Vagotomy reduces obesity in MSG-treated rats

In order to study the role of vagus nerve activity at the onset of obesity induced by monosodium glutamate (MSG), 30-day-old MSG-rats were vagotomized or sham operated. Body weight and food intake were recorded until animals were 90 days old and then sacrificed. Naso-anal length was recorded for all animals. Periepididymal and retroperitoneal fat pads were isolated and weighed. Reduction of body weight and naso-anal length were registered in 30-day-old MSG-rats. Obesity could also be observed, as increase of Lee index indicated. Results were most evident in 90-day-old MSG-rats. In both groups neither body weight gain nor food intake was changed by vagotomy. However, fat accumulation on tissues was reduced by vagotomy in MSG-rats. The results showed that MSG-obesity is not related to an increment in food intake behavior. Vagotonia might play a role at the onset of MSG-obesity.     

Modulation of Cytokeratin Expression in The Hamster Thymus: Evidence For a Plasticity of The Thymic Epithelium

Cytokeratin (CK) expression was investigated, by means of immunocytochemistry, in the hamster thymic epithelium during ontogeny, as well as in primary cultures and upon glucocorticoid hormone treatment in vivo. As compared to the distribution pattern of distinct monoclonal antibody-defined cytokeratins in the normal adult thymus, CK modulation was evidenced in the three situations studied. During thymus ontogeny, both cytokeratins of simple lining epithelia, as CK8 and CK18, as well as the CK1/CK10 pair (typical marker of terminal stage of keratinization), were expressed since early stages of thymus development. They were located in the central region of thymic lobules preceding the cortical-medullary distinctions. This differed from what had been previously shown for mouse thymus ontogeny, revealing that the interspecific diversity in the distribution pattern of thymic cytokeratins occurred early in fetal life. A modulation of CK expression was also detected when hamster thymic epithelial cells (TEC) were led to grow in culture, with a down-regulation of CK19 contrasting with an enhancement of CK18 expression. This diverged from the maintenance of the in situ pattern when human TEC were cultured. Last, in vivo hydrocortisone treatment, known to increase the numbers of KL1⁺ cells in the mouse thymus medulla, promoted a cortical expression of the CK1/CK10 pair in the hamster thymus. Taken together, our findings demonstrate a continuous plasticity of the thymic epithelium, at least regarding cytokeratin expression, and enlarge the concept of interspecific diversity of intrathymic CK distribution in conditions as morphogenesis, in vitro system, and responsiveness to glucocorticoid hormone treatment.     

Serotonergic-1a activity and contingent negative variation

While cholinergic, dopaminergic, noradrenergic, and gabaergic effects on contingent negative variation (CNV) have been largely described, little is known about serotonergic influence. Therefore, the relationship between CNV and serotonergic activity as reflected by prolactin (PRL) response to flesinoxan, a 5-HT(1A) full agonist, has been investigated in 28 healthy volunteers. To investigate the clinical implications of the relationship between CNV and serotonergic-1a activity, a group of 43 depressed patients was included in the study. Results among healthy volunteers showed a significant negative relationship between PRL response to flesinoxan and CNV amplitude at Fz, but no relationship for the other electrodes (Cz and Pz). In depressed patients, the relationships were not significant. Overall, this study does not support serotonergic effects on CNV. However, this information is indirect (correlations) and is limited to 5-HT(1A) activity.     

Mechanisms of uterine specificity of vaginal progesterone

Endometrial transformations achieved by vaginal progesterone exceed those normally expected from the circulating concentrations obtained, this suggests some degree of direct vagina to uterus transport. We speculate on the different mechanisms involved in uterine specificity of vaginal progesterone and report data of a preliminary randomized study comparing progesterone concentrations in serum and endometrial tissue obtained from hysterectomy specimens after vaginal or i.m. administration. Eight post-menopausal women undergoing transabdominal hysterectomy were randomized to receive either vaginal progesterone gel, 90 mg, or i.m. progesterone formulation, 50 mg, at 08.00 and 20.00 on the day before surgery and at 06.00 on the day of surgery. Venous blood samples for progesterone measurement were drawn at 08.00 on the day before surgery and during the surgery. Endometrial progesterone concentrations were markedly higher in women who received vaginal progesterone (1.38+/-0.66 and 0.38+/-0.19 ng/mg protein, for vaginal and i.m. groups respectively) (P < 0.02) despite lower serum concentrations (4.17 < 0.56 and 32.32+/-11.06 ng/ml, for vaginal and i.m. groups respectively) (P < 0.001). The vaginal route induces endometrial progesterone concentrations that far exceed those expected from the serum progesterone concentrations achieved.     

