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Background: Although CoronaVac was the only Covid-19 vaccine adopted in the first months of the Brazilian vaccination campaign, randomized clinical trials to evaluate its efficacy in elderly adults were limited. In this study, we use routinely collected surveillance and SARS-CoV-2 vaccination and testing data comprising the population of the fifth largest city of Brazil to evaluate the effectiveness of CoronaVac in adults 60+ years old against severe outcomes., Methods: Using large observational databases on vaccination and surveillance data from the city of Fortaleza, Brazil, we defined a retrospective cohort including 324,302 eligible adults aged ≥60 years to evaluate the effectiveness of the CoronaVac vaccine. The cohort included individuals vaccinated between January 21, 2021, and August 31, 2021, who were matched with unvaccinated persons at the time of rollout following a 1:1 ratio according to baseline covariates of age, sex, and Human Development Index of the neighborhood of residence. Only Covid-19-related severe outcomes were included in the analysis: hospitalization, ICU admission, and death. Vaccine effectiveness for each outcome was calculated by using the risk ratio between the two groups, with the risk obtained by the Kaplan-Meier estimator., Results: We obtained 62,643 matched pairs for assessing the effectiveness of the two-dose regimen of CoronaVac. The demographic profile of the matched population was statistically representative of the population of Fortaleza. Using the cumulative incidence as the risk associated with each group, starting at day 14 since the receipt of the second dose, we found an 82.3 % (95 % CI 66.3-93.9) effectiveness against Covid-19-related death, 68.4 % (95 % CI 42.3-86.4) against ICU admission, and 55.8 % (95 % CI 42.7-68.3) against hospital admission., Conclusions: Our results show that, despite critical delays in vaccine delivery and limited evidence in efficacy trial estimates, CoronaVac contributed to preventing deaths and severe morbidity due to Covid-19 in elderly adults., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The Caatinga lancehead, Bothrops erythromelas, is a medically relevant species, responsible for most of the snakebite accidents in most parts of its distribution range in northeastern Brazil. The spectrum and geographic variability of its venom toxins were investigated applying a venomics approach to venom pools from five geographic areas within the Caatinga ecoregion. Despite its wide habitat, populations of B. erythromelas from Ceará, Pernambuco, Juazeiro, Paraiba, and Ilha de Itaparica exhibit highly conserved venom proteomes. Mirroring their compositional conservation, the five geographic venom pools also showed qualitatively and quantitatively overlapping antivenomic profiles against antivenoms generated in Vital Brazil (BR) and Clodomiro Picado (CR) Institutes, using different venoms in the immunization mixtures. The paraspecificity exhibited by the Brazilian SAB and the Costa Rican BCL antivenoms against venom toxins from B. erythromelas indicates large immunoreactive epitope conservation across genus Bothrops during the last ~14 million years, thus offering promise for the possibility of generating a broad-spectrum bothropic antivenom. Biological Significance Accidental snakebite envenomings represent an important public health hazard in Brazil. Ninety per cent of the yearly estimated 20-30,000 snakebite accidents are caused by species of the Bothrops genus. Bothrops erythromelas, a small, moderately stocky terrestrial venomous snake, is responsible for most of the snakebite accidents in its broad distribution range in the Caatinga, a large ecoregion in northeastern Brazil. To gain a deeper insight into the spectrum of medically important toxins present in the venom of the Caatinga lancehead, we applied a venomics approach to define the proteome and geographic variability of adult B. erythromelas venoms from five geographic regions. Although intraspecific compositional variation between venoms among specimens from different geographic regions has long been appreciated by herpetologists and toxinologists as a general feature of highly adaptable and widely distributed snake species, the five B. erythromelas populations investigated exhibit highly conserved venom proteomes. The overall toxin profile of the Caatinga lancehead's venom explains the local and systemic effects observed in envenomations by B. erythromelas. The five geographic venom pools sampled also showed qualitatively and quantitatively overlapping antivenomic profiles against antivenoms generated using different bothropic venoms in the immunization mixtures. The large immunoreactive epitope conservation across genus Bothrops offers promise for the generation of a broad-spectrum bothropic antivenom., (Copyright © 2014 Elsevier B.V. All rights reserved.)

