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1.
Vet Surg ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38558291

RESUMO

OBJECTIVES: To evaluate the feasibility of correcting penile urethral strictures at the bulbus glandis using buccal mucosal graft (BMG) urethroplasty in dogs. STUDY DESIGN: Prospective clinical trial. ANIMALS: Five male dogs with urethral strictures located at the bulbus glandis. METHODS: Urethrotomy was performed throughout the entire length of the urethral stricture including ~0.5 cm healthy urethra proximal and distal. The scarred tissue and unhealthy mucosa of the strictured urethra were completely excised. The graft was harvested from the buccal mucosa and tubularized at the stricture site using a urethral catheter as the skeleton. The catheter was maintained for 14 days after surgery and removed when no urethral leakage was identified on a positive-contrast retrograde urethrogram. The dogs were discharged after spontaneous urination was confirmed. Six months postoperative follow-up was completed for all dogs with repeated positive contrast urethrogram and an owner questionnaire to score urinary function and quality of life. RESULTS: The five dogs recovered well following surgery and only one dog experienced a minor complication. All dogs were able to urinate normally after catheter removal. No evidence of leakage was identified on a 14 day postoperative retrograde positive contrast urethrogram and clinically at a median follow-up time of 182 days (range, 182-186). All owners scored the urinary function as excellent and ranked their satisfaction very high 6 months after the procedure. CONCLUSION: Buccal mucosal graft urethroplasty has positive outcomes for dogs with penile urethral strictures.

2.
J Hypertens ; 42(4): 610-619, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38441184

RESUMO

OBJECTIVE: We investigated the interrelationship between hyperglycemia and hypertension on cardiovascular mortality in the middle-aged and elderly people. METHODS: In this retrospective cohort study that used data from the Hiroshima Study on Glucose Metabolism and Cardiovascular Diseases, we included 16,564 participants without cardiovascular disease (mean age: 65.8 years; 6179 normoglycemic people, 3017 people with newly diagnosed type 2 diabetes, and 7368 people with prediabetes per the 75-g oral glucose tolerance test). Hypertension was defined as the use of antihypertensive medications and/or having a systolic/diastolic blood pressure of at least 140/90 mm Hg. RESULTS: During a median follow-up period of 12.4 years, a total of 1513 cardiovascular death occurred. Cardiovascular death rates per 1000 participant-years were 4.01, 4.98, 8.33, 8.22, 8.81, and 11.1 among normotensive participants with normal glycemia, prediabetes, and diabetes and hypertensive participants with normal glycemia, prediabetes, and diabetes, respectively. Prediabetes was significantly associated with a high risk of cardiovascular mortality in normotensive individuals [hazard ratio: 1.24, 95% confidence interval (95% CI): 1.02-1.50] but not in hypertensive individuals. Type 2 diabetes was associated with a high risk of cardiovascular mortality in both normotensive (hazard ratio: 1.94, 95% CI: 1.55-2.43) and hypertensive individuals (hazard ratio: 1.35, 95% CI: 1.13-1.62). Stratified analyses revealed no significant impact of type 2 diabetes on cardiovascular mortality in hypertensive individuals aged at least 65 years. CONCLUSION: The effect of hyperglycemia on cardiovascular death differed with age and the presence or absence of hypertension, demonstrating the clinical importance of case-specific risk assessments.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Hiperglicemia , Hipertensão , Estado Pré-Diabético , Idoso , Pessoa de Meia-Idade , Humanos , Pressão Sanguínea , Estado Pré-Diabético/complicações , Diabetes Mellitus Tipo 2/complicações , Estudos Retrospectivos , Hipertensão/complicações
3.
Intern Med ; 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38369360

