Isolation And Characterisation Of Rapamycin, Temsirolimus Regio Isomer (MONOESTER) And Temsirolimus Diester In Temsirolimus Drug

Objective: Separation and identification of the process impurities in the manufacture of temsirolimus drug viz., rapamycin, temsirolimus regioisomer (monoester) (TS monoester), and temsirolimus diester (TS diester). Methods: During the process development of temsirolimus (TS), three process impurities-rapamycin, temsirolimus regioisomer (monoester) and temsirolimus diester-were detected by high-performance liquid chromatography (HPLC). Impurities were isolated by medium pressure liquid Chromatography (MPLC) and characterized by ESI-MS/MS, 1H NMR, FT-IR spectral data. Results: These impurities are characterised with the help of ESI MS/MS, 1H NMR, and FT-IR data. The impurities are identified and characterised as the process impurities. One of them is the starting material i.e. rapamycin and the other two are formed during the manufacture of the drug. This method offers advantages over using photodiode-array UV detection (LC-PDA) for the determination of peak purity, viz. components with similar UV spectra can be distinguished. Conclusion: The structures of these impurities were characterized as rapamycin, TS Monoester, and TS Diester. Out of these process impurities, rapamycin has been previously identified while the other two are previously unreported.

Role of gastric antioxidant and anti-Helicobactor pylori activities in antiulcerogenic activity of plantain banana (Musa sapientum var. paradisiaca).

Studies with plantain banana (Musa sapientum var. paradisiaca) have indicated its ulcer protective and healing activities through its predominant effect on various mucosal defensive factors [Sanyal et.al, Arch Int Pharmacodyn, 149 (1964) 393; 155 (1965) 244]. Oxidative stress and Helicobactorpylori colonization are considered to be important factors in the pathogenesis of gastric ulcers. In the present study methanolic extract of plantain banana pulp (BE) was evaluated for its (i) antiulcer and antioxidant activities in 2 hr cold restraint stress and (ii) anti-H.pylori activity in vitro. The extract (BE, 50 mg/kg, twice daily for 5 days) showed significant antiulcer effect and antioxidant activity in gastric mucosal homogenates, where it reversed the increase in ulcer index, lipid peroxidation and super oxide dismutase values induced by stress. However it did not produce any change in catalase values, which was significantly decreased by stress. Further, in the in vitro study. BE (0.32-1,000 microg/ml) did not show any anti-H.pylori activity. The results suggest absence of anti-H. pyloric activity of methanolic extract of banana in vitro and its antioxidant activity may be involved in its ulcerprotective activity.

Absent coronary venous sinus: a rare anomaly.

A 42-year-old man, presenting with dyspnea on exertion and ST segment depression on treadmill test, was found to have absent coronary venous sinus on coronary angiography. We report this case of isolated congenital absence of coronary venous sinus because of its rarity.

Effect of Convolvulus pluricaulis Chois on gastric ulceration and secretion in rats.

Convolvulus pluricaulis is an indigenous plant commonly mentioned in Ayurveda, an ancient system of Indian medicine, as a rasayana which is mainly advocated for use in rejuvenation therapy. The present study was conducted to evaluate the potential anti-ulcerogenic effect of juice of fresh whole plants of C. pluricaulis (CPJ) against various experimental gastric ulcer models induced by ethanol, aspirin, 2 hr cold restraint stress and 4 hr pyloric ligation in rats. The drug was given orally twice daily for five days in the doses of 375 and 750 mg/kg body weight. CPJ showed anti-ulcerogenic effect at both doses in all the experimental gastric ulcer models and was comparable to the reference drug sucralfate (250 mg/kg). Gastric juice secretion and mucosal studies were undertaken to find out the possible mechanism of action of antiulcer effect by studying its effects both on offensive and defensive mucosal factors. The antiulcerogenic effect of CPJ was found to be due to augmentation of mucosal defensive factors like mucin secretion, lifespan of mucosal cells and glycoprotiens rather than on the offensive factors like acid-pepsin.

Effect of Centella asiatica Linn on physical and chemical factors induced gastric ulceration and secretion in rats.

