Therapeutic leukapheresis and thrombapheresis in medical emergencies.

The management of hyperleukocytosis or thrombocytosis by therapeutic cytapheresis in the early 21 st century is far from codified (universal). Therapeutic cytapheresis have been proposed to achieve more rapid cytoreduction in peripheral blood than old universal support in order to quickly prevent potential complications. But, there are no randomized studies demonstrating the superiority of cytapheresis over other treatments alone. In this short review, based on our own experience (since 1980), we will give the indications and the role of cytapheresis procedures and we will try to answer the questions: when is therapeutic cytapheresis appropriate and do they still have a place in 2020, especially as a medical emergency?

Thoughts on a new surgical assistance method for implanting the glenoid component during total shoulder arthroplasty. Part 1: Statistical modeling of the native premorbid glenoid.

INTRODUCTION: The aim of this study was to identify points on the scapula that can be used to predict the anatomy of the native premorbid glenoid. MATERIAL AND METHODS: Forty-three normal scapulas reconstructed in 3D and positioned in a common coordinate system were used. Twenty points distributed over the blade of the scapula (portion considered normal and used as a reference) and the glenoid (portion considered pathological and needing to be reconstructed) were captured manually. Thirteen distances (X) between two points not on the glenoid and 31 distances (Y) between two points of which at least one was on the glenoid were then calculated automatically. A multiple linear regression model was applied to calculate the Y distances from the X distances. The best four equations were retained based on their coefficient of determination (R2) to explain a point on the glenoid being reconstructed (p<0.05). In the first scenario, the glenoid was modeled assuming it was completely destroyed. In the second scenario, only the inferior portion of the glenoid was worn. RESULTS: For a completely destroyed glenoid, the mean error for a chosen distance for a given point on the glenoid was 2.4 mm (4.e-3mm; 12.5mm). For a partially damaged glenoid, the mean error was 1.7mm (4.e-3mm; 6.5mm) for the same distance evaluated for a given point on the glenoid. DISCUSSION/CONCLUSION: The proposed statistical model was used to predict the premorbid anatomy of the glenoid with an acceptable level of accuracy. A surgeon could use this information during the preoperative planning stage and during the actual surgery by using a new surgical assistance method.

Maternal HLA-G*01:01:01:04 protects from anti-HLA-class II immunization in pregnant women.

Factors determining anti-HLA immunization are poorly understood, although anti-HLA immunization following pregnancy is well described. The HLA-G molecule has been extensively described for its implication in immunological tolerance, especially during pregnancy. Transplant studies show an association between HLA-G haplotypes and alloimmunization. Our aim was to investigate the association of HLA-G haplotypes with anti-HLA class I and II immunization in a cohort of women having experienced one or more pregnancies and with no transfusion history. Maternal blood samples (n=270) collected at delivery and formerly screened for anti-HLA antibodies, HLA-A and HLA-B antigens, were screened by NGS for HLA-G gene polymorphism. Univariate analysis further confirmed that the number of pregnancies was significantly associated with anti-HLA class I immunization, whereas no other variable remained significant after Bonferroni correction. Our results showed however that anti-HLA class II immunization was associated with the number of children whereas the HLA-G*01:01:01:04 allele was protective against this immunization.

Views on a new surgical assistance method for implanting the glenoid component during total shoulder arthroplasty. Part 2: From three-dimensional reconstruction to augmented reality: Feasibility study.

INTRODUCTION: The main goal of this study was to propose a new method of surgical assistance for the implantation of a total shoulder prosthesis, with the use of augmented reality (AR). The advantage of this approach is that it supplements information, on the one hand pre-existing or disappeared due to a pathological process, such as the premorbid glenoid, and on the other hand already existing but not accessible to the surgeon during the procedure, such as the so-called "hidden" face of the scapula. MATERIAL AND METHODS: Several information preparation steps were needed. The first consisted in the three-dimensional (3D) rendering of the pathological glenoid, from a point cloud corresponding to the premorbid glenoid based on previously developed regression equations. A library of "healthy" generic glenoids was then created by hierarchical bottom-up analysis. From this database, a so-called adequate normal generic glenoid was fused and matched to the pathological glenoid reconstructed using a morphing technique. An experimental AR application was constructed. Smart glasses were used to display the prepared 3D information. RESULTS: A pathological 3D glenoid was reconstructed and used for the AR application. A complete display of the scene, reconstructed glenoid and full scapula was obtained. However, an offset from reality was observed. The main limitations were technical, related to the connected tool itself and the operating software. DISCUSSION/CONCLUSION: This was a feasibility study of the different steps required to apply AR, from information preparation to its visualization. A new parameter crossing experiment is needed to optimize each step of this process. LEVEL OF EVIDENCE: IV, Basic science study.