RESUMO

Objective Atrial fibrillation (AF) is the most common cause of tachycardia-induced cardiomyopathy (TIC). However, which patients with AF are prone to developing TIC remains unclear. In this study, we investigated the clinical features of AF patients with TIC. Methods This single-center study included 722 patients with AF (average age, 63.1±10.2 years old; 191 women) who underwent radiofrequency catheter ablation. We defined TIC as an initial left ventricular ejection fraction (LVEF) of <40% and a >20% recovery of the LVEF after successful AF ablation and compared the clinical characteristics between the TIC and control groups. Results The proportions of type 2 diabetes (30.5% vs. 14.7%), renal dysfunction (34.2% vs. 23.8%), hypertension (67.1% vs. 54.8%), and persistent AF (62.2% vs. 32.2%) were significantly higher in the TIC group (n=82) than in the control group (n=640). The atrioventricular nodal effective refractory period (AVNERP) (303±72 ms vs. 332±86 ms; p=0.017) was significantly shorter in the TIC group than in the control group. A multivariable analysis found that persistent AF [odds ratio (OR), 3.19; 95% confidence interval (CI), 1.94-5.24], renal dysfunction (OR, 1.87; 95% CI, 1.06-3.32), and type 2 diabetes (OR, 2.30; 95% CI, 1.31-4.05) were significantly associated with TIC. Conclusion Comorbid renal dysfunction and type 2 diabetes were clinical features of AF patients with TIC. Persistent AF, and short AVNERP may be involved in the development of TIC.

5.
J Vet Med Sci ; 86(1): 66-70, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37952973

RESUMO

A retrospective study involving 14 pet rabbits histopathologically diagnosed with malignant peripheral nerve sheath tumors (MPNSTs) was conducted. The age at diagnosis was 4-12 years, with a median age of 8.6 years. All rabbits had solid subcutaneous tumor masses in varied locations. Surgical excision of the tumors was performed in all cases. Recurrence was observed in 10 cases (71%), and postoperative metastasis to the lung was suspected in 4 cases (29%). The postoperative mean and median survival times were 11 months and 9 months, respectively. Hence, MPNSTs should be considered in the differential diagnosis for subcutaneous masses in rabbits and it is essential to inform the owners of the potentially high recurrence and metastasis rates.


Assuntos
Neoplasias de Bainha Neural , Neurofibrossarcoma , Coelhos , Animais , Neurofibrossarcoma/veterinária , Neoplasias de Bainha Neural/cirurgia , Neoplasias de Bainha Neural/veterinária , Estudos Retrospectivos , Diagnóstico Diferencial
6.
J Hypertens ; 42(2): 292-300, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37851003

RESUMO

OBJECTIVE: This study aimed to investigate the relationship between serum uric acid (SUA) levels and hypertension in the middle-aged and elderly populations. METHODS: The cross-sectional analysis included 13 349 middle-aged and elderly general health checkup examinees without cardiovascular disease. The retrospective cohort analysis included 6659 normotensive participants (mean age: 64.6 years). Participants were divided into three groups based on their SBP/DBP levels: normal (<120/<80 mmHg), high normal (120-129/<80 mmHg), and elevated (130-139/80-89 mmHg), and were classified into three groups based on the results of 75 g oral glucose tolerance test: normoglycemia, prediabetes, and diabetes. RESULTS: SUA levels were significantly associated with SBP and DBP in this cross-sectional study. Over a mean 6.5-year follow-up period, 2038 participants developed hypertension. According to the SUA quartiles, the incidence of hypertension increased [26.1% in quartile (Q1) (≤4.1 mg/dl), 28.6% in Q2 (4.2-4.9 mg/dl), 32.6% in Q3 (5.0-5.8 mg/dl), 34.9% in Q4 (≥5.9 mg/dl); P for trend <0.001]. In multivariable analyses, SUA levels were positively associated with hypertension incidence only in the normal BP group [Q4 vs. Q1 odds ratio (OR): 1.64, 95% confidence intervals (CIs): 1.11-2.44; Q3 vs. Q1 OR: 1.69, 95% CI: 1.19-2.42] and in the normoglycemic group (Q4 vs. Q1 OR: 1.34, 95% CI: 1.02-1.76; Q3 vs. Q1 OR: 1.36, 95% CI: 1.07-1.74). CONCLUSION: In the middle-aged and elderly populations, normotensive or normoglycemic individuals with SUA levels at least 5 mg/dl may be potential targets for SUA management to prevent hypertension.


