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Objective Systemic sclerosis (SSc) is characterized by vasculopathy, fibrosis of skin and internal organs, and autoimmunity with complications including interstitial lung disease, pulmonary hypertension, and digital ulcers with substantial morbidity and disability. Patients with SSc may require considerable healthcare resources with economic impact. The purpose of this systematic review was to provide a narrative synthesis of the economic impact and healthcare resource utilization associated with SSc. Methods MEDLINE and EMBASE were searched from inception to 20 January 2021. Studies were included if they provided information regarding the total, direct and indirect cost of SSc. The cost of SSc subtypes and associated complications was determined. Risk of bias assessments through the Joanna Briggs Institute cross-sectional and case series checklists, and the Newcastle–Ottawa Cohort and Case–Control study scales were performed. A narrative synthesis of included studies was planned. Results The number of publications retrieved was 1778, of which 34 were included representing 20 cross-sectional, 11 cohort, and three case–control studies. Studies used various methods of calculating cost including prevalence-based cost-of-illness approach and health resource units cost analysis. Overall SSc total annual cost ranged from USD $14 959 to $23 268 in USA, CAD $10 673 to $18 453 in Canada, €4607 to €30 797 in Europe, and AUD $7060 to $11 607 in Oceania. Annual cost for SSc-associated interstitial lung disease and pulmonary hypertension was USD $31 285–55 446 and $44 454–63 320, respectively. Conclusion Cost-calculation methodology varied greatly between included studies. SSc represents a significant patient and health resource economic burden. SSc-associated complications increase economic burden and are variable depending on geographical location and access. [ABSTRACT FROM AUTHOR]

Skin secretions of frogs have a high chemical complexity. They have diverse types of biomolecules, such as proteins, peptides, biogenic amines, and alkaloids. These compounds protect amphibians' skin against growth of bacteria, fungi, and protozoa and participate in defense system against attack from predators. Therewith, this work performed biochemical and biological profile of macroglands parotoid secretion from cane toad. For poison analysis, we performed molecular exclusion and reverse phase chromatography, electrophoresis, and mass spectrometry. Antimicrobial, antiplasmodial, leishmanicidal, cytotoxicity, genotoxicity, and inflammatory activity of crude and/or fractions of R. marina secretion were also evaluated. Fractionation prior to filtration from poison showed separation of low mass content (steroids and alkaloids) and high molecular mass (protein). Material below 10 kDa two steroids, marinobufagin and desacetylcinobufagin, was detected. Crude extract and fractions were active against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Plasmodium falciparum, Leishmania guyanensis, and Leishmania braziliensis. Crude extract was also active against cancer cells although it was not cytotoxic for normal cells. This extract did not show significant DNA damage but it showed an important inflammatory effect in vivo. The information obtained in this work contributes to the understanding of the constituents of R. marina secretion as well as the bioactive potential of these molecules. [ABSTRACT FROM AUTHOR]

Antivenoms, produced using animal hyperimmune plasma, remains the standard therapy for snakebites. Although effective against systemic damages, conventional antivenoms have limited efficacy against local tissue damage. Additionally, the hypersensitivity reactions, often elicited by antivenoms, the high costs for animal maintenance, the difficulty of producing homogeneous lots, and the instability of biological products instigate the search for innovative products for antivenom therapy. In this study, camelid antibody fragments (VHH) with specificity to Bothropstoxin I and II (BthTX-I and BthTX-II), two myotoxic phospholipases from Bothrops jararacussu venom, were selected from an immune VHH phage display library. After biopanning, 28 and 6 clones recognized BthTX-I and BthTX-II by ELISA, respectively. Complementarity determining regions (CDRs) and immunoglobulin frameworks (FRs) of 13 VHH-deduced amino acid sequences were identified, as well as the camelid hallmark amino acid substitutions in FR2. Three VHH clones (KF498607, KF498608, and KC329718) were capable of recognizing BthTX-I by Western blot and showed affinity constants in the nanomolar range against both toxins. VHHs inhibited the BthTX-II phospholipase A2 activity, and when tested for cross-reactivity, presented specificity to the Bothrops genus in ELISA. Furthermore, two clones (KC329718 and KF498607) neutralized the myotoxic effects induced by B. jararacussu venom, BthTX-I, BthTX-II, and by a myotoxin from Bothrops brazili venom (MTX-I) in mice. Molecular docking revealed that VHH CDRs are expected to bind the C-terminal of both toxins, essential for myotoxic activity, and to epitopes in the BthTX-II enzymatic cleft. Identified VHHs could be a biotechnological tool to improve the treatment for snake envenomation, an important and neglected world public health problem. [ABSTRACT FROM AUTHOR]

