Current Issue : October - December Volume : 2012 Issue Number : 4 Articles : 10 Articles
Oxidative stress is a reflection of excessive intracellular concentrations of reactive Oxygen species (ROS) and one of the important indicators of cellular damages. Oxidative stress implicated in various pathological conditions such as cardiovascular disease, neurological disorder, diabetes, ischemia/ reperfusion, aging and various other alignments. It can result from diminished antioxidant protection as well as increased free radical production. The free radicals are biochemical toxins produce highly active singlet oxygen, hydroxyl radicals, and peroxynitrite that can attack proteins, lipids, and DNA and cause irritation or inflammation of the cells and tissues which further lead to various pathological conditions. These free radicals and other reactive oxygen species are derived either from normal essential metabolic processes in the human body or from external sources. These free radicals are known to cause oxidative stress, comes from the cell’s own metabolism. Several sites of ROS production are mitochondrial electron transport, peroxisomal fatty acid, cytochrome P-450, and phagocytic cells.. Detoxification is the process of clearing toxins from the body or neutralizing or transforming in less toxic radical by using different enzymes like dismutase, catalyse and glutathione peroxidase. There are several approaches that may be adopted, including measurements of the depletion of antioxidant reserves, changes in the activities of antioxidant enzymes, free radical production, and presence of protein, lipid, and DNA free radical adducts....
The pathogenesis of human sepsis involves a complex interplay between the infecting organism and the host response, with the consequent multiple organ dysfunction. Sepsis is the systemic inflammatory response to severe microbial infection which initiates important alterations in immune, metabolic, and hemodynamic function that in their most dramatic forms are recognized as sepsis and septic shock. The sepsis syndrome occurs commonly in response to lipopolysaccharide membrane (LPS) from gram-negative bacteria. LPS is a major constituent of gram-negative bacteria cell walls and is essential for membrane integrity. Injured cells releases preformed mediators and synthesize proinflammatory substances, including eicosanoids and the cytokines and tumor necrosis factor [TNF]. These mediators are responsible for the initiation of a nonspecific inflammatory response. The treatment of sepsis is multifaceted and typically requires multidisciplinary competencies. Successful treatment requires great attention to detail in the management of all aspects of the disease, including antibiotic therapy, choice of vasopressors, ventilator management, tight glucose control, and deep venous thrombosis and stress ulcer prophylaxis. Effective anti-ET (Endotoxin) or antimediator treatment such as anticytokine or other anti-proinflammatory mediator strategies need to be directed at a wide spectrum of host inflammatory mediators. Activated protein C decreases inflammation by inhibiting platelet activation, neutrophil recruitment and mast cell degeneration. Recombinant human activated protein C (drotrecogin alfa [activated]) is the first anti-inflammatory agent that has proved effective in the treatment of sepsis....
Huntington’s chorea or disease is a progressive, autosomal, fatal, and inherited disorder of the central nervous system chararacterized by widespread degenerative changes of the cerebral cortex, basal ganglia and other brain regions and the development of prominent chorea and dementia. Huntington’s disease is an inherited disease of the central nervous system that usually has its onset between 30 and 50 years of age. The patient has progressive dementia involuntary movements of chorea. A patient with Huntington’s disease may present with neurological or psychiatric symptoms or both. Huntington’s disease caused by the expansion of CAG (cytosine-adenine-guanine) in HD gene resulting in mutant form of the protein huntingtin. Symptomatic treatment of Huntington’s disease involves use of Dopamine antagonists, presynaptic dopamine depletes, Antidepressants, Tranquillizers, Anxiolytic Benzodiazepines, Anticonvulsants and Antibiotics. Several medications including Baclofen, Idebenone and vitamin E have studied in clinical trials with limited samples. In the present discussion, we have concentrated on introduction, history, epidemiology, inheridity, neurologic & hypothalamic-endocrine aspects, sign & symptoms, diagnosis, symptomatic approaches and other possible therapies involved in the management of Huntington’s disease. The aim of present discussion is to provide in depth knowledge about HD disease and symptomatic treatment and other therapies involved in the management of Huntington’s disease. This reviews current therapeutic agents for treatment of the symptoms of Huntington’s disease....
