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1.
Cancer Med ; 13(9): e7189, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38706442

RESUMO

OBJECTIVES: Endoscopic ultrasound-guided tissue acquisition (EUS-TA) is used for pathological diagnosis and obtaining samples for molecular testing, facilitating the initiation of targeted therapies in patients with pancreatic cancer. However, samples obtained via EUS-TA are often insufficient, requiring more efforts to improve sampling adequacy for molecular testing. Therefore, this study investigated the use of oil blotting paper for formalin fixation of samples obtained via EUS-TA. METHODS: This prospective study enrolled 42 patients who underwent EUS-TA for pancreatic cancer between September 2020 and February 2022 at the Osaka International Cancer Institute. After a portion of each sample obtained via EUS-TA was separated for routine histological evaluation, the residual samples were divided into filter paper and oil blotting paper groups for analysis. Accordingly, filter paper and oil blotting paper were used for the formalin fixation process. The total tissue, nuclear, and cytoplasm areas of each sample were quantitatively evaluated using virtual slides, and the specimen volume and histological diagnosis of each sample were evaluated by an expert pathologist. RESULTS: All cases were cytologically diagnosed as adenocarcinoma. The area ratios of the total tissue, nuclear, and cytoplasmic portions were significantly larger in the oil blotting paper group than in the filter paper group. The frequency of cases with large amount of tumor cells was significantly higher in the oil blotting paper group (33.3%) than in the filter paper group (11.9%) (p = 0.035). CONCLUSIONS: Oil blotting paper can increase the sample volume obtained via EUS-TA on glass slides and improve sampling adequacy for molecular testing.


Assuntos
Formaldeído , Neoplasias Pancreáticas , Fixação de Tecidos , Humanos , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/diagnóstico por imagem , Estudos Prospectivos , Masculino , Feminino , Fixação de Tecidos/métodos , Idoso , Pessoa de Meia-Idade , Endossonografia/métodos , Manejo de Espécimes/métodos , Adenocarcinoma/patologia , Adenocarcinoma/diagnóstico por imagem , Idoso de 80 Anos ou mais , Papel , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos
2.
PLoS One ; 19(4): e0283915, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38635782

RESUMO

Anaphylaxis is a severe life-threatening hypersensitivity reaction induced by mast cell degranulation. Among the various mediators of mast cells, little is known about the role of tryptase. Therefore, we aimed to elucidate the role of protease-activating receptor-2 (PAR-2), a receptor activated by tryptase, in murine anaphylactic models using PAR-2-deficient mice and newly generated tryptase-deficient mice. Anaphylaxis was induced by IgE-dependent and IgE-independent mast cell degranulation in mice. PAR-2 deficiency exacerbated the decrease in body temperature and hypotension during anaphylaxis; however, the number of skin mast cells, degree of mast cell degranulation, and systemic and local vascular hyperpermeability were comparable in PAR-2 knockout and wild-type mice. Nitric oxide, which is produced by endothelial nitric oxide synthase (eNOS), is an indispensable vasodilator in anaphylaxis. In the lungs of anaphylactic mice, PAR-2 deficiency promoted eNOS expression and phosphorylation, suggesting a protective effect of PAR-2 against anaphylaxis by downregulating eNOS activation and expression. Based on the hypothesis that the ligand for PAR-2 in anaphylaxis is mast cell tryptase, tryptase-deficient mice were generated using CRISPR-Cas9. In wild-type mice, the PAR-2 antagonist exacerbated the body temperature drop due to anaphylaxis; however, the effect of the PAR-2 antagonist was abolished in tryptase-deficient mice. These results suggest that tryptase is a possible ligand of PAR-2 in anaphylaxis and that the tryptase/PAR-2 pathway attenuates the anaphylactic response in mice.


