Appraisal of Antiophidic Potential of Marine Sponges against Bothrops jararaca and Lachesis muta Venom

Snakebites are a health problem in many countries due to the high incidence of such accidents. Antivenom treatment has regularly been used for more than a century, however, this does not neutralize tissue damage and may even increase the severity and morbidity of accidents. Thus, it has been relevant to search for new strategies to improve antiserum therapy, and a variety of molecules from natural sources with antiophidian properties have been reported. In this paper, we analyzed the ability of ten extracts from marine sponges (Amphimedon viridis, Aplysina fulva, Chondrosia collectrix, Desmapsamma anchorata, Dysidea etheria, Hymeniacidon heliophila, Mycale angulosa, Petromica citrina, Polymastia janeirensis, and Tedania ignis) to inhibit the effects caused by Bothrops jararaca and Lachesis muta venom. All sponge extracts inhibited proteolysis and hemolysis induced by both snake venoms, except H. heliophila, which failed to inhibit any biological activity. P. citrina inhibited lethality, hemorrhage, plasma clotting, and hemolysis induced by B. jararaca or L. muta. Moreover, other sponges inhibited hemorrhage induced only by B. jararaca. We conclude that Brazilian sponges may be a useful aid in the treatment of snakebites caused by L. muta and B. jararaca and therefore have potential for the discovery of molecules with antiophidian properties.     

Connective tissue mast cells are the target of formaldehyde to induce tracheal hyperresponsiveness in rats: Putative role of leukotriene B4 and nitric oxide

Formaldehyde (FA) exposure induces upper airways irritation and respiratory abnormalities, but its mechanisms are not understood. Since mast cells are widely distributed in the airways, we hypothesized that FA might modify the airways reactivity by mechanism involving their activation. Tracheal rings of rats were incubated with Dulbecco's modified medium culture containing FA (0.1 ppm) in 96-well plastic microplates in a humid atmosphere. After 30 min, 6 h, and 24–72 h, the rings were suspended in an organ bath and dose–response curve to methacholine (MCh) were determined. Incubation with FA caused a transient tracheal hyperresponsiveness to MCh that was independent from tracheal epithelium integrity. Connective tissue mast cell depletion caused by compound 48/80 or mast cell activation by the allergic reaction, before exposure of tracheal rings to FA prevented the increased responsiveness to MCh. LTB₄ concentrations were increased in the culture medium of tracheas incubated with FA for 48 h, whereas the LTB₄-receptor antagonist MK886 (1 μM) added before FA exposure rendered the tracheal rings normoreactive to MCh. In addition, FA exposure did not cause hyperresponsiveness in tracheal segments incubated with l-arginine (1 μM).     

Epidemiological research on dementia in developing countries

As the world population is ageing, dementia becomes an important public health problem, particularly in developing countries. Epidemiological research in these settings is scarce and present additional methodological difficulties, mainly regarding the socio-cultural adequacy of instruments used to identify cases of dementia. As a result of these concerns the 10/66 Dementia Research Group was founded to fill this gap. This is an international network of investigators, mostly from developing countries, and the group's name was based on the paradox that less than 10% of the population-based studies on dementia are directed to 2/3 or more cases of people with dementia living in developing countries. The aim of the paper is to update data in the literature regarding the differences in dementia prevalence and incidence seen in developed and developing countries.     

Fish consumption, mercury exposure and serum antinuclear antibody in Amazonians

Exposure to intrinsic Hg in fish was studied in Amazon populations with high prevalence of malaria disease. High fish-eater riverines were compared to urban (Manaus residents) low fish-eater riverines in regards to Hg exposure (hair-Hg) and serum antinuclear antibodies (ANA). Most riverines (99.0%) ate fish daily compared to only 3% of controls. Fish species high in MeHg was consumed more frequently (45.5%) by riverines than controls (18.8%). Mean hair-Hg (34.5 ppm) of riverines was significantly higher than controls (1.0 ppm). Although positive serum ANA was more frequently observed in riverine fish-eaters (12.4%) than controls (2.9%), there was no significant association between hair-Hg and ANA. High prevalence of malaria reporting among riverines was neither associated with Hg exposure nor with serum ANA. An autoimmune dysfunction is unlikely to occur as a result of MMHg exposure due to fish consumption.     

