Incidence of the Mucopolysaccharidoses in Tunisia, 1999 - 2021.

BACKGROUND: This cross-sectional study aimed to describe and discuss the epidemiology of mucopolysaccharidoses (MPS) in Tunisia. METHODS: Patients diagnosed with a MPS disorder in two referral laboratories in Tunisia between 1999 and 2021 were included. Diagnosis was based on clinical and radiological features and analysis of urinary glycosaminoglycans, and enzyme assay in some of the patients. RESULTS: Over the twenty-two years, 199 patients were diagnosed with MPS in Tunisia. The disorder was classified as MPS I, MPS II, MPS III, MPS IV, and MPS VI in 15.07%, 1.5%, 38.69%, 17.08% and 7.03% patients, respectively. Due to the lack of enzyme analysis, the disorder was classified as MPS I or II in 20.6% of patients, and no cases of MPS VII and IX were documented. Gender-ratio was 1.5 and age at diagnosis varied from 3 months to 18 years with a median of 46 months. Patients originated from across Tunisia, and no hotspot site was identified. During the survey period, 3,822,983 births occurred, which provides an estimated global incidence of MPS of 1:20,123 live births (4.97 per 100,000). MPS III was the most frequent type with an estimated incidence of 1.91 cases per 100,000 newborns. CONCLUSIONS: MPS disorders, especially MPS III are relatively frequent in Tunisia, likely due to a high rate of consanguineous marriages. Implementation of enzyme and genetic tests in Tunisia will allow diagnosis confirmation and subtype recognition, as well as accurate genetic counseling and prenatal diagnosis for MPS.

Molecular characterization of CTNS mutations in Tunisian patients with ocular cystinosis.

BACKGROUND: Ocular cystinosis is a rare autosomal recessive disorder characterized by intralysosomal cystine accumulation in renal, ophthalmic (cornea, conjunctiva), and other organ abnormalities. Patients with ocular cystinosis are mostly asymptomatic and typically experience mild photophobia due to cystine crystals in the cornea observed accidently during a routine ocular examination. The ocular cystinosis is associated with different mutations in CTNS gene. Cysteamine therapy mostly corrects the organ abnormalities. METHODS: This study was performed in collaboration with the department of ophthalmology of Farhat Hached Hospital. The Optical Coherence Tomography (OCT) of the cornea and retinal photography were used to search cystine crystals within the corneas and conjunctiva in eight Tunisian patients. Screening for the common 57-kb deletion was performed by standard multiplex PCR, followed by direct sequencing of the entire CTNS gene. RESULTS: The studied patients were found to have cystine crystal limited anterior corneal stroma and the conjunctiva associated with retinal crystals accumulation. CTNS gene sequencing disclosed 7 mutations: three missense mutations (G308R, p.Q88K, and p.S139Y); one duplication (C.829dup), one framshift mutation (p.G258f), one splice site mutation (c.681 + 7delC) and a large deletion (20,327-bp deletion). Crystallographic structure analysis suggests that the novel mutation p.S139Y is buried in a first transmembrane helix closed to the lipid bilayer polar region, introducing a difference in hydrophobicity which could affect the hydrophobic interactions with the membrane lipids. The second novel mutation p.Q88K which is located in the lysosomal lumen close to the lipid membrane polar head region, introduced a basic amino acid in a region which tolerate only uncharged residue. The third missense mutation introduces a positive change in nonpolar tail region of the phospholipid bilayer membrane affecting the folding and stability of the protein in the lipid bilayer. CONCLUSIONS: Our data demonstrate that impaired transport of cystine out of lysosomes is the most common, which is obviously associated with the mutations of transmembrane domains of cystinosine resulting from a total loss of its activity.

Risk factors in autism spectrum disorder: A Tunisian case-control study.

