The Crystal and Molecular Structures of N4-(5-Bromosalicylidene)-N1-(3,4-dimethyl-5-isoxazolyl)sulfanilamide

The structure of the title compound was determined by X-ray analysis. Medicinal compounds with Schiff base structure have been widely synthesized and investigated in recent years. The functional group-CH?N- of the Schiffbases has been shown to have considerable biological importance¹⁾ . Many compounds with such a structure have important analgesic, anti-inflammatory, antibiotic, antimicrobial and especi ally anticancer activities^2-8). Medicinal sulphonamides, having a primary amino group in their molecule, react very easily with salicylaldehyde or its derivatives⁹⁾. Information about the exact structure of the reac tion products is rather scanty, however, even though the formation reaction of the base has been utilized in many analytical pr ocedures for medicinal sulphonamides^9-12) and many such Schiff bases have been found to possess good bac teriostatic properties^13-14).     

Characterization of nephropathy induced by immunization with high molecular weight dextran

Background. Injection of DEAE dextran into Lewis rats can produce proteinuria and has been reported as a model of IgA nephropathy. Methods. Cationic diethyl aminoethyl (DEAE) dextran of molecular weight 500 KDa was injected into male Lewis rats. After a pre-immunization period of 3 weeks, the animals were divided into two groups: group 1 (n=14) received daily i.v. injections of 3.5 mg of antigen, group 2 (n=14) was injected with 1.5 mg three times per week for a total period of 6 weeks. I.v. treatment was initiated with gradually increasing doses of DEAE dextran in both groups for 1 week, after which the maintenance dose was reached. Results. We observed the appearance of proteinuria in a nephrotic range after 5 weeks of i.v. injections in group 1 (urinary excretion: 332±83 mg/24 h, controls: 53±14 mg/24 h). In group 2, the proteinuria was almost equal to protein excretion of healthy rats of the same weight (67±20 mg/24 h). The serum and urine creatinine were normal. By light microscopy of kidney biopsies, the presence of focal and segmental proliferation of mesangial cells after 6 weeks of i.v. injections was identified. Immunohistochemistry revealed no deposition of IgA, IgM, IgG, or C3. Using anti-ED1 antibodies, there was no evidence of interstitial infiltration of monocytes/macrophages after 6 weeks of i.v. injections. Staining for proliferating cell nuclear antigen (PCNA) did not show the presence of proliferating cells either in glomeruli or in the interstitium. Staining with FITC-WGA lectin revealed focal and segmental loss of the negative charge in the capillary wall. By electron microscopy there was deposition of dextran in the basal membrane and segmental and focal damage of the podocyte foot processes. As the chemokine RANTES may be involved in glomerular injury, we examined the kidneys of proteinuric and non-proteinuric rats for the presence of RANTES. By indirect immunofluorescence only the proteinuric rats showed RANTES deposition in mesangium. Conclusions. Injection of rats with DEAE dextran leads to dose-dependent proteinuria without deposition of immune complexes but with podocyte damage. This is associated with local expression of the chemokine RANTES which may play a role in proteinuria of glomerular disease.     

Cost-effectiveness analysis of guidelines for antihypertensive care in Finland

Background  

Hypertension is one of the major causes of disease burden affecting the Finnish population. Over the last decade, evidence-based care has emerged to complement other approaches to antihypertensive care, often without health economic assessment of its costs and effects. This study looks at the extent to which changes proposed by the 2002 Finnish evidence-based Current Care Guidelines concerning the prevention, diagnosis, and treatment of hypertension (the ACCG scenario) can be considered cost-effective when compared to modelled prior clinical practice (the PCP scenario).     

SCL-25 and recognition of mental disorders reported by primary health care physicians

A marked proportion of primary care patients have mental disorders and problems that remain unrecognized by the patients and their general practitioners. There is furthermore a great variation in the physicians’ ability to detect mental disorders. The aim of the present study was to find out the overall prevalence of mental disorders among patients receiving primary health care. The material consisted of 1000 randomly selected adult patients attending primary care facilities in Turku. The mental disorders were assessed by using the Symptom Checklist (SCL-25) and by general practitioners. According to the SCL-25, one fourth of the sample had a mental disorder. Only two fifths of them could be identified by the general practitioners.     

