Squamous metaplasia of tracheal submucosal glands induced by benzo[a]pyrene and vitamin A deficiency

The effects on tracheal glands of benzo[a]pyrene and of vitaminA deficiency were examined in explants derived from normal andvitamin A deficient hamsters, respectively. Both treatmentscaused hyperplasia and squamous metaplasia of the tracheal glands.It is suggested that a proportion of respiratory tract lesionsmay originate in tracheal glands.     

Preventing HIV transmission to children: quality of counselling of mothers in South Africa

AIM: To assess the quality of counselling provided to mothers through the programme to prevent mother-to-child transmission (PMTCT) of HIV in South Africa. METHODS: Structured observations of consultations and exit interviews with 60 mothers attending clinics at three purposively selected PMTCT sites across South Africa were conducted. RESULTS: Twenty-two counsellors were observed. The general quality of communication skills was very good, and 73% of HIV-negative mothers were informed of the advantages of exclusive breastfeeding (EBF). However, only one of 34 HIV-positive mothers was informed about the possible side effects of nevirapine, and none was told what to do when it occurred. Only two HIV-positive mothers were asked about essential conditions for safe formula feeding before a decision about an infant feeding option was made. None of the 12 mothers choosing to breastfeed was shown how to position the baby correctly on the breast or asked whether they thought EBF was feasible. Fewer than a quarter of mothers expressed confidence in performing the actions required, and 85% could not define the term EBF. CONCLUSION: The poor quality of counselling in the PMTCT programme will reduce the effectiveness of these programmes. As they are being scaled up, there needs to be far more attention paid towards the counselling of mothers, especially with regards to optimal infant feeding.     

Anti-staphylococcal activity and mode of action of clofazimine

OBJECTIVES: Infections caused by Staphylococcus aureus might be treated with agents whose primary indications are for other infections. Clofazimine, an established anti-mycobacterial drug, could be such a candidate. However, the anti-staphylococcal properties of clofazimine have not been fully described and its mode of action, possibly involving inhibition of both RNA polymerase and a membrane-located target, has not been explored in detail. We have now conducted experiments to address these issues. METHODS: Using established procedures, we examined the activity of clofazimine against a range of clinical isolates of S. aureus and determined whether it was bactericidal, exhibited a post-antibiotic effect (PAE), or interacted synergically with other agents. The potential for emergence of clofazimine-resistant mutants was also examined. Mode of action studies involved macromolecular synthesis assays, cross-screening against rifampicin-resistant mutants, susceptibility of RNA polymerase to clofazimine in vitro and several methods to detect drug-induced membrane damage. RESULTS: Clofazimine demonstrated good anti-staphylococcal activity encompassing MSSA, MRSA and GISA. It was bactericidal and resistant mutants could not be isolated. Clofazimine did not exhibit a PAE and failed to act synergically with other drugs. No evidence for specific inhibition of RNA polymerase was obtained. Clofazimine caused non-specific inhibition of DNA, RNA and protein synthesis, consistent with membrane-damaging activity that was detected in three independent assays for membrane disrupting agents. CONCLUSIONS: Clofazimine is a potent anti-staphylococcal agent. It appears to be a membrane-disrupting agent and does not inhibit RNA polymerase.     

Fluoxetine attenuates thermal hyperalgesia through 5-HT1/2 receptors in streptozotocin-induced diabetic mice

Diabetic neuropathic pain, an important microvascular complication in diabetes mellitus, is recognised as one of the most difficult types of pain to treat. A lack of understanding of its aetiology, inadequate relief, development of tolerance and potential toxicity of classical antinociceptives warrant the investigation of newer agents to relieve this pain. The aim of the present study was to explore the antinociceptive effect and possible mechanism of action of a serotonin reuptake inhibitor, fluoxetine, in streptozotocin-induced diabetic mice. Four weeks after a single intraperitoneal injection of streptozotocin (200 mg/kg), mice were tested in the tail-immersion and hot-plate assays. Diabetic mice exhibited significant hyperalgesia compared with control mice. Fluoxetine (10 and 20, but not 5 mg/kg, i.p.) injected into diabetic mice produced an antinociceptive effect in both the tail-immersion and hot-plate assays. The percentage maximum possible effect (% MPE) produced by fluoxetine (20 mg/kg, i.p.) was significantly lower in diabetic mice than in control mice. The antinociceptive effect of fluoxetine (20 mg/kg) in diabetic mice was dose-dependently potentiated by pindolol (5 and 10 mg/kg, i.p., a selective 5-HT(1A/1B) receptor antagonist), attenuated by ritanserin (1 and 2 mg/kg, i.p., a selective 5-HT(2A/2C) receptor antagonist) and remained unaffected by ondansetron (1 and 2 mg/kg, i.p., a selective 5-HT(3) receptor antagonist) in both test systems. These results suggest that fluoxetine-induced antinociception primarily involves serotonin pathway modulation through 5-HT(1) and 5-HT(2) receptors, but not through 5-HT(3) receptors, in the chronic pain associated with streptozotocin-induced diabetic neuropathy. Further, the potentiation of the antinociceptive effect of fluoxetine by pindolol indicates the usefulness of a combination of an antidepressant and a 5-HT(1A/1B) receptor antagonist in the treatment of diabetic neuropathic pain in humans.     

Darier's disease following radiotherapy for carcinoma of cervix

Darier-White disease is due to a defect in the ATP2A2 gene encoding the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA2b). We report a case of carcinoma cervix in whom Darier's disease manifested after the initiation of radiation therapy. Conventional cytogenetics on peripheral blood revealed non-clonal constitutional autosomal and X chromosome abnormalities suggesting radiation induced gene toxicity. Occurrence of Darier's disease in our case could be due to treatment induced sustained differentiation in the Darier's affected skin by an unknown mechanism. Late onset or sporadic Darier's disease is the other possibility.     

Cutaneous reactions in patients with solitary cysticercus granuloma on phenytoin sodium

Several medical conditions are believed to be associated with an increased risk of cutaneous adverse reactions to anti-epileptic drugs. The aim of this study was to study the frequency and nature of cutaneous reactions in a cohort of patients being treated with phenytoin sodium for seizures, who were divided into those with a solitary cysticercus granuloma (SCG) and those with a condition other than SCG, to determine if the presence of SCG increases the risk of cutaneous adverse reaction to phenytoin. A cohort of 117, consecutively begun on treatment with phenytoin for seizure control, were followed up prospectively for the development of cutaneous reactions. There were 63 patients with SCG upon imaging and 54 patients to whom phenytoin was administered for seizures due to causes other than SCG or multiple neurocysticercosis. Cutaneous reactions were significantly more common (p = 0.02) in patients with SCG (9/63 patients; 14.3%) than in controls (2/54 patients; 3.7%). The spectrum of skin reactions in patients with SCG included benign skin rash (n = 3), anticonvulsant hypersensitivity syndrome (n = 4), Stevens-Johnson syndrome (n = 1), and urticaria (n = 1). Individuals with seizures due to SCG have a high incidence of cutaneous adverse reactions to phenytoin. This fact should be kept in mind when initiating them on treatment with this anti-epileptic drug.