Lesão renal aguda causada pelo veneno das cobras Crotalus e Bothrops: revisão da epidemiologia, das manifestações clínicas e do tratamento

SUMMARY Ophidic accidents are an important public health problem due to their incidence, morbidity and mortality. An increasing number of cases have been registered in Brazil in the last few years. Several studies point to the importance of knowing the clinical complications and adequate approach in these accidents. However, knowledge about the risk factors is not enough and there are an increasing number of deaths due to these accidents in Brazil. In this context, acute kidney injury (AKI) appears as one of the main causes of death and consequences for these victims, which are mainly young males working in rural areas. Snakes of the Bothrops and Crotalus genera are the main responsible for renal involvement in ophidic accidents in South America. The present study is a literature review of AKI caused by Bothrops and Crotalus snake venom regarding diverse characteristics, emphasizing the most appropriate therapeutic approach for these cases. Recent studies have been carried out searching for complementary therapies for the treatment of ophidic accidents, including the use of lipoic acid, simvastatin and allopurinol. Some plants, such as Apocynaceae, Lamiaceae and Rubiaceae seem to have a beneficial role in the treatment of this type of envenomation. Future studies will certainly find new therapeutic measures for ophidic accidents.RESUMO Os acidentes ofídicos são importante problema de saúde pública devido à incidência, morbidade e mortalidade. Aumento do número de casos tem sido registrado no Brasil nos últimos anos. Vários estudos apontam para a importância do conhecimento das complicações clínicas e do tratamento adequado desses acidentes. Entretanto o conhecimento dos fatores de risco não é suficiente, e existe número crescente de óbitos devido a esses acidentes no Brasil. Neste contexto, a injúria renal aguda (IRA) aparece como uma das principais causas de óbito e sequela nestas vítimas, que são principalmente homens trabalhadores de zonas rurais. Os gêneros Bothrops e Crotalus são os principais responsáveis pelo envolvimento renal nos acidentes ofídicos na América do Sul. O presente estudo faz uma revisão da literatura sobre a IRA causada pela picada das serpentes dos gêneros Bothrops e Crotalus em suas diversas características, enfatizando a abordagem terapêutica mais adequada para estes casos. Estudos recentes tem sido realizados para a busca de terapias complementares para o tratamento dos acidentes ofídicos, incluindo o uso de ácido lipóico, sinvastatina e alopurinol. Algumas plantas, como a Apocynaceae, Lamiaceae e Rubiaceae parecem ter papel benéfico no tratamento destes envenenamentos. Estudos futuros irão certamente encontrar novas estratégias terapêuticas para os acidentes ofídicos

Candida auris: a literature review

Background: Emerging pathogen Candida auris has been associated with nosocomial outbreaks demonstrating widespread antifungal resistance. This microorganism is associated with systemic infections with a high mortality rate, and studies that contribute to a better understanding of this agent are important. Objectives: The present article aimed to carry out bibliographic research on Candida auris. Therefore, a literature search was carried out between January 2018 and January 2022, applying the following: C. auris; Candida auris and Infection, in Portuguese, English and Spanish. This review considers the available literature on C. auris and highlights key unknowns, which will provide guidance for future work in this field. Results: The data collected in the present review allowed us to divide the theme into topics on Pathophysiology, Epidemiology/clinical and drug resistance mechanisms, so that the understanding of Candida auris can be better detailed and understood. Conclusion: The predilection of C. auris by the most vulnerable and immunosuppressed patients or with comorbidities and with the potential to cause invasive and bloodstream infections with a propensity to cause outbreaks and concerns regarding resistance to antifungal agents, the fungus Candida auris, is of increasing clinical relevance. The increase in the number of detected cases and the occurrence of strains with multiple drug resistance prove to be worrisome, and applied research is essential to contribute to the knowledge of this strain and effective therapy

Revisão acerca da tuberculose genitourinária com foco na insuficiência renal crônica terminal

