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1.
Neuro Endocrinol Lett ; 45(2)2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38583186

RESUMO

OBJECTIVES: This preliminary study aims to examine the effects of tomato juice, which can be easily consumed regularly, on the physical and psychological states of healthy adults in the Coronavirus era. DESIGN: Prospective observational study. MATERIALS AND METHODS: Ten healthy adults (mean age, 39.7±4.2 years) who consumed 180 mL of tomato juice twice daily for 4 weeks were enrolled. Measurements were taken before and after 4 weeks of consumption for the items below. Five salivary stress biomarkers (cortisol, α-amylase, secretory immunoglobulin A, chromogranin A, and oxytocin) were measured using approximately 1ml of passively pooled saliva samples, which were stored at -20°C until measurement. Autonomic nervous system (ANS) activity was evaluated using an acceleration pulse wave meter. Skin moisture content and transepidermal water loss (TEWL) were measured using Multi Display devices® MDD4 with specific probes. Subjective psychological states were assessed using Profile of Mood Status (POMS2®) and a survey on skin condition was conducted. RESULTS: As for salivary stress biomarkers, tomato juice intake reduced cortisol and significantly increased oxytocin levels (p = 0.0427). No significant changes were observed in ANS activity. POMS2® results showed a significant decrease in confusion and bewilderment (p = 0.0207). Skin moisture content increased significantly (p = 0.0011), whereas TEWL decreased. The skin condition survey revealed significant changes in 10 parameters. CONCLUSIONS: Tomato juice, which can be easily consumed regularly, may alleviate the stress of healthy adults in the Coronavirus era, supported by positive changes in salivary stress biomarker levels, skin moisture content, TEWL, and POMS2® results of this preliminary study.

2.
Gut Microbes ; 16(1): 2333463, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38545880

RESUMO

The ectopic gut colonization by orally derived pathobionts has been implicated in the pathogenesis of various gastrointestinal diseases, including inflammatory bowel disease (IBD). For example, gut colonization by orally derived Klebsiella spp. has been linked to IBD in mice and humans. However, the mechanisms whereby oral pathobionts colonize extra-oral niches, such as the gut mucosa, remain largely unknown. Here, we performed a high-density transposon (Tn) screening to identify genes required for the adaptation of an oral Klebsiella strain to different mucosal sites - the oral and gut mucosae - at the steady state and during inflammation. We find that K. aerogenes, an oral pathobiont associated with both oral and gut inflammation in mice, harbors a newly identified genomic locus named "locus of colonization in the inflamed gut (LIG)" that encodes genes related to iron acquisition (Sit and Chu) and host adhesion (chaperon usher pili [CUP] system). The LIG locus is highly conserved among K. aerogenes strains, and these genes are also present in several other Klebsiella species. The Tn screening revealed that the LIG locus is required for the adaptation of K. aerogenes in its ectopic niche. In particular, we determined K. aerogenes employs a CUP system (CUP1) present in the LIG locus for colonization in the inflamed gut, but not in the oral mucosa. Thus, oral pathobionts likely exploit distinct adaptation mechanisms in their ectopically colonized intestinal niche compared to their native niche.


Assuntos
Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Humanos , Animais , Camundongos , Klebsiella/genética , Doenças Inflamatórias Intestinais/patologia , Inflamação , Mucosa Bucal
3.
Kyobu Geka ; 77(1): 27-33, 2024 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-38459842

RESUMO

BACKGROUND: Occlusion of the left atrial appendage( LAA) may prevent stroke in patients with atrial fibrillation. In this study, we reviewed various types of LAA occlusion techniques and results of patients underwent surgical LAA closure. METHODS: Between 2004 and 2022, 182 patients who underwent surgical LAA closure were enrolled in this study. RESULTS: The surgical LAA closure consisted of 90 cases of closure device, AtriCure, 63 cases of surgical excision, 13 cases of stapler excision, 3 cases of ligation, and 13 cases of internal suture ligation. During the follow-up period, there were no deaths owing to cardiogenic emboli and no cerebral infarctions. CONCLUSIONS: Regardless of the surgical techniques, LAA closure was effective in preventing cardiogenic stroke. The AtriClip is a safe, simple, and effective and thoracoscopic LAA closure using AtriClip is expected as a less-invasive LAA management.


