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1.
Math Biosci ; : 108258, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31562868

RESUMO

A system of partial differential equations is developed to describe the formation and clearance of amyloid ß (Aß) and the subsequent buildup of Aß plaques in the brain, which are associated with Alzheimer's disease. The Aß related proteins are divided into five distinct categories depending on their size. In addition to enzymatic degradation, the clearance via diffusion and the outflow of interstitial fluid (ISF) into the surrounding cerebral spinal fluid (CSF) are considered. Treating the brain tissue as a porous medium, a simplified two-dimensional circular geometry is assumed for the transverse section of the brain leading to a nonlinear, coupled system of PDEs. Asymptotic analysis is carried out for the steady states of the spatially homogeneous system in the vanishingly small limit of Aß clearance rate. The PDE model is studied numerically for two cases, a spherically symmetric case and a more realistic 2D asymmetric case, allowing for non-uniform boundary conditions. Our investigations demonstrate that ISF advection is a key component in reproducing the clinically observed accumulation of plaques on the outer boundaries. Furthermore, ISF circulation serves to enhance Aß clearance over diffusion alone and that non-uniformities in ISF drainage into the CSF can lead to local clustering of plaques. Analysis of the model also demonstrates that plaque formation does not directly correspond to the high presence of toxic oligomers.

2.
Colorectal Dis ; 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31260150

RESUMO

AIM: The clinical benefits of a combination of leucovorin and fluorouracil have been established in the treatment of colorectal cancer. Due to a leucovorin shortage in 2008, many institutions revised their protocols to reduce the dose of leucovorin. After the shortage was resolved, some hospitals still maintained their modified protocols. Thus, we conducted a systematic review to evaluate the efficacy and safety of low- vs high-dose leucovorin in the treatment of colorectal cancer. METHOD: The PubMed, Embase and Cochrane databases were searched for studies published before May 2019. The meta-analysis was performed to estimate the pooled effect sizes by using a random effect model. The primary outcomes were median survival time and tumour response rate. Secondary outcomes were haematological and nonhaematological toxicities. RESULTS: Eight randomized controlled trials and four retrospective studies were reviewed. The pooled median survival time was similar between the two dose levels (standard mean difference -0.06, 95% CI -0.19 to 0.08). The pooled tumour response rate was comparatively higher in the high-dose leucovorin regimen (OR 0.81; 95% CI 0.55-1.18). No statistically significant difference was found between the haematological and nonhaematological toxicities of the two groups. However, there were fewer diarrhoea events in the low-dose leucovorin regimen. CONCLUSION: Low-dose leucovorin regimens seemed feasible approaches for colorectal cancer treatment when the shortage happened, because both regimens manifested comparable outcomes in survival time and tumour response rate.

3.
Crit Rev Food Sci Nutr ; : 1-38, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31267783

RESUMO

Fruit and vegetables (F&V) have been a cornerstone of healthy dietary recommendations; the 2015-2020 U.S. Dietary Guidelines for Americans recommend that F&V constitute one-half of the plate at each meal. F&V include a diverse collection of plant foods that vary in their energy, nutrient, and dietary bioactive contents. F&V have potential health-promoting effects beyond providing basic nutrition needs in humans, including their role in reducing inflammation and their potential preventive effects on various chronic disease states leading to decreases in years lost due to premature mortality and years lived with disability/morbidity. Current global intakes of F&V are well below recommendations. Given the importance of F&V for health, public policies that promote dietary interventions to help increase F&V intake are warranted. This externally commissioned expert comprehensive narrative, umbrella review summarizes up-to-date clinical and observational evidence on current intakes of F&V, discusses the available evidence on the potential health benefits of F&V, and offers implementation strategies to help ensure that public health messaging is reflective of current science. This review demonstrates that F&V provide benefits beyond helping to achieve basic nutrient requirements in humans. The scientific evidence for providing public health recommendations to increase F&V consumption for prevention of disease is strong. Current evidence suggests that F&V have the strongest effects in relation to prevention of CVDs, noting a nonlinear threshold effect of 800 g per day (i.e., about 5 servings a day). A growing body of clinical evidence (mostly small RCTs) demonstrates effects of specific F&V on certain chronic disease states; however, more research on the role of individual F&V for specific disease prevention strategies is still needed in many areas. Data from the systematic reviews and mostly observational studies cited in this report also support intake of certain types of F&V, particularly cruciferous vegetables, dark-green leafy vegetables, citrus fruits, and dark-colored berries, which have superior effects on biomarkers, surrogate endpoints, and outcomes of chronic disease.

