Anasarca associated with restrictive cardiomyopathy in cats

Background: Cardiomyopathies are a primary heart disorder and are one of the most causes of heart failure and sudden death in cats. Restrictive cardiomyopathy is a diastolic dysfunction resulting from endomyocardial fibrosis, with filling restriction and ventricular distention. In these cases, a poor outcome is expected. Anasarca in animals is often associated with dystocia secondary to congenital changes. In adults, this is a rare condition, since subcutaneous edema in animals with congestive heart failure is an uncommon finding. Therefore, this report describes clinical and pathological findings in an unusual presentation of anasarca in two adult cats with restrictive cardiomyopathy. Cases: A 12-year-old female mixed breed cat (case 1) and a 6-year-old male mixed-breed cat (case 2) were present on an emergent basis at the veterinary hospital with a history of respiratory distress. Case 1 showed on physical examination intense restrictive mixed dyspnea and lethargy, with muffled heart sounds and respiratory noises in cardiorespiratory auscultation. The cat exhibited abdominal distension resulting from ascites. Generalized subcutaneous edema was evident mainly in the abdominal and submandibular areas and the thoracic and pelvic limbs. In these regions, a positive Godet signal was observed. Thoracic radiography revealed pleural effusion, and the cat underwent fluid drainage on both sides of the thoracic cavity. Drainage material was sent to the laboratory for clinical analysis, which indicated that it was a modified transudate. The clinical signs worsened, and the cat was euthanized. In case 2, physical examination showed severe restrictive mixed dyspnea, lethargy, and low body temperature (< 32°C). Abdominal distension resulting from ascites and generalized edema in the subcutaneous tissue with a positive Godet sign was observed. On cardiorespiratory auscultation, cardiac sounds and breathing noises were muffled. Thoracic radiography revealed pleural effusion. The cat was immediately placed in an incubator for clinical stabilization with oxygen therapy and warm-up. After 2 h of hospitalization, thoracentesis and drainage of cavity fluids were performed, which were classified as modified transudate. The patient remained in critical condition during hospitalization, evolving to death. The two cats were referred for a complete post mortem examination. Grossly, both cats showed distension of the abdomen and marked edema of subcutaneous tissue, mainly in the abdominal, ventral cervical, and thoracic and pelvic members. In the abdominal and thoracic cavities, a moderate amount of serous-free liquid, slightly reddish was observed. The heart of both cats was enlarged, with a globose appearance and a slightly whitish epicardium. The left ventricular endocardium was mild and diffusely thick and whitish, in addition to moderate dilation of the left atrium. Histological analyses of the heart showed in both cats moderate and diffuse proliferation of fibrous connective tissue in the endocardial region. Discussion: Restrictive cardiomyopathy has major importance in feline medicine due to its severity and poor outcome. Pleural effusion, pulmonary edema, and ascites are common findings in cats with congestive heart failure; however, generalized subcutaneous edema is uncommon. To the author’s knowledge, there are no published cases in the literature of anasarca in adult cats with restrictive cardiomyopathy. In human cardiology, this presentation is commonly related to congestive heart failure, and it is reported under several conditions, such as restrictive cardiomyopathy and constrictive pericarditis. The present study suggests that anasarca should be included in the list of associated clinical signs suggestive of severe congestive heart failure, mainly related to restrictive cardiomyopathy

Remielinização em camundongos Knockout para conexina 32 desmielinizados experimentalmente