Assuntos
Apêndice Atrial , Fibrilação Atrial , Procedimentos Cirúrgicos Cardíacos , Acidente Vascular Cerebral , Humanos , Resultado do Tratamento , 60589 , Procedimentos Cirúrgicos Cardíacos/métodos , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Fibrilação Atrial/cirurgia , Apêndice Atrial/cirurgia , Ecocardiografia Transesofagiana
4.
BMC Cardiovasc Disord ; 24(1): 139, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38438846

RESUMO

OBJECTIVE: In patients with stable hemodynamic status after an acute coronary syndrome (ACS), coronary artery bypass grafting (CABG) after preoperative investigations can provide outcomes comparable to those of emergency surgery. However, no established guidelines exist regarding the preparation period before surgery. We report the results of the use of an inpatient cardiac rehabilitation program followed by CABG after an ACS to improve post-operative outcomes and prognosis after discharge. METHODS: From 2005 to 2017, 471 patients underwent either isolated or combined CABG at our institution, and of those, the 393 who received isolated CABG were included in the analysis. Twenty-seven patients (6.9%) were admitted with ACS and underwent preoperative rehabilitation before undergoing CABG, with a subsequent review of surgical morbidity and mortality rates. Propensity score matching yielded a cohort of 26 patients who underwent preoperative rehabilitation (group A) and 26 controls (group B). Preoperative characteristics were similar between groups. RESULTS: The completion rate of the rehabilitation program was 96.3%. All programs were conducted with inpatients, with an average length of stay of 23 ± 12 days. All patients completed in-bed exercises, and 85% completed out-of-bed exercises. The 30-day postoperative mortality was 0% in both groups A and B, and the rate of postoperative major adverse cardiac or cerebrovascular events at 12 months did not differ significantly between groups (7.7% vs 3.9%, respectively; p = 1.0). The duration of mechanical ventilation (1.3 ± 0.3 vs 1.5 ± 0.3 days, respectively; p = 0.633), length of intensive care unit stay (4.4 ± 2.1 vs 4.8 ± 2.3 days, respectively; p = 0.584) and length of hospital stay (25 ± 13 vs 22 ± 9 days, respectively; p = 0.378) did not differ significantly between groups. CONCLUSIONS: No complications of preoperative rehabilitation were observed, suggesting that it is an acceptable option for patients who experience ACS and undergo CABG. These results are promising in offering more robust designs of future trials.


Assuntos
Síndrome Coronariana Aguda , Humanos , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/cirurgia , Exercício Pré-Operatório , Ponte de Artéria Coronária/efeitos adversos , Coração , Hospitais
5.
Biochem Biophys Res Commun ; 704: 149673, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38401305

RESUMO

Epidermal growth factor receptor (EGFR)-mediated signal transduction controls cell growth and proliferation. The signaling pathway is regulated so that it is activated only by external EGF stimuli, but the mechanisms that prevent EGF-independent spontaneous activation of EGFR-mediated signaling are unknown. Here we report cholesterol depletion activates EGFR-mediated signaling without EGF. We applied automated single-molecule imaging to EGFR and characterized the lateral diffusion and cluster formation on cholesterol-depleted and cholesterol-supplemented membranes. In cells in which cholesterol was depleted by methyl-ß-cyclodextrin (MßCD) treatment, EGFR exhibited a reduction in lateral diffusion, an acceleration of cluster formation, and autophosphorylation without EGF. Concurrently, extracellular signal-regulated kinase (ERK), which is regulated by EGFR-mediated signaling, exhibited phosphorylation and nuclear translocation without EGF. These cholesterol depletion-induced changes were similar, albeit less efficient, to those that occurred with EGF stimulation in normal cells without MßCD, indicating the spontaneous activation of EGFR signaling. The exogenous supplementation of cholesterol suppressed the MßCD-induced spontaneous activation of EGFR and ERK nuclear translocation. Single-molecule imaging of EGFR in a large number of cells revealed cell-to-cell heterogeneity, with a sub-population showing a high ability for spontaneous activation. These results provide evidence that EGFR-mediated signaling is properly regulated by cholesterol metabolism to prevent uncontrolled spontaneous activation.


