Efficacy assessment of an intramammary formulation based on soluble polypyrrole in cows with experimentally induced mastitis / Avaliação da eficácia de uma formulação intramamária à base de polipirrol solúvel em vacas com mastite experimentalmente induzida

Considerando a necessidade de terapias alternativas para a mastite bovina, uma inflamação, normalmente de causa infecciosa, de alta prevalência e de alto impacto econômico nas fazendas leiteiras, avaliou-se a eficácia antimicrobiana, in vivo, de uma formulação intramamária à base de polipirrol (PPy) solúvel, um polímero condutor promissor para aplicações biomédicas, especialmente como potente antibacteriano. Neste ensaio, quartos mamários de vacas holandesas sadias (n = 8) foram inoculados com Staphylococcus aureus e tratados, por via intramamária, com formulação experimental à base de PPy solúvel (5%) e com formulação comercial à base de sulfato de gentamicina. O efeito desses tratamentos foi avaliado com a realização de lactoculturas, da Contagem Bacteriana Total (TBC), da Contagem de Células Somáticas (SCC) e da análise da composição do leite das amostras obtidas de quartos mamários, em sete momentos experimentais. Avaliação hematológica dos animais também foi realizada. A aplicação intramamária de três doses da formulação experimental à base de PPy solúvel resultou em maiores log/mL da TBC e da SCC quando comparadas ao grupo controle positivo e ao grupo que recebeu sulfato de gentamicina. A administração da formulação experimental não induziu alterações na composição do leite e nos parâmetros hematológicos. Alguns fatores farmacocinéticos e farmacodinâmicos do PPy solúvel podem ser atribuídos a ineficácia antimicrobiana da pomada experimental. Outras pesquisas devem ser realizados em prol do desenvolvimento de formulações que permitam a atuação antibacteriana do PPy solúvel no ambiente intramamário de vacas leiteiras.

Given the need for alternative therapies for bovine mastitis, an infectious disease of high prevalence and significant economic impact in dairy farms, this study evaluated the in vivo antimicrobial efficacy of an intramammary formulation based on soluble polypyrrole (PPy), a promising conductive polymer for biomedical applications, especially as an effective antimicrobial agent. In this assay, mammary quarters of healthy Holstein Friesian cows (n = 8) were inoculated with Staphylococcus aureus and treated, via the intramammary route, with an experimental formulation based on soluble PPy (5%) and a commercial formulation based on gentamicin sulfate. The effect of these treatments was evaluated based on milk cultures, Total Bacterial Count (TBC), Somatic Cell Count (SCC), and milk composition analysis of mammary quarter samples in seven experimental moments. In addition, hematological evaluations of the animals were also performed. The intramammary application of three levels of the experimental formulation based on soluble PPy resulted in higher log/mL of the TBC and SCC compared to a positive control group and a group that received gentamicin sulfate. The experimental formulation did not induce changes in milk composition or in hematological parameters. Certain factors related to pharmacokinetics, such as the type of carrier used in the formulation and the pharmacodynamics of soluble PPy, may have contributed to the antimicrobial ineffectiveness of the experimental formulation. The results of this study neither define nor decrease the antimicrobial potential of soluble PPy. Further research is required to develop formulations that enable the antibacterial action of soluble PPy in the intramammary environment of dairy cows.

Use of polymethylmethacrylate plaque as a treatment of cranioschisis associated with meningocele in a Girolando heifer: A case report / Uso de placa de polimetilmetacrilato (PMMA) no tratamento de craniosquise associada à meningocele em uma bezerra girolando: relato de caso

Most genetic diseases affect purebred animals and are inherited as recessive genes. Cranioschisis refers to dysraphism, which occurs in the midline of the skull due to failure to close the cranial symphysis, which can lead to herniation of the meninges filled with cerebrospinal fluid (meningocele), where there is usually a projection of the meningeal tissue. Diagnosis is performed based on clinical examination, characteristic anatomopathological data, and complementary imaging tests. The surgical approach for correction of cranioschisis is the only described as a therapeutic solution and is indicated in cases in which the cranial synthesis defect does not allow for brain protrusion and there is only the occurrence of meningocele, in addition to the absence of severe signs of neurological alteration. This paper reports a case of the use of polymethylmethacrylate (PMMA) plaque to treat cranioschisis associated with meningocele in a Girolando heifer. The surgical opening of the frontonasal sacculation allowed draining a total liquid content of 488 mL, inspection, and suture of the envelope membrane. APMMA plaque, molded to the bone surface and anchored in the adjacent soft tissue, was used to cover the evidenced frontonasal bone opening. Despite the unfavorable prognosis of the disease, the cranioplasty surgery for the treatment of cranioschisis associated with meningocele using PMMA plaque obtained satisfactory results relative to the quality and maintenance of this animal's life, evaluated at 19 months postoperatively.(AU)

A maioria das doenças genéticas acometem animais de raça pura e herdados como genes recessivos.Acraniosquise refere-se à disrafia, que acontece na linha média do crânio pelo não fechamento da sínfise craniana, podendo levar a herniação das meninges repletas de líquido cefalorraquidiano (meningocele), onde geralmente existe projeção do tecido meningeal. O diagnóstico é realizado a partir do exame clínico, dados anatomopatológicos característicos e através da realização de exames complementares de imagem. Como solução terapêutica, a abordagem cirúrgica para correção das craniosquises é a única descrita, e é indicada em casos em que o defeito de síntese craniana não permita a protrusão encefálica e exista a ocorrência apenas da meningocele, além da inexistência de sinais graves de alteração neurológica. O artigo relata um caso de uso de placa de polimetilmetacrilato (PMMA) no tratamento de craniosquise associada à meningocele em uma bezerra Girolando. Instituiu-se a abertura cirúrgica da saculação fronto-nasal, permitindo a drenagem de conteúdo líquido total de 488 mL, inspeção e rafia de membrana envoltória. Para recobrimento da abertura óssea fronto-nasal evidenciada, utilizou-se uma placa de polimetilmetacrilato (PMMA), moldada à superfície óssea e ancorada em tecido mole adjacente. Concluiu-se que, apesar do prognóstico desfavorável da enfermidade, a cirurgia de cranioplastia para tratamento de craniosquise associada à meningocele, com a utilização de placa de PMMA, neste caso, obteve resultados satisfatórios em relação a qualidade e manutenção da vida deste animal, avaliando-se em 19 meses pós-operatório.(AU)

