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Two male Japanese Black calves developed an enlarged scrotum and testis. Orchiectomy was performed and pus was collected during surgery. After removal of the testis, bacteriological and histopathological examinations were conducted to investigate the cause and confirm the diagnosis. Based on the results obtained, both cases were diagnosed with epididymitis caused by an infection with Pasteurella multocida. This is the first study to show that P. multocida causes epididymitis in male calves. Further studies are required to clarify the details underlying the infection of calves with P. multocida.
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Enfermedades de los Bovinos , Epididimitis , Pasteurella multocida , Bovinos , Animales , Masculino , Epididimitis/veterinaria , TestículoRESUMEN
Rabies is a type of acute fetal encephalitis caused by rabies virus (RABV). While it becomes incurable after symptom onset, it can be prevented by post-exposure prophylaxis (PEP) during the long incubation period. While preclinical diagnosis aids the appropriate PEP administration, it is mostly nonfeasible owing to the absence of viremia or a specific antibody response during the incubation period. Here, an attempt was made to identify a serum biomarker for the preclinical diagnosis of rabies. Using the serum from a mouse inoculated intramuscularly (i.m.) with 5 × 105 focus-forming units (FFU) of recombinant RABV expressing red firefly luciferase (1088/RFLuc) immediately before symptom onset, two-dimensional differential gel electrophoresis was conducted, followed by mass spectrometry, and it was confirmed that apolipoprotein A1 (ApoA1) was up-regulated. ELISA showed that the serum ApoA1 and specific antibody levels increased during the incubation period and on the day of symptom onset. Since a lower infectious dose can be used to induce the unstable and long incubation period generally observed in natural infection, the ApoA1 level in mice inoculated i.m. with 103 FFU of 1088/RFLuc was examined by monitoring viral dynamics using in vivo imaging. The serum ApoA1 and specific antibody levels were up-regulated in 50% and 58.3% of mice exhibiting robust RABV replication, respectively, but not in mice exhibiting weak RABV replication. In addition, it was reported that ApoA1 was found to be a biomarker for neuronal damage. Additional biomarker candidates will be needed for the effective preclinical diagnosis of rabies.
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Virus de la Rabia , Rabia , Animales , Anticuerpos Antivirales , Apolipoproteína A-I , Biomarcadores , Ratones , Rabia/diagnósticoRESUMEN
A 7-month-old castrated French bulldog was presented with a left-sided mandibular tumor. The initial tumor biopsy diagnosis was ameloblastoma. The owner brought this dog the Kitasato University Veterinary Teaching Hospital for more detailed examination and treatment. Computed tomography revealed a tumor on the left lateral mandibular gingiva from the caudal third of the incisor tooth to the right canine tooth, associated with severe amorphous osteolysis of the mandibular bone. The tumor was surgically excised and diagnosed as papillary squamous cell carcinoma. Currently, 2514 d (6.9 y) since the operation, the dog is healthy, without recurrence. Key clinical message: Although papillary squamous cell carcinoma is rare, many cases have been reported in the oral cavity of medium-to large-sized dogs. Based on this report, papillary squamous cell carcinoma can occur in small dogs such as young French bulldogs and a good prognosis can be achieved with proper resection.
Un cas de carcinome épidermoïde papillaire de la mandibule d'un jeune bouledogue français. Un bouledogue français castré de 7 mois a été présenté avec une tumeur mandibulaire gauche. Le diagnostic initial de biopsie tumorale était un améloblastome. Le propriétaire a amené ce chien à l'hôpital universitaire vétérinaire de Kitasato pour un examen et un traitement plus détaillés. La tomodensitométrie a révélé une tumeur de la gencive mandibulaire latérale gauche du tiers caudal de l'incisive à la canine droite, associée à une ostéolyse amorphe sévère de l'os mandibulaire. La tumeur a été excisée chirurgicalement et diagnostiquée comme un carcinome épidermoïde papillaire. Actuellement, 2514 jours (6,9 ans) depuis l'opération, le chien est en bonne santé, sans récidive.Message clinique clé :Bien que le carcinome épidermoïde papillaire soit rare, de nombreux cas ont été rapportés dans la cavité buccale de chiens de taille moyenne à grande. Sur la base de ce rapport, le carcinome épidermoïde papillaire peut survenir chez les petits chiens tels que les jeunes bouledogues français et un bon pronostic peut être obtenu avec une résection appropriée.(Traduit par Dr Serge Messier).
