Extensive intraocular melanoma with secondary glaucoma in a 15-month-old Thoroughbred filly.

A 15-month-old, grey, Thoroughbred filly presented for investigation of a 6-week history of corneal oedema and blepharospasm on the right eye (OD). The filly was otherwise healthy. Following ophthalmic examination, glaucoma on the OD was diagnosed. A space occupying mass within the anterior chamber was documented on transpalpebral ultrasonographic examination. This mass obliterated most of the anterior intraocular structures on the peripheral nasal side (corneal endothelium and drainage angle), leading to secondary glaucoma. After systemic and topical treatment addressing secondary glaucoma, the corneal oedema reduced. The mass was visualised as an irregularly rounded brown structure associated with the iris on the peripheral nasal side of the anterior chamber. Given the filly's signalment, location and appearance of the mass, a tentative diagnosis of intraocular melanoma was made and enucleation was performed. Histopathological evaluation of the globe revealed solid sheets of heavily pigmented melanocytic cells, disrupting the normal ciliary body architecture and extending into the iris and subretinal. The cells were pleomorphic, polyhedral to round with occasional spindle-shaped cells, and contained moderate to large amounts of granular black-brown pigment (melanin). The iridal component expanded into the anterior chamber, with cells directly opposed to Descemet's membrane, with loss of the endothelium and expanding and occluding the filtration angle in this area. The lesion infiltrated locally into the edge of the sclera, but did not extend through the sclera, though occasional perivascular clusters of melanophages were observed within the scleral stroma adjacent to the optic nerve. Diagnosis of a uveal melanocytic neoplasm was confirmed, with characteristics similar to only one reported case . This is a unique case of a rapidly growing, invasive, uveal melanoma in a young horse. Intraocular melanoma should be considered as a differential diagnoses for glaucoma in grey horses, regardless of the age and absence of melanocytic skin lesions.

Use of recombinant tissue plasminogen activator (rTPA) for treatment of fibrin in the anterior chamber of the horse.

BACKGROUND: Recombinant intracameral tissue plasminogen activator (rTPA) administration can aid clearance of fibrin from the anterior chamber. MATERIALS AND METHODS: In this retrospective multicentre case series, the effect of intracameral rTPA administration to treat fibrin in the anterior chamber resulting from trauma or inflammatory ocular disease was evaluated. Clinical data from 30 treatments in 29 horses were obtained from medical records from 2003 to 2022. Association between time from onset of clinical signs and time for rTPA treatment to effect was studied with regression analysis. RESULTS: Twenty-seven horses (93.1%) had no previous history of ophthalmic disease; one had an iridic cyst, and another had equine recurrent uveitis. The majority of cases were related to trauma (79.3%). Median time from the onset of clinical signs to treatment was 12 h (IQR = 4-48 h). rTPA (72% 20 µg; 24% 25 µg; 3.3% 40 µg) was administered once in all but one eye, which was treated twice. Resolution of fibrin was seen in 96.9% (29/30) of treatments. Fibrin accumulation recurred in one case but resolved 14 days after the second treatment. Complications were seen in four treatments (13.3%): moderate pain for 24 h, intracameral debris and mild intracameral haemorrhage in a horse that received 40 µg of tissue plasminogen activator. Recurrence of fibrin accumulation was absent in 96.7% of cases. Median time to effect was 20 min (IQR = 10-45 min). Time for rTPA treatment to effect was not associated with time from fibrin formation (R2 = 0.09; p = 0.11). CONCLUSION: Intracameral rTPA treatment can be considered at 20-25 µg in 0.1 mL solution to aid resolution of fibrin accumulation.

Evaluation of peritoneal l-lactate concentration in horses in the early post-partum period.

BACKGROUND: Peritoneal fluid lactate concentration is an important diagnostic tool in horses with abdominal pain. Information on peritoneal lactate concentrations is lacking following parturition in the mare. OBJECTIVES: To compare blood and peritoneal lactate concentrations in a population of mares within 36 h post-partum, report a normal reference range and identify any impact of retained foetal membranes (RFMs). METHODS: This is a retrospective study evaluating healthy mares from which blood and peritoneal samples had been obtained within 36 h of parturition. Exclusion criteria included signs of abdominal pain within this period. Data was interrogated for normality using a Shapiro-Wilk test. Wilcoxon signed-rank test and Bland-Altman analysis were used to compare blood and peritoneal lactate concentrations. Linear regression was used to compare age and breed data with peritoneal lactate concentrations. Significance was defined as p < 0.05. RESULTS: Forty mares met the inclusion criteria. Mean age was 12.6 ± 4.1 years, and most mares were multiparous (65%). Peritoneal lactate ((1.2 (IQR = 0.9-1.6) mmol/L) was increased compared to blood lactate concentration (0.7 (IQR = 0-1.1)mmol/L; p < 0.001). Plasma total protein (TP) concentrations were 68 (IQR = 64-74) g/L and peritoneal protein concentrations 8 (IQR = 4-9.7) g/L. Six mares developed RFM. The median fold-increase in peritoneal lactate concentration compared to blood lactate concentration was 0.9 (IQR: 0.01-1.7; range: 0-2.5). The reference range for peritoneal fluid lactate concentration was 0-2.5 mmol/L. CONCLUSION: Peritoneal lactate concentrations in healthy post-partum mares remained within the normal reference range and were not influenced by RFM or parturition. Increased peritoneal lactate in this group warrants further investigation.