Background: Autism spectrum disorder (ASD) is a neurodevelopmental condition that causes disability in social interaction, communication, and restrictive and repetitive behaviors. Common environmental factors like prenatal, perinatal, and/or postnatal factors play a key role in ASD etiologies. Moreover, specific metabolic disorders can be associated with ASD. Subjects and methods: We performed a retrospective case-control study in child psychiatry clinics, involving 51 children with ASD and 40 typical development controls (TDC). Results: We found a correlation between children being breastfed for less than 6 months, having fathers more than 40 years old at childbirth in ASD compared to TDC group. Our study also associated low blood cholesterol and low erythrocyte magnesium levels with increased risk for ASD. Conclusion: Findings support the implication of total cholesterol (TC) and erythrocyte magnesium level in defining autism outcome.

The Relationship Between Menopause and Metabolic Syndrome: Experimental and Bioinformatics Analysis.

Menopausal hormonal changes have been associated with the emergence of the metabolic syndrome (MetS) and its consequences such as type 2 diabetes (T2D) and cardiovascular diseases (CVD). The common gene signature and the associated signaling pathways of MetS, T2D, CVD and menopause status have not been widely studied. We analyzed a total of 314 women aged between 35 and 75 years. The sample was divided into two groups: Group I, including women in the premenopausal period and Group II, comprising women in the post-menopausal period. The presence of MetS and its components were evaluated, as well as occurrence of T2D and CVD in both groups. We also exploited the translational bioinformatics approach to choose the common gene signatures for MetS, T2D, CVD and the menopause status. The frequency of the MetS was significantly higher in postmenopausal women than in premenopausal ones (67.1 vs. 27.2%, p < 0.001). Gene mining analysis revealed that a total of 47 genes were commonly associated with MetS, T2D, CVD and the menopausal changes. The gene enrichment analysis showed that these genes were markedly enriched in biological processes, including positive regulation of binding, positive regulation of leukocyte cell-cell adhesion, regulation of lipid localization. Furthermore, P53 signaling pathway, prolactin signaling pathway, parathyroid hormone synthesis, secretion and action were the top enriched pathways. Additionally, network analysis revealed TGFB1, SPP1, MMP2, MMP9, CCL2, IGF1, EGFR, ICAM1, TNF and IL6 as important hub genes with significant interacting partners. These hub genes identified in our study may play key role in menopausal changes and influence the risks of MetS, T2D and CVD.

Potential functions of hsa-miR-155-5p and core genes in chronic myeloid leukemia and emerging role in human cancer: A joint bioinformatics analysis.

Considering the critical roles of hsa-miR-155-5p participated in hematopoietic system, this study aims to clarify the possible pathogenesis of chronic myeloid leukemia (CML) induced by hsa-miR-155-5p.Three different strategies were employed, namely a network-based pipeline, a survival analysis and genetic screening method, and a simulation modeling approach, to assess the oncogenic role of hsa-miR-155-5p in CML. We identified new potential roles of hsa-miR-155-5p in CML, involving the BCR/ABL-mediated leukemogenesis through MAPK signaling. Several promising targets including E2F2, KRAS and FLI1 were screened as candidate diagnostic marker genes. The survival analysis revealed that mRNA expression of E2F2, KRAS and FLI1 was negatively correlated with hsa-miR-155-5p and these targets were significantly associated with poor overall survival. Furthermore, an overlap between CML-related genes and hsa-miR-155-5p target genes was revealed using competing endogenous RNA (ceRNA) networks analysis. Taken together, our results reveal the dynamic regulatory aspect of hsa-miR-155-5p as potential player in CML pathogenesis.

Comprehensive in-silico analysis of damage associated SNPs in hOCT1 affecting Imatinib response in chronic myeloid leukemia.