Tuberculosis (TB) is a current public health problem, remaining the most common worldwide cause of mortality from infectious disease. Recent studies indicate that genitourinary TB is the third most common form of extra-pulmonary disease. The diagnosis of renal TB can be hypothesized in a non-specific bacterial cystitis associated with a therapeutic failure or a urinalysis with a persistent leukocyturia in the absence of bacteriuria. We report on the case of a 33-year-old man who presented on admission end stage renal disease (ESRD) secondary to renal TB and a past history of pulmonary TB with important radiologic findings. The diagnosis was based on clinical findings despite all cultures being negative. Empiric treatment with tuberculostatic drugs was started and the patient became stable. He was discharged with no symptom, but without renal function recovery. He is on maintenance hemodialysis three times a week. TB is an important cause of kidney disease and can lead to irreversible renal function loss.A tuberculose (TB) é um problema atual de saúde pública, persistindo como a causa mais comum de óbito por doenças infecciosas. Estudos recentes indicam que a TB genitourinária é a terceira forma mais comum de doença extra-pulmonar. O diagnóstico da TB renal pode ser suspeito na presença de cistite bacteriana não-específica associada a falha terapêutica ou com exame de urina apresentando leucocitúria persistente na ausência de bacteriúria. Relatamos o caso de um paciente de 33 anos, sexo masculino, que apresentou na admissão insuficiência renal crônica terminal secundária à TB renal, que tinha história prévia de TB pulmonar, com importantes achados radiológicos. O diagnóstico foi baseado nos achados clínicos apesar de todas as culturas terem sido negativas. Tratamento empírico com drogas tuberculostáticas foi iniciado e o paciente evoluiu estável. Foi de alta assintomático, mas sem recuperação da função renal. Ele encontra-se em hemodiálise três vezes por semana. A TB é uma causa importante de doença renal e pode levar à perda irreversível da função renal

Diversity of metalloproteinases in Bothrops neuwiedi snake venom transcripts: evidences for recombination between different classes of SVMPs

<p>Abstract</p> <p>Background</p> <p>Snake venom metalloproteinases (SVMPs) are widely distributed in snake venoms and are versatile toxins, targeting many important elements involved in hemostasis, such as basement membrane proteins, clotting proteins, platelets, endothelial and inflammatory cells. The functional diversity of SVMPs is in part due to the structural organization of different combinations of catalytic, disintegrin, disintegrin-like and cysteine-rich domains, which categorizes SVMPs in 3 classes of precursor molecules (PI, PII and PIII) further divided in 11 subclasses, 6 of them belonging to PII group. This heterogeneity is currently correlated to genetic accelerated evolution and post-translational modifications.</p> <p>Results</p> <p>Thirty-one SVMP cDNAs were full length cloned from a single specimen of <it>Bothrops neuwiedi </it>snake, sequenced and grouped in eleven distinct sequences and further analyzed by cladistic analysis. Class P-I and class P-III sequences presented the expected tree topology for fibrinolytic and hemorrhagic SVMPs, respectively. In opposition, three distinct segregations were observed for class P-II sequences. P-IIb showed the typical segregation of class P-II SVMPs. However, P-IIa grouped with class P-I cDNAs presenting a 100% identity in the 365 bp at their 5' ends, suggesting post-transcription events for interclass recombination. In addition, catalytic domain of P-IIx sequences segregated with non-hemorrhagic class P-III SVMPs while their disintegrin domain grouped with other class P-II disintegrin domains suggesting independent evolution of catalytic and disintegrin domains. Complementary regions within cDNA sequences were noted and may participate in recombination either at DNA or RNA levels. Proteins predicted by these cDNAs show the main features of the correspondent classes of SVMP, but P-IIb and P-IIx included two additional cysteines cysteines at the C-termini of the disintegrin domains in positions not yet described.</p> <p>Conclusions</p> <p>In <it>B. neuwiedi </it>venom gland, class P-II SVMPs were represented by three different types of transcripts that may have arisen by interclass recombination with P-I and P-III sequences after the divergence of the different classes of SVMPs. Our observations indicate that exon shuffling or post-transcriptional mechanisms may be driving these recombinations generating new functional possibilities for this complex group of snake toxins.</p