Establishing phenotypic features associated with morbidity in human T-cell lymphotropic virus type 1 infection

The human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HT). Although it is widely believed that virus infection and host immune response are involved in the pathogenic mechanisms, the role of the immune system in the development and/or maintenance of HT remains unknown. We performed an analysis of the peripheral blood leukocyte phenotype for two different subcohorts of HTLV-1-infected individuals to verify the existence of similar immunological alterations, possible laboratory markers for HT. The leukocyte population balance, the activation status of the T lymphocytes, and the cellular migratory potential of T lymphocytes, monocytes, and neutrophils were evaluated in the peripheral blood of HTLV-1-infected individuals classified as asymptomatic individuals, oligosymptomatic individuals, and individuals with HT. Data analysis demonstrated that a decreased percentage of B cells, resulting in an increased T cell/B cell ratio and an increase in the CD8+ HLA-DR+ T lymphocytes, exclusively in the HT group could be identified in both subcohorts, suggesting its possible use as a potential immunological marker for HT for use in the laboratory. Moreover, analysis of likelihood ratios showed that if an HTLV-1-infected individual demonstrated B-cell percentages lower than 7.0%, a T cell/B cell ratio higher than 11, or a percentage of CD8+ HLA-DR+ T lymphocytes higher than 70.0%, this individual would have, respectively, a 12-, 13-, or 22-times-greater chance of belonging to the HT group. Based on these data, we propose that the T cell/B cell ratios and percentages of circulating B cells and activated CD8+ T lymphocytes in HTLV-1-infected patients are important immunological indicators which could help clinicians monitor HTLV-1 infection and differentiate the HT group from the asymptomatic and oligosymptomatic groups.     

Purification of the paraflagellar rod of the trypanosomatid Herpetomonas megaseliae and identification of some of its minor components

The paraflagellar rod (PFR) is a component of the flagellar cytoskeleton of trypanosomatid protozoa, representing a filamentous structure that runs alongside the common 9 + 2 microtubular axoneme. The high degree of ultrastructural complexity and organization of the PFR suggests that it might be formed by numerous biochemical components. However, biochemical analysis of the PFR has revealed, to date, a modest degree of complexity in what concerns both major and minor PFR proteins. In this paper the preparation of purified PFR fractions by a combination of conventional cell-fractionation procedures, non-ionic detergent treatment and limited proteolysis is described. Comparative SDS-PAGE analysis of the different purification steps indicates that the purified PFR fractions possess high amounts of the well-known major PFR proteins (77 and 83 kDa). Also, bands of 147, 139, 129 and 122 kDa are clearly enriched in such fractions and may correspond to minor PFR components. A slight enrichment in a specific fraction of a doublet of bands of 181/188 kDa suggest the participation of these proteins in the composition of the bridges between the PFR and the axoneme.     

Anti-platelet autoantibodies from ITP patients recognize an epitope in GPIIb/IIIa deduced by complementary hydropathy.

Idiopathic thrombocytopenic purpura (ITP) is a frequent platelet disorder due to the presence of anti-platelet autoantibodies. Recently a fibronectin/fibrinogen receptor in platelets, integrin GPIIb/IIIa, has been implicated as the antigen in chronic ITP. To examine the epitopes involved in the autoimmune response against GPIIb/IIIa we have used concepts from the complementary hydropathy principle. We used the peptide Trp-Thr-Val-Pro-Thr-Ala, WTVPTA (deduced from the complementary nucleotide sequence to that which codes for the Arg-Gly-Asp, RGD, domain in fibronectin), to test the immunologic activity of ITP sera. Sera from 31 patients with clinically defined ITP were tested in ELISA for reactivity towards WTVPTA and affinity purified GPIIb/IIIa. Seventeen sera (57%) reacted strongly with the glycoprotein complex, five of which reacted with the peptide. By affinity chromatography of one of these sera, we were able to show that antibodies that bind to the peptide are within the population that binds to GPIIb/IIIa. Liquid phase competition experiments revealed that binding of ITP serum to WTVPTA was inhibited only by a hydropathically compatible peptide. Our data indicate that autoantibodies can bind to hydropathically generated antigenic determinants and thus, render these peptides clinically important as diagnostic tools.