4.
Cancer Prev Res (Phila) ; 12(7): 421-432, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31177203

RESUMO

Chronic obstructive pulmonary disease (COPD) and lung cancer share the same etiologic factor, cigarette smoking. Higher consumption of dietary lycopene has been associated with lower risks of COPD and lung cancer in smokers. We investigated whether lycopene feeding protects against COPD and lung cancer in ferrets, a nonrodent model that closely mimics cigarette smoke (CS)-induced chronic bronchitis, emphysema, and lung tumorigenesis in human. We also explored whether the protective effect of lycopene is associated with restoring reverse cholesterol transport (RCT), a key driver in persistent inflammation with CS exposure. Ferrets (4 groups, n = 12-16/group) were exposed to a combination of tobacco carcinogen (NNK) and CS with or without consuming lycopene at low and high doses (equivalent to ∼30 and ∼90 mg lycopene/day in human, respectively) for 22 weeks. Results showed that dietary lycopene at a high dose significantly inhibited NNK/CS-induced chronic bronchitis, emphysema, and preneoplastic lesions, including squamous metaplasia and atypical adenomatous hyperplasia, as compared with the NNK/CS alone (P < 0.05). Lycopene feeding also tended to decrease the lung neoplastic lesions. Furthermore, lycopene feeding significantly inhibited NNK/CS-induced accumulation of total cholesterol, and increased mRNA expression of critical genes related to the RCT (PPARα, LXRα, and ATP-binding cassette transporters ABCA1 and ABCG1) in the lungs, which were downregulated by the NNK/CS exposure. The present study has provided the first evidence linking a protective role of dietary lycopene against COPD and preneoplastic lesions to RCT-mediated cholesterol accumulation in lungs.

5.
Zhonghua Xin Xue Guan Bing Za Zhi ; 47(5): 393-398, 2019 May 24.
Artigo em Chinês | MEDLINE | ID: mdl-31142084

RESUMO

Objective: To explore the effects of oxidative stress on renal dopamine D(1) receptor dysfunction in offspring of diabetic rat dams. Methods: The pregnant Sprague Dawley (SD) rats (n=10) were randomly divided into the diabetic group (a single intraperitoneal injection of 35 mg/kg streptozotocin on day 0 of gestation) and control group (injected with the equal volume of 0.9% saline on day 0 of gestation) according to the random number table (n=5 each group). The offspring rats were divided into 4 groups including offspring of control dams treated with vehicle, offspring of control dams treated with antioxidant, offspring of diabetic dams treated with vehicle and offspring of diabetic dams treated with antioxidant (n=10 each group). After birth, the offspring rats were treated with normal drinking water or antioxidant (tempol, 1.0 mmol/L) from the age of 4 weeks until the end of the study (20 weeks). The blood pressure was monitored continuously by non-invasive tail-cuff method. The renal oxidative markers including superoxide dismutase (SOD) and malondialdehyde (MDA) activity and D(1) receptor agonist (fenoldopam)-mediated urinary and sodium excretion were detected. Furthermore, the protein expression of renal G protein-coupled receptor kinase 2 (GRK2), GRK4, dopamine D(1) receptor and the phosphorylation level of D(1) receptor were detected. Results: The mean arterial pressure of offspring from the diabetic dams treated with vehicle was significantly higher than that of offspring from control dams treated with vehicle (P=0.013), while the mean arterial pressure of offspring from diabetic dams treated with antioxidant was significantly lower than that of offspring from the diabetic dams treated with vehicle (P=0.038). The fenoldopam-mediated urinary flow and urinary sodium excretion rate were significantly lower in offspring of diabetic dams treated with vehicle than those in offspring of control dams treated with vehicle (P<0.01), which were significantly higher in offspring of diabetic dams treated with antioxidant as compared to offspring of diabetic dams treated with vehicle (both P<0.01). There was no significant difference in fenoldopam-mediated urinary flow and urinary sodium excretion rate in offspring of control dams treated with antioxidant or vehicle (urinary flow: P=0.772; urinary sodium excretion rate: P=0.716). Compared with offspring of control dams treated with vehicle, the renal MDA activity was significantly increased, while the SOD activity was significantly decreased in offspring of diabetic dams treated with vehicle (MDA: P<0.01; SOD: P=0.013). The renal MDA activity was significantly decreased, while the SOD activity was significantly increased in offspring of diabetic dams treated with antioxidant in comparison with offspring of diabetic dams treated with vehicle (MDA: P<0.01; SOD: P=0.035).The renal GRK2 and GRK4 protein expression in offspring of diabetic dams treated with vehicle were significantly higher than those in offspring of control dams treated with vehicle (P<0.01), while the expression levels of renal GRK2 and GRK4 in offspring of diabetic dams treated with antioxidant were significantly downregulated compared with offspring of diabetic dams treated with vehicle (P<0.01). There was no significant difference in the protein expression of dopamine D(1) receptor among 4 groups (P=0.735). The level of dopamine D(1) receptor phosphorylation in offspring of diabetic dams treated with vehicle was significantly higher than that in offspring of control dams treated with vehicle (P<0.01), while the dopamine D(1) receptor phosphorylation level was significantly lower in offspring of diabetic dams treated with antioxidant compared to that in offspring of diabetic dams treated with vehicle (P<0.01). Conclusion: Oxidative stress is involved in the dopamine D(1) receptors dysfunction in the offspring of diabetic dams.