Este estudo visou avaliar o papel da conexina 32 (Cx 32) durante a remielinização no sistema nervoso periférico. Uma injeção local de 0,1% de solução de brometo de etídio foi realizada no nervo ciático de camundongos deletados para a Cx 32, com eutanásia dos animais aos 1, 2, 3, 7, 15, 21 e 30 dias pós-injeção. Avaliações histoquímicas, imunoistoquímicas, por imunofluorescência e por microscopia eletrônica de transmissão foram utilizadas na análise do desenvolvimento das lesões. Nos nervos ciáticos, células de Schwann mostraram inicialmente sinais de intoxicação e rejeitaram suas bainhas. Após sete dias, observaram-se finas bainhas neoformadas, com compactação desigual e alças redundantes (tomácula). Conclui-se que a regeneração de bainhas de mielina perdidas no SNP seguiu o padrão já relatado deste modelo em outras espécies de laboratório. Portanto, estes resultados sugerem que a ausência da Cx 32 não interferiu com o padrão normal de remielinização em camundongos jovens neste modeloThe aim of this study was to evaluate the role of connexin 32 (Cx 32) during remyelination of the peripheral nervous system, through a local injection of either 0,1% ethidium bromide solution or saline in the sciatic nerve of Cx 32 knockout mice. Euthanasia was performed ranging from 1, 2, 3, 7, 15, 21 to 30 days after injection. Histochemical, immunohistochemical, immunofluorescence and transmission electron microscopical techniques were used to analyze the development of the lesions. Within the sciatic nerves, Schwann cells initially showed signs of intoxication and rejected their sheaths; after seven days, some thin newly formed myelin sheaths with uneven compactness and redundant loops (tomacula) were conspicuous. We concluded that the regeneration of lost myelin sheaths within the PNS followed the pattern already reported for this model in other laboratory species. Therefore, these results suggest that absence of Cx 32 did not interfere with the normal pattern of remyelination in this model in young miceCNPq 475029/2004-6Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Clinical and pathological aspects of canine necrotizing meningoencephalitis

