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Purpose: To estimate the survival rates of breast cancer patients with reference to various factors like age, literacy status, residential status, T-stage and treatment. This is because there are very few studies reported from Indian subcontinent., Methods: Survival rates were obtained by using the actuarial method and loss-adjusted survival rate method (LAR) for the above factors and the rates were compared. The present study carried out at the Tata Memorial Hospital (TMH), includes newly diagnosed (who were not treated elsewhere before attending TMH) primary breast cancer patients and having completed the initial treatment., Results: The survival rates, actuarial survival and rates corrected for losses to follow-up (LAR) are presented. It showed that younger patients ( 50 years), with statistical significance ( p=0.024). There was no variation in survival with regard to the residential status but literate patients had a better ( non-significant) survival (77%) than their illiterate counterparts. T3-stage patients had the worst prognosis showing a 5-year survival of 60% (p=0.0002). Survival for those treated with surgery as the only modality and also in combination with other modalities did not show any remarkable differences except for the group that were treated with 'surgery in combination with chemotherapy'. The 5-year survival for those treated with surgery as the only modality was 83%. This study yielded useful information on breast cancer survival, especially in a situation with incomplete follow-up. The method applied (LAR) also clearly demonstrates the bias in estimates obtained by direct application of the standard actuarial method.

Aims: Archival fixed paraffin-embedded tissue (PET) is a valuable source for population-based molecular genetic studies but the extraction of high quality DNA is still a problematic issue. The present study tested the grade of DNA fragmentation and the DNA adequacy for genetic investigations in a large series of tissue specimens that were formalin- or Bouin-fixed and paraffin-embedded between 1979 and 1983. Specific aims were to: (1) estimate the amount of archival tissue samples from which DNA is recoverable by conventional methods and the influence of variables (origin, fixative, section size) on DNA recovery; and (2) evaluate the feasibility of genetic investigations in large scale population studies., Methods: DNA was extracted in 2005 from 365 PET samples from Italy and Spain and subjected to PCR analysis targeting fragments of 152, 268 and 676 bp of the beta-globin gene., Results: Amplification of a 152 bp fragment was obtained in 252/365 (69%) PET samples, a 268 bp fragment in 62/365 (17%), a 676 bp fragment in 19/365 (5%) and no amplification for any fragment was obtained in 113/365 (31%). A second processing of newly cut sections performed in a 25% simple random sample gave comparable results, with substantial concordance between the first and second tests (kappa value 0.62 [95% CI 0.59-0.64])., Conclusions: The results of this study show that DNA can be efficiently extracted from PETs archived for more than 20 years, and that large scale population studies based on PCR amplification of short target sequences are feasible.

Tea leaves are known for its antibacterial activity against many microorganisms. In this study we attempted to describe the synergistic antimicrobial activity of tea and antibiotics against enteropathogens. Antimicrobial activity of boiled water tea extract and organic solvent extract were studied against Salmonella typhimurium 1402/84, S. typhi, S. typhi Ty2a, Shigella dysenteriae, Yersinia enterocolitica C770, and Escherichia coli (EPEC P2 1265) determining minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and death rate kinetics at MBC of tea extract in presence of subinhibitory concentration of antibiotic. Both green tea or black tea extracts effectively inhibited the growth of S. typhimurium 1402/84, S. typhi, S. typhi Ty2a, S. dysenteriae, Y. enterocolitica C770, and E.coli (EPEC P2 1265). However, the growth inhibitory concentration of tea extract was lower for green tea as compared to black tea extract. Antimicrobial activity of green tea tea methanol: water extract tea was better as compared to boiled water tea extract of green tea. Based on death rate kinetics results, S.typhi Ty2a appeared to be highly sensitive and Y. enterocolitica C770 the most resistant. Chloramphenicol and tea extract in combination inhibited the growth of S.dysenteriae at 2.5 microg/ml chloramphenicol (MIC 5 microg/ml) and 5.094 mg/ml black tea extract (MIC 9.089 mg/ml). Tea extract showed synergistic activity with chloramphenicol and other antibiotics like gentamycin, methicillin and nalidixic acid against test strains.

