Subjects with sickle cell trait (SCT) carry one copy of mutated β-globin gene at position E6V at the origin of the production of sickle hemoglobin (HbS). Indeed, individuals with SCT have both normal ...hemoglobin and HbS, in contrast to patients with sickle cell disease who inherited of two copies of the mutated gene. Although SCT is generally benign/asymptomatic, carriers may develop certain adverse outcomes such as renal complications, venous thromboembolism, exercise-induced rhabdomyolysis … However, little is known about whether similar metabolic pathways are affected in individuals with SCT and whether these metabolic derangements, if present, correlate to clinically relevant parameters. In this study, we performed metabolomics analysis of plasma from individuals with sickle cell trait (
= 34) compared to healthy controls (
= 30). Results indicated a significant increase in basal circulating levels of hemolysis markers, mono- (pyruvate, lactate), di- and tri-carboxylates (including all Krebs cycle intermediates), suggestive of systems-wide mitochondrial dysfunction in individuals with SCT. Elevated levels of kynurenines and indoles were observed in SCT samples, along with increases in the levels of oxidative stress markers (advanced glycation and protein-oxidation end-products, malondialdehyde, oxylipins, eicosanoids). Increases in circulating levels of acyl-carnitines and fatty acids were observed, consistent with increased membrane lipid damage in individuals with sickle cell trait. Finally, correlation analyses to clinical co-variates showed that alterations in the aforementioned pathways strongly correlated with clinical measurements of blood viscosity, renal (glomerular filtration rate, microalbuminuria, uremia) and cardiovascular function (carotid-femoral pulse wave velocity, blood pressure).
Small airway remodeling (SAR) is a key phenomenon of airflow obstruction in smokers, leading to chronic obstructive pulmonary disease (COPD). SAR results in an increased thickness of small airway ...walls, with a combination of peribronchiolar fibrosis with increased fibrous tissue and accumulation of mesenchymal and epithelial cells. SAR pathogenesis is still unclear but recent data suggest that alterations in telomerase activity could represent a possible underlying mechanism of SAR. Our study was dedicated to identify a potential protective role of TA-65, a pharmacological telomerase activator, in a cigarette smoke (CS) model of SAR in mice, and to further precise if extra-telomeric effects of telomerase, involving oxidative stress modulation, could explain it. C57BL/6J mice were daily exposed to air or CS during 4 weeks with or without a concomitant administration of TA-65 starting 7 days before CS exposure. Morphological analyses were performed, and mucus production, myofibroblast differentiation, collagen deposition, as well as transforming growth factor-β1 (TGF-β1) expression in the small airway walls were examined. In addition, the effects of TA-65 treatment on TGF-β expression, fibroblast-to-myofibroblast differentiation, reactive oxygen species (ROS) production and catalase expression and activity were evaluated in primary cultures of pulmonary fibroblasts and/or mouse embryonic fibroblasts in vitro. Exposure to CS during 4 weeks induced SAR in mice, characterized by small airway walls thickening and peribronchiolar fibrosis (increased deposition of collagen, expression of α-SMA in small airway walls), without mucus overproduction. Treatment of mice with TA-65 protected them from CS-induced SAR. This effect was associated with the prevention of CS-induced TGF-β expression in vivo, the blockade of TGF-β-induced myofibroblast differentiation, and the reduction of TGF-β-induced ROS production that correlates with an increase of catalase expression and activity. Our findings demonstrate that telomerase is a critical player of SAR, probably through extra-telomeric anti-oxidant effects, and therefore provide new insights in the understanding and treatment of COPD pathogenesis.