Mastocitoma cutâneo canino após mastocitose acidental induzida por opioide: Relato de caso / Canine cutaneous mastocytoma after accidental opioid-induced mastocytosis: Case report

A aproximação entre petse tutores está cada vez mais presente na rotina atual das residências familiares. Essa aproximação aumenta a observação de quaisquer alterações físicas ou comportamentais dos animais levando-o a buscar um médico veterinário quando necessário. O papel do clínico, oncologista e do patologista veterinário vem a ser de extrema importância para detecção das neoplasias em suas fases iniciais. A utilização dos meios de diagnósticos complementares para os casos de neoplasias é de fundamental importância para ter ciência do prognóstico do animal e de qual tratamento será o melhor tratamento para os casos abordados. O mastocitoma é a neoplasia cutânea mais frequente do cão, é uma neoplasia maligna e sua etiologia é pouco compreendida. Independente do sexo, atingem machos e fêmeas, porém se apresentam de forma mais agressiva em machos. O diagnóstico, geralmente é estabelecido por meio de exames complementares, associados aos sinaisclínicos, devendo sempre prezar pelo diagnóstico precoce para que haja maior êxito no tratamento.O exame citológico para o diagnóstico de mastocitoma é um dos métodos mais eficientes e de baixo custo, sendo complementado pelo exame histopatológico para agraduação de malignidade e estadiamento da doença. Preconiza-se a associação da cirurgia com o tratamento quimioterápico com terapia antiblástica e eletroquimioterapia para um melhor prognóstico. O objetivo deste trabalho foi relatar um caso de mastocitoma cutâneo após um erro primário de manejo clinico, em um canino, macho, nove anos, da raça American Pitbull Terrier, trazendo sua complexidade e bases dos meios de diagnóstico(AU)

The approximation between pets and tutors is increasingly present in the current routine of family homes. This approach increases the observation of physical or behavioral changes in animals, leading them to seek a veterinarian when necessary. The role of the clinician, oncologist and veterinary pathologist is extremely important for the detection of neoplasms in their early stages. The use of complementary diagnostic means for cases of neoplasms is of fundamental importance to be aware of the animal's prognosis and which treatment will be the best treatment for the cases examined. Mastocytoma is the most frequent skin neoplasm in dogs, it is a malignant neoplasm and its etiology is poorly understood. Regardless of gender, they affect males and females, but are more aggressive in males. The diagnosis is usually established through complementary exams, associated with clinical signs. Cytological examination for the diagnosis of mast cell tumor is an inexpensive method and one of the most efficient methods, being complemented by histopathological examination for its evolution of malignancy and disease staging, recommended the association of surgery with chemotherapy treatment with antiblastic therapy and electrochemotherapy for better prognoses. The aim of this study was to report a case of cutaneous mastocytoma after a primary error in clinical management, in a canine, male, nine years old, of the American Pitbull Terrier breed, bringing its complexity and bases of the means of diagnosis(AU)

Doença policística felina tratada com homeopatia: relato de caso / Feline polycystic disease treated withhomeopathy: case report

Foi avaliado o tratamento homeopático de um felino com doença renal policística, moléstia hereditária muito comum na espécie felina. Por ser progressiva, o prognóstico depende do estágio de evolução da doença renal crônica, da resposta do felino ao tratamento inicial e do desejo do tutor em dar continuidade ao tratamento. A observação teve duração de 9 (nove) meses e a avaliação dos resultados foi realizada com o emprego de exame clínico e de exames complementares como imagens ultrassonográficas e exames laboratoriais. A terapia foi composta por medicamento homeopático constitucional Phosphorus 30CH e episódico Kresolum 6CH associado à introdução de dieta renal (ração seca adjuvante). O medicamento homeopático não provocou eventos adversos no animal. Os resultados sugerem que um animal com doença policística felina pode ser tratado pela homeopatia.(AU)

The homeopathic treatment of a feline with polycystic kidney disease was evaluated, a common hereditary disease in the feline species. Because it is progressive, the prognosis depends on the stage of evolution of the chronic kidney disease, the feline response to the initial treatment and the guardian's desire to continue the treatment. The observation lasted 9 (nine) months and the evaluation of the results was performed through clinical examination and complementary tests such as ultrasound images and laboratory tests. The therapy was composed of constitutional Phosphorus 30CH and episodic Kresolum 6CH homeopathic medication associated with the introduction of diet kidney diet (adjunct dry feed). The homeopathic medicine did not cause adverse events in the animal. The results suggest that an animal with feline polycystic disease can be treated by homeopathy.(AU)

B-mode and Doppler ultrasound of bitches' kidneys with mammary neoplasia submitted to adjuvant chemotherapy / Ultrassonografia modo-B e Doppler dos rins de cadelas com neoplasias mamárias submetidas à quimioterapia adjuvante

Mammary neoplasia represents the most frequently diagnosed type of neoplasia in bitches. Although surgical removal is the procedure of choice for therapeutic management, chemotherapy protocols appear as important allies and adjuvants. Despite the great advances that have occurred in the field of cancer therapy, the systemic repercussions of these drugs still impose important limitations on their use. In this sense, the development of increasingly targeted therapeutic protocols and preventive monitoring of patients represent important strategies to avoid possible complications - among them, Acute Kidney Injury (AKI). Routinely, ultrasound evaluation is used to identify morphological or metastatic variations in abdominal cavity organs. Acting complementary to the B-mode evaluation, Doppler mapping proves to be efficient in recognizing alterations in vascular hemodynamics. Therefore, the objective of the present study was to evaluate the use of B-mode and Doppler ultrasound to identify renal morphological and hemodynamic alterations in bitches with mammary neoplasia submitted to adjuvant chemotherapy protocols that associate gemcitabine with carboplatin. Thirteen bitches were included, without distinction of breed and between seven and 13 years of age. The animals were evaluated ultrasonographically at two different times during three consecutive chemotherapy cycles: before (T0) and one and a half hours after each cycle (T1), for 42 days. No morphological changes were observed in B-mode throughout the chemotherapy protocol. However, the Doppler velocimetry indices demonstrated statistical differences before (T0) and after (T1) the administration of the drugs. It was concluded that Doppler ultrasound could be used as a complementary method for monitoring the renal response of patients exposed to nephrotoxic drugs and potentially causing renal injury.

