Effect of dithiocarbamate thiram on Wistar rat growth plate and articular cartilage

Avaliou-se o efeito do tirame, ditiocarbamato largamente utilizado na agricultura como antifúngico e repelente de roedores, na ossificação endocondral de mamíferos, usando, como modelo, ratos Wistar. Não foram observadas lesões na cartilagem articular, nem nas placas de crescimento, o que pode ser atribuído à dose utilizada e à duração do ensaio. A diminuição da altura da placa de crescimento nos animais aos quais foi administrado o tirame parece traduzir o atraso verificado no crescimento em geral, e não um efeito específico na cartilagem, uma vez que as diferentes zonas da placa epifisária mantiveram as proporções dos animais do grupo-controle. Embora não tenham sido verificados, no presente trabalho, os efeitos registrados para outras espécies nos tecidos cartilaginosos, sugere-se a avaliação dos efeitos crónicos do tirame no crescimento e no desenvolvimento dos ossos longos em mamíferos

Neck and supraclavicular lymphadenopathy secondary to 9-valent human papillomavirus vaccination

We present two clinical cases of lymphadenopathy after vaccination with the human papillomavirus (HPV) 9-valent vaccine: an asymptomatic 11-year-old boy with inferior cervical and supraclavicular lymphadenopathy, and a 13-year-old girl who presented with lymphadenopathy. In both cases, medical history was unremarkable and there was no recent infection, or other clinical findings. Both adolescents had received the HPV 9-valent vaccine in the previous week. In the first case, blood tests, ultrasonography and biopsy were performed, while in the second, a watchful waiting strategy was adopted. In both cases, the lymphadenopathy resolved spontaneously. The boy received the second dose of the vaccine 6 months later and lymphadenopathy reappeared. The Naranjo scale was applied, classifying the events as definite (in the case of the boy) and probable (girl) adverse drug reactions. The vaccine is safe, but recognising this minor adverse event is important to prevent unnecessary investigation and reduce patient and parental anxiety.info:eu-repo/semantics/publishedVersio

Chronic pancreatitis in children: treat like an adult?

A 15-year-old boy with a medical background of obesity, familial hyperlipidemia and acute recurrent pancreatitis, presented to emergency department reporting a 3-day course of periumbilical abdominal pain and nausea. Pain was noticed on epigastric palpation. Laboratory evaluation revealed leucocytosis, neutrophilia and pancreatic enzymes elevation more than three times the upper limit of normal. An acute recurrence of pancreatitis was diagnosed, was admitted to the hospital, being discharged after 5 days. Four days after, he was readmitted because of symptoms recurrence. Elevation of transaminases, gamma-glutamyltransferase (GGT) and direct bilirubin were noticed. Pancreatic enzymes still elevated but lower than in the previous episode. An endoscopic ultrasound revealed a Wirsung with a cephalic stricture and diffuse structural abnormalities suggestive of chronic pancreatitis. The patients was submitted to endotherapy with several sessions of endoscopic retrograde cholangiopancreatography including stenting and pancreatoscopy with marked clinical and imaging improvement. A genetic variant was identified.info:eu-repo/semantics/publishedVersio

Efeitos da semicarbazida no esqueleto de ratos Wistar em crescimento.

The effects of semicarbazide hydrochloride on skeletal tissues were evaluated using Wistar rats. In the animals submitted to the administration of semicarbazide, radiological examination showed bone and articular alterations with growth plates enlargement. Histological exams showed irregular patterns and proliferation of chondrocytes and excessive accumulation of extracellular matrix. Immunohistochemical exams showed PCNA positive reaction in pre- and hypertrofic chondrocytes. These results confirm that semicarbazide induces important changes in skeletal tissues and that has potential utility in experimental osteolathryrism

Cumulative Effect of Cardiovascular Risk Factors on Regulation of AMPK/SIRT1-PGC-1 alpha-SIRT3 Pathway in the Human Erectile Tissue