Assuntos
Anafilaxia , Animais , Camundongos , Anafilaxia/metabolismo , Imunoglobulina E/metabolismo , Ligantes , Mastócitos/metabolismo , Receptor PAR-2/genética , Receptor PAR-2/metabolismo , Triptases/genética , Triptases/metabolismo
3.
J Chem Phys ; 160(10)2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38465685

RESUMO

A Belousov-Zhabotinsky (BZ) gel is a unique biomimetic system that undergoes autonomous volume oscillations induced by the redox oscillation of the BZ reaction. In a previous study, researchers reported that the oscillations of two BZ gels coupled by compression were synchronized by a mechanical interaction. They mathematically explained the synchronization behavior using a phase oscillator model. As a different approach to the previous study, a physicochemical investigation of the phenomenon will lead to a better understanding of the functional biological rhythms essential for life. In this study, we construct a simple phenomenological model to understand the synchronization of BZ gels. The model consists of two parts. One is the dynamics of the chemical reactions in the BZ gels. We use a phenomenological model based on the Oregonator for the BZ reaction. The other is the dynamics of the mechanical deformation of the BZ gel. Using approximations, we extract the parameters essential for the synchronization of a mechanical interaction. Thus, we can derive a novel equation for the deformation dynamics of mechanically coupled BZ gels. By combining these two parts, we perform numerical calculations. This allows us to find that the synchronization of the two BZ gels is less likely to occur under stronger compression. We explain this trend through one physicochemical parameter in our model: the volume fraction of the BZ gel in the reduced state.

4.
Gan To Kagaku Ryoho ; 51(3): 269-273, 2024 Mar.
Artigo em Japonês | MEDLINE | ID: mdl-38494807

RESUMO

BACKGROUND: This study aimed to describe the surgical procedures involved in laparoscopic rectal resection in patients with obesity and report the short-term outcomes. MATERIALS AND METHODS: A total of 194 consecutive patients who underwent laparoscopic rectal resection in our department from 2013 to 2018 were divided into non-obese(body mass index[BMI] <25 kg/m2; n=161)and obese groups(BMI≥25 kg/m2; n=33)and subsequently analyzed. RESULTS: The operative time was significantly longer in the obese group(225 vs 266 min; p=0.003)than in the non-obese group. No conversions to laparotomy occurred in either group, and no discernible differences in blood loss(1 vs 5 mL; p=0.582), number of harvested lymph nodes(20 vs 17; p=0.356), and postoperative complication rates(9.3 vs 6.1%; p=0.547)were observed. CONCLUSION: Establishing an appropriate operative field, clarifying landmarks, and standardizing the procedure are important to assure safe laparoscopic rectal resection with adequate lymph node dissection in patients with obesity.


Assuntos
Laparoscopia , Neoplasias Retais , Humanos , Neoplasias Retais/cirurgia , Neoplasias Retais/patologia , Estudos Retrospectivos , Excisão de Linfonodo/métodos , Linfonodos/patologia , Laparoscopia/métodos , Obesidade/complicações , Obesidade/cirurgia , Obesidade/patologia , Resultado do Tratamento
6.
ACS Appl Mater Interfaces ; 16(8): 10427-10438, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38375854

RESUMO

Capture and real-time recording of precise body movements using strain sensors provide personal information for healthcare monitoring and management. To acquire this information, a sensor that conforms to curved irregular surfaces, including biological tissue, is desired to record complex body movements while acting like a second skin to avoid interference with the movements. In this study, we developed a thin-film-type capacitive strain sensor that is flexible and stretchable on the surface of a living body. We fabricated conductive polymeric ultrathin films ("nanosheets") comprising polystyrene-block-polybutadiene (SB) elastomers and single-walled carbon nanotubes (SWCNTs) (i.e., SWCNT-SB nanosheets) via gravure coating; the SWCNT-SB-coated nanosheets were used as the flexible electrode in a capacitive strain sensor. The dielectric (DE) layer was then prepared using the silicone elastomer Ecoflex 00-30 because its Young's modulus is comparable to that of the epidermis. The normalized capacitance changes (ΔC/C0) in the sensor increased with increasing tensile strain over a range from 0-100%, indicating that the proposed sensor can measure the strain of biological movements, including those of skin and blood vessels. To improve sensor conformability further, the effect of sensor thickness on the gauge factor (GF) was investigated using thinner DE layers by focusing on their flexural rigidity. As a result, the GF increased from 0.64 to 1.13 as the DE layer thickness decreased from 260 to 40 µm. Finally, we evaluated the fabricated sensor's signal stability and mechanical durability, including during wireless sensing when applied to human skin and a vascular model. The ΔC/C0 values varied in response to the bending motion of a finger, dilation of a blood vessel, and the swallowing movement of the throat. These results indicate that our capacitive strain sensor is conformable and functional on biological tissue to enable monitoring of dynamic biological movements (e.g., pulse rate and arterial dilation) without wearer discomfort.


