Biochemical and ultrastructural alterations produced by miconazole and econazole in Trypanosoma cruzi

Miconazole and econazole, two fungicide imidazole derivatives, completely inhibited growth of Trypanosoma cruzi (Tulahuen strain) at concentrations of about 20 muM. Culturing of T. cruzi in the presence of lower doses of imidazole derivatives produced: decrease of 5,7-diene sterol content in epimastigotes (including ergosterol); disappearance of the nuclear chromatin, vacuolization and decrease in the electron density of the cytoplasm; selective surface alterations as revealed by an increased response to wheat-germ- and phytohemagglutinin. At variance with the effect of miconazole on Candida (De Nollin et al. (1977) Antimicrobial. Agents Chemother. 11, 500-513), miconazole and econazole, under the experimental conditions used, did not increase the rate of hydrogen peroxide generation by T. cruzi.     

Delayed-type hypersensitivity elicited by synthetic peptides complexed with Mycobacterium tuberculosis hsp 70.

Four synthetic peptides bearing dominant CD4+ T-cell epitopes of the 19,000 and 38,000 MW proteins of Mycobacterium tuberculosis were used to provoke a delayed-type hypersensitivity (DTH) reaction in mice previously immunized with recombinant 19,000 and 38,000 MW proteins. It was found that an effective enhancement of the DTH reaction was obtained if the peptides were administered as a complex with M. tuberculosis hsp 70 protein. The increase in reactivity was not obtained when hsp 70 and peptide were co-injected at the same site, but not in complex, or when the specific peptide was displaced from the complex by an irrelevant peptide with high capacity to bind hsp 70. One of the antigenic peptides whose capacity to complex with hsp 70 is low, failed to show the enhancement of DTH when injected together with hsp 70.     

Anal polypoid tumor formation as the form of presentation of rectal gastric heterotopia]

Heterotopic gastric epithelium occurs in all portions of the alimentary tract, but it is extremely rare in the rectum. The authors report the finding of a pedunculated anal polyp in a 9-year-old girl with a six-month history of rectal bleeding. Microscopically, the polyp consisted of epithelium of the fundic type. Both the age of the patient and the finding of heterotopic epithelium of the fundic type alone supports a congenital malformation and not an inflammatory condition.     

Alterations in the superoxide dismutase gene of an isoniazid-resistant strain of Mycobacterium tuberculosis.

Genetic analysis of a set of six Mycobacterium tuberculosis strains differing in virulence for the guinea pig revealed an altered restriction enzyme fragmentation pattern associated with the superoxide dismutase (SOD) gene in a low-virulence, isoniazid-resistant strain. In addition, it was found that the SOD enzyme produced by the isoniazid-resistant strain differed in its electrophoretic mobility from the SOD of other M. tuberculosis strains. Detailed analysis of these strain-specific differences showed that the restriction fragment length polymorphism resulted from the presence of a copy of a repetitive element 552 bp upstream of the SOD gene and that the anomalous electrophoretic mobility arose from a single nucleotide change, resulting in replacement of an aspartic acid residue by histidine in the SOD enzyme of the isoniazid-resistant strain. Possible relationships between genetic changes and strain-dependent differences in virulence are discussed.     

Changes in immunologic response in tonsillectomized children. I. Immunosuppression in recurrent tonsillitis.

The possible immunoregulatory role of the tonsils was studied by determining immunoglobulins IgG, A, M, E and factors C'3, C'4 and PFB of the complement system before and after tonsillectomy. The synthesis in vitro of IgG and IgM by lymphocytes stimulated with pokeweed mitogen was also measured. There were statistically significant differences between pre and post-operative levels of serum IgG, IgA and IgM, which decreased after surgery. Practically no change in the mean values of IgE and no significant differences in the levels of serum C'3, C'4, and PFB, were found. The in-vitro synthesis of both immunoglobulins (IgG, IgM) by lymphocytes increased significantly after tonsillectomy. Our results suggest that not only does tonsillectomy have no counterproductive effect on the immune system, but that, on the contrary, it seems to improve the immune response, since it appears to unblock the suppression to which the immune system was subject.     

