Effects of crotamine in human prostate cancer cell line.

Our study presents the anticancer potential of crotamine from Crotalus durissus terrificus in human prostate cancer cell line DU-145. Crotamine isolation was conducted through RP-FPLC, its molecular mass analyzed by MALDI-TOF was 4881.4 kDa, and N-terminal sequencing confirmed crotamine identity. Crotamine demonstrated no toxicity and did not inhibit migration in HUVEC cells. Although no cell death occurred in DU-145 cells, crotamine inhibited their migration. Thus, crotamine presented potential to be a prototype of anticancer drug.

Understanding the complexity of Tityus serrulatus venom: A focus on high molecular weight components.

Tityus serrulatus scorpion is responsible for a significant number of envenomings in Brazil, ranging from mild to severe, and in some cases, leading to fatalities. While supportive care is the primary treatment modality, moderate and severe cases require antivenom administration despite potential limitations and adverse effects. The remarkable proliferation of T. serrulatus scorpions, attributed to their biology and asexual reproduction, contributes to a high incidence of envenomation. T. serrulatus scorpion venom predominantly consists of short proteins acting as neurotoxins (α and ß), that primarily target ion channels. Nevertheless, high molecular weight compounds, including metalloproteases, serine proteases, phospholipases, and hyaluronidases, are also present in the venom. These compounds play a crucial role in envenomation, influencing the severity of symptoms and the spread of venom. This review endeavors to comprehensively understand the T. serrulatus scorpion venom by elucidating the primary high molecular weight compounds and exploring their potential contributions to envenomation. Understanding these compounds' mechanisms of action can aid in developing more effective treatments and prevention strategies, ultimately mitigating the impact of scorpion envenomation on public health in Brazil.

The complex repertoire of Tityus spp. venoms: Advances on their composition and pharmacological potential of their toxins.

Animal venoms are a rich and complex source of components, including peptides (such as neurotoxins, anionic peptides and hypotensins), lipids, proteins (such as proteases, hyaluronidases and phospholipases) and inorganic compounds, which affect all biological systems of the envenoming victim. Their action may result in a wide range of clinical manifestations, including tachy/bradycardia, hyper/hypotension, disorders in blood coagulation, pain, edema, inflammation, fever, muscle paralysis, coma and even death. Scorpions are one of the most studied venomous animals in the world and interesting bioactive molecules have been isolated and identified from their venoms over the years. Tityus spp. are among the scorpions with high number of accidents reported in the Americas, especially in Brazil. Their venoms have demonstrated interesting results in the search for novel agents with antimicrobial, anti-viral, anti-parasitic, hypotensive, immunomodulation, anti-insect, antitumor and/or antinociceptive activities. Furthermore, other recent activities still under investigation include drug delivery action, design of anti-epileptic drugs, investigation of sodium channel function, treatment of erectile disfunction and priapism, improvement of scorpion antivenom and chelating molecules activity. In this scenario, this paper focuses on reviewing advances on Tityus venom components mainly through the modern omics technologies as well as addressing potential therapeutic agents from their venoms and highlighting this abundant source of pharmacologically active molecules with biotechnological application.

Understanding the complexity of Tityus serrulatus venom: A focus on high molecular weight components

Tityus serrulatus scorpion is responsible for a significant number of envenomings in Brazil, ranging from mild to severe, and in some cases, leading to fatalities. While supportive care is the primary treatment modality, moderate and severe cases require antivenom administration despite potential limitations and adverse effects. The remarkable proliferation of T. serrulatus scorpions, attributed to their biology and asexual reproduction, contributes to a high incidence of envenomation. T. serrulatus scorpion venom predominantly consists of short proteins acting as neurotoxins (α and ß), that primarily target ion channels. Nevertheless, high molecular weight compounds, including metalloproteases, serine proteases, phospholipases, and hyaluronidases, are also present in the venom. These compounds play a crucial role in envenomation, influencing the severity of symptoms and the spread of venom. This review endeavors to comprehensively understand the T. serrulatus scorpion venom by elucidating the primary high molecular weight compounds and exploring their potential contributions to envenomation. Understanding these compounds' mechanisms of action can aid in developing more effective treatments and prevention strategies, ultimately mitigating the impact of scorpion envenomation on public health in Brazil.

Transcriptomic analysis reveals that RasGEF1b deletion alters basal and LPS-induced expression of genes involved in chemotaxis and cytokine responses in macrophages.