Topical Intervention of Natural Products Applied in Patients with Pressure Injuries: A Scoping Review.

OBJECTIVE: Pressure injuries (PIs) represent a major medical and nursing problem in individuals with decreased or limited mobility. This scoping review aimed to map the controlled clinical trials with topical interventions of natural products applied to patients with PIs and to verify the existence of phytochemical similarities among these products. DATA SOURCES: This scoping review was developed according to the JBI Manual for Evidence Synthesis. Controlled trials were searched in the following electronic databases from their inceptions until February 1, 2022: Cochrane Central Register of Controlled Trials, EMBASE, PubMed, SciELO, Science Direct, and Google Scholar. STUDY SELECTION: Studies involving individuals with PIs, individuals treated with topical natural products compared to a control treatment, and outcomes with wound healing or wound reduction were included in this review. DATA EXTRACTION: The search identified 1,268 records. Only six studies were included in this scoping review. Data were independently extracted using a template instrument from the JBI. DATA SYNTHESIS: The authors summarized the characteristics of the six included articles, synthesized outcomes, and compared similar articles. Honey and Plantago major dressings were the topical interventions that significantly reduced wound size. The literature suggests that the effect on wound healing of these natural products may be related to the presence of phenolic compounds. CONCLUSIONS: The studies included in this review show that natural products can positively impact the healing of PIs. However, there are limited controlled clinical trials addressing natural products and PIs in the literature.

A DFT analysis of electronic, reactivity, and NLO responses of a reactive orange dye: the role of Hartree-Fock exchange corrections.

An experimental and theoretical study based on DFT/TD-DFT approximations is presented to understand the nature of electronic excitations, reactivity, and nonlinear optical (NLO) properties of reactive orange 16 dye (RO16), an azo chromophore widely used in textile and pharmacological industries. The results show that the solvent has a considerable influence on the electronic properties of the material. According to experimental results, the absorption spectrum is formed by four intense transitions, which have been identified as [Formula: see text] states using TD-DFT calculations. However, the TD-DFT results reveal a weak [Formula: see text] in the low-lying spectral region. Continuum models of solvation indicate that these states suffer from bathochromic (ca. 15 nm) and hypsochromic shifts (ca. 4 nm), respectively. However, the expected blue shift for the absorption [Formula: see text] is only described using long-range or dispersion-corrected DFT methods. RO16 is classified as a strong electrophilic system, with electrophilicity ω > 1.5 eV. Concerning the nucleophilicity parameter (N), from vacuum to solvent, the environment is active and changes the nucleophilic status from strong to moderate nucleophile (2.0 ≤ N ≤ 3.0 eV). The results also suggest that all electrical constants are strongly dependent on long-range and Hartree-Fock exchange contributions, and the absence of these interactions gives results far from reality. In particular, the results for the NLO response show that the chromophore presents a potential application in this field with a low refractive index and first hyperpolarizability ca. 214 times bigger than the value usually reported for urea (ß = 0.34 × 10- 30 esu), which is a standard NLO material. Concerning the solvent effects, the results indicate that the polarizability increases [Formula: see text] esu from gas to solvent while the first hyperpolarizability is calculated as [Formula: see text] esu, ca. 180%, regarding the vacuum. The results suggest RO16 is a potential compound in NLO applications. Graphical Abstract The frontier molecular orbitals, and the inverse relation between the energy-gap (Egap) and the first hyperpolarizability (ß).

Effectiveness of a new rutin Cu(II) complex in the prevention of lipid peroxidation and hepatotoxicity in hypercholesterolemic rats.