As neoplasias mamárias representam o tipo de neoplasma mais frequentemente diagnosticado em fêmeas da espécie canina. Embora a remoção cirúrgica seja o procedimento de eleição para a conduta terapêutica, os protocolos quimioterápicos aparecem como importantes aliados e adjuvantes. Apesar dos grandes avanços ocorridos na área da terapia oncológica, as repercussões sistêmicas destes fármacos ainda impõem importantes limitações ao seu uso. Neste sentido, o desenvolvimento de protocolos terapêuticos cada vez mais direcionados e o monitoramento preventivo dos pacientes representam estratégias importantes para evitar possíveis complicações - dentre elas, a injúria renal aguda (IRA). Rotineiramente, a avaliação ultrassonográfica é utilizada para identificação de variações morfológicas ou metastáticas em órgãos da cavidade abdominal. Atuando de forma complementar à avaliação em modo-B, o mapeamento Doppler mostra-se eficiente no reconhecimento de alterações na hemodinâmica vascular. Portanto, o objetivo do presente estudo foi avaliar a utilização da ultrassonografia modo-B e Doppler como método para identificação de alterações morfológicas e hemodinâmicas renais em cadelas com neoplasias mamárias submetidas a protocolos quimioterápicos adjuvantes que associam a gencitabina à carboplatina. Foram incluídas 13 fêmeas caninas, sem distinção quanto a raça e com idades entre sete e 13 anos. Os animais foram avaliados ultrassonograficamente em dois momentos distintos durante três ciclos quimioterápicos consecutivos: antes (T0) e uma hora e meia após a realização de cada ciclo (T1), totalizando 42 dias. Não foram observadas alterações morfológicas em modo-B ao longo do protocolo quimioterápico. Entretanto, os índices dopplervelocimétricos demonstraram diferenças estatísticas antes (T0) e após (T1) a administração dos fármacos. Concluiu-se que a ultrassonografia Doppler pode ser utilizada como método complementar para o monitoramento da resposta renal de pacientes expostos a fármacos nefrotóxicos e potencialmente causadores de injúrias renais.

Congenital extrahepatic portosystemic deviation of gastric vein with azygos in a bitch

Background: Portosystemic shunt (PSS), an alteration commonly found in toy dogs, is caused by an anastomosis between the systemic and portal circulation, interfering with the metabolism of several toxins. It can be of congenital or acquired origin and is classified as intra- or extrahepatic. Clinical signs include the gastrointestinal tract, nervous system, and urinary system according to the fraction of the shunt. It is diagnosed by several imaging tests and exploratory laparotomy. Therapy involves drug therapy and/or surgical correction of the anomalous vessels. Thus, the aim is to present an unusual case of extrahepatic cPSS originating from the left gastric vein and insertion into the azygos vein. Case: A 2-year-old female toy poodle, spayed, weighing 2.7 kg was treated with a history of recurrent cystitis and neurological signs such as focal seizures, ataxia, tremors, blindness, lethargy, head pressing, and compulsive gait. Complementary tests revealed normochromic microcytic anemia, neutrophilia-induced leukocytosis, monocytosis, and lymphopenia. Biochemical analysis revealed hypoproteinemia due to hypoglobulinemia, an increase in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyl transferase, and a decrease in urea. In the urinalysis, ammonium biurate crystals were detected, and Doppler ultrasound revealed microhepathy and the presence of an anomalous gastrosplenic vein inserted into the azygos vein, a finding compatible with the congenital extrahepatic PSS. Abdominal tomography confirmed vascular deviation with a sinuous path originating from the left gastric and splenic veins, inserting into the azygos vein, measuring approximately 5.95 cm in length. Cranial tomography revealed changes consistent with hepatic encephalopathy. Drug therapy was performed with hydration, liver chow, lactulose, probiotics, metronidazole, S-adenosyl-L-methionine, and ursodeoxycholic acid, and after 15 days, surgery was performed to place a 3.5 mm ameroid constrictor ring for gradual occlusion of the anomalous vessel. The animal recovered well, and a control abdominal ultrasound was repeated 30 days after the procedure, noting that the constrictor had not yet fully occluded the deviation. Doppler imaging revealed a favorable evolution with an increase in the diameter of the portal vein in the hepatopetal direction. The patient was followed-up for a year and had a normal and healthy life. Discussion: Extrahepatic PSS is frequently diagnosed in purebred and toy dogs, commonly occurring between the portal vein and one of its tributaries, with a lower frequency of anomalous vessels between the azygos veins, as in the present report. The patient's age and clinical signs were compatible with the disease, in addition to ammonia biurate crystals and hematological and biochemical alterations. The neurological clinical signs observed were compatible with hepatic encephalopathy secondary to congenital PSS. The imaging examinations facilitated the identification of the extrahepatic vascular anomaly, with the tomography being more accurate and helping in proper surgical planning. Clinical treatment should be performed for presurgical stabilization, and occlusion can be performed by placing cellophane bands or an ameroid constrictor, which is the technique of choice for congenital PSS, as it allows for slow constriction to avoid acute portal hypertension, as in this case, emphasizing that anesthesia in animals with portosystemic shunts must be performed with care.

Antifungal effect of (R) and (S)-citronellal enantiomers and their predictive mechanism of action on Candida albicans from voriconazole-resistant onychomycoses / Efeito antifúngico dos enantiômeros (R) e (S)-citronelal e seu mecanismo de ação preditivo sobre Candida albicans de onicomicoses resistentes ao voriconazol

Onychomycosis is the most common disease affecting the nail unit and accounts for at least 50% of all nail diseases. In addition, Candida albicans is responsible for approximately 70% of onychomycoses caused by yeasts. This study investigated the antifungal effect of (R) and (S)-citronellal enantiomers, as well as its predictive mechanism of action on C. albicans from voriconazole-resistant onychomycoses. For this purpose, in vitro broth microdilution and molecular docking techniques were applied in a predictive and complementary manner to the mechanisms of action. The main results of this study indicate that C. albicans was resistant to voriconazole and sensitive to the enantiomers (R) and (S)-citronellal at a dose of 256 and 32 µg/mL respectively. In addition, there was an increase in the minimum inhibitory concentration (MIC) of the enantiomers in the presence of sorbitol and ergosterol, indicating that these molecules possibly affect the integrity of the cell wall and cell membrane of C. albicans. Molecular docking with key biosynthesis proteins and maintenance of the fungal cell wall and plasma membrane demonstrated the possibility of (R) and (S)-citronellal interacting with two important enzymes: 1,3-ß-glucan synthase and lanosterol 14α-demethylase. Therefore, the findings of this study indicate that the (R) and (S)-citronellal enantiomers are fungicidal on C. albicans from onychomycoses and probably these substances cause damage to the cell wall and cell membrane of these micro-organisms possibly by interacting with enzymes in the biosynthesis of these fungal structures.

