Dioxin treatment of rats results in increased in vitro induction of sister chromatid exchanges by alpha-naphthoflavone: an animal model for human exposure to halogenated aromatics

Recent reports have shown that alpha-naphthoflavone (alpha-NF) in vivo enhances the sister chromatid exchange (SCE) frequency in lymphocytes from human populations exposed to cigarette smoke or polychlorinated biphenyls and dibenzofurans. In this study, female Sprague-Dawley rats (9-11 weeks old) were administered a single oral dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and killed 6 days after treatment. Blood cultures were established with or without alpha-NF. The baseline and alpha-NF-induced SCE frequencies were assessed in lymphocytes after a 72-hr culture period. No effect on the SCE baseline frequency (cultures without alpha-NF) was detected in rats exposed to 0-30 micrograms TCDD/kg. However, the SCE frequencies from cultures incubated in the presence of alpha-NF were significantly higher in lymphocytes from rats treated with TCDD. Moreover, delta SCE values (SCE alpha-NF minus SCE baseline) were significantly higher in lymphocytes from rats treated with TCDD than in controls. A dose-dependent increase in delta SCE values was observed between 0 and 3 micrograms TCDD/kg, followed by a plateau at higher doses. This induction pattern closely resembled the induction of the liver microsomal aryl hydrocarbon hydroxylase activity by TCDD. In contrast to TCDD, phenobarbital treatment of rats (75 mg/kg/day) had no effect on alpha-NF-induced SCE frequencies in lymphocytes. Liver microsomes from TCDD-treated rats metabolized alpha-NF at a rate much faster than that of control microsomes. These studies indicate that TCDD-exposed rats provide a useful model to investigate the mechanism of enhanced in vitro induction of SCE frequency in lymphocytes from humans exposed to toxic halogenated aromatics or cigarette smoke.     

Effect on mortality of inhalation injury

A retrospective analysis of 1,018 consecutive admissions with cutaneous burn injury over 32 months was carried out. Mortality probabilities as related to age, per cent TBSA burn, and presence of inhalation injury are presented. Incidence of and mortality from inhalation injury both rose with increasing burn area. The incidence of inhalation injury also rose with advancing age; mortality was lowest in the 5- to 14-year old age group and highest in those more than 59 years of age.     

Rice varieties with similar amylose content differ in starch digestibility and glycemic response in humans

Three high-amylose rice varieties, IR42, IR36, and IR62, with similar chemical composition including amylose content (26.7-27.0%), were cooked under the same conditions and tested for in vitro digestibility as well as blood glucose and insulin responses in healthy human volunteers. The starch-digestion rate and the glycemic and insulin responses were the highest in IR42, followed by IR36 and, then IR62. The differences were not due to unabsorbed carbohydrate but were related to their physicochemical properties, such as gelatinization temperature, minimum cooking time, amylograph consistency, and volume expansion upon cooking. When the three varieties were cooked for their minimum cooking time, they had the same degree of gelatinization and their starch-digestion rates and glycemic responses were similar. We conclude that amylose content alone is not a good predictor of starch-digestion rate or glycemic response. Rice varieties with similar high-amylose contents can differ in physicochemical (gelatinization) properties and this, in turn, can influence starch digestibility and blood glucose response.     

Genetic aspects of immotile cilia syndrome

The genetics of the immotile cilia syndrome has been analyzed in a series of 46 affected individuals from 38 families. Both sexes were equally affected: there were 20 males and 26 females in this series. All patients had upper and lower respiratory disease with chronic sinusitis, otitis, and chronic cough from early childhood. Bronchiectasis was common in older children and adults. Situs inversus occurred randomly, affecting 11 males and 15 females. Biopsies of nasal and bronchial mucosa from these subjects have been investigated by electron microscopy and identified as having specific ultrastructural defects of respiratory tract cilia including deficiencies in outer dynein arms (19), inner dynein arms (3), both inner and outer dynein arms (15), radial spoke defect (5); and microtubular transposition anomaly (4). Segregation analysis of proband sibships was consistent with autosomal recessive inheritance. However, the different ultrastructural defects that underly the immotile cilia syndrome involve presumably different genetic determinants, and the different types have not been analyzed separately. Examination of paternal age and birth order gave no evidence of new autosomal dominant mutation in the series.     

Lack of Major Effects on Mouse Brain Adenosine A1 Receptors of Oral Carbamazepine and Calcium Antagonists

Interaction with adenosine A1 receptors is a possible contributory mechanism to the anticonvulsant effects of carbamazepine (CBZ) and the dihydropyridine calcium antagonists. We measured the binding of [3H]cyclohexyladenosine to adenosine A1 receptors in mouse brain stem, cerebellum, and cortex after oral administration of nifedipine, nimodipine (NMD), and CBZ for 7 days and compared the results with binding in control mice. Equilibrium dissociation constant (Kd) and receptor numbers (Bmax) were calculated using Scatchard and saturation isotherm analyses. Mean Kds (SEM) in control brain stem, cerebellum, and cortex were 2.09 (0.31), 2.39 (0.2), and 3.12 (0.28) nM, respectively. Results of Bmax for the same areas were 188 (26), 280 (24), and 449 (54) fmol/mg protein. Nifedipine (p less than 0.005) and NMD (p less than 0.02) raised the Kd of A1 receptors only in the cerebellum, and CBZ increased cerebellar Bmax (p less than 0.05). These minor effects on A1 receptors in CF1 mice, when given in doses previously shown to have anticonvulsant properties in these animals, do not suggest that alteration in A1 receptor activity is an important mechanism for the anticonvulsant effects of these drugs.     

Cleft closure for the treatment of unhealed perineal sinus

OBJECTIVE: Despite improvements in surgical practice, persistent perineal wound sinus is still a common complication after proctectomy. This study presents the success of a modified cleft closure technique in dealing with this problem. METHODS: From May 1997 patients with a persistent perineal sinus after surgery underwent a cleft closure - similar to that performed for patients with pilonidal sinus disease. RESULTS: Eight patients (6 male, 2 female) with an average age of 52 years underwent a cleft closure for a persistent perineal sinus after surgery. Four patients had undergone a proctocolectomy (ulcerative colitis), 2 an abdominoperineal excision of the rectum (adenocarcinoma) and 2 a proctectomy (1 Crohn's disease, 1 complication of diverticular disease). Symptoms had been present for an average of 41 months (range 5-152 months) and 3 patients had undergone other procedures attempted previously to deal with the problem. The first three patients had the procedure as an inpatient with an average stay of 4.7 days. The next 5 patients had the procedure as a day case (2 local anaesthetic, 3 general anaesthetic). Two patients developed a postoperative wound infection and all but one wound had healed completely by 8 weeks. In this patient the procedure was repeated to achieve healing. There was no other associated morbidity and no postoperative deaths. There have been no recurrences to date. CONCLUSION: Modified cleft closure for persistent perineal sinus is a simple procedure with low morbidity that can be performed under local anaesthetic in the day surgery unit.