Percutaneous absorption of hexachlorophene in rats, guinea pigs and pigs

A comparative study of the percutaneous absorption of hexachlorophene (HCP) was undertaken in rats, guinea pigs and pigs. [14C]Hexachlorophene ([14C]HCP) was applied evenly over the shaved back of the animals at a dose of 40 microgram/cm2 skin surface. Urine and feces were collected at 24-h intervals for 5 days from animals kept in metabolism cages. Different methods were used for quantitating the percutaneous absorption of HCP. This study showed that skin permeability to HCP decreased in the following order: rat, guinea pig and pig. The permeability characteristics of the pig skin to topically applied HCP were comparable to the published human data. We suggest that pig may be a suitable animal model for studying the percutaneous absorption of antimicrobial drugs.     

Effect of the experimental chemopreventative agent, glucarate, on intestinal carcinogenesis in rats

Dietary calcium glucarate was previously shown to protect effectivelyagainst chemically-induced mammary, lung, liver and skin carcinogenesisin rodents, whereas the negative dietary calcium control, calciumgluconate, had no effect. In the present study the chemopreventativeactivity of dietary calcium glucarate was evaluated in the azoxymethaneintestinal carcinogenesis model using the Fischer strain rat.The protocol limited the duration of azoxymethane treatmentto 3 weeks to permit the evaluation of the separate effectsof glucarate on the initiation and promotion phases. Controlrats, treated with azoxymethane and maintained on a low fatchow diet throughout the 32-week experiment had an intestinaladenocarcinoma incidence of 55%, with an equal incidence of27.7% in the small and large intestines. There was no significantdifference between this control group and a negative calciumcontrol group fed 128 mmol/kg chow of calcium as calcium gluconate.In contrast to these two control groups, supplementation ofthe diet of azoxymethane-treated rats with 128 mmol/kg dietof calcium glucarate during both the initiation and promotionphases significantly inhibited the overall induction of adenocarcinomasin the intestine, the incidence in the entire intestine andin the small and large intestines being 11.8, 5.8 and 5.8%,respectively. When fed only during the initiation phase, theinhibition again was statistically significant, the correspondingvalues being 11.8%, 5.8 and 5.8%. When calcium glucarate wasfed during the promotion phase, a statistically significantinhibition of adenocarcinoma induction was observed only inthe colon where the incidence was 5.5%. Weight gain was similarin all groups. These and related data indicate that dietaryglucarate exerts a significant inhibitory effect on azoxymethane-inducedintestinal and in particular colon carcinogenesis in the rat,decreasing their incidence and size and reducing their metasticpotential.     

Evidence for local neural modulation of sympathetic influences on the feline bladder

It is known that resting conditions of bladder volume and pressure influence the response of the cat bladder in situ to sympathetic nerve stimulation. We observed that this was also true when the bladder was decentralized by cutting the sacral spinal roots, the hypogastric nerves, and one sympathetic chain. Under these conditions, elevating intravesical pressure by means of a reservoir of large surface area connected to the bladder resulted in an enhancement of the beta-adrenoceptor-mediated dilatory component of the response to stimulation of either the sympathetic chain or the hypogastric nerves. In order to test whether this enhancement was the result of mechanical or end-organ effects, the change in response to ia isoprenaline was also evaluated. Although the response to isoprenaline was modestly (2-fold) increased at intravesical pressures of 20–30 cm H₂O, the increase in response to hypogastric nerve stimulation (8.5-fold) was significantly greater. The increase in response to sympathetic chain stimulation was intermediate, but only one chain was stimulated. Thus, end-organ or physical factors have some influence on the dilatory response. However, there must be another modulatory component that exerts an effect on the neurally mediated dilatation but not on that produced by isoprenaline. This modulation appears to be activated by bladder distension and to be directed at the nerves, either on their terminals or at the intramural or plexus ganglia. Candidate mechanisms are humoral compounds (e.g., eicosanoids) or a local neural network.     

Adrenocortical suppression by synthetic corticosteroid drugs: a comparative study of prednisolone and betamethasone.

1 Single-dose studies were conducted to investigate the relative potency of prednisolone and betamethasone in suppressing adrenocortical function. 2 Betamethasone produced more profound suppression of plasma cortisol than an equivalent anti-inflammatory dose of prednisolone.     

Gamma glutamyl transpeptidase levels in arthritis: a correlation with clinical and laboratory indices of disease activity.

Gamma glutamyl transpeptidase (GGTP) was measured in 62 patients with rheumatoid arthritis (RA) and 27 with osteoarthrosis (OA). The values for GGTP were significantly higher in the subjects with RA compared with the OA group. The prevalence of elevation of GGTP was higher in the RA subjects (77%) than in the OA patients (33%). Levels of GGTP correlated significantly with a number of objective indices of activity of RA in a separate group of 28 patients. Following treatment with penicillamine, GGTP levels showed a significant drop towards normal levels.