An experimental study was conducted to evaluate the mechanism of toxicity due to maduramicin in broilers. The broiler chicks were fed on the diet containing 8 ppm of maduramicin for 6 weeks. The immune status, concentration of glutathione and the activities of antioxidant defense enzymes such as glutathione peroxidase (GSH-Px), glutathione reductase (GSH-R) and catalase were assessed at every 2 weeks interval. The study revealed significant (P< 0.05) increase in the activity of the antioxidant enzymes and a significant (P< 0.05) reduction in the glutathione and HI titre of the birds fed on maduramicin. From this study, it is concluded that the toxicity of maduramicin is due to induction of oxidative stress and immunosuppression....
Rheumatoid arthritis (R.A) is a systemic autoimmune disease that causes chronic inflammation of connective tissue primarily in the joints that involves synovial proliferation and cartilage destruction. R.A is the most common chronic inflammatory joint disease occurs in all races and ethnic groups. Risk factors for the development of R.A include genetic factors and adverse pregnancy outcome, smoking, obesity and recent infections. The “genetic predisposition appears to be related to the histocompatibility genetic marker HLA-DR4 especially in those patients who maintains high titers of immunoglobulin M (IgM) rheumatoid factor. Causes of rheumatoid arthritis include genetic factors, environmental factors, and other factors like various cytokines. Also involvement of the factors like TNF-α, IL-1, IL-6, neutrophills, IL-8, prostaglandins and proteases, and some other anti-inflammatory cytokines, The extraarticular feature includes skin, eyes, cardiovascular, aortitis. Treatment includes various pharmacological as well as nonpharmacological and treats by surgery. The Pharmacological treatment includes various disease modifying anti-rheumatoid drugs, anti-inflammatory, and drugs related to class of analgesics....
Calcium ion influx seems to play an essential role in the stimulation secretion coupling in mammalian oxyntic cells, an effect that can be inhibited by the calcium channel blockers. The present study aims to evaluate gastric anti-secretory and anti-ulcer effects of new calcium channel blocker lomerizine and its interaction with H2 blocker and proton pump inhibitor in rats. Gastric ulcers were induced in albino rats by pyloric ligation and cold restraint stress methods. Effects of two different doses of lomerizine, ranitidine and omeprazole on volume, pH, acidity of gastric secretion, ulcer index, mucus content were observed. In addition, the effects of low dose of lomerizine in combination with ranitidine or omeprazole on the above parameters were studied. Lomerizine (5 mg/kg, p.o), ranitidine (150 mg/kg, p.o) and omeprazole (20 mg/kg, p.o) produced significant antiulcer effects. Doses of lomerizine (20 mg/kg, p.o) did not alter the above parameters significantly. Combined administration of low dose of lomerizine (5 mg/kg) and ranitidine (150 mg/kg) showed significant antiulcer effects, which were apparent from the reduction in volume of gastric acid secretion, acidity and ulcer index with simultaneous increase in the intragastric pH and mucus content. Similarly, dose of omeprazole (20 mg/kg) when combined with low dose of lomerizine (5 mg/kg) also showed significant antiulcer effects. It is suggested that the patients who received lomerizine therapy for some other clinical conditions are less prone to develop peptic ulcers; and even if ulcers develop, they would require lower doses of antiulcer agents like ranitidine and omeprazole....
A study was conducted to evaluate the histological alterations in the progeny of dams treated with methimazole, monocrotophos and lead acetate. Female pregnant albino rats of Wistar Kyoto strain were divided into 5 groups and treated as follows from the day 3 of pregnancy till weaning of pups on post-natal day (PND) 21: Group 1 served as sham control, 2 received methimazole @ 0.02% in drinking water, 3 received monocrotophos (MCP; 0.3 mg/kg orally), 4 received lead acetate @ 0.2% in drinking water and 5 received MCP + lead acetate. Thyroid hormone profile was recorded on 14th day of gestation in dams. Eight pups from each group were euthanized on PND 90 for studying testicular lactate dehydrogenase (LDH) and brain, thyroid, liver, heart, kidney and testis tissues were collected for histopathology. Testicular LDH was significantly (P < 0.05) increased in all the test groups as compared to group 1. Groups 2 (methimazole) and 5 (MCP + lead acetate) showed marked congestion and degenerative changes in liver, heart, kidney, brain and testis, while thyroid gland showed moderate disruption of follicular epithelium. Groups 3 and 4 revealed mild abnormalities. From this study, it is concluded that both MCP and lead acetate have a possible influence on thyroid gland and other tissues of progeny rats that were born to the dams treated with MCP and lead acetate and the changes were comparable to that of methimazole group....
