Effects of high-intensity statin therapy on steroid hormones and vitamin D in type 2 diabetic men: A prospective self-controlled study.

The study aimed to assess the effect of high-intensity statin therapy on testicular and adrenal steroids and vitamin D levels in type 2 diabetic men. A prospective study, conducted between March 2021 and July 2022, including 60 men with type 2 diabetes, aged 40-65 years, statin-free, and in whom treatment with high-intensity statin was indicated. The patients had two visits, before and 6 months after a daily intake of 40 mg of atorvastatin. During each visit, they underwent a clinical examination, and a fasting blood sample was collected for biological and hormonal measurements. There was a significant increase in the prevalence of decreased libido (from 22% to 47%, p = 0.001) and a significant decrease in the frequency of sexual intercourse (from 4 [1-8] to 3 [0-4] per month, p = 0.005). The median ADAM's score significantly increased (from 4 [2-7] to 6 [3-8], p = 0.000). Twenty-two percent of the patients developed gynecomastia. The median total, bioavailable and free testosterone significantly decreased from 15.1 (11.4-17.4), 6.3 (5.0-7.8), and 0.27 (0.22-0.33) nmol/L to 12.7 (10.7-15.9), 5.7 (4.4-7.0), and 0.24 (0.19-0.30) nmol/L, respectively, with no change in FSH and LH levels. Three patients (5%) developed hypogonadism (testosterone <8 nmol/L). There was a significant decrease in DHEAS from 4.5 (2.8-6.1) to 3.8 µmol/L (2.6-5.6) and no change in cortisol and vitamin D levels. High-intensity statin therapy decreased androgen levels in type 2 diabetic men with significant clinical impact.

Association of MTHFR (C677T, A1298C) and MTRR A66G polymorphisms with fatty acids profile and risk of neural tube defects.

OBJECTIVE: This study aims to determine if 5,10-methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) and methionine synthase reductase (MTRR A66G) gene polymorphisms were associated with fatty acid (FA) levels in mothers of fetuses with neural tube defects (NTDs) and whether these associations were modified by environmental factors. METHODS: Plasma FA composition was assessed using capillary gas chromatography. Concentrations of studied FA were compared between 42 mothers of NTDs fetuses and 30 controls as a function of each polymorphism by the Kruskal-Wallis nonparametric test. RESULTS: In MTHFR gene C677T polymorphism, cases with (CT + TT) genotype had lower monounsaturated FAs (MUFA) and omega-3 polyunsaturated FA (n-3 PUFA) levels, but higher omega-6 polyunsaturated FAs (n-6 PUFA) and omega-6 polyunsaturated FAs: omega-3 polyunsaturated FAs (n-6:n-3) ratio levels. In MTRR gene A66G polymorphism, cases with (AG + GG) genotype had lower MUFA levels, but higher PUFA and n-6 PUFA levels. Controls with (AG + GG) genotype had lower n-6 PUFA levels. In MTHFR gene C677T polymorphism, cases with smoking spouses and (CT + TT) genotype had lower MUFA and n-3 PUFA levels, but higher PUFA, n-6 PUFA, and n-6:n-3 ratio levels. Cases with (CT + TT) genotype and who used sauna during pregnancy had lower n-3 PUFA levels. In MTRR gene A66G polymorphism, cases with (AG + GG) genotype and who used sauna during pregnancy had higher PUFA and n-6 PUFA levels. CONCLUSIONS: Further research is required to clarify the association of FA metabolism and (MTHFR, MTRR) polymorphisms with NTDs.

Immunologic effect and clinical impact of erythromycin in septic patients: A randomized clinical trial.

