PVB-7420 SA: Severe swelling in the nasal region due to feline sporotrichosis
PVB-7420 SA: Severe swelling in the nasal region due to feline sporotrichosis
Small Animal Diseases
Safety and efficacy of allogeneic bone marrow mesenchymal stem cells for treatment of canine leukopenia induced by canine parvovirus infection

Abstract in English:

This study aims to establish a therapy strategy for canine leukopenia induced by canine parvovirus (CPV) infection through intravenous infusion of allogeneic bone marrow mesenchymal stem cells (BMMSCs) and to evaluate the therapeutic effect of BMMSCs on canine parvovirus. Forty healthy 2-month-old dogs were randomly divided into four groups including the BMMSC treatment group (A), conventional treatment group (B), CPV infection group (C), and a normal control group (D). Then the A, B, and C groups were orally infected with CPV (103.25 TCID50/mL) at 1mL/kg, and the D group received the same dose of saline. After the onset of infection, Group A received mesenchymal stem cells (MSCs) and rehydration as the treatment; Group B was treated with anti-inflammatory therapeutics and rehydration; and Group C and D were injected with the same dose of physiological saline. The level of leukocytes rebounded significantly after the treatment with BMMSCs and returned to reference numbers on Day 3 after treatment, which was significantly higher than that in the conventional treatment group. The concentrations of IL-2 and IFN-α were gradually increased during the treatment, and the BMMSC treatment group exhibited significantly higher IL-2 and IFN-α concentrations than the conventional treatment group on Days 3 and 4. The expression of the virus in the blood gradually decreased during the treatment, and the BMMSC treatment group displayed a faster decrease than the conventional treatment group. These results showed the advantages of BMMSC treatment over conventional treatment. This study provides a new BMMSC treatment strategy for canine leukopenia induced by CPV infection and reveals the mechanism by which BMMSC increases leukocytes after CPV infection.

Abstract in Portuguese:

Este estudo tem como objetivo estabelecer uma estratégia terapêutica de leucopenia canina induzida pela infecção por parvovírus canino (CPV) através de infusão intravenosa de células tronco mesenquimais da medula óssea alogênica (BMMSCs) e avaliar o efeito terapêutico de BMMSCs no parvovírus canino. Quarenta cães saudáveis de dois meses de idade foram divididos aleatoriamente em quatro grupos: o grupo de tratamento de BMMSCs (A), o grupo de terapia convencional (B), o grupo de infecção por CPV (C) e um grupo controle (D). Os grupos A, B e C foram infectados oralmente com CPV (103.25 TCID50/mL) a 1mL/kg e o D recebeu a mesma dose de soro fisiológico. Após o início da infecção, o grupo A recebeu uma dose de derivadas da medula óssea (CTMMO) e hidratação como tratamento, o grupo B foi tratado com terapia anti-inflamatória e hidratação, e grupos C e D foram injetados com a mesma dose de soro fisiológico. As concentrações de IL-2 e IFN-α aumentaram gradualmente durante o tratamento, e o grupo de tratamento BMMSC mostrou concentrações significativamente maiores de IL-2 e IFN-α do que o grupo de tratamento convencional nos Dias 3 e 4. A expressão de vírus no sangue diminuiu gradualmente durante o tratamento, e o grupo de tratamento BMMSC mostrou uma diminuição mais rápida do que o grupo de tratamento convencional. Esses resultados mostraram as vantagens do tratamento BMMSC em relação ao tratamento convencional. Este estudo fornece uma nova estratégia de tratamento da BMMSC para leucopenia canina induzida pela infecção por VCP e revela o mecanismo pelo qual a BMMSC aumenta os leucócitos após infecção por VCP.