Centella asiatica is commonly mentioned as a Rasayana in Ayurveda, an ancient system of Indian medicine for various ailments including abdominal disorders. Rasayanas have been advocated for use in rejuvenation therapy. The present study was conducted to evaluate the possible anti-ulcerogenic activity of fresh juice of C. asiatica (CAJ) against ethanol-, aspirin-, cold-restraint stress- and pyloric ligation induced gastric ulcers in rats. The drug given orally in doses of 200 and 600 mg/kg twice daily for five days, showed significant protection against all the above experimental ulcer models and the results were comparable with those elicited by sucralfate (SF, 250 mg/kg, p.o., BD x 5 days). CAJ showed little or no effect on offensive acid-pepsin secretion. However, at 600 mg/kg CAJ significantly increased gastric juice mucin secretion and increased the mucosal cell glycoproteins signifying increase in cellular mucus. It also decreased cell shedding indicating fortification of mucosal barrier. Thus, the ulcer protective effect of CAJ may be due to strengthening of the mucosal defensive factors.

Experimental evaluation of Bocopa monniera on rat gastric ulceration and secretion.

The anti-ulcerogenic effect of fresh juice from the whole plant of Bocapa monniera Wettst. (BMJ) commonly known as Brahmi in Hindi was examined using gastric ulcer models induced by ethanol, aspirin, 2 h cold restraint stress and 4 h pylorus ligation. Bocapa monniera juice (BMJ) at doses of 100 and 300 mg/kg and sucralfate at a dose of 250 mg/kg were given orally, twice daily for 5 days. BMJ 100-300 mg/kg produced significant antiulcer activity in all the experimental gastric ulcer models except in case of ethanol-induced ulcers where 100 mg/kg was not found to decrease it significantly. BMJ (100-300 mg/kg) was found to have little or no effect on the offensive acid-pepsin secretion, while cell shedding (microgram DNA/mg of protein) and mucin secretion in terms of total carbohydrates:protein ration (TC:P), the two important parameters of defensive factors were significantly decreased and increased respectively indicating enhancement of protective mucosal factors. Both BMJ (300 mg/kg) and SF showed tendency to increase the mucosal glycoproteins in terms of TC:P, though individual carbohydrates and total carbohydrates were either increased or showed a tendency to increase. Thus, ulcer protective effect of BMJ may be due to its effect on mucosal defensive factors like enhanced mucin secretion, mucosal glycoprotein and decreased cell shedding rather than on offensive factors such as acid and pepsin.

Effect of Piper longum Linn, Zingiber officianalis Linn and Ferula species on gastric ulceration and secretion in rats.

Use of Dipaniya Mahakasaya, a group consisting of 10 herbal drugs, has been suggested in Charaka Samhita to improve digestion. Out of these 10 plants, three, viz. P. longum (water decoction), Z. officianalis (water decoction) and Ferula species (colloidal solution) were studied for their antiulcer and mechanism of antiulcer effects in rats. All the drugs in the dose of 50 mg/kg, p.o., 60 min prior to experiment, showed significant protection against gastric ulcers induced by 2 hr cold restraint stress, aspirin (200 mg/kg, 4 hr) and 4 hr pylorus ligation. The antiulcerogenic effect seemed to be due to the augmentation of mucin secretion and decreased cell shedding rather than offensive acid and pepsin secretion which however, were found to be increased by them.

Effect of mild irritant on gastric mucosal offensive and defensive factors.

The effect of hypotonic medium (Distilled water: DW) and hypertonic saline (HS: 5% NaCl) compared to control normal saline (NS) was studied on gastric ulcer induced by aspirin, 6 h cold restraint stress, ethanol, and pylorus ligation in rats. DW did not afford any protection while HS showed significant ulcer protective effects in all gastric ulcer models studied. The cytoprotective effect of HS seemed to be not only due to its effect on gastric acid secretion but also its effect on mucosal defensive factors like enhanced mucin secretion and decreased cell shedding. As determined by radioimmunoassay, DW did not produce any change in the accumulation of PGE and PGI2, while HS increased them significantly in the human gastric mucosal incubates compared to NS. However, in the incubates of human colonic mucosa, both DW and HS showed a significant increase in PGE with a tendency to increase in PGI2 accumulation.

Solitary plasmacytoma presenting as peripheral neuropathy: a case report.