To investigate the potential regulatory effect of erythromycin added to standard care in septic patients on sepsis biomarkers and clinical outcome. It was a single-blind randomized trial including critical septic patients. The primary endpoint was the change in the TNF/IL-10 ratio between days 0 and 6. Changes in other biomarkers, vasopressor use, and 28-day mortality were secondary endpoints. One hundred and ten patients were examined (erythromycin group, n = 55 versus placebo group, n = 55). Clinical features of the groups were well matched. Erythromycin addition had no beneficial effects on the TNF/IL-10 ratio or mortality (51% vs. 47%, p = 0.62). Both groups' serum TNF/IL-10 ratios did not significantly rise (from 0.48 [0.34-1.18] to 0.59 [0.21-1.10] vs. 0.65 [0.25-1.14] to 0.93 [0.24-1.88] in the erythromycin and placebo groups, respectively; p values = 0.86 and 0.12). Serum Procalcitonin (PCT) and CRP dropped considerably in the Erythromycin group, whereas only PCT showed a drop in the placebo group. On day 6, the non-survivors' serum TNF/IL-10 ratio was lower than that of the survivors (0.55 [0.17-1.04] vs 1.08 [0.4-2.28], p = 0.029). Neither the pro/anti-inflammatory imbalance nor the mortality were impacted by the addition of erythromycin to standard care in septic patients (ClinicalTrials.gov ID: NCT04665089 (11/12/2020)).

Altered mucosal and plasma polyunsaturated fatty acids, oxylipins, and endocannabinoids profiles in Crohn's disease.

Selected mucosal and plasma polyunsaturated fatty acids (PUFAs) and related oxylipins and endocannabinoids were determined in 28 Crohn's disease (CD) patients and 39 controls. Fasting blood and colonic biopsies were collected in all participants, during a disease flare for the patients. Thirty-two lipid mediators including PUFAs, oxylipins, and endocannabinoids were assessed by LC-MS/MS. The pattern of lipid mediators in CD patients is characterized by an increase in arachidonic acid-derived oxylipins and endocannabinoids and a decrease in n-3 PUFAs and related endocannabinoids. A model combining increased 6-epi-lipoxin A4 and 2-arachidonyl glycerol with decreased docoasapentaenoic acid in plasma fairly discriminates patients from controls and may represent a lipidomic signature for CD flare. The study findings suggest that lipid mediators are involved in CD pathophysiology and may serve as biomarkers for disease flare. Further research is required to confirm the role of these bioactive lipids and test their therapeutic potential in CD.

Anti Mullerian hormone as a diagnostic tool for polycystic ovary syndrome in women of reproductive age with morbid obesity.

OBJECTIVES: The aim of the study was to analyze the performance of the anti-mullerian hormone (AMH) level for the diagnosis of polycystic ovary syndrome in women with morbid obesity. STUDY DESIGN: A single-centre cross-sectional study was conducted in 50 women of reproductive age with a body mass index (BMI) ≥ 40 kg/m2. Each patient underwent a clinical examination, biological and hormonal assays, and an ovarian ultrasound between the third and the fifth day of the menstrual cycle. Polycystic ovary syndrome was diagnosed according to the Rotterdam's criteria. RESULTS: The mean age of participants was 34.2 ± 7.5 years. Polycystic ovary syndrome was diagnosed in 20 women (40%). Age and anthropometric parameters did not differ between women with and without polycystic ovary syndrome. The mean AMH level was significantly higher in women with polycystic ovary syndrome (3.4 ± 3.6 vs 1.3 ± 1.2 ng/ml, p=0.010). It was positively correlated with the Ferriman and Gallwey score (r=0.496, p=0.016), total testosterone level (r=0.524, p < 10-3) and the LH/FSH ratio (r=0.290, p=0.046). In women aged between 35 and 45 years, the optimum cut-off level for the diagnosis of polycystic ovary syndrome was 0.81 ng/mL, providing a sensitivity and a specificity of 90 and 71%, respectively with an area under the ROC curve of 0.857. CONCLUSIONS: AMH level was significantly higher in morbid obese women with polycystic ovary syndrome compared with those without polycystic ovary syndrome. Specific thresholds for this population must be assessed to improve the sensitivity and specificity of AMH for the diagnosis of polycystic ovary syndrome.

Chemical Composition and in vitro Anti-inflammatory Activity of Wheat Germ Oil Depending on the Extraction Procedure.

This study aimed to examine the chemical composition of wheat germ oil extracted by three different methods, and to evaluate its inhibitory effect on the cyclooxygenase and proteinase activities. The results showed that the contents of policosanols, tocopherols and phytosterols were affected by the extraction procedure. However, the fatty acid composition of the different oil extracts was nearly the same. Among the tested oils samples, cold pressed oil exhibited the strongest inhibitory activity against proteinase (93.4%, IC50 =195.7 µg/mL) and cyclooxygenase 1 (80.5%, IC50 =58.6 µg/mL). Furthermore, the cold pressed oil had the highest content of octacosanol, ß-sitosterol and α-linolenic acid, suggesting that those bioactive compounds could be essential for the potent ani-cyclooxygenase activity. The present data revealed that wheat germ oil contained cyclooxygenase and trypsin inhibitors, which are the promising therapeutic target for the treatment of various inflammatory diseases. Thus, wheat germ oil might be used to develop functional foods and pharmaceutic products for the human health.

