcl-2 and\r\nactivation of caspase-3. These findings suggest that casticin may be a promising candidate for treating\r\nhuman pancreatic cancer....
Since the pathomechanisms of primary open angle glaucoma are still not defined, different aspects related to this topic have to be\r\ndiscussed and further investigated. Possible candidates are the mineralocorticoids, which are known to lower intraocular pressure.\r\nA data search and personal investigations assume a limited role of mineralocorticoids for the development of glaucoma. Specific\r\nexperiments for a final conclusion are, however, not yet performed....
Creatine has been shown to be neuroprotective in aging, neurodegenerative conditions and brain injury. As a common\r\nmolecular background, oxidative stress and disturbed cellular energy homeostasis are key aspects in these conditions.\r\nMoreover, in a recent report we could demonstrate a life-enhancing and health-promoting potential of creatine in rodents,\r\nmainly due to its neuroprotective action. In order to investigate the underlying pharmacology mediating these mainly\r\nneuroprotective properties of creatine, cultured primary embryonal hippocampal and cortical cells were challenged with\r\nglutamate or H2O2. In good agreement with our in vivo data, creatine mediated a direct effect on the bioenergetic balance,\r\nleading to an enhanced cellular energy charge, thereby acting as a neuroprotectant. Moreover, creatine effectively\r\nantagonized the H2O2-induced ATP depletion and the excitotoxic response towards glutamate, while not directly acting as\r\nan antioxidant. Additionally, creatine mediated a direct inhibitory action on the NMDA receptor-mediated calcium response,\r\nwhich initiates the excitotoxic cascade. Even excessive concentrations of creatine had no neurotoxic effects, so that highdose\r\ncreatine supplementation as a health-promoting agent in specific pathological situations or as a primary prophylactic\r\ncompound in risk populations seems feasible. In conclusion, we were able to demonstrate that the protective potential of\r\ncreatine was primarily mediated by its impact on cellular energy metabolism and NMDA receptor function, along with\r\nreduced glutamate spillover, oxidative stress and subsequent excitotoxicity....
This study investigated the effect of Icariin (ICA) supplementation on diabetic\r\nretinopathy (DR) in a streptozotocin-induced diabetic rat model system. Fifty Sprague\r\nDawley rats were randomly distributed into a control group and a streptozotocin-induced\r\ndiabetes group. Diabetic rats were randomly divided into two groups; one group received\r\nICA 5 mg/kg/day for 12 weeks by oral gavage; the other group received saline gavage as a\r\nplacebo. Retinal morphological changes, endothelial markers (RECA), collagen IV (Col-IV),\r\nvascular endothelial growth factor (VEGF), and neuropathic changes (Thy-1 and Brn3a\r\nexpression) of the retinal ganglion cells (RGCs) were investigated. The effects of ICA at\r\nvarious concentrations (0, 101, 102, 103 nmol/mL) on neurite growth were investigated also\r\nin retinal ganglion cells (RGC) cultured from both diabetic and normal animals. Numerous\r\npathological changes (deceased expression of RECA, VEGF, Thy-1, and Brn3a as well as\r\ndecreased Collagen IV and M�¼ller cell content) were noted in the retinal vessels of diabetic\r\nrats; these changes were attenuated in diabetic animals that received ICA. ICA enhanced\r\nneurite growth in RGC from both normal rats and diabetic rats in a dose dependent fashion. ICA may be useful in the treatment of diabetic retinopathy. Further investigations\r\nare indicated....
Immune suppression medications contribute to multiple aspects of endocrine dysfunction including post-transplant\ndiabetes mellitus (PTDM), reproductive dysfunction and fracture. In this paper, we will review the available evidence,\npathophysiology and prevention/treatment strategies for immunosuppression-induced endocrine dysfunction. PTDM\ncan substantially reduce graft and patient survival after kidney transplant. Tacrolimus (TAC), which is among the most\ncommonly used immunosuppression drugs in organ transplantation, can suppress insulin gene expression, decrease\ninsulin release, and may cause islet cell apoptosis. Sirolimus (SIR), which is frequently used in combination with TAC for\nislet transplants, can decrease islet insulin secretion in vitro and may affect insulin action causing an insulin resistance\nstate. Animal studies have shown that short term treatment with TAC or SIR can independently cause hyperglycemia\nwith hyperinsulinemia in normal rats, suggesting insulin resistance, with greater hyperinsulinemia occurring with SIR\nthan with TAC treatment. Together, these agents reduce insulin secretion and increase islet apoptosis. SIR acts by\nbinding to mammalian target of rapamycin, which is a downstream protein in the insulin signal transduction cascade,\nbut how SIR causes insulin resistance is not known. SIR and TAC have been shown to induce islet apoptosis in\nvitro; however, regulation of this process by immunosuppressants has not been studied. While immunosuppressants\ncontribute to PTDM, little is known about whether it can be prevented with any current therapeutic intervention for\ntype 2 diabetes. SIR has been associated with irregular menses and ovarian cysts, and primary hypogonadism posttransplant.\nSIR has been associated with delayed fracture healing, but the effect on bone density is not clear. In\nconclusion, predominant endocrine effects of commonly used immunosuppressive medications appear to be on the\ndevelopment of PTDM and reproductive dysfunction, while also potentially contributing to fractures....
Background: Opioids exert a profound influence on immunomodulation and enhance HIV infection and replication.\r\nHowever, the mechanism(s) of their action remains to be determined. We thus investigated the impact of morphine on the\r\nintracellular innate antiviral immunity.\r\nMethodology/Principal Findings: Seven-day-cultured macrophages were infected with equal amounts of cell-free HIV Bal\r\nor SIV DeltaB670 for 2 h at 37uC after 24 h of treatment with or without morphine. Effect of morphine on HIV/SIV infection\r\nand replication was evaluated by HIV/SIV RT activity assay and indirect immunofluorescence for HIV p24 or SIV p28 antigen.\r\nThe mRNA expression of cellular factors suppressed or induced by morphine treatment was analyzed by the real-time RTPCR.\r\nWe demonstrated that morphine treatment of human blood monocyte-derived macrophages significantly inhibited\r\nthe expression of interferons (IFN-a, IFN-b and IFN-l) and IFN-inducible genes (APOBEC3C/3F/3G and 3H). The further\r\nexperiments showed that morphine suppressed the expression of several key elements (RIG-I and IRF-7) in IFN signaling\r\npathway. In addition, morphine treatment induced the expression of suppressor of cytokine signaling protein-1, 2, 3 (SOCS-\r\n1, 2, 3) and protein inhibitors of activated STAT-1, 3, X, Y (PIAS-1, 3, X, Y), the key negative regulators of IFN signaling\r\npathway.\r\nConclusions: These findings indicate that morphine impairs intracellular innate antiviral mechanism(s) in macrophages,\r\ncontributing to cell susceptibility to AIDS virus infection....
Acetylcholinesterase (AChE) remains a highly viable target for the symptomatic improvement in Alzheimer�s disease (AD) because\r\ncholinergic deficit is a consistent and early finding in AD. The treatment approach of inhibiting peripheral AchE for myasthenia\r\ngravis had effectively proven that AchE inhibition was a reachable therapeutic target. Subsequently tacrine, donepezil, rivastigmine,\r\nand galantamine were developed and approved for the symptomatic treatment of AD. Since then, multiple cholinesterase\r\ninhibitors (ChEI) continue to be developed. These include newer ChEIs, naturally derived ChEIs, hybrids, and synthetic analogues.\r\nIn this paper, we summarize the different types of ChEIs in development and their respective mechanisms of actions. This\r\npharmacological approach continues to be active with many promising compounds....
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