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The influence of various temperature and relative humidity conditions on changes in hardness and friability of five commercial brands of packaged paracetamol tablets stored over a period of six months has been investigated. At 75% RH all sample show deterioration in hardness at 25 degrees (5-10%) and at 45 degrees (10-39%). At 100% RH there is a little difference in deterioration in hardness at 25 degrees (16-24%) and 45 masculine (20-28%) suggesting that once the critical moisture content is reached by the tablets, further increase in relative humidity has little effect on changes in hardness. Under the same conditions, all tablets show an increase in friability ranging from 2.83 to 8.02%. The overall increase in friability with an increase in temperature from 25 degrees to 45 degrees at 75% and 100% RH is 0.0 to 25.2%. The results indicate that moisture sorption by tablet matrix through certain packaging materials may adversely affect the hardness and friability characteristics.

Penile tissue consisting of corps cavernosum (cc) and tunica albuginea (TA) was obtained from 35 impotent patients undergoing surgery for implantation of penile prostheses and was examined for nor adrenaline content. 10 patients were classified as a non diabetic non neuropathic group, on the basis of their clinical history and differential diagnostic symptoms which included Peyronie's disease, vascular disease, hypertension and psychogenic impotence. The nor adrenaline content was found to be significantly lower in tunica albuginea than the corpus cavernosum (P<0.02) in this group. The nor adrenaline content of corpus cavernosum from insulin dependent (IDDM) and non insulin dependent (NIDDM) diabetic neuropathic patients was also found to be significantly lower (P <0.02) than that of non diabetic non neuropathic patients. The nor adrenaline content of tunica albuginea however, was similar in both groups. A non significant association in the content of nor adrenaline in corpus cavernosum and tunica albuginea among IDDM and NIDDM diabetic neuropathics was also observed. These results provide evidence that an underlying neuropathic factor itself causes vascular as well as metabolic changes in the adrenergic nerves of the penis in diabetics due to neuropathy in addition to the effect of the disease and thus may contribute to the development of impotence in these patients irrespective of their type of diabetes.

Urethral or cervical swab of 255 patients attending Skin and Social Hygiene Centre and found positive for gram negative intracellular diplococci on direct microscopy were inoculated on Modified New York City (MNYC) medium and chocolate (heated blood) agar for isolation of neisseria gonorrhea. Growth of N. gonorrhea was obtained in 134 (52.5%) cases. These strains were tested for penicillin susceptibility by disc diffusion method and for the production of beta-lactamase by rapid penicillinase paper strip test and rapid chromogenic cephalosporin method. Penicillin resistance was found in 31 (23%) strains, of which twelve (9%) were beta-lactamase producers (PPNG), the remaining 19 (14%) strains were penicillin resistant beta-lactamase negative (Pen RB Neg). We conclude that PPNG as well as other penicillin resistant strains (Pen RB Neg) of neisseria gonorrhea are prevalent in our country and appropriate changes in the conventional therapeutic regime are desirable.

Value of the bulbocavernosus reflex latency versus nerve conduction velocity of the dorsal nerve of penis and penile brachial index was evaluated in HIV-1 infected asymptomatic and symptomatic men with and without an objective evidence of neuropathy. These studies revealed striking results in neuropathic group. Both asymptomatic and symptomatic patients with neuropathy exhibited a significant decrease (P < 0.0005) in the values of the nerve conduction velocity of the dorsal nerve of penis as well as penile brachial index in comparison with the controls of the same age group. However both types of non neuropathic patients showed a non significant difference in the above mentioned parameters with their respective controls. The latency of bulbocavernosus reflex showed no significant difference between the groups and was within the normal limits. A non significant association in the values of the study parameters among asymptomatic and symptomatic patients with and without neuropathy was also observed. These findings suggest an exclusively apparent sexual pathway for the penile dorsal nerve conduction and penile brachial index in both HIV-1 infected asymptomatic and AIDS positive men affected by neuropathic conditions, irrespective of their disease state. We thus conclude that a primary defective neuropathic mechanism may play an etiological role in the pathogenesis of erectile impotence in these patients.