Assuntos
Fator de Crescimento Epidérmico , Transdução de Sinais , Fator de Crescimento Epidérmico/farmacologia , Fator de Crescimento Epidérmico/metabolismo , Receptores ErbB/metabolismo , Fosforilação , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Colesterol/metabolismo
6.
Pediatr Nephrol ; 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38329589

RESUMO

Congenital anomalies of the kidney and urinary tract (CAKUT) can be a part of the VACTERL association, which represents the non-random combination of the following congenital anomalies: vertebral anomalies, anal anomalies, cardiac anomalies, tracheal-esophageal anomalies, kidney anomalies, and limb anomalies. VACTERL association is generally considered to be a non-genetic condition. Exceptions include a patient with a heterozygous nonsense SALL4 variant and anal stenosis, tetralogy of Fallot, sacro-vertebral fusion, and radial and thumb anomalies. SALL4 encodes a transcription factor that plays a critical role in kidney morphogenesis. Here, we report a patient with VACTERL association and a heterozygous 128-kb deletion spanning SALL4 who presented with renal hypoplasia, radial and atrio-septal defects, and patent ductus arteriosus. The present report of SALL4 deletion, in addition to a previously reported patient with VACTERL association phenotype and SALL4 nonsense mutation, further supports the notion that SALL4 haploinsufficiency can lead to VACTERL association.

7.
J Dermatol ; 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38414176

RESUMO

A 67-year-old man had taken the janus kinase (JAK) inhibitor, tofacitinib, for ulcerative colitis. He was referred to our department for a refractory ulcer on his lower leg. We suspected vasculitis and performed skin biopsy. Histopathological examination showed multinucleated giant cells in the epidermis and fibrinoid degeneration of small vessels in the upper dermis. Varicella zoster virus (VZV) DNA was detected by polymerase chain reaction and we diagnosed the patient with atypical vasculitis-like herpes zoster. The patient was treated with oral valacyclovir, but the rash persisted and took 2 months to heal. Immunostaining using anti-VZV antibody was positive mainly in epidermal keratinocytes, but was also observed to be positive in cells in the dermis. We further performed RNA in situ hybridization using a VZV ORF9 mRNA probe and clearly showed that the distribution of VZV mRNA extended into the dermis, including the dermal vessel walls and the eccrine sweat glands as well as the epidermis. The internal administration of JAK inhibitors may induce regional widespread VZV infection including vessels and involved in the formation of prolonged vasculitis-like manifestation. RNA in situ hybridization can be a potent tool for detecting the spread of VZV infection in the skin.

8.
Biosci Biotechnol Biochem ; 88(3): 237-241, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38006236

RESUMO

The yeast Saccharomyces cerevisiae plays a pivotal role in the production of fermented foods by converting sugars in ingredients into ethanol through alcoholic fermentation. However, how accurate is our understanding of its biological significance? Although yeast is essential to produce alcoholic beverages and bioethanol, yeast does not yield ethanol for humankind. Yeast obtains energy in the form of ATP for its own vital processes through alcoholic fermentation, which generates ethanol as a byproduct. The production of ethanol may have more significance for yeast, since many other organisms do not produce ethanol, a highly toxic substance, to obtain energy. The key to address this issue has not been found using conventional microbiology, where yeasts are isolated and cultured in pure form. This review focuses on a possible novel role of yeast alcohol fermentation, which is revealed through our recent studies of microbial interactions.