Circulating MMP-7 and VEGF as potential predictive biomarkers for recurrent implantation failures.

Recurrent implantation failure (RIF) is considered to be one of the major limiting factors of assisted reproductive technology (ART) programme success. The current study focused on the investigation of matrix metalloproteinases (MMPs), tissue inhibitors of MMPs (TIMPs), cytokines and cell adhesion molecules in peripheral blood (PB) and follicular fluid (FF) obtained from 44 women aged between 25 and 39 years old and undergoing intracytoplasmic sperm injection (ICSI). These women were divided into two groups: 22 RIF women with embryo implantation failures after the transfer of at least four fresh or frozen-thawed good quality embryos in a minimum of three ICSI cycles, and 22 ICSI success women (controls) who achieved a clinical pregnancy at their first ICSI attempt. The PB and FF samples were obtained from each patient on the day of oocyte retrieval. MMP-1, -2, -3, -7, -9, TIMP-1, -2, vascular endothelial growth factor (VEGF), leukaemia inhibitory factor (LIF), vascular cell adhesion molecule 1 (VCAM1) and intercellular adhesion molecules 1 (ICAM1) were analyzed using enzyme-linked immunosorbent assay of PB and FF. Our results showed significant decreases in PB MMP-7 and PB VEGF in the RIF group compared with controls [281.11 (33-614) pg/ml vs 119.92 (27-441) pg/ml; P-value = 0.030] and [82.54 (25.94-210.20) pg/ml vs 30.93 (13.62-193.33) pg/ml; P-value = 0.022; respectively]. Receiver operating characteristic (ROC) curve analysis showed informative area under the curve values for PB MMP-7, as well as for PB VEGF, making them able to be proposed as biomarkers of the RIF. Therefore, circulating MMP-7 and VEGF seem to play an interesting role in embryo implantation in in vitro fertilization (IVF)/ICSI cycles and could be proposed as circulating biomarkers of the RIF. These results could be helpful for clinicians and patients to choose the best rescue strategy and treatment to minimize implantation failure in women undergoing IVF/ICSI procedures after the first attempt.

Prognostic Significance of Plasma Folate and Cobalamin Concentrations in Non-Muscle-Invasive Bladder Cancer: A Prospective Cohort Study.

This cohort study aimed to investigate prognostic significance of plasma folate and cobalamin in non-muscle-invasive bladder cancer (NMIBC). A total of 177 NMIBC patients were followed over a period extending to 6 years. Cox regression models were applied to estimate risks for recurrence and progression according to plasma vitamins tertiles. Compared to first tertile, third tertile of plasma folate [HR (95% CI), 10.5 (1.32-83.4); p = 0.026] was associated, and of plasma cobalamin [2.12 (0.63-7.25); p = 0.116] tended to be associated with higher risk for progression. NIMBC patients with high folate/cobalamin statuses should make the physician more alert for a likely poor outcome.

Low Plasma 25-Hydoxyvitamin D at Diagnosis Predicts Poor Outcomes in Patients with Bladder Cancer: A Prospective Cohort Study.

This study aimed to investigate whether plasma 25-hydroxyvitamin D (25-OHD) at diagnosis predicts poor outcomes in patients with urothelial bladder cancer. A total of 177 patients with non-muscle-invasive bladder cancer (NMIBC) were prospectively followed up over a period extending beyond 6 years. Data on poor outcomes (ie., recurrence, progression, and mortality) were collected. Plasma 25-OHD was measured by immunoassay. Cutoff-Finder web application was used to determine the best 25-OHD cutoff point to predict a specific poor outcome. Cox-hazard models were applied to test how plasma 25-OHD affect patients outcome while adjusting for potential confounding factors. During the follow-up period, tumor recurrence and progression occurred in 40.7% and 14.1% of patients, respectively and 11.3% of patients died. Baseline 25-OHD was lower in patients who experienced poor outcome (12.2 ± 7.44 vs. 16.7 ± 10.6 ng/mL; p < 0.001). Multi-adjusted HR (95% CI) for vitamin D deficiency (25-OHD < 12 ng/mL) was 2.09 (1.27-3.44) for recurrence, 2.63 (1.06-6.49) for progression and 2.93 (1.04-8.25) for mortality in patients with NMIBC. Low plasma 25-OHD in NMIBC patients is associated with higher risk of poor outcome. Future work is required to test whether correction of vitamin D deficiency will improve quality of life and extend survival in these patients.