A new rutin copper(II) complex (R-Cu2) was prepared and characterized by spectroscopic methods and elemental analysis. The effects of rutin and R-Cu2 were evaluated on the prevention of hypercholesterolemia in animals feed with high-cholesterol diet (HCD) for 8 weeks. The animals (n = 5) were neither fed with HCD nor treated (control group), or were treated with vehicle, 10 mg/kg simvastatin, rutin (16 and 160 µmol/kg), and R-Cu2 (16 and 160 µmol/kg) administered orally. Total cholesterol (TC) levels were significantly increased (p < .01) in all HCD groups. In rutin and R-Cu2 groups, it was observed a discrete, but not significant, TC and LDL-induced increase inhibition compared with vehicle-treated group. R-Cu2 treatment significantly decreased (p < .05) plasma triglycerides compared with the vehicle-treated group. All groups receiving treatments maintained the malondialdehyde at normal levels. Serum NO levels were reduced in animals treated with rutin and R-Cu2 compared with the vehicle-treated group. In addition, the results also showed that the groups treated with rutin and R-Cu2 reduced significantly (p < .01), the number of neutrophils and prevented histological changes in all evaluated liver zones. R-Cu2 group maintained the ALT, AST, and ALP enzymes at normal levels. Thus, the effects of R-Cu2 in modulating inflammation and protecting liver damage were confirmed. PRACTICAL APPLICATIONS: Rutin, a plant-derived flavonoid, is one of phenolic compounds well known as a nutraceutical due to its antioxidant and anti-inflammatory properties. Findings of this study demonstrate the effects of both rutin and R-Cu2 in modulating inflammation and protecting liver damage in hypercholesterolemic rats. However, some effects analyzed became more evident in R-Cu2. Thereby, it was shown that the synthesis of a new flavonoid compound (R-Cu2) could be applied as a nutraceutical benefit option to prevent hypercholesterolemia condition.

Renewable energy consumption and economic growth: a note reassessing panel data results.

We contribute to the renewable energy consumption-income (and growth) nexus literature by performing an empirical study on a worldwide panel database that, depending on data availability, covers between 146 and 161 countries for the period of 1960 to 2019 (59 years), enabling much more observations than most of the literature on the subject. The empirical methodology used accounts for cross-country dependency, heterogeneity and common effects amongst countries using a parsimonious specification that controls for traditional sources of income differences as well as institutional features of the countries. We also run an error correction model to check the impact of the share of the renewables on the income on the long run. Our results give support to the use of models that control for cross dependence giving a more accurate depiction of the renewable energy consumption-income nexus, showing either a negative or nonsignificant influence of the share of renewable energies consumption in the short run and a possible positive effect in the long run.

Evaluation of Volatilomic Fingerprint from Apple Fruits to Ciders: A Useful Tool to Find Putative Biomarkers for Each Apple Variety.

Aroma is a crucial criterion to assess the quality of apple fruits, juices, and ciders. The aim of this study was to explore similarities and differences in volatile profiles among apple fruits, juices, and ciders from different apple varieties (Festa, Branco, and Domingos) by headspace solid-phase microextraction gas chromatography-mass spectroscopy (HS-SPME/GC-MS). A total of 142 volatile organic compounds (VOCs) were identified, but only 9 were common in all analysed matrices and apple-tested varieties. Esters, alcohols, and aldehydes presented a higher concentration in apple fruits and juices, whereas esters, alcohols, and acids were dominant in ciders. Moreover, there were unique VOCs for each matrix and for each variety, highlighting the importance of the selection of apple varieties as an important factor to obtain good sensory and quality ciders, multiple benefits, and legal protection against the misuse of local products.

Clinical randomized trial study of hearing aids effectiveness in association with Ginkgo biloba extract (EGb 761) on tinnitus improvement / Estudo clínico randomizado da eficácia da prótese auditiva associada ao extrato de Ginkgo biloba (EGb 761) na melhoria do zumbido

Abstract Introduction: Tinnitus is defined as the perception of sound without its actual presence in the environment. It has been the subject of a great number of studies, especially considering its consequences on patient's quality of life. Objective: This study aimed to investigate the effect of hearing aids and/or Ginkgo biloba extract EGb 761 on tinnitus in patients with hearing loss. Methods: This is a trial randomized-controlled treatment, parallel, double-blind, with three-arm. Thirty-three adults subjects were divided into three groups: group 1 — subjects undergoing drug therapy with Ginkgo biloba extract EGb 761; group 2 — individuals fitted with digital hearing aids; group 3 — individuals submitted to drug therapy with Ginkgo biloba extract EGb 761 and using hearing aids. The tinnitus handicap inventory and visual analogue scale were used to evaluate self-perception of tinnitus loudness and severity before treatment and 90 days after treatment. Results: This study demonstrated a significant correlation between tinnitus handicap inventory and visual analogue scale, before and after treatment. We observed a significant improvement in self-perception of tinnitus loudness and severity after 90 days of treatment with Ginkgo biloba extract EGb 761 and/or hearing aids. No correlation was found between tinnitus onset time and self-perception of tinnitus loudness and severity. Hearing aids were more effective in patients with a shorter tinnitus onset time and Ginkgo biloba extract was effective regardless of tinnitus duration. Conclusions: It was possible to prove the effectiveness of the hearing aids and/or Ginkgo biloba extract EGb 761 treatment, which shows success in the control of tinnitus contributing to the improvement of this symptom.