Assuntos
Diabetes Mellitus , Estresse Oxidativo , Receptores de Dopamina D1 , Animais , Diabetes Mellitus/metabolismo , Dopamina/metabolismo , Feminino , Rim , Gravidez , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Receptores de Dopamina D1/metabolismo
6.
Placenta ; 80: 12-17, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31103061

RESUMO

OBJECTIVES: To investigate changes of placental vascular indices and volume in pre-gravid overweight Chinese women during the first trimester using three-dimensional power Doppler ultrasound. METHODS: This was a prospective observational study of the morphology of placentas in pre-gravid overweight (body mass index (BMI) ≥ 24 kg/m2) and non-overweight (BMI < 24 kg/m2) Chinese women during the first trimester of pregnancy. Data on placental vascular indices (vascularization index, flow index, and vascularization flow index (VFI)), placental volume, uterine artery pulsatility index (PI), and neonatal outcomes were obtained during the first trimester and analyzed. Linear regression analysis was used to evaluate confounding factors between BMI and ultrasound indices. RESULTS: Of the 429 pregnant women enrolled, 68 (15.9%) were pre-gravid overweight. Placental VFI was significantly lower in the overweight group (p = 0.037). Conversely, placental volume was significantly larger in the overweight group (p = 0.044), and uterine artery PI was significantly higher in the overweight group (p = 0.021). After adjustments for confounding factors, there were still significant differences in placental VFI (unstandardized coefficient (B) -0.666, 95% confidence interval (CI) -1.306 - (-0.025)), placental volume (B 2.458, 95% CI 0.071-4.844), and uterine artery PI (B 0.152, 95% CI 0.030-0.274) between the two groups. CONCLUSIONS: Placental vascular indices using three-dimensional power Doppler ultrasound can provide an insight into placental vascularization in pre-gravid overweight women in early pregnancy. Alterations in placental VFI, placental volume, and uterine artery PI occur during the first trimester in pre-gravid overweight women.

7.
Sci Total Environ ; 666: 1316-1326, 2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-30970496

RESUMO

The fate and mobility of mercury, and its bioaccumulation primarily as methylmercury (MeHg), in marine ecosystems are influenced by climate related environmental factors, including increased temperature and carbon loading. To investigate the interactions between sediment organic carbon and temperature MeHg bioaccumulation, mesocosm experiments were conducted examining relationships between sediment, water column and biota (sediment-dwelling amphipod and juvenile oyster) MeHg concentration. Experimental treatments consisted of a two by two design of high and low temperature (15 & 25 °C) and high and low sediment organic carbon (4-5% and 13% LOI, pre-experiment). Sediment organic carbon had significant individual effects on MeHg concentration in water and biota, with higher carbon associated with lower MeHg. Temperature individual effects were significant for sediment, water, and only amphipod MeHg concentration, with higher temperature treatments indicating higher MeHg concentration. There were significant temperature × carbon interactions observed for sediment, dissolved, and oyster MeHg concentration. Sediment carbon reduction had greater influence than temperature on increasing MeHg concentrations in both the water column and biota. MeHg concentrations in the bulk sediment were not correlated with MeHg in the water column or in the biota, indicating that even when sediments are the only source of MeHg, bulk sediment measurements do not provide a good proxy for bioaccumulation and that the concentration in bulk sediments is not the primary determinant of MeHg entry into the food web.