Protective Effect of Tunisian Flaxseed Oil against Bleomycin-Induced Pulmonary Fibrosis in Rats.

The aims of this study are to investigate the preventive effect of flaxseed oil (FO) on bleomycin (BLM)-induced pulmonary fibrosis (PF). Thirty adult male Wistar rats (180-220 g) were randomly divided into three groups. The control group (G1) received no treatment, the group (G2) received only intratracheally BLM, and the group (G3) received FO (2 mL/kg body weight) once a day for 60 days + BLM (4 mg/kg body weight "bw"). Our results demonstrated that FO protected against BLM-induced PF, by increasing proline, fructose, glucose, glyceride, choline, lactate, and malate metabolites in bronchoalveolar lavage fluid (Balf) which are involved in anti-inflammatory reactions. Also, FO-treatment reduced the score of fibrosis and the inflammatory index and revealed a decrease in tumor growth factor beta (TGFß) density in alveoli, inflammatory infiltrate and fibrocytes, comparatively to the BLM group. As well, our data demonstrated that acute BLM-induced fibrosis was accompanied by an oxidative stress in lung tissue as assessed by an increase of lipid peroxidation as well as antioxidant enzyme activities depletion such as superoxide dismutase (SOD) and catalase (CAT). The FO treatment reversed all disturbances of BLM-induced oxidative stress parameters, and increased fatty acids levels promoting anti-inflammatory reactions especially in erythrocytes (linoleic, α-linolenic, docosapentaenoic acids).

Association of MTHFR C677T, MTHFR A1298C, and MTRR A66G Polymorphisms with Neural Tube Defects in Tunisian Parents.

OBJECTIVE: This study aims to investigate the association of 5,10-methylenetetrahydrofolate reductase (MTHFR C677T and A1298C) and methionine synthase reductase (MTRR A66G) gene polymorphisms with neural tube defects (NTDs) in a Tunisian population. METHODS: Genotyping was performed by polymerase chain reaction with restriction fragment length polymorphisms (PCR-RFLPs) using the restriction enzymes. Allele and genotype frequencies were compared between mothers and fathers of fetuses with NTDs with matched controls based on an association analysis using SPSS software. RESULTS: MTHFR (C677T, A1298C) and MTRR A66G polymorphisms were found to be protector factors for NTD fetuses in the mother group. In addition, a combination of the three wild-type alleles C677/A1298/A66 has increased four-fold the incidence of NTDs (p = 0.004, OR = 3.96, 95% CI: 1.53-10.23). In the father group, MTHFR C677T was a risk factor for NTDs. However, no association was found between MTHFR A1298C, MTRR A66G, and the occurrence of this anomaly. The analysis of MTHFR C677T and MTRR A66G polymorphisms has demonstrated a significant difference in vitamin B12 levels between recessive and dominant genotypes in case mothers (p < 0.05). CONCLUSION: Additional studies are required to better understand the roles of parental gene polymorphisms related to folate-homocysteine metabolism in the pathogenesis of NTD.

Interaction Effects of Plasma Vitamins A, E, D, B9, and B12 and Tobacco Exposure in Urothelial Bladder Cancer: A Multifactor Dimensionality Reduction Analysis.