Background Obesity and related metabolic disorders are associated with genetic and epigenetic alterations. In this study, we have examined the association between polymorphisms and hypermethylation ...of the CD36 gene promoter with obesity in Senegalese females with or without type 2 diabetes mellitus to identify novel molecular markers of these pathologies (obesity and type 2 diabetes mellitus). Materials and methods The study was conducted in Senegal with healthy lean control, obese, and obese diabetic (age; 49.98 years + or - 7.52 vs 50.50 years + or - 8.76 vs 51.06 + or - 5.78, and body mass index (BMI); 24.19 kg/m.sup.2 + or - 2.74 vs 34.30 kg/m.sup.2 + or - 4.41 vs 33.09 kg/m.sup.2 + or - 4.30). We determined three genetic polymorphisms of CD36 i.e., rs1761667, rs1527483, and rs3211867 by real-time polymerase chain reaction, and methylation of CPG islands of CD36 was assessed by methylation-specific polymerase chain reaction (MS-PCR) in DNA isolated from peripheral blood of each participant. Plasma sCD36 levels and DNA methyltransferase 3a (DNMT3a) levels were determined by enzyme-linked immunosorbent assay (ELISA). According to the standard laboratory protocol, all biochemical parameters were analyzed from fasting serum or plasma. Results For rs1761667, obese and obese diabetic subjects had statistically significant different parameters depending on the genotypic distribution. These were waist size for obese and HDL cholesterol for obese diabetic, they were significantly higher in subjects harboring GG genotype of rs1761667 (respectively p = 0.04 and p = 0.04). For rs3211867, obese subjects harboring the AA/AC genotype had significantly higher BMI (p = 0.02) and total cholesterol (p = 0.03) than obese subjects harboring the CC genotype. At the same time, the obese diabetic subjects harboring the AA/AC genotype had total cholesterol levels significantly higher than the obese diabetic subjects harboring the CC genotype (p = 0.03). For rs1527483, only the control subjects had statistically significant different parameters depending on the genotypic distribution. The control subjects harboring the GG genotype had a significantly higher BMI than the control subjects harboring the AA/AG genotype (p = 0.003). The CD36 gene methylation was significantly 1.36 times more frequent in obese and obese diabetic compared to lean control (RR = 1.36; p = 0.04). DNMT3a levels were higher in subjects with CD36 gene methylation than in subjects without CD36 gene methylation in each group. Obese diabetic subjects with CD36 gene methylation had significantly fewer plasmas sCD36 (p = 0.03) and more LDL-cholesterol (p = 0.01) than obese diabetic subjects without CD36 gene methylation. In the control group, an increase in sCD36 levels would be associated with a decrease in total cholesterol and triglyceride levels (coef = -7647.56 p = 0.01 and coef = -2528.50 p = 0.048, respectively) would be associated with an increase in LDL cholesterol levels. For the obese group, an increase in sCD36 levels would be associated with an increase in fasting insulin levels (coef = 490.99 p = 0.02) and a decrease in glycated hemoglobin levels (coef = -1196.26 p = 0.03). An increase in the sCD36 levels would be associated with an increase in the triglyceride levels in the obese diabetic group (coef = 9937.41 p = 0.02). The AA/AC genotype of SNP rs3211867 polymorphism was significantly associated with CD36 gene methylation in the control and obese diabetic groups (respectively p = 0.05, p = 0.002; 95% CI). Conclusion These observations suggest that polymorphisms and epigenetic changes in CD36 gene promoters may be implicated in the onset of obesity and its related complication type 2 diabetes mellitus. Keywords: Obesity, Type 2 diabetes, CD36 gene, Polymorphisms, Methylation
Musculoskeletal pains (MSPs) in sport are cause of poor performances and loss of competition in athletes. The present study aimed at determining the prevalence of MSPs with regard to sport ...disciplines and athletic status.
A cross-sectional study was conducted among 320 Senegalese professional and amateur athletes practicing football, basketball, rugby, tennis, athletics, and wrestling. Rates of MSPs in the past year (MSPs-12) and week (MSPs-7d) were assessed using standard questionnaires.