IL-1ß gene polymorphism and serum levels in a Tunisian population with acute heart failure.

AIM: The aim of this study was to explore the relationship between IL-1ß-31T/C polymorphism and serum levels of IL-1ß and the risk of acute heart failure (AHF). METHODS: A total of 320 dyspnea patients (160 with AHF and 160 without AHF) and 100 healthy subjects were included in this study. IL-1ß genotyping was performed by PCR-restriction fragment length polymorphism technique. RESULTS: Concentration of IL-1ß was significantly higher in patients with heart failure (HF) compared with non-HF and control groups. Results of the distribution of IL-1ß-31T/C genotypes and allele frequencies did not show any significant difference between the three groups. Serum levels of IL-1ß were found to be higher among TT genotype than TC and CC genotype. CONCLUSION: IL-1ß levels may be useful for the evaluation of diagnosis in acutely decompensated HF.

Effect of PPAR-ß/δ agonist GW0742 treatment in the acute phase response and blood-brain barrier permeability following brain injury.

The systemic response to ischemic stroke is associated with the hepatic acute phase response (APR) that modulates leukocytes recruitment to the injured brain. The inappropriate recruitment of leukocytes to the brain parenchyma can result in blood-brain barrier (BBB) breakdown. Emerging data suggest that peroxisome proliferator-activated receptor beta/delta (PPAR-ß/δ) activation has a potential neuroprotective role in ischemic stroke. However, mechanisms of PPAR-ß/δ mediated protection in ischemic insults remain unclear. In the present study, we determined for the first time, the effects of GW0742, a PPAR-ß/δ agonist on the APR following brain injury and assessed the effects on BBB permeability and tight junction integrity via claudin-5, occludin, and zona occludens-1 expression. C57/BL6 mice were exposed to 1 hour of ischemia and received 10 minutes before reperfusion either a vehicle solution or GW0742. Hepatic expression of chemokines (C-X-C motif ligand: CXCL1, CXCL2, and CXCL10), serum amyloid A-1, tumor necrosis factor alpha, interleukin-1ß, and interleukin-6 was measured, and the extent of brain and hepatic neutrophil infiltration was determined. The results showed that GW0742 treatment decreased infarct volume and edema, reactant production and neutrophil recruitment to the brain and liver, which is a hallmark of the APR. GW0742 significantly reduced BBB leakage and metalloproteinase 9 expression and upregulated the expression of tight junction proteins. These findings may help to guide the experimental and clinical therapeutic use of PPAR-ß/δ agonists against brain injury.

Correlation of Oxidative Stress Parameters and Inflammatory Markers in Ischemic Stroke Patients.

BACKGROUND: Ischemic stroke (IS) usually initiates inflammation and oxidative stress leading to neuronal death. Diabetes and impaired fasting glucose are associated with incidence of cerebrovascular and cardiovascular diseases. METHODS: In the present study, we assessed the relationship of fasting glucose with antioxidative parameters (erythrocyte glutathione peroxidase [GPx] and superoxide dismutase [SOD] activities) and inflammatory markers (high-sensitivity C-reactive protein [hs-CRP] and fibrinogen) in IS patients with and without type 2 diabetes mellitus (T2DM). In addition, we determined factors associated with the risk of IS among these patients. Antioxidative, inflammatory, and lipid parameters were measured in 196 patients with IS (117diabetics and 79 nondiabetics). RESULTS: After adjustment of covariates, multiple logistic regression analysis showed that SOD and GPx significantly decreased the risk of IS among patients with and without T2DM. However, hs-CRP increased the risk of IS. For the diabetic patients, fasting glucose was positively correlated with hs-CRP and fibrinogen and was negatively correlated with GPx and SOD levels. In addition, fasting glucose and hemoglobin A1c or glycosylated hemoglobin (HbA1c) have been shown to increase the risk of IS in diabetic patients. CONCLUSIONS: These data suggest that the antioxidant activity of plasma may be an important factor that provides protection from IS. hs-CRP concentrations can be used as a clinical screening tool to identify individuals with higher risk of IS. Finally, fasting glucose and HbA1c may also be useful indicators for cerebrovascular risk in diabetic patients that may be mediated by low levels of antioxidative defense markers and high inflammation status.