Histopathological characterization and analysis of cell proliferation in 162 cases of canine subcutaneous mast cell tumors in Brazil

Abstract in English:

here are limited publications about canine subcutaneous mast cell tumors (MCT). International studies have shown that subcutaneous MCT has longer survival times than cutaneous MCT, with lower recurrence and metastasis rates. In addition, subcutaneous MCT has a specific histopathological classification (circumscribed, combined, or infiltrative pattern). Our study evaluated 162 cases of subcutaneous MCT diagnosed from 2014 to 2017 in Brazil. The mean age of the animals was 8.6 years, with a predominance of females and higher incidence in dogs with mixed breed (n=40), followed by Boxer (n=20), Labrador Retriever (n=14), Golden Retriever (n=11) and Pug (n=10). Regarding histopathological characterization, the most common infiltrative pattern represented 54.3% of cases, followed by circumscribed (34.8%) and combined (11%) patterns. The mean mitotic index (MI) was 1.04, with 93.9% of cases presenting MI≤4 and 53.1% MI=0. The data found in this Brazilian study regarding subcutaneous MCT does not differ from those described in American studies, suggesting similar genetic and epidemiological factors. The evaluated proliferation indices suggest that subcutaneous MCT presents slow progression and should be evaluated as a distinct form of cutaneous MCT.

Abstract in Portuguese:

Há poucas informações prognósticas sobre o mastocitoma (MCT) subcutâneo em cães, apresentando maiores tempos de sobrevida e menores taxas de recidiva e metástase em comparação ao MCT cutâneo. Além disso, o MCT subcutâneo canino segue a classificação histopatológica própria, sendo subdivididos de acordo com o padrão em: circunscrito, combinado ou infiltrativo. Sendo assim, o principal objetivo desse estudo foi caracterizar a incidência e as características histopatológicas de MCT subcutâneos no Brasil. Para isso, foram avaliadas 164 amostras de MCT subcutâneos diagnosticados entre o período de 2014 a 2017 no Brasil. A média de idade dos animais foi de 8,6 anos (variação de 3 a 20 anos), com predomínio de fêmeas (64,8%) e maior incidência em cães sem raça definida (n=40), seguido de Boxer (n=20), Labrador Retriever (n=14), Golden retriever (n=11) e Pug (n=10). Em relação a caracterização histopatológica, o padrão infiltrativo foi o mais comum representando 54,3% dos casos, seguido dos padrões circunscritos (34,8%) e combinados (11%). Quanto a contagem de mitose (CM), 93,8% dos casos apresentam CM≤4 e, em 53,1%, CM=0. Os dados encontrados nesse estudo brasileiro em relação ao MCT subcutâneo reforçam outros trabalhos realizados em diferentes regiões demográficas, sugerindo fatores genéticos e epidemiológicos para a doença. Por fim, os índices de proliferação avaliados sugerem que o MCT subcutâneo apresenta progressão lenta devendo ser avaliado como uma forma distinta do MCT cutâneo.


Expression of TLR2, FOXP3, and COX2 in the synovial membrane of dogs with canine leishmaniasis-induced arthritis

Abstract in English:

Canine leishmaniasis (CanL) is a multifaceted disease triggered by the protozoan Leishmania infantum, characterized by diverse clinical presentations, including osteoarticular complications. Immune-mediated joint diseases invariably initiate at the synovial membrane, implicating its pivotal role in arthritis pathogenesis. This study aimed to investigate the influence of natural L. infantum infection on synovial fluid characteristics and the expression of immune markers, including TLR-2, FOXP3, and COX-2, in the synovial membrane. Twenty naturally infected dogs (NID) with L. infantum were sourced from the Zoonosis Surveillance Unit (ZSU). Clinical-orthopedic assessments were conducted, encompassing lameness, joint edema, crepitus, patellar luxation, and the drawer test. Synovial fluid (SF) parameters, including volume, appearance, viscosity, total nucleated cell count (TNC), neutrophil count, and total protein (TP) content, were determined. After anesthesia and euthanasia, synovial membrane specimens were obtained. SF protein concentrations categorized dogs into three groups: GI (2 to 2.5g/dL), GII (2.5 to 6.0g/dL), and GIII (>6g/dL). Inflammatory infiltrates and synovial membrane changes were assessed, and immunohistochemistry evaluated TLR-2, FOXP3, and COX-2 marker expressions. Clinical evaluations revealed various osteoarticular abnormalities in NID dogs, including lameness (55%), joint edema (25%), crepitus (30%), patellar luxation (20%), and positive drawer test (25%). Post mortem examinations revealed bilateral subchondral bone, meniscus, and trochlea erosion in 30% of cases. Amastigotes of L. infantum were identified extracellularly and within macrophages (60%). An inflammatory infiltrate was predominant in 70% of dogs, with varying intensity among the groups. Mononuclear cells, chiefly macrophages and lymphocytes, and neutrophils comprised the infiltrate. TLR-2 and COX-2 expression levels were elevated in GIII compared to GII and GI. Conversely, FOXP3 showed moderate expression in GI and minimal expression in GII and GIII. This study underscores the contributory role of L. infantum infection in the development of joint lesions in CanL. Additionally, alterations in the expression of immune markers TLR2, FOXP3, and COX2 within the synovial membrane imply the perpetuation and exacerbation of the inflammatory processes, shedding light on the intricate pathogenesis of CanL-induced arthritis.