Ras guanine nucleotide exchange factor member 1b (RasGEF1b) of the RasGEF/CDC25 domain-containing family is preferentially expressed by macrophages. However, information is lacking about its role in macrophage function. In this study, we generated mice with ubiquitous deletion of Rasgef1b and used RNA-seq-based transcriptomics to compare the global gene expression in wild-type and knock-out primary bone-marrow-derived macrophages under basal conditions and after lipopolysaccharide (LPS) treatment. Transcriptional filtering identified several genes with significantly different transcript levels between wild-type and knock-out macrophages. In total, 49 and 37 differentially expressed genes were identified at baseline and in LPS-activated macrophages, respectively. Distinct biological processes were significantly linked to down-regulated genes at the basal condition only, and largely included chemotaxis, response to cytokines, and positive regulation of GTPase activity. Importantly, validation by RT-qPCR revealed that the expression of genes identified as down-regulated after LPS stimulation was also decreased in the knock-out cells under basal conditions. We used a luciferase-based reporter assay to showcase the capability of RasGEF1b in activating the Serpinb2 promoter. Notably, knockdown of RasGEF1b in RAW264.7 macrophages resulted in impaired transcriptional activation of the Serpinb2 promoter, both in constitutive and LPS-stimulated conditions. This study provides a small collection of genes that shows relative expression changes effected by the absence of RasGEF1b in macrophages. Thus, we present the first evidence that RasGEF1b mediates the regulation of both steady-state and signal-dependent expression of genes and propose that this GEF plays a role in the maintenance of the basal transcriptional level in macrophages.

Snake venom disintegrins update: insights about new findings.

Snake venom disintegrins are low molecular weight, non-enzymatic proteins rich in cysteine, present in the venom of snakes from the families Viperidae, Crotalidae, Atractaspididae, Elapidae, and Colubridae. This family of proteins originated in venom through the proteolytic processing of metalloproteinases (SVMPs), which, in turn, evolved from a gene encoding an A Disintegrin And Metalloprotease (ADAM) molecule. Disintegrins have a recognition motif for integrins in their structure, allowing interaction with these transmembrane adhesion receptors and preventing their binding to proteins in the extracellular matrix and other cells. This interaction gives disintegrins their wide range of biological functions, including inhibition of platelet aggregation and antitumor activity. As a result, many studies have been conducted in an attempt to use these natural compounds as a basis for developing therapies for the treatment of various diseases. Furthermore, the FDA has approved Tirofiban and Eptifibatide as antiplatelet compounds, and they are synthesized from the structure of echistatin and barbourin, respectively. In this review, we discuss some of the main functional and structural characteristics of this class of proteins and their potential for therapeutic use.

Beyond Angiogenesis: The Multitasking Approach of the First PEGylated Vascular Endothelial Growth Factor (CdtVEGF) from Brazilian Rattlesnake Venom.

A pioneering study regarding the isolation, biochemical evaluation, functional assays and first PEGylation report of a novel vascular endothelial growth factor from Crotalus durissus terrificus venom (CdtVEGF and PEG-CdtVEGF). CdtVEGF was isolated from crude venom using two different chromatographic steps, representing 2% of soluble venom proteins. Its primary sequence was determined using mass spectrometry analysis, and the molecule demonstrated no affinity to heparin. The Brazilian crotalid antivenom recognized CdtVEGF. Both native and PEGylated CdtVEGF were able to induce new vessel formation and migration, and to increase the metabolic activity of human umbilical endothelial vascular cells (HUVEC), resulting in better wound closure (~50% within 12 h) using the native form. CdtVEGF induced leukocyte recruitment to the peritoneal cavity in mice, with a predominance of neutrophil influx followed by lymphocytes, demonstrating the ability to activate the immune system. The molecule also induced a dose-dependent increase in vascular permeability, and PEG-CdtVEGF showed less in vivo inflammatory activity than CdtVEGF. By unraveling the intricate properties of minor components of snake venom like svVEGF, this study illuminates the indispensable significance of exploring these molecular tools to unveil physiological and pathological processes, elucidates the mechanisms of snakebite envenomings, and could possibly be used to design a therapeutic drug.

Type I collagen proteolysis by matrix metalloproteinase-2 contributes to focal adhesion kinase activation and vascular smooth muscle cell proliferation in the aorta in early hypertension.