Inhibition of the Inflammasome NLRP3 by Arglabin Attenuates Inflammation, Protects Pancreatic ß-Cells from Apoptosis, and Prevents Type 2 Diabetes Mellitus Development in ApoE2Ki Mice on a Chronic High-Fat Diet.

Intraperitoneal injection of arglabin (2.5 ng/g of body weight, twice daily, 13 weeks) into female human apolipoprotein E2 gene knock-in (ApoE2Ki) mice fed a high-fat Western-type diet (HFD) reduced plasma levels of glucose and insulin by ∼20.0% ± 3.5% and by 50.0% ± 2.0%, respectively, in comparison with vehicle-treated mice. Immunohistochemical analysis revealed the absence of active caspase-3 in islet sections from ApoE2Ki mice fed a HFD and treated with arglabin. In addition, arglabin reduced interleukin-1ß (IL-1ß) production in a concentration-dependent manner in Langerhans islets isolated from ApoE2Ki mice treated with lipopolysaccharide (LPS) and with cholesterol crystals. This inhibitory effect is specific for the inflammasome NOD-like receptor family, pyrin domain-containing 3 (NLRP3) because IL-1ß production was abolished in Langerhans islets isolated from Nlrp3(-/-) mice. In the insulin-secreting INS-1 cells, arglabin inhibited, in a concentration-dependent manner, the maturation of pro-IL-1ß into biologically active IL-1ß probably through the inhibition of the maturation of procaspase-1 into active capsase-1. Moreover, arglabin reduced the susceptibility of INS-1 cells to apoptosis by increasing Bcl-2 levels. Similarly, autophagy activation by rapamycin decreased apoptosis susceptibility while autophagy inhibition by 3-methyladenin treatment promoted apoptosis. Arglabin further increased the expression of the autophagic markers Bcl2-interacting protein (Beclin-1) and microtubule-associated protein 1 light chain 3 II (LC3-II) in a concentration-dependent manner. Thus, arglabin reduces NLRP3-dependent inflammation as well as apoptosis in pancreatic ß-cells in vivo and in the INS-1 cell line in vitro, whereas it increases autophagy in cultured INS-1 cells, indicating survival-promoting properties of the compound in these cells. Hence, arglabin may represent a new promising compound to treat inflammation and type 2 diabetes mellitus development.

Gene Variant and Level of IL-1ß in Ischemic Stroke Patients With and Without Type 2 Diabetes Mellitus.

Evidence is emerging that inflammation plays a key role in the pathophysiology of ischemic stroke (IS). The aim of this study was to explore, for the first time, the relationship between IL-1ß -31 T/C polymorphism and the risk of ischemic stroke (IS) among patients with type 2 diabetes mellitus (T2DM). One hundred ninety-six patients with IS (117 diabetics and 79 nondiabetics) and 192 controls were recruited to enroll in this study. IL-1ß genotyping was performed by PCR-RFLP technique. After adjusting for sex, age, smoking, obesity, dyslipidemia, and hypertension, there was no significant difference in the distribution of IL-1ß -31 T/C genotypes and allele frequencies between IS patients with or without type 2 diabetes mellitus and control group (p > 0.05). Moreover, a significant positive correlation between serum IL-1ß level and glucose (p1 = 0.044) was showed. In addition, serum levels of IL-1ß were found to be higher among TT genotype carriers than TC and CC genotype carriers in ischemic stroke patients with or without T2DM but these differences were not significant. These results indicate that IL-1ß gene polymorphism might not be a risk factor in the development of ischemic stroke in Tunisian population.

PPAR-ß/δ activation promotes phospholipid transfer protein expression.

