The effects of voluntary running on the skeletal muscle of rats with pulmonary arterial hypertension (PAH) were tested in the present study. PAH was induced in rats by a single injection of ...monocrotaline (MCT, 60 mg/kg). Rats in the sedentary hypertension (HS) group had their tolerance to physical exertion reduced throughout the experiment, while those in the sedentary control (SC), exercise control (EC), exercise hypertension (EH) and median exercise (EM) groups maintained or increased. Despite that, the muscular citrate synthase activity was not different between groups. The survival time was higher in the EH (32 days) than in the SH (28 days) (
= 0.0032). SH and EH groups showed a lower percentage of muscle fiber and a higher percentage of extracellular matrix compared to control groups (
< 0.0001). However, the EM and EH groups presented higher percentage of muscle fiber and lower percentage of extracellular matrix than SH group (
< 0.0001). Regarding muscular gene expression, the SH and EM groups showed a lower expression of PGC1-α (
= 0.0024) and a higher expression of VEGF (
= 0.0033) compared to SC, while PGC1-α was elevated in the EH. No difference between groups was found for the carbonylated protein levels (
> 0.05), while the TNF-α/IL-10 ratio was augmented in the EH (
= 0.0277). In conclusion, voluntary running augments the proportion of fiber and affects the gene expression of inflammatory and mitochondrial biogenesis' markers in the skeletal muscle of rats with MCT-induced PAH, which benefits their survival and tolerance to physical effort.
There are numerous sources of multipotent mesenchymal stromal cells (MSC) with therapeutic potential, and bone marrow is the main one. However, pain, lack of donors and comorbidities associated with ...harvesting stimulate the search for new sources of MSCs. The aim of this work is to obtain cells from umbilical cord (UC) perivascular tissue of dogs and characterize them as MSCs. For this, the UC was obtained from therapeutic cesarean sections and submitted to enzymatic digestion. The obtained cells were subjected to growth and proliferation tests, as well as the analysis of surface markers, differentiation test in three mesenchymal lineages and analysis of differentiation markers expression. From all the UC used in this study an adherent with fibroblastoid shape cell was obtained, with an initial number of 4.8 × 105 of cells. The growth curves showed a lag phase from 0 to 24 h, followed by a phase of growth of 24 to 168 h, and then phase of cell decay. The doubling time was kept around 15 h until the sixth passage, from which there were signs of cellular senescence. The differentiation assays demonstrated the ability of cells to differentiate into osteoblasts, adipocytes and chondrocytes when subjected to the induction mediums. The study of surface markers was positive for adhesion markers and negative for hematopoietic markers. Thus, cells obtained from canine UC perivascular tissue by enzymatic digestion are multipotent MSC and the protocol developed ensures the perivascular origin of these cells.
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•Simple and efficient method to obtain canine perivascular MSCs.•We ensure the perivascular origin of the cells, unlike all previous studies.•The niche is restricted to perivascular compartment.•More efficient yield: shorter time for homogeneous culture and duplication rate.•This method has the potential to be used in translational medicine.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Mesenchymal stromal cells (MSCs) have long been used in research for bone regeneration, with evidence of their beneficial properties. In the segmental area of MSC-based therapies, MSC-derived ...extracellular vesicles (EVs) have also shown great therapeutic effects in several diseases, including bone healing. This study aimed to assess whether the conditioning of MSCs improves the therapeutic effects of their derived extracellular vesicles for bone regeneration. Electronic research was performed until February 2021 to recover the studies in the following databases: PubMed, Scopus, and Web of Science. The studies were screened based on the inclusion criteria. Relevant information was extracted, including in vitro and in vivo experiments, and the animal studies were evaluated for risk of bias by the SYRCLE tool. A total of 463 studies were retrieved, and 18 studies met the inclusion criteria (10 studies for their in vitro analysis, and 8 studies for their in vitro and in vivo analysis). The conditioning methods reported included: osteogenic medium; dimethyloxalylglycine; dexamethasone; strontium-substituted calcium silicate; hypoxia; 3D mechanical microenvironment; and the overexpression of miR-375, bone morphogenetic protein-2, and mutant hypoxia-inducible factor-1α. The conditioning methods of MSCs in the reported studies generate exosomes able to significantly promote bone regeneration. However, heterogeneity regarding cell source, conditioning method, EV isolation and concentration, and defect model was observed among the studies. The different conditioning methods reported in this review do improve the therapeutic effects of MSC-derived EVs for bone regeneration, but they still need to be addressed in larger animal models for further clinical application.