Assuntos
Hipertensão , Ácido Úrico , Pessoa de Meia-Idade , Idoso , Humanos , Pressão Sanguínea , Estudos Transversais , Estudos Retrospectivos , Incidência , Hipertensão/epidemiologia , Fatores de Risco
7.
J Comp Pathol ; 207: 6-9, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37866218

RESUMO

A 6-years and 6-months-old, neutered male mongrel dog had a skin mass between the left eye and nose. Fine needle aspiration biopsy of the mass revealed giant epithelial cells containing many neutrophils in the cytoplasm. The mass was excised and histopathologically diagnosed as an infundibular cyst with giant epithelial-like cells containing neutrophils in part of the lumen. The giant cells were immunopositive for cytokeratin and immunonegative for vimentin. Cell cannibalism is a cell engulfing phenomenon in which a cell incorporates either the same or a different type of cell and the incorporated cells are degenerate or necrotic. In this case, epithelial cells in the lumen of the cyst incorporated neutrophils, which corresponds to neutrophil cannibalism by squamous epithelial cells.


Assuntos
Cistos , Doenças do Cão , Masculino , Cães , Animais , Neutrófilos , Canibalismo , Células Epiteliais/patologia , Cistos/veterinária , Doenças do Cão/patologia
8.
Cell Mol Gastroenterol Hepatol ; 16(6): 1011-1031, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37567385

RESUMO

BACKGROUND & AIMS: D-amino acids, the chiral counterparts of protein L-amino acids, were primarily produced and utilized by microbes, including those in the human gut. However, little was known about how orally administered or microbe-derived D-amino acids affected the gut microbial community or gut disease progression. METHODS: The ratio of D- to L-amino acids was analyzed in feces and blood from patients with ulcerative colitis (UC) and healthy controls. Also, composition of microbe was analyzed from patients with UC. Mice were treated with D-amino acid in dextran sulfate sodium colitis model and liver cholangitis model. RESULTS: The ratio of D- to L-amino acids was lower in the feces of patients with UC than that of healthy controls. Supplementation of D-amino acids ameliorated UC-related experimental colitis and liver cholangitis by inhibiting growth of Proteobacteria. Addition of D-alanine, a major building block for bacterial cell wall formation, to culture medium inhibited expression of the ftsZ gene required for cell fission in the Proteobacteria Escherichia coli and Klebsiella pneumoniae, thereby inhibiting growth. Overexpression of ftsZ restored growth of E. coli even when D-alanine was present. We found that D-alanine not only inhibited invasion of pathological K. pneumoniae into the host via pore formation in intestinal epithelial cells but also inhibited growth of E. coli and generation of antibiotic-resistant strains. CONCLUSIONS: D-amino acids might have potential for use in novel therapeutic approaches targeting Proteobacteria-associated dysbiosis and antibiotic-resistant bacterial diseases by means of their effects on the intestinal microbiota community.


Assuntos
Colangite , Colite Ulcerativa , Colite , Doenças Inflamatórias Intestinais , Humanos , Animais , Camundongos , Aminoácidos , Proteobactérias , Escherichia coli , Doenças Inflamatórias Intestinais/tratamento farmacológico , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Alanina , Colangite/tratamento farmacológico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico
9.
Int J Mol Sci ; 24(3)2023 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-36768545

RESUMO

Tissue inhibitors of metalloproteinases (TIMPs) are endogenous matrix metalloproteinase inhibitors. TIMP1 is produced by cancer cells and has pleiotropic activities. However, its role and source in multiple myeloma (MM) are unclear. Here, we evaluated TIMP1 protein and mRNA levels in bone marrow (BM) plasma cells and assessed the effects of TIMP1 expression on fibroblast invasive capacity using three-dimensional spheroid cell invasion assays. TIMP1 mRNA and protein levels were elevated when patients progressed from monoclonal gammopathy of undetermined significance or smouldering myeloma to MM. Furthermore, TIMP1 levels decreased at complete response and TIMP1 protein levels increased with higher international staging. TIMP1 mRNA levels were markedly higher in extramedullary plasmacytoma and MM with t(4;14). Overall survival and post-progression survival were significantly lower in MM patients with high TIMP1 protein. Recombinant TIMP1 did not directly affect MM cells but enhanced the invasive capacity of fibroblasts; this effect was suppressed by treatment with anti-TIMP1 antibodies. Fibroblasts supported myeloma cell invasion and expansion in extracellular matrix. Overall, these results suggested that MM-derived TIMP1 induces the invasive phenotype in fibroblasts and is involved in disease progression. Further studies are required to elucidate the specific roles of TIMP1 in MM and facilitate the development of novel therapies targeting the TIMP1 pathway.