A T-helper cell epitope overlaps a major B-cell epitope in human papillomavirus type 18 E2 protein.

Cultivated CD4+ T-helper cells from two patients with cervical adenocarcinoma showed responses to a peptide EKTGILTVTYHSETQRTK derived from an E2 protein of human papillomavirus type 18 (HPV 18), but not to a corresponding HPV 16 peptide (HKSAIVTLTYDSEWQRDQ). Serum antibodies in the HPV 18 peptide were also demonstrated in these patients. The GILT motif resembles a common pattern present in many T-cell epitopes, and is located at the beginning of an 11-amino acid-long A-helix structure close to the carboxyterminal end of HPV 18 E2. We conclude that two epitopes (a T-helper cell epitope and a B-cell epitope) overlap in the HPV 18 E2.     

Behavioral and enzymatic interactions between benzyl alcohol and ethanol.

Acute IP injection of benzyl alcohol but not benzaldehyde (0.5 g/kg) caused aversion to voluntary drinking of 5% ethanol solution by male rats with preference to ethanol. Benzyl alcohol noncompetitively inhibited hepatic alcohol dehydrogenase of rats maintained for a short term on 5% ethanol compared to control. The results suggest an adverse interaction between benzyl alcohol and ethanol underlying the observed aversion to ethanol.     

Serological responses to human papillomavirus type 6 and 16 virus-like particles in patients with cervical neoplastic lesions.

Serum samples from 36 cervical carcinoma patients, 33 patients with high-grade squamous intraepithelial lesions, and 31 cytologically normal women were tested by enzyme-linked immunosorbent assay (ELISA) using human papilloma virus type 6 (HPV 6) and HPV 16 virus-like particles as antigens. Forty serum specimens from 1-year-old children were used to assign cutoff points. When serum samples from the subjects infected with HPV 16 were tested in an HPV 16 ELISA detecting immunoglobulin A (IgA), IgG, and IgM binding, 61% showed IgA, 44% showed IgG, and 39% showed IgM reactivity. Of HPV 6- or 11- or HPV 18-infected subjects. fewer than 17% showed IgA or IgG responses and 33% showed IgM reactivity. In contrast, 13% showed IgA, 10% showed IgG, and 16% showed IgM reactivity in the HPV DNA-negative controls. The results suggest that the IgA and IgG responses are HPV 16 specific and the IgM response is cross-reactive to different HPV types. On the other hand, the serological responses to HPV 6 did not differ in the patient and control groups. The percentages of patients positive for both IgA and IgG antibodies were significantly higher in the groups with high-grade squamous intraepithelial lesions (12% [4 of 33]; P = 0.04) and cancer (17% [6 of 36]; P = 0.02) than in the healty women (0% [0 of 31]), and the percentages for either IgA or IgG were higher for the cancer group (47% [17 of 36]; P = 0.01) than in the normal group (19% [6 of 31]). Most sera positive for IgA and IgG in the patient groups showed higher titers than those in the normal group. All these results suggest that high IgA and IgG responses are good indicators for estimating HPV 16 infection.     

Heteroplasmic Segregation Associated with Trisomy-9 in Cultured Human Cells

In cybrid cells carrying the mitochondrial A3243G MELAS mutation, which were also heteroplasmic for the G12300A suppressor mutation, we observed a transient episode of heteroplasmic instability, resulting in a wide diversification in G12300A heteroplasmy levels and a shift in the average heteroplasmy level from 11 to 29%. These cells were found to be trisomic for chromosome 9, whereas a minority of cells that retained disomy-9 showed no instability. Coculture experiments implied that trisomy-9 cells exhibited a significant growth advantage, but neither heteroplasmy levels, respiratory phenotype nor trisomy-9 itself had direct selective value under standard culture conditions. Mitochondrial nucleoid number was the same (50–100) in cells that had or had not experienced transient heteroplasmic instability, but 1–2 orders of magnitude less than the segregation number in such cells. These findings support the idea that mtDNA partition is under nuclear genetic control, and implicate a locus on chromosome 9 in this regulation.