Resumo Fundamento A hipertrofia e a dilatação do ventrículo direito observadas na hipertensão arterial pulmonar (HAP) prejudicam a dinâmica do ventrículo esquerdo (VE) achatando o septo ...interventricular. Objetivo Investigar se o treinamento físico resistido (TFR) de intensidade baixa a moderada é benéfico para funções contráteis do VE e de cardiomiócitos em ratos durante o desenvolvimento de HAP induzida por monocrotalina (MCT). Métodos Foram usados ratos Wistar machos (Peso corporal: ~ 200 g). Para avaliar o tempo até o possível surgimento de insuficiência cardíaca (ou seja, ponto de desfecho), os ratos foram divididos em dois grupos, hipertensão com sedentarismo até a insuficiência (HSI, n=6) e hipertensão com treinamento até a insuficiência (HTI, n=6). Para testar os efeitos do TFR, os ratos foram divididos entre grupos de controle sedentários (CS, n=7), hipertensão com sedentarismo (HS, n=7) e hipertensão com treinamento (HT, n=7). A HAP foi induzida por duas injeções de MCT (20 mg/kg, com um intervalo de 7 dias). Os grupos com treinamento foram submetidos a um protocolo de TFR (subir escadas; 55-65% da máxima carga carregada), 5 dias por semana. A significância estatística foi definida em p <0,05. Resultados O TFR prolongou o ponto de desfecho (~25%), melhorou a tolerância ao esforço físico (~55%) e atenuou as disfunções de contratilidade de VE e de cardiomiócitos promovidas pela MCT preservando a fração de ejeção e o encurtamento fracional, a amplitude do encurtamento, e as velocidades de contração e relaxamento nos cardiomiócitos. O TFR também preveniu os aumentos de fibrose e colágeno tipo I no ventrículo esquerdo causados pela MCT, além de manter as dimensões de miócitos e colágeno tipo III reduzidas por MCT. Conclusão O TFR de intensidade baixa a moderada é benéfico para funções contráteis de VE e cardiomiócitos em ratos durante o desenvolvimento de HAP induzida por MCT.
Analyze the effects of voluntary running during the development of pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT) on the right ventricle (RV) structure, RV myocyte contractility ...and intracellular Ca2+ transient in rats with MCT-induced PAH.
Male Wistar rats were housed sedentary or with free access to a running wheel after MCT or saline injection for until HF or median end-point day of HF in sedentary animals (24 days). Echocardiographic examination and exercise tolerance test were carried out at specific time points of the experimental period. After euthanasia, the heart was dissected, weighed and processed for either histological or single myocyte contractility and intracellular Ca2+ transient analyzes.
Voluntary running delayed the onset of HF (29 days) and the increase in pulmonary artery resistance, and improved exercise tolerance. In the median end-point day of HF, exercise retarded RV adverse remodeling (i.e. increase in extracellular matrix and collagen content). At this stage, exercise also delayed impairments in cell contractile function (i.e. amplitude and times to peak and to half relaxation) and intracellular calcium cycling (i.e. amplitude and times to peak and to half decay) in RV single myocytes.
Along with HF onset delay and physical effort tolerance enhancement, voluntary running during the development of PAH postpones pulmonary artery resistance increases, RV adverse remodeling and myocyte contractility and intracellular calcium cycling deterioration in rats. Therefore, self-paced intermittent exercise of high intensity may contribute positively to the health and survival of individuals with PAH.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Under the adverse remodeling of the right ventricle and interventricular septum in pulmonary arterial hypertension (PAH) the left ventricle (LV) dynamics is impaired. Despite the benefits of combined ...aerobic and resistance physical trainings to individuals with PAH, its impact on the LV is not fully understood.
To test whether moderate-intensity combined physical training performed during the development of PAH induced by MCT in rats is beneficial to the LV's structure and function.