Assuntos
Carbono/análise , Monitoramento Ambiental , Sedimentos Geológicos/química , Invertebrados/metabolismo , Compostos de Metilmercúrio/análise , Poluentes Químicos da Água/análise , Animais , Biota , Cadeia Alimentar , Invertebrados/efeitos dos fármacos , Compostos Orgânicos/análise , Temperatura Ambiente
8.
AJNR Am J Neuroradiol ; 40(4): 601-608, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30923084

RESUMO

BACKGROUND AND PURPOSE: The effects of multiple head impacts, even without detectable primary injury, on subsequent behavioral impairment and structural abnormality is yet well explored. Our aim was to uncover the dynamic changes and long-term effects of single and repetitive head injury without focal contusion on tissue microstructure and macrostructure. MATERIALS AND METHODS: We introduced a repetitive closed-head injury rodent model (n = 70) without parenchymal lesions. We performed a longitudinal MR imaging study during a 50-day study period (T2-weighted imaging, susceptibility-weighted imaging, and diffusion tensor imaging) as well as sequential behavioral assessment. Immunohistochemical staining for astrogliosis was examined in a subgroup of animals. Paired and independent t tests were used to evaluate the outcome change after injury and the cumulative effects of impact load, respectively. RESULTS: There was no gross morphologic evidence for head injury such as skull fracture, contusion, or hemorrhage on micro-CT and MR imaging. A significant decrease of white matter fractional anisotropy from day 21 on and an increase of gray matter fractional anisotropy from day 35 on were observed. Smaller mean cortical volume in the double-injury group was shown at day 50 compared with sham and single injury (P < .05). Behavioral deficits (P < .05) in neurologic outcome, balance, and locomotor activity were also aggravated after double injury. Histologic analysis showed astrogliosis 24 hours after injury, which persisted throughout the study period. CONCLUSIONS: There are measurable and dynamic changes in microstructure, cortical volume, behavior, and histopathology after both single and double injury, with more severe effects seen after double injury. This work bridges cross-sectional evidence from human subject and pathologic studies using animal models with a multi-time point, longitudinal research paradigm.

9.
Environ Pollut ; 246: 639-649, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30605819

RESUMO

Estuaries are dynamic ecosystems which vary widely in loading of the contaminant methylmercury (MeHg), and in environmental factors which control MeHg exposure to the estuarine foodweb. Inputs of organic carbon and rates of primary production are important influences on MeHg loading and bioaccumulation, and are predicted to increase with changes in climate and land use pressures. To further understand these influences on MeHg levels in estuarine biota, we used a field study approach in sites across different temperature regions, and with varying organic carbon levels. In paired comparisons of sites with high vs. low organic carbon, fish had lower MeHg bioaccumulation factors (normalized to water concentrations) in high carbon sites, particularly subsites with large coastal wetlands and large variability in dissolved organic carbon levels in the water column. Across sites, MeHg level in the water column was strongly tied to dissolved organic carbon, and was the major driver of MeHg concentrations in fish and invertebrates. Higher primary productivity (chlorophyll-a) was associated with increased MeHg partitioning to suspended particulates, but not to the biota. These findings suggest that increased inputs of MeHg and loss of wetlands associated with climate change and anthropogenic land use pressure will increase MeHg concentrations in estuarine food webs.


Assuntos
Organismos Aquáticos/efeitos dos fármacos , Monitoramento Ambiental/métodos , Estuários , Compostos de Metilmercúrio/análise , Poluentes Químicos da Água/análise , Áreas Alagadas , Animais , Organismos Aquáticos/metabolismo , Biota/efeitos dos fármacos , Cadeia Alimentar , New England
10.
QJM ; 112(5): 343-350, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30690642

RESUMO

BACKGROUND: Brugada syndrome (BrS) is a heritable sudden cardiac death (SCD) disease with male predominance. Information on gender difference of BrS remains scarce. AIM: To investigate the gender difference of BrS in Han Chinese. DESIGN: We consecutively enrolled 169 BrS patients (153 males and 16 females) from Han Chinese in Taiwan from 1998 to 2017. METHODS: Clinical characteristics, electrocardiographic parameters and SCN5A mutation status were compared between genders. RESULTS: The percentage of family history of SCD in females was slightly higher (31.3% vs. 15%, P = 0.15). Females exhibited longer QTc (457.8 ± 33.0 vs. 429.5 ± 42.1 ms, P < 0.01). Regarding cumulative event occurrence by age, Mantel-Cox test showed females had earlier age of onset of first cardiac events (SCD or syncope) than males (P = 0.049), which was mainly attributed to syncope (P < 0.01). Males with SCD exhibited longer QRS duration (114.2 ± 26.8 vs. 104.8 ± 15.3 ms, P = 0.02) and QTc (442.5 ± 57.4 vs. 422.9 ± 28.8 ms, P = 0.02). Males with syncope exhibited longer PR interval (181.2 ± 33.7 vs. 165.7 ± 27.1 ms, P = 0.01), whereas females with SCD or syncope had a trend towards slower heart rates (69.1 ± 9.6 vs. 82.2 ± 16.3 bpm, P = 0.10) than female with no or mild symptoms. There was no difference in the percentage of SCN5A mutation between genders. CONCLUSION: Gender difference is present in BrS. Females have longer QTc and suffer from syncope earlier than males. Risk of SCD in males is associated with boarder QRS complex and longer QTc, whereas risk of syncope is associated with longer PR interval in males and slower heart rate in females.