INTRODUCTION: Increased matrix metalloproteinase (MMP)-2 activity contributes to increase vascular smooth muscle cell (VSMC) proliferation in the aorta in early hypertension by cleaving many proteins of the extracellular matrix. Cleaved products from type I collagen may activate focal adhesion kinases (FAK) that trigger migration and proliferation signals in VSMC. We therefore hypothesized that increased activity of MMP-2 proteolyzes type I collagen in aortas of hypertensive rats, and thereby, induces FAK activation, thus leading to increased VSMC proliferation and hypertrophic remodeling in early hypertension. METHODS: Male Sprague-Dawley rats were submitted to renovascular hypertension by the two kidney-one clip (2K1C) model and treated with doxycycline (30 mg/kg/day) by gavage from the third to seventh-day post-surgery. Controls were submitted to sham surgery. Systolic blood pressure (SBP) was measured daily by tail-cuff plethysmography and the aortas were processed for zymography and Western blot for MMP-2, pFAK/FAK, integrins and type I collagen. Mass spectrometry, morphological analysis and Ki67 immunofluorescence were also done to identify collagen changes and VSMC proliferation. A7r5 cells were stimulated with collagen and treated with the MMP inhibitors (doxycycline or ARP-100), and with the FAK inhibitor PND1186 for 24 h. Cells were lysed and evaluated by Western blot for pFAK/FAK. RESULTS: 2K1C rats developed elevated SBP in the first week as well as increased expression and activity of MMP-2 in the aorta (p < 0.05 vs. Sham). Treatment with doxycycline reduced both MMP activity and type I collagen proteolysis in aortas of 2K1C rats (p < 0.05). Increased pFAK/FAK and increased VSMC proliferation (p < 0.05 vs. Sham groups) were also seen in the aortas of 2K1C and doxycycline decreased both parameters (p < 0.05). Higher proliferation of VSMC contributed to hypertrophic remodeling as seen by increased media/lumen ratio and cross sectional area (p < 0.05 vs Sham groups). In cell culture, MMP-2 cleaves collagen, an effect reversed by MMP inhibitors (p < 0.05). Increased levels of pFAK/FAK were observed when collagen was added in the culture medium (p < 0.05 vs control) and MMP and FAK inhibitors reduced this effect. CONCLUSIONS: Increase in MMP-2 activity proteolyzes type I collagen in the aortas of 2K1C rats and contributes to activate FAK and induces VSMC proliferation during the initial phase of hypertension.

Effects of an exercise program plus manual therapy in a patient with failed neck surgery syndrome: A case report.

BACKGROUND: Patients who have undergone cervical surgery may present pain and dysfunction in the upper limb, which is often referred to as failed neck surgery syndrome. Little is known about the effects of an exercise program plus manual therapy in the treatment of prolonged neuropathic pain of the upper quadrant in a patient with failed neck surgery. CASE DESCRIPTION: A 66-year-old woman consulted for neuropathic pain and dysfunction during grasping activities, as a result of failed neck surgery after 12 months. Clinical, functional, and electromyographic measurements were recorded at baseline and after treatment. The patient underwent a treatment for six weeks based on manual therapy for the upper limb and cervical spine and an exercise program for the scapular muscles, rotator cuff and wrist extensor muscles. OUTCOMES: Positive clinically significant changes were observed in the Neuropathic Pain Questionnaire (DN4) (baseline = 7 points; post-treatment = 4 points), Neck Disability Index (NDI) (baseline = 36; post-treatment = 18 points), QuickDASH (baseline = 78; post- treatment = 32 points), Upper Limb Neurodynamic Test 1 (ULNT-1) (baseline = 75°; post- treatment = 42°) and grip strength (GS) (baseline = 23 kgf; post-treatment = to 32 kgf). Improvements in the surface electromyographic (sEMG) activity of the upper trapezius (UT), infraspinatus (IS) and radial wrist extensors (RWE) muscles also seemed to occur after treatment. CONCLUSION: Treatment helped relieve neuropathic pain, decrease neck disability, and improve general upper limb function.

Snake venom disintegrins update: insights about new findings

ABSTRACT Snake venom disintegrins are low molecular weight, non-enzymatic proteins rich in cysteine, present in the venom of snakes from the families Viperidae, Crotalidae, Atractaspididae, Elapidae, and Colubridae. This family of proteins originated in venom through the proteolytic processing of metalloproteinases (SVMPs), which, in turn, evolved from a gene encoding an A Disintegrin And Metalloprotease (ADAM) molecule. Disintegrins have a recognition motif for integrins in their structure, allowing interaction with these transmembrane adhesion receptors and preventing their binding to proteins in the extracellular matrix and other cells. This interaction gives disintegrins their wide range of biological functions, including inhibition of platelet aggregation and antitumor activity. As a result, many studies have been conducted in an attempt to use these natural compounds as a basis for developing therapies for the treatment of various diseases. Furthermore, the FDA has approved Tirofiban and Eptifibatide as antiplatelet compounds, and they are synthesized from the structure of echistatin and barbourin, respectively. In this review, we discuss some of the main functional and structural characteristics of this class of proteins and their potential for therapeutic use.

Ensino da pesquisa científica na graduação médica: há interesse e envolvimento dos estudantes? / Teaching scientific research in medical graduation: is there interest and involvement of the students?