Assuntos
Lactobacillales , Saccharomyces cerevisiae , Bebidas Alcoólicas/análise , Simbiose , Fermentação , Etanol
9.
Heart Vessels ; 39(1): 65-74, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37695542

RESUMO

The causes of adrenal Cushing's syndrome (CS) encompass a wide spectrum of adrenal cortisol proliferations that exhibit clinical and molecular heterogeneity. The aims of our study were to investigate whether clinical and molecular heterogeneity influences endothelial function and metabolic abnormalities in patients with cortisol-producing adenoma (CPA). We retrospectively enrolled 25 patients with CPA and 45 patients with essential hypertension (EH). All CPAs were studied by direct sequencing of PRKACA. Flow-mediated vasodilation (FMD), an index of vascular endothelial function, was significantly lower in CS and subclinical CS (SCS) groups than in the EH group. FMD impairment did not differ significantly between CS and SCS groups. No differences in FMD were seen between PRKACA mutant and wild-type groups. FMD correlated negatively with hemoglobin A1c (HbA1c) in both PRKACA mutant and wild-type groups, as well as in CS and SCS groups. After adrenalectomy, systolic blood pressure (SBP) and HbA1c decreased significantly from baseline in the CS group, and SBP and low-density lipoprotein cholesterol (LDL-C) decreased significantly from baseline in the SCS group. While SBP and LDL-C decreased significantly from baseline in patients with wild-type PRKACA, only HbA1c decreased from baseline in patients harboring PRKACA mutations. Our data showed that patients with CPA have impaired endothelial function compared with EH patients and suggest the need for strict monitoring of atherosclerosis, even in patients with SCS or without PRKACA mutation.


Assuntos
Adenoma , Doenças Cardiovasculares , Síndrome de Cushing , Humanos , Hidrocortisona/metabolismo , Síndrome de Cushing/genética , Estudos Retrospectivos , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/genética , LDL-Colesterol , Hemoglobinas Glicadas , Fatores de Risco , Adenoma/genética
10.
Forensic Toxicol ; 42(1): 1-6, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37480483

RESUMO

PURPOSE: The analysis of water-soluble herbicides, including glyphosate (Glyp), glufosinate (Gluf), paraquat (PQ), and diquat (DQ), is time-consuming and expensive because they cannot be analyzed using general toxicological screening methods. Thus, this study aimed to develop a simple and rapid method to simultaneously analyze these compounds without any derivatization nor ion-pairing reagents. METHODS: The analytes were separated using hydrophilic interaction liquid chromatography and detected using tandem mass spectrometry. The developed method was applied to plant and biological samples assuming criminal damage and poisoning cases, respectively. RESULTS: All analytes were separated well and detected with good peak shapes. For plant samples, the herbicides were specifically detected from withered leaves using a simple extraction method. For biological samples, quantitative analysis was successfully validated, and the limit of quantification values of Glyp and Gluf were 0.2 µg/mL, and those of PQ and DQ were 1 ng/mL. CONCLUSION: The developed method had sufficient performance for practical forensic applications including poisoning cases and malicious uses to damage commercial crops.


Assuntos
Aminobutiratos , Herbicidas , Diquat , Paraquat , Água
11.
J Dermatol ; 51(2): 234-242, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38149403

