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61.
Synergistic interaction between diene valepotriates from Valeriana glechomifolia Meyer (Valerianaceae) and classical antidepressants: an isobolographic analysis
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63.
Stephen I. Stone Damien Abreu Janet B. McGill Fumihiko Urano 《Journal of diabetes and its complications》2021,35(1):107618
The endoplasmic reticulum (ER) lies at the crossroads of protein folding, calcium storage, lipid metabolism, and the regulation of autophagy and apoptosis. Accordingly, dysregulation of ER homeostasis leads to β-cell dysfunction in type 1 and type 2 diabetes that ultimately culminates in cell death. The ER is therefore an emerging target for understanding the mechanisms of diabetes mellitus that captures the complex etiologies of this multifactorial class of metabolic disorders. Our strategy for developing ER-targeted diagnostics and therapeutics is to focus on monogenic forms of diabetes related to ER dysregulation in an effort to understand the exact contribution of ER stress to β-cell death. In this manner, we can develop personalized genetic medicine for ERstress-related diabetic disorders, such as Wolfram syndrome. In this article, we describe the phenotypes and molecular pathogenesis of ERstress-related monogenic forms of diabetes. 相似文献
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65.
Richarda M. de Voer Illja J. Diets Rachel S. van der Post Robbert D.A. Weren Eveline J. Kamping Tessa J.J. de Bitter Lisa Elze Rob H.A. Verhoeven Elisa Vink-Börger Astrid Eijkelenboom Arjen Mensenkamp Iris D. Nagtegaal Marjolijn C.J. Jongmans Marjolijn J.L. Ligtenberg 《Clinical gastroenterology and hepatology》2021,19(8):1642-1651.e8
66.
The effects of postponing prophylactic treatment on long-term outcome in patients with severe hemophilia 总被引:7,自引:1,他引:7
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Fischer K van der Bom JG Mauser-Bunschoten EP Roosendaal G Prejs R de Kleijn P Grobbee DE van den Berg M 《Blood》2002,99(7):2337-2341
To prevent hemophilic arthropathy, prophylactic treatment of children with severe hemophilia should be started before joint damage has occurred. However, treatment is expensive, and the burden of regular venipunctures in young children is high. With the aim of providing information on starting prophylaxis on the basis of individual patient characteristics, the effect of postponing prophylaxis on long-term arthropathy was studied in a cohort of 76 patients with severe hemophilia born between 1965 and 1985. The median age at first joint bleed was 2.2 years (range, 0.2-5.8). Prophylaxis was started at a median age of 6 years (interquartile range [IQR], 4-9), and the median annual clotting factor use on prophylaxis was 1750 IU/kg/y (31 IU/kg/wk). Hemophilic arthropathy was measured by the Pettersson score (maximum, 78 points). At a median age of 19 years, the median Pettersson score was 7 points (IQR, 0-17). After 2 decades of follow-up, the Pettersson score was 8% higher (95% confidence interval, 1%-16%) for every year prophylaxis was postponed after the first joint bleed. This effect was independent of age at Pettersson score, age at first joint bleed, and prophylactic dose used. In conclusion, most patients have their first joint bleed after the age of 2 years. Patients who start prophylaxis soon after the first joint bleed show little arthropathy in adulthood. The longer the start of prophylaxis is postponed after the first joint bleed, the higher the risk of developing arthropathy. 相似文献
67.
P.L.M. Dalpiaz A.Z. Lamas I.F. Caliman A.R.S. Medeiros G.R. Abreu M.R. Moysés T.U. Andrade M.F. Alves A.K. Carmona N.S. Bissoli 《Brazilian journal of medical and biological research》2013,46(2):171-177
Sex hormones modulate the action of both cytokines and the renin-angiotensin
system. However, the effects of angiotensin I-converting enzyme (ACE) on the
proinflammatory and anti-inflammatory cytokine levels in male and female
spontaneously hypertensive rats (SHR) are unclear. We determined the
relationship between ACE activity, cytokine levels and sex differences in SHR.
Female (F) and male (M) SHR were divided into 4 experimental groups each (n =
7): sham + vehicle (SV), sham + enalapril (10 mg/kg body weight by gavage),
castrated + vehicle, and castrated + enalapril. Treatment began 21 days after
castration and continued for 30 days. Serum cytokine levels (ELISA) and ACE
activity (fluorimetry) were measured. Male rats exhibited a higher serum ACE
activity than female rats. Castration reduced serum ACE in males but did not
affect it in females. Enalapril reduced serum ACE in all groups. IL-10 (FSV =
16.4 ± 1.1 pg/mL; MSV = 12.8 ± 1.2 pg/mL), TNF-α (FSV = 16.6 ± 1.2 pg/mL; MSV =
12.8 ± 1 pg/mL) and IL-6 (FSV = 10.3 ± 0.2 pg/mL; MSV = 7.2 ± 0.2 pg/mL) levels
were higher in females than in males. Ovariectomy reduced all cytokine levels
and orchiectomy reduced IL-6 but increased IL-10 concentrations in males.