This paper presents a novel serine protease (SP) isolated from Bothrops pirajai, a venomous snake found solely in Brazil that belongs to the Viperidae family. The identified SP, named BpirSP-39, was isolated by three chromatographic steps (size exclusion, bioaffinity, and reverse phase chromatographies). The molecular mass of BpirSP-39 was estimated by SDS-PAGE and confirmed by mass spectrometry (39,408.32Da). The protein was able to form fibrin networks, which was not observed in the presence of serine protease inhibitors, such as phenylmethylsulfonyl fluoride (PMSF). Furthermore, BpirSP-39 presented considerable thermal stability and was apparently able to activate factor XIII of the blood coagulation cascade, unlike most serine proteases. BpirSP-39was capable of hydrolyzing different chromogenic substrates tested (S-2222, S-2302, and S-2238) while Cu2+ significantly diminished BspirSP-39 activity on the three tested substrates. The enzyme promoted platelet aggregation and also exhibited fibrinogenolytic, fibrinolytic, gelatinolytic, and amidolytic activities. The multiple alignment showed high sequence similarity to other thrombin-like enzymes from snake venoms. These results allow us to conclude that a new SP was isolated from Bothrops pirajai snake venom. [ABSTRACT FROM AUTHOR]

Bothrops mattogrossensis snake is widely distributed throughout eastern South America and is responsible for snakebites in this region. This paper reports the purification and biochemical characterization of three new phospholipases A2 (PLA2s), one of which is presumably an enzymatically active Asp49 and two are very likely enzymatically inactive Lys49 PLA2 homologues. The purification was obtained after two chromatographic steps on ion exchange and reverse phase column. The 2D SDS-PAGE analysis revealed that the proteins have pI values around 10, are each made of a single chain, and have molecular masses near 13 kDa, which was confirmed by MALDI-TOF mass spectrometry. The N-terminal similarity analysis of the sequences showed that the proteins are highly homologous with other Lys49 and Asp49 PLA2s from Bothrops species. The PLA2s isolated were named BmatTX-I (Lys49 PLA2-like), BmatTX-II (Lys49 PLA2-like), and BmatTX-III (Asp49 PLA2). The PLA2s induced cytokine release from mouse neutrophils and showed cytotoxicity towards JURKAT (leukemia T) and SK-BR-3 (breast adenocarcinoma) cell lines and promastigote forms of Leishmania amazonensis. The structural and functional elucidation of snake venoms components may contribute to a better understanding of the mechanism of action of these proteins during envenomation and their potential pharmacological and therapeutic applications. [ABSTRACT FROM AUTHOR]

Bothrops asper (Squamata: Viperidae) is the most important venomous snake in Central America, being responsible for the majority of snakebite accidents. Four basic PLA2s (pMTX-I to -IV) were purified from crude venom by a single-step chromatography using a CM-Sepharose ion-exchange column (1.5 x 15 cm). Analysis of the N-terminal sequence demonstrated that pMTX-I and III belong to the catalytically active Asp49 phospholipase A2 subclass, whereas pMTX-II and IV belong to the enzymatically inactive Lys49 PLA2s-like subclass. The PLA2s isolated from Panama Bothrops asper venom (pMTX-I, II, III, and IV) are able to induce myotoxic activity, inflammatory reaction mainly leukocyte migration to the muscle, and induce J774A.1 macrophages activation to start phagocytic activity and superoxide production. [ABSTRACT FROM AUTHOR]

The antihyperglycemic effects of several plant extracts and herbal formulations which are used as antidiabetic formulations have been described and confirmed to date. The main objective of this work was to evaluate the hypoglycemic activity of the aqueous extract of Anacardium humile. Although the treatment of diabetic animals with A. humile did not alter body weight significantly, a reduction of the other evaluated parameters was observed. Animals treated with A. humile did not show variation of insulin levels, possibly triggered by a mechanism of blood glucose reduction. Levels of ALT (alanine aminotransferase) decreased in treated animals, suggesting a protective effect on liver. Levels of cholesterol were also reduced, indicating the efficacy of the extract in reestablishing the balance of nutrients. Moreover, a kidney protection may have been achieved due to the partial reestablishment of blood glucose homeostasis, while no nephrotoxicity could be detected for A. humile. The obtained results demonstrate the effectiveness of A. humile extracts in the treatment of alloxan-induced diabetic rats. Therefore, A. humile aqueous extract, popularly known and used by diabetic patients, induced an improvement in the biochemical parameters evaluated during and following treatment of diabetic rats. Thus, a better characterization of the medicinal potential of this plant will be able to provide a better understanding of its mechanisms of action in these pathological processes. [ABSTRACT FROM AUTHOR]

The article focuses on the geographic distribution of the amphibian Leptodactylus chaquensis. It says that leptodactylus chaquensis frog belongs to the L. ocellatus, in which its species extends across various biomes in Amazonia, Argentina, Bolivia, Brazil, Paraguay, and Uruguay. Meanwhile, the first record of the L. chaquensis were noted in the state of Rondô, Brazil including three males and one female at Porto Velho, another female at the same area found on November 22, 2008, and another male was collected at Cujubim. Moreover, the records extend the geographic distribution from its closest records approximately 350 kilometer eastwards from Beni, Bolivia wherein voucher specimens were deposited in the Federal University of Rondô in the anuran collection.

The article offers information on the geographic distribution of the Elachistocleis Magnus frog species in Brazil.