A onicomicose é a doença mais comum que afeta a unidade ungueal e representa pelo menos 50% de todas as doenças ungueais. Além disso, a Candida albicans é responsável por aproximadamente 70% das onicomicoses causadas por leveduras. Nesse estudo, foi investigado o efeito antifúngico dos enantiômeros (R) e (S)-citronelal, bem como seu mecanismo de ação preditivo sobre C. albicans de onicomicoses resistentes ao voriconazol. Para este propósito, foram aplicadas técnicas in vitro de microdiluição em caldo e docking molecular de forma preditiva e complementar para os mecanismos de ação. Os principais resultados deste estudo indicam que C. albicans foi resistente ao voriconazol e sensível aos enantiômeros (R) e (S)-citronelal na dose de 256 e 32 µg/mL respectivamente. Além disso, houve aumento da concentração inibitória mínima (CIM) dos enantiômeros na presença do sorbitol e do ergosterol, indicando que estas moléculas possivelmente afetem a integridade da parede e da membrana celular de C. albicans. O docking molecular com proteínas chave da biossíntese e manutenção da parede celular e da membrana plasmática fúngica, demonstraram a possibilidade do (R) e (S)-citronelal interagir com duas importantes enzimas: 1,3-ß-glucan sintase e lanosterol 14α-demetilase. Portanto, os achados desse estudo indicam que os enantiômeros (R) e (S)-citronelal são fungicidas sobre C. albicans de onicomicoses e provavelmente essas substâncias causem danos a parede e a membrana celular desses microrganismos possivelmente por interagir com as enzimas da biossíntese destas estruturas fúngicas.

Síndrome da feminização em cão com sertolioma / Feminization syndrome in a dog with Sertoli cell tumor

Background: The uncontrolled multiplication of Sertoli cells causes Sertoli cell tumor or Sertolioma. Because of this, the level of estrogen in the bloodstream increases rapidly and approximately 25% of dogs with this tumor develop feminization syndrome. Testicular neoplasms are more common in dogs than cats, and are often found in elderly patients. This work aims to describe the clinical signs of the feminization syndrome and the treatment instituted in a canine diagnosed with sertolioma. Case: A 18-year-old male canine, 19.5 kg of body mass, with an increase in testicular volume for about 2 years, was treated at the University Veterinary Hospital. On clinical examination, a matte and brittle coat, alopecia on the hind limbs and gynecomastia were observed. Also noted, non-harmonious aspect of the scrotum, pendular foreskin, atrophied right testicle and hyperplastic left, scrotal hyperthermia and absence of pain. In addition, as a result of the hyperestrogenism resulting from the neoplasm, the paraneoplastic syndrome of feminization, the patient also presented galactorrhea, pendular foreskin, atrophy of the penis and the contralateral testicle, dermatopathies, such as bilateral symmetrical alopecia of the flanks, easily removable hair and variable hyperpigmentation. Rectal body temperature of 38.6°C, clear lung auscultation and muffled cardiac auscultation. The results of laboratory tests showed changes such as thrombocytopenia, platelet counts below the reference levels, platelet count of 163,000/uL. There were no alterations that represented metastases in the imaging exams, such as in the chest X-ray in three incidences and in the abdominal ultrasonography. Then, we opted for the surgical procedure of orchiectomy, with the traditional technique of three clamps, associated with total ablation of the scrotum. Samples were sent to the histopathology laboratory and the diagnosis of sertolioma was confirmed. At 10, 30 and 90 days after the operation, the patient was reassessed for possible recurrences or alterations, but there were no complications or recurrence after the procedure. Discussion: Neoplasms of the male reproductive system are common in dogs. Sertolioma is considered one of the most frequent neoplasms in elderly dogs and that results in systemic clinical signs. This is in line with the 18-year-old dog described in the present report. In addition, it may result in clinical signs resulting from hyperestrogenism resulting from the neoplasm that is called paraneoplastic feminization syndrome. The characteristics of this syndrome are: gynecomastia, galactorrhea, pendular foreskin, atrophy of the penis and contralateral testicle, associated with dermatopathies, such as symmetrical bilateral alopecia. All these clinical signs were present. The diagnosis is made through complete anamnesis, complete clinical examination and complementary examination such as ultrasound help in the presumptive diagnosis, but only with histopathology can it be confirmed. In the clinical approach, histopathology was performed to close the diagnosis. Treatment is behind orchiectomy and total ablation of the scrotum, which was performed in the reported case. The treatment of choice was easy to apply, in addition to improving the patient's quality of life, promoting rapid post-surgical healing and an early return to normal life. However, for the effectiveness of the technique, the early diagnosis and collaboration of tutors is fundamental.

O efeito da ozonioterapia no tratamento de fratura de fêmur em filhote canino: relato de caso / The effect of ozone therapy in the treatment of femur fracture in puppies: case report

Fraturas de fêmur são casos recorrentes na clínica veterinária de pequenos animais, ocorrendo principalmente em filhotes. O seu diagnóstico considera histórico e sinais clínicos apresentados, como sensibilidade dolorosa e apoio do membro em pinça, e é confirmado por exame radiográfico do membro lesionado. Geralmente, esse tipo de fratura tem o tratamento cirúrgico como indicação, entretanto, com o perigo de submeter o animal a riscos tanto anestésicos quanto cirúrgicos. O presente relato de caso descreve o uso da ozonioterapia, uma forma diferente e menos invasiva de se tratar fratura femoral, com um maior potencial de adesão do tutor por ser um tratamento mais acessível e com excelentes resultados.(AU)

Femur fractures are recurrent cases in the small animal veterinary clinic, occurring mainly in puppies. It's diagnosis is based on the history and clinical signs presented, such as painful sensitivity and support of the limb on tweezers, and defined by radiographic examination of the injured limb. Generally, this type of fracture has surgical treatment indication, however, with the danger of subjecting the animal to both anesthetic and surgical risks. The present case report describes the use of ozone therapy, a different and less invasive way of treating a femoral fracture, with a greater potential for adherence by the tutor, as it is a more accessible treatment and with excellent results.(AU)