The study aimed to examine circulating vitamins A, E, D, and B12 and folate in patients with urothelial bladder cancer (UBC) and detect potential interaction effects of these micronutrients on UBC risk. A case-control study was conducted on 262 UBC patients and 254 matched controls. Vitamins A and E were assessed by ultra performance liquid chromatography, and vitamins D and B12 and folate were assessed by immunological methods. Binary logistic regression models were used to test associations of plasma vitamins tertiles with UBC risk. A multifactor dimensionality reduction method (MDR) was applied to assess interactive effects of the vitamins and tobacco on UBC risk. Higher levels in vitamins A, E, and D were associated with lower occurrence of UBC. No significant association was observed in plasma folate or vitamin B12 with UBC. There were redundancy interactions of plasma vitamin D with tobacco and with plasma vitamin A on UBC risk. Even though the study could not ascertain causality, the findings suggest that vitamins A, E, and D might be protective against UBC. Vitamins A and D interact antagonistically with each other's and with tobacco to modulate UBC risk. These interactions should be taken in consideration for the prevention of UBC.

Associations of rs1883832 and rs4810485 polymorphisms of CD40 gene with myocardial infarction in the Tunisian population.

Context: Cluster of differentiation 40 (CD40), and its ligand CD40L, are major co-stimulatory molecules whose interactions are important in both cellular and humoral immunity, and has been suggested to play a role in the pathogenesis of acute coronary syndrome. Objective: The aim of this study was to examine the association of CD40 polymorphisms (-1 C>T (rs1883832) and 945G>T (rs4810485)) and myocardial infarction (MI), and to test the association of CD40 gene haplotypes with MI in Tunisians. Materials and methods: Three hundred and fifty MI patients and 301 apparently healthy controls were included in the study. The polymorphisms of CD40 were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: There were significant differences in the genotype and allele frequencies of CD40 gene -1 C>T (rs1883832) polymorphism between cases and controls. Stratifying according to gender, the association between the TT genotype and MI was statistically significant in males, only. Haplotype analysis revealed that the C-T and T-G haplotypes were associated with an increased risk of MI (p = 0.012 and p < 0.001, respectively). Conclusions: Our work showed a significant association between the -1 C>T (rs1883832) polymorphism of the CD40 gene and MI in the Tunisians.

Association of matrix metalloproteinase 3 and endogenous inhibitors with inflammatory markers in mitral valve disease and calcification.

Calcific mitral valve stenosis (MVS) is a common disease characterized by extensive remodeling of the extracellular matrix via matrix metalloproteinases (MMPs). The mechanism of calcification due to extensive matrix remodeling remains unclear. In this study, we investigated the relationship between MMP-3, tissue inhibitors of metalloproteinases (TIMPs) as well as pro-inflammatory cytokines and the phenomenon of calcification in MVS. 212 patients having rheumatic mitral stenosis (RMS) and 155 healthy control subjects were recruited in the Cardiology Department of La Rabta Hospital University. Levels of MMP-3, TIMPs, IL-6 and TNF-α were measured by ELISA sandwich assay, hs-CRP was measured by immunoturbidimetry. Plasma levels of MMP-3, TIMP-1 and MMP-3/TIMP-2 ratio were lower only in RMS women in comparison to the control group. Calcification degree correlated positively with MMP-3 in women and men. In addition, calcification was correlated positively with MMP-3/TIMPs ratio in women patients. The inflammatory parameters were positively associated with extracellular matrix turnover biomarkers in men patients. In patients, the level of MMP-3 was increased in men and women with a calcification score ≥ 5. In addition, MMP-3 level predicted the occurrence of calcification. At ROC curves analysis, the cut-off MMP-3 level was in women was 9.21 ng/ml (sensitivity 51.1%, specificity 89.3%) and in men was 12.84 ng/ml (sensitivity 78.6%, specificity 77.8%). The high levels of MMP-3 and the biomarkers of inflammation contribute to valvular remodeling and calcification of the mitral valve.

Decreased Oleic Acid and Marine n - 3 Polyunsaturated Fatty Acids in Tunisian Patients with Urothelial Bladder Cancer.

Fatty acids (FAs) are thought to impact carcinogenesis by affecting cell signaling. A case-control study including 250 patients with urothelial bladder cancer (UBC) and 250 controls was conducted. Plasma FAs composition was assessed using capillary gas chromatography. Associations of individual and classes of FAs with UBC were controlled for the main risk factors for UBC. Plasma FAs profile was different in patients compared to controls. Higher levels (third tertile vs. first tertile) in palmitic acid (PA) [multi-adjusted OR (95% CI), 1.83 (1.14-2.92)], and n - 6:n - 3 FA ratio [4.13 (2.38-7.16)] were associated with increased risk for UBC [multi-adjusted OR (95% CI), 1.83 (1.14-2.92)]. In contrast, higher levels (third tertile vs. first tertile) in oleic [0.54 (0.34-0.86)], dihomo-γ-linolenic (DGLA) [0.47 (0.29-0.74)], eicosapentaenoic (EPA) [0.32 (0.19-0.52)], and docosahexaenoic (DHA) acids [0.33 (0.20-0.53)] were associated with lower risk for UBC. Although the study design does not allow proving causality, the findings suggest a possible protective role of oleic acid and marine n - 3 polyunsaturated FAs (PUFAs) against bladder carcinogenesis.