Overall proportions of MSPs-12 and MSPs-7d were 70 and 74.2%, respectively. MSPs-12 were more frequently reported on shoulders (40.6%), neck (37.1%) and hips/thigh (34.4%), while MSPs-7d were predominant on hips/thigh (29.5%), shoulders (25.7%), and upper back (17.2%). Proportions of MSPs-12 and MSPs-7d varied significantly by sport disciplines, with highest values among basketball players. Again, highest MSPs-12 proportions on shoulders (29.7%, P = 0.02), wrists/hands (34.6%, P = 0.001), (40.2%, P = 0.0002), and knees (38.8%, P = 0.002) were seen among basketball players. High proportions of MSPs-7d were seen on shoulders (29.6%, P = 0.04) for tennis players, wrists/hands (29.4%, P = 0.03) for basketball and football players, and hips/thigh (38.8%, P < 0.00001) for basketball players. Football players had reduced risk of MSPs-12 by 75% on lower back (OR = 0.25; 95% CI. 0.10-0.63; P = 0.003) and by 72% on knees (OR = 0.28; 95% CI. 0.08-0. 95; P = 0.04). In contrast, tennis players were more at risk of MSPs-12 on shoulders (OR = 3.14; 95% CI. 1.14-8.68; P = 0.02), wrists/hands (OR = 5.18; 95% CI.1.40-11.13; P = 0.01), and hips/thigh (OR = 2.90; 95% CI. 1.1-8.38; P = 0.04). Professionals were protected from MSPs-12 on neck pain with a significant reduction of risk by 61% (OR = 0.39, 95% CI. 0.21-0.75, P = 0.03).
MSPs are a reality among athletes and their risk is modulated by sport disciplines, athletic status and gender.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Fasting glucose (FG) and glycated hemoglobin A1c (HbA1c) perform sub-optimally in people of African origin, especially in individuals with sickle-cell trait (SCT). The purpose of this study was to ...compare the relationships between HbA1c, FG, and fructosamine in individuals from Senegal with and without SCT. HbA1c, FG, and fructosamine were measured in 203 adults from Senegal (100 control: 45 with type 2 diabetes (T2D); 103 SCT: 51 with T2D). Significant, positive correlations were observed between HbA1c and FG, fructosamine and FG, and fructosamine and HbA1c in both groups. The limits of agreement were inappropriately large in both groups for the Bland-Altman plots of HbA1c and FG (control: -95.97 to 83.97%; SCT: -115.9 to 91.52%), fructosamine and FG (control: -100.6 to 99.89%; SCT: -105.6 to 100.6%), and fructosamine and HbA1c (control: -52.03 to 38.98%; SCT: -88.04 to 71.41%). In both groups, the greatest proportion of subjects were considered above the clinical cut-point for hyperglycemia when fructosamine was used as the criterion (control: 33%; SCT: 44.6%), and the lowest percentage of subjects were classified as over the clinical cut-point when HbA1c was used as the criterion (control: 21%; SCT: 27.7%).Substantial disparities between HbA1c, FG, and fructosamine were observed in both groups, and these differences were exaggerated in the SCT group. Therefore, these three biomarkers should not be considered to be interchangeable measures of glycemic control. These biomarkers should be used thoughtfully, and special care should be taken when using them in individuals with SCT.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Several predisposing factors for diabetes mellitus have been identified, including cluster determinant 36 (CD36) receptor expression. We aimed to determine the effects of CD36 gene polymorphisms and ...hypermethylation on the plasma CD36 protein levels in type 2 diabetes. We conducted a cross-sectional study involving 100 females (lean healthy control subjects and subjects with type 2 diabetes). This study was conducted at the Human Physiology Laboratory at the Dakar Faculty of Medicine in Senegal. Circulating sCD36 levels and DNA methyltransferase 3a levels were determined by enzyme-linked immunosorbent assay. The other biological parameters were evaluated in a biochemical laboratory. CD36 gene polymorphisms and methylation were explored by real-time polymerase chain reaction and methylation-specific polymerase chain reaction, respectively. sCD36 was negatively correlated with HDL-cholesterol levels (r = - 0.52 p = 0.0001) and triglyceride levels (r = - 0.36 p = 0.01) in control subjects. However, in the type 2 diabetes group, sCD36 levels were positively correlated with total cholesterol levels (r = 0.28 p = 0.04). For rs3211867, control subjects harboring the CC genotypes had significantly higher sCD36 levels than control subjects harboring the AA/AC genotype (p = 0.02); in the type 2 diabetes group, the sCD36 level was not significantly lower in subjects harboring the AA/AC genotype than in subjects harboring the CC genotype (p = 0.27). CD36 gene methylation reduced the sCD36 level in the control subjects compared to control subjects without CD36 gene methylation (p = 0.03). This difference was not significant in the type 2 diabetes group comparing subjects with diabetes with CD36 gene methylation to subjects with diabetes without CD36 gene methylation (p = 0.09). We noted a nonsignificant increase in sCD36 levels in subjects with diabetes with CD36 gene methylation compared to control subjects with CD36 gene methylation (p = 0.27). A combination of the CD36 polymorphism effect and the CD36 methylation effect did not significantly reduce sCD36 levels in subjects with type 2 diabetes. CD36 gene polymorphisms and CD36 gene methylation separately reduce sCD36 levels. Their impacts are compensated for in subjects with type 2 diabetes by an increase in sCD36 levels, the mechanism of which needs to be elucidated.