A meningoencefalite necrosante canina (MNC) é uma doença inflamatória idiopática que afeta principalmente os hemisférios cerebrais de cães de raças pequenas. A sintomatologia apresentada pelos animais é progressiva, sendo as crises convulsivas o principal sinal clínico. A etiologia da MNC ainda é pouco conhecida, sendo possivelmente multifatorial e influenciada por fatores genéticos e ambientais. Até o momento, os tratamentos têm sido paliativos, com uso de anti-inflamatórios corticoides em dosagens imunossupressoras e anticonvulsivos. Nesta revisão são descritos seis casos recentes de MNC no Brasil, ocorridos nas raças pug (dois casos), Yorkshire (dois casos) e maltês (dois casos). Deste total, três casos foram provenientes da Faculdade de Medicina Veterinária e Zootecnia - Universidade de São Paulo - SP e três do Laboratório de Patologia Veterinária - Universidade Federal de Santa Maria - RSThe canine necrotizing meningoencephalitis complex (CNM) is an inflammatory disease characterized by multifocal nonsuppurative idiopathic meningoencephalitis, which mainly affects the cerebral hemispheres of small and miniatute breed dogs. This paper presents clinical and pathological data regarding cases registered in Brazil, compared with cases in literature. The disease has been reported in pug, maltese, papillon, Shih tzu, chihuahua and pekingese dogs. More recent reports describe the occurrence of CNM in greyhound, West Highland white terrier and French bulldog. In Brazil, there have been cases of this disease in pug, maltese and Yorkshire dogs (Figure 3). Although the etiology of CNM is much still unknown; it is most likely a multifactorial disease, influenced by genetic and environmental factors. The viral etiology of meningoencephalitis was suggested by some authors in the first case reports. However, several studies have shown negative results to testing (PCR and serological tests) for viruses such as canine distemper, as well as protozoa and agents of dirofilariasis, ehrlichiosis and borreliosis in the cases presented. Still, etiologic agents are not discarded as possible factors triggering a secondary autoimmune response to a prior exposition. An epidemiological study with 60 affected pug dogs indicated higher frequency (though not statistically significant) in females (40 affected individuals). This evidence is supported by the fact that autoimmune encephalitis tend to affect more females than males in different species. The most likely pathogenesis of CNM is the autoimmune hypothesis reinforced by signs of autoantibodies against astrocytic glial fibrillary acidic protein (GFAP) in cerebrospinal fluid (CSF) of dogs affected by this disease. Determination of autoantibodies in CSF or serum of affected dogs has provided relevant data on the etiology of the disease, besides assisting diagnosis. The autoimmune hypothesis is also supported by the occurrence of glomerulonephritis in recent cases, with the presence of autoantibodies and its complexes in serum. The symptoms onset in cases of CNM is variable, and dog owners often fail to perceive the neurological signs of the disease, which are rather subtle in the beginning. With Chihuahuas, clinical service was sought after a period of time that varied from 5 days to 2.5 years. With pugs, clinical signs may appear from one to six months before death. Seizures are the most consistent clinical manifestations in CNM, and the neurological syndrome develops progressively. Other clinical signs include nystagmus, ataxia, head tilt, ipsilateral circling, incoordination, paralysis, changes in behavior and consciousness, depression and coma. Neurological examination may reveal changes / loss / decrease of sight, but in most cases the pupillary reflexes remain unalterared. Computerized tomography, magnetic resonance imaging and ultrasound examinations may provide evidence of tissue lesion, cystic areas, malacia and dilation of ventricles. Examination of CSF may indicate important changes such as increased protein, red blood cells or presence of occult blood and predominantly mononuclear pleocytosis. Definitive diagnosis, nevertheless, is still based on histopathological examinations done