Avaliação da função renal em cães diabéticos : análise de indicadores

Dissertação de Mestrado Integrado em Medicina VeterináriaA diabetes mellitus (DM) é a doença mais comum do pâncreas endócrino no cão. É uma síndrome caracterizada por hiperglicemia crónica, glicosúria, polifagia, poliúria/polidipsia e perda de peso. A nefropatia diabética (ND) corresponde a uma possível complicação da DM que, no caso dos humanos, corresponde à principal causa de doença renal crónica nos países ocidentais. A ND é caracterizada por microalbuminúria, proteinúria, hipertensão arterial sistémica e perda de função renal. Os estudos realizados no âmbito da ND canina são escassos e, apesar da sua existência estar documentada, a sua expressão na prática clínica é baixa, o que a torna um tópico pouco discutido. Este estudo teve como principal objetivo avaliar a função renal em cães com diagnóstico de DM, assim como a ocorrência de proteinúria, de modo a identificar a presença, ou não, de ND. Foi também avaliada a correlação entre estas variáveis e o tempo desde o diagnóstico de DM e a dose de insulina instituída. O estudo incluiu 18 cães diabéticos e 17 cães saudáveis de idades e pesos idênticos. Nos cães diabéticos, 38,9% apresentaram um RPCU superior a 0,5. Este grupo apresentou ainda uma razão de possibilidades (odds ratio) de 10,87 (95% IC, 1,71-127,08, p <0,05) de desenvolver proteinúria em relação aos saudáveis. Apesar de os níveis de ureia não diferirem significativamente entre os dois grupos, o grupo diabético apresentou concentrações de creatinina e DMAS inferiores às encontradas no grupo saudável (p<0,05). Não foi encontrada uma correlação significativa entre as concentrações de ureia, creatinina, DMAS ou o RPCU e a duração do diagnóstico de DM, ou com a dose de insulina em curso. Apesar de a ND clínica ser improvável em cães, os resultados obtidos evidenciam o possível efeito da DM a nível renal. Os níveis inferiores de creatinina e DMAS nos cães diabéticos sugerem a ocorrência de hiperfiltração glomerular, o que pode indicar a presença de alterações hemodinâmicas renais. Além disto, estes cães apresentam uma maior possibilidade de desenvolver proteinúria, o que reforça a importância da monitorização do RPCU nestes animais. Este é o primeiro estudo de que temos conhecimento que não só avalia os valores de DMAS em cães diabéticos, como também os compara com os encontrados em cães saudáveis. Dos resultados obtidos poderemos inferir que os animais do nosso estudo com DM se possam encontrar numa fase de pré-nefropatia diabética, numa fase silenciosa, ou numa fase de nefropatia diabética incipiente. Continuam a ser necessários mais estudos que elucidem o impacto da DM sobre os biomarcadores de função e lesão renal de modo a melhor esclarecer a sua relevância na prática clínica veterinária.ABSTRACT - Diabetes mellitus (DM) is the most common disease of the endocrine pancreas in dogs. It’s a syndrome characterized by chronic hyperglycaemia, glycosuria, polyphagia, polyuria/polydipsia and weight loss. Diabetic nephropathy (DN) is a possible complication of DM that, in humans, is the main cause of chronic kidney disease in western countries. DN includes microalbuminuria, proteinuria, systemic hypertension and impaired kidney function. There are only a few studies regarding canine DN and, even though there are some reports of its occurrence in dogs, it isn’t a popular topic because of how rare it is in clinical practice. The aim of this study was to evaluate the renal function of dogs diagnosed with DM, as well as the occurrence of proteinuria, in order to identify the presence or absence of DN. We also tested if there was a correlation between these biomarkers and the time of diagnosis of DM and the insulin dosage they were being treated with. The study included 18 diabetic dogs and 17 healthy dogs with similar ages and weights. 38,9% of the diabetic dogs had an UPC ratio higher than 0,5. This group had an odds ratio of 10,87 (95% IC, 1,71-127,08, p<0,05) of developing proteinuria when compared to healthy ones. Even though the serum urea concentration didn’t differ between the two groups, diabetic dogs had significatively lower serum concentrations of creatinine and SDMA (p<0,05). There was no significant correlation between serum urea, creatinine or SDMA and UPC ratio and the time of diagnosis. We also didn’t find an association between any of these variables and insulin dosage. Even though the occurrence of clinical DN is unlikely in dogs, our results show the possible impact of DM on the kidney. The lower levels of serum creatinine and SDMA seen in diabetic dogs when compared to healthy ones suggest that glomerular hyperfiltration is present, which may be related with hemodynamic changes in the kidney. Besides, these dogs showed a higher chance of developing proteinuria, which reinforces the importance of UPC ratio assessment when monitoring these patients. To our knowledge, this is the first study that not only evaluates SDMA levels in diabetic dogs, but also compares them to those found in healthy ones. Our results suggest that the diabetic dogs in our study can be in a pre-diabetic nephropathy phase, in a silent phase or in an incipient diabetic nephropathy phase. More studies are needed in order to better understand how DM impacts kidney’s function and injury biomarkers and their relevance in veterinary practice.N/