Resumo Introdução: O zumbido é definido como a percepção de um som sem a sua presença real no ambiente e tem sido objeto de um grande número de estudos, especialmente devido às suas consequências na qualidade de vida do paciente. Objetivo: Investigar o efeito de próteses auditivas e/ou extrato de Ginkgo biloba EGb 761 sobre o zumbido em pacientes com perda auditiva. Método: Ensaio clínico randomizado controlado, paralelo, duplo-cego, com três braços. Trinta e três indivíduos adultos foram divididos em três grupos: Grupo 1 - indivíduos submetidos à terapia medicamentosa com extrato de Ginkgo biloba EGb 761; Grupo 2 - indivíduos equipados com próteses auditivas digitais; Grupo 3 - indivíduos submetidos à terapia medicamentosa com extrato de Ginkgo biloba EGb 761 e próteses auditivas. O Tinnitus handicap inventory e a escala visual analógica foram usados para avaliar a autopercepção de intensidade e da gravidade do zumbido antes do tratamento e 90 dias após o tratamento. Resultados: Este estudo demonstrou uma correlação significante entre o Tinnitus handicap inventory e a escala visual analógica, antes e após o tratamento. Observou-se melhoria significativa na autopercepção de loudness e da intensidade do zumbido após 90 dias de tratamento com extrato de Ginkgo biloba EGb 761 e/ou prótese auditiva. Não foi encontrada correlação entre o tempo de início do zumbido e a autopercepção da intensidade e gravidade do zumbido. As próteses auditivas foram mais eficazes em pacientes com menor tempo de início de zumbido e o extrato de Ginkgo biloba foi eficaz, independentemente da duração do zumbido. Conclusões: Foi possível comprovar a eficácia do tratamento com a prótese auditiva e/ou extrato de Ginkgo biloba EGb 761, o que demonstra sucesso no controle do zumbido e contribui para a melhoria desse sintoma.

Geographical differentiation of apple ciders based on volatile fingerprint.

With the globalization of food trade, it's traceability and genuineness becomes increasingly more difficult. Therefore, it is necessary to develop analytical tools to define the authenticity and genuineness of food-derived products. In the current work, headspace solid-phase microextraction followed by gas chromatography-mass spectrometry (HS-SPME/GC-MS) combined with chemometric tools was used to establish the volatile fingerprint of apple ciders produced in different geographical regions of Madeira Island, in order to define their typicity and to identify putative geographical markers. A total of 143 volatile organic compounds (VOCs) belonging to different chemical families have been identified, of which 28 were found in all apple ciders independently of geographical region. Esters, terpenic and furanic compounds presented on average a higher contribution for the total volatile fingerprint in cider produced in northern region of the Island, whereas alcohols, acids, volatile phenols, carbonyl compounds and lactones in cider from southern region. Considering the relative areas of the VOCs, 43 revealed statistically significant differences (p < 0.001) between geographical regions, and 11 between northern and southern regions. A clear differentiation among cider-producing regions was observed on the developed partial least squares-discriminant analysis (PLS-DA) model. Two alcohols (1-hexanol, 1-octanol), 6 esters (methyl acetate, (Z)-3-hexen-1-ol acetate, ethyl hexanoate, ethyl nonanote, ethyl octanoate, isoamyl octanoate) and 1 terpenic compound (limonene), can be considered putative geographic markers due to their discriminatory ability. The results obtained recognize the specific and typical geographical characteristics of the cider, which will allow the forthcoming guarantee for the construction of a sustainable platform for the establishment of the authenticity and typicality of the regional cider.

Application of Natural Pigments in Ordinary Cooked Ham.

The possibility of obtaining a carmine or pink color on ordinary cooked ham by applying natural dyes from three plant species, namely red radish (Raphanus sativus L.), hibiscus (Roselle sabdariffa L.) and red beetroot (Beta vulgaris L.), was investigated. The extracts were evaluated for the stability at physical-chemical parameters and subjected to cytotoxicity assays in the gastric cell line AGS Encapsulation of the extracts in soybean lecithin liposomes and maltodextrin microcapsules was performed. Lyophilized extracts before and after encapsulation in maltodextrin were applied in the formulation of ordinary cooked ham and used in a pilot scale of production. The color of cooked ham samples from different assays was evaluated visually and by colorimetry. The results suggest that the coloration of ordinary cooked ham obtained with extracts of red beetroot is very promising for future applications in this type of meat product.