through brain biopsy or post-mortem. Alterations occur primarily in the cerebral hemispheres, but there may be morphological differences and varying location according to the dog's breed. Macroscopic alterations in CNM are relatively common, and were observed in most cases in São Paulo and Santa Maria, with lateral ventricular dilatation (4 / 6) (Figure 4), areas of change in color, and malacia in the cerebral cortex (5 / 6) (Figure 5). Kidney alterations may occur, such as proliferative membranous glomerulonephritis, characterized by a diffuse lesion in the cortical area, with thickening of Bowman's capsule, lymphoplasmacytic interstitial infiltrates and proteinaceous cylinders, as described in West Highland white terrier breeds 10 and pugs dogs. Prognosis for dogs affected by CNM is unfavorable. To present date, patients have received palliative care, with the use of steroidal anti-inflammatories such as prednisone, employed in immunosuppressive dosages, associated to anticonvulsants. This treatment may help extend the survival period, which has varied from less than 60 days to four months. Reports of combined treatment with prednisone and cyclosporine suggest greater efficacy in the treatment of clinical signs and increased survival periods, exceeding 300 days. Anticonvulsant drugs and steroid therapy usually show little eficacy. The study of neurological disorders in small animals has gained increased attention from veterinary practitioners in the past years. The information exchange among professionals (breeders, practitioners and pathologists) is of vital importance and will certainly prompt reporting of CNM cases. At present, the disease is probably under diagnosed in Brazil, since the definitive diagnosis still depends on histopathological examinations, usually post-mortem. The occurrence of seizures in affected animals is the symptom that usually leads them to the veterinary clinic. Thus, when CNM is considered for diagnosis, it is usually late. Practitioners are advised to inform the owners of predisposed breeds so that they are aware of the more subtle neurological symptoms of the disease, as listed in figures 1 and 2. They should also consider CNM as a possibility in differential diagnosesLa meningoencefalitis necrosante canina (MNC) es una enfermedad inflamatoria idiopática que afecta los hemisferios cerebrales de perros de razas pequeñas. Crisis convulsivas son la señal clínica más característica de un proceso progresivo que puede durar días o años. La etiología de este complejo no es conocida mas se cree que factores genéticos y ambientales puedan estar implicados. La terapia usada actualmente es paliativa y se usan corticosteroides inmunosupresores y anticonvulsivos. En esta revisión son descritos seis casos de MNC en Brasil, en las razas Pug (dos casos), Yorkshire (dos casos) y Maltés (dos casos). Tres casos fueron procedentes de la Faculdade de Medicina Veterinária e Zootecnia de la Universidade de São Paulo, SP, y tres del Laboratório de Patologia Veterinária de la Universidade Federal de Santa Maria, R

Severe enteritis in dogs associated with single and mixed infections

ABSTRACT: Infectious enteritis is highly prevalent among dogs worldwide and, in some cases, it can be fatal. This study describes the clinical and laboratorial findings of single and mixed infections associated with severe enteritis in 76 dogs from Southern Brazil. Intestinal segments and/or fecal samples were subjected to histopathology and molecular detection of DNA viruses, bacteria and protozoa. Severe intestinal lesions were observed in most cases. Single infections were detected in 52.6% of cases, double (36.8%) and triple (10.5%) infections were also identified. Carnivore protoparvovirus 2 (CPV-2) was the most frequent agent in single infections (36.8%). Coinfection by CPV-2 and Giardia spp. was the most common in dual infections (19.7%), followed by CPV-2 and Cryptosporidium spp. (10.5%). The most frequent triple infection was CPV-2, Giardia sp. and Cryptosporidium spp. (6.6%). Our results shown that single and mixed infections are associated with severe enteritis in dogs in southern Brazil, mainly involving CPV-2 and Giardia sp