Assuntos
Síndrome de Brugada/genética , Morte Súbita Cardíaca/epidemiologia , Síndrome do QT Longo/epidemiologia , Canal de Sódio Disparado por Voltagem NAV1.5/genética , Fatores Sexuais , Síncope/etiologia , Adulto , Síndrome de Brugada/complicações , Síndrome de Brugada/fisiopatologia , Morte Súbita Cardíaca/etiologia , Eletrocardiografia , Feminino , Humanos , Síndrome do QT Longo/etiologia , Masculino , Pessoa de Meia-Idade , Mutação , Sistema de Registros , Medição de Risco , Distribuição por Sexo , Síncope/epidemiologia , Taiwan/epidemiologia
11.
Transplant Proc ; 50(9): 2606-2610, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30401360

RESUMO

BACKGROUND: The safety of the living donor in living-donor liver transplantation (LDLT) is always the first priority, meanwhile, the graft-to-recipient weight ratio (GRWR) and the anatomy of the liver allograft must also not be compromised in order to warrant tranplatation success. When it comes to the allograft of the right lobe of the liver without the middle hepatic vein (R-M), the outflow and adequate drainage for the territory of middle hepatic vein (MHV) is one critical concern. Despite publications in some high-volume transplant centers on the positive results of using expanded polytetrafluoroethylene (ePTFE) grafts to substitute those of autologous veins, complications related to the ePTFE graft have not been well discussed. METHODS: From July 2012 to June 2016, 129 adult patients who underwent living donor liver transplantation in Taipei Veterans General Hospital were analyzed. There were 3 cases of adjacent organ erosion with gas bubbles in the lumen of an ePTFE graft, including gastrointestinal (GI) tract penetration in 2 out of the first 15 cases that used the venous graft of ringed expanded polytetrafluoroethylene (rPTFE). The patient survival rate during this period was compared and radiological findings of rPTFE function and clinical signs of erosion with infection were also examined to raise the concerns of safety as well as early detection of complications of rPTFE. RESULTS: The overall 1-year patient survival rate was 90%, of which the right lobe wih MHV (R+M) group was 93.5% and the R-M group was 91.9%. For the mean of GRWR, the R+M group was 1.05 ± 0.19 and R-M group was 1.19 ± 0.27, while those who needed reconstruction with vein grafts was 0.96 ± 0.11. Among the R-M group, 24 out of 88 cases (27.3%) needed reconstruction of MHV tributaries. Of the 24 cases, 15 cases were done with rPTFE and the 1-year patient survival rate of the rPTFE group was 73%, which is significantly worse (P = .008) than the non-rPTFE (89%) and non-reconstructed (97%) groups. The mean GRWR is significantly higher (P = .001) in the non-reconstructed group (1.19 ± 0.27) than in the rPTFE (0.99 ± 0.11) and non-rPTFE (0.94 ± 0.11) groups. The venous grafts patency rate between the different graft types is no different, and there is also significance in warm ischemic time (P = .009) between the non-reconstructed (49 ± 15), rPTFE (81 ± 51), and non-rPTFE (56 ± 18) groups in the mean minutes. CONCLUSION: In cases of fever of unknown cause in patients receiving LDLT with rPTFE graft, a regular computed tomography (CT) scan with contrast and gas bubbles within the graft lumen is the best way for early detection of graft related infection and suspicious GI tract penetration. To decrease the risks of tissue reaction induced by ePTFE graft in LDLT, omentum patches or other inert agents can be introduced as a buffer between the graft and adjacent organs, especially the GI tracts. However, research in material science shall be explored to solve the problem in the future.