Prevalence of contamination by intestinal parasites in vegetables (Lactuca sativa L. and Coriandrum sativum L.) sold in markets in Belém, northern Brazil.

BACKGROUND: Previous studies have recorded a high prevalence of intestinal parasites in lettuce (Lactuca sativa L.) and coriander (Coriandrum sativum L.) destined for human consumption. This study determined the prevalence of contamination by intestinal parasites in these two plants sold in two street markets and two supermarkets in the city of Belém, northern Brazil. RESULTS: A total of 200 plant samples were analyzed (100 of each species). The samples were collected randomly between August and October 2018, examined by the spontaneous sedimentation method with two washes, and stored for 24 h. The analysis found that 89% (89/100) of the lettuce samples and 86% (86/100) of the coriander samples were contaminated. Polyparasitism was more frequent in lettuce, but monoparasitism predominated in the coriander. A total of 226 intestinal parasites were found in the lettuce, with a predominance of non-pathogenic parasites in the supermarket samples and more pathogenic parasites in the samples from street markets. In the coriander samples, 172 intestinal parasites were identified, with a predominance of pathogenic parasites in samples from both types of market. In the case of the protozoans, the most prevalent species was Endolimax nana, followed by Blastocystis hominis, in both vegetables. In the helminths, hookworms predominated in the lettuce, and Trichuris trichiura in the coriander. CONCLUSIONS: These results highlight the need for the monitoring of parasite contamination in vegetables destined for human consumption. Public health initiatives should include educational campaigns on the importance of disinfecting vegetables prior to consumption. © 2020 Society of Chemical Industry.

Clinical randomized trial study of hearing aids effectiveness in association with Ginkgo biloba extract (EGb 761) on tinnitus improvement.

INTRODUCTION: Tinnitus is defined as the perception of sound without its actual presence in the environment. It has been the subject of a great number of studies, especially considering its consequences on patient's quality of life. OBJECTIVE: This study aimed to investigate the effect of hearing aids and/or Ginkgo biloba extract EGb 761 on tinnitus in patients with hearing loss. METHODS: This is a trial randomized-controlled treatment, parallel, double-blind, with three-arm. Thirty-three adults subjects were divided into three groups: group 1 - subjects undergoing drug therapy with Ginkgo biloba extract EGb 761; group 2 - individuals fitted with digital hearing aids; group 3 - individuals submitted to drug therapy with Ginkgo biloba extract EGb 761 and using hearing aids. The tinnitus handicap inventory and visual analogue scale were used to evaluate self-perception of tinnitus loudness and severity before treatment and 90 days after treatment. RESULTS: This study demonstrated a significant correlation between tinnitus handicap inventory and visual analogue scale, before and after treatment. We observed a significant improvement in self-perception of tinnitus loudness and severity after 90 days of treatment with Ginkgo biloba extract EGb 761 and/or hearing aids. No correlation was found between tinnitus onset time and self-perception of tinnitus loudness and severity. Hearing aids were more effective in patients with a shorter tinnitus onset time and Ginkgo biloba extract was effective regardless of tinnitus duration. CONCLUSIONS: It was possible to prove the effectiveness of the hearing aids and/or Ginkgo biloba extract EGb 761 treatment, which shows success in the control of tinnitus contributing to the improvement of this symptom.

COVID-19: ações multiprofissionais em cuidados paliativos / COVID-19: multiprofessional actions in palliative care

A pandemia Covid-19 tem se mostrado de elevado contágio e gravidade, cau-sando preocupação em todo o mundo. Sem forma efetiva para combatê-la, exceto medidas de prevenção e suporte clínico, com pessoas infectadas, evidenciando grandes proporções de contaminação e óbitos na população, revela uma situação de emergência mundial, que modifica as rotinas de serviços de saúde, obrigan-do-os a uma mobilização e reorganização para suprir tais demandas. Pacientes manifestam sintomas importantes, familiares a distância vivem intenso sofrimento por não poderem ter contato com seus entes enfermos, profissionais de saúde com impacto na sua própria saúde devido a mudanças na realidade de trabalho, isolamento social exacerbando desequilíbrio emocional e escassez de recursos de saúde para suprir todas as demandas são apenas algumas alterações causadas pelo fenômeno do novo coronavírus. Neste contexto, os cuidados paliativos devem ser indicados como prática assistencial, ampliando os cuidados aos familiares e entes queridos, à equipe de saúde e qualquer pessoa que sofra por estar envolvida neste panorama de uma doença grave ou incurável. A equipe multiprofissional en-volvida no cuidado terá por objetivo identificar, acolher, controlar e tratar sofrimentos físicos, psicológicos, sociais e espirituais, buscando qualidade de vida, conforto, autonomia, respeito e dignidade a todos os envolvidos. Deste modo, os cuidados paliativos devem ser mais amplamente praticados, agregando qualidade na atenção às pessoas afetadas pela doença durante a pandemia Covid-19, uma vez que tem sua importância reconhecida universalmente.