Anasarca associated with restrictive cardiomyopathy in two cats

Background: Cardiomyopathies are a primary heart disorder and are one of the most causes of heart failure and sudden death in cats. Restrictive cardiomyopathy is a diastolic dysfunction resulting from endomyocardial fibrosis, with filling restriction and ventricular distention. In these cases, a poor outcome is expected. Anasarca in animals is often associated with dystocia secondary to congenital changes. In adults, this is a rare condition, since subcutaneous edema in animals with congestive heart failure is an uncommon finding. Therefore, this report describes clinical and pathological findings in an unusual presentation of anasarca in two adult cats with restrictive cardiomyopathy. Cases: A 12-year-old female mixed breed cat (case 1) and a 6-year-old male mixed-breed cat (case 2) were present on an emergent basis at the veterinary hospital with a history of respiratory distress. Case 1 showed on physical examination intense restrictive mixed dyspnea and lethargy, with muffled heart sounds and respiratory noises in cardiorespiratory auscultation. The cat exhibited abdominal distension resulting from ascites. Generalized subcutaneous edema was evident mainly in the abdominal and submandibular areas and the thoracic and pelvic limbs. In these regions, a positive Godet signal was observed. Thoracic radiography revealed pleural effusion, and the cat underwent fluid drainage on both sides of the thoracic cavity. Drainage material was sent to the laboratory for clinical analysis, which indicated that it was a modified transudate. The clinical signs worsened, and the cat was euthanized. In case 2, physical examination showed severe restrictive mixed dyspnea, lethargy, and low body temperature (&lt; 32°C). Abdominal distension resulting from ascites and generalized edema in the subcutaneous tissue with a positive Godet sign was observed. On cardiorespiratory auscultation, cardiac sounds and breathing noises were muffled. Thoracic radiography revealed pleural effusion. The cat was immediately placed in an incubator for clinical stabilization with oxygen therapy and warm-up. After 2 h of hospitalization, thoracentesis and drainage of cavity fluids were performed, which were classified as modified transudate. The patient remained in critical condition during hospitalization, evolving to death. The two cats were referred for a complete post mortem examination. Grossly, both cats showed distension of the abdomen and marked edema of subcutaneous tissue, mainly in the abdominal, ventral cervical, and thoracic and pelvic members. In the abdominal and thoracic cavities, a moderate amount of serous-free liquid, slightly reddish was observed. The heart of both cats was enlarged, with a globose appearance and a slightly whitish epicardium. The left ventricular endocardium was mild and diffusely thick and whitish, in addition to moderate dilation of the left atrium. Histological analyses of the heart showed in both cats moderate and diffuse proliferation of fibrous connective tissue in the endocardial region. Discussion: Restrictive cardiomyopathy has major importance in feline medicine due to its severity and poor outcome. Pleural effusion, pulmonary edema, and ascites are common findings in cats with congestive heart failure; however, generalized subcutaneous edema is uncommon. To the author’s knowledge, there are no published cases in the literature of anasarca in adult cats with restrictive cardiomyopathy. In human cardiology, this presentation is commonly related to congestive heart failure, and it is reported under several conditions, such as restrictive cardiomyopathy and constrictive pericarditis. The present study suggests that anasarca should be included in the list of associated clinical signs suggestive of severe congestive heart failure, mainly related to restrictive cardiomyopathy. Keywords: cardiomyopathy, endomyocardial fibrosis, feline, generalized edema.Background: Cardiomyopathies are a primary heart disorder and are one of the most causes of heart failure and sudden death in cats. Restrictive cardiomyopathy is a diastolic dysfunction resulting from endomyocardial fibrosis, with filling restriction and ventricular distention. In these cases, a poor outcome is expected. Anasarca in animals is often associated with dystocia secondary to congenital changes. In adults, this is a rare condition, since subcutaneous edema in animals with congestive heart failure is an uncommon finding. Therefore, this report describes clinical and pathological findings in an unusual presentation of anasarca in two adult cats with restrictive cardiomyopathy. Case: A 12-year-old female mixed breed cat (case 1) and a six-year-old male mixed-breed cat (case 2) were present on an emergent basis at the veterinary hospital with a history of respiratory distress. Case 1 showed on physical examination intense restrictive mixed dyspnea and lethargy, with muffled heart sounds and respiratory noises in cardiorespiratory auscultation. The cat exhibited abdominal distension resulting from ascites. Generalized subcutaneous edema was evident mainly in the abdominal and submandibular areas and the thoracic and pelvic limbs. In these regions, a positive Godet signal was observed. Thoracic radiography revealed pleural effusion, and the cat underwent fluid drainage on both sides of the thoracic cavity. Drainage material was sent to the laboratory for clinical analysis, which indicated that it was a modified transudate. The clinical signs worsened, and the cat was euthanized. In case 2, physical examination showed severe restrictive mixed dyspnea, lethargy, and low body temperature (&lt; 32°). Abdominal distension resulting from ascites and generalized edema in the subcutaneous tissue with a positive Godet sign was observed. On cardiorespiratory auscultation, cardiac sounds and breathing noises were muffled. Thoracic radiography revealed pleural effusion. The cat was immediately placed in an incubator for clinical stabilization with oxygen therapy and warm-up. After 2 h of hospitalization, thoracentesis and drainage of cavity fluids were performed, which were classified as modified transudate. The patient remained in critical condition during hospitalization, evolving to death. The two cats were referred for a complete post-mortem examination. Grossly, both cats showed distension of the abdomen and marked edema of subcutaneous tissue, mainly in the abdominal, ventral cervical, and thoracic and pelvic members. In the abdominal and thoracic cavities, a moderate amount of serous-free liquid, slightly reddish was observed. The heart of both cats was enlarged, with a globose appearance and a slightly whitish epicardium. The left ventricular endocardium was mild and diffusely thick and whitish, in addition to moderate dilation of the left atrium. Histological analyses of the heart showed in both cats moderate and diffuse proliferation of fibrous connective tissue in the endocardial region. Discussion: Restrictive cardiomyopathy has major importance in feline medicine due to its severity and poor outcome. Pleural effusion, pulmonary edema, and ascites are common findings in cats with congestive heart failure; however, generalized subcutaneous edema is uncommon. To the author’s knowledge, there are no published cases in the literature of anasarca in adult cats with restrictive cardiomyopathy. In human cardiology, this presentation is commonly related to congestive heart failure, and it is reported under several conditions, such as restrictive cardiomyopathy and constrictive pericarditis. The present study suggests that anasarca should be included in the list of associated clinical signs suggestive of severe congestive heart failure, mainly related to restrictive cardiomyopathy. &nbsp; Keywords: cardiomyopathy, endomyocardial fibrosis, feline, generalized edema