Ozone therapy in veterinary medicine: clinical indications and techniques / Ozonioterapia na medicina veterinária: técnicas e indicações clínicas

Ozone therapy application and research have increased recently. The mixture of oxygen-ozone (O2-O3) has been used as a therapeutic agent for the treatment of several diseases with beneficial effects. This brief literature review has the objective of disclosing the mechanisms of action and main clinical indications and possibilities of ozone therapy for different conditions. The local and systemic approaches and techniques described for human treatment can be easily transposed for use in animals, such as rectal insufflation; bag therapy; ozonated oil; intradiscal and paravertebral applications; in acupuncture points; minor autohemotherapy, and major autohemotherapy. The possibilities of clinical indications and dosages were also described, including immunological and infectious diseases. Although it is a minimally invasive and relatively safe approach, more clinical studies are necessary to standardize techniques, doses, and clinical indications.

A aplicação e a pesquisa da terapia com ozônio aumentaram recentemente. A mistura de oxigênio-ozônio (O2-O3) tem sido utilizada como agente terapêutico para o tratamento de diversas doenças com efeitos benéficos. Esta breve revisão de literatura tem o objetivo de divulgar os mecanismos de ação e as principais indicações clínicas e possibilidades da ozonioterapia para diferentes condições. As abordagens e técnicas locais e sistêmicas descritas para o tratamento em humanos podem ser facilmente transpostas para uso em animais, como insuflação retal; terapia tópica de "bagging"; óleo ozonizado; aplicações intradiscal e paravertebral; em pontos de acupuntura; auto-hemoterapia menor e auto-hemoterapia maior. Também foram descritas as possibilidades de indicações clínicas e dosagens, incluindo doenças imunológicas e infecciosas. Embora seja uma abordagem minimamente invasiva e relativamente segura, mais estudos clínicos são necessários para padronizar técnicas, doses e indicações clínicas.

Conventional vs. advanced echocardiographic parameters for predicting fluid responsiveness in healthy dogs

Background: Volume replacement is considered an essential component in the treatment of critically ill patients, but excess f luid administration can be as harmful as the lack of fluid therapy. Therefore, the volume replacement is only beneficial in patients deemed to be fluid responsive, that is, when the individual has an increase in their stroke volume after administration of a volume challenge. This study aim to assess whether conventional and advanced echocardiographic parameters for assessing left ventricular systolic function are able to predict fluid responsiveness in healthy spontaneously breathing dogs. The hypothesis was that some of these parameters would differ between responsive and non-responsive animals and could be used as a complementary measure for assessment of fluid responsiveness. Materials, Methods & Results: A prospective study was carried out in which 22 client-owned healthy dogs over 1 year of age that presented to the Veterinary Medical Teaching Hospital for elective neutering procedure were included. All dogs underwent conventional and advanced echocardiographic examination to obtain the left ventricular internal diameter in diastole normalized (LVIDDn), left ventricular internal diameter in systole normalized (LVIDSn), ejection fraction (EF) and shortening fraction (SF) according to the Teischholz methodology, global longitudinal strain (GLS) and tissue motion annular displacement (TMAD). There parameters were evaluated before and after administration of a volume challenge with 10 mL/kg lactate ringer intravenously for 20 min. Based on the variation in aortic velocity integral time, 31.82% of dogs were considered responsive and 68.18% were non-responsive to the volume challenge. For advanced echocardiography, TMAD indexed by body weight (mm/kg) > 0.89 (P = 0.004) and body surface area (mm/m2) >18.9 (P = 0.004) after volume challenge had the best area...

Atypical transmissible venereal tumor in dogs

Background: The Transmissible Venereal Tumor (TVT), classified as a round cell tumor, is considered one of the oldestexisting tumors. It affects dogs all over the world and has a contagious characteristic. Despite the good response to clinicaltreatment in most cases, it can sometimes have non-classical presentations and even different behavior. Thus, the presentstudy aims to report 3 cases of atypical TVT treated at the Veterinary Medical Teaching Hospital of the State University ofMaringá (UEM) in Umuarama, Paraná, aiming to describe the epidemiology and clinical-pathological aspects, focusingon the diagnostic method used, the treatment of choice and the clinical follow-up of each case.Cases: Case records of 3 intact male mongrel dogs with atypical Transmissible Venereal Tumor (case 1: intranasal; case2: intra-abdominal and case 3: cutaneous with lymph node metastasis) were reviewed regarding history, clinical signs,duration of clinical signs, examination findings, results and findings of complementary exams (hematological, biochemical,radiographic, ultrasonographic and cytological), treatment, follow-up and final result. Case 1: had an ulcerated mass in thenasal plane causing significant airway obstruction and respiratory difficulty. Case 2: had a lesion in a typical location (penilemucosa in the glans area) but with a large intra-abdominal mass in the lumbar paravertebral region, causing compressionof important structures. Case 3: on the other hand, had cutaneous TVT with several ulcerated plaque lesions all over theskin, in addition to popliteal lymph node enlargement due to metastasis later confirmed by microscopy. All dogs reportedwere mixed breed, intact males with free access to the street. Despite...

Cutaneous candidiasis caused by antifungal-resistant Candida sp. strain in canine individual / Candidíase cutânea causada por cepa de Candida sp. resistente a antifúngicos em indivíduo canino

The aim of the current report is to describe a cutaneous candidiasis case affecting a canine individual treated at the University Veterinary Hospital of State University of Maranhão (UEMA), in São Luís City. The patient had three-month history of skin diseases; it had been previously subjected to several treatments based on antibiotics, corticosteroids and antifungal drugs that have failed to show clinical improvements. Dermatological assessment has indicated generalized moist dermatitis, intense skin desquamation, alopecia, pruritus and meliceric crusts along the animal's body, mainly in its dorsal region. Complementary tests, such as skin cytology and microscopy, trichogram, qualitative PCR and serology for canine visceral leishmaniasis, as well as fungal culture and antifungigram were requested based on this scenario. Serology recorded inconclusive results for leishmaniasis, whereas PCR recorded negative results in the presence of the agent's DNA. Cytology, microscopy and trichogram results have evidenced fungal infection in the assessed samples. Moreover, mycological culture and antifungigram resulted in the growth of Candida sp. specimens capable of resisting antifungal agents such as amphotericin B, fluconazole, itraconazole and nystatin. The therapy adopted after candidiasis diagnosis confirmation comprised oral doses of manipulated ketoconazole, in combination to topical therapy with shampoo based on moisturizing formulas associated with Miconazole and Chlorhexidine (at 2%), for four weeks. After 30 days, when the adopted therapy was over, the aforementioned animal presented remission of the previously observed lesions and fully improved condition.