RESUMO

Acute zoster-associated pain develops in most patients with herpes zoster. Nonopioid analgesics are usually used to treat acute zoster-associated pain but are frequently ineffective. We administered intravenous fosphenytoin, the prodrug of phenytoin, to patients with acute zoster-associated pain to examine its analgesic efficacy and safety. At 13 medical institutions in Japan, we conducted a phase II, double-blind, placebo-controlled, randomized trial of intravenous fosphenytoin in Japanese inpatients with acute zoster-associated pain for whom nonopioid analgesics had shown an insufficient analgesic effect. The patients were randomly assigned (1:1:1) to receive a single intravenous dose of fosphenytoin at 18 mg/kg (high dose), a single intravenous dose of fosphenytoin at 12 mg/kg (low dose), or placebo. The primary endpoint was the mean change per hour (slope) in the numerical rating scale score from the baseline score until 120 min after dosing. Seventeen patients were randomly assigned to the low-dose fosphenytoin group (n = 6, median age 62.5 years, range 39-75 years), high-dose fosphenytoin group (n = 5, median age 69.0 years, range 22-75 years), and placebo group (n = 5, median age 52.0 years, range 38-72 years). One patient was excluded because of investigational drug dilution failure. This study was discontinued because of the influences of coronavirus disease 2019. The slope was significantly lower in the high- and low-dose fosphenytoin groups than in the placebo group (P < 0.001 and P = 0.016, respectively). Responsiveness to intravenous fosphenytoin (≥2-point reduction in the numerical rating scale score from baseline to 120 min after dosing) was inferred at plasma total phenytoin concentrations of 10-15 µg/mL. Treatment-emergent adverse events caused no safety concerns in the clinical setting and intravenous fosphenytoin was well tolerated. Intravenous fosphenytoin appears to be an effective and promising alternative treatment for acute zoster-associated pain. Trial Registration: ClinicalTrials.gov NCT04139330.


Assuntos
Herpes Zoster , Dor , Fenitoína , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Analgésicos , Analgésicos não Narcóticos/farmacologia , Método Duplo-Cego , Herpes Zoster/complicações , Herpes Zoster/tratamento farmacológico , Herpesvirus Humano 3 , Dor/tratamento farmacológico , Dor/etiologia , Fenitoína/efeitos adversos
12.
Endocrine ; 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-38087188

RESUMO

OBJECTIVE: Aldosterone-producing adenoma (APA) and bilateral idiopathic hyperaldosteronism (IHA) are the most common subtypes of primary aldosteronism (PA), and the PA subtype dictates the treatment options. This study aimed to identify predictors of declined estimated glomerular filtration rate (eGFR) following each treatment in patients with APA and IHA. METHODS: We retrospectively investigated 45 patients with APA who had undergone adrenalectomy (ADX) and 37 patients with IHA who had received treatment with a mineralocorticoid receptor antagonist (MRA) to identify pre-treatment risk factors for eGFR decline during the post-treatment follow-up period. RESULTS: Patients with APA who underwent ADX exhibited higher eGFR declines than patients with IHA treated with MRA at the 6-month post-treatment evaluation point. A high preoperative plasma aldosterone concentration (PAC) in patients with APA and a high body mass index (BMI) in patients with IHA were identified as independent predictors of higher eGFR decline at 6 months post-treatment (ß=0.42 and ß=0.36, respectively). In patients with APA, the cutoff PAC to best predict a 20% decrease in eGFR following ADX, as determined by receiver operating characteristic analysis, was 524 pg/mL. In patients with IHA, the cutoff BMI to best predict a 10% decrease in eGFR following MRA administration was 25.3 kg/m2. In addition, lower preoperative flow-mediated vasodilation was associated with eGFR decline after ADX in patients with APA. CONCLUSIONS: Greater attention should be given to the above-mentioned risk factors to prevent renal impairment following each treatment in patients with both APA and IHA.

13.
Acta Med Okayama ; 77(6): 651-653, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38145940

RESUMO

A patient was born with a mass at the base of the thumb approximately 1.5 cm in diameter on the radial side of the fingers. The mass had globular swelling filled with hemorrhagic fluid and was dark red. X-rays and histology of the excised specimen suggested the diagnosis of gangrene and torsion of polydactyly. Prenatal torsion of polydactyly is not a common occurrence; moreover, prenatal torsion of polydactyly has only been found in ulnar polydactyly. Our case is a novel case of radial polydactyly that was gangrenous at birth owing to prenatal torsion. Diagnosing such a mass at the base of the thumb is important.