Anasarca associated with restrictive cardiomyopathy in two cats

Background: Cardiomyopathies are a primary heart disorder and are one of the most causes of heart failure and sudden death in cats. Restrictive cardiomyopathy is a diastolic dysfunction resulting from endomyocardial fibrosis, with filling restriction and ventricular distention. In these cases, a poor outcome is expected. Anasarca in animals is often associated with dystocia secondary to congenital changes. In adults, this is a rare condition, since subcutaneous edema in animals with congestive heart failure is an uncommon finding. Therefore, this report describes clinical and pathological findings in an unusual presentation of anasarca in two adult cats with restrictive cardiomyopathy. Cases: A 12-year-old female mixed breed cat (case 1) and a 6-year-old male mixed-breed cat (case 2) were present on an emergent basis at the veterinary hospital with a history of respiratory distress. Case 1 showed on physical examination intense restrictive mixed dyspnea and lethargy, with muffled heart sounds and respiratory noises in cardiorespiratory auscultation. The cat exhibited abdominal distension resulting from ascites. Generalized subcutaneous edema was evident mainly in the abdominal and submandibular areas and the thoracic and pelvic limbs. In these regions, a positive Godet signal was observed. Thoracic radiography revealed pleural effusion, and the cat underwent fluid drainage on both sides of the thoracic cavity. Drainage material was sent to the laboratory for clinical analysis, which indicated that it was a modified transudate. The clinical signs worsened, and the cat was euthanized. In case 2, physical examination showed severe restrictive mixed dyspnea, lethargy, and low body temperature (&lt; 32°C). Abdominal distension resulting from ascites and generalized edema in the subcutaneous tissue with a positive Godet sign was observed. On cardiorespiratory auscultation, cardiac sounds and breathing noises were muffled. Thoracic radiography revealed pleural effusion. The cat was immediately placed in an incubator for clinical stabilization with oxygen therapy and warm-up. After 2 h of hospitalization, thoracentesis and drainage of cavity fluids were performed, which were classified as modified transudate. The patient remained in critical condition during hospitalization, evolving to death. The two cats were referred for a complete post mortem examination. Grossly, both cats showed distension of the abdomen and marked edema of subcutaneous tissue, mainly in the abdominal, ventral cervical, and thoracic and pelvic members. In the abdominal and thoracic cavities, a moderate amount of serous-free liquid, slightly reddish was observed. The heart of both cats was enlarged, with a globose appearance and a slightly whitish epicardium. The left ventricular endocardium was mild and diffusely thick and whitish, in addition to moderate dilation of the left atrium. Histological analyses of the heart showed in both cats moderate and diffuse proliferation of fibrous connective tissue in the endocardial region. Discussion: Restrictive cardiomyopathy has major importance in feline medicine due to its severity and poor outcome. Pleural effusion, pulmonary edema, and ascites are common findings in cats with congestive heart failure; however, generalized subcutaneous edema is uncommon. To the author’s knowledge, there are no published cases in the literature of anasarca in adult cats with restrictive cardiomyopathy. In human cardiology, this presentation is commonly related to congestive heart failure, and it is reported under several conditions, such as restrictive cardiomyopathy and constrictive pericarditis. The present study suggests that anasarca should be included in the list of associated clinical signs suggestive of severe congestive heart failure, mainly related to restrictive cardiomyopathy. Keywords: cardiomyopathy, endomyocardial fibrosis, feline, generalized edema.Background: Cardiomyopathies are a primary heart disorder and are one of the most causes of heart failure and sudden death in cats. Restrictive cardiomyopathy is a diastolic dysfunction resulting from endomyocardial fibrosis, with filling restriction and ventricular distention. In these cases, a poor outcome is expected. Anasarca in animals is often associated with dystocia secondary to congenital changes. In adults, this is a rare condition, since subcutaneous edema in animals with congestive heart failure is an uncommon finding. Therefore, this report describes clinical and pathological findings in an unusual presentation of anasarca in two adult cats with restrictive cardiomyopathy. Case: A 12-year-old female mixed breed cat (case 1) and a six-year-old male mixed-breed cat (case 2) were present on an emergent basis at the veterinary hospital with a history of respiratory distress. Case 1 showed on physical examination intense restrictive mixed dyspnea and lethargy, with muffled heart sounds and respiratory noises in cardiorespiratory auscultation. The cat exhibited abdominal distension resulting from ascites. Generalized subcutaneous edema was evident mainly in the abdominal and submandibular areas and the thoracic and pelvic limbs. In these regions, a positive Godet signal was observed. Thoracic radiography revealed pleural effusion, and the cat underwent fluid drainage on both sides of the thoracic cavity. Drainage material was sent to the laboratory for clinical analysis, which indicated that it was a modified transudate. The clinical signs worsened, and the cat was euthanized. In case 2, physical examination showed severe restrictive mixed dyspnea, lethargy, and low body temperature (&lt; 32°). Abdominal distension resulting from ascites and generalized edema in the subcutaneous tissue with a positive Godet sign was observed. On cardiorespiratory auscultation, cardiac sounds and breathing noises were muffled. Thoracic radiography revealed pleural effusion. The cat was immediately placed in an incubator for clinical stabilization with oxygen therapy and warm-up. After 2 h of hospitalization, thoracentesis and drainage of cavity fluids were performed, which were classified as modified transudate. The patient remained in critical condition during hospitalization, evolving to death. The two cats were referred for a complete post-mortem examination. Grossly, both cats showed distension of the abdomen and marked edema of subcutaneous tissue, mainly in the abdominal, ventral cervical, and thoracic and pelvic members. In the abdominal and thoracic cavities, a moderate amount of serous-free liquid, slightly reddish was observed. The heart of both cats was enlarged, with a globose appearance and a slightly whitish epicardium. The left ventricular endocardium was mild and diffusely thick and whitish, in addition to moderate dilation of the left atrium. Histological analyses of the heart showed in both cats moderate and diffuse proliferation of fibrous connective tissue in the endocardial region. Discussion: Restrictive cardiomyopathy has major importance in feline medicine due to its severity and poor outcome. Pleural effusion, pulmonary edema, and ascites are common findings in cats with congestive heart failure; however, generalized subcutaneous edema is uncommon. To the author’s knowledge, there are no published cases in the literature of anasarca in adult cats with restrictive cardiomyopathy. In human cardiology, this presentation is commonly related to congestive heart failure, and it is reported under several conditions, such as restrictive cardiomyopathy and constrictive pericarditis. The present study suggests that anasarca should be included in the list of associated clinical signs suggestive of severe congestive heart failure, mainly related to restrictive cardiomyopathy. &nbsp; Keywords: cardiomyopathy, endomyocardial fibrosis, feline, generalized edema

