Orlistat inhibits pancreatic carboxyl ester lipase, the enzyme necessary for hydrolysis of vitamin esters and absorption of fat soluble vitamins (Roche Pharmaceuticals, 1999; Hadvary et al., 1991, Ransac et al., 1991). During clinical trials, it decreased fat soluble vitamin absorption (Roche Pharmaceuticals, 1999; Davidson et al., 1999; Sjöström et al., 1998; Hollander et al., 1998, Hill et al., 1999). The effect is most notable with vitamins D and E and beta carotene (Roche Pharmaceuticals, 1999; McNeely and Benfield, 1998). Neither absorption of vitamin A nor steady state serum concentrations of retinol appears to be significantly affected after long term treatment (Zhi et al.,
Instead, axons from two groups of hypothalamic neurons - the supraoptic nucleus (SON) and paraventricular nucleus (PVN) – terminate in the posterior pituitary. These specialized neurons produce the hormones ADH (antidiuretic hormone), also known as vasopressin, and oxytocin. When a person becomes dehydrated, osmoreceptors in the brain trigger ADH release into the systemic circulation. ADH travels to the kidneys where it promotes water reuptake in the epithelial cells lining the collecting ducts. The exact mechanism of action of ADH remained obscure until 1990, when Peter Agre discovered a class of protein channels, now called aquaporins, which selectively allow water molecules to cross the cell membrane.
Acetylcholinesterase (AchE) is responsible for degradation of acetylcholine at these sites. Inhibition of AchE results in prolonged post synaptic cholinergic transmission time and protracted cholinergic over stimulation. OP compounds react competitively with AchE for binding to Ach receptors and firmly or irreversibly phosphorylated. Unlike Ach the stable phosphorous - enzyme bond requires a period of 60 minutes to several weeks for
The antioxidant activity of the extracts was measured on the basis of the scavenging activity of the stable DPPH free radical (as cited in Dong et al., 2014). Evaluation of antioxidant activity of astaxanthin through DPPH assay was modified according to the procedures reported by Lewis (2012). 12 mls of 0.1 mM DPPH solution with methanol was prepared. A measurement of 0.005 g of DPPH was added to 12 mls of methanol which was measured with a graduated cylinder into a small foil-wrapped flask. A number of 11 two ml microcentrifuge tubes were assembled and was labeled as: Tubes 1a-c through 3a-c: Product Extract Dilution 1 through 3 (repeat three times for 9 tubes), Tube 4: Positive control, α-tocopherol and Tube 5: Negative control, solvent only.
3.Pharmacology 3.1.Mechanism of action Febuxostat is a non purine compound and selective inhibitor of xanthine oxidase that has been developed for the treatment of hyperurecemia and gout. It has been found to have inhibitory activity for xanthine oxidase(XO)/xanthine dehydrogenase(XDH) during evaluation of a range of newly synthesized molecules. In humans, the xanthine oxidoreductase enzyme(XOR) catalyzes the last 2 steps in uric acid synthesis,the oxidation of hypoxanthine to xanthine and xanthine to uric acid. febuxostat was shown to inhibit both oxidized and reduced forms of XO unlike allopurinol or oxypurinol which binds only to one form of enzyme. Figure 3. mechanism of action of febuxostat Febuxostat reduces the production of uric acid by non-competitively blocking the molybdenum-pterin center which is the active site on xanthine oxidase.
ADH, elaborated by the supraoptic and paraventricular nuclei of the hypothalamus and stored in the posterior pituitary, increases the permeability of the collecting ducts with reabsorption of water from the urine leading to antidiuresis. Factor that stimulate its secretion include • Osmoreceptors that detect increased osmolality of the plasma (above 280 mOsm1L) near the supraoptic and paraventricular nuclei • Haemorrhage is a very potent stimulator • Decreased tension of the atrial walls, great veins and pulmonary vessels, as occurs in hypovolaemia, stimulates increased ADH • Renin-angiotensin mechanism: Angiotensin, released as a result of decreased renal blood volume or pressure, directly stimulates ADH secretion • Cutaneous and Visceral Pain: Visceral manipulation, pain and emotional stress also stimulate ADH secretion. • Drugs: Ether, nicotine, morphine and barbiturates can stimulate ADH secretion while alcohol inhibits
Rats were fed on high fat diet and received (12 mg/kg) of orlistat daily dissolved in saline (1ml/kg) by intraperitoneal injection (Calderon et al., 2011) for six weeks. Group 4 (G4): represented the group that was treated with amphetamine. The animals received high fat diet and amphetamine in a dose of (1.5 mg/kg) daily dissolved in saline (1ml/kg) by intraperitoneal injection (Geigera et al., 2009) for six
IDH is a cytosolic enzyme which occurs in three isoforms. The enzyme catalyses the oxidative decarboxylation of Isocitrate producing alpha-ketoglutaric acid and carbon dioxide. This step of citric acid cycle is an irreversible step and hence it is carefully regulated to avoid unnecessary depletion of isocitrate. Specific mutations of IDH1 and IDH2 have been found in many cancer cells such as gliomal cancers, astrocytomas and acute myeloid leukemia (AML). These mutations produce (D)-2- hydroxyglutarate from alpha-ketoglutarate.
The 1H NMR spectra confirmed the synthesis of the alkyd resins. The characteristic peaks at = 7.2-7.3 ppm are for the proton for –CH- of the glycerol moiety . It was observed due to the deshielding effect of the anhydride group acquiring the aromatic ring, which are absent in the 1H NMR spectra of oils. The peaks at = 7.4-7.8 ppm are observed for the aromatic protons of phthalic anhydride-containing
Of the 79 patients studied, serum Amylase was found to be elevated (> 200 S.U) in 37 patients (46.95%), among them in three patients it was 800 S.U. One of them showed swollen pancreas on ultrasonography which was confirmed by Computerised Tomography. In other two patients, evidence of pancreatitis was not observed. There was no significant correlation between the nature of compounds (OP or carbamates), duration and severity of cholinergic syndrome and increase in serum Amylase. It has been concluded that mild elevation of serum Amylase is common in patients with OP poisoning, however acute pancreatitis is rare