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Carcinoma de Células Escamosas , Enfermedades de los Perros , Animales , Carcinoma de Células Escamosas/cirugía , Carcinoma de Células Escamosas/veterinaria , Enfermedades de los Perros/diagnóstico por imagen , Enfermedades de los Perros/cirugía , Perros , Hospitales Veterinarios , Hospitales de Enseñanza , Mandíbula , Tomografía Computarizada por Rayos X/veterinariaRESUMEN
BACKGROUND: Infrared radiation (IR) exposure generates reactive oxygen species and induces matrix metalloproteinase-1 expression in human skin. Moreover, while not as acute as ultraviolet radiation, repeated infrared irradiation can result in the photoaging of skin. Broad-spectrum sunscreens can protect skin from IR, but no human in vivo test methods for the evaluation of sunscreens' IR protection effect have been developed. We aimed to develop such a method. MATERIALS AND METHODS: We included 155 Korean subjects in our three-part clinical study. The IR reflectance of subjects' skin was measured using a benchtop model of an IR light source and a reflectance measuring probe. We measured the IR reflectance in relation to skin color and hydration level to set up our experimental conditions. We then calculated the infrared protection factors (IPFs) of cosmetic emulsions as the IR reflectance ratio between cosmetic sunscreen-applied skin and non-sunscreen-applied skin and assessed the relationship between IPFs and the amount of sunscreen ingredients. Finally, this method was validated using several commercial sunscreen cosmetics. RESULTS: Skin color and hydration level did not influence the IR reflectance of subjects' skin. The IPFs of cosmetic sunscreens showed a positive correlation with the amount of inorganic sunscreen ingredients. CONCLUSION: In this study, we developed a simple, fast, and ethically acceptable human in vivo test method for evaluating the IPFs of cosmetic sunscreens.
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Cosméticos/farmacología , Pigmentación de la Piel , Piel , Protectores Solares/farmacología , Adulto , Agua Corporal/metabolismo , Cosméticos/química , Femenino , Humanos , Rayos Infrarrojos , Persona de Mediana Edad , Piel/efectos de los fármacos , Piel/metabolismo , Piel/efectos de la radiación , Pigmentación de la Piel/efectos de los fármacos , Pigmentación de la Piel/efectos de la radiación , Protectores Solares/química , Adulto JovenRESUMEN
During rabies virus infections, the minor salivary glands are one of the important organs for virus replication and excretion into the oral cavity. However, details of pathological findings and viral antigen distribution in the minor salivary glands remain poorly understood. In this study, we conducted pathological tests on the tongues of 71 rabid dogs in the Philippines; the minor salivary glands (von Ebner's glands, lingual glands), circumvallate papilla, autonomic ganglia, and skeletal muscles were evaluated. Inflammatory changes were observed in the von Ebner's glands of 20/71 dogs, in the circumvallate papilla of 10/71, and in the tongue muscle of 1/71. Conversely, no morphological changes were observed in the lingual glands and autonomic ganglia. Viral antigens were detected via immunohistochemistry-based methods in the cytoplasm of the acinar epithelium in the von Ebner's glands of all 71 dogs. Virus particles were confirmed in the intercellular canaliculi and acinar lumen via electron microscopy. In the autonomic ganglia, viral antigens were detected in 67/71 rabid dogs. Viral antigens were detected in the taste buds of all 71 dogs, and were distributed mainly in type II and III taste bud cells. In tongue muscle fibers, viral antigens were detected in 11/71 dogs. No virus antigens were detected in lingual glands. These findings suggest that rabies virus descends in the tongue along the glossopharyngeal nerve after proliferation in the brain, and von Ebner's glands and taste buds are one of the portals of virus excretion into the saliva in rabid dogs.