BONE MINERAL DENSITY AND BODY COMPOSITION IN ELDERLY RUNNERS: SIX-YEAR FOLLOW-UP.

OBJECTIVE: To evaluate bone mineral density (BMD) and body composition over a six-year period in elderly long-distance runners. METHODS: We analyzed the medical records of elderly athletes who were long-distance runners, were participants of the IOT-HCFMUSP Orthogeriatric Group, and had their BMD evaluated between 2001 and 2007; of these athletes, 11 were included in the study. Inclusion criteria: athletes should be long-distance runners, should not stop long-distance running during the six-year period, and should have undergone BMD and body composition evaluations. Body composition was evaluated using bone densitometry with dual-energy X-ray absorptiometry with a Lunar-DPX device. RESULTS: Over the six-year period, body composition remained stable, but there was a significant increase only in the fat percentage (p = 0.003). CONCLUSION: Long-distance running may maintain BMD but may lead to an increase in the fat percentage in elderly runners. Level of Evidence II; Prognostic Study - Investigating the Effect of Patient Characteristics on Disease Outcome.

OBJETIVO: Acompanhar a densidade mineral óssea (DMO) e a composição corporal, ao longo de seis anos, em idosos corredores de longa distância. MÉTODOS: analisamos os prontuários médicos de um grupo de atletas idosos, corredores de longa distância, participantes do Grupo de Ortogeriatria do IOT-HC-FMUSP, e reunimos todos os atletas que tiveram a DMO avaliada no ano de 2001 e de 2007, sendo destes, 11 prontuários selecionados. Critérios de inclusão: ser corredor de longa distância; não parar de correr ao longo dos seis anos e ter os dois exames de DMO e composição corporal avaliados. A composição corporal foi avaliada por meio de densitometria óssea, com uma dupla energia de absorção de raios-X (DEXA), em um aparelho LUNAR-DPX. RESULTADOS: Ao longo dos seis anos, a composição corpórea se manteve estável, havendo apenas um aumento significante na gordura expressa em (%) (p=0,003). CONCLUSÃO: A corrida de longa distância parece conservar a DMO de idosos corredores, porém com aumento de gordura. Nível do Evidência II; Estudos prognósticos - Investigação do efeito de características de um paciente sobre o desfecho da doença.

Bone mineral density and body composition in elderly runners: six-year follow-up / Densidade mineral óssea e composição corporal de idosos corredores: follow-up de seis anos

ABSTRACT Objective: To evaluate bone mineral density (BMD) and body composition over a six-year period in elderly long-distance runners. Methods: We analyzed the medical records of elderly athletes who were long-distance runners, were participants of the IOT-HCFMUSP Orthogeriatric Group, and had their BMD evaluated between 2001 and 2007; of these athletes, 11 were included in the study. Inclusion criteria: athletes should be long-distance runners, should not stop long-distance running during the six-year period, and should have undergone BMD and body composition evaluations. Body composition was evaluated using bone densitometry with dual-energy X-ray absorptiometry with a Lunar-DPX device. Results: Over the six-year period, body composition remained stable, but there was a significant increase only in the fat percentage (p = 0.003). Conclusion: Long-distance running may maintain BMD but may lead to an increase in the fat percentage in elderly runners. Level of Evidence II; Prognostic Study - Investigating the Effect of Patient Characteristics on Disease Outcome.

RESUMO Objetivo: Acompanhar a densidade mineral óssea (DMO) e a composição corporal, ao longo de seis anos, em idosos corredores de longa distância. Métodos: analisamos os prontuários médicos de um grupo de atletas idosos, corredores de longa distância, participantes do Grupo de Ortogeriatria do IOT-HC-FMUSP, e reunimos todos os atletas que tiveram a DMO avaliada no ano de 2001 e de 2007, sendo destes, 11 prontuários selecionados. Critérios de inclusão: ser corredor de longa distância; não parar de correr ao longo dos seis anos e ter os dois exames de DMO e composição corporal avaliados. A composição corporal foi avaliada por meio de densitometria óssea, com uma dupla energia de absorção de raios-X (DEXA), em um aparelho LUNAR-DPX. Resultados: Ao longo dos seis anos, a composição corpórea se manteve estável, havendo apenas um aumento significante na gordura expressa em (%) (p=0,003). Conclusão: A corrida de longa distância parece conservar a DMO de idosos corredores, porém com aumento de gordura. Nível do Evidência II; Estudos prognósticos - Investigação do efeito de características de um paciente sobre o desfecho da doença.