The potential of Asparagopsis armata to control the bacterial load associated to live feed to improve Seabream (Sparus aurata) larvae performance

Dissertação de mestrado, Aquacultura e Pescas, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2014Seaweeds are a source of bioactive compounds producing a large variety of metabolites with a broad spectrum of biological activities. This work attempted to understand the use of A. armata metabolites in larval rearing of Sparus aurata, assessing its development and larval quality, by reducing the bacterial load associated with the live feed. Two A. armata products (a laboratory made extract and a commercial powder, Ysaline®100 - YSA) were tested in Brachionus spp. and Artemia sp. at different concentrations. YSA at 0.5 % was selected to be used during 30 min with live feed. The gilthead seabream larvae trial comprised one treatment where live feed was bathed with YSA vs. a Control (bathed with clear water) (each n = 4). Larval quality parameters (growth, survival, swimbladder inflation, body anomalies and caudal fin development), digestive capacity (digestive system histology and enzymatic activity), immune response (lysozyme activity and cortisol concentration) and microbiological parameters were monitored. Fish larvae from YSA exhibited higher growth rate than Control (P < 0.05). A higher food intake or a reduction of the bacterial load might justify this result. Still, lower survival rates were observed for YSA. This result might be related with variations of the bacterial community or/and to a possible ichthyotoxic effect of A. armata metabolites carried by the live feed. Treatment with YSA also influenced the whole body cortisol since lower concentrations were observed for this group. Further research on how cortisol mechanisms are affected is required to fully understand its effects. Seabream larvae from YSA exhibited lower number of bacteria, either for larvae ability to prevent or reduce the bacteria colonization, which can be related to an enhancement of larval fitness, or to the possibility that A. armata metabolites were carried to the larvae. The reduction of the bacterial load accomplished with live feed immersed for 30 min in YSA improved S. aurata larvae fitness, although the effects are not fully understood

Influence of Inappropriate Basic Sanitation and Lack of Access to Drinking Water in the Community Development of Azama, Otavalo Canton

This research work focuses on describing how inappropriate basic sanitation systems and the lack of accessibility to water suitable for human consumption (potable or safe) influence the community development of Azama. This urban community is part of the Otavalo canton. Through the identification of the characteristics of the basic sanitation service, access to safe water and the management classes implemented, as well as the particularities of the community development of the referred sector given the significance that each of these elements represents integral health, both physical and psychological of each human being at any stage of the life cycle. Throughout this research, it is possible to identify that the sanitation service and drinking water systems correspond to human rights that guarantee a dignified life for people and favor community development that strengthens the organization and participation of the community. However, there is still a lot to work from the public field and, where appropriate, also the collaboration of private entities to promote the comprehensive well-being of the inhabitants of the Azama community from their active social participation

Swimming abilities of temperate pelagic fish larvae prove that they may control their dispersion in coastal areas

The Sense Acuity and Behavioral (SAAB) Hypothesis proposes that the swimming capabilities and sensorial acuity of temperate fish larvae allows them to find and swim towards coastal nursery areas, which are crucial for their recruitment. To gather further evidence to support this theory, it is necessary to understand how horizontal swimming capability varies along fish larvae ontogeny. Therefore, we studied the swimming capability of white seabream Diplodus sargus (Linnaeus, 1758) larvae along ontogeny, and their relationship with physiological condition. Thus, critical swimming speed (U-crit) and the distance swam (km) during endurance tests were determined for fish larvae from 15 to 55 days post-hatching (DPH), and their physiological condition (RNA, DNA and protein contents) was assessed. The critical swimming speed of white seabream larvae increased along ontogeny from 1.1 cm s(-1) (15 DPH) to 23 cm s(-1) (50 and 55 DPH), and the distance swam by larvae in the endurance experiments increased from 0.01 km (15 DPH) to 86.5 km (45 DPH). This finding supports one of the premises of the SAAB hypothesis, which proposes that fish larvae can influence their transport and distribution in coastal areas due to their swimming capabilities. The relationship between larvae's physiological condition and swimming capabilities were not evident in this study. Overall, this study provides critical information for understanding the link between population dynamics and connectivity with the management and conservation of fish stocks.Funding Agency Portuguese Foundation for Science and Technology SFRH/BD/104209/2014 Portuguese Foundation for Science and Technology UID/Multi/04326/2019 FCT, under the Transitional Norm DL57/2016/CP[1361]/CT[CT0008 CLIMFISH project-A framework for assess vulnerability of coastal fisheries to climate change in Portuguese coast n2/SAICT/2017-SAICTinfo:eu-repo/semantics/publishedVersio