From the leaves of Solanum campaniforme (Solanaceae), eight solanidane alkaloids were isolated, four of which contain a p-hydroxyphenylethylamine unit. Their structures were established as: 22β,23β-epoxy-solanida-1,4-dien-3-one; 22α,23α-epoxy-10-epi-solanida-1,4,9-trien-3-one; 22α,23α-epoxy-solanida-4-en-3-one; 22β,23β-epoxy-solanida-4-en-3-one; (E)-N-[8'(4-hydroxyphenyl)ethyl]-22α,23α-epoxy-solanida-1,4,9-trien-3-imine; (E)-N-[8'(4-hydroxyphenyl)ethyl]-22α,23α-epoxy-solanida-1,4-dien-3-imine; (Z)-N-[8'(4-hydroxyphenyl)ethyl]-22α,23α-epoxy-solanida-1,4,9-trien-3-imine and (Z)-N-[8'(4-hydroxyphenyl)ethyl]-22α,23α-epoxy-solanida-1,4-dien-3-imine. All structures were determined using spectroscopic techniques, such as 1D and 2D NMR, and HRESIMS. The cytotoxicity and the antiophidic activities of the alkaloids were evaluated. The alkaloids did not show any cytotoxicity, but inhibited the main toxic actions of Bothrops pauloensis venom., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Mammalian natriuretic peptides (NPs) have been extensively investigated for use as therapeutic agents in the treatment of cardiovascular diseases. Here, we describe the isolation, sequencing and tridimensional homology modeling of the first C-type natriuretic peptide isolated from scorpion venom. In addition, its effects on the renal function of rats and on the mRNA expression of natriuretic peptide receptors in the kidneys are delineated. Fractionation of Tityus serrulatus venom using chromatographic techniques yielded a peptide with a molecular mass of 2190.64 Da, which exhibited the pattern of disulfide bridges that is characteristic of a C-type NP (TsNP, T. serrulatus Natriuretic Peptide). In the isolated perfused rat kidney assay, treatment with two concentrations of TsNP (0.03 and 0.1 μg/mL) increased the perfusion pressure, glomerular filtration rate and urinary flow. After 60 min of treatment at both concentrations, the percentages of sodium, potassium and chloride transport were decreased, and the urinary cGMP concentration was elevated. Natriuretic peptide receptor-A (NPR-A) mRNA expression was down regulated in the kidneys treated with both concentrations of TsNP, whereas NPR-B, NPR-C and CG-C mRNAs were up regulated at the 0.1 μg/mL concentration. In conclusion, this work describes the isolation and modeling of the first natriuretic peptide isolated from scorpion venom. In addition, examinations of the renal actions of TsNP indicate that its effects may be related to the activation of NPR-B, NPR-C and GC-C., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Three new solanidane alkaloids bearing a 22,23-epoxy ring (1-3) and four known compounds were isolated from leaves of Solanum campaniforme. The structures were determined using spectroscopic techniques, including 1D and 2D NMR, and HRESIMS experiments. The antiophidic activity of the alkaloids was tested against Bothrops pauloensis venom. Compounds 1-3 completely inhibited myotoxicity without inhibiting phospholipase A2 activity of the venom, while hemorrhage and skin necrosis were significantly reduced in the presence of alkaloids 1 and 2.

Objective: We examined the effect of a diet supplemented with alanyl-glutamine (AG) or placebo glycine (G) on intestinal barrier function and growth in children in northeastern Brazil., Patients and Methods: One hundred seven children ages 7.9 to 82.2 months with a weight-for-age (WAZ), height-for-age (HAZ), or weight-for-height (WHZ) z-score less than -1 were studied. From July 2003 to November 2004, 51 study patients received AG (24 g/d) and 56 received G (25 g/d; isonitrogenic concentration) control for 10 days. Lactulose/mannitol excretion ratio was used as a measure of intestinal permeability and was performed on days 1 and 10 of nutritional supplementation. Weight and height were measured on days 1, 10, 30, and 120 of the protocol., Results: The patients were similar on admission with regard to age, sex, birth weight, nutritional status, lactulose/mannitol ratio, and serum concentrations of glutamine and arginine. The percentage of lactulose urinary excretion significantly improved (decreased) in children receiving AG for 10 days but not in those receiving glycine controls. AG significantly increased cumulative change over 120 days in WHZ and WAZ scores but not HAZ scores after adjustment for age and season in comparison with the placebo glycine group., Conclusions: Children tolerated AG-supplemented enteral formula well, and it significantly improved cumulative WHZ and WAZ over 120 days in comparison with children in the placebo glycine group. The data also suggested a beneficial effect of AG in the barrier function paracellular pathway, albeit with reduced mannitol excretion. Thus, although the effect of AG on reduced mannitol concentration requires clarification, AG appears to improve nutrition and barrier function.