Pentylenetetrazole (PTZ)-induced convulsions and the maximal electroshock (MES) seizure test were employed to study the anticonvulsant effects of nifedipine (2, 3.5 and 5 mg kg-1), flunarizine (10, 20 and 40 mg kg-1) and diltiazem (10, 15 and 30 mg kg-1). Nifedipine and flunarizine prolonged the latent period and reduced the mean duration of PTZ induced seizures. They also reduced the severity of convulsions and the number of deaths due to PTZ significantly. Nifedipine was more potent in this regard (P < 0.01). All these drugs prolonged the latent period and reduced the duration of tonic extensor phase of MES seizures in a significant manner. Flunarizine was most potent in this test. Complete protection from tonic extensor phase was observed in 10-50% animals pretreated with nifedipine and flunarizine in a dose dependent manner. The response of diltiazem was weak in both these tests. It is concluded that all three calcium channel blockers possess an important but different anticonvulsant effect and their significant clinical use can be made while keeping in view the characteristics of their pharmacological action.

Spontaneous motor activity, rotarod test and observational rating of sedation were employed to study effect of nifedipine on sedation produced by reserpine, clonidine and propranolol. Reserpine (2 mg kg-1), clonidine (4 mg kg-1), and propranolol (40 mg kg-1) significantly reduced spontaneous motor activity and staying capacity of animals on accelerating rotarod (P < 0.01). Observational sedation was also caused significantly as indicated by a higher score in test. Nifedipine (2 mg kg-1) produced no sedation or excitation on its own. Reduction in spontaneous motor activity produced by reserpine and clonidine was partially reversed in animals treated with nifedipine (P < 0.01). A similar effect of nifedipine was also evident on the observational sedation induced by reserpine and clonidine. Effect of these drugs on rotarod times was nearly totally antagonised by nifedipine. Nifedipine did not oppose the sedation produced by propranolol which actually became significantly greater in the animals pretreated with nifedipine in all three tests. It is concluded that nifedipine antagonizes the sedation produced by reserpine and clonidine, probably by blocking central alpha 2-adrenoceptors. The sedative effect of propranolol can be potentiated by nifedipine possibly because of a pharmacokinetic interaction.

Two Escherichia coli mutants that lack both cytochrome o and d terminal oxidases are able to grow with glucose as the carbon source but not with the aerobic substrates succinate or lactate. One of these, GV101, is a deletion mutant of cytochrome o and a point mutation of cytochrome d. The other, GK100, is a total deletion mutant of all the genes for both cytochromes. When these mutants were transformed with a plasmid containing the gene for the bacterial hemoglobin from Vitreoscilla, they were capable of growth in the presence of succinate or lactate and showed aerobic respiration in the presence of these substrates, unlike the parent strains. Cells transformed with a plasmid containing the gene for the hemoglobin but lacking the native promoter did not express the hemoglobin and did not respire. Membrane vesicles prepared from the cells consumed oxygen in the presence of succinate. This succinate-supported respiration decreased with successive washings of the vesicles but was restored by adding E. coli cytosol containing the hemoglobin or by adding the hemoglobin purified from Vitreoscilla. This respiration was inhibited by cyanide.

A sound knowledge of pharmacology and clinical therapeutics could help future prescribers in India to master the principles and practice of rational therapy. The teaching of pharmacology in medical schools should be restructured accordingly, and greater attention should be given to the applied aspects of the subject. Practicals in experimental pharmacology and dispensing pharmacy should be discontinued and useful exercises should be introduced. Methods of evaluation should be modified.

Effect of four calcium salts, three calcium antagonists, calcium ionophore (A 23187) and calmodulin was studied in vitro on the motility and viability of ejaculated normal human spermatozoa at different time intervals. Effect of calcium salts was also studied on the oligoasthenospermic samples with an original motility of 10 to 30 per cent. Calcium salts were found to improve the sperm motility by 6 to 16 per cent and this may be due to a direct excitatory influence and a protective action of calcium on the spermatozoa since the viability was also improved by 4 to 11 per cent in these cases. A similar improvement in motility (8 to 11%) and viability (5 to 9%) was observed in hypokinetic samples also, Calcium antagonists inhibited the sperm motility and viability significantly. Diltiazem was the most potent drug in this respect, the reduction in motility being by 11 to 22 per cent and in viability by 6 to 14 per cent, after 30 sec of incubation. Calcium ionophore and calmodulin were found to be more potent than calcium antagonists to produce a dose-dependent decrease in sperm motility and viability. The results confirm that ionized calcium plays an important role in the regulation of sperm motility. Although intracellular concentration of calcium may be a better determinant physiologically, the manipulation of extracellular levels in a critical range may promote the sperm motility, viability and other vital functions. This has a potential use in situations like artificial insemination, in vitro fertilization and semen banking. Calcium ionophores and calmodulin need further investigation for a possible use as vaginal spermicides.