Assuntos
Mieloma Múltiplo , Humanos , Mieloma Múltiplo/genética , Mieloma Múltiplo/metabolismo , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Fibroblastos/metabolismo , RNA Mensageiro/metabolismo , Fenótipo , Progressão da Doença
10.
Cell Prolif ; 56(6): e13398, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36642815

RESUMO

Cellular senescence is linked to a wide range of age-related diseases and can be triggered by a variety of stresses, including DNA damage. A variety of genotoxic stressors, such as anti-cancer drugs, cause DNA double-strand breaks (DSBs), which trigger the accumulation of the tumour suppressor protein p53 in the nucleus. Cellular stresses stabilize and activate the p53 signalling pathway, which regulates various cellular processes, such as apoptosis, DNA repair, and senescence. Although p53 signalling is a well-known tumour suppressor pathway, it remains unclear how it is regulated during cellular senescence. Here, we show that p53-binding protein 1 (53BP1) accumulation in the nuclear foci is required for DNA damage-induced cellular senescence via p53 activation. In human immortalized fibroblast, shRNA-mediated 53BP1 depletion decreased not only the expression of p53-target genes but also the cellular senescence induced by adriamycin treatment. Furthermore, we confirmed that DSBs trigger the hyperaccumulation of 53BP1 in the nuclear foci, which plays a key role in the regulation of cellular senescence. To prevent the accumulation of 53BP1 in the nuclear foci, we used phase separation inhibitors, and siRNA against RNF168, which accumulates at DSB loci and forms complexes with 53BP1. This blocks the formation of 53BP1 nuclear foci and DNA damage-induced cellular senescence by activating the p53 signaling pathway. In conclusion,   we demonstrated that increased accumulation of 53BP1 in the nuclear foci following DNA damage activates p53 and governs cellular senescence via a liquid-liquid phase separation mechanism.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular , Proteína Supressora de Tumor p53 , Humanos , Núcleo Celular/metabolismo , Senescência Celular , Dano ao DNA , Reparo do DNA , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/genética , Proteína 1 de Ligação à Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
11.
J Vet Med Sci ; 85(1): 19-29, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36385043

RESUMO

There is no nationwide necropsy database of animals in Japan, and most of the records are available from the postwar period. To clarify the chronological transition of animal necropsy cases in Tokyo, Japan, the records accumulated in The University of Tokyo from 1902 were investigated. Of necropsy records on paper or electronic from 1902 to 2021 kept at the Laboratory of Veterinary Pathology, The University of Tokyo, totally 3,137 cases including 572 in 1903-1914 (the Meiji-Taisho period), 1,258 in 1956-1969 (the Showa period) and 1,307 in 2006-2020 (the Heisei-Reiwa period), respectively, were examined for species, breed, age and pathological diagnosis. Dogs (44.6%) and horses (34.8%) in the Meiji-Taisho period, dogs (62.9%) and cats (17.3%) in the Showa period, and dogs (46.0%), cats (26.1%) and exotic animals (20.5%) in the Heisei-Reiwa period were the most necropsied animal species. With the passage of time, the number of animal species increased, and the breeds of dogs and cats came to be more various. The median ages of death were 2 years, 3 years and 10 years old in dogs in the Meiji-Taisho, Showa and Heisei-Reiwa periods, respectively, and 2 years and 10 years old in cats in the Showa and Heisei-Reiwa periods, respectively. Viral, bacterial and parasitic infections were decreased, and inversely tumor cases increased due to the prolonged lifespan.