Assuntos
Nanotubos de Carbono , Dispositivos Eletrônicos Vestíveis , Humanos , Nanotubos de Carbono/química , Módulo de Elasticidade , Movimento , Movimento (Física)
7.
Vet Immunol Immunopathol ; 269: 110716, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38308864

RESUMO

Myeloid-derived suppressor cells (MDSCs) are immature cells with immunosuppressive properties found in the tumor microenvironment. MDSCs are divided into two major subsets: polymorphonuclear MDSCs (PMN-MDSCs) and monocytic MDSCs (M-MDSCs). Both MDSC subsets contribute to the creation of an immunosuppressive environment for tumor progression. In humans, patients with high levels of MDSCs show worse outcomes for several types of cancers. However, the association between MDSCs and clinical features has rarely been investigated in canine studies. In the present study, we measured the proportion of PMN-MDSCs and M-MDSCs in the peripheral blood and tumor tissue of dogs with hepatocellular carcinoma (HCC), prostate cancer (PC), transitional cell carcinoma (TCC), lymphoma, and pulmonary adenocarcinoma. Additionally, we examined immunosuppressive ability of PMN-MDSCs and M-MDSCs in peripheral blood mononuclear cells of TCC case on CD4+, CD8+ and interferon-γ+ cells and investigated the relationships of MDSCs with clinical features and outcomes. PMN-MDSCs increased in HCC, PC, TCC, and lymphoma. In contrast, M-MDSCs increased in the TCC. Both PMN-MDSCs and M-MDSCs exhibited immunosuppressive effects on CD8+, CD4+ and interferon-γ+ cells. In dogs with TCC, lymph node metastasis was associated with high level of PMN-MDSCs but not with M-MDSCs. High levels of both PMN-MDSCs and M-MDSCs were related to advanced tumor stage. Kaplan-Meier analysis revealed that high levels of both PMN-MDSCs and M-MDSCs were significantly associated with shorter overall survival. In addition, the Cox proportional hazard regression model showed that M-MDSCs and the tumor stage were independent prognostic factors for TCC. These results suggest that PMN-MDSCs and M-MDSCs may be involved in tumor progression and could be prognostic factors and promising therapeutic targets in dogs with TCC.


Assuntos
Carcinoma Hepatocelular , Carcinoma de Células de Transição , Doenças do Cão , Neoplasias Hepáticas , Linfoma , Células Supressoras Mieloides , Humanos , Masculino , Animais , Cães , Células Supressoras Mieloides/metabolismo , Carcinoma Hepatocelular/veterinária , Neoplasias Hepáticas/veterinária , Interferon gama/metabolismo , Leucócitos Mononucleares , Carcinoma de Células de Transição/veterinária , Prognóstico , Linfoma/veterinária , Microambiente Tumoral , Doenças do Cão/metabolismo
8.
Cyborg Bionic Syst ; 5: 0091, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38318499

RESUMO

The conventional electrohydrodynamic (EHD) pump is limited to pumping functional and dielectric liquids, which restricts its applications in fields like microfluidics, food safety, and materials production. In this study, we present a flexible water pump driven by EHD fluid, achieved by integrating valveless elements into the fluidic channel. Our approach leverages the water-EHD interface to propel the immiscible aqueous liquid and reciprocate this process using the nozzle-diffuser system. All components of the water pump are digitally fabricated and assembled. The valveless parts are created using a laser cutting machine. Additionally, we develop a model for the EHD pump and nozzle-diffuser system to predict the generated flow rate, considering factors such as the asymmetrical performance of the EHD pump, pulse frequency, applied voltage, and structural parameters. Finally, we experimentally characterize the flow rates of both the EHD pump and water pump and apply the newly developed device to air bubble manipulation and droplet generation. This research broadens the range of specialized liquids pumped by EHD pumps to include other aqueous liquids or mixtures.