The peroxisome proliferator-activated receptor (PPAR)-ß/δ has emerged as a promising therapeutic target for treating dyslipidemia, including beneficial effects on HDL cholesterol (HDL-C). In the current study, we determined the effects of the PPAR-ß/δ agonist GW0742 on HDL composition and the expression of liver HDL-related genes in mice and cultured human cells. The experiments were carried out in C57BL/6 wild-type, LDL receptor (LDLR)-deficient mice and PPAR-ß/δ-deficient mice treated with GW0742 (10mg/kg/day) or a vehicle solution for 14 days. GW0742 upregulated liver phospholipid transfer protein (Pltp) gene expression and increased serum PLTP activity in mice. When given to wild-type mice, GW0742 significantly increased serum HDL-C and HDL phospholipids; GW0742 also raised serum potential to generate preß-HDL formation. The GW0742-mediated effects on liver Pltp expression and serum enzyme activity were completely abolished in PPAR-ß/δ-deficient mice. GW0742 also stimulated PLTP mRNA expression in mouse J774 macrophages, differentiated human THP-1 macrophages and human hepatoma Huh7. Collectively, our findings demonstrate a common transcriptional upregulation by GW0742-activated PPAR-ß/δ of Pltp expression in cultured cells and in mouse liver resulting in enhanced serum PLTP activity. Our results also indicate that PPAR-ß/δ activation may modulate PLTP-mediated preß-HDL formation and macrophage cholesterol efflux.

Anti-inflammatory and antiatherogenic effects of the NLRP3 inflammasome inhibitor arglabin in ApoE2.Ki mice fed a high-fat diet.

BACKGROUND: This study was designed to evaluate the effect of arglabin on the NLRP3 inflammasome inhibition and atherosclerotic lesion in ApoE2Ki mice fed a high-fat Western-type diet. METHODS AND RESULTS: Arglabin was purified, and its chemical identity was confirmed by mass spectrometry. It inhibited, in a concentration-dependent manner, interleukin (IL)-1ß and IL-18, but not IL-6 and IL-12, production in lipopolysaccharide and cholesterol crystal-activated cultured mouse peritoneal macrophages, with a maximum effect at ≈50 nmol/L and EC50 values for both cytokines of ≈ 10 nmol/L. Lipopolysaccharide and cholesterol crystals did not induce IL-1ß and IL-18 production in Nlrp3(-/-) macrophages. In addition, arglabin activated autophagy as evidenced by the increase in LC3-II protein. Intraperitoneal injection of arglabin (2.5 ng/g body weight twice daily for 13 weeks) into female ApoE2.Ki mice fed a high-fat diet resulted in a decreased IL-1ß plasma level compared with vehicle-treated mice (5.2±1.0 versus 11.7±1.1 pg/mL). Surprisingly, arglabin also reduced plasma levels of total cholesterol and triglycerides to 41% and 42%, respectively. Moreover, arglabin oriented the proinflammatory M1 macrophages into the anti-inflammatory M2 phenotype in spleen and arterial lesions. Finally, arglabin treatment markedly reduced the median lesion areas in the sinus and whole aorta to 54% (P=0.02) and 41% (P=0.02), respectively. CONCLUSIONS: Arglabin reduces inflammation and plasma lipids, increases autophagy, and orients tissue macrophages into an anti-inflammatory phenotype in ApoE2.Ki mice fed a high-fat diet. Consequently, a marked reduction in atherosclerotic lesions was observed. Thus, arglabin may represent a promising new drug to treat inflammation and atherosclerosis.

PCSK9 polymorphism in a Tunisian cohort: identification of a new allele, L8, and association of allele L10 with reduced coronary heart disease risk.