Assuntos
Autopsia , Animais , Gatos , Cães , Autopsia/história , Autopsia/estatística & dados numéricos , Autopsia/veterinária , Doenças do Gato , Doenças do Cão , Doenças dos Cavalos , Cavalos , Japão , Tóquio/epidemiologia
12.
Front Neurol ; 13: 928803, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35911880

RESUMO

Pregnancy-associated cervicocephalic arterial dissection is rare, and its pathophysiology remains poorly understood. Despite the hypothesized contribution to pathogenesis, connective tissue diseases and genetic factors are rarely identified in clinical cases. We describe a case of postpartum arterial dissection involving all four cervicocephalic arteries resulting in acute cerebral infarction. The patient underwent successful endovascular thrombectomy and angioplasty and recovered fully without sequelae. Genetic screening for connective tissue diseases identified a heterozygous missense COL5A1 variant with unknown clinical significance. Two genetically related family members later developed arterial abnormalities, and one of them tested positive for the same COL5A1 gene variant as our patient, while the other was scheduled for genetic testing. The extensive clinical presentation of our patient and the prevalence of arterial abnormalities in her family warrant further assessment of the association between the identified COL5A1 gene variant and the pathogenesis of arterial dissections.

13.
Diabetes Care ; 45(10): 2309-2315, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35944240

RESUMO

OBJECTIVE: Experimental studies suggest that excess serum free fatty acid (FFA) levels result in impaired glucose metabolism. This study investigated the relationship between changes in serum FFA levels after glucose intake and type 2 diabetes risk. RESEARCH DESIGN AND METHODS: This observational study included 6,800 individuals without diabetes who underwent a 75-g oral glucose tolerance test. Serum FFA levels were measured before and 30 and 60 min after glucose intake. The percentages of changes in serum FFA levels from 0 to 30 and from 30 to 60 min were compared, and a low rate of change in FFA levels was determined using the receiver operating characteristic curve analysis. RESULTS: Over a mean 5.3-year follow-up period, 485 participants developed type 2 diabetes. After adjusting for plasma glucose levels and indices of insulin resistance and ß-cell function, low rates of change in FFA levels at 0-30 min (adjusted odds ratio [aOR] 1.91; 95% CI 1.54-2.37) and 30-60 min (aOR 1.48; 95% CI 1.15-1.90) were associated with the incidence of type 2 diabetes. Stratified analysis revealed that the low rate of change in FFA levels at 30-60 min (aOR 1.97; 95% CI 1.05-3.69) was associated with the incidence of type 2 diabetes even in participants with normal fasting glucose levels or glucose tolerance. CONCLUSIONS: Changes in serum FFA levels within the 1st h after glucose intake could be a primary predictor of type 2 diabetes. This change may occur prior to the onset of impaired glucose metabolism.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Resistência à Insulina , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/epidemiologia , Ácidos Graxos não Esterificados , Teste de Tolerância a Glucose , Humanos , Insulina
14.
Hypertens Res ; 45(11): 1763-1771, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35948666

RESUMO

We investigated the association of adipose tissue insulin resistance with blood pressure and hypertension incidence, comparing it with hepatic and skeletal muscle insulin resistance. The cross-sectional analysis included 6892 general health checkup examinees (mean age: 69.3 years; 51.3% women and 48.7% men) who had no cardiovascular disease. Of those, 3948 normotensive participants (mean age: 68.4 years; 54.8% women and 45.2% men) were enrolled in the retrospective cohort analysis. The adipose insulin resistance index (Adipo-IR) was calculated as the product of fasting serum insulin and free fatty acid levels. A high adipo-IR, high homeostasis model assessment of insulin resistance (HOMA-IR), and low Matsuda index were indicated based on the optimal cutoff values in a receiver operating characteristic curve analysis. Adipo-IR (ß = 0.096, P < 0.001), HOMA-IR (ß = 0.052, P < 0.001), and Matsuda index (ß = -0.055, P < 0.001) were associated with systolic blood pressure in the cross-sectional analysis. Over a mean 5.3-year follow-up period, 1310 participants developed hypertension. A high adipo-IR (adjusted OR, 1.29; 95% CI, 1.11-1.51), but not HOMA-IR or Matsuda index, was significantly associated with the incidence of hypertension. Moreover, the combination of high adipo-IR with high HOMA-IR or low Matsuda index showed no higher odds of hypertension than a high adipo-IR alone. These results suggest that insulin resistance is associated with blood pressure control regardless of the tissue in which it occurs; however, the risk of hypertension is determined by insulin resistance in adipose tissue rather than in liver or muscle tissue.