Resumo: Introdução: O conhecimento sobre pesquisa científica e a compreensão dela são habilidades que devem ser desenvolvidas por todos os profissionais de saúde. Especificamente na Medicina, essas habilidades compõem uma parcela importante da graduação e da educação médica continuada. Considerando que a formação médica possui estreita relação com a compreensão sobre evidências científicas, torna-se relevante analisar o envolvimento dos estudantes de Medicina com as atividades científicas durante o curso. Objetivo: Este estudo teve como objetivos verificar o interesse e o envolvimento em pesquisas científicas entre os estudantes de Medicina por meio da análise do perfil acadêmico e das atividades extracurriculares realizadas, avaliar a produção científica e identificar as motivações e dificuldades enfrentadas. Método: Trata-se de um estudo transversal, realizado com estudantes de Medicina de Salvador, na Bahia, maiores de 18 anos. Aplicou-se, por meio do Microsoft Forms, um questionário virtual, estruturado e anônimo contendo 21 perguntas acerca do perfil acadêmico e das atividades extracurriculares realizadas, além de dados sobre a produção científica e as motivações e dificuldades enfrentadas pelos estudantes. Resultado: Dos 460 estudantes participantes, houve predominância de mulheres (63,3%), com idade de 24,1+6,1 anos, cursando os ciclos básico (45,4%) e clínico (46,7%), que não possuem desejo prévio de trabalhar com pesquisa (54,8%). Dentre os participantes, 54,6% integraram ligas acadêmicas, 31,1% possuem envolvimento com grupos de pesquisa e 29,1% participaram de monitoria. Verificou-se que apenas 33,9% dos estudantes possuem resumos publicados em congressos, 12,2% são coautores de artigos científicos e 7,4% são autores principais. O interesse em trabalhar com pesquisa aumenta durante a graduação (p = 0,010), estando os estudantes motivados para produzir cientificamente (66,1%). A experiência em pesquisa (27,4%) e o interesse genuíno na descoberta científica (20,9%) foram os principais fatores motivadores. Entretanto, 81,1% dos discentes identificaram dificuldades para produzir conteúdo científico e apontaram como empecilhos a orientação inadequada (16,0%) e a falta de tempo (15,5%). Não foi observada relação entre a motivação e a dificuldade para produzir cientificamente e o ciclo acadêmico em curso. Conclusão: Os estudantes de Medicina demonstram interesse e participação em pesquisa científica, entretanto aqueles que, de fato, estão envolvidos com atividades científicas representam a minoria.

Abstract: Introduction: Knowledge and understanding of scientific research are skills that must be developed by all health professionals. Specifically in Medicine, these skills make up an important part of undergraduate and continuing medical education. Considering that medical training is closely related to the understanding of scientific evidence, it becomes relevant to analyze the involvement of medical students with scientific activities during the course. Objective: This study aimed to investigate the interest and involvement in scientific research among medical students, analyzing the academic profile and the extracurricular activities carried out, in addition to evaluating the scientific production and identifying the motivations and difficulties faced. Method: A cross-sectional study carried out with medical students from Salvador/Bahia, over 18 years of age. A virtual, structured, anonymous questionnaire was applied through Microsoft Forms, containing 21 questions about the academic profile and extracurricular activities carried out, in addition to data on scientific production and the motivations and difficulties faced by students. Result: Of the 460 participating students, there was a predominance of women (63.3%), aged 24.1+6.1 years, attending the basic (45.4%) and clinical (46.7%) cycles, who have no previous desire to work with research (54.8%). Among the participants, 54.6% were part of academic leagues, 31.1% were involved in research groups and 29.1% participated in monitoring. It was found that only 33.9% of students have abstracts published in congresses, 12.2% are co-authors of scientific articles and 7.4% are main authors. Interest in working with research increases during graduation (p = 0.010), with students motivated to produce scientifically (66.1%). Research experience (27.4%) and genuine interest in scientific discovery (20.9%) were the main motivating factors. However, 81.1% of students identify difficulties in producing scientific content, with inadequate guidance (16.0%) and lack of time (15.5%) being the main obstacles. No relationship was observed between motivation and difficulty to produce scientifically and the current academic cycle. Conclusion: Medical students show interest and participation in scientific research, however those who are actually involved in scientific activities represent the minority.

Medical Management after Lancehead Snakebite in North Amazon: A Case Report of Long-Term Disability.

Snakebites are a major public health problem in indigenous communities in Brazil, leading to acute local and systemic damage with resulting deficiencies. Long-term musculoskeletal disabilities related to snakebites have been a neglected area of research. Bothrops (lancehead) snakes are responsible for most of the permanent sequelae related to snakebites in Latin America. Here, we present a case report of a 32-year-old male indigenous patient who was envenomed by a Bothrops species. The patient was clinically followed for a period of approximately 2 years and 6 months, during which time he experienced a loss of musculoskeletal tissue and required several medical procedures such as debridement, tissue reconstruction, and physical therapy, which resulted in a recovery of mobility, though with a permanent sequelae in gait. This case report shows how snakebites have a significant impact on health systems, as victims require physiotherapy, plastic surgery, and orthopedics services, as well as social support for reintegration into their local communities.