We report a 26 year old woman presenting with a chronic predominantly motor radiculoneuropathy. A biopsy proven solitary lytic plasmacytoma was detected in the left sixth rib. Serum immunoelectrophoresis revealed 'M' band (IgG, l light chain). Excision of the plasmacytoma resulted in gradual but steady recovery. We suggest that all patients with 'cryptogenic' polyneuropathy be investigated for this potentially treatable condition. A high index of suspicion assists the organization of appropriate diagnostic investigations.

Perceptions on effects of environmental pollutants in Hyderabad City.

Five hundred twenty adults were interviewed on the perceptions of effects of the environmental pollutants in Hyderabad city of Andhra Pradesh. The information was gathered on polluted water, polluted air, solid wastes, food contamination and readiness to participate in corrective actions. Both initial response and response after probing were recorded. Analysis was done basing on the level of literacy. The correct initial responses on effects of pollutants ranged from 28.3 to 35.4% while responses after probing ranged from 79.2 to 88.1%. 45.8% were ready to participate manually in the corrective actions while 24.6% were eager to contribute financially in remedial actions. The study reveals the need for the initiation of aggressive environmental education.

Serological response to Japanese encephalitis vaccine in a group of school children in South Arcot district of Tamil Nadu.

A trial with Biken Japanese encephalitis (JE) vaccine made in Japan was carried out in South Arcot district of Tamil Nadu state, India. A total of 113 school children were included in the trial. The efficacy (as determined by serological response) and safety of the vaccine were evaluated. Side effects, though minor, were noted in 54.9 per cent of the children after each dose. The serum antibody titres were determined by mouse neutralization test, plaque reduction neutralization test and haemagglutination inhibition test. An antibody response to two-dose primary vaccination schedule was observed in 72.7 per cent, whereas 87.8 per cent of the vaccines responded positively after the booster dose administered one year after. Only about 20 per cent of the children had persisting antibodies one year after the primary vaccination. The results indicated a probable need of the third dose in the primary vaccination schedule.

Post-epidemic serological survey for JE virus antibodies in south Arcot district (Tamil Nadu).

Following an extensive epidemic of Japanese encephalitis (JE) in 1981, a serological survey was carried out in the South Arcot district of Tamil Nadu in April 1982. Serum specimens were obtained from 10 villages with serologically proven infections and 6 villages with no reported case of encephalitis during the 1981 epidemic. The serum specimens tested for haemagglutination inhibition, complement fixing and neutralizing antibodies, showed a high prevalence of JE (49.17%), West Nile (40.78%) and dengue (18.14%) viruses with predominance of JE. The prevalence did not differ between the villages with or without Japanese encephalities. There was also no difference between the family members and neighbours.

Effect of feeding polychlorinated biphenyl (Aroclor 1260) on hepatic enzymes of rats.

Significant increase in the activity of liver succinate dehydrogenase (SDH) was observed in male Wistar rats, fed Aroclor 1260 (PCB; polychlorinated biphenyl) at 50 and 100 ppm level for 120 days. Lactate dehydrogenase (LDH) activity increased in 50 ppm PCB fed animals and decreased in 100 ppm PCB fed rats. On the other hand, enzymes like alanine and aspartate aminotransferase, alkaline and acid phosphatase showed remarkable decrease in activity in PCB fed animals. Slab gel electrophoresis of LDH isozymes showed remarkable increase in LDH2 and LDH3 and to some extent increase in LDH1 isozymes of livers of 50 ppm PCB fed animals but not in 100 ppm PCB fed groups as compared to controls. In both the PCB fed groups, liver showed centrilobular hypertrophy, hepatocellular damage, hyperplasia, karyolysis and karyorrhexis.

Effect of polychlorinated biphenyl (Aroclor 1260) on histology of kidney and thyroid of rats.

Gross histological alteration in kidney and thyroid structures were observed in male Wistar rats fed polychlorinated biphenyls (PCBs; Aroclor 1260) at 50 and 100 ppm level in normal commercial diet for 120 days. While the kidney showed glomerulonephritis, degenerative changes in the proximal and distal tubules and increased cellularity of glomeruli, thyroid showed degeneration of follicles, fibrosis of follicles and lymphocytic infiltration followed by thyroiditis.