Many researchers have worked extensively in past 3 decades in developing better chemotherapeutic agents to cure cancer. Several combination chemotherapy regimens were developed to improve cure rate in cancer. Intrinsic and acquired resistance poses challenges in developing effective and safe chemotherapeutic agents. It is evident that the expression of genes that regulate apoptotic cell death plays an important role in determining the sensitivity of tumor cells to chemotherapy. Proteins of EGFR family and Bcl-2 family are key regulators of apoptosis. Some members of this family, notably Her-2, Bcl-2 and Bcl-xL are overexpressed in cancer cells, which have been associated with chemoresistance. This pioneered new approach in cancer treatment i.e. chemo-signal therapy. This approach is now being tested in clinical research. Several chemosignal modulators are being developed and many of them have shown promising results in clinical studies....
Present study was undertaken to evaluate cardiogenic intoxication of lead (Pb), cadmium (Cd) and their combination, and to evaluate therapeutic potential of N-Acetyl L-cysteine (NAC) against the toxicity. A total of 48 male wistar rats were randomly divided into 8 groups comprising of 6 rats in each. Group 1 was kept as normal control throughout the experimental period, 2 was given NAC @ 300 mg per kg body weight by gavage, 3 was given lead (lead acetate @ 1000 ppm in feed), 4 was given cadmium (cadmium chloride @ 300 ppm in feed), 5 was given lead + cadmium as per above doses in feed, 6 was given lead + NAC, 7 was given cadmium + NAC, and group 8 was given lead + cadmium + NAC as per above schedule for 3 months. Erythrocytic SOD, sero-biochemical parameters like CPK, troponins, plasma thiobarbituric acid reacting ubstances (TBARS) were estimated at monthly intervals. The antioxidant profile (reduced glutathione; GSH, glutathione S-transferase; GST, TBARS and protein carbonyls) in heart tissue homogenate and also interaction of lead and cadmium with zinc and copper were assessed at the end of the experiment. The results of the investigation revealed that toxic effects were more pronounced in the group that received a combination of lead and cadmium suggesting positive toxicodynamic interaction. Use of NAC countered the adverse effects of Pb and Cd induced toxicity to a major extent suggesting its antioxidant potential owing to replenishment of tissue pool of GSH. Further, NAC administration reduced the extent of accumulation of Pb and Cd in heart....
TLRs are a family of pattern recognition receptors that play a critical role in the innate immune system by activating pro-inflammatory signaling pathways in response to microbial pathogens. The TLR family now consists of 13 members (TLR1–TLR13). In general, TLR stimulation leads to activation of both the innate and adaptive immune system. Though predominantly expressed on immune cells, TLRs are also widely distributed on non-immune resident renal cells, namely mesangial cells, podocytes, parietal epithelial cells of bowman’s capsule, and tubular epithelial cells. TLR2 and TLR4 mRNA was expressed on murine renal tubular cells and upregulated by ischemia. TLR4 expression is significantly increased during renal obstruction and induces fibroblast accumulation and fibrotic renal injury independent of alterations in TNF-α and TGF-β1 gene expression. Lipopolysaccharide (LPS) is a unique glycolipid a major constituent of the gram-negative bacterial outer membrane. TLR4 uses Myd88-dependent and -independent pathways to activate NF-κB. Toll like receptor 2 and 4 expression increased in the diseases like diabetes nephropathy, ischemic reperfusion injury, lupus nephritis. Lipopolysaccharide induced renal failure used model to target validation tool in various kidney diseases....
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