Non-synonymous single nucleotide polymorphisms (nsSNPs) in hOCT1 (encoded by SLC22A1 gene) are expected to affect Imatinib uptake in chronic myeloid leukemia (CML). In this study, sequence homology-based genetic analysis of a set of 270 coding SNPs identified 18 nsSNPs to be putatively damaging/deleterious using eight different algorithms. Subsequently, based on conservation of amino acid residues, stability analysis, posttranscriptional modifications, and solvent accessibility analysis, the possible structural-functional relationship was established for high-confidence nsSNPs. Furthermore, based on the modeling results, some dissimilarities of mutant type amino acids from wild-type amino acids such as size, charge, interaction and hydrophobicity were revealed. Three highly deleterious mutations consisting of P283L, G401S and R402G in SLC22A1 gene that may alter the protein structure, function and stability were identified. These results provide a filtered data to explore the effect of uncharacterized nsSNP and find their association with Imatinib resistance in CML.

Contribution of ADIPOQ Variants to the Genetic Susceptibility of Recurrent Pregnancy Loss.

Adiponectin is a hormone implicated in regulating energy, lipid, and glucose metabolism and is encoded by the ADIPOQ gene. ADIPOQ variants can regulate the circulating levels of adiponectin. Irregular adiponectin concentrations have been associated with numerous reproductive diseases including recurrent pregnancy loss (RPL). The main objective of this study was to determine whether the 14 selected polymorphisms of the ADIPOQ gene are linked with RPL. The retrospective case-control study comprised a total of 332 women with RPL, adjusted as more than three consecutive abortions of unknown etiology, and 286 healthy controls. They were genotyped for the ADIPOQ variants using allele exclusion method on real-time PCR. Significantly higher rs1501299 minor allele frequencies (MAF) and lower rs2241767 and rs2241766 MAF were seen among RPL women, thereby assigning disease susceptibility and protective aspect to the mentioned variants, respectively. Different associations of ADIPOQ genotypes with RPL were noticed according to the genetic model exploited: rs1501299 and rs2241767 were significantly linked with RPL under the three models, while rs17366568 and rs2241766 were associated with RPL under codominant and dominant models, and rs7649121 was related to RPL under the dominant and recessive models. rs4632532 was linked according to the recessive model only. Based on LD pattern, 2-haplotype blocks were specified. Reduced frequency of AGG and GAGG and increased frequency of TAAG were noted in cases, compared with controls, hence indicating these haplotypes as RPL-protective and RPL-susceptible, respectively. These results support a significant role of ADIPOQ as an RPL candidate locus.

Association of the methylene-tetrahydrofolate reductase gene rs1801133 C677T variant with serum homocysteine levels, and the severity of coronary artery disease.

This study aimed to investigate whether the single nucleotide polymorphism C677T (rs1801133) of the methylene-tetrahydrofolate reductase (MTHFR) gene was associated with the risk of coronary artery disease (CAD) and circulating homocysteine (Hcy) levels in Tunisian population. 310 angiografically diagnosed CAD patients and 210 controls were enrolled in this study. The MTHFR C677T (rs1801133) polymorphism was genotyped, and the Hcy concentrations were measured. The severity of CAD was evaluated using the Gensini scoring system. Compared to the CC genotype, the TT genotype confers a higher risk for CAD severity with an OR = 9.07 and 95% CI = 3.78-21.8. The T allele was the predisposing allele for CAD and that it was probably associated with CAD severity. The area under the ROC curve for Hcy was 0.764 (95% CI 0.660 to 0.868, p = 0.001). The receiver operating characteristics curve (ROC) for Hcy showed its useful prediction of CAD. Hcy levels were not significantly associated with CAD severity expressed by Gensini Score (GS). The MTHFR C677T (rs1801133) polymorphism influences circulating Hcy levels. The MTHFR C677T polymorphism and hyperhomocysteinemia could have an important role in the prediction of the presence and not the severity expressed by GS of CAD.

Identification of genes and miRNA associated with idiopathic recurrent pregnancy loss: an exploratory data mining study.