Do weekly and fast-rotating shiftwork schedules differentially affect duration and quality of sleep?

 Characteristics of shiftwork schedules can have distinct impacts on workers’ sleep. This report presents comparisons of the effects of two different shiftwork schedules on duration and quality of the main sleep episodes in comparable worker populations at two different petrochemical plants. No significant differences were found for sleep duration in comparing the two plants. However, within each plant’s shift cycles, morning and night shifts showed shorter sleep durations than all other workdays and days off. Quality of sleep was perceived as lowest for night shifts of both plant schedules, and of lesser quality for weekly than for fast-rotating shifts. These results support recommendations for reducing the number of consecutive nights of shiftwork. However, before recommending any optimal shift schedule, interactions of sleep duration and quality with shift schedules need much further evaluation. Received: 18 December 1995/Accepted: 18 July 1996     

Endothelial Vascular Function in Hypertensive Patients After Renin—Angiotensin System Blockad

It is unclear whether single and combined pharmacologic inhibition of the renin-angiotensin-aldosterone system have similar effects on endothelial function and blood pressure (BP). The authors evaluated 63 hypertensive patients divided into 4 groups (hydrochlorothiazide 25 mg/d; irbesartan [IRBE] 150 mg/d; quinapril [QUIN] 20 mg/d; or IRBE 150 mg/d + QUIN 20 mg/d) and 25 healthy normotensive subjects (normal) followed for 12 weeks. Endothelium-dependent dysfunction measured as flow-mediated dilation at Weeks 0 and 12 were: normal, 11.5%±2.4% vs 13.5%±2.0%; hydrochlorothiazide, 7.3%±2.0% vs 12.8%±3.1%; QUIN, 7.2%±2.8% vs 13.2%±2.1%; IRBE, 7.1%±2.8% vs 13.0%±2.9%; and IRBE + QUIN, 7.5%±1.9% vs 12.8%±3.0%. Nitroglycerin-mediated responses were: normal, 26.0%±1.9% vs 24.0%±2.5%; hydrochlorothiazide, 17.0%±2.2% vs 18.3%±2.6%; QUIN, 17.8%±3.2% vs 23.4%±3.0%; IRBE, 16.8%±3.6% vs 24.7%±2.0%; and IRBE + QUIN, 17.3%±3.0% vs 25.1%±2.5%. Antihypertensive therapy restored BP to normal and improved the endothelium-dependent and -independent dysfunction after renin-angiotensin-aldosterone system blockade. In a further finding, the combined effect of angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor blockade was not superior to the action of either of these treatments separately.     

A REPRODUCIBLE MODEL OF CHRONIC REJECTION IN RAT RENAL ALLOGRAFTS

A reproducible animal model is essential for the study of the pathogenesis of chronic rejection. This study investigates: (i) the optimal pre-transplant blood transfusion conditions to induce tolerance in a strongly rejecting rat kidney allograft model (Dark Agouti to Albino-Surgery) and avoiding post-transplant immunosuppression; (ii) the functional and histological changes that occur in long-term surviving kidneys and their similarity to chronic rejection; and (iii) the maintenance of tolerance. Prolonged survival occurred after administration of at least two donor blood transfusions with concomitant cyclosporin A (5 mg/kg per day). The time-span between transfusions appeared to be critical: 4 days was more effective than 2 or 7 days. Ineffective treatment led to death within the first 2 weeks post-transplant with histological evidence of acute graft rejection. Seventy-five per cent of long-term survivors experienced impaired renal function in the first week which improved spontaneously and remained stable in 93% of the surviving animals after 100 days and in 668 after 200 days. The morphology of long-term allografts was extremely variable from minor to extensive tubular atrophy, interstitial fibrosis, glomerular hypertrophy, focal and segmental glomerulosclerosis and vascular changes. Glomerular hypertrophy occurred in uninephrectomized controls and probably denoted a response to uninephrectomy. Glomerulosclerosis increased with time and was absent in controls. Although chronic damage was evident, the rats remained tolerant to fresh donor skin. Replacement of the original kidney allograft with a fresh donor kidney resulted in 70% survival. These second grafts showed less severe renal dysfunction and morphological damage than the original allografts in the long-term follow up.