Glutathione conjugation of chlorobenzylidene malononitriles in vitro and the biotransformation to mercapturic acids in rats

The glutathione conjugation of 2-chloro-, 3-chloro-, 4-chloro- and 2,6-dichlorobenzylidene malononitrile (chloroBMNs) was investigated in vitro. In incubation mixtures containing rat liver cytosol (9000 g), the decrease in the initial amount of glutathione due to the various chloroBMNs ranged from 40 to 60% and occurred both enzymatically and spontaneously at physiological conditions (37°C, pH7.4). 2,6-DichloroBMN, however, depleted glutathione largely spontaneously (38±3%). The steric hindrance of the two chlorosubstituents probably plays an important role during the glutathione-S-transferase catalyzed reaction.The hydrolysis of the chloroBMNs to the corresponding chlorobenzaldehydes and malononitrile was studied in a mixture of buffer pH 7.4 and ethanol. The rate of hydrolysis of 2,6-dichloroBMN was slower than those of the related chloroBMNs. This means that 2,6-dichloroBMN will be the most stable compound in the presence of water.Only IP administration of 2-chloroBMN (CS) to adult male Wistar rats gave enhancement of urinary thioether excretion. A thioether could be isolated and was identified as the N-acetyl-S-[2-chlorobenzyl]-L-cysteine. The quantity of this benzylmercapturic acid in the urine of rats amounted to 4.4% dose (0.07 mmol/kg, n=12).After IP administration of 2-chloro- and 3-chlorobenzaldehyde to rats benzylmercapturic acid excretion in the urine was found to be 7.6 and 1.1% of the dose, respectively. Administration of the related 4-chloro- and 2,6-dichlorobenzaldehyde, however, resulted in _no urinary mercapturic acid excretion.It is very likely that in rats the initial biotransformation of chloroBMNs is mainly hydrolysis to corresponding chlorobenzaldehydes, leading in the case of 3-chloro-, 4-chloro- and 2,6-dichloroBMN to no mercapturic acid excretion in the urine.Nevertheless, 2,6-dichloroBMN will be the most reactive compound with proteins and therefore the best haptene in comparison with the related chloroBMNs.This work was financially supported by a grant from the Dutch Foundation for Medical Research FUNGO, grant no. 13-28-57     

Comparative efficacy of Hanifin and Rajka''s criteria and the UK working party''s diagnostic criteria in diagnosis of atopic dermatitis in a hospital setting in North India

BACKGROUND: Diagnosis of atopic dermatitis (AD) depends on clinical features because no definitive diagnostic test exists. Criteria proposed by Hanifin and Rajka (Acta Derm Venereol (Stockh) 1980; Suppl 92: 44-47) were acceptable for hospital-based studies but were found not to be suitable for field studies. A UK working party formulated clinical diagnostic criteria that could be used in both hospital and epidemiological settings. Validation studies of the criteria showed widely variable results, probably due to different clinical settings and ethnicity. AIM AND OBJECTIVE: This study was undertaken to validate Hanifin and Rajka's criteria and to assess the comparative efficacy of their criteria and the UK working party's diagnostic criteria in the diagnosis of AD in a hospital setting in North India. SUBJECTS AND METHODS: This study serially included 101 patients with AD and 48 controls of paediatric age group. The study period was from July 2003 to December 2004. RESULTS: Hanifin and Rajka's criteria (sensitivity 96%, specificity 93.75%, positive predictive value 97% (PPV) and negative predictive value (NPV) 91.84%) had a statistical advantage over the UK working party's diagnostic criteria (sensitivity 86%, specificity 95.83%, PPV 97.75% and NPV 76.67%), with a P-value < 0.005.     

IMPOTENCE AND ITS NON-SURGICAL MANAGEMENT

SUMMARY Impotence is a common symptom which can cause considerable distress to both the sufferer and his partner. The use of pharmacotherapy to improve erectile function will continue to increase as safe and effective drugs are developed. However, restoring erectile function should not be the only treatment objective. It is also essential to address personal and emotional factors in the sufferer, conflicts in his relationship with his partner, and sexual problems in his partner, all of which may be instrumental in causing or maintaining the presenting impotence. We advocate a combined approach with appropriate medical treatment and sex and couple therapy     

Treatment of stones in caliceal diverticula: extracorporeal shock wave lithotripsy versus percutaneous nephrolitholapaxy.

Stones in caliceal diverticula may cause symptoms for which treatment is indicated. Both extracorporeal shock wave lithotripsy (ESWL) and percutaneous nephrolitholapaxy (PNL) are recommended. We have evaluated the results of ESWL treatment of stone-containing caliceal diverticula and compared these with the results obtained by percutaneous surgery. In the ESWL group, 15 patients were treated with an electromagnetic lithotriptor (Siemens Lithostar). After 3 months, plain abdominal X-rays revealed that only 2 patients were both stone-free and symptom-free. Of the 13 patients with residual fragments, 7 had no symptoms. The remaining 6 were treated by a lower pole resection (n = 3), a percutaneous procedure (n = 2) and long-term administration of antibiotics (n = 1). Sixteen patients were treated percutaneously. Puncture failed in 3 and they underwent a lumbotomy. In the remaining 13 patients the stones were reached by direct puncture (n = 12) or via an adjacent calix (n = 1). After 3 months, 10 patients were stone-free and had no symptoms. Morbidity consisted of post-operative bleeding (n = 3) and high fever (n = 1). It was concluded that caution should be exercised in the treatment of stone-containing caliceal diverticula. Only in symptomatic cases is treatment indicated and ESWL is the first choice. If ESWL fails (residual stones and persistent symptoms), PNL should be performed, although it is associated with a higher morbidity rate.     

A midface swelling in a child – A possible diagnostic dilemma

A lump on the midface of a child can pose as a diagnostic dilemma. There is a wide variety of possible differential diagnoses, ranging from simple benign conditions such as a sebaceous cyst, dermoid cyst, lipoma, neuroma and neurofibroma, to potentially devastating conditions such as odontogenic myxoma.A case of a child in which the formulation of a definite diagnosis was clinically and histologically challenging is presented.