Cardiovascular disease risk factors (CVDRF), especially diabetes mellitus (DM), disrupt oxidative stress response. This condition underlies endothelial dysfunction, early manifested in men as erectile dysfunction. The current study is aimed at elucidating the impact of CVDRF in the oxidation responsive AMPK/SIRT1-PGC-1 alpha-SIRT3 pathway and related miRNAs in the human corpus cavernosum. Human penile tissue fragments from individuals submitted to programmed urological surgeries (n=27), aged 43-63 years, were clustered depending on the presence of CVDRF; the control group included samples from patients without CVDRF, and groups A and B included samples from patients with DM and additional CVDRF, totalizing = 3 CVDRF (group B). Dual-immunolabelling of SIRT3, SOD2, or GPX1 with alpha-actin in tissue sections was carried out. The assessment of expression levels of NOX1, phospho-AMPK alpha, total AMPK alpha, SIRT1, PGC-1 alpha, SIRT3, SOD2, and GPX1 was performed by western blotting and of miR-200a, miR-34a, miR-421, and miR-206 by real-time PCR. Phospho-AMPK alpha and SIRT3 expression was found significantly increased in group B relative to other groups, suggesting a marked influence of CVDRF, additional to DM, in the regulation of these enzymes. NOX1 was also increased in group B relative to controls. Only an increasing tendency was observed in the phospho-AMPK alpha/total AMPK alpha ratio, SIRT1, and PGC-1 alpha expression in groups A and B when compared with controls. Concerning antioxidant enzymes, GPX1 expression was found incremented in group A, but SOD2 expression was decreased in groups A and B, comparative with controls. Group B presented significantly diminished levels of miR-421 and miR-200a, but only a decreasing trend on miR-34 and miR-206 expression was observed. Taken together, our findings demonstrated that besides DM, additional CVDRF presented a cumulative effect in the cellular response to oxidative unbalance, contributing to AMPK/SIRT1-PGC-1 alpha-SIRT3 pathway activation. SOD2, a major mitochondrial antioxidant defence, did not follow the same variation

Identification of clinical predictors of flare in systemic lupus erythematosus patients: a 24-month prospective cohort study

Objective. SLE has a relapsing-remitting course with disease activity flares over time. This study aims to identify clinical predictors of SLE flares.Methods. This prospective cohort study over 24 months included all SLE patients on follow-up at one academic lupus clinic. Flare was defined as an increase in SLEDAI-2K score ≥4 points. Baseline clinical and demographic parameters were compared using survival analysis for time-to-flare outcome with univariate log-rank tests. Variables with significant differences were further evaluated as predictors with multivariate Cox regression models adjusting for potential confounding or contributing factors and hazard ratio (HR) calculation.Results. A total of 202 SLE patients were included. Over the follow-up period, 1083 visits were documented and 16.8% of patients presented with flares. In multivariate analysis, the following parameters emerged as flare predictors: SLE diagnosis up to 25 years of age (HR = 2.14, P = 0.03), lupus nephritis previous to baseline visit (HR = 4.78, P < 0.0001) and immunosuppressor treatment for severe SLE (HR = 3.22, P < 0.001). Baseline disease activity, disease duration and treatment with prednisone or HCQ were not predictive factors.Conclusion. Patients with an SLE diagnosis before age 25 years, lupus nephritis or immunosuppressor treatment for severe SLE present greater HRs for flares, suggesting the need for tighter clinical monitoring. Current immunosuppressive strategies seem to be inefficient in providing flare prevention

Measuring and mapping the effectiveness of the European Air Quality Directive in reducing N and S deposition at the ecosystem level