Assuntos
Doenças Cardiovasculares , Hipertensão , Resistência à Insulina , Masculino , Feminino , Humanos , Idoso , Resistência à Insulina/fisiologia , Estudos Transversais , Incidência , Estudos Retrospectivos , Tecido Adiposo/metabolismo , Insulina , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/metabolismo , Hipertensão/epidemiologia , Hipertensão/metabolismo , Glucose/metabolismo , Glicemia/metabolismo
15.
J Oral Microbiol ; 14(1): 2110194, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35966937

RESUMO

Background: The effect of oral microbiota on the intestinal microbiota has garnered growing attention as a mechanism linking periodontal diseases to systemic diseases. However, the salivary microbiota is diverse and comprises numerous bacteria with a largely similar composition in healthy individuals and periodontitis patients. Aim: We explored how health-associated and periodontitis-associated salivary microbiota differently colonized the intestine and their subsequent systemic effects. Methods: The salivary microbiota was collected from a healthy individual and a periodontitis patient and gavaged into C57BL/6NJcl[GF] mice. Gut microbial communities, hepatic gene expression profiles, and serum metabolites were analyzed. Results: The gut microbial composition was significantly different between periodontitis-associated microbiota-administered (PAO) and health-associated oral microbiota-administered (HAO) mice. The hepatic gene expression profile demonstrated a distinct pattern between the two groups, with higher expression of lipid and glucose metabolism-related genes. Disease-associated metabolites such as 2-hydroxyisobutyric acid and hydroxybenzoic acid were elevated in PAO mice. These metabolites were significantly correlated with characteristic gut microbial taxa in PAO mice. Conversely, health-associated oral microbiota were associated with higher levels of beneficial serum metabolites in HAO mice. Conclusion: The multi-omics approach used in this study revealed that periodontitis-associated oral microbiota is associated with the induction of disease phenotype when they colonized the gut of germ-free mice.

16.
Cell Rep ; 39(6): 110773, 2022 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-35545035

RESUMO

CD4+Foxp3+ regulatory T cells (Tregs) are essential for homeostasis in the colon, but the mechanism by which local environmental cues determine the localization of colonic Tregs is unclear. Here, we administer indigo naturalis (IN), a nontoxic phytochemical aryl hydrocarbon receptor (AhR) agonist used for treating patients with ulcerative colitis (UC) in Asia, and we show that IN increases Helios+ Tregs and MHC class II+ epithelial cells (ECs) in the colon. Interactions between Tregs and MHC class II+ ECs occur mainly near the crypt bottom in the steady state, whereas Tregs dramatically increase and shift toward the crypt top following IN treatment. Moreover, the number of CD25+ T cells is increased near the surface of ECs in IN-treated UC patients compared with that in patients treated with other therapies. We also highlight additional AhR-signaling mechanisms in intestinal ECs that determine the accumulation and localization of Helios+ Tregs in the colon.


Assuntos
Colite Ulcerativa , Receptores de Hidrocarboneto Arílico , Células Epiteliais , Humanos , Linfócitos T Reguladores
17.
Clin Obes ; 12(1): e12496, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34821047

RESUMO

We investigated the associations of prediabetes categories and obesity with serum free fatty acid (FFA) levels and adipose tissue insulin resistance. This study included 5006 male participants (1779, 1025, 629, 874, and 699 with normal fasting glucose/normal glucose tolerance, isolated impaired fasting glucose [IFG], isolated impaired glucose tolerance [IGT], IFG plus IGT, and diabetes, respectively). Serum FFA levels were assessed before and 30, 60, and 120 min after glucose ingestion, and the total area under the FFA curve (AUCFFA ) was calculated. Adipose insulin resistance index (adipo-IR) was assessed based on fasting FFA and insulin concentrations. Isolated IFG was associated with high fasting FFA levels (OR, 1.35; p < 0.001) and high adipo-IR (OR, 1.82; p < 0.001) only in the nonobesity group. Isolated IGT, IFG plus IGT, and diabetes were associated with high fasting FFA levels, regardless of obesity. Obesity was significantly associated with AUCFFA , and the duration of obesity-related impairment in lipolysis inhibition after glucose ingestion was prolonged in IFG plus IGT and diabetes. These results suggest that IFG and obesity may overlap in their effects on FFA metabolism whereas IGT has significant effects on FFA independent of obesity. Obesity impact on lipolysis may be involved in worsening glucose metabolism.