Abstract in Portuguese:

A leishmaniose canina (LC) é uma doença causada pelo protozoário Leishmania infantum com diversas manifestações clínicas, incluindo alterações osteoarticulares. A membrana sinovial é o local inicial de eventos patogênicos em todos os tipos de doenças articulares mediadas pelo sistema imunológico. Devido a essa relação, o objetivo foi avaliar a influência da infecção natural por L. infantum nas características do líquido sinovial e na expressão de TLR-2, FOXP3 e COX-2 na membrana sinovial. Cães naturalmente infectados por L. infantum (NID, N=20) foram obtidos na Unidade de Vigilância de Zoonoses (UVZ). Critérios clínicos ortopédicos foram avaliados, assim como foram obtidas amostras de líquido sinovial por artrocentese. O volume, aspecto, viscosidade, contagem total de células nucleadas (TNC) e contagem de neutrófilos e proteína total (PT) no líquido sinovial (LS) foram determinados. Os cães foram anestesiados e posteriormente eutanasiados para obtenção da membrana sinovial. Os animais do estudo apresentaram claudicação (55%), edema (25%), crepitação na articulação do joelho (30%) e luxação patelar medial (20%) e foram positivos no teste da gaveta (25%). Trinta por cento (30%) dos cães apresentaram erosão bilateral do osso subcondral, menisco e tróclea. Amastigotas de L. infantum foram visualizadas extracelularmente e dentro de macrófagos (60% dos animais). Os cães foram ainda divididos em três grupos de acordo com a concentração de proteína no líquido sinovial: GI: 2 a 2,5g/dL (valor de referência normal), GII: 2,5 a 6,0g/dL, GIII: >6g/dL. Infiltrado celular inflamatório, bem como aumento da camada da membrana sinovial, foram identificados em 70% (14/20) dos cães. O infiltrado inflamatório estava ausente em membranas sinoviais originadas de GI, presente em GII com intensidade moderada e presente em GIII com intensidade alta. O infiltrado inflamatório era predominantemente composto por macrófagos, linfócitos e neutrófilos. Houve um aumento na expressão dos marcadores TLR2 e COX2 em GIII em comparação com os grupos GII e GI. Contudo, em relação à expressão de FOXP3, houve uma marcação moderada em GI e apenas uma marcação leve em GII e GIII. Este trabalho reforça o papel da infecção por L. infantum no desenvolvimento de lesões articulares em cães. Além disso, nosso estudo indica que a LC modifica a expressão de TLR2, FOXP3 e COX2 na membrana sinovial, o que implica a manutenção e progressão do processo inflamatório.


Detection of multiple circulating sandflies species and investigation of dogs and vectors naturally infected with Leishmania in the city of Ribeirão Vermelho, southeastern Brazil

Abstract in English:

Leishmaniasis is a zoonotic disease caused by parasites of the Leishmania genus, resulting in various clinical forms, including a highly lethal visceral form. This study aimed to identify Leishmania spp. in sandflies and dogs in a small Brazilian town. DPP® Visceral Canine Leishmaniasis (CVL) was used for screening, and ELISA and conventional PCR were used for confirmatory testing, while sandflies were captured using CDC light traps and conventional PCR targeting ITS1. The Hill series was used to identify the diversity profile of species in the sampled area using R software. The study identified a Leishmania spp. prevalence of 4.02% in dogs, exceeding the 2% limit required by the Brazilian Ministry of Health. A total of 443 sandflies belonging to 14 different species were identified, with Lutzomyia longipalpis being the most abundant (73.81%). Negligence regarding leishmaniasis in small towns can lead to late diagnosis, hence the need to implement effective strategies, including early diagnosis and treatment of human and canine cases, vector control programs, and awareness campaigns to educate the public about risks and preventive measures. These measures can help prevent the spread of leishmaniasis and improve health outcomes for affected individuals and animals.