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Ganglios Autónomos/patología , Virus de la Rabia/patogenicidad , Glándulas Salivales Menores/patología , Papilas Gustativas/patología , Lengua/patología , Virión/patogenicidad , Animales , Antígenos Virales/genética , Antígenos Virales/inmunología , Perros , Femenino , Ganglios Autónomos/ultraestructura , Ganglios Autónomos/virología , Inmunohistoquímica , Masculino , Músculo Esquelético/patología , Músculo Esquelético/ultraestructura , Músculo Esquelético/virología , Filipinas , Rabia/patología , Rabia/virología , Virus de la Rabia/fisiología , Virus de la Rabia/ultraestructura , Saliva/virología , Glándulas Salivales Menores/ultraestructura , Glándulas Salivales Menores/virología , Papilas Gustativas/ultraestructura , Papilas Gustativas/virología , Lengua/ultraestructura , Lengua/virología , Virión/fisiología , Virión/ultraestructura , Esparcimiento de Virus/fisiologíaRESUMEN
H9N2 avian influenza virus causes sporadic human infection. Since humans do not possess acquired immunity specific to this virus, we examined the pathogenicity of an H9N2 virus isolated from a human and then analyzed protective effects of a vaccine in cynomolgus macaques. After intranasal challenge with A/Hong Kong/1073/1999 (H9N2) (HK1073) isolated from a human patient, viruses were isolated from nasal and tracheal swabs in unvaccinated macaques with mild fever and body weight loss. A formalin-inactivated H9N2 whole particle vaccine derived from our virus library was subcutaneously inoculated to macaques. Vaccination induced viral antigen-specific IgG and neutralization activity in sera. After intranasal challenge with H9N2, the virus was detected only the day after inoculation in the vaccinated macaques. Without vaccination, many bronchus-associated lymphoid tissues (BALTs) were formed in the lungs after infection, whereas the numbers of BALTs were smaller and the cytokine responses were weaker in the vaccinated macaques than those in the unvaccinated macaques. These findings indicate that the H9N2 avian influenza virus HK1073 is pathogenic in primates but seems to cause milder symptoms than does H7N9 influenza virus as found in our previous studies and that a formalin-inactivated H9N2 whole particle vaccine induces protective immunity against H9N2 virus.
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Subtipo H9N2 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/inmunología , Infecciones por Orthomyxoviridae/inmunología , Infecciones por Orthomyxoviridae/patología , Animales , Anticuerpos Antivirales/sangre , Bronquios/patología , Tejido Linfoide/patología , Macaca fascicularis , Infecciones por Orthomyxoviridae/virología , Vacunación , Vacunas de Productos Inactivados/inmunologíaRESUMEN
Inactivation of the NF-κB signaling pathway by inhibition of IKKß is a well-known approach to treat inflammatory diseases such as rheumatoid arthritis and cancer. Thienopyrimidine-based analogues were designed through modification of the known IKKß inhibitor, SPC-839, and then biologically evaluated. The resulting analogues had good inhibitory activity against both nitric oxide and TNF-α, which are well-known inflammatory responses generated by activated NF-κB. However, no inhibitory activity against IKKß was observed with these compounds. The thienopyrimidine-based analogues were subsequently screened for a target kinase, and FLT3, which is a potential target for acute myeloid leukemia (AML), was identified. Thienopyrimidine-based FLT3 inhibitors showed good inhibition profiles against FLT3 under 1µM. Overall, these compounds represent a promising family of inhibitors for future development of a treatment for AML.