Renal function evaluation in patients with American Cutaneous Leishmaniasis after specific treatment with pentavalent antimonial

Background: Renal evaluation studies are rare in American Cutaneous Leishmaniasis (ACL). The aim of this study is to investigate whether specific treatment reverts ACL-associated renal dysfunction. Methods: A prospective study was conducted with 37 patients with ACL. Urinary concentrating and acidification ability was assessed before and after treatment with pentavalent antimonial. Results: The patients mean age was 35.6 +/- 12 years and 19 were male. Before treatment, urinary concentrating defect (U/P-osm &lt; 2.8) was identified in 27 patients (77%) and urinary acidification defect in 17 patients (46%). No significant glomerular dysfunction was observed before and after specific ACL treatment. There was no reversion of urinary concentrating defects, being observed in 77% of the patients before and in 88% after treatment (p = 0.344). Urinary acidification defect was corrected in 9 patients after treatment, reducing its prevalence from 40% before to only 16% after treament, (p = 0.012). Microalbuminuria higher than 30 mg/g was found in 35% of patients before treatment and in only 8% after treatment. Regarding fractional excretion of sodium, potassium, calcium, phosphorus and magnesium, there was no significant difference between pre and post-treatment period. Conclusion: As previously described, urinary concentrating and acidification defects were found in an important number of patients with ACL. Present results demonstrate that only some patients recover urinary acidification capacity, while no one returned to normal urinary concentration capacity.Brazilian National Council for Scientific and Technological Development (CNPq)Brazilian National Council for Scientific and Technological Development (CNPq

Renal function evaluation in patients with American Cutaneous Leishmaniasis after specific treatment with pentavalent antimonial

Background\ud Renal evaluation studies are rare in American Cutaneous Leishmaniasis (ACL). The aim of this study is to investigate whether specific treatment reverts ACL-associated renal dysfunction.\ud \ud Methods\ud A prospective study was conducted with 37 patients with ACL. Urinary concentrating and acidification ability was assessed before and after treatment with pentavalent antimonial.\ud \ud Results\ud The patients mean age was 35.6 ± 12 years and 19 were male. Before treatment, urinary concentrating defect (U/Posm <2.8) was identified in 27 patients (77%) and urinary acidification defect in 17 patients (46%). No significant glomerular dysfunction was observed before and after specific ACL treatment. There was no reversion of urinary concentrating defects, being observed in 77% of the patients before and in 88% after treatment (p = 0.344). Urinary acidification defect was corrected in 9 patients after treatment, reducing its prevalence from 40% before to only 16% after treament, (p = 0.012). Microalbuminuria higher than 30 mg/g was found in 35% of patients before treatment and in only 8% after treatment. Regarding fractional excretion of sodium, potassium, calcium, phosphorus and magnesium, there was no significant difference between pre and post-treatment period.\ud \ud Conclusion\ud As previously described, urinary concentrating and acidification defects were found in an important number of patients with ACL. Present results demonstrate that only some patients recover urinary acidification capacity, while no one returned to normal urinary concentration capacity.This research was supported by the Brazilian National Council for Scientific and Technological Development (CNPq). The desmopressin acetate was provided by Ferring of Brazil

Renal function evaluation in patients with American Cutaneous Leishmaniasis after specific treatment with pentavalent antimonial

