Pharmacokinetics and metabolism of the cholecystokinin antagonist dexloxiglumide in male human subjects

1. Mean concentrations of total 14 C and of dexloxiglumide at the end of single 20-min infusion doses of 14 C-dexloxiglumide (200?mg) to four healthy male subjects were 18.5 µ?g eq. ml ? 1 and 19.5 µ?g ml ? 1, respectively. The mean plasma clearance (0.22 l?h ? 1 kg ? 1) and mean volume of distribution (V ss = 0.18?l kg ? 1) were low. 2. Single oral doses of a solid formulation of 14 C-dexloxiglumide (200?mg) to the same subjects appeared to be rapidly and well absorbed. Mean peak plasma concentrations (C max) of total 14 C (2.8 µ?g eq. ml ? 1) and of dexloxiglumide (2.2 µ?g ml ? 1) occurred at about 1.5?h. Systemic availabilities of the oral dose based on total 14 C and dexloxiglumide were 70 and 48%, respectively. Thus, a proportion of an oral dose was subjected to presystemic elimination and the absorbed dose mainly eliminated by metabolism. Binding of dexloxiglumide to plasma proteins was extensive (96.6-99.2%). 3. Total 14 C was excreted mainly in the faeces. Mass balance of 14 C excretion was almost complete within 7 days when a mean of > 93% of the dose had been recovered. After the intravenous (i.v.) dose, mean totals of 23.7 and 69.8% of the dose were excreted in urine and faeces, respectively, during 7 days, and 19.5 and 73.7% of the dose, respectively, after the oral dose. The data were consistent with biliary excretion and perhaps some enterohepatic circulation of conjugates of dexloxiglumide and at least one of its metabolites. 4. LC-MS/MS of urine extracts showed that dexloxiglumide was metabolized by oxidation and conjugation. The former included at least two metabolites formed by monohydroxylation in the N- (3-methoxypropyl) pentyl side chain, and O-demethylation of this side chain followed by subsequent oxidation of the resultant alcohol to the dicarboxylic acid. At least one glucuronide was also present in urine. The main components in faeces appeared to be dexloxiglumide and a dicarboxylic metabolite formed by O-demethylation followed by oxidation of the N- (3-methoxypropyl) side chain. Both compounds were identified as their corresponding methyl esters formed because acid and methanol were used in the extraction procedure. Dexloxiglumide and the dicarboxylic acid were presumably excreted in bile as the glucuronic acid conjugates.     

Iodine deficiency disorders in school age children in Kullu district, Himachal Pradesh

Iodine deficiency disorder is a major public health problem in Himachal Pradesh. A study was conducted in district Kullu to assess the prevalence of IDD in school age children. Clinical examination of the thyroid of 1986 children was conducted. On the spot urine and salt samples were collected. The Total Goiter Rate was found to be 23.4% and median urinary iodine excretion was 175μg/L. The population is possibly in transition phase from iodine deficient to iodine sufficient nutrition.     

Autologous embedded foreign body of mobile tongue

Foreign bodies of upper aerodigestive tract are common otorhinolarygological emergencies. The foreign bodies of mobile tongue are however very rare and there are only limited case reports in literature. The case of a young female with an autologous foreign body mobile tongue with unusual presentation is presented.     

Efficient amelioration of carbon tetrachloride induced toxicity in isolated rat hepatocytes by Syzygium cumini Skeels extract.

Syzygiumcumini, Indian black plum or Java plum, is a rich source for anthocyanins (230mg/100g DW) showing high antioxidant activity in vitro. In the following study it is further demonstrated that S. cumini peel extract rich in anthocyanins (SCA) offers considerable protection against carbon tetrachloride (CCl(4))-induced damage in rat hepatocytes. SCA itself being non-toxic to primary rat hepatocytes at concentrations ranging from 50 to 500ppm, was found to suppress CCl(4)-induced LDH leakage by 54% at 50ppm, thereby improving the cell viability by 39%. The SCA significantly reversed the CCl(4) induced changes in cellular glutathione (GSH) level, lipid peroxidation and activity of the antioxidant enzyme glutathione peroxidase. Exposure of hepatocytes to SCA after CCl(4) treatment was found to elevate GSH and GPx activities by 2-folds, whereas the activities of catalase and superoxide dismutase were not significantly affected. The fruit pulp extract (SPE) was less effective in offering protection to rat hepatocytes, particularly in terms of total GSH content and a consequent increase in lipid peroxidation although the higher GPx activity suggests the probable involvement of GSH as a substrate for GPx. These observations suggest that the fruit peel extract of S. cumini, is largely responsible for the reversal of CCl(4)-induced oxidative damage in rat hepatocytes. Both peel and pulp extract appear to offer protection to rat hepatocytes through GPx along with other biological pathways independent of catalase and superoxide dismutase.     

Therapeutic significance of elevated tissue transglutaminase expression in pancreatic cancer.

PURPOSE: Tissue transglutaminase (TG2) is a multifunctional protein that is implicated in development of drug resistance and metastasis. Therefore, we examined therapeutic targeting of TG2 for inhibiting growth and metastasis of in vivo growing pancreatic ductal adenocarcinoma (PDAC) in nude mice. EXPERIMENTAL DESIGN: We implanted Panc-28 pancreatic cancer cells to induce orthotopic PDAC tumors in nude mice and determined the efficacy of liposomal TG2 small interfering RNA (siRNA) either alone or in combination with gemcitabine. RESULTS: We show that down-regulation of endogenous TG2 by siRNA could effectively block the growth of PDAC. Moreover, down-regulation of TG2 significantly enhanced the therapeutic efficacy of gemcitabine against PDAC and inhibited metastatic spread of the disease. The antitumor activity was related to inhibition of proliferation, angiogenesis, and Akt phosphorylation. CONCLUSION: siRNA-mediated down-regulation of TG2 represents a promising therapeutic approach for improved treatment of PDAC.     

Knowledge amongst adolescent girls about nutritive value of foods and diet during diseases, pregnancy and lactation.

Knowledge about nutritive value of food, diet during diseases and antenatal and postnatal period was assessed amongst 152 adolescent school girls. A total of 23.69 and 55.93% students had incorrect knowledge that pulses and non-vegetarian foods should be avoided during later half of the pregnancy. A total of 63.82, 66.45 and 71.72% of subjects had incorrect knowledge that almonds have more nutritive value than groundnuts, fruits are rich sources of calories and desi ghee has more nutritive value than vanaspathi, respectively. Majority (90.78%) had correct knowledge that obesity is caused due to excess intake of calories than required by an individual and low iron content and poor availability of iron from food is a major cause of anemia in mothers and children.