Assuntos
Polidactilia , Polegar , Recém-Nascido , Humanos , Polegar/cirurgia , Polegar/patologia , Gangrena/cirurgia , Polidactilia/diagnóstico por imagem , Polidactilia/cirurgia , Dedos/patologia
14.
Sci Rep ; 13(1): 20262, 2023 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-37985889

RESUMO

Not all patients with ulcerative colitis (UC) respond initially to treatment with biologic agents, and predicting their efficacy prior to treatment is difficult. Vedolizumab, a humanized monoclonal antibody against alpha 4 beta 7 (α4ß7) integrin, suppresses immune cell migration by blocking the interaction between α4ß7 integrin and mucosal addressin cell adhesion molecule 1. Reports about histological features that predict vedolizumab efficacy are scarce. So, we examined the association between histological features and vedolizumab efficacy. This was a multicenter, retrospective study of patients with UC treated with vedolizumab. Biopsy specimens taken from the colonic mucosa prior to vedolizumab induction were used, and the areas positively stained for CD4, CD68, and CD45 were calculated. Clinical and histological features were compared between those with and without remission at week 22, and the factors associated with clinical outcomes were identified. We enrolled 42 patients. Patients with a high CD4+ infiltration showed a better response to vedolizumab [odds ratio (OR) = 1.44, P = 0.014]. The concomitant use of corticosteroids and high Mayo scores had a negative association with the vedolizumab response (OR = 0.11, P = 0.008 and OR = 0.50, P = 0.009, respectively). Histological evaluation for CD4+ cell infiltration may be helpful in selecting patients who can benefit from vedolizumab.


Assuntos
Colite Ulcerativa , Humanos , Colite Ulcerativa/metabolismo , Estudos Retrospectivos , Fármacos Gastrointestinais/uso terapêutico , Fármacos Gastrointestinais/farmacologia , Integrinas , Resultado do Tratamento
15.
J Endocr Soc ; 7(12): bvad137, 2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-38024646

RESUMO

Context: GH supplementation for GH deficiency (GHD) has been reported to decrease high-sensitivity C-reactive protein (hs-CRP), an inflammatory marker; however, the association between GHD and hs-CRP remains unclear. Objective: We aimed to clarify the impact of impaired GH secretion due to pituitary masses on hs-CRP levels. Methods: We retrospectively examined the association between GH secretion, assessed using GH-releasing peptide-2, and serum hs-CRP levels before and a year after the pituitary surgery in patients with nonfunctioning pituitary neuroendocrine tumor or Rathke cleft cyst. Results: Among 171 patients, 55 (32%) presented with severe GHD (peak GH response to GH-releasing peptide-2 < 9 ng/mL). Serum hs-CRP levels were significantly higher in patients with severe GHD than in those without (P < .001) and significantly correlated with the peak GH (r = -0.50, P < .001). Multiple regression analyses showed that the peak GH significantly and negatively predicted hs-CRP levels (ß = -0.345; 95% CI, -0.533 to -0.158) and the lowest quartile of the peak GH (<5.04 ng/mL) were significantly associated with increase in hs-CRP levels (exp [ß] = 1.840; 95% CI, 1.209 to 2.801), after controlling for other anterior hormones and metabolic parameters. Postoperative change in the peak GH (N = 60) significantly predicted change in hs-CRP levels (ß = -0.391; 95% CI, -0.675 to -0.108), independent of alterations in other anterior hormones and metabolic parameters. Conclusion: The inverse association between GH secretion and hs-CRP levels highlights the protective role of GH in the increase in hs-CRP.