9.
JFMS Open Rep ; 10(1): 20551169231220290, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38268764

RESUMO

Case summary: The patient was a castrated male American Shorthair cat, approximately 14 years old, weighing 3.4 kg. The patient had chronic kidney disease (CKD) (International Renal Interest Society stages 3-4) as an underlying disease. The cat was examined at a hospital for intermittent lethargy and seizures. Hypoglycaemia was repeatedly observed, and the insulin level was 1.78 ng/ml (reference interval 0.27-0.69) when the blood glucose was 49 mg/dl. Although the cat was tentatively diagnosed with insulinoma, surgery was not recommended because of the severe CKD. Although frequent feeding and prednisolone treatment were initially attempted, blood glucose decreased to 24-42 mg/dl. Diazoxide was additionally prescribed at a dose of 5.2 mg/kg q12h. The cat's clinical signs improved, and the blood glucose was in the range of 75-103 mg/dl during the first 2 months. It was maintained at >50 mg/dl until the patient died of renal failure 161 days after the start of diazoxide treatment. With regard to adverse events, vomiting once every 2-3 days without weight loss and non-regenerative anaemia were observed, which might have been at least partially caused by diazoxide treatment. An insulinoma was definitively diagnosed via pathological autopsy. Relevance and novel information: This is the first reported case of long-term treatment with diazoxide in a cat with insulinoma. Since it was effective in situations where conventional therapies were unsuccessful, diazoxide could be useful as a new therapeutic option for cats with insulinoma. Since adverse events, such as progression of vomiting frequency and non-regenerative anaemia, were observed, careful monitoring was required during administration.

10.
ACS Appl Mater Interfaces ; 16(1): 1883-1891, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38096263

RESUMO

Seamlessly fusing fashion and functionality can redefine wearable technology and enhance the quality of life. We propose a pocketable and smart electrohydrodynamic pump (PSEP) with self-sensing capability for wearable thermal controls. Overcoming the constraints of traditional liquid-cooled wearables, PSEP with dimensions of 10 × 2 × 1.05 cm and a weight of 10 g is sufficiently compact to fit into a shirt pocket, providing stylish and unobtrusive thermal control. Silent operation coupled with the unique self-sensing ability to monitor the flow rate ensures system reliability without cumbersome additional components. The significant contribution of our study is the formulation and validation of a theoretical model for self-sensing in EHD pumps, thereby introducing an innovative functionality to EHD pump technology. PSEP can deliver temperature changes of up to 3 °C, considerably improving personal comfort. Additionally, the PSEP system features an intuitive, smartphone-compatible interface for seamless wireless control and monitoring, enhancing user interaction and convenience. Furthermore, the ability to detect and notify users of flow blockages, achieved by self-sensing, ensures an efficient and long-term operation. Through its blend of compact design, intelligent functionality, and stylish integration into daily wear, PSEP reshapes the landscape of wearable thermal control technology and offers a promising avenue for enhancing personal comfort in daily life.