BACKGROUND: Recurrent pregnancy loss (RPL) is a significant adverse pregnancy complication, with an incompletely understood pathology. While many entities were proposed to elucidate the pathogenic basis of RPL, only few were significant enough to warrant investigation in all affected couples.. The aim of this study was to provide novel insights into the biological characteristics and related pathways of differentially expressed miRNA (DEMs) and genes (DEGs), in RPL, and construct a molecular miRNAs-mRNAs network. METHODS: miRNAs and gene expression data were collected, and a number of DEMs and (DEGs) were obtained, and regulatory co-expression network were constructed. Function and enrichment analyses of DEMs were conducted using DIANA-miRPath. DEGs were screened, and were used in generation of protein-protein interaction (PPI) network, using STRING online database. Modularity analysis, and pathway identification operations were used in identifying graph clusters and associated pathways. DEGs were also used for further gene ontology (GO) analysis, followed by analysis of KEGG pathway. RESULTS: A total of 34 DEMs were identified, and were found to be highly enriched in TGF-ß signaling pathway, Fatty acid metabolism and TNF signaling pathway. Hub miRNAs were selected and were found to be involved in several functional pathways including progesterone-mediated oocyte maturation and Thyroid hormone signaling pathway. Five dysregulated feedback loops involving miRNA and TFs were identified and characterized. Most notably, PPI network analysis identified hub-bottleneck protein panel. These appear to offer potential candidate biomarker pattern for RPL diagnosis and treatment. CONCLUSIONS: The present study provides novel insights into the molecular mechanisms underlying RPL.

Relationship between high sensitivity C-reactive protein and angiographic severity of coronary artery disease.

BACKGROUND: Coronary artery disease (CAD) remains a leading cause of morbidity and mortality. Cytokines play a potential role in atherosclerosis pathogenesis and progression. We investigated the association between high sensitive C-reactive protein (hsCRP) and severity of CAD. METHODS: CAD patients were stratified according to hsCRP cut-off value into high levels hsCRP group (≥ 8.4 mg/L) and low levels hsCRP group (< 8.4 mg/L). Severity of CAD was assessed according to artery stenosis degree and the number of vessel involved. Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS, version 23.0). RESULTS: The mean age was 60.3 ± 11.0 years. The level of hsCRP was increased and ranged from 0.2 to 1020.0 mg/L. Biochemical risk factors and severity of CAD didn't show significant differences between the two groups. In multivariate linear analysis, cardiac troponin I (cTnI) and serum amyloid A (SAA) were predictors of hsCRP. As shown in receiver operating characteristic (ROC) curve analysis performed in patients with ST-segment elevation myocardial infarction (STEMI) and compared to myonecrosis biomarkers, hsCRP (area under the curve (AUC): 0.905; 95%CI: 0.844-0.966; P < 0.001) could be a powerful predictor marker in evaluating the infarct size after myocardial infarction but not better than cTnI. CONCLUSIONS: HsCRP levels were not associated with the severity of CAD but could be useful in the evaluation of myocardial necrosis in patients with STEMI.

Single nucleotide polymorphisms of SCN5A and SCN10A genes increase the risk of ventricular arrhythmias during myocardial infarction.

BACKGROUND: Coronary artery disease (CAD) and its ultimate consequence - myocardial infarction (MI) - are major causes of sudden cardiac death (SCD). Previous studies have demonstrated the role of genetic polymorphisms in the risk of SCD and ventricular arrhythmia (VA) during MI. OBJECTIVES: To investigate the association between single nucleotide polymorphisms (SNPs) of genes implicated in congenital cardiac arrhythmias and the risk of developing VA in the context of MI. MATERIAL AND METHODS: We performed a case-control study in which we genotyped 4 SNPs (rs11708996, rs10428132, rs9388451, and rs2200733) in 469 subjects using amplification refractory mutation system (ARMS) and a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). These SNPs are located in the SCN5A, SCN10A, HEY2, and PITX2 genes, respectively. We first compared 70 patients who had developed VA in the context of MI with 141 healthy controls; next, we compared VA patients with 258 MI patients who did not develop VA during a 1-year follow up. The statistical analyses were adjusted for sex and age. RESULTS: Compared to the controls, 2 polymorphisms were significantly associated with the development of VA during MI, located in SCN5A rs11708996 (p = 0.001) and SCN10A rs10428132 (p = 0.001). Similar results were found when comparing VA cases with patients without VA. No associations of HEY2 and PITX2 polymorphisms were observed. CONCLUSIONS: Our results suggest that the rs11708996 and rs10428132 polymorphisms of the SCN5A and SCN10A genes may contribute to an elevated risk of developing VA in the context of MI. The associated alleles or genotypes may be used to predict the risk, and thus prevent eventual SCD.