Castration eliminated the differences in all inflammatory cytokine levels (IL-6
and TNF-α) between males and females. Enalapril increased IL-10 in all groups
and reduced IL-6 in SV rats. In conclusion, serum ACE inhibition by enalapril
eliminated the sexual dimorphisms of cytokine levels in SV animals, which
suggests that enalapril exerts systemic anti-inflammatory and anti-hypertensive
effects. 相似文献
68.
Nicolas J. Abreu Bhavani Selvaraj Kristen V. Truxal Melissa Moore-Clingenpeel Nicholas A. Zumberge Kelly A. McNally Kim L. McBride Mai-Lan Ho Kevin M. Flanigan 《Molecular genetics and metabolism》2021,132(2):193-200
ObjectiveTo quantify changes in segmented brain volumes over 12 months in children with mucopolysaccharidosis types IIIA and IIIB (MPS IIIA and IIIB).MethodsIn order to establish suitable outcome measures for clinical trials, twenty-five children greater than 2 years of age were enrolled in a prospective natural history study of MPS IIIA and IIIB at Nationwide Children's Hospital. Data from sedated non-contrast brain 3 T MRIs and neuropsychological measures were reviewed from the baseline visit and at 12-month follow-up. No intervention beyond standard clinical care was provided. Age- and sex-matched controls were gathered from the National Institute of Mental Health Data Archive. Automated brain volume segmentation with longitudinal processing was performed using FreeSurfer.ResultsOf the 25 subjects enrolled with MPS III, 17 children (4 females, 13 males) completed at least one MRI with interpretable volumetric data. The ages ranged from 2.8 to 13.7 years old (average 7.2 years old) at enrollment, including 8 with MPS IIIA and 9 with MPS IIIB. At baseline, individuals with MPS III demonstrated reduced cerebral white matter and corpus callosum volumes, but greater volumes of the lateral ventricles, cerebellar cortex, and cerebellar white matter compared to controls. Among the 13 individuals with MPS III with two interpretable MRIs, there were annualized losses or plateaus in supratentorial brain tissue volumes (cerebral cortex ?42.10 ± 18.52 cm3/year [mean ± SD], cerebral white matter ?4.37 ± 11.82 cm3/year, subcortical gray matter ?6.54 ± 3.63 cm3/year, corpus callosum ?0.18 ± 0.62 cm3/yr) and in cerebellar cortex (?0.49 ± 12.57 cm3/year), with a compensatory increase in lateral ventricular volume (7.17 ± 6.79 cm3/year). Reductions in the cerebral cortex and subcortical gray matter were more striking in individuals younger than 8 years of age. Greater cerebral cortex volume was associated with higher fine and gross motor functioning on the Mullen Scales of Early Learning, while greater subcortical gray matter volume was associated with higher nonverbal functioning on the Leiter International Performance Scale. Larger cerebellar cortex was associated with higher receptive language performance on the Mullen, but greater cerebellar white matter correlated with worse adaptive functioning on the Vineland Adaptive Behavioral Scales and visual problem-solving on the Mullen.ConclusionsLoss or plateauing of supratentorial brain tissue volumes may serve as longitudinal biomarkers of MPS III age-related disease progression compared to age-related growth in typically developing controls. Abnormally increased cerebellar white matter in MPS III, and its association with worse performance on neuropsychological measures, suggest the possibility of pathophysiological mechanisms distinct from neurodegeneration-associated atrophy that warrant further investigation. 相似文献
69.
Andressa Kelly Alves Ferreira Srgio Henrique Gonalves de Carvalho Ana Flvia Granville-Garcia Dmitry Jos de Santana Sarmento Gustavo Gomes Agripino Mauro Henrique Nogueira Guimares de Abreu Maria Cecília Freire de Melo Arnaldo de Frana Caldas Jr Gustavo Pina Godoy 《Medicina oral, patología oral y cirugía bucal》2021,26(3):e387
Background This study aimed to evaluate sociodemographic and clinical factors influencing overall survival (OS) in patients with oral squamous cell carcinoma (OSCC). Material and Methods Medical charts of 547 patients with OSCC from a public hospital in northeastern Brazil seen between 1999 and 2013 were evaluated. Survival analysis was performed using the Kaplan-Meier method. The influence of age, sex, ethnicity, clinical stage, anatomical location, type of treatment, and comorbidities on the patients’ prognosis was evaluated. Cox proportional hazards regression model was used to identify independent prognostic factors. Results The 5-year OS was 39%. Multivariate analysis showed that age < 40 years (HR = 2.20; 95%CI: 1.02-4.72) and a single treatment modality (HR = 1.91; 95%CI: 1.37-2.67) were associated with a poor prognosis, while early clinical stage resulted in better outcomes (HR = 0.38; 95%CI: 0.25-0.58). Conclusions OSCC patients in advanced clinical stages, diagnosed at a younger age, and submitted to a single therapeutic modality have a poorer prognosis. Key words:Head and neck cancer, oral cancer, oral squamous cell carcinoma, survival, prognosis. 相似文献
70.