Epidemiological Profile of Cryptococcal Meningitis Patients in Rio Grande do Sul,Brazil

Cryptococcosis is a major opportunistic mycosis which has meningitis as its most frequent clinical presentation and can be fatal in the absence of antifungal therapy. The aetiological agents are Cryptococcus neoformans, which affects mainly immunocompromised subjects, and C. gattii, the aetiologic agent for cryptococcosis in healthy individuals. A recent outbreak of cryptococcosis on Vancouver Island, Canada, raised the level of concern about the epidemiology of this disease. In Brazil, between 1980 and 2002, six per cent of AIDS patients had cryptococcosis in course at the time of diagnosis. To identify the profile of cryptococcal meningitis patients in Rio Grande do Sul (RS), Brazil, a retroactive study was realized using data from patients registered at Laboratório Central de Saúde Pública IPB-LACEN/RS from 2000 to 2005. Most of the patients were men (77.12%), Caucasian (83.5%), median age between thirty and thirty-nine years old (46.24%) and HIV positive (95%).     

Natural killers and biogenic amines: the paracrine regulation in the immune system

Natural killers are referred to the category of cells well known for their assistance in cyto-differentiation control. Mechanisms of such assistance include cytolytic and secretory effects on the target. In this aspect, the NK capacity to assist in local aminoregulatory processes by adrenalin, serotonin, histamine release contained in these cells granules is considered to be the least studied and the most problematic issue. The solution of this problem demands taking into consideration a number of conditions: the NK ability to receipt biogenic amines and peculiarities of receptor structure; principal differences in mechanism of action of biogenic amines which enter the cell through exogenous pathway or which are synthesized endogenously; correlation between biogenic amines presence in the granules and functional NK state. Hypothesis of generation connected with the problem suggests the NK assistance in cytolysis in concomitant mechanisms of paracrine regulation of cellular microenvironmental proliferative response, induction of local inflammatory and immunomodulating processes.     

Homology modeling identifies C-terminal residues that contribute to the Ca2+ sensitivity of a BKCa channel

Activation of BK(Ca) channels by direct Ca(2+) binding and membrane depolarization occur via independent and additive molecular processes. The "calcium bowl" domain is critically involved in Ca(2+)-dependent gating, and we have hypothesized that a sequence within this domain may resemble an EF hand motif. Using a homology modeling strategy, it was observed that a single Ca(2+) ion may be coordinated by the oxygen-containing side chains of residues within the calcium bowl (i.e., (912)ELVNDTNVQFLD(923)). To examine these predictions directly, alanine-substituted BK(Ca) channel mutants were expressed in HEK 293 cells and the voltage and Ca(2+) dependence of macroscopic currents were examined in inside-out membrane patches. Over the range of 1-10 microM free Ca(2+), single point mutations (i.e., E912A and D923A) produced rightward shifts in the steady-state conductance-voltage relations, whereas the mutants N918A or Q920A had no effect on Ca(2+)-dependent gating. The double mutant E912A/D923A displayed a synergistic shift in Ca(2+)-sensitive gating, as well as altered kinetics of current activation/deactivation. In the presence of 1, 10, and 80 mM cytosolic Mg(2+), this double mutation significantly reduced the Ca(2+)-induced free energy change associated with channel activation. Finally, mutations that altered sensitivity of the holo-channel to Ca(2+) also reduced direct (45)Ca binding to the calcium bowl domain expressed as a bacterial fusion protein. These findings, along with other recent data, are considered in the context of the calcium bowl's high affinity Ca(2+) sensor and the known properties of EF hands.     

Computational Investigation on the ∙OOH Scavenging Sites of Gnetin C

Melinjo seed extract contains melinjo resveratrol compounds that has antioxidant activity. The radical-scavenging sites required for the antioxidant activity, however, is yet to be located. We report a computational study that aims to locate scavenging sites of the simplest resveratrol dimer, gnetin C. We consider the reaction of gnetin C and hydroperoxyl radical energetically with the basis of density-functional calculations, to be compared with the reaction of the resveratrol monomer, trans-resveratrol, and hydroperoxyl radical. The results show that OH group at the para position is the most reactive scavenging site for both molecules. Besides the OH group, gnetin C also provides two CH groups in the furan ring that are favorable as scavenging sites. Therefore, furan ring plays an important role in the scavenging activity, which is contrary to the experimental speculation that propose resorcinol ring. Our study shows the prospect of density-functional calculation for studying the radical-scavenging reaction.

     

Physiological Activity of Peptides Isolated from Human Gastric and Duodenal Ulcerous Tissues

Some drug formulations containing digestive enzymes were shown to stimulate gastric and duodenal secretion owing to low-molecular-weight peptides (LMWPs) generated during isolation of the enzymes from raw biological materials. Similar LMWPs were found in gastric and duodenal ulcerous tissues. It was concluded that, transferred with the blood and the lymph, the LMWPs produced in such tissues continuously stimulate the exocrine function of the pancreas (probably, through a system of immunoreceptors). Persistent pancreatic hypersecretion results in functional failure of the gland and in chronic pancreatitis.