Correlation between chemical composition and antibacterial activity of some Lamiaceae species essential oils from Tunisia.

BACKGROUND: Lamiaceae family is one of the most diverse and common plant families in terms of ethnomedicine due to their potential therapeutic effects. The aim of this study is to investigate the correlation between the chemical composition and the antibacterial effect of five essential oils from this family against five reference bacterial strains responsible of nosocomial diseases and foodborne illnesses. METHODS: The commercial essential oils of Tunisian Rosmarinus officinalis, Thymus capitatus, Origanum majorana and Salvia officinalis were analyzed by GC/FID and GC-MS. Essential oils were evaluated for their antibacterial activities by disc diffusion and microbroth dilution methods against five reference bacterial strains: Pseudomonas aeruginosa, Escherichia coli, Salmonella enterica, Bacillus subtilis and Staphylococcus aureus. The inhibition zone diameter values and the twenty major compounds of the selected essential oils were subjected to PCA and HCA analysis. RESULTS: Analysis by GC/FID and GC/MS allowed the identification of ninety-one components representing 96.0 to 98.2% of the total oils. The different component contents varied according to the species. The main components were carvacrol, 1,8-cineole, α-thujone, α-terpineol and α-pinene. The PCA and the HCA of the selected essential oil components and the inhibition zone diameter (IZD) values identified four species groups and subgroups. Each essential oils group constituted a chemotype responsible for their bacterial inhibition ability. Thymus capitatus essential oil showed the strongest antibacterial activity with MBC ranging from 0.73 to 2.94 mg mL- 1. CONCLUSION: Rosmarinus officinalis, Thymus capitatus, Origanum majorana and Salvia officinalis essential oils have shown promising antibacterial activities against reference bacterial strains responsible for nosocomial diseases and foodborne illnesses.

Association of genetic variants in Estrogen receptor (ESR)1 and ESR2 with susceptibility to recurrent pregnancy loss in Tunisian women: A case control study.

Estrogen receptor (ER) signaling is key regulator for maintaining successful pregnancy. Several research suggested that genetic variation in ER genes (ESR)1 and ESR2 is associated with the susceptibility to unexplained recurrent pregnancy loss (RPL), often with inconclusive results. In this study, we investigate the relationship between ESR1 and ESR2 polymorphisms and idiopathic RPL. A total of 444 patients with RPL, defined as three or more consecutive pregnancy losses of unknown etiology, and 446 control women were recruited to the study and their genotypes for ESR1-rs2234693, ESR1-rs3020314, and ESR2-rs928554 variants were determined using allelic exclusion method on real-time polymerase chain reaction. Minor allele frequencies (MAF) of tagging SNPs ESR1 rs2234693 and rs3020314, and ESR2 rs928554 were not significantly different between RPL cases and control women. Considerable higher frequencies of homozygous (2/2) ESR1 rs2234693 genotype carriers were seen between patients vs. control women, which maintained after controlling for age, body mass index (BMI), and menarche. ESR1 haplotype analysis demonstrated two common haplotype (rs2234693-rs3020314) with no linkage disequilibrium between both polymorphisms, and no 2-locus haplotype linked with RPL risk was revealed. The present study confirmed a significant association of specific ESR1 variant (rs2234693) with an increased risk of RPL, further supporting a role for ESR1 as an important candidate locus inducing RPL.