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Quinasa I-kappa B/antagonistas & inhibidores , Pirimidinas/síntesis química , Bibliotecas de Moléculas Pequeñas/química , Tirosina Quinasa 3 Similar a fms/antagonistas & inhibidores , Activación Enzimática/efectos de los fármacos , Humanos , Quinasa I-kappa B/química , Maleimidas/química , Estructura Molecular , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/farmacología , Pirimidinas/química , Pirimidinas/farmacología , Quinazolinas/química , Bibliotecas de Moléculas Pequeñas/síntesis química , Bibliotecas de Moléculas Pequeñas/farmacologíaRESUMEN
Primary cardiac tumors in animals are very rare. The purpose of this report was to describe the first case of a cardiac tumor comprising a malignant peripheral nerve sheath tumor and spontaneous atrial osseous metaplasia in a Corriedale sheep. Histologically, the tumor in the bilateral atrial pericardium consisted of dense cellular components comprising tumor cells and a sparse cellular area, and non-neoplastic mature bone tissue. The tumor cells were spindle-shaped, round, or polygonal, and proliferating, with fascicular, storiform, palisading, and sheet patterns. Immunohistochemically, the tumor cells were positive for vimentin, S-100, occasionally positive for myeline basic protein, glial fibrillary acidic protein, neurofilament, neuron specific enolase, and neuron growth factor receptor suggesting that they originated from the nervous system. On the basis of these findings, the final diagnosis was a malignant peripheral nerve sheath tumor and spontaneous atrial osseous metaplasia.
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Neoplasias Cardíacas , Neoplasias de la Vaina del Nervio , Neurofibrosarcoma , Enfermedades de las Ovejas , Animales , Ovinos , Neurofibrosarcoma/veterinaria , Neoplasias de la Vaina del Nervio/veterinaria , Inmunohistoquímica , Proteínas S100 , Neoplasias Cardíacas/veterinariaRESUMEN
Nasal granuloma in cattle results from inflammation within, and attendant proliferation of, the nasal mucosa possibly in response to an allergic response. However, the relationship between nasal granuloma and allergies remains unclear. Furthermore, severe cases have a poor prognosis because there is currently no effective treatment. Herein, we report three cases of nasal granuloma with severe stertorous breathing that were treated surgically. We also conducted an allergological exploration. Following surgical removal clinical signs did not recur in two of the three cases; however, stertorous breathing persisted in one case, and the cow was sacrificed 4 months later. A histopathological examination revealed that all nasal granulomas featured varying infiltrations of macrophages eosinophils, mast cells, and lymphocytes. The number of mast cells and the proportion of these cells that had degranulated were significantly higher in the granulomas than in normal nasal mucosae. In addition, serum histamine levels were higher in nasal granuloma cases than in normal cows, although serum immunoglobulin E levels were similar, and lymphocyte infiltration in the submucosal layer suggested type I and type IV allergies. Collectively, the results indicate the efficacy of complete surgical curettage for the treatment of allergic nasal granuloma in cattle. Further studies are required to identify the causes and risk factors of allergic nasal granuloma in cows.