Neuropeptide kyotorphin (tyrosyl-arginine) has decreased levels in the cerebro-spinal fluid of Alzheimer’s disease patients: potential diagnostic and pharmacological implications

In Alzheimer’s disease (AD), besides the characteristic deterioration of memory, studies also point to a higher pain tolerance in spite of sensibility preservation. A change in the normal tau protein phosphorylation is also characteristic of AD, which contributes to the pathogenesis of the disease and is useful in early diagnosis. Kyotorphin (KTP) is an endoge-nous analgesic dipeptide (Tyr-Arg) for which there is evidence of eventual neuroprotective and neuromodulatory properties. The objective of this work was to study the possible cor-relation between KTP and phosphorylated tau protein (p-tau) levels in cerebro-spinal fluid (CSF) samples of AD patients. CSF samples were collected from 25 AD patients and 13 age-matched controls (N), where p-tau and KTP levels were measured.We found a statis-tically significant difference between p-tau/KTP values in AD and N groups with an inverse correlation between p-tau and KTP values in AD samples. These results suggest that in the future KTP may be a candidate biomarker for neurodegeneration and may be a lead compound to be used pharmacologically for neuroprotection.Fundação para a Ciência e Tecnologia (FCT, Portugal) is acknowledged for fellowship SFRH/BPD/79542/2011 to Sónia Sá Santos and Grant PTDC/QUI-BIQ/112929/2009. MarieCurie International Research Staff Exchange Scheme (IRSES) is also acknowledged forfunding (FP7-PEOPLE-2009-IRSES, project MEMPEPACROSS)

Influence of Inappropriate Basic Sanitation and Lack of Access to Drinking Water in the Community Development of Azama, Otavalo Canton

This research work focuses on describing how inappropriate basic sanitation systems and the lack of accessibility to water suitable for human consumption (potable or safe) influence the community development of Azama. This urban community is part of the Otavalo canton. Through the identification of the characteristics of the basic sanitation service, access to safe water and the management classes implemented, as well as the particularities of the community development of the referred sector given the significance that each of these elements represents integral health, both physical and psychological of each human being at any stage of the life cycle. Throughout this research, it is possible to identify that the sanitation service and drinking water systems correspond to human rights that guarantee a dignified life for people and favor community development that strengthens the organization and participation of the community. However, there is still a lot to work from the public field and, where appropriate, also the collaboration of private entities to promote the comprehensive well-being of the inhabitants of the Azama community from their active social participation

Effect of pH on the influenza fusion peptide properties unveiled by constant-pH molecular dynamics simulations combined with experiment

© The Author(s) 2020. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.The influenza virus fusion process, whereby the virus fuses its envelope with the host endosome membrane to release the genetic material, takes place in the acidic late endosome environment. Acidification triggers a large conformational change in the fusion protein, hemagglutinin (HA), which enables the insertion of the N-terminal region of the HA2 subunit, known as the fusion peptide, into the membrane of the host endosome. However, the mechanism by which pH modulates the molecular properties of the fusion peptide remains unclear. To answer this question, we performed the first constant-pH molecular dynamics simulations of the influenza fusion peptide in a membrane, extending for 40 µs of aggregated time. The simulations were combined with spectroscopic data, which showed that the peptide is twofold more active in promoting lipid mixing of model membranes at pH 5 than at pH 7.4. The realistic treatment of protonation introduced by the constant-pH molecular dynamics simulations revealed that low pH stabilizes a vertical membrane-spanning conformation and leads to more frequent contacts between the fusion peptide and the lipid headgroups, which may explain the increase in activity. The study also revealed that the N-terminal region is determinant for the peptide's effect on the membrane.This work was financially supported by FCT—Fundação para a Ciência e a Tecnologia, Portugal, through projects PTDC/QUI-BIQ/114774/2009, PTDC/CCI-BIO/28200/2017 and Pest-OE/EQB/LA0004/2011. This work was also financially supported by Project LISBOA-01-0145-FEDER-007660 (Microbiologia Molecular, Estrutural e Celular) funded by FEDER funds through COMPETE2020—Programa Operacional Competitividade e Internacionalização (POCI) and by national funds through FCT—Fundação para a Ciência e a Tecnologia. DL was supported by FCT post-doc fellowship SFRH/BPD/92537/2013.info:eu-repo/semantics/publishedVersio

Amidated and ibuprofen-conjugated kyotorphins promote neuronal rescue and memory recovery in cerebral hypoperfusion dementia model