Biochemical parameters and oxidative stress markers in Tunisian patients with periodontal disease.

BACKGROUND: Oxidative stress is involved in many diseases including diabetes and cancer. Numbers of studies have suggested its involvement in the pathogenesis of periodontal diseases. The aim of this study was to evaluate the levels of biochemical parameters and oxidative stress markers in plasma of healthy and chronic periodontitis patients. METHODS: One hundred thirty subjects were divided into two groups; patients (mean age = 42 ± 13.6 y.o) and control (mean age = 44.8 ± 12.6 y.o). Patients and healthy subjects were free from any infection, coronary or heart disease, diabetes or liver failure. Total cholesterol, LDLc, HDLc, Triglycerides (TG), creatinine, uric acid (UA), glucose and urea levels as well as the activities of enzymatic antioxidants such as catalase, glutathione reductase (GR) and total antioxidant capacity (TAOC), were measured in plasma samples using colorimetric assays. Statistical differences between groups were determined by Student's t-test and p ≤ 0.05 was considered as significant. RESULTS: Periodontitis patients exhibited significant decrease in the activities of catalase, TAOC, GR and TG, cholesterol, LDLc, glucose, HDLc, uric acid levels in plasma samples in comparison with healthy subjects. However, no statistically significant differences in the levels of creatinine and urea were observed between the two groups. CONCLUSION: The reduction of plasma antioxidant activities (Catalase, TAOC, GR) may have a role in the pathogenesis of periodontal diseases. Our findings suggest a decrease in the host capacity to control the damage caused by oxidative stress. Therefore, therapeutic strategies, aiming at modulating the oxidative stress could be considered as potential tools for the prevention or treatment of periodontal diseases and their potential systemic effects on the general health.

The Impacts of Ramadan Intermittent Fasting on Oxidant/Antioxidant Stress Biomarkers of Stable Chronic Obstructive Pulmonary Disease Male Patients.

No prior study has evaluated the impacts of Ramadan intermittent fasting (RIF) on oxidant/antioxidant stress (OS/AOS) biomarkers in patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to assess the impacts of RIF on some OS/AOS biomarkers measured in male patients with stable COPD. Fifteen COPD patients (mean age: 71 ± 6 years) fasting Ramadan in 2017 volunteered to take part in the study. Three sessions (before Ramadan [BR], end Ramadan [ER], after Ramadan [AR]) were selected. Blood samples of OS (homocysteine [µmol/L], thiobarbituric acid reactive substances [TBARS, µmol/L]) and AOS (catalase [U/ml], ceruloplasmin [g/L], superoxide dismutase [SOD, ng/ml], zinc [µmol/L], albumin [g/L]) biomarkers were consistently taken 4.5 to 2.5 hr before the iftar. Findings were analyzed by applying Friedman or Kruskal-Wallis ANOVA. Comparisons of the number of patients with high OS [high homocysteine and/or TBARS] and low AOS (low catalase and/or ceruloplasmin and/or SOD and/or zinc and/or albumin) blood values between the three sessions were performed using the Cochran test. The median ± interquartile of homocysteine (BR: 21.48 [18.98-24.49], ER: 23.15 [21.77-26.45], AR: 24.87 [21.91-37.12]), ceruloplasmin (BR: 0.27 [0.24-0.30], ER: 0.28 [0.26-0.33], AR: 0.28 [0.25-0.32]), SOD (BR: 288.00 [112.00-400.00], ER: 182.00 [152.00-386.00], AR: 234.00 [190.00-420.00]) and the mean ± SD of TBARS (BR: 5.66 ± 1.26, ER: 4.59 ± 0.78, AR: 5.29 ± 1.69), catalase (BR: 120.97 ± 54.62, ER: 106.73 ± 50.92, AR: 137.39 ± 40.88), zinc (BR: 11.85 ± 2.01, ER: 12.47 ± 2.34, AR: 12.21 ± 2.58) and albumin (BR: 39.78 ± 3.19, ER: 40.74 ± 2.26, AR: 40.56 ± 2.38) were not significantly affected by RIF. The number of patients with high OS (BR [ n = 13], ER [ n = 15], AR [ n = 14]) or low AOS (BR [ n = 12], ER [ n = 13], AR [ n = 13]) statuses were not significantly influenced by RIF. In conclusion, RIF did not induce any significant statistical or clinical changes in OS/AOS biomarkers or statuses in COPD patients.