12.
Food Funct ; 9(11): 5653-5659, 2018 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-30302465

RESUMO

Coenzyme Q10 (CoQ10) exerts its functions in the body through the ability of its benzoquinone head group to accept and donate electrons. The primary functions are to relay electrons for ATP production in the electron transport chain and to act as an important lipophilic antioxidant. Ubiquinone, the oxidized form of CoQ10, is commonly formulated in commercial supplements, and it must be reduced to ubiquinol to exert CoQ10's functions after consumption. Thus, we aimed to examine whether as compared to ubiquinone, ubiquinol would be more effective to enhance the CoQ10 status in older men. We conducted a double-blind, randomized, crossover trial with two 2-week intervention phases and a 2-week washout between crossovers. Ten eligible older men were randomized to consume either the ubiquinol or ubiquinone supplement at a dose of 200 mg d-1 with one of the main meals. A total of 4 blood samples were collected after an overnight fast for the determination of ubiquinone and ubiquinol in plasma and PBMC and the assessment of FRAP, total thiol, and malondialdehyde (MDA) in plasma and ATP in PBMC. After 2 weeks of the supplementation, the ubiquinol supplement significantly increased plasma ubiquinone 1.7 fold from 0.2 to 0.6 µmol L-1 and total CoQ10 (the sum of 2 forms) 1.5 fold from 1.3 to 3.4 µmol L-1 (p < 0.05) and tended to increase the plasma ubiquinol status 1.5 fold from 1.1 to 2.8 µmol L-1, but did not alter the ratio of ubiquinol to total CoQ10. The ubiquinone supplement insignificantly increases plasma ubiquinol, ubiquinone, and total CoQ10 and did not affect the ratio. Of 10 subjects, six were more responsive to the ubiquinol supplement and 2 were more so to the ubiquinone. The supplementation of both CoQ10 forms did not alter the CoQ10 status in PBMC. FRAP, total thiol, and MDA in plasma and ATP in PBMC were not changed during the intervention. The significant increase in plasma CoQ10 status observed after the 2-week supplementation suggested that ubiquinol appeared to be a better supplemental form to enhance the CoQ10 status than ubiquinone in older men. Neither ubiquinol nor ubiquinone supplement affected the measured biomarkers of oxidative stress.

13.
J Nutr Biochem ; 62: 76-86, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30269035

RESUMO

Cranberries have multiple health effects but their impact on gut microbiota has not been examined in randomized controlled feeding trials. We evaluated the relationship between the microbiota and cranberries in the context of an animal-based diet. In a randomized, double-blind, cross-over, controlled design trial, 11 healthy adults consumed for 5 days each a control diet (animal-based diet plus 30 g/day placebo powder) and a cranberry diet (animal-based diet plus 30 g/day freeze-dried whole cranberry powder). The animal-based diet included meats, dairy products, and simple sugars. Stool, urine, and blood samples were obtained before and after each intervention phase. As compared to the pre-control diet, control diet modified 46 taxonomic clades, including an increase in the abundance of Firmicutes and decrease in Bacteroidetes. Moreover, it increased bacteria-derived deoxycholic acid and decreased acetate and butyrate in stool. As compared to the post-intervention phase of control diet, the cranberry diet modified 9 taxonomic clades, including a decrease in the abundance of Firmicutes and increase in Bacteroidetes. Further, the cranberry diet attenuated control diet-induced increase in secondary bile acids and decrease in short-chain fatty acids (SCFA), and increased urinary anthocyanins and bacterially derived phenolic acids. No changes were found in fecal trimethylamine and plasma cytokines. In conclusion, an animal-based diet altered the microbiota composition to a less favorable profile, increased carcinogenic bile acids, and decreased beneficial SCFA. Cranberries attenuated the impact of the animal-based diet on microbiota composition, bile acids, and SCFA, evidencing their capacity to modulate the gut microbiota.