Carcinossarcoma tireoidiano em um cão Thyroid carcinosarcoma in a dog

Uma cadela de dois anos de idade, sem raça definida, apresentou disfagia e aumento de volume da região cervical ventral, correspondendo à região tireoidiana. Duas massas localizadas nessa região foram removidas cirurgicamente. O cão morreu poucos dias após a cirurgia e não foi necropsiado. O diagnóstico de carcinossarcoma de tireóide baseou-se na presença de componentes neoplásicos epiteliais e mesenquimais malignos, os quais foram confirmados pela reação imunoistoquímica positiva para citoqueratina e vimentina, respectivamente. A origem tireoidiana foi confirmada pela imunomarcação positiva para tireoglobulina nas células epiteliais foliculares e no colóide. Este é um neoplasma raramente diagnosticado em cães.<br>A two year-old female mongrel dog was presented with dysphagia and focal swelling at the thyroid region. Two masses were surgically removed from that site. The dog died a few days after surgery and it was not submitted to necropsy. The diagnosis of thyroid carcinosarcoma was based on malignant epithelial and mesenchymal cell components of the neoplasm and confirmed by immunohistochemistry for cytokeratin and vimentin, respectively. The thyroid origin was confirmed based on the positive immunostaining for thyroglobulin on the follicular epithelial cells and colloid. This is a neoplasm rarely diagnosed in dogs

Remyelination in experimentally demyelinated connexin 32 KnockOut mice Remielinização em camundongos KnockOut para conexina 32 desmielinizados experimentalmente

The aim of this study was to evaluate the role of connexin 32 (Cx 32) during remyelination of the peripheral nervous system, through a local injection of either 0,1% ethidium bromide solution or saline in the sciatic nerve of Cx 32 knockout mice. Euthanasia was performed ranging from 1, 2, 3, 7, 15, 21 to 30 days after injection. Histochemical, immunohistochemical, immunofluorescence and transmission electron microscopical techniques were used to analyze the development of the lesions. Within the sciatic nerves, Schwann cells initially showed signs of intoxication and rejected their sheaths; after seven days, some thin newly formed myelin sheaths with uneven compactness and redundant loops (tomacula) were conspicuous. We concluded that the regeneration of lost myelin sheaths within the PNS followed the pattern already reported for this model in other laboratory species. Therefore, these results suggest that absence of Cx 32 did not interfere with the normal pattern of remyelination in this model in young mice.<br>Este estudo visou avaliar o papel da conexina 32 (Cx 32) durante a remielinização no sistema nervoso periférico. Uma injeção local de 0,1% de solução de brometo de etídio foi realizada no nervo ciático de camundongos deletados para a Cx 32, com eutanásia dos animais aos 1, 2, 3, 7, 15, 21 e 30 dias pós-injeção. Avaliações histoquímicas, imunoistoquímicas, por imunofluorescência e por microscopia eletrônica de transmissão foram utilizadas na análise do desenvolvimento das lesões. Nos nervos ciáticos, células de Schwann mostraram inicialmente sinais de intoxicação e rejeitaram suas bainhas. Após sete dias, observaram-se finas bainhas neoformadas, com compactação desigual e alças redundantes (tomácula). Conclui-se que a regeneração de bainhas de mielina perdidas no SNP seguiu o padrão já relatado deste modelo em outras espécies de laboratório. Portanto, estes resultados sugerem que a ausência da Cx 32 não interferiu com o padrão normal de remielinização em camundongos jovens neste modelo