Urinary cytokine profiles according to the site of blockade of the renin-angiotensin system in nephrectomized rats.

INTRODUCTION: It is still unknown how the pharmacological inhibition of the Renin Angiotensin System (RAS) impacts the levels of inflammation and fibrosis biomarkers. OBJECTIVE: This study sought to evaluate the effect of enalapril, candesartan and aliskiren on urinary levels of cytokines in a model of chronic kidney disease (CKD). METHODS: Male Wistar rats were submitted to surgical removal of ¾ of renal parenchyma to induce CKD (¾ nephrectomy), or subjected to sham surgery (control). Animals were then randomized into five groups: Sham surgery receiving vehicle; ¾ Nephrectomy receiving vehicle; ¾ Nephrectomy receiving enalapril (10 mg/kg); ¾ Nephrectomy receiving candesartan (10 mg/kg) and ¾ Nephrectomy receiving aliskiren (10 mg/kg). Urine output, water intake, mean arterial pressure (MAP) and urinary concentrations of creatinine, urea, albuminuria, Na+, K+, interleukin (IL) -1ß, IL-6, IL-10 and transforming growth factor beta (TGF-ß) were measured. RESULTS: Nephrectomy significantly impaired renal function, increased MAP and altered the levels of all evaluated cytokines in urine. Enalapril, candesartan and aliskiren improved renal function and decreased MAP and IL-6 when compared to vehicle-treated nephrectomized group. Candesartan and aliskiren decreased IL-1ß, while only candesartan reduced TGF-ß and only aliskiren increased IL-10. CONCLUSION: Enalapril, candesartan and aliskiren presented similar effects on improving renal function and reducing MAP and urinary levels of IL-6 in rats with CKD. On the other hand, cytokine profile differed according to the treatment, suggesting that differential mechanisms were triggered in response to the site of RAS blockade.

Urinary cytokine profiles according to the site of blockade of the renin-angiotensin system in nephrectomized rats / Perfil de citocinas urinárias de acordo com o local de bloqueio do sistema renina angiotensina em ratos nefrectomizados

Abstract Introduction: It is still unknown how the pharmacological inhibition of the Renin Angiotensin System (RAS) impacts the levels of inflammation and fibrosis biomarkers. Objective: This study sought to evaluate the effect of enalapril, candesartan and aliskiren on urinary levels of cytokines in a model of chronic kidney disease (CKD). Methods: Male Wistar rats were submitted to surgical removal of ¾ of renal parenchyma to induce CKD (¾ nephrectomy), or subjected to sham surgery (control). Animals were then randomized into five groups: Sham surgery receiving vehicle; ¾ Nephrectomy receiving vehicle; ¾ Nephrectomy receiving enalapril (10 mg/kg); ¾ Nephrectomy receiving candesartan (10 mg/kg) and ¾ Nephrectomy receiving aliskiren (10 mg/kg). Urine output, water intake, mean arterial pressure (MAP) and urinary concentrations of creatinine, urea, albuminuria, Na+, K+, interleukin (IL) -1β, IL-6, IL-10 and transforming growth factor beta (TGF-β) were measured. Results: Nephrectomy significantly impaired renal function, increased MAP and altered the levels of all evaluated cytokines in urine. Enalapril, candesartan and aliskiren improved renal function and decreased MAP and IL-6 when compared to vehicle-treated nephrectomized group. Candesartan and aliskiren decreased IL-1β, while only candesartan reduced TGF-β and only aliskiren increased IL-10. Conclusion: Enalapril, candesartan and aliskiren presented similar effects on improving renal function and reducing MAP and urinary levels of IL-6 in rats with CKD. On the other hand, cytokine profile differed according to the treatment, suggesting that differential mechanisms were triggered in response to the site of RAS blockade.