11.
Open Vet J ; 13(7): 942-947, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37614731

RESUMO

Background: The anti-epileptic effects of docosahexaenoic acid (DHA) in dogs and humans remain controversial. The dosage and efficacy of DHA were various in the previous reports. Aim: The effects of high-dose DHA supplementation as add-on therapy for idiopathic epilepsy in dogs were evaluated. Methods: An open-label clinical trial was designed in this pilot study. Six dogs (median age: 6 years) with idiopathic epilepsy were included. All the patients were diagnosed with idiopathic epilepsy using magnetic MRI and cerebrospinal fluid examination (median: 2.0 years before the trial). They had 5-45 seizures and/or auras (median: 9.0) in the month before starting DHA supplementation. DHA was adjunctively administered at doses of 69-166 mg/kg/day without changing other prescriptions. Results: Four of the six patients completed the 6-month observation period. All the patients showed a decrease in seizure frequency of 50% or more within 2-3 months after the start of the administration, and three patients decreased to a frequency of 0-1 per month after 5-6 months. No clear adverse events were observed in the general condition or blood test results in any patients. Conclusion: Although the sample size was small and the study was not a randomized controlled trial, the data suggest that add-on supplementation of DHA could be useful in reducing the frequency of seizures in canine idiopathic epilepsy.


Assuntos
Doenças do Cão , Epilepsia , Animais , Cães , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/uso terapêutico , Doenças do Cão/tratamento farmacológico , Epilepsia/tratamento farmacológico , Epilepsia/veterinária , Projetos Piloto , Convulsões/veterinária
12.
Open Vet J ; 13(7): 846-853, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37614732

RESUMO

Background: Idiopathic epilepsy in cats is a more common disease than previously thought, but little information is available about the medical treatment of feline idiopathic epilepsy. Aim: To assess the therapeutic efficacy and safety of antiseizure medication (ASM) for a minimum of 6 months, including zonisamide (ZNS), in feline idiopathic epilepsy at a referral hospital in Japan. Methods: Twenty cats diagnosed with idiopathic epilepsy treated with ASMs were retrospectively included. Results: Nine cats that were finally treated with phenobarbital (PB) monotherapy reached the primary goal (the seizure frequency after the treatment intervention was less than one seizure every 3 months). Three cats were treated with ZNS monotherapy and two reached the primary goal. Eight cats finally received combination therapy. Two of the three cats receiving PB and ZNS therapy achieved the primary goal, but one was considered no responder. Five cats [PB + diazepam (DZP), ZNS + DZP, and ZNS + levetiracetam + DZP] decreased the seizure frequency and reached the primary goal in all but one cat reached the secondary goal. Adverse events were observed in eight patients, but these were curable. Two patients had vomiting after ZNS monotherapy, one had diarrhea, and another was an increase in sleeping hours. Conclusion: PB was frequently used and seemed effective as both monotherapy and combination therapy. Some cats were treated with ASM protocols containing ZNS. ZNS may be available to treat idiopathic epilepsy in cats. However, ZNS administration may cause adverse events, such as gastrointestinal toxicity, in cats.


Assuntos
Doenças do Gato , Epilepsia , Gatos , Animais , Zonisamida/uso terapêutico , Japão , Estudos Retrospectivos , Epilepsia/tratamento farmacológico , Epilepsia/veterinária , Convulsões/veterinária , Hospitais , Encaminhamento e Consulta , Doenças do Gato/tratamento farmacológico
14.
Rinsho Shinkeigaku ; 63(9): 592-595, 2023 Sep 20.
Artigo em Japonês | MEDLINE | ID: mdl-37648476

RESUMO

A 47-year-old woman developed right femoral head necrosis during long-term steroid use for neuromyelitis optica spectrum disorder. She underwent a total hip arthroplasty because her right hip pain persisted after satralizumab treatment. There were no postoperative infections. Under oral administration of tacrolimus 3 mg, prednisolone 11 mg, and acetaminophen 2,275 mg, her postoperative body temperature was less than 38°C and normalized in about 2 days after the operation. No parameters indicating worsening of inflammation were observed in the blood test. In satralizumab-treated patients, infection cannot be ruled out even without inflammatory findings. In particular, if a slight fever of the 37°C-range or a mildly high white blood cell count persists, paying attention to signs of infection and actively investigating the presence or absence of infection using medical image diagnostic devices are necessary.