Male Wistar rats were divided into two groups: Sedentary Hypertensive Survival (SHS, n = 7); and Exercise Hypertensive Survival (EHS, n = 7) to test survival. To investigate the effects of combined physical training, another group of rats were divided into three groups: Sedentary Control (SC, n = 7); Sedentary Hypertensive (SH, n = 7); and Exercise Hypertensive (EH, n = 7). PAH was induced through an intraperitoneal injection of MCT (60 mg/kg). Echocardiographic evaluations were conducted on the 22nd day after MCT administration. Animals in the EHS and EH groups participated in a combined physical training program, alternating aerobic (treadmill running: 50 min, 60% maximum running speed) and resistance (ladder climbing: 15 climbs with 1 min interval, 60% maximum carrying load) exercises, one session/day, 5 days/week for approximately 4 weeks.
The physical training increased survival and tolerance to aerobic (i.e., maximum running speed) and resistance (i.e., maximum carrying load) exertions and prevented reductions in ejection fraction and fractional shortening. In addition, the physical training mitigated oxidative stress (i.e., CAT, SOD and MDA) and inhibited adverse LV remodeling (i.e., Collagen, extracellular matrix, and cell dimensions). Moreover, the physical training preserved the amplitude and velocity of contraction and hindered the reductions in the amplitude and velocity of the intracellular Ca
transient in LV single myocytes.
Moderate-intensity combined physical training performed during the development of MCT-induced PAH in rats protects their LV from damages to its structure and function and hence increases their tolerance to physical exertion and prolongs their survival.
Doppler ultrasonography is used in the evaluation of hemodynamics, and the resistivity (RI) and pulsatility (PI) indexes provide information about resistance to blood flow within a vessel. This ...systematic review was carried out to evaluate renal RI and PI in clinically healthy and nonsedated cats and as well as their usefulness in the evaluation of kidney disease in cats. An electronic search in the PubMed, Scopus, and Web of Science databases was carried out using the terms “resistive index” or “resistivity index” or “pulsatility index;” “Doppler;” “renal” or “kidney;” and “cat” or “feline” in titles, s, and keywords. Variables of interest related to experimental model features, research methods, and technical resources were extracted from the studies. The methodological quality was assessed with SYRCLE's risk of bias tool. Thus, 14 studies involving healthy and sick cats were selected. Interestingly, the upper limits estimated for both RI and PI varied among studies. The upper limits of renal RI for healthy cats varied between 0.64 and 0.72, while for PI, the values varied from 1.06 to 1.29. A limited number of studies evaluated cats with kidney disease. In most studies, RI values of kidneys with different conditions were significantly different from kidneys of healthy animals, indicating that RI values increase with kidney disease. The parameters body weight, heart rate, and age seem to influence the RI values. Standardized studies regarding its realization and description are still necessary to define normal values and analyze its applicability in the clinical diagnostic routine.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The study aimed to evaluate biocompatibility, osteoconduction and osseointegration of a pasty composite of hydroxyapatite (20%) and lignin (80%) as a promoter of metal implant and bone tissue ...integration. An intramedullary Schanz pin was implanted in both tibias of fifteen bitches. In the left tibia, the pin was coated with the biomaterial at the time of surgery. Marrow cavity was also filled with the biomaterial. Right limb did not receive the biomaterial, then constituting the control group. Tibias were harvested from five animals at 8, 60 and 150 days after surgery; three of them were analyzed by histological and biomechanical assessment and the two remaining tibias by X-ray diffraction. Results showed that the biomaterial is biocompatible, with osteoconductivity and osseointegration properties. Histological analysis and diffractograms showed the presence of hydroxyapatite in samples in all periods, although the presence of organic material of low crystallinity was variable. There was no statistical difference in the forces required for removal of the biocompatibility, osteoconductivity and osseointegration, it was not able to promote a better intramedullary pin anchorage.