To isolate and identify the compounds in the essential oils from the leaves of Callistemon viminalis (D.R.) and Melaleuca leucadendron (Linn.) collected in Dakar, Senegal.
The essential oils from the ...leaves of these two myrtaceaes were extracted by steam distillation and analyzed by gas chromatograph and gas chromatography–mass spectrometer.
A total of 34 constituents were identified in the oil of Callistemon viminalis and the major compounds were 1.8-cineole (58.12%), limonene (9.72%), α-terpineol (9.56%), geranial (6.02%), δ-elemene (3.53%), myrcene (2.96%) and α-pinene (2.49%). For the essential oil of Melaleuca leucadendron, 43 constituents were identified, and 1.8-cineole (28.87%), epiglobulol (23.06%), α-pinene (12.22%), limonene (11.65%) and α-terpineol (7.06%) were major compounds.
Considering properties of the identified major compounds, essential oils of both studied myrtaceae could be used in the medicine field including the food, pharmaceutical and cosmetic industry.
Previous studies reported that poor sleep quality (PSQ) was associated with musculoskeletal pains (MSP) and poor physical performance in athletes.
The current study aimed at determining PSQ and its ...associations with MSP in some sub-Saharan athletes.
A cross sectional study was conducted among 205 highly trained and 115 elite athletes (aged: 25 ± 2 years, Body mass index: 22.8 ± 0.9 kg/m
) in Dakar, Senegal, during a competitive season in a variety of sport disciplines including athletics, basketball, football, rugby, wrestling, tennis. Quality of sleep and MSP were assessed using the French version Pittsburgh Sleep Quality Index (PSQI) and French version of Nordic questionnaire respectively. Pain on body joints during a week was defined as seven-day MSP (MSP-7d) and PSQ for a PSQI > 5.
27.8% (95%CI: 23.2-32.9) of the overall sample suffered PSQ, with 33.7% (95%CI: 24.7-44.0) in basketball and 24.7% (95%CI: 16.9-34.6) in football. According to athletic status and gender, PSQ was more prevalent among highly trained (66.3; 95%CI: 55.9-75.3) and men (69.7%; 95%CI: 59.5-78.7). Among athletes with PSQ 43.8% (95%CI: 33.9-54.2) suffered MSP-7d, with 36.6%; highly trained (95%CI: 23.7-42.9) and 28.1% female. Considering body region, hips/thigh (14.6%; 95% CI: 8.74-23.4) and upper back (13.5%; 95%CI: 7.88 -21, 1) were more affected. Basketball players were more affected from MSP (MSP-7d = 38.5%; 95%CI: 24. 9-54.1) on high on wrists/hands (MSP-7d = 44.4%; 95%CI: 18.9 -73.3; P = 0.04). Based on athletic status, MSP-7d were higher on highly trained necks (100%; 95%CI: 56.1-100; p = 0.04). PSQ was associated with basketball (OR: 3.062, 95%CI: 1.130-8.300, p = 0.02) compared to Athletic. PSQ and MSP-7d were associated on Wrist/hands (OR: 3.352, 95%CI: 1.235-9.099, p = 0.01), and at the upper back (OR: 5.820, 95%CI: 2.096-16.161, p = 0.0007).