To protect human health and the environment (namely ecosystems), international air quality protocols and guidelines, like the Gothenburg protocol (1999) and the 2001 EU Air Quality Directive (NECD), conveyed national emission ceilings for atmospheric pollutants (Directive 2001/81/EC), including the reduction of sulfur (S) and nitrogen (N) emissions by 2010. However, to what degree this expected reduction in emissions had reflections at the ecosystem level (i.e. pollutant levels reaching and impacting ecosystems and their organisms) remains unknown. Here, we used lichens as ecological indicators, together with reported air and precipitation pollutant concentrations, to determine and map the consequences of the S and N atmospheric emission's reduction, during the implementation of the 2001 Directive (in 2002 and 2011), due primarily to the industrial-sector. The study area is a mixed-land-use industrialized Mediterranean agroforest ecosystem, in southwest Europe. The reduction of S emissions (2002-2011) was reflected at the ecosystem level, as the same S-declining trend was observed in atmospheric measurement stations and lichens alike (-70%), indicating that most S deposited to the ecosystem had an industrial origin. However, this was not the case for N with a slight N-reduction near industrial facilities, but mostly N-deposition in lichens increased in areas dominated by agricultural land-uses. Taken together, these results highlight the importance of going beyond emissions estimation and modeling, to assess the success of the implementation of the NECD in lowering pollutant accumulation in living organisms and their environment. This can only be achieved by measuring pollutant deposition at the ecosystem level (e.g. living organisms). By doing so, we were able to show that the 2001 NECD was successful in reducing S concentrations from Industry, whereas N remains a challenge. Despite the small reduction in N-emissions, deposition into ecosystems did not reflect these changes as agriculture and transport sectors must reduce NH3 and NOx emissions. (C) 2018 Published by Elsevier B.V.The research was supported by project GISA [funded by private companies: GALP, Repsol, APS, AdSA, AICEP, CARBOGAL, EDP, EuroResinas, KIMAXTRA, REN and GENERG; and managed by local authorities: CCDRA, ARSA and Municipalities of Sines, Santiago do Cacem, Grandola, Alcacer do Sal and Odemira]; article preparation was supported by project NitroPortugal [European Union's Horizon 2020 research and innovation programme under grant agreement No 692331]. NitroPortugal is a co-financer for the project Towards INMS, implemented by UN Environment. Concentration of pollutants in precipitation available in the EBAS database has largely been funded by the UN-ECE CLRTAP (EMEP) and through NILU internal resources

SYBR Green-based Real-Time PCR targeting kinetoplast DNA can be used to discriminate between the main etiologic agents of Brazilian cutaneous and visceral leishmaniases

<p>Abstract</p> <p>Background</p> <p>Leishmaniases control has been hampered by the unavailability of rapid detection methods and the lack of suitable therapeutic and prophylactic measures. Accurate diagnosis, which can distinguish between <it>Leishmania </it>isolates, is essential for conducting appropriate prognosis, therapy and epidemiology. Molecular methods are currently being employed to detect <it>Leishmania </it>infection and categorize the parasites up to genus, complex or species level. Real-time PCR offers several advantages over traditional PCR, including faster processing time, higher sensitivity and decreased contamination risk.</p> <p>Results</p> <p>A SYBR Green real-time PCR targeting the conserved region of kinetoplast DNA minicircles was able to differentiate between <it>Leishmania </it>subgenera. A panel of reference strains representing subgenera <it>Leishmania </it>and <it>Viannia </it>was evaluated by the derivative dissociation curve analyses of the amplified fragment. Distinct values for the average melting temperature were observed, being 78.95°C ± 0.01 and 77.36°C ± 0.02 for <it>Leishmania </it>and <it>Viannia</it>, respectively (p < 0.05). Using the Neighbor-Joining method and Kimura 2-parameters, the alignment of 12 sequences from the amplified conserved minicircles segment grouped together <it>L</it>. (<it>V</it>.) <it>braziliensis </it>and <it>L</it>. (<it>V</it>.) <it>shawii </it>with a bootstrap value of 100%; while for <it>L</it>. (<it>L</it>.) <it>infantum </it>and <it>L</it>. (<it>L</it>.) <it>amazonensis</it>, two groups were formed with bootstrap values of 100% and 62%, respectively. The lower dissociation temperature observed for the subgenus <it>Viannia </it>amplicons could be due to a lower proportion of guanine/cytosine sites (43.6%) when compared to species from subgenus <it>Leishmania </it>(average of 48.4%). The method was validated with 30 clinical specimens from visceral or cutaneous leishmaniases patients living in Brazil and also with DNA samples from naturally infected <it>Lutzomyia </it>spp. captured in two Brazilian localities.</p> <p>Conclusions</p> <p>For all tested samples, a characteristic amplicon melting profile was evidenced for each <it>Leishmania </it>subgenus, corroborating the data from reference strains. Therefore, the analysis of thermal dissociation curves targeting the conserved kinetoplast DNA minicircles region is able to provide a rapid and reliable method to identify the main etiologic agents of cutaneous and visceral leishmaniases in endemic regions of Brazil.</p