Haplotype-based association of Vascular Endothelial Growth Factor gene polymorphisms with urothelial bladder cancer risk in Tunisian population.

BACKGROUND/AIM: Accumulated data suggested that Vascular Endothelial Growth Factor is a major mediator in vasculogenesis, angiogenesis and recently in tumorigenesis. Therefore, we aimed to investigate for the first time the association between VEGF gene variants (-2549I/D (rs35569394), -2578C/A (rs699947), and +936C/T (rs3025039)) with urothelial bladder cancer (UBC) in Tunisian population. METHODS: A total of 218 UBC patients and 204 controls were recruited and genotyped by Polymerase Chain Reaction technique. Odds ratios (OR) and 95% confidence intervals (CIs) were used to access the association between the VEGFA gene polymorphisms and UBC. RESULTS: We found a significant decreased risk association of -2578 C/A polymorphism with UBC (OR (95% CI), 0.62 (0.41-0.94), P = .026) for CA genotype and (OR (95% CI), 0.40 (0.21-0.76), P = .005) for double homozygous mutant genotype. No associations were found in case of both polymorphic sites of VEGF, vis. -2549I/D and +936C/T, respectively. Haplotype analysis revealed a strong linkage disequilibrium between -2578C/A and -2549I/D and CIC combination is the significant haplotype associated with increased risk of UBC (OR (95% CI), 3.63 (1.47-8.97), P = .005). Regarding tumor grade/stage and family history of cancer, no associations were found for -2578C/A polymorphism. CONCLUSION: CIC haplotype of VEGF gene may be important risk factor for UBC development in Tunisia.

Inflammations mediators and circulating levels of matrix metalloproteinases: Biomarkers of diabetes in Tunisians metabolic syndrome patients.

AIMS: This study investigates the relationships between matrix metalloproteinases, inflammations mediators and type 2 diabetes mellitus in Tunisians metabolic syndrome (Mets) patients. METHODS: The study has included 239 MetS patients and 247 controls. Mets was defined according to the NCEP-ATPIII report. Mets patients were also divided into two categories: 29 MetS non-diabetics and 210 MetS diabetics. Dysglycemia markers, matrix metalloproteinase-9 (MMP-9), Tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2), tumor necrosis factor α (TNF-α), C-reactive protein (CRP) levels and White Blood Cells (WBC) counts were determined in patients and controls. RESULTS: In our study, the level of inflammatory markers WBC, TNF-α and matrix metalloproteinases (MMP-8 and MMP-9) were significantly higher in diabetic patients with MetS, as compared with non-diabetic MetS patients. Inflammation mediators and MMP-9 were significantly associated with many clinical characteristics of MetS. The use of ROC "Receiver Operating Characteristic" analysis revealed the impact of TNF alpha on diabetes patients with MetS. In fact TNF alpha was found as a sensitive parameter in these patients with a sensitivity of 85%. CONCLUSION: Inflammation, matrix metalloproteinases and dysglycemia markers are not expressed in isolation but rather concurrently and are continuously interacting with each other, in MetS and diabetics patients. These markers fit with an early stage of cardiovascular disease (CVD); and measuring them could improve the risk evaluation, an early diagnosis, and the prognosis of CVD.

Vitamin D Deficiency is Widespread in Tunisian Pregnant Women and Inversely Associated with the Level of Education.