Assuntos
Resistência à Insulina , Estado Pré-Diabético , Glicemia , Jejum , Ácidos Graxos não Esterificados , Teste de Tolerância a Glucose , Humanos , Insulina , Masculino , Obesidade
18.
J Atheroscler Thromb ; 29(5): 654-666, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-34011802

RESUMO

AIM: Diameter, intima-media thickness (IMT), and flow parameters, including resistance index (RI) and pulsatility index (PI), in the common carotid artery (CCA) are markers of arterial remodeling, atherosclerosis, and vascular resistance, respectively. We investigated the differences among these markers in association with plasma glucose level, serum insulin level, and insulin resistance in participants without cardiovascular disease. METHODS: CCA parameters (including the CCA interadventitial diameter and mean IMT at the time of 75-g oral glucose tolerance testing) were assessed in 4218 participants. RI and PI were assessed in 3380 of these participants. To assess plasma glucose and serum immunoreactive insulin profiles during oral glucose tolerance testing, we used the total areas under the curves (AUCglu and AUCins, respectively). We used the homeostasis model assessment of insulin resistance (HOMA-IR) and the Matsuda index to assess insulin resistance. Insulin secretion was assessed with the HOMA-ß. RESULTS: AUCglu was significantly associated with CCA interadventitial diameter (ß=0.048, P<0.001), RI (ß=0.144, P<0.001), and PI (ß=0.103, P<0.001) but not with mean IMT. AUCins (ß=-0.064, P<0.001) and HOMA-ß (ß=-0.054, P<0.001) were significantly and negatively associated with CCA interadventitial diameter, but not with mean IMT. Both HOMA-IR and Matsuda index were significantly associated with RI and PI. CONCLUSIONS: These findings indicate that all CCA parameters except IMT are associated with impaired glucose metabolism in patients without cardiovascular disease.


Assuntos
Doenças Cardiovasculares , Doenças das Artérias Carótidas , Resistência à Insulina , Insulinas , Glicemia/metabolismo , Doenças Cardiovasculares/metabolismo , Artéria Carótida Primitiva/diagnóstico por imagem , Espessura Intima-Media Carotídea , Humanos , Fatores de Risco
19.
J Am Vet Med Assoc ; 260(1): 56-63, 2021 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-34780349

RESUMO

OBJECTIVE: To evaluate the feasibility of buccal mucosal graft urethroplasty for repairing complete urethral rupture in cats. ANIMALS: 15 male domestic shorthair cats with traumatic complete urethral rupture. PROCEDURES: In each cat, a section of buccal mucosa was harvested, sutured, and formed into a tubule by use of an 8F indwelling catheter as support. This tubular graft was connected to both ruptured ends of the urethra to renew the urinary passage. The catheter was left in place until the absence of leakage was confirmed by positive contrast retrograde urethrography. After spontaneous urination was confirmed, cats were discharged from the hospital. Six months later, urethrography was repeated and owners were asked to score their cats' urinary function and quality of life. RESULTS: 13 cats recovered well following surgery, with no complications in the oral cavity or surgical site and no signs of difficulty or discomfort when urinating. Urethrography 2 weeks and 6 months after surgery revealed no stricture or leakage in the abdominal cavity. The 2 remaining cats developed a urethral stricture and underwent second surgery with a successful outcome. At the 6-month follow-up, 14 cats had only mild urinary signs, and 1 cat had incontinency. Owners indicated they were delighted (n = 14) or pleased (1) with their cats' quality of life. CLINICAL RELEVANCE: Buccal mucosa was found to be a good source of graft tissue for performance of urethroplasty in male cats, yielding satisfactory outcomes with few postoperative complications. The described technique may be suitable for severe and complicated cases of urethral rupture in male cats.


Assuntos
Doenças do Gato , Estreitamento Uretral , Animais , Doenças do Gato/cirurgia , Gatos , Masculino , Mucosa Bucal/transplante , Qualidade de Vida , Resultado do Tratamento , Uretra/cirurgia , Estreitamento Uretral/cirurgia , Estreitamento Uretral/veterinária
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