The aim of the current report is to describe a cutaneous candidiasis case affecting a canine individual treated at the University Veterinary Hospital of State University of Maranhão (UEMA), in São Luís City. The patient had three-month history of skin diseases; it had been previously subjected to several treatments based on antibiotics, corticosteroids and antifungal drugs that have failed to show clinical improvements. Dermatological assessment has indicated generalized moist dermatitis, intense skin desquamation, alopecia, pruritus and meliceric crusts along the animal's body, mainly in its dorsal region. Complementary tests, such as skin cytology and microscopy, trichogram, qualitative PCR and serology for canine visceral leishmaniasis, as well as fungal culture and antifungigram were requested based on this scenario. Serology recorded inconclusive results for leishmaniasis, whereas PCR recorded negative results in the presence of the agent's DNA. Cytology, microscopy and trichogram results have evidenced fungal infection in the assessed samples. Moreover, mycological culture and antifungigram resulted in the growth of Candida sp. specimens capable of resisting antifungal agents such as amphotericin B, fluconazole, itraconazole and nystatin. The therapy adopted after candidiasis diagnosis confirmation comprised oral doses of manipulated ketoconazole, in combination to topical therapy with shampoo based on moisturizing formulas associated with Miconazole and Chlorhexidine (at 2%), for four weeks. After 30 days, when the adopted therapy was over, the aforementioned animal presented remission of the previously observed lesions and fully improved condition.

Granuloma caused by Acanthocheilonema spp. in a canine: case report / [Granuloma por Acanthocheilonema spp. em um cão: relato de caso]

A canine patient, 13-year-old mixed breed male, 24kg, was seen at a private clinic in the city of Guayaquil, Ecuador. The main reason for consultation was the evaluation of a mass in the right knee and neck that had previously been cytologically diagnosed of neoplastic origin by another team of veterinarians through fine needle puncture and cytology. The contacts were asymptomatic. At the time of the consultation, a detailed exploration and complementary methods were performed that included hematological and urinary exams, mass cytology, serological test, chest radiography and biopsy for further histopathological study. The final diagnosis was a cutaneous granuloma due to microfilariae of Acanthocheilonema spp. and its subsequent surgical and medical treatment with excellent results. The canine heartworm is a cosmopolitan disease caused by nematodes of the genus Dirofilaria, with D. immitis being the best-known species. Less frequently, the species Acanthocheilonema spp., found in this patient, is also reported in Americas, with little knowledge about it. This is the first report of its kind hoping that it will serve as a basis for future studies.

Foi atendido, em uma clínica particular, na cidade de Guaiaquil, Equador, um paciente canino, sem raça definida, de 13 anos de idade, macho, não castrado, de 24kg. O motivo da consulta foi a avaliação de uma massa em região de articulação de joelho direito e de pescoço, que havia sido previamente diagnosticada como de origem neoplásica por outra equipe de médicos veterinários, mediante punção por agulha fina e citologia. Os contactantes eram assintomáticos. No momento da consulta, realizaram-se detalhadas avaliações clínica e complementar, que incluíram exames hematológicos, urinálise, citologia da massa, teste sorológico, radiografia torácica e biopsia para posterior estudo histopatológico. O diagnóstico final foi granuloma cutâneo por microfilária de Acanthocheilonema spp., para o qual os tratamentos clínico e cirúrgico apresentaram excelentes resultados. A dirofilariose é uma enfermidade cosmopolita causada por nematódeos do gênero Dirofilaria, sendo a espécie D. immitis a mais conhecida. Em menor frequência, a espécie Acanthocheilonema spp. encontrada neste paciente é também relatada na América, existindo pouco conhecimento a seu respeito. Este é o primeiro relato de caso sobre este tema e espera-se que sirva como base para futuros estudos.

Icterícia: da manifestação ao manejo clínico-terapêutico / Icterus: from manifestation to clinical-therapeutic management / Ictericia: de la manifestación al manejo clínico-terapéutico

A icterícia é considerada como a pigmentação amarelada de regiões corpóreas como esclera, pele e mucosas. É uma manifestação presente em variadas doenças e pode ser classificada em icterícia pré-hepática, hepática ou pós-hepática. A categorização dos tipos de icterícia e suas identificações são fundamentais para que haja um maior conhecimento acerca do seu local de ocorrência, da sua gravidade e progressão. A condição pode ser observada em cães e gatos, e cada tipo pode estar associado a doenças distintas como processos hemolíticos, doenças hepatocelulares, obstruções de fluxo biliar, dentre outros. O diagnóstico da manifestação pode ser determinado por meio dos dados coletados na anamnese, exame clínico e/ou complementar, este último mediante necessidade. O tratamento varia e depende da causa base que esteja associada como terapias medicamentosas a intervenções cirúrgicas.

Jaundice is considered the yellowish pigmentation of body regions such as the sclera, skin and mucous membranes. It is a manifestation present in several diseases and can be classified as pre-hepatic, hepatic or post-hepatic jaundice. The categorization of types of jaundice and their identification are essential for greater knowledge about its place of occurrence, its severity and progression. The condition can be observed in dogs and cats, and each type can be associated with different diseases such as hemolytic processes, hepatocellular diseases, bile flow obstructions, among others. The diagnosis of the manifestation can be determined through data collected through anamnesis, clinical and/or complementary examination, the latter as needed. Treatment varies and depends on the underlying cause that is associated with drug therapies and surgical interventions.

La ictericia se considera la pigmentación amarillenta de regiones del cuerpo como la esclerótica, la piel y las membranas mucosas. Es una manifestación presente en varias enfermedades y puede clasificarse en ictericia prehepática, hepática o poshepática. La categorización de los tipos de ictericia y su identificación son fundamentales para un mayor conocimiento sobre su lugar de aparición, su gravedad y progresión. La afección se puede observar en perros y gatos, y cada tipo puede asociarse con diferentes enfermedades como procesos hemolíticos, enfermedades hepatocelulares, obstrucciones del flujo biliar, entre otras. El diagnóstico de la manifestación se puede determinar mediante la recogida de datos mediante anamnesis, exploración clínica y / o complementaria, esta última según sea necesario. El tratamiento varía y depende de la causa subyacente asociada con las terapias farmacológicas y las intervenciones quirúrgicas.