Copyright © 2016 Sá Santos, Santos, Pinto, Ramu, Heras, Bardaji, Tavares and Castanho. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Chronic brain ischemia is a prominent risk factor for neurological dysfunction and progression for dementias, including Alzheimer's disease (AD). In rats, permanent bilateral common carotid artery occlusion (2VO) causes a progressive neurodegeneration in the hippocampus, learning deficits and memory loss as it occurs in AD. Kyotorphin (KTP) is an endogenous antinociceptive dipeptide whose role as neuromodulator/neuroprotector has been suggested. Recently, we designed two analgesic KTP-derivatives, KTP-amide (KTP-NH2) and KTP-NH2 linked to ibuprofen (IbKTP-NH2) to improve KTP brain targeting. This study investigated the effects of KTP-derivatives on cognitive/behavioral functions (motor/spatial memory/nociception) and hippocampal pathology of female rats in chronic cerebral hypoperfusion (2VO-rat model). 2VO-animals were treated with KTP-NH2 or IbKTP-NH2 for 7 days at weeks 2 and 5 post-surgery. After behavioral testing (week 6), coronal sections of hippocampus were H&E-stained or immunolabeled for the cellular markers GFAP (astrocytes) and NFL (neurons). Our findings show that KTP-derivatives, mainly IbKTP-NH2, enhanced cognitive impairment of 2VO-animals and prevented neuronal damage in hippocampal CA1 subfield, suggesting their potential usefulness for the treatment of dementia.Funding was provided by the Portuguese Agency Fundação para a Ciência e a Tecnologia SFRH/BPD/79542/2011 fellowship)info:eu-repo/semantics/publishedVersio

GENE DAS COVINHAS NAS BOCHECHAS: Uma análise sobre recessivos e dominantes

O presente trabalho apresenta uma atividade interdisciplinar realizada para asdisciplinas de biologia e matemática envolvendo genética e estatística. Acaracterística genética, covinha nas bochechas é o objeto de estudo, sendo esteum erro genético de caráter dominante. O desenvolvimento deste resumo fez-seestudando o conceito de genes recessivos e dominantes e pela análise dos cálculosobtidos do formulário aplicado aos discentes do IFC-CAS, para assim cumprir com oobjetivo: avaliar a veracidade do senso comum diante este assunto, juntamente coma análise sobre os recessivos e dominantes da característica referida. Pararesponder ao objetivo a metodologia mais qualificada foi a pesquisa quantitativa.Assim descobrimos que a característica referida apresenta predominânciarecessiva nos indivíduos, sem ter importância onde está inserido

The Neuroprotective Action of Amidated-Kyotorphin on Amyloid β Peptide-Induced Alzheimer’s Disease Pathophysiology

Kyotorphin (KTP, l-tyrosyl-l-arginine) is an endogenous dipeptide initially described to have analgesic properties. Recently, KTP was suggested to be an endogenous neuroprotective agent, namely for Alzheimer’s disease (AD). In fact, KTP levels were shown to be decreased in the cerebrospinal fluid of patients with AD, and recent data showed that intracerebroventricular (i.c.v.) injection of KTP ameliorates memory impairments in a sporadic rat model of AD. However, this administration route is far from being a suitable therapeutic strategy. Here, we evaluated if the blood-brain permeant KTP-derivative, KTP-NH2, when systemically administered, would be effective in preventing memory deficits in a sporadic AD animal model and if so, which would be the synaptic correlates of that action. The sporadic AD model was induced in male Wistar rats through i.c.v. injection of amyloid β peptide (Aβ). Animals were treated for 20 days with KTP-NH2 (32.3 mg/kg, intraperitoneally (i.p.), starting at day 3 after Aβ administration) before memory testing (Novel object recognition (NOR) and Y-maze (YM) tests). Animals were then sacrificed, and markers for gliosis were assessed by immunohistochemistry and Western blot analysis. Synaptic correlates were assessed by evaluating theta-burst induced long term potentiation (LTP) of field excitatory synaptic potentials (fEPSPs) recorded from hippocampal slices and cortical spine density analysis. In the absence of KTP-NH2 treatment, Aβ-injected rats had clear memory deficits, as assessed through NOR or YM tests. Importantly, these memory deficits were absent in Aβ-injected rats that had been treated with KTP-NH2, which scored in memory tests as control (sham i.c.v. injected) rats. No signs of gliosis could be detected at the end of the treatment in any group of animals. LTP magnitude was significantly impaired in hippocampal slices that had been incubated with Aβ oligomers (200 nM) in the absence of KTP-NH2. Co-incubation with KTP-NH2 (50 nM) rescued LTP toward control values. Similarly, Aβ caused a significant decrease in spine density in cortical neuronal cultures, and this was prevented by co-incubation with KTP-NH2 (50 nM). In conclusion, the present data demonstrate that i.p. KTP-NH2 treatment counteracts Aβ-induced memory impairments in an AD sporadic model, possibly through the rescuing of synaptic plasticity mechanisms.publishersversionpublishe