Assuntos
Artroplastia de Quadril , Necrose da Cabeça do Fêmur , Neuromielite Óptica , Humanos , Feminino , Pessoa de Meia-Idade , Neuromielite Óptica/diagnóstico , Neuromielite Óptica/tratamento farmacológico , Artroplastia de Quadril/efeitos adversos , Necrose da Cabeça do Fêmur/diagnóstico por imagem , Necrose da Cabeça do Fêmur/etiologia , Necrose da Cabeça do Fêmur/cirurgia , Inflamação
15.
World Neurosurg X ; 20: 100236, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37435396

RESUMO

Objective: Idiopathic normal-pressure hydrocephalus (iNPH) is characterized by symptoms of dementia, urinary incontinence, and gait disturbance; however, gait disturbance tends to persist after shunt surgery. Gait disturbance and urinary dysfunction are also major symptoms of lumbar spinal stenosis (LSS). Currently, the epidemiology of the complications of LSS in iNPH is unclear. Here, we evaluated the coexistence rate of LSS in iNPH cases. Methods: This was a retrospective case-control study. Between 2011 and 2017, 224 patients with a median age of 78 years, including 119 males, were diagnosed with iNPH and underwent lumboperitoneal shunts or ventriculoperitoneal shunts. LSS was diagnosed with magnetic resonance imaging by two spine surgeons. Age, sex, body mass index (BMI), Timed Up and Go (TUG) test, Mini Mental State Examination (MMSE) score, and urinary dysfunction were examined. We compared the changes in these variables in the group of patients with iNPH without LSS versus those with both iNPH and LSS. Results: Seventy-three iNPH patients (32.6%) with LSS had significantly higher age and BMI. The existence of LSS did not alter the postoperative improvement rates of MMSE and urinary dysfunction; however, TUG improvement was significantly impaired in the LSS-positive group. Conclusions: LSS affects improvements in gait disturbance of iNPH patients after shunt operation. Because our results revealed that one-third of iNPH patients were associated with LSS, gait disturbance observed in iNPH patients should be considered a potential complication of LSS.

16.
J Feline Med Surg ; 25(7): 1098612X231185393, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37489504

RESUMO

OBJECTIVES: Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited disease in cats. In most cases, the responsible abnormality is a nonsense single nucleotide polymorphism in exon 29 of the PKD1 gene (chrE3:g.42858112C>A, the conventional PKD1 variant). The aim of this study was to conduct a large-scale epidemiological study of ADPKD caused by the conventional PKD1 variant in Japan and to search for novel polymorphisms by targeted resequencing of the PKD1 using a next-generation sequencer. METHODS: A total of 1281 cats visiting the Veterinary Medical Center of the University of Tokyo were included in this study. DNA was extracted from the blood of each cat. We established a novel TaqMan real-time PCR genotyping assay for the conventional PKD1 variant, and all cases were examined for the presence of this variant. Targeted resequencing of all exons of the PKD1 was performed on the DNA of 23 cats with the conventional PKD1 variant, six cats diagnosed with cystic kidneys but without this variant, and 61 wild-type normal cats. RESULTS: Among the 1281 cats examined in this study, 23 (1.8%) harboured the conventional PKD1 variant. The odds of having the conventional PKD1 variant were significantly higher in Persian cats, Scottish Folds and Exotic Shorthairs than in the other breeds, although the number of cases in each breed was small. Furthermore, we identified four variants unique to cats with cystic kidneys that were not found in wild-type normal cats, all of which were in exon 15. In particular, two (chrE:g.42848725delC, pGly1641fs and chrE:g.42850283C>T, pArg2162Trp) were candidate variants. CONCLUSIONS AND RELEVANCE: This study revealed that the conventional PKD1 variant was prevalent in Scottish Fold, Persian and Exotic Shorthair breeds in Japan, and variants in exon 15 of PKD1, in addition to the conventional variant in exon 29, would be key factors in the pathogenesis of ADPKD in cats.