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Enfermedades de los Bovinos , Granuloma , Animales , Bovinos , Femenino , Enfermedades de los Bovinos/cirugía , Enfermedades de los Bovinos/patología , Granuloma/veterinaria , Granuloma/cirugía , Granuloma/patología , Enfermedades Nasales/veterinaria , Enfermedades Nasales/cirugía , Enfermedades Nasales/patología , Inmunoglobulina E/sangre , Mucosa Nasal/cirugía , Mucosa Nasal/patologíaRESUMEN
Background: The enhanced recovery after surgery (ERAS) protocols have been consistently associated with improved patient experience and surgical outcomes. Despite the release of ERAS Society guidelines specific to gynecologic oncology, the adoption of ERAS in gynecology on global level has been disappointingly low and some centers have shown minimal improvement in clinical outcomes after adopting ERAS. The aim of this study is to describe the development and early experience of ERAS protocols in gynecologic surgery at an urban academic tertiary medical center. Methods: This was an observational prospective cohort study. The target patient population included those with low comorbidities who were scheduled to undergo various types of gynecologic surgeries for both benign and malignant diseases between October 2020 and February 2021. Two attending surgeons implemented the protocols for their patients (ERAS cohort) while three attending surgeons maintained the conventional perioperative care for their patients (non-ERAS cohort). Baseline characteristics, surgical outcomes and patients' answers to a 12-question survey were compared. A case-matched comparative analysis was also performed between the ERAS cohort and the historical non-ERAS cohort (those who received the same types of surgical procedures from the two ERAS attending surgeons prior to the implementation of the protocols). Results: A total of 244 patients were evaluated (122 in the ERAS cohort vs. 122 in the non-ERAS cohort). The number of vials of opioid analgesia used during the first two postoperative days was significantly lower whereas the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen was more frequent in the ERAS cohort group. The patients in the ERAS group reported less postoperative pain, feelings of hunger and thirst, and greater amount of exercise postoperatively. These benefits of the ERAS cohort were more pronounced in the patients who underwent laparotomic surgeries than those who underwent laparoscopic surgeries. The case-matched comparative analysis also showed similar results. The length of hospital stay did not differ between those who underwent the ERAS protocols and those who did not. Conclusions: The results of the study demonstrated the safety, clinical feasibility and benefits of the ERAS protocols for patients undergoing gynecologic surgeries for both benign and malignant indications.
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Immunization of egg-laying hens with viral antigens efficiently produces large amounts of virus-specific IgY antibodies from egg yolks. A supply of practical and economical antibodies against the rabies virus is being desired worldwide. We immunized hens with the antigen gene DNA of the rabies virus, purified specific IgY antibodies from the egg yolk, and characterized the immuno-protein chemistry for use as a diagnosis. To prepare specific IgY antibodies against rabies virus nucleoprotein (RV-N) by DNA immunization, laying hens were pre-injected with λ-carrageenan or Freund's complete adjuvant to increase local immune activity (pre-immune stimulation), and then immunized with RV-N recombinant plasmid DNA. RV-N-specific IgY antibodies were prepared from egg yolks of immunized hens. For comparison, conventional protein antigen immunization was also used to induce the production of RV-N-specific IgY antibodies. Laying hens were immunized with an RV-N protein antigen and RV-N-specific IgY was purified from egg yolks. The binding activity against RV-N antigens was examined using IgY samples prepared by DNA (with pre-immune stimulation) and protein immunization. Immunohistochemical staining showed that IgY antibodies prepared by protein immunization strongly detected viral antigens in the brain sections of dogs infected with the virus, whereas IgY antibodies prepared by DNA immunization did not. Enzyme-linked immunosorbent assay was performed using a commercially available rabies vaccine (inactivated virus) treated with 10% formalin and heating (60°C, 30 min and 90°C, 5 min). IgY prepared by DNA immunization had weaker reactivity with denatured antigens and lower antigen concentrations than IgY prepared by protein immunization. These results suggest that it is necessary to develop a DNA immunization method for inducing IgY antibodies against the rabies virus that strongly bind to native and denatured antigens to prepare specific IgYs that can be used for antigen detection in clinical tests.
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A 2-day-old male black calf presented with neurological symptoms, including opisthotonus. It was unable to stand due to hindquarter paresis. At 5 days old, the calf was able to stand, but exhibited a crossed forelimb gait. Computed tomography and magnetic resonance imaging revealed the expansion of the sutures between the squamous-lateral part of the occipital bone and between the occipital-temporal bone, cerebellar tonsillar herniation, posterior displacement of the brainstem, and cervical syringomyelia at 12 days old. This is the first case report of a live calf diagnosed with Arnold Chiari malformation classified as Chiari type 1.5 malformation in humans.