Clinical outcome analysis in surgical patients enrolled in a Second Opinion Program in spine surgery.

OBJECTIVE: To analyze pain, functional capacity, quality of life, anxiety and depression outcomes in patients undergoing lumbar spine surgery following use of the Second Opinion Program, and to present disagreements regarding diagnoses and therapeutic indications between the first and second opinions. METHODS: A prospective, observational cohort study with 100 patients enrolled in the Second Opinion Program who underwent lumbar spine surgery. Questionnaires addressing pain intensity, level of disability, quality of life, anxiety and depression were applied prior to and within 1, 3, 6 and 12 months of surgery. Descriptive and comparative statistical analyses were performed. The following clinical outcomes were analyzed: pain intensity, level of disability, quality of life, anxiety, and depression. RESULTS: In this sample, 88% and 12% out of 100 patients were submitted to lumbar decompression and arthrodesis, respectively. Patients reported improvements in function, pain intensity, and quality of life factors following surgery and were able to attain the minimal clinically important difference relative to the preoperative period. Agreement between the first and second opinions was observed in 44% of diagnoses, and in 27% of therapeutic indications. CONCLUSION: Patients had favorable postoperative outcomes regarding pain, disability, and quality of life. These findings and the high rates of diagnostic and therapeutic indication disagreements corroborate the need of a second opinion in cases of spine disease with surgical indications.

Oxidative stress and changes in hematological and biochemical biomarkers in Crotalus durissus terrificus (South American rattlesnake) venom-induced acute kidney injury in rats / Estrés oxidativo y alteraciones en biomarcadores hematológicos y bioquímicos en lesión renal aguda inducida por el veneno de Crotalus durissus terrificus (cascabel de America del Sur) en ratones

Abstract Acute kidney injury (AKI) is the major cause of mortality following bites by the South American rattlesnake Crotalus durissus terrificus. We investigated the early onset of Crotalus durissus terrificus venom-induced AKI in rats within 2 h of venom injection and its attenuation by antivenom. Several biomarkers were used to monitor AKI in the absence or presence of antivenom. Male Wistar rats were divided into five groups (n=5 each): G1, rats injected with saline (control); G2, rats injected with venom (6 mg kg-1, intraperitoneally) and euthanized after 2 h to evaluate AKI; G3 and G4, rats injected with 0.9% sterile saline or antivenom 2 h after venom, respectively, and monitored until death or up to 24 h post-venom, and G5, rats injected with antivenom alone and monitored for 24 h. Blood, urine and renal tissue samples were collected immediately after death to assess oxidative stress, hematological and biochemical alterations, and renal histological damage. Venom caused AKI within 2 h (G2) that persisted for up to 8.2 ± 1.6 h (G3), as confirmed by increases in blood urea, creatinine, and renal proteinuria; these increases were attenuated by antivenom. There were no changes in blood protein concentrations in G2 and G3, whereas there were increases in blood reduced glutathione, glutathione peroxidase, and plasma TBARS (but not in catalase) that were attenuated to varying extents by antivenom. There were no marked changes in platelets or leukocytes, but an increase in erythrocytes after 8.2 h with venom alone was attenuated by antivenom. Renal glomerular and tubular damage was greatest after 2 h post-venom groups alone was attenuated by antivenom. Renal glomerular and tubular damage was greatest after 2 h post-venom and declined thereafter. Venom caused early-onset AKI, with variable effects on lipid peroxidation and oxidative stress. Antivenom attenuated the AKI, as shown by the decrease in blood urea and the normalization of proteinuria, without protecting against lipid peroxidation.