Bacterial hemoglobin (VtHb) is produced by the gram-negative bacterium, Vitreoscilla, in large quantity in response to hypoxic environmental conditions. The vgb gene coding for VtHb has been cloned in E. coli where it is expressed strongly by its natural promoter. The expression of the vgb gene in Vitreoscilla is transcriptionally regulated by oxygen. When E. coli cells were shifted from 20% to 5% oxygen, vgb specific transcript increased. In E. coli cells with plasmids carrying transcriptional fusions of the vgb gene promoter to either CAT (chloramphenicol acetyl transferase) or xylE (catechol-2,3-dioxygenase) genes, the promoter activity depended on the oxygen level. The concentration of CAT and xylE gene products in cells grown under 5% oxygen was 5-7 times that of aerobically (20% oxygen) grown cells. When the vgb gene promoter was deleted, VtHb was not produced under any conditions. When the promoter was replaced by the E. coli tac promoter, hypoxic oxygen did not affect the level of expression of vgb, but adding IPTG did increase the expression of this gene. These results indicate that the vgb gene promoter is transcriptionally regulated by oxygen even in E. coli, and that microaerobiosis is sufficient to induce vgb expression. The size of S1 nuclease-resistant hybrids, prepared using RNA transcripts protected with restriction enzyme fragments containing the promoter proximal region of vgb, was the same for both Vitreoscilla and E. coli, further evidence that the same promoter is used in both organisms. Transcriptional fusion of the vgb gene promoter to the xylE reporter gene on the broad host range plasmid, pKD-49, was used to demonstrate that the vgb promoter can be expressed in other gram-negative organisms, including Pseudomonas, Azotobacter, and Rhizobium.

Growth inhibitory effect of pentazocine was studied in young rats for a duration of 4 weeks. The animals were subjected to various drug treatments, namely (1) distilled water 0.5 ml/kg s.c.; (2) pentazocine 10 mg/kg s.c.; (3) pentazocine 10 mg/kg s.c. plus metoclopramide 10 mg/kg s.c., and (4) pentazocine 10 mg/kg s.c. plus l-dopa 100 mg/kg s.c. Body weight was taken as a measure for the assessment of growth rate. The results of group 2 were compared with group 1 and that of groups 3 and 4 were compared with group 2. Pentazocine alone markedly inhibited the growth from the second to fourth weeks of treatment. Dopamine antagonist metoclopramide has almost completely prevented the growth inhibitory effect of pentazocine. Combination of l-dopa with pentazocine produced a significant growth inhibition in the first week but subsequently this effect was significantly less marked as compared to that of pentazocine alone. The growth inhibitory effect of pentazocine may possibly be mediated through alterations in dopaminergic mechanisms which are known to exert controlling influence on the release of several of the pituitary hormones.

Effect of tobacco use (by chewing or smoking) on semen quality has been seen. Semen analysis of 119 tobacco chewers and 219 smokers was compared with those of 288 control patients. Some decrease in the ejaculate volume, sperm density, and total count was observed in tobacco users, but it was statistically insignificant. No difference was found in other parameters, like motility and morphology. It is concluded that tobacco use by chewing or smoking is not associated with impaired semen quality in males selected from an idiopathically hypofertile population.

The Pseudomonas aeruginosa capsule, composed of polysaccharide alginate, is an important Pseudomonas virulence factor encountered primarily in cystic fibrosis. The regulatory algR gene positively controls transcription of a key alginate biosynthetic gene, algD. The algR gene was subcloned and sequenced by creating a set of nested deletions in M13 bacteriophage. DNA sequence analysis of algR revealed the homology of its gene product with a recently recognized class of environmentally responsive bacterial regulatory genes, including ompR, phoB, sfrA, ntrC, spoOA, dctD, and virG; these transcriptional activators control cellular reactions to osmotic pressure, phosphate limitations, or specific chemical compounds present in the medium or released from wounded host tissue. These findings indicate that novel conditions in lungs affected by cystic fibrosis may be participating in the control of mucoidy.

The effects of morphine and verapamil have been assessed on the gastrointestinal propulsion of charcoal meal and egg yolk-induced gall bladder emptying in mice. Each drug significantly inhibited these functions. In combination, an additive effect was seen on the inhibition of gastrointestinal transit, whilst verapamil potentiated the morphine-induced inhibition of gall bladder emptying. It is concluded that calcium ion channel antagonists may potentiate the activity of opiate drugs.