Chemical modifications of band 3 protein affect the adhesion of Plasmodium falciparum-infected erythrocytes to CD36

The role of the erythrocyte anion exchanger, band 3 protein (AE1), in the adhesion of Plasmodium falciparum-infected erythrocytes to CD36 and thrombospondin (TSP) was studied. Two specific anion exchange inhibitors that bind covalently to different regions of the band 3 molecule affected cytoadherence in dissimilar ways. Modification of lysine 539 by diisothiocyanostilbene sulfonic acid (DIDS) resulted in a significant reduction in the adhesive properties of parasitized erythrocytes for CD36, but not TSP, whereas treatment with fluorescein-5-maleimide, which modifies lysine 430, was without effect on both TSP and CD36 binding. The adhesive properties of the DIDS binding region (DBR) was demonstrated by competition experiments using synthetic peptides and by direct interaction of such peptides with CD36 transfected CHO cells. The results suggest that host membrane proteins such as AE1 contribute to the adhesion of malaria-infected erythrocytes to CD36.     

Coxsackievirus-mediated hyperglycemia is enhanced by reinfection and this occurs independent of T cells

The induction of autoimmunity by viruses has been hypothesized to occur by a number of mechanisms. Coxsackievirus B4 (CB4) induces hyperglycemia in SJL mice resembling diabetes in humans. While virus is effectively cleared within 2 weeks, hyperglycemia does not appear until about 8-12 weeks postinfection at a time when replicative virus is no longer detectable. In SJL mice, reinfection with CB4 enhanced the development of hyperglycemia. As predicted, the immune system responded more rapidly to the second infection and virus was cleared more swiftly. However, while infiltrating T cells were found within the pancreas, depletion of the CD4 T cell population prior to secondary infection or use of CD8 knock-out mice had no effect on the development of virus-mediated hyperglycemia. In conclusion, enhanced hyperglycemia induced by CB4 occurs independent of the T cell response.     

Hemostatic coronary risk factors in a healthy population of Maracaibo,Venezuela

The purpose of the present work was to determine the plasma concentrations of fibrinogen and Von Willebrand Factor (VWF) as well as platelet aggregation, in an apparently healthy population of 306 men and 41 women, 33 to 65 years of age, workers of the national oil industry (PDVSA, Maracaibo), as a base investigation in a 5-year prospective national collaborative study. The participants were previously subjected to a thorough clinical examination with cardiovascular evaluation and laboratory tests. Clottable fibrinogen and VWF concentrations were determined in platelet poor plasma, the last one by immunoclectrophoresis, and a multimeric analysis of VWF was performed on those plasmas with concentrations higher than 150 U/dL by SDS agarose electrophoresis, followed by cellulose membrane transference. Platelet aggregation was studied in platelet rich plasma with no addition of stimulants and after collagen and ristocetin were added. Forty per cent of men and 65.8% of women, showed fibrinogen concentrations above 300 mg/dL (p < 0.01) and 12.2% of men and 15.4% of women had VWF values higher than 150 U/dL, with normal multimeric distribution. Fourteen individuals presented spontancous platelet aggregation and increased aggregation in 12 and 13 of them, after induction with collagen and ristocetin respectively. Comparing these findings with those of previous collaborative studies from other countries, the present results could mean that an important proportion of the population here studied, could be at risk for a future coronary event; however, as these are the base findings in Maracaibo, the significance of our results will be better evaluated at the end of the five year study.     

Comparison of the allergenicity and Ole e 1 content of 6 varieties of Olea europaea pollen collected during 5 consecutive years.