Acute renal failure is the most common complication in the lethal cases caused by snakebites in Brazil. Among the Brazilian venom snakes, Bothrops erythromelas is responsible for the majority of accidents in Northeastern Brazil. Didelphis marsupialis serum could inhibit myonecrotic, hemorrhagic, edematogenic hyperalgesic and lethal effects of envenomation determined by ophidian bites. In the present study, we evaluated the action of the anti-bothropic factor isolated from D. marsupialis on the renal effects promoted by B. erythromelas venom without systemic interference. Isolated kidneys from Wistar rats were perfused with Krebs-Henseleit solution containing 6% bovine serum albumin. We analyzed renal perfusion pressure (PP), renal vascular resistance (RVR), glomerular filtration rate (GFR), urinary flow (UF), and the percentages of sodium and potassium tubular transport (%TNa+, %TK+). The B. erythromelas venom (10 microg mL(-1)) decreased the PP (ct = 108.71+/-5.09 mmHg; BE = 65.21+/-5.6 mmHg*) and RVR (ct = 5.76+/-0.65 mmHg mL(-1) g(-1) min(-1); BE = 3.10+/-0.45 mmHg mL(-1) g(-1) min(-1)*). On the other hand, the GFR decreased at 60 min (ct60 = 0.76+/-0.07 mL g(-1) min(-1); BE60 = 0.42+/-0.12 mL g(-1) min(-1)*) and increased at 120 min (ct120 = 0.72+/-0.01 mL g(-1) min(-1); BE120 = 1.24+/-0.26 mL g(-1) min(-1)*). The UF increased significantly when compared with the control group (ct = 0.14+/-0.01 mL g(-1) min(-1); BE = 0.47+/-0.08 mL g(-1) min(-1)*). The venom reduced the %TNa(+) (ct90 = 79.18+/-0.88%; BE90 = 58.35+/-4.86%*) and %TK+ (ct90 = 67.20+/-4.04%; BE90 = 57.32+/-5.26%*) The anti-bothropic factor from D. marsupialis (10 microg mL(-1)) incubated with B. erythromelas venom (10 microg mL(-1)) blocked the effects on PP, RVR, %TNa+, and %TK+, but was not able to reverse the effects in UF and GFR promoted by venom alone. However, the highest concentration of D. marsupialis serum (30 microg mL(-1)) reversed all the renal effects induced by the venom. In conclusion, B. erythromelas venom altered all the renal functional parameters evaluated and the anti-bothropic factor from D. marsupialis was able to inhibit the effects induced by the venom in isolated kidney.

In Ceará State (1992 to 2002) 16 cases of envenomation by Thalassophryne nattereri occurred in the seaside of Ceará, 87.5% of cases in the region of Fortaleza and 12.5% in the interior of Ceará State. Ninety four percent were men and 6% women. Age range: 75% between 21 and 40 years and 19% between 41 and 60 years old. The time between medical assistance and the accident varied from 1 to 5 hours (4 cases), 6 to 12 hours (3 cases), over 12 hours in 4 cases and 5 patients did not know. Clinical manifestations observed were pain, local edema, transitory ischemia, paresthesia, ecchymosis and burned skin sensation. Anti inflammatory and analgesic drugs were used. In some cases, anesthetic, hot water, surgical peeling and anti-histaminic drugs were used. In 75% of cases cure was confirmed and in 12% cure was not confirmed. The number of accidents is probably higher than was found due to subnotification.

From 1992 to 1995, 688 accidents by venomous snakes (mean of 192 cases/year) have been notified to the Health Ministry of the State of Ceará, with an incidence between 0.9 and 5.8/100.000 inhabitants. Among 473 cases, 88.3% were of the genus. Bothrops, 10.7% Crotalus, 0.8% Micrurus and 0.2% Lachesis. The highest incidence occurred from April to September. Male (75.6%) predominated with ages from 10 to 49 years old (72.3%). The more frequently bitten anatomical region were the lower limbs (81.9%) and upper limbs (14.7%). The attendance at health unit which notified the accident took place within 6 hours in 66.9% of the cases. Lethality was 0.7%. The afflicted people were mainly peasants (62.7%), and most of the accidents took place in their own work place. The authors emphasize that the snake bites in the state of Ceará may be considered work accidents, concern mainly peasants and constitute a cause of death.