Granulomatous nephritis and uremia associated with Klossiella equi in a horse from Rio Grande do Sul, Brazil / Nefrite granulomatosa e uremia associada a Klossiella equi em um equino no Rio Grande do Sul, Brasil

Klossiella equi is an unusual protozoan of equids. In most cases, it does not cause renal injury. A case of K. equi-associated granulomatous nephritis leading to uremia in a brazilian mare is described. The animal presented colic, and among the complementary exams, increased urea and creatinine was observed. The kidneys were unremarkable on gross exam; however, a multifocal granulomatous nephritis with tubular degeneration associated with intraepithelial and intraluminal protozoa was observed histologically. The large intestines were edematous and hemorrhagic. The importance of including K. equi infection among the differential diagnosis of horses with kidney disease in southern Brazil is highlighted.

Klossiella equi é um protozoário incomum de rim de equídeos, geralmente considerado de pouca importância clínica. Descreve-se um caso de klosselliose associada a lesão renal e uremia em uma égua. O animal foi atendido com quadro de cólica, e dentre os exames, foi constatado aumento de ureia e creatinina. Na necropsia, os rins não apresentavam lesões macroscópicas, no entanto, na histopatologia, observou-se nefrite granulomatosa com degeneração tubular associada a protozoários intraepiteliais e intraluminais. A parede do intestino grosso estava edemaciada e hemorrágica. Se destaca a importância da inclusão de infecção por K. equi nos diagnósticos diferenciais de equinos com doença renal no sul do Brasil.

Tratamento da epilepsia idiopática canina - quadro clínico após interação medicamentosa / Treatment of canine idiopathic epilepsy - clinical picture after drug interaction

Background: The large number of diseases demand perennial development of the pharmaceutical industry. The drugtesting phase is essential to make them available safely. Awareness of pharmacological properties, adverse effects and drug interactions is required. Drug interactions are common in veterinary medicine and should be avoided. At times, epileptic seizures require polydrug therapy, predisposing patients to drug interactions. The interaction between carbamazepine and phenobarbital reported in the literature is an example. The aim of this paper is to report a clinical picture of drug interaction in the treatment of idiopathic epilepsy. Case: A 1-year-old Border Collie male dog, was admitted at the Veterinary Hospital of the Federal University of Lavras in post-ictal. The tutor reported that a year ago the animal had epileptic seizures and clusters with intervals of 21 to 25 days. Despite the continued use of previously prescribed phenobarbital (7.4 mg/kg, v.o., BID, until new recommendations) and carbamazepine (7.5 mg/kg, v.o., BID, until new recommendations), seizure control was not achieved. The physical examination indicated, tachypnea, ptialism, mydriasis, intense fatigue, and alienation from the environment. The patient did not respond to the threat-reflex test. Blood count, hepatic and renal blood chemistry, serum electrolyte (potassium, sodium, calcium and phosphorus), and phenobarbital dosages were requested. Based on the animal's history, breed characteristics, and alterations in the physical examination associated with normal results in complementary exams, idiopathic epilepsy was diagnosed. After analyzing the case, it was observed that the inefficiency in the control of seizures was possibly due to the drug interaction between phenobarbital and carbamazepine. Carbamazepine and phenobarbital reciprocally reduce their half-lives. To confirm the raised hypothesis, the serum concentration of carbamazepine was gradually reduced through weaning from its dose administered to the patient. Serial dosage of the concentration of phenobarbital in the bloodstream was performed. As a result, the serum phenobarbital, previously dosed at a concentration of 13.3 mg/dL with concomitant administration of carbamazepine, increased to 22 mg/dL 40 days after the beginning of weaning from carbamazepine (T0), and then to 36 mg/dL 100 days after T0. There was an increase in the concentration of phenobarbital in the bloodstream while the serum concentration of carbamazepine declined. The patient spaced out his seizures to every 50 to 60 days with phenobarbital monotherapy at a dose of 6 mg/kg. Discussion: Efficient control of clusters, such as the reduction of seizures by 50%, was only possible due to the meticulous perception of the possible interaction reported in medicine. Carbamazepine and phenobarbital are P450 isoenzyme inducers. The concomitant administration of both drugs potentiated the action of isoenzymes in the hepatic microsomal system, which led to an accelerated metabolic processing of the drugs. After weaning from carbamazepine, that is, reducing the action of carbamazepine on the isoenzymes of the P450 enzyme system, the concentration of phenobarbital normalized at 36 mg/ dL. Such concentration is within the reference range reported in the literature: 25 mg/dL to 35 mg/dL of serum phenobarbital for treatment efficacy. Therefore, the control of convulsive crises was achieved. The increase in the concentration of phenobarbital due only to weaning from carbamazepine, even after decreasing the daily dose of barbiturate prescribed to the animal, contributed to evidence of the interaction of these drugs. It is noted that prior knowledge of pharmacological properties, careful study of the patient's history, and the cooperation of the tutor were essential for the therapeutic success and practice of evidence-based veterinary medicine.

Fluconazol intra-estromal - eficácia na cirurgia de abscesso estromal em equino / Intrastromal fluconazole - effectiveness in the surgery of stromal abscess in a horse

Background: Due to its ocular microflora, the equine species is predisposed to develop mycotic ulcers which, when notproperly treated, can lead to the formation of a stromal abscess. A stromal abscess occurs through the introduction ofmicroorganisms into the corneal stroma. During re-epithelialization, the foreign body is encapsulated, thus creating abarrier that protects bacteria or fungi from treatment with antimicrobial medication. This framework can end up resultingin blindness due to chronic iridocyclitis, putting the animal’s vision at risk. The current work aims to report a case of corrective surgery for stromal abscess in a mare with the administration of intraoperative intrastromal fluconazole, in orderto corroborate the effectiveness of the technique.Case: A 9-year-old mare was evaluated, with the complaint that her right eye was closed and “yellowish” and that she hadalready been treated with intramuscular injectable anti-inflammatory drugs based on flunexin meglumine (Banamine® -50 mg) for 15 days, referring to a possible ulcer in the right eye. Ophthalmic screening resulted in a negative direct reflexand no threat response in the right eye. Examination of the conjunctiva showed congestion and chemosis. Examination ofthe cornea of the right eye was negative for Fluorescein and Green Lissamine tests, and opacity and corneal neovascularization were noted. The final diagnosis was a corneal abscess of probable fungal origin secondary to a keratomycosis. Afterthe consultation, complementary blood and biochemical tests were performed, which showed normal results for the speciesin question, and treatment was started with eye drops based on atropine 1% (Fagra® - 20 mL), ciprofloxacin antimicrobialeye drops (Ciprovet Colirio® - 5 mL), and antifungal eye drops based on ketoconazole...