BACKGROUND: Numerous varieties of Olea europaea have been described in Mediterranean countries. OBJECTIVE: To investigate the immunochemical characteristics of 6 varieties of Olea europaea collected during 5 consecutive years. METHODS: The varieties Carrasquefio, Manzanillo, Acebuche (wild olive), Hojiblanco, Picual, and Nevado were analyzed. Pollen samples from each variety were collected for 5 consecutive years from the same cultivars by trained personnel. The antigenic and allergenic profiles of these extracts were evaluated by means of sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot using the serum of 29 O. europaea-allergic individuals. Ole e 1 was measured using enzyme-linked immunosorbent assay and purified Ole e 1 and rabbit polyclonal antibodies. Allergenic potency was determined using enzyme-linked immunosorbent assay inhibition and is expressed in histamine equivalent prick units per gram of raw material. RESULTS: Hojiblanco and Acebuche had the lowest mean +/- SD Ole e 1 content in the 5 years (0.045 +/- 0.029 and 0.059 +/-0.031 microg/microg of freeze-dried material, respectively). The variety with the highest mean +/- SD Ole e 1 content was Picual (0.19 +/-0.075 microg/microg). Hojiblanco had the lowest total biological potency throughout the study. A positive correlation was obtained between rainfall in the winter months and total allergenicity of the 6 varieties. CONCLUSIONS: The different varieties of O. europaea pollen demonstrated great differences in allergenic potency and Ole e 1 content. These differences were maintained throughout the study, suggesting that they are due to genetic differences intrinsic to the varieties, although certain climatic effects may also play a role.     

Zinc Nutritional Status in a Series of Children with Chronic Diseases: A Cross-Sectional Study

Background: Zinc is an essential trace element for the normal growth and development of human beings. The main objective was to evaluate the nutritional status of zinc and its association with nutritional indicators in a series of children with chronic diseases. Methods: The prevalence of patients with dietary zinc deficiency or deficit zinc intake (<80% DRI: dietary reference intake) was analyzed through prospective 72 h dietary surveys, and serum zinc deficiency or hypozincemia (≤70 µg/dL in children under 10 years of age in both sexes and in females older than 10 years and <74 μg/dL in males older than 10 years) was measured through atomic absorption spectrophotometry. The participants were classified according to their nutritional status by body mass index (BMI). Results: Mean serum zinc level in obese (87 µg/dL), undernourished (85 µg/dL), and eutrophic children (88 µg/dL) were normal, but in the undernutrition (60% DRI) and eutrophic (67% DRI) groups the mean dietary zinc intake was low compared to that in the obesity group (81% DRI). There were different associations between nutritional parameters, dietary zinc intake, and serum zinc. All patients with hypozincemia had dietary zinc deficiency. Conclusions: In the whole series, 69% of participants showed a zinc intake lower than recommended and might be at high risk of zinc deficiency.     

β-Cyclodextrin tetradecasulfate/tetrahydrocortisol±minocycline as modulators of cancer therapies in vitro and in vivo against primary and metastatic lewis lung carcinoma

Tetrahydrocortisol, -cyclodextrin tetradecasulfate, and minocycline used alone or in combination are not very cytotoxic toward EMT-6 mouse mammary tumor cells growing in monolayer. Tetrahydrocortisol (100 M, 24 h) and -cyclodextrin tetradecasulfate (100 M, 24 h) protected EMT-6 cells from the cytotoxicity of CDDP, melphalan, 4-hydroperoxycyclophosphamide, BCNU, and X-rays under various conditions of oxygenation and pH. Minocycline (100 M, 24 h) either had no effect upon or was additive with the antitumor alkylating agents or X-rays in cytotoxic activity toward the EMT-6 cells in culture. The combination of the three modulators either had no effect upon or was to a small degree protective against the cytotoxicity of the antitumor alkylating agents or X-rays. The Lewis lung carcinoma was chosen for primary tumor growth-delay studies and tumor lung-metastases studies. Tetrahydrocortisol and -cyclodextrin tetradecasulfate were given in a 1:1 molar ratio by continuous infusion over 14 days, and minocycline was given i.p. over 14 days, from day 4 to day 18 post tumor implantation. The combination of tetrahydrocortisol/-cyclodextrin tetradecasulfate diminished the tumor growth delay induced by CDDP and melphalan and produced modest increases in the tumor growth delay produced by cyclophosphamide and radiation. Minocycline co-treatment increased the tumor growth delay produced by CDDP, melphalan, radiation, bleomycin, and, especially cyclophosphamide, where 4 of 12 animals receiving minocycline (14×5mg/kg, days 4–18) and cyclophosphamide (3×150 mg/kg, days, 7, 9, 11) were long-term survivors. The 3 modulators given in combination produced further increases in tumor growth delay with all of the cytotoxic therapies, and 5 of 12 of the animals treated with the 3-modulator combination and cyclophosphamide were long-term survivors. Although neither tetrahydrocortisol/-cyclodextrin tetradecasulfate, minocycline, nor the three modulator combination impacted the number of lung metastases, there was a decrease in the number of large lung metastases. Treatment with the cytotoxic therapies alone reduced the number of lung metastases. Addition of the modulators to treatment with the cytotoxic therapies resulted in a further reduction in the number of lung metastases. These results indicate that agents that inhibit the breakdown of the extracellular matrix can be useful additions to the treatment of solid tumors.Abbreviations 14(SO₄)ßCD -cyclodextrin tetradecasulfate - THC tetrahydrocortisol - CDDP cis-diamminedichloroplatinum(II) - 4-HC 4-hydroperoxycyclophosphamide - BCNU N,N-bis(2-chloroethyl)-N-nitrosourea - CAM chick embryo chorioallantoic membrane; IC₅₀, concentration of a drug required to kill 50% of the cells This work was supported by NIH grant P01-CA38493 and a grant from Bristol-Myers-Squibb, Inc., Wallingford, Connecticut     