Resumo Introdução: Ainda não se sabe como a inibição farmacológica do Sistema Renina Angiotensina (SRA) afeta os níveis de biomarcadores de inflamação e fibrose. Objetivo: Este estudo pretendeu avaliar o efeito de enalapril, candesartan e alisquireno sobre os níveis urinários de citocinas em um modelo de doença renal crônica (DRC). Métodos: Ratos Wistar machos foram submetidos à remoção cirúrgica de ¾ do parênquima renal para induzir DRC (nefrectomia), ou submetidos à cirurgia fictícia (controle). Animais foram então randomizados em cinco grupos: Cirurgia fictícia recebendo veículo; Nefrectomia recebendo veículo; Nefrectomia recebendo enalapril (10 mg/kg); Nefrectomia recebendo candesartan (10 mg/kg) e Nefrectomia recebendo alisquireno (10 mg/kg). Débito urinário, ingesta hídrica, pressão arterial media (PAM) e concentrações urinárias de creatinina, ureia, albumina, Na+, K+, interleucina (IL) -1β, IL-6, IL-10 e fator de transformação e crescimento beta (TGF-β) foram medidas. Resultados: A nefrectomia comprometeu significativamente a função renal, aumentou a PAM e alterou os níveis de todas as citocinas avaliadas na urina. Enalapril, candesartan e alisquireno melhoraram a função renal e diminuíram a PAM e a IL-6 quando comparado aos grupo de animais nefrectomizados tratados com veículo. Candesartan e alisquireno reduziram IL-1β, enquanto somente candesartan diminuiu o TGF-β e somente alisquireno aumentou a IL-10. Conclusão: Enalapril, candesartan e alisquireno apresentaram efeitos similares em relação à melhora da função renal e redução da PAM e dos níveis urinários de IL-6 em ratos com DRC. Por outro lado, o perfil de citocinas diferiu de acordo com o tratamento, sugerindo que diferentes mecanismos sejam desencadeados em resposta ao local de bloqueio do SRA.

Sitagliptin inhibit human lymphocytes proliferation and Th1/Th17 differentiation in vitro.

Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of anti-diabetic agents that are widely used in clinical practice to improve glycemic control in patients with type 2 diabetes. DPP-4 is also known as lymphocyte cell surface protein, CD26, and plays an important role in T-cell immunity. Recent studies suggest that DPP-4 inhibitors improve beta-cell function and attenuate autoimmunity in type 1 diabetic mouse models. To investigate the direct effect of DPP4 in immune response, human peripheral blood mononuclear cells (PBMC) from healthy volunteers were obtained by Ficoll gradient and cultivated in the absence (control) or presence of phytohemagglutinin (PHA), or stimulated with PHA and treated with sitagliptin. The immune modulation mechanisms analyzed were: cell proliferation, by MTT assay; cytokine quantification by ELISA or cytometric bead array (CBA), Th1/Th2/Th17 phenotyping by flow cytometric analysis and CD26 gene expression by real time PCR. The results showed that sitagliptin treatment inhibited the proliferation of PBMC-PHA stimulated cells in a dose dependent manner and decreased CD26 expression by these cells, suggesting that sitagliptin may interfere in CD26 expression, dimerization and cell signaling. Sitagliptin treatment not only inhibited IL-10 (p<0.05) and IFN-gamma (p=0.07) cytokines, but also completely abolish IL-6 expression by PBMCs (p<0.001). On the other hand, IL-4 were secreted in culture supernatants from sitagliptin treated cells. A statistically significant increase (p<0.05) in the ratio of TGF-beta/proliferation index after sitagliptin treatment (2627.97±1351.65), when comparing to untreated cells (646.28±376.94), was also demonstrated, indicating higher TGF-beta1 production by viable cells in cultures. Sitagliptin treatment induced a significantly (p<0.05) decrease in IL-17 and IFN-gamma intracellular expression compared with PHA alone. Also, the percentage of T CD4+IL-17+, T CD4+IFNgamma+ and T CD4+IL-4+ cells were significantly reduced (p<0.05) by sitagliptin. Our data demonstrated an immunosuppressive effect of sitagliptin on Th1, Th17 and Th2 lymphocytes differentiation that leads to the generation of regulatory TGF-beta1 secreting cells with low CD26 gene expression that may influence the state of pancreatic beta-cells and controlling DM1 patients.

Characterization of an experimental model of progressive renal disease in rats.

PURPOSE:: To characterize an experimental model of progressive renal disease induced by different degrees of nephrectomy in rats. METHODS:: Eighty male Wistar rats were divided into four experimental groups (n=20/group): sham surgery (control group), progressive degrees of nephrectomy leading to mild uremia (group 1), moderate uremia (group 2) and severe uremia (group 3). Ten animals of each group were followed for two or four weeks. At the end, blood and 24-hour urine samples were collected to determine renal function parameters. Urine output and water and food intake were daily monitored. RESULTS:: In rats of group 1, serum levels of creatinine and urea and microalbuminuria were increased, while reduced creatinine clearance (p<0.05, compared with control group), without changing blood pressure. Animals of group 2 had more accentuated alterations: increases in urinary output, blood pressure, serum concentrations of urea, creatinine, sodium, potassium, and in microalbuminuria, and reduction of creatinine clearance (p<0.05). Group 3 exhibited even more increased serum concentrations of urea, creatinine, sodium and potassium, blood pressure and microalbuminuria, and decreased creatinine clearance (p<0.05) in comparison with control group and unilateral nephrectomy. CONCLUSION:: Progressive nephrectomy in rats seems to be useful to study the physiopathology of chronic kidney disease and its mechanisms of progression.