Hiperplasia endometrial cística em uma coelha-doméstica (Oryctolagus cuniculus domesticus) / Cystic endometrial hyperplasia in a domestic rabbit (Oryctolagus cuniculus domesticus)

Background: Cystic endometrial hyperplasia is a hormone-dependent disease induced by systemic increase in progesteronethat can occur in several domestic species, such as the rabbit. This disease may be associated with sex steroid hormones,especially progesterone, and may be asymptomatic, and it is diagnosed using complementary imaging tests such as totalabdominal ultrasound. However, surgical excisional biopsy with histopathological tissue analysis is the gold standard. Thisstudy reports a case of asymptomatic cystic endometrial hyperplasia in a female Miniature Lion Lop rabbit (Oryctolaguscuniculus domesticus) treated with therapeutic ovariohysterectomy.Case: A domestic, adult, female Miniature Lion Lop rabbit (Oryctolagus cuniculus domesticus), aged approximately 5 yearsand weighing 3.2 kg, was referred to specialized care to undergo ovariohysterectomy, an elective procedure. The tutor onlyreported the occurrence of a single episode of vulvar secretion more than 2 years ago, treated with antibiotics, with remissionof clinical signs. In the intraoperative period after celiotomy, the uterine horn and uterine body showed a significant increasein volume, with abnormal color changes and tissue consistency; however, both changes were clinically asymptomatic. Subsequently, biopsy was performed during the ovariohysterectomy procedure. The excised uterus and ovaries were placed in 10%formalin and histopathologically analyzed. The macroscopic histopathological examination of the sectioned tissue revealed aslight amount of brownish fluid inside the uterine horns, in addition to multiple cystic areas in the uterine mucosa. Microscopicexamination revealed marked hyperplasia of well-differentiated endometrial epithelial cells, occasionally forming cystic structuresof different sizes. Moderate congestion, mild multifocal hemorrhage, and mild multifocal inflammatory infiltrate in the lamina...

Uso da miltefosina no tratamento clínico de cães com leishmaniose visceral: revisão de literatura / Use of miltefosin in the clinical treatment of dogs with visceral leishmaniosis / Uso de miltefosina en el tratamiento clínico de perros con leishmaniosis visceral: revisión de la literatura

A leishmaniose visceral canina é uma doença de caráter zoonótico, acometendo os seres humanos e diversas espécies de animais silvestres e domésticos. Objetivou-se com o presente estudo realizar uma revisão de literatura sobre o uso da miltefosina no tratamento clínico de cães com leishmaniose visceral. Trata- se de uma revisão de literatura, a qual foi realizada por meio de consultas à periódicos e livros presentes na biblioteca do Cesmac. Foram utilizadas bases de dados como: portal Capes, SCIELO, Google Acadêmico; pesquisa em monografias, teses e dissertações. Causada pelo protozoário Leishmania chagasi, sendo o cão doméstico o principal reservatório desse protozoário. Por representar um problema grave de saúde pública e ser considerada uma doença potencialmente fatal (quando não tratada precocemente e adequadamente), faz- se importante que o clínico esteja familiarizado com os sinais clínicos, exames complementares e principais protocolos terapêuticos, em especial a utilização da miltefosina no tratamento da leishmaniose visceral em cães. Por ser uma zoonose que causa graves problemas de saúde pública e que vem crescendo cada vez mais no Brasil, cabe aos médicos veterinários assumirem o compromisso na conscientização sobre a importância do diagnóstico precoce além de promoverem o bem-estar animal e a saúde pública.(AU)

Canine visceral leishmaniasis is a zoonotic disease, affecting humans and several species of wild and domestic animals. The objective of the present study was to carry out a literature review on the use of miltefosine in the clinical treatment of dogs with visceral leishmaniasis. This is a literature review, which was carried out through consultations with periodicals and books present in the Cesmac library. Databases such as: Capes portal, SCIELO, Google Scholar; research in monographs, theses and dissertations. Caused by the protozoan Leishmania chagasi, with the domestic dog being the main reservoir of this protozoan. As it represents a serious public health problem and is considered a potentially fatal disease (when not treated early and properly), it is important that the clinician is familiar with the clinical signs, complementary exams and main therapeutic protocols, especially the use of miltefosine in the treatment of visceral leishmaniasis in dogs. As it is a zoonosis that causes serious public health problems and that has been growing more and more in Brazil, it is up to veterinarians to make a commitment to raise awareness of the importance of early diagnosis in addition to promoting animal welfare and public health.(AU)

La leishmaniosis visceral canina es una enfermedad zoonótica que afecta a los seres humanos y a varias especies de animales salvajes y domésticos. El objetivo de este estudio fue realizar una revisión bibliográfica sobre el uso de la miltefosina en el tratamiento clínico de perros con leishmaniosis visceral. Se trata de una revisión bibliográfica, que se realizó mediante consultas a publicaciones periódicas y libros presentes en la biblioteca del Cesmac. Se utilizaron bases de datos como: portal Capes, SCIELO, Google Académico; investigación en monografías, tesis y disertaciones. Causada por el protozoo Leishmania chagasi, siendo el perro doméstico el principal reservorio de este protozoo. Dado que representa un grave problema de salud pública y se considera una enfermedad potencialmente mortal (cuando no se trata de forma temprana y adecuada), es importante que el clínico esté familiarizado con los signos clínicos, las pruebas adicionales y los principales protocolos terapéuticos, especialmente el uso de miltefosina en el tratamiento de la leishmaniosis visceral en perros. Siendo una zoonosis que causa graves problemas de salud pública y que viene creciendo cada vez más en Brasil, corresponde a los veterinarios asumir el compromiso de concienciar sobre la importancia del diagnóstico precoz y promover el bienestar animal y la salud pública.(AU)