Safety and efficacy of rozanolixizumab in patients with generalised myasthenia gravis (MycarinG): a randomised, double-blind, placebo-controlled, adaptive phase 3 study

Background: Generalised myasthenia gravis is a chronic, unpredictable, and debilitating autoimmune disease. New treatments for this disease are needed because conventional therapies have limitations, such as side-effects (eg, increased infection risk) or inadequate control of symptoms. Rozanolixizumab is a neonatal Fc receptor blocker that might provide a novel therapeutic option for myasthenia gravis. We aimed to assess the safety and efficacy of rozanolixizumab for generalised myasthenia gravis. Methods: MycarinG is a randomised, double-blind, placebo-controlled, adaptive phase 3 study done at 81 outpatient centres and hospitals in Asia, Europe, and North America. We enrolled patients (aged ≥18 years) with acetylcholine receptor (AChR) or muscle-specific kinase (MuSK) autoantibody-positive generalised myasthenia gravis (Myasthenia Gravis Foundation of America class II-IVa), a Myasthenia Gravis Activities of Daily Living (MG-ADL) score of at least 3 (non-ocular symptoms), and a quantitative myasthenia gravis score of at least 11. Patients were randomly assigned (1:1:1) to receive subcutaneous infusions once a week for 6 weeks of either rozanolixizumab 7 mg/kg, rozanolixizumab 10 mg/kg, or placebo. Randomisation was stratified by AChR and MuSK autoantibody status. Investigators, patients, and people assessing outcomes were masked to random assignments. The primary efficacy endpoint was change from baseline to day 43 in MG-ADL score, assessed in the intention-to-treat population. Treatment-emergent adverse events (TEAEs) were assessed in all randomly assigned patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov (NCT03971422) and EudraCT (2019-000968-18); an open-label extension study has been completed (NCT04124965; EudraCT 2019-000969-21) and another is underway (NCT04650854; EudraCT 2020-003230-20). Findings: Between June 3, 2019, and June 30, 2021, 300 patients were assessed for eligibility, of whom 200 were enrolled. 66 (33%) were randomly assigned to rozanolixizumab 7 mg/kg, 67 (34%) to rozanolixizumab 10 mg/kg, and 67 (34%) to placebo. Reductions in MG-ADL score from baseline to day 43 were greater in the rozanolixizumab 7 mg/kg group (least-squares mean change -3·37 [SE 0·49]) and in the rozanolixizumab 10 mg/kg group (-3·40 [0·49]) than with placebo (-0·78 [0·49]; for 7 mg/kg, least-squares mean difference -2·59 [95% CI -4·09 to -1·25], p&lt;0·0001; for 10 mg/kg, -2·62 [-3·99 to -1·16], p&lt;0·0001). TEAEs were experienced by 52 (81%) of 64 patients treated with rozanolixizumab 7 mg/kg, 57 (83%) of 69 treated with rozanolixizumab 10 mg/kg, and 45 (67%) of 67 treated with placebo. The most frequent TEAEs were headache (29 [45%] patients in the rozanolixizumab 7 mg/kg group, 26 [38%] in the rozanolixizumab 10 mg/kg group, and 13 [19%] in the placebo group), diarrhoea (16 [25%], 11 [16%], and nine [13%]), and pyrexia (eight [13%], 14 [20%], and one [1%]). Five (8%) patients in the rozanolixizumab 7 mg/kg group, seven (10%) in the rozanolixizumab 10 mg/kg group, and six (9%) in the placebo group had a serious TEAE. No deaths occurred. Interpretation: Rozanolixizumab showed clinically meaningful improvements in patient-reported and investigator-assessed outcomes in patients with generalised myasthenia gravis, for both 7 mg/kg and 10 mg/kg doses. Both doses were generally well tolerated. These findings support the mechanism of action of neonatal Fc receptor inhibition in generalised myasthenia gravis. Rozanolixizumab represents a potential additional treatment option for patients with generalised myasthenia gravis. Funding: UCB Pharma