Background\ud Renal evaluation studies are rare in American Cutaneous Leishmaniasis (ACL). The aim of this study is to investigate whether specific treatment reverts ACL-associated renal dysfunction.\ud \ud Methods\ud A prospective study was conducted with 37 patients with ACL. Urinary concentrating and acidification ability was assessed before and after treatment with pentavalent antimonial.\ud \ud Results\ud The patients mean age was 35.6 ± 12 years and 19 were male. Before treatment, urinary concentrating defect (U/Posm <2.8) was identified in 27 patients (77%) and urinary acidification defect in 17 patients (46%). No significant glomerular dysfunction was observed before and after specific ACL treatment. There was no reversion of urinary concentrating defects, being observed in 77% of the patients before and in 88% after treatment (p = 0.344). Urinary acidification defect was corrected in 9 patients after treatment, reducing its prevalence from 40% before to only 16% after treament, (p = 0.012). Microalbuminuria higher than 30 mg/g was found in 35% of patients before treatment and in only 8% after treatment. Regarding fractional excretion of sodium, potassium, calcium, phosphorus and magnesium, there was no significant difference between pre and post-treatment period.\ud \ud Conclusion\ud As previously described, urinary concentrating and acidification defects were found in an important number of patients with ACL. Present results demonstrate that only some patients recover urinary acidification capacity, while no one returned to normal urinary concentration capacity.This research was supported by the Brazilian National Council for Scientific and Technological Development (CNPq). The desmopressin acetate was provided by Ferring of Brazil

2017 recommendations of the Brazilian Society of Rheumatology for the pharmacological treatment of rheumatoid arthritis

The objective of this document is to provide a comprehensive update of the recommendations of Brazilian Society of Rheumatology on drug treatment of rheumatoid arthritis (RA), based on a systematic literature review and on the opinion of a panel of rheumatologists. Four general principles and eleven recommendations were approved. General principles: RA treatment should (1) preferably consist of a multidisciplinary approach coordinated by a rheumatologist, (2) include counseling on lifestyle habits, strict control of comorbidities, and updates of the vaccination record, (3) be based on decisions shared by the patient and the physician after clarification about the disease and the available therapeutic options; (4) the goal is sustained clinical remission or, when this is not feasible, low disease activity. Recommendations: (1) the first line of treatment should be a csDMARD, started as soon as the diagnosis of RA is established; (2) methotrexate (MTX) is the first-choice csDMARD; (3) the combination of two or more csDMARDs, including MTX, may be used as the first line of treatment; (4) after failure of first-line therapy with MTX, the therapeutic strategies include combining MTX with another csDMARD (leflunomide), with two csDMARDs (hydroxychloroquine and sulfasalazine), or switching MTX for another csDMARD (leflunomide or sulfasalazine) alone; (5) after failure of two schemes with csDMARDs, a bDMARD may be preferably used or, alternatively a tsDMARD, preferably combined, in both cases, with a csDMARD; (6) the different bDMARDs in combination with MTX have similar efficacy, and therefore, the therapeutic choice should take into account the peculiarities of each drug in terms of safety and cost; (7) the combination of a bDMARD and MTX is preferred over the use of a bDMARD alone; (8) in case of failure of an initial treatment scheme with a bDMARD, a scheme with another bDMARD can be used; in cases of failure with a TNFi, a second bDMARD of the same class or with another mechanism of action is effective and safe; (9) tofacitinib can be used to treat RA after failure of bDMARD; (10) corticosteroids, preferably at low doses for the shortest possible time, should be considered during periods of disease activity, and the risk-benefit ratio should also be considered; (11) reducing or spacing out bDMARD doses is possible in patients in sustained remission

Cigarette smoke induces miR-132 in Th17 cells that enhance osteoclastogenesis in inflammatory arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint destruction and severe morbidity. Cigarette smoking (CS) can exacerbate the incidence and severity of RA. Although Th17 cells and the Aryl hydrocarbon receptor (AhR) have been implicated, the mechanism by which CS induces RA development remains unclear. Here, using transcriptomic analysis, we show that microRNA-132 is specifically induced in Th17 cells in the presence of either AhR agonist or CS-enriched medium. miRNA-132 thus induced is packaged into extracellular vesicles produced by Th17 and acts as a proinflammatory mediator increasing osteoclastogenesis through the down-regulation of COX2. In vivo, articular knockdown of miR-132 in murine arthritis models reduces the number of osteoclasts in the joints. Clinically, RA patients express higher levels of miR-132 than do healthy individuals. This increase is further elevated by cigarette smoking. Together, these results reveal a hitherto unrecognized mechanism by which CS could exacerbate RA and further advance understanding of the impact of environmental factors on the pathogenesis of chronic inflammatory diseases