O trabalho objetivou avaliar a biocompatibilidade, a osteocondução e a osseointegração de um compósito pastoso de hidroxiapatita (20%) e lignina (80%) como promotor de integração entre implante metálico e tecido ósseo. Um pino intramedular de Schanz foi implantado em ambas as tíbias de quinze cadelas. Na tíbia esquerda, o pino foi coberto com o biomaterial no momento da cirurgia. A cavidade medular também foi preenchida com o biomaterial. O membro direito não recebeu o biomaterial, constituindo assim o grupo controle. As tíbias foram coletadas de cinco animais aos oito, 60 e 150 dias após a cirurgia, sendo três encaminhadas para avaliação histológica e biomecânica e as duas restantes, para difração de raios X. Os resultados revelaram biocompatibilidade do material, com propriedades de osteocondução e osseointegração. As análises histológicas e os difratogramas mostraram presença da hidroxiapatita no tecido em todos os períodos avaliados, embora a presença de material orgânico de baixa cristalinidade tenha sido variável. Não houve diferença estatística na força necessária para remoção do pino intramedular entre os tempos ou tratamentos. Embora o biomaterial tenha apresentado biocompatibilidade, osteocondutividade e osseointegração, ele não foi capaz de promover uma melhor ancoragem do pino intramedular.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In this work, biocompatibility, osteointegration, osteoconductivity, and biodegradation of a hydroxyapatite polyhydroxybutyrate new composite were evaluated. The composite was implanted in rabbits' ...bone defects and clinical, radiographic, histological, and histomorphometric data of these animals were compared with those of unfilled defects on the days 8th, 45th, and 90th after surgery. No significant differences existed between the groups for the evaluated clinical parameters. Radiographs showed bone-composite direct contact. Bone formed within the defect, interface and inside the composite. Significant differences were found between the bone and connective tissues percentage within the defect at all dates and at the interface on the 45th day, bone tissue prevailing. Composite's biodegradation signs were evident: giant cells on the surface of composite fragments separated from the original block in the absence of inflammatory infiltrate. These data supported that such composite was biocompatible, biodegradable, osteoconductive and integrate to bone.
A biocompatibilidade, osteointegração, osteocondução e biodegradação de um novo compósito de hidroxiapatita e polihidroxibutirato foram avaliados. O compósito foi implantado em defeitos ósseos em coelhos e dados clínicos, radiográficos, histológicos e histomorfométricos foram comparados aos de defeitos não preenchidos aos 8, 45 e 90 dias após a cirurgia. Não foram observadas diferenças significantes entre os grupos para os parâmetros clínicos avaliados. Contato direto entre osso e compósito foi observado nas radiografias. Tecido ósseo se formou dentro do defeito, interface e dentro do compósito. Foram observadas diferenças significativas entre a porcentagem dos tecidos ósseo e conjuntivo dentro do defeito em todas as datas de avaliação e na interface aos 45 dias, com predominância do tecido ósseo. Sinais de biodegradação foram observados: células gigantes na superfície de fragmentos do compósito separados do bloco original, na ausência de infiltrado inflamatório. Os dados permitem concluir que o compósito é biocompatível, biodegradável, osteocondutor e se integra ao tecido ósseo.
The study of wound healing and its treatment is extremely important in veterinary medicine due to the high frequency of wounds and the difficulty in treating wounds by second intention. Thus, the ...objective of this study was to evaluate the use of a nanofiber membrane made of biodegradable polymers as a method of wound treatment in dogs. This study comprised two dogs with bite wounds. Debridement and cleaning was performed followed by the application of the membrane. In one dog, the wound was in the left proximal calcaneal region with clinical signs of infection, necrotic tissue, and muscle and the gastrocnemius tendon were exposed. The wound displayed rapid formation of granulation tissue which became excessive, so it was necessary to debride several times. However, with the suspension of the use of the membrane, formation of this tissue was not observed, and the wound evolved to epithelialization and fast contraction. In the second dog, there was a deep wound on the medial aspect of the proximal right hind limb, with clinical signs of infection, with muscle exposure. Once the membrane was placed, granulation tissue formed, and the membrane was used until the level of this tissue reached the skin. The wound underwent rapid epithelialization and contraction, without developing exuberant granulation tissue. Efficient wound repair was observed and the dogs exhibited greater comfort during application and use of the membrane. More studies should be conducted in dogs focusing on the application of this membrane until the appearance of healthy granulation tissue, as continued use seems to stimulate the formation of exuberant granulation tissue.
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