Molecular identification and phylogenetical analysis of dermatophyte fungi from Latin America

Dermatophytes constitute a complex group of fungi, comprised of by the genera Trichophyton, Epidermophyton and Microsporum. They have the ability to degrade keratin and cause human and animal infections. Molecular techniques have made their identification faster and more accurate, and allowed important advances in phylogenetic studies. We aim to identify molecularly and to determine the phylogenetic relationships in dermatophyte fungi from Brazil and other Latin American countries, using DNA sequencing of the nuclear ribosome regions ITS1‐5.8S‐ITS2 and D1/D2. DNA of 45 dermatophytes was extracted and amplified by PCR for identification at the species level by sequencing of those ribosomal regions. The software mega 6.0 was used to establish the phylogenetic relationships via the Maximum Likelihood method. Out of 45 strains, 43 were identified by ITS (95.5%) and 100% by D1/D2 sequencing. Two strains could not be identified by ITS. Phylogenetic analyses separated the genera Trichophyton and Microsporum, which presented an uncertain relationship with Epidermophyton floccosum, depending on the ribosomal marker. Both regions can provide efficient identification of dermatophytes, whereas phylogenetic analysis revealed complex relations among dermatophyte fungi.     

MRP1 expression in CTCs confers resistance to irinotecan‐based chemotherapy in metastatic colorectal cancer

Circulating tumor cells are important markers of tumor progression and can reflect tumor behavior in metastatic colorectal cancer (mCRC). Identification of proteins that confer resistance to treatment is an important step to predict response and better selection of treatment for patients. Multidrug resistance‐associated protein 1 (MRP1) and Multidrug resistance‐associated protein 4 (MRP4) play a role in irinotecan‐resistance, and Excision Repair Cross‐Complementation group 1 (ERCC1) expression can confer resistance to platinum compounds. Here, we included 34 patients with mCRC and most of them received FOLFIRI or FOLFOX chemotherapy (91.1%). CTCs were isolated by ISET^® Technology and identified in 30 patients (88.2%), with a median of 2.0 CTCs/mL (0–31.0). We analyzed the immunocytochemical expression of MRP1, MRP4 and ERCC1 only in patients who had previously detectable CTCs, accordingly to treatment received (n = 19, 15 and 13 patients, respectively). Among patients treated with irinotecan‐based chemotherapy, 4 out of 19 cases with MRP1 positive CTCs showed a worse progression free survival (PFS) in comparison to those with MRP1 negative CTCs (2.1 months vs. 9.1 months; p = 0.003). None of the other proteins studied in CTCs had significant association with PFS. We analyzed also histological sections of primary tumors and metastases by immunohistochemistry, and found no association with clinicopathological characteristics or with PFS. Our results show MRP1 as a potential biomarker of resistance to treatment with irinotecan when found in CTCs from mCRC patients. This is a small proof‐of‐principle study and these early findings need to be validated in a larger cohort of patients.     

Pulmonary neutrophil recruitment and bronchial reactivity in formaldehyde-exposed rats are modulated by mast cells and differentially by neuropeptides and nitric oxide

We have used a pharmacological approach to study the mechanisms underlying the rat lung injury and the airway reactivity changes induced by inhalation of formaldehyde (FA) (1% formalin solution, 90 min once a day, 4 days). The reactivity of isolated tracheae and intrapulmonary bronchi were assessed in dose-response curves to methacholine (MCh). Local and systemic inflammatory phenomena were evaluated in terms of leukocyte countings in bronchoalveolar lavage (BAL) fluid, blood, bone marrow lavage and spleen. Whereas the tracheal reactivity to MCh did not change, a significant bronchial hyporesponsiveness (BHR) was found after FA inhalation as compared with naive rats. Also, FA exposure significantly increased the total cell numbers in BAL, in peripheral blood and in the spleen, but did not modify the counts in bone marrow. Capsaicin hindered the increase of leukocyte number recovered in BAL fluid after FA exposure. Both compound 48/80 and indomethacin were able to prevent the lung neutrophil influx after FA, but indomethacin had no effect on that of mononuclear cells. Following FA inhalation, the treatment with sodium cromoglycate (SCG), but not with the nitric oxide (NO) synthase inhibitor L-NAME, significantly reduced the total cell number in BAL. Compound 48/80, L-NAME and SCG significantly prevented BHR to MCh after FA inhalation, whereas capsaicin was inactive in this regard. On the other hand, indomethacin exacerbated BHR. These data suggest that after FA inhalation, the resulting lung leukocyte influx and BHR may involve nitric oxide, airway sensory fibers and mast cell-derived mediators. The effect of NO seemed to be largely restricted to the bronchial tonus, whereas neuropeptides appeared to be linked to the inflammatory response, therefore indicating that the mechanisms responsible for the changes of airway responsiveness caused by FA may be separate from those underlying its inflammatory lung effects.     