Resumen La injuria o lesión renal aguda (LRA) es la mayor causa de mortalidad debido a las mordeduras por cascabeles Crotalus durissus terrificus. Se estudió la instalación precoz de LRA, en ratas, inducida por el veneno de Crotalus durissus terrificus después de 2 h de su inoculación y la atenuación por el antiveneno. Se utilizaron diversos biomarcadores para monitorear LRA en ausencia o presencia del antiveneno. Ratas Wistar machos fueron divididos en 5 grupos (n=5 por grupo): G1, ratas inoculadas con solución salina (control); G2, ratas inoculadas con veneno (6 mg kg-1 dosis, vía intraperitoneal), y sacrificadas después de 2 h para evaluar LRA; G3 y G4, ratas inoculadas con 0.9% de solución salina esterilizada o antiveneno luego de 2 h después de inoculado el veneno, respectivamente, y monitoreadas hasta su muerte o hasta 24 h después de inoculado el veneno; y G5, ratas inoculadas con antiveneno solo y monitoreadas durante 24 h. Las muestras de sangre, orina, y tejido renal fueron colectadas inmediatamente después de la muerte de los animales para evaluar estrés oxidativo, alteraciones hematológicas y bioquímicas, y daño histológico renal. El veneno causó LRA dentro de las 2 h (G2) persistiendo durante más de 8,2 ± 1,6 h (G3), estando esto confirmado por el incremento de urea sanguínea, creatinina, y proteinuria renal; estos aumentos disminuyeron con la aplicación del antiveneno. No se observaron alteraciones en las concentraciones de proteínas sanguíneas en G2 y G3, mientras que se encontraron incrementos en glutatión reducido sanguíneo, glutatión peroxidasa y TBARS plasmática (pero no en catalasa), que disminuyeron con la aplicación del antiveneno aunque en diferente grado. No ocurrieron alteraciones marcadas de plaquetas o leucocitos, mientras que el aumento de glóbulos rojos observado luego de 8,2 h de la inoculación con veneno, disminuyó con el antiveneno. El daño renal glomerular y tubular fue más importante luego de 2 h de la inoculación con veneno y posteriormente disminuyó. El veneno causó LRA precoz a las 2 h, con efectos variables sobre la peroxidación lipídica y el estrés oxidativo. El antiveneno redujo el daño renal, conforme lo demostrado por la disminución en la urea sanguínea y por la normalización de la proteinuria, aunque no se observó protección contra la peroxidación lipídica.

Amiloidose pulmonar com apresentação traqueobrônquica: relato de caso clínico / Pulmonary amyloidosis with tracheobronchial presentation: clinical case report

Introdução: Amiloidose é o termo utilizado para designar doenças que fazem deposição extracelular de proteínas fibrilares patológicas em órgãos e tecidos, podendo ser sistêmica ou restrita a um único órgão. As manifestações clínicas são diversas, como cardiomiopatia, falência renal, esplenomegalia, problemas intestinais, neuropatias, problemas pulmonares, entre outros. Objetivo: relatar um caso clínico de paciente com amiloidose traqueobrônquica. Metodologia: revisão de bibliografias em comparação ao relato de caso, o qual foi descrito a partir de dados retirados do prontuário e de exames complementares da paciente. Caso clínico: paciente do sexo feminino, 70 anos, procurou assistência médica por dorsalgia, apresentando também chiado, tosse seca, dispneia paroxística noturna e ortopneia. Realizou-se investigação diagnóstica durante a internação, na qual biópsia da mucosa traqueobrônquica e coleta de lavado alveolar foram positivos para o teste Vermelho Congo, o que confirmou o diagnóstico de amiloidose. A paciente, então, foi encaminhada para terapia de ablação a laser. Conclusão: portanto, diante de um paciente com quadro clínico inespecífico e suspeita diagnóstica principal de amiloidose pulmonar, é imprescindível investigar e descartar diagnósticos diferenciais como neoplasia ou discrasia de células plasmáticas. Para isso, é necessário que haja alta precisão na análise dos exames de imagem, de modo a sugerir esse diagnóstico, o qual deve ser confirmado através da fibrobroncoscopia com biópsia de tecido brônquico, que através da coloração Vermelho do Congo, evidenciará presença de substância amorfa e birrefringente, compatível com substância amiloide [au]

Introduction: Amyloidosis is the term used to describe diseases that cause extracellular deposition of pathological fibrillar proteins in organs and tissues, which can be systemic or restricted to a single organ. The clinical manifestations are diverse, such as cardiomyopathy, renal failure, splenomegaly, intestinal problems, neuropathies, lung problems, among others. Objective: to report a clinical case of a patient with pulmonary amioloidosis. Methodology: review of bibliographies in comparison to the case report, which was described based on data taken from the patient's record and complementary exams. Clinical case: a seventy-year-old female patient sought medical assistance because of back pain, also presenting wheezing, dry cough, paroxysmal nocturnal dyspnea and orthopnea. Diagnostic investigation was carried out during hospitalization, in which biopsy of the tracheobronchial mucosa and collection of alveolar lavage were positive for the Congo Red test,wich confirmed the amyloidosis diagnosis. The patient was then referred for laser ablation therapy.Conclusion: hence, in a patient with a nonspecific clinical presentation and main diagnostic suspicion of pulmonary amyloidosis, it is essential to investigate and rule out differential diagnoses such as malignancy or plasma cell dyscrasia. Therefore, it is necessary to use high precision in the analysis of image exams in order to suggest this diagnosis, which should be confirmed through fibrobronchoscopy with bronchial tissue biopsy, that through the Congo Red dye, will show the presence of amorphous and birefringent substance, compatible with amyloid substance [au]