α-Amylase and α-glucosidase inhibitor effects and pancreatic response to diabetes mellitus on Wistar rats of Ephedra alata areal part decoction with immunohistochemical analyses.

Ephedra alata, known as a medicinal plant in China, was used in this study as aqueous extract from aerial parts, for diabetes mellitus treatment. This study was carried out on two parts, in vitro, we tested the effect of the studied extract on the inhibition of α-glucosidase and α-amylase activities, and in vivo on Wistar male rats receiving alloxan intraperitoneally at a rate of 125 mg/kg. Extract (100, 200, and 300 mg/kg of body weight) was administrated for 28 days by oral gavage. Blood glucose, amylase, lipase, and lipid profile level were determined. Oxidative stress was evaluated by enzymatic activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), and by estimation of lipid peroxidation and protein carbonyl (PC) level. Histopathological changes in pancreas were investigated under photonic microscopy using immunohistochemical procedure. Our findings showed that aqueous extract inhibited in vitro both α-glucosidase and α-amylase activities and its use in vivo at 300 mg/kg of body weight restored pancreas weight and weight gain, ameliorated significantly (p Ë‚ 0.05) biochemical parameters; it prevented the increase in lipid and protein oxidation and the decrease in enzymatic and non-enzymatic defense system. Histological study of treated animals showed a comparable healed regeneration of beta cells.

Relationship of activin A levels with clinical presentation, extent, and severity of coronary artery disease.

OBJECTIVE: We aimed to evaluate the relationship of serum activin A levels with risk factors, clinical presentation, biochemical marker levels, extent, and severity of atherosclerotic coronary artery disease (CAD). METHODS: In total, 310 CAD patients [92 with ST-segment elevation myocardial infarction (STEMI), 111 with non-STEMI (NSTEMI), and 107 with unstable angina (UA)] and 207 healthy subjects (controls) were enrolled. Activin A levels in all participants were measured using ELISA. Angiographic measurements were performed in patients and not in the healthy subjects. RESULTS: Activin A levels were higher in all patient groups than in controls (patients vs. controls, p=0.041; NSTEMI vs. UA, p=0.744; STEMI vs. UA, p=0.172; NSTEMI vs. STEMI, p=0.104). According to the cut-off value of activin A level, patients with high and low activin A levels had a similar distribution of clinical and biochemical variables but the prevalence of severe stenosis was observed in groups with high activin A levels. Our results revealed that activin A levels did not decrease as thrombolysis in myocardial infarction (risk score increased (p=0.590). The area under the ROC curve for activin A levels in patients was 0.590±0.047 (95% CI: 0.439-0.591, p=0.193). In multiple analysis of the overall population, male gender (ß=-0.260; 95% CI: -617.39 to -110.04; p=0.005) was an independent predictor of activin A levels. CONCLUSION: This study indicated that activin A can not be a predictive marker in CAD and is not associated with extensive and severe CAD. In contrast, the increase in activin A levels in patients, especially in patients with different clinical groups of acute coronary syndromes, suggested its involvement in atherosclerosis.

Hepatic Proteins and Inflammatory Markers in Rheumatoid Arthritis Patients.