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Malformación de Arnold-Chiari , Enfermedades de los Bovinos , Animales , Bovinos , Humanos , Masculino , Malformación de Arnold-Chiari/diagnóstico por imagen , Malformación de Arnold-Chiari/veterinaria , Enfermedades de los Bovinos/diagnóstico por imagen , Imagen por Resonancia Magnética/veterinaria , Siringomielia/diagnóstico por imagen , Siringomielia/veterinaria , Hueso Temporal , Tomografía Computarizada por Rayos X/veterinariaRESUMEN
The study aimed to evaluate pork loin quality after short-term (ten-day) storage in a supercooling refrigerator. Pork loin samples were stored for 10 days in a traditional refrigerator (control) and a commercially available supercooling refrigerator (SC). Pork quality measurements included meat pH, meat color, water holding capacity (drip loss and cooking loss), tenderness (hardness), and a sensory evaluation. Temperature changes of 0.45 ± 0.2°C and 0.02 ± 0.25°C occurred in the control and the SC, respectively, during 10 days of storage. The temperature in the SC chamber did not remain below freezing point, failing to meet expectations. Regarding the pork quality measurements, only the drip losses in the control and the SC were significantly different (4.45% vs. 2.59%, p < 0.01) after 10 days of storage. There were no significant differences between the two types of refrigerator in terms of the other measurements. Additionally, the overall acceptability of the pork loin did not vary significantly between the control and the SC when the sensory evaluation was performed. Therefore, a commercial SC could prove beneficial in terms of water holding capacity during the short-term storage of meat. Further research should be performed to evaluate quality changes that occur during long-term storage of meat in SC s and evaluate a wide range of meat, such as beef and chicken.
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The aim of this study was to compare the histochemical and meat quality characteristics between the normal and white-striping (WS) pectoralis major muscles. Additionally, this study investigated the effects of oven cooking (OV) and sous-vide (SV) cooking methods on objective texture parameters and sensory quality characteristics of the normal and WS chicken breast meats. Results showed that the WS condition broilers had higher body and breast weights (P < 0.001), and a greater area of muscle fiber than the normal broilers (P < 0.001). The WS fresh fillets exhibited a lower preference of visual appearance compared to the normal fillets (P < 0.05), although no differences were detected in the characteristics of meat quality between the groups (P > 0.05). After cooking, there was greater cooking loss, Warner-Bratzler shear force, and texture parameter analysis-hardness values for breast fillets cooked by OV treatment at 180°C for reached core temperature to 71°C compared to the fillets cooked by SV treatment at 60°C for 2 h (P < 0.05), whereas the normal and WS groups were exhibited similar values within each cooking methods (P > 0.05). Regarding sensory quality characteristics, WS breast fillets cooked by SV (SV+WS) were rated as tenderer and juicier, and given a higher overall acceptability score compared to normal and WS fillets cooked by OV (P < 0.05). However, owing to a lesser developed flavor in SV+WS fillets, the panelists assigned a lower overall acceptability rating in these fillets compared to SV+Normal fillets (P < 0.05). Overall, the SV cooking can be an effective method for improving the sensory quality characteristics of WS and normal chicken breast.