Anti-vaccination movements in the world and in Brazil

ABSTRACT Over the years, vaccinations have provided significant advances in public health, because they substantially reduce the morbimortality of vaccine-preventable diseases. Nevertheless, many people are still hesitant to be vaccinated. Brazil is a region of many anti-vaccine movements, and several outbreaks of vaccine-preventable diseases, such as yellow fever and measles, have occurred in the country during the last few years. To avoid new outbreaks, immunization coverage must be high; however, this is a great challenge to achieve due to the countless anti-vaccine movements. The World Health Organization has suggested new actions for the next decade via the Immunization Agenda 2030 to control, reduce, or eradicate vaccine-preventable diseases. Nonetheless, the vaccination coverage has decreased recently. To resolve the anti-vaccine issue, it is necessary to propose a long-term approach that involves innovative education programs on immunization and critical thinking, using different communication channels, including social media. Cooperation among biology and health scientists, ethicists, human scientists, policymakers, journalists, and civil society is essential for an in-depth understanding of the social action of vaccine refusal and planning effective education measures to increase the vaccine coverage.

Clinical outcome analysis in surgical patients enrolled in a Second Opinion Program in spine surgery

ABSTRACT Objective To analyze pain, functional capacity, quality of life, anxiety and depression outcomes in patients undergoing lumbar spine surgery following use of the Second Opinion Program, and to present disagreements regarding diagnoses and therapeutic indications between the first and second opinions. Methods A prospective, observational cohort study with 100 patients enrolled in the Second Opinion Program who underwent lumbar spine surgery. Questionnaires addressing pain intensity, level of disability, quality of life, anxiety and depression were applied prior to and within 1, 3, 6 and 12 months of surgery. Descriptive and comparative statistical analyses were performed. The following clinical outcomes were analyzed: pain intensity, level of disability, quality of life, anxiety, and depression. Results In this sample, 88% and 12% out of 100 patients were submitted to lumbar decompression and arthrodesis, respectively. Patients reported improvements in function, pain intensity, and quality of life factors following surgery and were able to attain the minimal clinically important difference relative to the preoperative period. Agreement between the first and second opinions was observed in 44% of diagnoses, and in 27% of therapeutic indications. Conclusion Patients had favorable postoperative outcomes regarding pain, disability, and quality of life. These findings and the high rates of diagnostic and therapeutic indication disagreements corroborate the need of a second opinion in cases of spine disease with surgical indications.

Lumbar Decompression Versus Spinal Fusion ina Private Outpatient Setting: A Retrospective Study with Three Years of Follow-up / Descompressão lombar versus fusão espinhal em ambiente ambulatorial privado: Um estudo retrospectivo com três anos de acompanhamento

Abstract Objective To compare pain, function, quality of life and adverse events of lumbar decompression and spinal fusion in patients with degenerative spinal pathologies who participated in a second opinion program for spinal surgeries with a 36-month followup. Methods The data for this retrospective cohort were withdrawn from a private healthcare system between June 2011 and January 2014. The study sample consisted of 71 patients with a lumbar spine surgical referral. The outcomes for the comparisons between lumbar decompression and spinal fusion were quality of life (evaluated through the EuroQoL 5D), pain (measured by the Numerical Rating Scale) and function (assessed through the Roland Morris Disability Questionnaire) measured at baseline, and at 12 and 36 months after the surgical procedures. The definitions of recovery were established by the minimal clinically important difference (MCID). The baseline differences between the groups were analyzed by non-paired t-test, and the differences in instrument scores between time points, by generalized mixed models. The results were presented as mean values adjusted by the models and 95% confidence intervals. Results Concerning the surgical techniques, 22 patients were submitted to spinal fusion and 49 patients, to lumbar decompression. As for the comparisons of the findings before and after the surgical interventions, the MCID was achieved in all outcomes regarding quality of life, pain and function at both time points when compared to baseline scores Moreover, concerning the complication rates, only lumbar decompression presented a surgical rate of 4% (n = 3) for recurrence of lumbar disc hernia. Conclusion Patients with degenerative spinal pathologies present improvements in long-term outcomes of pain, function and quality of life which are clinically significant, no matter the surgical intervention.