The c.61_63dupCTG (L10) allele of rs72555377 polymorphism in PCSK9 has been reported to be associated with low-density lipoprotein-cholesterol (LDL-C) levels and with a decreased risk of coronary artery disease (CAD). We investigated the effect of two known alleles for rs72555377, L10 and L11, on the risk of CAD in a Tunisian cohort (218 patients diagnosed by angiography and 125 control subjects). Two subgroups of patients were defined by their level of stenosis: ≥50% for CAD and <50% for no-CAD. The genotypes were obtained by the size measurement of fluorescent-labeled PCR products. We identified a novel allele for the rs72555377 polymorphism: an in-frame deletion, c.61_63delCTG (L8). The frequency of the L10 allele was significantly higher in the no-CAD subgroup than in the CAD subgroup (0.210 vs 0.114, p = 0.045), and than in the subgroup of CAD patients presenting a stenosis ≥50% in two or three major coronary arteries (0.210 vs 0.125, p = 0.028). Multiple regression analysis showed that the L10 allele was significantly associated with a reduced risk of CAD (p = 0.049, OR = 0.51[0.26-1.00]), and with its reduced severity (p = 0.045, OR = 0.44[0.20-0.98]). The L10 allele is associated with a reduced risk and severity of CAD, seemingly independently of its LDL-lowering effect, suggesting a direct effect of PCSK9 on atherogenesis.

Matrix metalloproteinase-1 and matrix metalloproteinase-12 gene polymorphisms and the risk of ischemic stroke in a Tunisian population.

Matrix metalloproteinases (MMPs) play an important role in early atherosclerosis, extracellular matrix remodeling, plaque rupture and myocardial infarction. MMP gene polymorphisms contribute to the risk of developing cardiovascular diseases. In this study, we investigated, for the first time, the association between MMP-1-16071G/2G, MMP-12 -82A/G and MMP-12 1082A/G genotypes and haplotypes and the risk of ischemic stroke (IS) among patients with type 2 diabetes mellitus (T2DM). To examine whether these genetic polymorphisms are associated with susceptibility to IS, 196 patients with IS and 192 controls were examined by PCR-based RFLP. When the analyses were adjusted for multiple risk factors, no interaction between T2DM and MMP-1-1607 1G/2G polymorphism on the risk of ischemic stroke was found (p=0.074). However, MMP-12 polymorphisms genotypes were associated with the higher risk of IS in diabetic patients compared with total patients. The -82G-1082G haplotype of MMP-12 polymorphisms was associated with higher risk of ischemic stroke in diabetic patients [AOR=2.33; 95% CI (1.25-3.62), P=0.032]. These findings showed that there was an important joint effect of the MMP-12 polymorphisms and T2DM on the risk of IS and therefore it can be considered as a potential marker of cerebrovascular disorders in diabetic patients.

Effect of the PPARγ C161T gene variant on serum lipids in ischemic stroke patients with and without type 2 diabetes mellitus.

Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-activated transcription factor involved in the regulation of lipid metabolism, diabetes, obesity, atherogenesis and inflammation. PPARγ genetic variation has been associated with metabolic and cardiovascular diseases. The aim of this study was to explore, for the first time, the relationship between PPARγ C161T polymorphism and the risk of ischemic stroke (IS) among patients with type 2 diabetes mellitus (T2DM). A total of 196 patients with IS (117 diabetics and 79 nondiabetics) and 192 controls were recruited to enroll in this study. PPARγ C161T genotyping was performed by PCR-RFLP technique. The 161T allele as compared with C allele was found to be higher in controls than in IS patients (with or without T2DM). After adjusting for multiple risk factors, the T allele carriers had significantly reduced IS risk (OR=0.575, 95% CI 0.348-0.951, p=0.030) compared to the CC homozygotes which increased significantly the risk in IS patients with T2DM (OR=1.85, 95% CI 1.23-2.62). Moreover, the triglycerides (TG) and ApoB levels in CC homozygote carriers were significantly higher than those in T allele carriers. These results indicate that the C161T of PPARγ may reduce the risk of IS by modulation of adipose metabolism especially TG and ApoB in IS patients with T2DM.

Effect of E670G Polymorphism in PCSK9 Gene on the Risk and Severity of Coronary Heart Disease and Ischemic Stroke in a Tunisian Cohort.