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Pollos , Carne , Animales , Culinaria , Carne/análisis , Fibras Musculares Esqueléticas , Músculos PectoralesRESUMEN
This study aimed to investigate the influence of Astragalus membranaceus (AM), Adenophora triphylla (AT), and Ulmus pumila (UP) extracts on the quality traits, palatability, and storage stability of sous-vide (SV) cooked chicken breasts. Chicken breasts were marinated in AM, AT, or UP extracts for 1 h, and then consistently cooked at a constant temperature of 60°C for 2 h. SV cooked chicken breasts with the UP extract exhibited lower lightness and higher yellowness values on the surface region compared to those with the AM and AT extracts (p<0.05). The control and UP groups displayed a similar overall visual acceptability (p>0.05), although the UP group had lower color acceptability (p<0.01). The UP group also had higher flavor and lower off-flavor intensities compared to the control group (p<0.05), although similar scores were observed in tenderness attributes and juiciness among the groups (p>0.05). Owing to these results regarding overall sensory acceptability, samples from the UP group were more preferred by the trained panelists compared to samples from the control group (p<0.001). On 14 d of cold storage, all the groups with herbal medicinal extracts exhibited a lower concentration of thiobarbituric acid-reactive substances than the control group (p<0.05), and the AT and UP groups showed lower values compared to the AM group due to their higher flavonoid contents (p<0.001). Therefore, meat marination with herbal plant extracts before SV cooking can be effective for enhancing the overall quality of SV cooked chicken breast.
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The rabies virus is one of the most neurotropic of all viruses infecting mammals. During the terminal phases of infection, the virus spreads to peripheral tissues, including the skin. The external skin of the nose, called the nasal planum, is a sensory organ where numerous nerve bundles and terminal nerves are distributed. Therefore, the nasal planum is expected to serve as a postmortem diagnostic material. However, the distribution of rabies virus antigens in the nasal planum in rabid animals has not yet been studied. In this study, the nasal planum was obtained from 45 rabid dogs. In all rabid dogs, the viral antigen was detected in the peripheral nerve tissues, Merkel cells, and squamous cells. The viral antigen in the epidermis exhibited three patterns: first, a diffuse positive pattern from the basal layer to the squamous layer; second, a reticular positive pattern along the cell membrane in the squamous layer; and third, a basal layer pattern of the epidermis. In the dermis, viral antigens were detected more often in lamellated corpuscles just beneath the rete pegs. These results suggest that the nasal planum could serve as a useful alternative source for postmortem diagnosis in rabies endemic countries.
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Antígenos Virales , Animales , Autopsia/veterinaria , PerrosRESUMEN
BACKGROUND: The Philippines is one of the major endemic countries for canine rabies in Southeast Asia. However, detailed description and analysis of laboratory-confirmed animal rabies are limited. Highly accurate surveillance requires a thorough understanding of the target area-specific problems and obstacles. Therefore, we aim to describe and analyze the rabies suspect animals in Central Luzon, Philippines, to clarify the characteristics of management and clinical signs by conducting interviews with the owners. METHODS: We prospectively collected information on the rabies suspect animals submitted to the Regional animal laboratory in Central Luzon through passive laboratory-based rabies surveillance between 1st April 2019 and 30th September 2020. We performed active interviews directly or telephonically with the owner. The direct fluorescent antibody test was performed on the hippocampus, brain stem, and cerebellum for laboratory confirmation. Descriptive statistics were used to characterize the number of rabies cases according to management methods and characteristics of suspected animals during the observation period. Clinical symptoms of suspected rabid animals were analyzed by univariate logistic regression analysis. RESULTS: There were 292 sample submissions during the study period. Of these, 160 were positive for dFAT. Samples of pet animals (85.3%) provided by owners or their acquaintances (59.2%) accounted for the majority of laboratory confirmed cases. Case mapping showed that more rabies-suspected cases were sent from areas near the regional laboratory than from those far from the laboratory, despite the incidence of rabies being high in these areas. The management and clinical symptoms of 227 animal cases showed that most owners were managing their animals at home and were allowing them to roam outside (69.6%) and be unvaccinated (78.9%). Rabid animals were more likely to manifest aimless running, restlessness, and agitation. CONCLUSIONS: Our study provided some features of animals with laboratory-confirmed rabies in Central Luzon. However, most of the samples were submitted from areas near the rabies diagnosis laboratory, and the number of samples submitted from remote areas was low. To improve the surveillance capacity, it is necessary to increase sample submissions from remote areas.