Assuntos
Doenças do Gato , Rim Policístico Autossômico Dominante , Gatos , Animais , Rim Policístico Autossômico Dominante/epidemiologia , Rim Policístico Autossômico Dominante/genética , Rim Policístico Autossômico Dominante/veterinária , Canais de Cátion TRPP/genética , Éxons/genética , Estudos Epidemiológicos , DNA , Mutação , Doenças do Gato/epidemiologia , Doenças do Gato/genética
17.
Elife ; 122023 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-37461309

RESUMO

Ossification of the posterior longitudinal ligament of the spine (OPLL) is an intractable disease leading to severe neurological deficits. Its etiology and pathogenesis are primarily unknown. The relationship between OPLL and comorbidities, especially type 2 diabetes (T2D) and high body mass index (BMI), has been the focus of attention; however, no trait has been proven to have a causal relationship. We conducted a meta-analysis of genome-wide association studies (GWASs) using 22,016 Japanese individuals and identified 14 significant loci, 8 of which were previously unreported. We then conducted a gene-based association analysis and a transcriptome-wide Mendelian randomization approach and identified three candidate genes for each. Partitioning heritability enrichment analyses observed significant enrichment of the polygenic signals in the active enhancers of the connective/bone cell group, especially H3K27ac in chondrogenic differentiation cells, as well as the immune/hematopoietic cell group. Single-cell RNA sequencing of Achilles tendon cells from a mouse Achilles tendon ossification model confirmed the expression of genes in GWAS and post-GWAS analyses in mesenchymal and immune cells. Genetic correlations with 96 complex traits showed positive correlations with T2D and BMI and a negative correlation with cerebral aneurysm. Mendelian randomization analysis demonstrated a significant causal effect of increased BMI and high bone mineral density on OPLL. We evaluated the clinical images in detail and classified OPLL into cervical, thoracic, and the other types. GWAS subanalyses identified subtype-specific signals. A polygenic risk score for BMI demonstrated that the effect of BMI was particularly strong in thoracic OPLL. Our study provides genetic insight into the etiology and pathogenesis of OPLL and is expected to serve as a basis for future treatment development.


Assuntos
Diabetes Mellitus Tipo 2 , Ossificação do Ligamento Longitudinal Posterior , Animais , Camundongos , Osteogênese , Estudo de Associação Genômica Ampla , Diabetes Mellitus Tipo 2/patologia , Coluna Vertebral/patologia , Ossificação do Ligamento Longitudinal Posterior/genética , Ossificação do Ligamento Longitudinal Posterior/patologia
18.
J Feline Med Surg ; 25(6): 1098612X231173519, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37318844

RESUMO

OBJECTIVES: Oxidative stress is associated with the development and progression of chronic kidney disease (CKD) in humans. The aim of this study was to evaluate the concentrations of oxidative stress markers, 8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA), in the plasma and urine of cats with different stages of CKD. METHODS: Plasma and urine samples were collected from cats with CKD that were referred to the Veterinary Medical Center of the University of Tokyo between April 2019 and October 2022. Plasma and urine samples were collected from healthy cats (n = 6 at most), cats with stage 2 CKD (n = 8) and stage 3-4 CKD (n = 12), and cats with idiopathic cystitis (disease control, n = 5). Plasma and urine concentrations of 8-OHdG and MDA were measured using ELISA and thiobarbituric acid reactive substances assay kits, respectively. RESULTS: The median plasma 8-OHdG concentrations were 0.156 ng/ml (<0.125-0.210 ng/ml) in the healthy group, <0.125 ng/ml (range <0.125 ng/ml) in the idiopathic cystitis group, 0.246 ng/ml (range 0.170-0.403 ng/ml) in cats with stage 2 CKD and 0.433 ng/ml (range 0.209-1.052 ng/ml) in cats with stage 3-4 CKD. Concentrations in stage 3-4 CKD were significantly higher than those in the healthy and disease control groups. Plasma MDA concentrations were low in the healthy and disease control groups and significantly higher in cats with stage 3-4 CKD. In every cat with CKD, plasma 8-OHdG and MDA concentrations were positively correlated with plasma creatinine concentrations (8-OHdG, rs = 0.68; MDA, rs = 0.67). Urinary 8-OHdG/urinary creatinine (u-CRE) and urinary MDA/u-CRE levels did not differ significantly between the groups; however, it was difficult to evaluate them because of the small sample size. CONCLUSIONS AND RELEVANCE: This report shows that plasma 8-OHdG and MDA concentrations increase with the severity of feline CKD. These markers may be useful for assessing oxidative stress in cats with CKD.