These results indicate that PSQ is considerable among Senegalese athletes and is associated with MSP during a week. Hence, we recommend to look for strategies optimizing good quality of sleep in order to reduce pains, to improve health.
•The potential symptomatic and neuroprotective effects of chronic treatment with a VOC bark extract are tested in a mouse model of early Parkinson's disease•VOC treatment improves motor coordination ...and reduces depression-like behavior•VOC treatment reduces microglial reaction but does not prevent nigrostriatal neurodegeneration•VOC may provide benefit in the symptomatic treatment of prodromal phase of PD.
Voacanga africana (VOC) has been widely used for many years in the African traditional medicine system for the treatment of a wide range of diseases, including mental disorders but VOC has never been tested in vivo in the context of neurodegenerative diseases for its potential symptomatic and/or disease-modifying action.
We aim to evaluate the behavioral, neuroprotective and anti-inflammatory effects of VOC bark extracts in a mouse model of Parkinson's disease (PD) mimicking the early stages of the disease characterized by non-motor deficits and mild motor symptoms.
Bilateral injections of 6-hydroxydopamine (6-OHDA) were performed in the striatum of mice and VOC was injected intraperitoneally every day for 20 days in a group of 6-OHDA-injected mice. Rotarod, forced swim test and open field test were used to examine behavioral deficits. Dopaminergic neurodegeneration and microglial activation were assessed using quantitative immunohistochemistry.
VOC treatment reversed the lesion-induced decrease in fall latency in the rotarod test and the increase in immobility time measured in the forced swim test, suggesting improved motor coordination and reduced depressive-like behavior. In the open field test, the distance travelled, which assesses gross locomotor activity, and the time spent in the center, which is considered as an index of anxiety, were not significantly modified in 6-OHDA lesioned mice either treated or not with VOC. VOC treatment in 6-OHDA-lesioned mice mitigated the increase of IBA1 immunoreactivity but had no effect on the lesion-induced loss of TH-positive fibers in the striatum and neurons in the substantia nigra, suggesting a modest anti-inflammatory effect that did not translate into efficient neuroprotection.
These experiments, which evaluate for the first time the effect of VOC bark extracts in a model of early PD, show that VOC treatment improves depressive-like and motor behaviors without inducing a generalized hyperactivity and attenuates neuroinflammation, suggesting its possible use in prodromal PD.
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Background Apolipoprotein E is a multifunctional protein that plays an important role in lipid metabolism. It is encoded by the
gene. However,
gene polymorphism has not been very well studied in the ...Senegalese population. Therefore, we studied allele frequencies, genotype distributions, and the relationship between
gene polymorphisms and lipid parameters in the Senegalese women population. Methodology This study included 110 healthy women aged 35-72 years. The mean age was 49.8 ± 8.1 years. For all subjects, lipid parameters were analyzed from fasting serum, and
genotypes were identified by PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) based analysis. Results Variations in the frequencies and distribution of the
alleles and genotypes were observed (ε3: 47.3%; ε2: 43.2%; ε4: 9.6%; and ε2/ε3: 70%; ε2/ε4: 16.4%; ε3/ε3: 10.9%; ε2/ε4: 2.7%). Compared to the ε3ε3 genotype carriers, carriers of the ε3ε4 genotype had a significantly higher rate of total cholesterol (p=0.03) and no high-density lipoprotein-cholesterol (p=0.02). Univariate analysis showed that the
ε4 allele increases the low-density lipoprotein-cholesterol rate (OR=3.06; 95% CI: 1.16-8.22; p=0.02). Conclusion Our study has shown a difference in
allele frequencies and genotype distributions with a total absence of ε2ε2 and ε4ε4 genotypes in a sample of Senegalese women. We also found that
gene polymorphism might play a role in plasma lipid levels.
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