BACKGROUND: Vitamin D deficiency seems to be common in pregnant women and would be associated with an increased risk of maternal and fetal poor outcomes. This study aimed to determine the prevalence and the main risk factors for vitamin D deficiency in pregnant women living in a sun-rich environment. METHODS: A total of 255 pregnant women living in Tunis City (latitude, 36 degrees N) were randomly selected at 12 - 18 weeks of gestation. Plasma 25-hydroxyvitamin D (25-OHD) was assessed by chemiluminescence immunoassay method. A logistic regression model adjusting for confounding variables was used to identify the independent risk factors for vitamin D deficiency. RESULTS: Plasma 25-OHD concentrations ranged from 4.02 to 78.3 nmol/L [median (IQR), 18.0 (13.6)]. More than 96% of the study population had 25-OHD levels below 50 nmol/L with 82.3% of women having vitamin D deficiency (25-OHD < 30 nmol/L) and 31.4% of women having severe vitamin D deficiency (25-OHD < 15 nmol/L). Daily dietary vitamin D intake [median (IQR), 3.49 (2.92) µg] was clearly lower than the recommended dose. Vitamin D deficiency was more frequent during the low-sunshine season, and in veiled women and those with an average level of education. In multivariate analysis, the independent predictors of vitamin D deficiency were low sunshine season [multi-adjusted OR (95% CI), 2.29 (1.24 - 4.22); p < 0.01], covering clothing [OR (95% CI), 2.54 (1.23 - 5.24); p < 0.05], and average level of education [OR (95% CI), 2.11 (1.09 - 5.91); p < 0.05]. CONCLUSIONS: Tunisian pregnant women, especially those with average/high level of education, are exposed to a high risk of vitamin D deficiency. The main causes of hypovitaminosis D are low sunshine exposure and little dietary vitamin D intake. Public health policies should target the awareness for optimal and safe sun exposure and adequate vitamin D dietary intake. Otherwise, tolerable vitamin D supplementation should be prescribed.

Maternal 25-hydroxyvitamin D level and the occurrence of neural tube defects in Tunisia.

OBJECTIVE: To determine whether low vitamin D levels in pregnant women are associated with the occurrence of neural tube defects (NTDs) in Tunisia. METHODS: In a prospective study, pregnant women were recruited at a center in Tunis between January 1, 2012, and December 30, 2013. Women carrying a fetus with a severe NTD were recruited before elective termination. Matched, healthy pregnancy women were enrolled into a control group. Plasma levels of 25-hydroxyvitamin D were measured by a competitive chemiluminescence immunoassay. RESULTS: Overall, 68 women formed the NTD group and 64 the control group. The mean maternal vitamin D level was significantly lower in the NTD group (20.65±10.25nmol/L) than in the control group (28.30±13.82nmol/L; P<0.001). Vitamin D deficiency was recorded for 53 (78%) women in the NTD group and 39 (61%) in the control group. Vitamin D insufficiency was recorded for 15 (22%) women in the NTD group and 20 (31%) in the control group. Vitamin D sufficiency was found only in the control group (n=5 [8%]; P<0.001). CONCLUSION: The findings confirm an association between a decreased vitamin D level in pregnant women and the risk of fetal NTDs.

Bladder Cancer is Associated with Low Plasma 25-hydroxyvitamin D Concentrations in Tunisian Population.

Little evidence suggests an impact of vitamin D on bladder cancer risk in Caucasians. This study aimed to investigate association of plasma 25-hydroxyvitamin D (25-OHD) with urothelial bladder cancer (UBC) risk in Tunisians. A case-control study included 250 patients with UBC and 250 healthy controls. Plasma 25-OHD was assessed by a competitive chemiluminescence immunoassay. Vitamin D deficiency and insufficiency were defined as 25-OHD <30 nmol/L and 30 to 49.99 nmol/L, respectively. Logistic regression models adjusting for gender, age, smoking status, duration of smoking, occupational exposure, and season were applied. Vitamin D deficiency (50.4% vs. 34.8%; P < 0.001) and insufficiency (40.4% vs. 26.8%; P < 0.001) were more frequent in patients than controls. Multivariate analysis showed that UBC is associated with vitamin D deficiency [odd-ratio (95% confidence interval), 3.71 (1.76-7.80); P = 0.001] and vitamin D insufficiency [2.65 (1.40-5.01); P = 0.003]. Other predictors of UBC were female gender, tobacco use, smoking duration, and occupational exposure. Plasma 25-OHD concentrations are low in Tunisian patients with UBC. These findings support experimental and epidemiological evidence of protective role of vitamin D against UBC but could not ascertain causal relationship. Further prospective studies and clinical trials are warranted to check causality.