Assuntos
Doenças do Gato , Insuficiência Renal Crônica , Gatos , Humanos , Animais , 8-Hidroxi-2'-Desoxiguanosina , Desoxiguanosina/urina , Creatinina , Malondialdeído/urina , Insuficiência Renal Crônica/veterinária , Gravidade do Paciente
19.
J Vet Med Sci ; 85(8): 790-798, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37380433

RESUMO

The development of molecular biology and bioinformatics using next-generation sequencing has dramatically advanced the identification of molecules involved in various diseases and the elucidation of their pathogenesis. Consequently, many molecular-targeted therapies have been developed in the medical field. In veterinary medicine, the world's first molecular-targeted drug for animals, masitinib, was approved in 2008, followed by the multikinase inhibitor toceranib in 2009. Toceranib was originally approved for mast cell tumors in dogs but has also been shown to be effective in other tumors because of its ability to inhibit molecules involved in angiogenesis. Thus, toceranib has achieved great success as a molecular-targeted cancer therapy for dogs. Although there has been no progress in the development and commercialization of new molecular-targeted drugs for the treatment of cancer since the success of toceranib, several clinical trials have recently reported the administration of novel agents in the research stage to dogs with tumors. This review provides an overview of molecular-targeted drugs for canine tumors, particularly transitional cell carcinomas, and presents some of our recent data.


Assuntos
Antineoplásicos , Doenças do Cão , Neoplasias , Cães , Animais , Neoplasias/tratamento farmacológico , Neoplasias/veterinária , Doenças do Cão/tratamento farmacológico , Antineoplásicos/uso terapêutico
20.
JACC Clin Electrophysiol ; 9(8 Pt 3): 1730-1740, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37354187

RESUMO

BACKGROUND: In current practice, the ablation target of atypical atrioventricular nodal re-entrant tachycardia (AVNRT) is the earliest atrial activation site in the coronary sinus (CS) or conventional slow pathway region. OBJECTIVES: The purposes of this study were to map the site of earliest retrograde atrial activation using electroanatomic three-dimensional mapping during atypical AVNRT and to evaluate successful ablation sites. METHODS: A total of 42 patients with a total of 49 AVNRTs (slow/fast: 30; fast/slow: 15; slow/slow: 4) underwent electrophysiological study and ablation. Among them there were 14 patients (10 women; 60 ± 19 years of age) in whom 19 atypical AVNRT (fast/slow: 15; slow/slow: 4) were induced. RESULTS: The intracardiac electrocardiograms or three-dimensional mapping of the exit site during tachycardia revealed that 7 patients had exit sites solely inside the CS (left inferior extension [LIE]), 3 solely in the right postero-septal tricuspid annulus (TA; right inferior extension [RIE]), and 4 had both LIE and RIE exits. The distance from the CS ostium to LIE exits was 14 ± 6 mm. RIE exits were located on the TA posterior to the CS ostium (between 5 and 6 o'clock in the left anterior oblique projection). Ablation targeting these exits or conventional slow pathway succeeded in long-term elimination of AVNRT in 13 of the 14 patients (93%). There were no complications. CONCLUSIONS: Catheter ablation targeting the exit sites of LIE or RIE mapped at the CS or TA holds promise as an effective and safe alternative approach to the current targets of ablation for atypical AVNRT cases.


Assuntos
Ablação por Cateter , Taquicardia por Reentrada no Nó Atrioventricular , Feminino , Humanos , Ablação por Cateter/métodos , Taquicardia por Reentrada no Nó Atrioventricular/fisiopatologia , Taquicardia por Reentrada no Nó Atrioventricular/cirurgia , Masculino , Pessoa de Meia-Idade , Idoso , Adulto , Resultado do Tratamento
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