Restraint-induced stress ulcer. I. Hypothalamic,urinary, and adrenal biochemical studies

The purpose of these experiments was to study the incidence of stress ulcers in restrained rats and to correlate it with hypothalamic and adrenal cortical and medullary activity, with and without vagotomy. A total of 217 adult rats were used, grouped into 56 sets, and distributed at random in 5 experimental groups. Restraint was followed by a 79% incidence of ulceration in the glandular portion of the gastric mucosa. Vagotomy made these worse (p<0.01). Hypothalamic levels of catecholamines and serotonin showed no significant changes. Urinary measurements revealed decreased excretion of 17-ketosteroids (p<0.001), increased excretion of uropepsinogen (p<0.01), and no significant changes in vanillylmandelic acid among the rats submitted to immobilization. In the adrenal glands of stressed animals, there was a decreased level of catecholamines (p<0.01) and no significant changes in corticosteroid content (17-ketosteroids). These results suggest that hypothalamic stimulation and the participation of the adrenal glands are not essential factors in the pathogenesis of restraint-induced experimental stress ulcer.     

Liposomally-entrapped ganciclovir for the treatment of cytomegalovirus retinitis in AIDS patients

Treatment of retinitis by cytomegalovirus (CMV) in AIDS patients requires frequent repetitive injections of intravitreal ganciclovir (GCV). This study was undertaken to establish experimentally whether the intravitreal application of liposomally-entrapped GCV could prolong intraocular therapeutic levels when compared with the intravitreal injection of free GCV, and the clinical effectiveness of this approach in AIDS patients. Intraocular concentration of GCV was determined by means of an ELISA test in rabbit vitreous 2, 3, 7, and 14 days after a single intravitreal injection of either different doses of the free drug (0.2–20 mg) or 1 mg of liposomally-entrapped GCV. After 72 h, only the vitreous of rabbits injected with doses of free GCV greater than or equal to 5 mg showed therapeutic levels of the drug; no GCV was detected after 72 h with any of the doses applied. Moreover, the microscopic study revealed GCV-induced damage in retinal structures in the animals injected with a free GCV dose greater than or equal to 15 mg. Intravitreal injection to rabbits of 1 mg of liposomally-encapsulated GCV showed no retinal toxicity at any of the time points studied, and therapeutic levels were detected up to 14 days after injection (4.67 ± 0.39 g/ml). Five AIDS patients suffering CMV retinitis were injected with 0.5 mg of liposomally-entrapped GCV (2 mg of lecithin). Complete remission of the CMV retinitis was observed already at the third injection of 0.5 mg GCV (one per week) and relapse did not occur during the 2–4 month follow-up of the patients. In view of the results presented, it can be concluded that intravitreal injection of liposomally-encapsulated GCV increases the time period required for reinjections in the treatemnt of CMV retinitis.Abbreviations AIDS acquired immunodeficiency syndrome - AZT zidovudine - CMV cytomegalovirus - GCV ganciclovir     

Double tumor of the larynx: a case report

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