Resumo Objetivo Comparar a dor, a função, a qualidade de vida e os eventos adversos da descompressão lombar e da fusão espinhal em pacientes com patologias degenerativas da coluna vertebral que participaram de um programa de segunda opinião para cirurgias de coluna com acompanhamento de 36 meses. Métodos Os dados desta coorte retrospectiva foram obtidos de um sistema de saúde privado entre junho de 2011 e janeiro de 2014. A amostra do estudo foi composta por 71 pacientes encaminhados para cirurgia de coluna lombar. Os desfechos para comparações entre a descompressão lombar e a fusão espinhal foram qualidade de vida (avaliada pelo questionário EuroQoL 5D), dor (medida pela Escala Numérica de Classificação de Dor) e função (avaliada pelo Questionário de Incapacidade de Roland Morris) no início do estudo e aos 12 e 36 meses de acompanhamento pós-cirúrgico. As definições de recuperação foram estabelecidas pela diferença mínima clinicamente importante (DMCI). As diferenças basais entre os grupos foram analisadas por teste t não pareado, e as diferenças nas pontuações dos instrumentos entre os momentos, por modelos mistos generalizados. Os resultados foram apresentados como valores médios ajustados pelos modelos e intervalos de confiança de 95%. Resultados No total, 22 pacientes foram submetidos à artrodese, e 49 pacientes, à descompressão lombar. Quanto às comparações de achados antes e depois das intervenções cirúrgicas, a DMCI foi alcançada em todos os desfechos de qualidade de vida, dor e função nos dois pontos de acompanhamento em relação aos escores basais Em relação às complicações, apenas a descompressão lombar apresentou 4% (n = 3) de taxa cirúrgica de recidiva da hérnia de disco lombar. Conclusão Pacientes com patologias espinhais degenerativas apresentam melhoras nos desfechos de dor, função e qualidade de vida em longo prazo que são clinicamente significativas e independentes da intervenção cirúrgica.

Towards toxin PEGylation: The example of rCollinein-1, a snake venom thrombin-like enzyme, as a PEGylated biopharmaceutical prototype.

PEGylation was firstly described around 50 years ago and has been used for more than 30 years as a strategy to improve the drugability of biopharmaceuticals. However, it remains poorly employed in toxinology, even though it may be a promising strategy to empower these compounds in therapeutics. This work reports the PEGylation of rCollinein-1, a recombinant snake venom serine protease (SVSP), able to degrade fibrinogen and inhibit the hEAG1 potassium channel. We compared the functional, structural, and immunogenic properties of the non-PEGylated (rCollinein-1) and PEGylated (PEG-rCollinein-1) forms. PEG-rCollinein-1 shares similar kinetic parameters with rCollinein-1, maintaining its capability of degrading fibrinogen, but with reduced activity on hEAG1 channel. CD analysis revealed the maintenance of protein conformation after PEGylation, and thermal shift assays demonstrated similar thermostability. Both forms of the enzyme showed to be non-toxic to peripheral blood mononuclear cells (PBMC). In silico epitope prediction indicated three putative immunogenic peptides. However, immune response on mice showed PEG-rCollinein-1 was devoid of immunogenicity. PEGylation directed rCollinein-1 activity towards hemostasis control, broadening its possibilities to be employed as a defibrinogenant agent.

MMP inhibition attenuates hypertensive eccentric cardiac hypertrophy and dysfunction by preserving troponin I and dystrophin.

PURPOSE: Cardiac transition from concentric (C-LVH) to eccentric left ventricle hypertrophy (E-LVH) is a maladaptive response of hypertension. Matrix metalloproteinases (MMPs), in particular MMP-2, may contribute to tissue remodeling by proteolyzing extra- and intracellular proteins. Troponin I and dystrophin are two potential targets of MMP-2 examined in this study and their proteolysis would impair cardiac contractile function. We hypothesized that MMP-2 contributes to the decrease in troponin I and dystrophin in the hypertensive heart and thereby controls the transition from C-LVH to E-LVH and cardiac dysfunction. METHODS: Male Wistar rats were divided into sham or two kidney-1 clip (2K-1C) hypertensive groups and treated with water (vehicle) or doxycycline (MMP inhibitor, 15 mg/kg/day) by gavage from the tenth to the sixteenth week post-surgery. Tail-cuff plethysmography, echocardiography, gelatin zymography, confocal microscopy, western blot, mass spectrometry, in silico protein analysis and immunofluorescence were performed. RESULTS: 6 out of 23 2K-1C rats (26%) had E-LVH followed by reduced ejection fraction. The remaining had C-LVH with preserved cardiac function. Doxycycline prevented the transition from C-LVH to E-LVH. MMP activity is increased in C-LVH and E-LVH hearts which was inhibited by doxycycline. This effect was associated with an increase in troponin I cleavage products and a decline in dystrophin in the left ventricle of E-LVH rats, which was prevented by doxycycline. CONCLUSION: Hypertension causes increased cardiac MMP-2 activity which proteolyzes troponin I and dystrophin, contributing to the transition from C-LVH to E-LVH and cardiac dysfunction.