14.
Zhonghua Er Ke Za Zhi ; 56(9): 651-656, 2018 Sep 02.
Artigo em Chinês | MEDLINE | ID: mdl-30180402

RESUMO

Objective: To compare the efficacy and safety of mycophenolate mofetil versus cyclosporine A in treating children with primary refractory nephrotic syndrome. Methods: Conducted a prospective randomized controlled clinical trial in 62 pediatric patients (including 44 boys and 18 girls), age ranged from 2.1 to 17.0 years; 32 cases presented with frequently relapsing nephrotic syndrome (FRNS) and 30 cases presented with steroid-resistant nephrotic syndrome (SRNS), who were admitted to department of Nephrology, Children's Hospital Affiliated to Capital Institute of Pediatrics from October 2013 to October 2015. The patients received either mycophenolate mofetil (20-30)mg/(kg·d) or cyclosporine A (3-5)mg/(kg·d) randomly, on the basis of prednisone treatment. Follow-up interview was conducted regularly for at least one year. Efficacy rate, relapse rate, time required for induction of remission, relapse-free period and prednisone dosage were compared between the two groups. Results: (1) Renal histologic examination, which was available for 17 patients, revealed minimal change disease in 8 patients, mesangial proliferative glomerulonephritis (MsPGN) in five, membranous nephropathy in two, and focal segmental glomerulosclerosis (FSGS) in two. (2) Comparison of mycophenolate mofetil versus cyclosporine A in children with FRNS: There were 14 patients with FRNS in mycophenolate mofetil group and 18 patients with FRNS in cyclosporine A group respectively. The relapse rate (episodes/year) in cyclosporine A group was lower than that of mycophenolate mofetil group (1.0 (0.0, 1.0) vs. 1.0 (1.0, 3.0), Z=-2.405, P=0.016). The relapse-free period (months) in cyclosporine A group was longer than that of mycophenolate mofetil group (10.0 (5.7, 12.1) vs. 5.0 (1.0, 11.0), Z=-1.984, P=0.047). No significant difference in dosage of prednisone was found between cyclosporine A and mycophenolate mofetil groups when followed up for 1 year. (3) Comparison of mycophenolate mofetil versus cyclosporine A in children with SRNS: The efficacy rate was 6/14 in mycophenolate mofetil group and 13/16 in cyclosporine A group. The complete remission rate was 4/14 in mycophenolate mofetil group and 12/16 in cyclosporine A group (P<0.05). The time (months) required for induction of remission in cyclosporine A group was significantly shorter than that of mycophenolate mofetil group (1.0 (1.0, 2.0) vs. 3.0 (2.5, 4.0), Z=-2.529, P=0.011). No significant differences were found between the two groups with respect to relapse-free period and relapse rate. (4) Except that one patient developed hypertensive encephalopathy in cyclosporine A group, no other serious adverse events were recorded. There were no significant differences between two groups with respect to adverse events. Conclusion: Our results indicated that both mycophenolate mofetil and cyclosporine A were effective in the treatment of children with refractory nephrotic syndrome. Cyclosporine A was superior to mycophenolate mofetil in preventing relapses in patients with FRNS and inducing complete remission in patients with SRNS. Although most patients were able to tolerate mycophenolate mofetil and cyclosporine A, but the toxicity and safety of cyclosporine A should be monitored closely.

15.
Theor Popul Biol ; 2018 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-30165060

RESUMO

In-host mutation of a cross-species infectious disease to a form that is transmissible between humans has resulted with devastating global pandemics in the past. We use simple mathematical models to describe this process with the aim to better understand the emergence of an epidemic resulting from such a mutation and the extent of measures that are needed to control it. The feared outbreak of a human-human transmissible form of avian influenza leading to a global epidemic is the paradigm for this study. We extend the SIR approach to derive a deterministic and a stochastic formulation to describe the evolution of two classes of susceptible and infected states and a removed state, leading to a system of ordinary differential equations and a stochastic equivalent based on a Markov process. For the deterministic model, the contrasting timescale of the mutation process and disease infectiousness is exploited in two limits using asymptotic analysis in order to determine, in terms of the model parameters, necessary conditions for an epidemic to take place and timescales for the onset of the epidemic, the size and duration of the epidemic and the maximum level of the infected individuals at one time. Furthermore, the basic reproduction number R0 is determined from asymptotic analysis of a distinguished limit. Comparisons between the deterministic and stochastic model demonstrate that stochasticity has little effect on most aspects of an epidemic, but does have significant impact on its onset particularly for smaller populations and lower mutation rates for representatively large populations. The deterministic model is extended to investigate a range of quarantine and vaccination programmes, whereby in the two asymptotic limits analysed, quantitative estimates on the outcomes and effectiveness of these control measures are established.