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The direct fluorescent antibody test (dFAT) using brain sample after opening the skull is the standard rabies diagnostic test in animal rabies. However, it is not feasible in many resource-limited settings. Lateral flow devices (LFD) combined with a simple sampling methodology is quicker, simpler, and less hazardous than the standard test and can be a useful tool. We conducted a prospective on-site study to evaluate the diagnostic accuracy of the LFD with the straw sampling method compared with that of the dFAT with the skull opening procedure for post-mortem canine rabies diagnosis. We collected 97 rabies-suspected animals between December 1, 2020 and March 31, 2021. Among the 97 samples, 53 and 50 cases were positive tests for dFAT and LFD, respectively. The sensitivity and specificity of LFD with straw sampling method were 94.3% (95% confidence interval [CI], 84.3-98.8%) and 100% (95% CI, 92.0-100%), respectively. The performance of LFD by the straw sampling method showed relatively high sensitivity and 100% specificity compared with that of dFAT performed on samples collected after opening the skull. This methodology can be beneficial and is a strong tool to overcome limited animal surveillance in remote areas. However, because of our limited sample size, more data using fresh samples on-site and the optimizations are urgently needed for the further implementation in endemic areas.
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Encéfalo/virología , Pruebas Diagnósticas de Rutina/veterinaria , Rabia/diagnóstico , Rabia/veterinaria , Manejo de Especímenes/instrumentación , Animales , Autopsia/instrumentación , Autopsia/métodos , Cromatografía de Afinidad/instrumentación , Cromatografía de Afinidad/métodos , Pruebas Diagnósticas de Rutina/instrumentación , Pruebas Diagnósticas de Rutina/métodos , Perros , Femenino , Pruebas Inmunológicas/métodos , Masculino , Estudios Prospectivos , Rabia/virología , Virus de la Rabia/inmunología , Sensibilidad y EspecificidadRESUMEN
Highly potent poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors, including 9-hydroxy-1,2-dihydro-4H-thiopyrano[3,4-c]quinolin-5(6H)-one derivatives with a non-aromatic A-ring, were synthesized. Among the derivatives, 12a showed low nanomolar enzyme and cellular activity (IC(50) = 42 nM, ED(50) = 220 nM) with good water solubility. Further, 12a exhibited microsomal stability in vitro and brain permeability in vivo.
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Amidas/farmacología , Inhibidores Enzimáticos/farmacología , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Poli(ADP-Ribosa) Polimerasas/metabolismo , Compuestos Policíclicos/farmacología , Amidas/química , Amidas/farmacocinética , Animales , Encéfalo/metabolismo , Células CHO , Cricetinae , Cricetulus , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacocinética , Humanos , Microsomas Hepáticos/metabolismo , Modelos Moleculares , Poli(ADP-Ribosa) Polimerasa-1 , Poli(ADP-Ribosa) Polimerasas/química , Compuestos Policíclicos/química , Compuestos Policíclicos/farmacocinética , Ratas , Relación Estructura-ActividadRESUMEN
A series of coumarin based TACE inhibitors were designed to bind in S1' pocket of TACE enzyme based on their docking study. Twelve analogues were synthesized and most of compounds were active in vitro TACE enzyme inhibition as well as cellular TNF-α inhibition. Among these, 15l effectively inhibited the production of serum TNF-α by oral administration at a dose of 30 mg/kg. Compound 15l also showed a good oral bioavailability at 42% and effectively inhibited paw edema in rat carrageenan model. Quantitative structure-activity relationship (QSAR) study using genetic function approximation technique (GFA) and docking study were performed to confirm the series of coumarin core TACE inhibitors. QSAR model have been evaluated internally and externally using test set prediction. Through docking study of each molecule, it is validated that the electrostatic descriptors from the QSAR equation could explain the importance of S1' pocket and the TACE inhibitory activity well.