16.
Eur J Med Genet ; 66(12): 104870, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37879495

RESUMO

Tricho-rhino-phalangeal syndrome type I (TRPS1), caused by pathogenic variants in the transcriptional repressor GATA-binding 1 gene (TRPS1), is characterized by ectodermal and skeletal anomalies including short stature and sparse scalp hair during infancy. TRPS1 encodes a zinc finger protein transcription factor that contributes to bone homeostasis by regulating perichondral mineralization, chondrocyte proliferation, and apoptosis. Here, a male infant aged 14 months presented with sparse scalp hair, deformed nails, fused teeth, and postnatal growth retardation without neurodevelopmental disorder. As endocrinological measurements revealed low serum zinc levels, he was treated with zinc acetate hydrate, which improved his growth velocity and scalp hair. Whole-exome sequencing revealed that this patient harbored a novel pathogenic de novo heterozygous TRPS1 frameshift variant, c.2819_2822del, p.(His940Argfs*6). Zinc deficiency induces zinc finger protein dysfunction via effects on protein folding and assembly, affecting target gene transcription and apoptosis. The symptoms of TRPS1 are similar to those caused by inadequate levels of zinc, an essential trace element with important roles in tissue growth and repair. Accompanying zinc deficiency may have affected the function of important zinc finger proteins, resulting in phenotypic deterioration. Analysis of zinc metabolism in patients harboring TRPS1 variants will enhance understanding the variety of phenotypes of TRPS1.


Assuntos
Proteínas de Ligação a DNA , Síndrome de Langer-Giedion , Humanos , Masculino , Proteínas de Ligação a DNA/genética , Proteínas Repressoras/genética , Fatores de Transcrição/genética , Síndrome de Langer-Giedion/genética , Zinco
17.
Kidney Blood Press Res ; 48(1): 688-700, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37866351

RESUMO

INTRODUCTION: Renin-angiotensin system inhibitors have been reported to exert protective effects against organ damage and failure; however, the impact of the direct renin inhibitor as monotherapy has not been assessed. Here, we investigated the effects of 24-week monotherapy with aliskiren compared to amlodipine in hypertensive patients with type 2 diabetes or obesity. METHODS: In this randomized intervention study, 62 adult hypertensive patients with visceral obesity (defined as a body mass index [BMI] greater than 25 kg/m2 and a visceral adipose tissue area [VFA] greater than 100 cm2) or type 2 diabetes mellitus (age 57 ± 13, 65% men, BMI 28.8 ± 4.8 kg/m2, VFA 134.8 ± 47.0 cm2, blood pressure 141 ± 16/86 ± 13 mm Hg) were randomized to receive 24-week treatment with aliskiren (max. 300 mg) or amlodipine (max. 10 mg). The primary outcome was the change in VFA at 24 weeks post-treatment. RESULTS: Change in VFA did not differ significantly from baseline in either group. Systolic blood pressure significantly decreased at 12 weeks (-10 mm Hg, p = 0.001) and 24 weeks (-10 mm Hg, p = 0.001) in the amlodipine group and at 24 weeks (-11 mm Hg, p = 0.001) in the aliskiren group. Diastolic blood pressure significantly decreased at 24 weeks (-6 mm Hg, p = 0.009) only in the amlodipine group. Although the estimated glomerular filtration rates did not significantly change in either group, the logarithm of urinary albumin excretion significantly decreased at 24 weeks only in the aliskiren group (-0.60, p < 0.001). The 24-week changes in the urinary albumin excretion significantly correlated with the changes in the plasma renin activity in the aliskiren group (r = 0.51, p = 0.008). CONCLUSION: Aliskiren monotherapy did not show any superiority to amlodipine monotherapy on VFA, estimated glomerular filtration rates, or urinary albumin excretion in obese or type 2 diabetic hypertensive patients.


Assuntos
Diabetes Mellitus Tipo 2 , Hipertensão , Masculino , Adulto , Humanos , Pessoa de Meia-Idade , Idoso , Feminino , Anlodipino/farmacologia , Anlodipino/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Renina/farmacologia , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Amidas/farmacologia , Amidas/uso terapêutico , Fumaratos/farmacologia , Fumaratos/uso terapêutico , Pressão Sanguínea , Obesidade/complicações , Obesidade/tratamento farmacológico , Quimioterapia Combinada , Albuminas
18.
Microscopy (Oxf) ; 2023 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-37702250