17.
Zhonghua Fu Chan Ke Za Zhi ; 53(8): 547-553, 2018 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-30138965

RESUMO

Objective: To investigate whether the suppressive effects of lipoxin A4 (LXA4) on endometriosis are mediated by the regulation of autophagic activity, and to further explore the actual molecular mechanism. Methods: (1) Eutopic and ectopic endometria were obtained from 13 patients with endometriosis, and 10 eutopic endometria collected from non-endometriosis patients were used as control. The expression of the autophagy-related biochemical markers [microtubule-associated protein 1 light chain 3 (LC3) and p62] were detected by western blot. Levels of LXA4 in the biopsies were measured by ELISA. (2) Primary human endometrial stromal cells (ESC) were isolated and cultured in vitro from eutopic endometria of infertility patients with endometriosis. After treatment with exogenous LXA4 or autophagy inhibitor 3-methyladenine (3-MA) or autophagy inducer rapamycin, cell migration and invasion were evaluated by transwell assay, and autophagy was detected by western blot. (3) ESC were treated with LXA4, the gene expressions of nuclear factor kappa B (NF-κB) etc. were examined by quantitative real-time PCR, and the activation of NF-κB signaling was detected by western blot. (4) ESC were incubated with 10 µmol/L NF-κB inhibitor BAY11-7080, the autophagic activation was detected by western blot. Results: (1) Autophagy-related marker, LC3-Ⅱ and LC3-Ⅱ/LC3-Ⅰ ratio, showed a significant up-regulation in ectopic lesions of endometriosis compared with eutopic endometria of affected or healthy women (all P<0.05) . However, the LXA4 level significantly decreased in ectopic tissue (P<0.05) . There was a significant negative correlation between LXA4 concentration and relative expression of LC3-Ⅱ in ectopic lesions (r= -0.780, P=0.002) . (2) 10 and 100 nmol/L exogenous LXA4 could significantly down-regulate the LC3-Ⅱ protein expression and up-regulate the p62 protein expression (all P<0.05) . LXA4 markedly inhibited the invasion and migration of ESC (P<0.05) ;while the reactivation of autophagy by rapamycin almost reversed the anti-invasion and anti-migration effects of LXA4. (3) After LXA4 treatment, the expression level of NF-κB gene significantly decreased (P<0.05) . Furthermore, the results of western blot analysis showed that the nuclear translocation of NF-κB p65 was markedly down-regulated under LXA4 treatment (P<0.05) . (4) The NF-κB inhibitor BAY11-7080 markedly suppressed the autophagic activation of LXA4 (P<0.05) . Conclusion: LXA4 could inhibit the invasion and migration of ESC by down-regulating the NF-κB signaling-mediated autophagy.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Autofagia/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Endométrio/citologia , Lipoxinas/farmacologia , NF-kappa B/fisiologia , Células Estromais/efeitos dos fármacos , Células Estromais/metabolismo , Regulação para Baixo , Endometriose , Células Epiteliais/metabolismo , Feminino , Humanos , Proteínas I-kappa B , Inibidor de NF-kappaB alfa , NF-kappa B/genética , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Regulação para Cima
19.
J Intensive Care Med ; : 885066618789114, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30021499

RESUMO

Ubiquinol is a fundamental component of cellular metabolism. Low ubiquinol levels have been associated with mortality. This was a substudy of a randomized trial in patients undergoing coronary artery bypass grafting. We drew blood before and after surgery. Ubiquinol or placebo was added to peripheral blood mononuclear cells for oxygen consumption (OCR) measurements. In vivo ubiquinol levels were lower postsurgery compared to presurgery (0.16 µmol/L [quartiles: 0.02-0.39], P = .01), although the difference disappeared when adjusting for hemoglobin levels ( P = .30). There was no difference in presurgical basal (1.0 mL/min/mg [95% confidence interval [CI]: -0.9 to 2.2], P = .08) and maximal (0.5 mL/min/mg [95% CI: -4.3 to 7.3], P = .56) OCR in cells receiving ubiquinol or placebo. There was a difference in postsurgical basal (1.1 mL/min/mg [95% CI: 0.9-1.6], P < .001) and maximal (4.2 mL/min/mg [95% CI: 0.3-7.0], P = .01) OCR between the groups. We found no association between ubiquinol and OCR levels (all P > .05).

20.
Mutat Res ; 832-833: 61-64, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30057022

RESUMO

Operating room professionals are scarcely aware of their individual occupational exposure to waste anesthetic gases (WAGs). Medical residents spend several hours per day in operating rooms and consequently experience occupational exposure to WAGs. Considering that no studies have yet evaluated the potential toxicity in medical residents exposed to WAGs using the buccal micronucleus cytome (BMCyt) assay, this pioneering study aimed to compare the BMCyt assay markers, including DNA damage, cell proliferation, and cell death in the exfoliated buccal cells of surgery and anesthesiology residents occupationally exposed to WAGs. The study enrolled a total of 60 physicians, including internal medicine residents (unexposed group), and residents from surgery and anesthesiology programs who were occupationally exposed to sevoflurane, isoflurane and nitrous oxide. WAGs were measured, and the mean values were higher than the international recommendation. The anesthesiology residents (high exposure) showed statistically significant lower frequencies of basal cells, and statistically significant higher frequencies of micronuclei, karyorrhexis, pyknosis, and differentiated cells than did the unexposed group; karyolysis frequencies were significantly higher in anesthesiology residents than were those in the unexposed group or in surgical residents (low exposure). The findings suggest a genetic risk for young professionals exposed to WAGs at the beginning of their careers. Thus, exposure to high WAGs concentrations leads to impairment of the buccal cell proliferative potential, genomic instability and cell death, especially in anesthesiology residents, demonstrating an early impact on their health.

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