Mortality, TB/HIV co-infection, and treatment dropout: predictors of tuberculosis prognosis in Recife, Pernambuco State, Brazil

This non-concurrent cohort study aims to identify predictors of tuberculosis mortality in a large population database in Brazil. Tuberculosis, death, and TB/HIV cases were validated respectively from the tuberculosis surveillance (SINAN/TB), mortality (SIM), and SINAN/AIDS databases for a five-year period. Analysis included proportional hazard models with relative risk estimates. Out of 5,451 individuals reported with tuberculosis, 320 (5.9%) died (incidence and mortality rates of 98.6 and 12.2/100 thousand inhabitants, respectively). After adjustment, relative risk of dying from tuberculosis was 9.8 for individuals>50 years of age; 9.0 for TB/HIV co-infection; 3.0 for mixed TB clinical presentation; and 2.0 for treatment dropout. In the multivariate model, using cases with HIV/AIDS, all adjusted predictors lost significance except mixed clinical presentation (RR 1.9; 1.1-3.1). TB/HIV co-infection is an important predictor of TB mortality. However, among individuals without HIV/AIDS, mortality is still highly associated with older age, mixed clinical forms, and treatment dropout.     

The African contribution to the present‐day population of the Azores Islands (Portugal): Analysis of the Y chromosome haplogroup E

Among the settlers that, from 1432 onwards, arrived to the Azores Islands were individuals of North and sub‐Saharan African origin. A previous study of markers of the Y chromosome revealed that haplogroup E is the second more frequent in the Azores (13%). Since this haplogroup is heterogeneous and may contain subtypes of African or non‐African origin, we analyzed an extended sample of 319 Azoreans, originating from the three groups of islands (Eastern, Central, and Western), to evaluate the African contribution to the present‐day population of the Azores. Samples belonging to the E clade were distributed into six haplogroups, from which the most frequent was E3b1a, representing 47.2% of the E chromosomes (6.3% of the total sample). The sub‐Saharan haplogroup E3a was found in 7.1% of E chromosomes (0.9% of the total), corresponding to the highest frequency reported so far in a Portuguese population. No significant differences were detected in the haplogroup distribution among groups of islands, as well as between Azores and most of other European populations compared. The present‐day representation of sub‐Saharan lineages in Azores, although reduced, is higher than in other Portuguese populations, where the demographic representation of sub‐Saharan slaves is reported as similar. Am. J. Hum. Biol., 2007. © 2007 Wiley‐Liss, Inc.     

Evaluation of the antiurolithiatic activity of the extract of Costus spiralis Roscoe in rats.

The antiurolithiatic activity of the water extract of Costus spiralis Roscoe was tested on formation of calculi on implants of calcium oxalate crystals or zinc disc in the urinary bladder of rats. The plant is a species from the family Zingiberaceae used in Brazilian folk medicine in urinary affections and for expelling urinary stones. Implantation of the foreign body in the urinary bladder of adult rats induced formation of urinary stones and hypertrophy of the smooth musculature. Oral treatment with the extract of Costus spiralis Roscoe (0.25 and 0.5 g/kg per day) after 4 weeks surgery reduced the growth of calculi, but it did not prevent hypertrophy of the organ smooth musculature. The contractile responses of isolated urinary bladder preparations to the muscarinic agonist bethanecol, in the presence and absence of the extract (0.3-3 mg/ml) or atropine (0.3-3 nM) did not differ among the experimental groups. The results indicate that the extract of Costus spiralis Roscoe is endowed with antiurolithiatic activity confirming thus folk information. The effect, however, was unrelated to increased diuresis or to a change of the muscarinic receptor affinity of the bladder smooth musculature to cholinergic ligands.