A study of the effect of various temperature and humidity conditions on the disintegration time of different brands of packaged paracetamol tablet formulations has been made over a period of six months. Under all the storage conditions paracetamol tablets show an increase in disintegration time ranging from 9.1 to 65.5% (200 mg tablets) and 1.2 to 150.0% (500 mg tablets) on increasing the temperature from 25 to 45 degrees C (75% RH). The increase in disintegration time on increasing the temperature from 25 to 45 degrees C (100% RH) ranges from 14.3 to 157.7% (200 mg tablets) and 15.3 to 92.3% (500 mg tablets). The overall increase in disintegration time from 25-45 degrees C at 75% and 100% RH is 36.4 to 564% (200 mg tablets) and 10.0 to 140.5% (500 mg tablets) and 101.3 to 122.9% (200 mg tablets) and 2.6 to 46.8% (500 mg tablets) respectively. These results indicate that PVC/PVDC/Al foil packaging cause relatively less change in disintegration time of the tablets compared to that of the polycoated paper and viscose film.

A study of the influence of various temperature and humidity conditions on the stability of a number of commercial paracetamol tablet formulations in original packaging has been conducted over a period of six months. Paracetamol degradation in tablets follows apparent first-order kinetics and the shelf-lives (t(90)) range from 9.8 to 23.0 months. PVC/PVDC/Al foil and polycoated paper packaging offer better protection to the tablets compared to that of viscose film.

The phenotype in the rd mouse is similar to the clinical presentation of Leber congenital amaurosis (LCA) in humans. Recently a nonsense mutation in the beta subunit of the cGMP phosphodiesterase (Pdeb) gene has been defined as the cause for the rd phenotype in the mouse and has raised the question as to whether mutations in the human PDEB gene might cause LCA. We have previously cloned and characterized the human homologue of the mouse Pdeb gene and have mapped it to chromosome 4p16.3. In this study, a total of 23 LCA families of various ethnic backgrounds have been investigated. Linkage analysis using highly polymorphic (CA)n microsatellites has excluded the PDEB gene as a cause for LCA in 6 families. In the remaining 17 families, we have searched for mutations in the 22 exons of the PDEB gene using single-strand gel electrophoresis (SSGE). Multiple exonic polymorphisms have been determined. However, no DNA changes in the PDEB gene have been identified in our study population which could be causative for the LCA phenotype.

Serial precordial mapping was done in 30 patients with acute anterior myocardial infarction, 27 transmural and 3 subendorcardial. The sum of ST elevations in the 48 lead map was designated as sigma ST. Normal sigma ST was calculated as 27.1+/-3.1 in males and 14.3+/-2.8 in females. In infarction it was 100.4+/-58.2 in males and 84.8+/-50.9 in females on the 1st day of admission. Sigma ST was elevated on day 1 and tended to fall gradually. In 6 patients it was normal by day 7 and in 7 it was still abnormal by day 21. This fall roughly correlated with fall in SGOT and CPK levels. Significant elevation of sigma ST occurred in 14 of 27 cases after day 1. In 10 of 27 cases significant re-elevation occurred on day 4 or after i.e. when the patient was outside the ICCU. In 10 of the 14 re-elevations there was pain or worsening of clinical picture and in 12 there was re-elevation of SGOT. This elevation presumably implied infarct extension. There was a tendency to more arrhythmias in the patients with higher sigma ST and of the 4 deaths in the series 3 had very high sigma ST and high levels of SGOT. The patient with the highest sigma ST 295 died in cardiogenic shock. The number of risk factors was found to be higher in the high sigma ST group.