Abstract in Portuguese:

A leishmaniose é uma doença zoonótica causada por parasitas do gênero Leishmania, resultando em várias formas clínicas, incluindo uma forma visceral altamente letal. Este estudo teve como objetivo identificar Leishmania spp. DNA em flebotomíneos e cães em uma pequena cidade brasileira. A investigação usou DPP® Visceral Canine Leishmaniasis (CVL) para triagem, e ELISA e PCR convencional para teste confirmatório, enquanto flebotomíneos foram capturados usando armadilhas de luz CDC e PCR convencional visando ITS1. A série Hill foi utilizada para identificar o perfil de diversidade das espécies na área amostrada, utilizando o software R. O estudo identificou uma prevalência de Leishmania spp. em 4,02% dos cães, ultrapassando o limite de 2% exigido pelo Ministério da Saúde do Brasil. Foi identificado um total de 443 flebotomíneos, pertencentes a 14 espécies diferentes, com Lutzomyia longipalpis sendo o mais abundante (73,81%). A negligência com a leishmaniose em cidades pequenas pode levar ao diagnóstico tardio, daí a necessidade de implementar estratégias eficazes, incluindo diagnóstico precoce e tratamento de casos humanos e caninos, programas de controle de vetores e campanhas de conscientização para educar o público sobre riscos e medidas preventivas. Essas medidas podem ajudar a prevenir a propagação da leishmaniose e melhorar os resultados de saúde para indivíduos e animais afetados.


Obesity outcomes on electrocardiographic, echocardiographic, and blood pressure parameters in cats

Abstract in English:

Obesity is considered a chronic inflammatory process that is related to metabolic impairment, respiratory distress, and cardiovascular disease. In cats, few studies have evaluated the implications of obesity on the cardiovascular system, and the existing literature is controversial. Therefore, the aim of this study is to detect pressure, electrocardiographic, and morphofunctional changes in overweight and obese cats. After clinical and laboratory evaluation, 45 animals were selected for the study. Cats were separated according to body condition score (BCS) into three groups (control, overweight, and obese). All animals underwent blood pressure measurement, electrocardiogram, and transthoracic echocardiogram. Results are presented as mean ± standard deviation (SD). Data were considered statistically significant at p<0.05. GraphPad Prism® 7.04 software was used for statistical analyses. Mean arterial pressure in obese cats was higher than in animals with ideal weight (CT 123.60 ± 8.97mmHg vs OB 143.00 ± 22.12mmHg, p<0.0138), but hypertension was not detected. On the electrocardiogram, P wave duration (CT 33.67 ± 1.56ms vs OB 37.76 ± 2.76ms; p<0.0003) and QRS complex (CT 48.14 ± 2.56ms vs OB 54.48 ± 5.51ms; p<0.002) were significantly higher in the obese group. There were no significant echocardiographic changes. There was a direct correlation between blood pressure and BCS (r:0.36, p<0.01). The P wave was positively correlated with the BCS (r:0.56, p<0.0001). Likewise, the QRS complex correlated directly with the BCS (r:0.52, p<0.0003). The results indicate cat obesity can directly affect the cardiovascular system, promoting pressure and electrocardiographic changes. Therefore, monitoring the cardiovascular system of cats with obesity is essential.

Abstract in Portuguese:

A obesidade é considerada um processo inflamatório crônico que está relacionada ao comprometimento metabólico, dificuldade respiratória e doenças cardiovasculares. Em gatos, poucos estudos avaliaram as implicações da obesidade no sistema cardiovascular e a literatura é controversa. Portanto, o objetivo deste trabalho é detectar as alterações pressóricas, eletrocardiográficas e morfofuncionais em gatos com sobrepeso e obesidade. Quarenta e cinco animais, após avaliação clínica e laboratorial, foram selecionados para o estudo. Os gatos foram separados conforme o escore de condição corporal (ECC) em três grupos (controle, sobrepeso e obesidade). Todos os animais realizaram mensuração de pressão arterial, eletrocardiograma e ecocardiograma transtorácico. Os resultados foram apresentados como média ± desvio padrão (DP). Os dados foram considerados estatisticamente significativos se p<0,05. O software GraphPad Prism® 7.04 foi usado para análises estatísticas. A pressão arterial média dos gatos obesos era maior que nos animais com peso ideal (CT 123,60 ± 8,97mmHg vs OB 143,00 ± 22,12mmHg, p<0,0138), porém não se detectou hipertensão. No eletrocardiograma, a duração da onda P (CT 33,67 ± 1,56ms vs OB 37,76 ± 2,76ms; p<0,0003) e complexo QRS (CT 48,14 ± 2,56ms vs OB 54,48 ± 5,51ms; p<0,002) foi significativamente maior no grupo obeso. Não houve alterações ecocardiográficas significativas. Houve correlação direta da pressão arterial com o ECC (r:0,36, p<0,01). A onda P correlacionou-se positivamente com o ECC (r:0,56, p<0,0001). Do mesmo modo, o complexo QRS se correlacionou diretamente com o ECC (r:0,52, p<0,0003). Os resultados indicam que a obesidade em gatos pode afetar diretamente o sistema cardiovascular, promovendo alterações pressóricas e eletrocardiográficas. Sendo assim, é indispensável o acompanhamento do sistema cardiovascular dos gatos com obesidade.


Causes of death in domestic cats during COVID-19 pandemic (2020-2021): A multi-institutional necropsy study from Mato Grosso and Rio de Janeiro, Brazil

Abstract in English:

Retrospective studies that address the diseases in the feline species are scarce. Herein, we presented the cause of death or euthanasia of cats from January 2020 to December 2021, during the first and second years of the SARS-CoV-2 pandemic. The data were obtained from necropsies performed by the Federal Rural University of Rio de Janeiro and the Federal University of Mato Grosso. A total of 96 feline necropsies were performed. In 87 cases (90.6%), we established the reason for death, while in nine cases (9.4%), the diagnoses were inconclusive. We established the diagnostic groups: infectious and parasitic (37.5%), neoplasm (14.5%), malformation (7.3%), lower urinary tract disease (7.3%), degenerative (6.2%), traumas (6.2%), other causes (8.4%) and iatrogenic (3.1%). The most common cat diseases in Mato Grosso and Rio de Janeiro were infectious. The most common inflammatory lesions were bacterial and viral pneumonia. Alphaherpesvirus (FeHV), Mycoplasma sp., and Pseudomonas sp. were the main detected agents.

Abstract in Portuguese:

Estudos retrospectivos que abordam doenças em felinos domésticos são escassos. Apresentamos aqui a causa da morte ou razões para eutanásia de gatos domésticos entre janeiro de 2020 e dezembro de 2021, durante o primeiro e segundo ano da pandemia de SARS-CoV-2. Os dados foram obtidos em necropsias realizadas pela Universidade Federal Rural do Rio de Janeiro e Universidade Federal de Mato Grosso. Foram realizadas 96 necropsias de felinos. Em 87 casos (90,6%) foi estabelecido a causa da morte e em nove casos (9,4%) os diagnósticos foram inconclusivos. Estabelecemos os grupos diagnósticos: infecciosos e parasitários (37,5%), neoplasias (14,5%), malformações (7,3%), doenças do trato urinário inferior (7,3%), degenerativas (6,2%), traumas (6,2%), outras causas (8,4%) e iatrogênicas (3,1%). As doenças mais frequentes em gatos do Mato Grosso e Rio de Janeiro foram as infecciosas. As lesões inflamatórias mais frequentes foram as pneumonias bacterianas e virais. Os principais agentes detectados foram Alphaherpesvirus (FeHV), Mycoplasma sp. e Pseudomonas sp.


Feline application/inflammation-associated sarcoma: Gross aspects and histomorphological

Abstract in English:

Feline injection-site sarcomas in felines account for more than 40% of cutaneous and subcutaneous neoplasms in felines. The present study aimed to describe the macroscopic and histomorphological findings of feline application/injection sarcomas. Samples from 31 feline tumors with a history of feline application/inflammation sarcoma were re-evaluated regarding histological subtype, mitotic index and score, depth of tissue invasion, and presence of inflammation considering the location, intensity and predominant cell types. Of the 31 samples from felines diagnosed with sarcoma at the application/inflammation site, 87.15% were cats with no defined breed (NDB), with a mean age of 8.5 years. The predominant anatomical sites were the back and flank/abdomen, both with 29% (9/31), and the prevalent histological subtype was fibrosarcoma at 77.4% (24/31), followed by anaplastic giant cell sarcoma at 12.9% (4/31) and myxosarcoma 9.6% (3/31). The histological grade with the highest number of cases was III (51.6%), followed by Grade II (35.4%) and I (12.9%). The mean of the longest axis measurements varied between the different tumor grades without being significant, with the average being 2.5±2.79cm in Grade I tumors and 3.2±2.28cm in Grade II tumors. and 4.68±2.07cm in Grade III tumors. Necrosis was observed in 74.2% of tumors. The tissue inflammation score was mild to moderate in 58% of cases and severe in 32.2%, with lymphocytic and lymphoplasmacytic infiltrates being prevalent, with 25.8% each, followed by lymphoplasmohistiocytic with 22.6%. The infiltration depth was 38.7% in muscle tissue, followed by 32.2% in the subcutaneous tissue. Pleomorphism was accentuated in 51.6%. Desmoplasia was moderate in 45.1%. Satellite nodules were present in 29% of cases, and 19.4% had macrophages with intracytoplasmic content suggestive of adjuvants. Surgical margins were infiltrated (M1) in 48.4% and narrowed in 25.8% (M2). The anatomical locations observed were different from those recommended by the Vaccine-Associated Feline Sarcoma Task Force (VAFST); in most cases, the adjuvanted macrophage was not present. From this data, we can suggest that sarcomas in felines are not only correlated to the vaccine application, corroborating the hypothesis that any material, whether liquid or solid, and any chronic inflammatory process in the subcutaneous tissue of cats can induce the entity if they are predisposed to do so. The detailed histomorphological data evaluated in this study were key points and provided important information about tumor behavior, being a tool for clinical-oncological decision-making.

Abstract in Portuguese:

Feline injection-site sarcomas in felines account for more than 40% of cutaneous and subcutaneous neoplasms in felines. The present study aimed to describe the macroscopic and histomorphological findings of feline application/injection sarcomas. Samples from 31 feline tumors with a history of feline application/inflammation sarcoma were re-evaluated regarding histological subtype, mitotic index and score, depth of tissue invasion, and presence of inflammation considering the location, intensity and predominant cell types. Of the 31 samples from felines diagnosed with sarcoma at the application/inflammation site, 87.15% were cats with no defined breed (NDB), with a mean age of 8.5 years. The predominant anatomical sites were the back and flank/abdomen, both with 29% (9/31), and the prevalent histological subtype was fibrosarcoma at 77.4% (24/31), followed by anaplastic giant cell sarcoma at 12.9% (4/31) and myxosarcoma 9.6% (3/31). The histological grade with the highest number of cases was III (51.6%), followed by Grade II (35.4%) and I (12.9%). The mean of the longest axis measurements varied between the different tumor grades without being significant, with the average being 2.5±2.79cm in Grade I tumors and 3.2±2.28cm in Grade II tumors. and 4.68±2.07cm in Grade III tumors. Necrosis was observed in 74.2% of tumors. The tissue inflammation score was mild to moderate in 58% of cases and severe in 32.2%, with lymphocytic and lymphoplasmacytic infiltrates being prevalent, with 25.8% each, followed by lymphoplasmohistiocytic with 22.6%. The infiltration depth was 38.7% in muscle tissue, followed by 32.2% in the subcutaneous tissue. Pleomorphism was accentuated in 51.6%. Desmoplasia was moderate in 45.1%. Satellite nodules were present in 29% of cases, and 19.4% had macrophages with intracytoplasmic content suggestive of adjuvants. Surgical margins were infiltrated (M1) in 48.4% and narrowed in 25.8% (M2). The anatomical locations observed were different from those recommended by the Vaccine-Associated Feline Sarcoma Task Force (VAFST); in most cases, the adjuvanted macrophage was not present. From this data, we can suggest that sarcomas in felines are not only correlated to the vaccine application, corroborating the hypothesis that any material, whether liquid or solid, and any chronic inflammatory process in the subcutaneous tissue of cats can induce the entity if they are predisposed to do so. The detailed histomorphological data evaluated in this study were key points and provided important information about tumor behavior, being a tool for clinical-oncological decision-making.


Colégio Brasileiro de Patologia Animal SciELO Brasil CAPES CNPQ UNB UFRRJ CFMV