RESUMO

We developed an in-situ shear test system suitable for transmission electron microscopy (TEM) observations, which enabled us to examine the shear deformation behaviours inside soft materials at nanoscale resolutions. This study was conducted on a nanoparticle-filled rubber to investigate its nanoscale deformation behaviour under a large shear strain. First, the shear deformation process of a large area in the specimen was accurately examined and proven to exhibit an almost perfect simple shear. At the nanoscale, voids grew along the maximum principal strain during shear deformation. In addition, the nanoscale regions with rubber and silica aggregates exhibited deformation behaviours similar to the global shear deformation of the specimen. Although the silica aggregates exhibited displacement along the shearing directions, rotational motions were also observed owing to the torque generated by the local shear stress. This in-situ shear deformation system for TEM enabled us to understand the nanoscale origins of the mechanical properties of soft materials, particularly polymer composites.

19.
Polymers (Basel) ; 15(18)2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37765692

RESUMO

In this paper, novel colorless polyimides (PIs) derived from 5,5'-bis(2,3-norbornanedicarboxylic anhydride) (BNBDA) were presented. The results of single-crystal X-ray structural analysis using a BNBDA-based model compound suggested that it had a unique steric structure with high structural linearity. Therefore, BNBDA is expected to afford new colorless PI films with an extremely high glass transition temperature (Tg) and a low linear coefficient of thermal expansion (CTE) when combined with aromatic diamines with rigid and linear structures (typically, 2,2'-bis(trifluoromethyl)benzidine (TFMB)). However, the polyaddition of BNBDA and TFMB did not form a PI precursor with a sufficiently high molecular weight; consequently, the formation of a flexible, free-standing PI film via the two-step process was inhibited because of its brittleness. One-pot polycondensation was also unsuccessful in this system because of precipitation during the reaction, probably owing to the poor solubility of the initially yielded BNBDA/TFMB imide oligomers. The combinations of (1) the structural modification of the BNBDA/TFMB system, (2) the application of a modified one-pot process, in which the conditions of the temperature-rising profile, solvents, azeotropic agent, catalysts, and reactor were refined, and (3) the optimization of the film preparation conditions overcame the trade-off between low CTE and high film toughness and afforded unprecedented PI films with well-balanced properties, simultaneously achieving excellent optical transparency, extremely high Tg, sufficiently high thermal stability, low CTE, high toughness, relatively low water uptake, and excellent solution processability.

20.
J Cutan Med Surg ; 27(5): 481-486, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37537972

RESUMO

BACKGROUND: The most important problem with local injections of botulinum toxin type A (BTX-A) in palmar hyperhidrosis is pain during the injections. OBJECTIVES: We evaluated therapeutic effectiveness and pain of local injections of BTX-A using needle-free direct administration system. METHODS: We performed BTX-A local injection therapy using a conventional injection needle in the left hand and a needle-free direct administration system in the right hand. RESULTS: A reduction in the quantity of perspiration was observed 4 weeks after administration of both Needle and Needle-free BTX-A, and reduction was maintained throughout 28 weeks observation period. Both hyperhidrosis Disease Severity Scale scores and Dermatology Life Quality Index for hands treated with Needle BTX-A and hands treated with Needle-free BTX-A had decreased significantly by 4 weeks after treatment. Pain visual analog scale scores and the degree of pain were significantly lower in hands treated with Needle-free BTX-A than in hands treated with Needle BTX-A. CONCLUSIONS: When the trigger of the pressurized needle-free injector device is activated, the gas powered driving pressure propels BTX-A through an orifice (0.13 mm) about four times narrower than a 30 G needle at very high speed. As most pain occurs during the needle prick itself, the advantage of a small orifice coupled with high-speed penetration of BTX-A through the pressurized device results in reduced pain during administration. The needle-free direct administration system administers the injectate under the skin without a visible needle.


Assuntos
Toxinas Botulínicas Tipo A , Hiperidrose , Humanos , Toxinas Botulínicas Tipo A/uso terapêutico , Resultado do Tratamento , Hiperidrose/tratamento farmacológico , Dor/tratamento farmacológico , Dor/etiologia , Dor/prevenção & controle , Mãos
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