Clones of stably transformed rat cells from the F-111 (Fisher rat embryo) and NRK (normal rat kidney) cell lines have been obtained by complementation using pairs of nontransforming polyoma mutants of the hr-t and ts-a classes. A total of 78 clones were isolated and studied, 21 from the NRK line, and 57 from the F-111 line. These "complementation transformed clones" were then examined for the presence and expression of each of the parental mutant viruses. The expression of viral T (tumor) antigens was analyzed by immunoprecipitation. Every one of 54 clones examined express the 22K (small) and 56K (middle) T antigens which are the products of the hr-t viral gene. This indicates a requirement for the presence of a wild-type hr-t allele contributed by the ts-a mutant parent. Ten clones lack detectable large T antigen, while four show thermolabile large T antigen. These results support the conclusion that middle and small but not large T antigen(s) are essential for the maintenance of the transformed phenotype. Most of the 57 F-111 clones are virogenic when fused to mouse cells under permissive conditions and yield both mutant types. Surprisingly, wild-type recombinants have been recovered from 40 of the F-111 clones. Three clones show evidence of retention of only the ts-a mutant genome. Virus cannot be rescued from the majority of the 21 NRK clones. The few clones which are virogenic, however, yield both hr-t and ts-a mutants. Integration patterns of several clones analyzed by Southern blotting confirm the expectations based on viral T antigen(s) and virus rescue analyses. Hr-t mutant genomes, though not required for the maintenance of the transformed state, are frequently retained in complementation transformed clones. Tandem integration of the two parental mutants is clearly demonstrated in one clone and implicated in the other eight out of nine virogenic F-111 complementation transformed clones examined. This observation provides the basis of a model for the generation of wild-type recombinants following fusion of F-111 clones.

Contamination of Pharmaceuticals with micro-organisms irrespective of being harmful or objectionable or nonpathogenic, can bring about changes in their physical characteristics, including the breaking of emulsions, the thinning of creams, Fermentation of syrups, and appearance of turbidity or deposit, besides producing possible off ordors and color changes.

The responsiveness of 5 human squamous cell carcinoma (SCC) lines derived from tumors of the epidermis and tongue to 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) was assessed by measuring the induction of the cytochrome P1-450-mediated monooxygenase activity, 7-ethoxycoumarin O-deethylase (ECOD). In 4 of the SCC lines the EC50 for this response was approximately 10(-9)M, whereas in one line the EC50 was 10(-10)M. In each of the less sensitive lines a concentration of 10(-10)M TCDD elicited less than 5% of the maximal enzyme activity. Specific binding of radiolabeled TCDD was detected in the cytosol fraction from all the SCC lines. The relative amount of receptor measured in each line correlated with maximally-induced ECOD activity. The data indicate that human cell lines derived from a target tissue for TCDD toxicity contain the TCDD receptor and show differential sensitivity to TCDD analogous to the murine strain differences in sensitivity regulated by the Ah locus.

One-hit formulas are widely believed to be "conservative" when used to analyze carcinogenesis bioassays, in the sense that they will rarely underestimate risks of cancer at low exposures. Such formulas are generally applied to the lifetime incidence of cancer at a specific site, with risks estimated from animal data at zero dose (control), and two or more additional doses that are appreciable fractions of a maximum tolerated dose. No empirical study has demonstrated that the one-hit formula is conservative in the sense described. The Carcinogenesis Bioassay Database System contains data on 1212 separate bioassays of 308 chemical substances tested at exactly three evaluable doses. These provided sufficient data to examine 8432 specific combinations of cancer site with sex, species, and chemical. For each of these we fitted a one-hit formula to the zero and maximum dose data points, then examined the relation of the fitted curve to the incidence rate observed at the mid-dose, with and without adjustment for intercurrent mortality. Both underestimates and overestimates of risk at mid-dose occurred substantially more often than expected by chance. We cannot tell whether such underestimates would occur at lower doses, but offer six biological reasons why underestimates might be expected. In a high percentage of animal bioassays, the one-hit formula is not conservative when applied in the usual way to animal data. It remains possible that the one-hit formula may indeed be conservative at sufficiently low doses (below the observational range), but the usual procedure, applied to the usual dose range, can be nonconservative in estimating the slope of the formula at such low doses. Risk assessments for regulation of carcinogens should incorporate some measure of additional uncertainty.