BACKGROUND: Rheumatoid arthritis is an autoimmune inflammatory rheumatic disease that causes chronic synovial inflammation eventually leading to joint destruction and disability. The aim of this study was to determine the variations of hepatic proteins, myeloperoxidase, and iron in rheumatoid arthritis Tunisian patients and their implications in inflammation and in iron metabolism. METHODS: Overall, 172 patients from the Rheumatology Department of the University Hospital "Farhat Hached", Sousse-Tunisia between 2011 and 2012, with rheumatoid arthritis (97.1% women, average age: 48±13 yr) and 147 healthy volunteers (70.1% women, average age: 46± 7 yr) were included in this study. Serum hepatic proteins (high-sensitive C-reactive protein, ceruloplasmin, albumin, transferrin, α-1-acid glycoprotein and haptoglobin) were assessed by immunoturbidimetry (COBAS INTEGRA 400, Roche) and ferritin was measured by a microparticulate immunoenzymatic technic (AxSYM, ABBOTT, Germany), Plasma myeloperoxidase was determined by Enzyme-Linked Immunosorbent Assay. Serum iron was measured according to a colorimetric method at 595 nm (CX9-BECKMANN Coulter-Fuller-Ton, CA). RESULTS: Significantly higher levels of high-sensitive C-reactive protein, α-1-acid glycoprotein, Haptoglobin and myeloperoxidase in patients compared to controls (P<10-3). Albumin and iron rates were significantly decreased in patients compared to healthy group (P=0.026 and P<10-3, respectively). There were no differences between cases and controls for levels of ceruloplasmin, transferrin and ferritin (P=0.782, P=0.808, and P=0.175, respectively). CONCLUSION: The high-sensitive C-reactive protein, α-1-acid glycoprotein, and haptoglobin increased in acute phase proteins in rheumatoid arthritis disease. The pro-inflammatory cytokines affect iron metabolism leading to the iron deficiency and rheumatoid anemia, which influenced Tf and ferritin levels.

Pathological interactions between the endothelin-1 and the angiotensin- converting enzyme among Tunisian coronary patients.

BACKGROUND: The correct understanding of the biochemical and metabolic interactions between coronary risk factors contribute to the exploration of cardiovascular pathophysiology and improves therapeutic care. The aim of this study was to explore the endothelin-1 (ET-1) concentration and the angiotensin converting enzyme (ACE) activity among Tunisian patients with coronary heart disease, and to investigate the metabolic relationships between these two markers,… and to assess the possible relationship between them and the different risk factors. In this present study, ET-1 concentration was determined by an analytical method (High Performance Chromatography, coupled by Mass Spectrometry), ACE activity was measured by a kinetic method for patients and healthy controls. These subjects (157 patients and 142 controls) beneficed also by a biochemical exploration (lipid, apolipoproteins and glucose profiles) to quantify cardiovascular risk. RESULTS: A statistically significant increase of the ET-1 concentration was found among patients compared to healthy controls (15.2 ± 5.3 nM vs 7.1 ± 2.7 nM, p < 0,00001). For the ACE activity, in spite the treatment of the majority of patients (97%) with ACE inhibitors, this activity was statistically elevated in patients compared to healthy subjects (86.7 ± 25.4 IU/L vs 42.8 ± 12.1 IU/L, p < 0.00001). Furthermore, a statistically positive correlation was identified between these two cardiac markers (r = 0.68 p < 0.00001). CONCLUSION: The study of the metabolic relationship between the ET-1 and ACE among coronary patients reveals other therapeutics targets.

Gaucher Disease: Clinical, Biological and Therapeutic Aspects.

We present a brief review of Gaucher disease (GD), the most common lysosomal storage disease. GD is a rare autosomal recessive disorder characterized by the defective function of the catabolic enzyme ß-glucocerebrosidase (GBA), leading to an accumulation of its substrate, glucocerebroside. Clinical signs and symptoms include neurological dysfunctions, bone infarcts and malformations, hepatosplenomegaly and hypersplenism leading to anemia, neutropenia and thrombocytopenia. Enzyme replacement therapy with recombinant GBA is the mainstay of treatment for GD, which became the first successfully managed lipid storage disease. Future treatments may include oral enzyme replacement and/or gene therapy interventions.