The association of E670G (rs505151) polymorphism in PCSK9 gene with an increased risk of coronary artery disease (CAD) and ischemic stroke (IS) was reported in previous studies. We investigated the effect of the E670G (rs505151) on the risk of CAD and IS in a Tunisian cohort. Genotyping of the PCSK9 E670G was performed using polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) and then confirmed by direct sequencing. The frequency of the 670G allele was significantly higher in the CAD than in the no-CAD subgroup (0.132 vs. 0.068, p = 0.030). As expected, the incidence of E670G was significantly important in IS subgroup than control group (0.122 vs. 0.073, p = 0.032). Furthermore in CAD patients, the 670G carriers showed significantly increased plasma total cholesterol and LDL-cholesterol levels compared to E670 carriers (6.78 [6.47-7.00] vs. 4.92 [4.02-5.46] mmol/l, p < 0.0001 and 4.60 [4.00-5.04] vs. 3.00 [2.22-3.70] mmol/l p = 0.001, respectively). The risk and severity of CAD were significantly increased in 670G carriers between no-CAD subgroup and CAD patients presenting a stenosis ≥50 % in two or three major coronary arteries (0.068 vs. 0.198, p = 0.001, OR = 3.39 [1.55-7.37]). The E670G polymorphism of the PCSK9 gene is mainly associated with a increased risk and severity of CAD and IS in Tunisian cohort.

Autosomal dominant hypercholesterolemia: needs for early diagnosis and cascade screening in the tunisian population.

Autosomal dominant hypercholesterolemia (ADH) is characterized by an isolated elevation of plasmatic low-density lipoprotein (LDL), which predisposes to premature coronary artery disease (CAD) and early death. ADH is largely due to mutations in the low-density lipoprotein receptor gene (LDLR), the apolipoprotein B-100 gene (APOB), or the proprotein convertase subtilisin/kexin type 9 (PCSK9). Early diagnosis and initiation of treatment can modify the disease progression and its outcomes. Therefore, cascade screening protocol with a combination of plasmatic lipid measurements and DNA testing is used to identify relatives of index cases with a clinical diagnosis of ADH. In Tunisia, an attenuated phenotypic expression of ADH was previously reported, indicating that the establishment of a special screening protocol is necessary for this population.

Interaction Effects of the Leu162Val PPAR α and Pro12Ala PPAR γ 2 Gene Variants with Renal Function in Metabolic Syndrome Population.

Leu162Val PPAR α and Pro12Ala PPAR γ 2 were investigated for their individual and their interactive impact on MS and renal functionality (RF). 522 subjects were investigated for biochemical and anthropometric measurements. The diagnosis of MS was based on the IDF definition (2009). The HOMA 2 was used to determine HOMA- ß , HOMA-S and HOMA-IR from FPG and FPI concentrations. RF was assessed by estimating the GFR. PCR-RFLP was performed for DNA genotyping. Allele frequencies were 0.845 for Pro and 0.155 for Ala, and were 0.915 for Leu and 0.085 for Val. We showed that carriers of the PPAR α Val 162 allele had lower urea, UA and higher GFR compared to those homozygous for the Leu162 allele. Subjects carried by PPAR γ 2Ala allele had similar results. They also had reduced FPG, FPI and HOMA-IR, and elevated HOMA- ß and HOMA-S compared to those homozygous for the Pro allele. Subjects were divided into 4 groups according to the combinations of genetic alleles of the 2 polymorphisms. Subjects carrying the Leu/Val with an Ala allele had lower FPG, PPI, HOMA-IR, urea, UA levels, higher HOMA- ß , HOMA-S and GFR than different genotype combinations. Leu162Val PPAR α and Pro12Ala PPAR γ 2 can interact with each other to modulate glucose and insulin homeostasis and expand their association with overall better RF.

Molecular characterization of Tunisian families with abetalipoproteinemia and identification of a novel mutation in MTTP gene.

BACKGROUND: Abetalipoproteinemia (ABL; OMIM 200100) is a rare monogenic disorder of lipid metabolism characterized by reduced plasma levels of total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C) and almost complete absence of apolipoprotein B (apoB). ABL results from genetic deficiency in microsomal triglyceride transfer protein (MTP; OMIM 157147). In the present study we investigated two unrelated Tunisian patients, born from consanguineous marriages, with severe deficiency of plasma low-density lipoprotein (LDL) and apo B. METHODS: Intestinal biopsies were performed and The MTTP gene was amplified by Polymerase chain reaction then directly sequenced in patients presenting chronic diarrhea and retarded growth. RESULTS: First proband was homozygous for a novel nucleotide deletion (c. 2611delC) involving the exon 18 of MTTP gene predicted to cause a non functional protein of 898 amino acids (p.H871I fsX29). Second proband was homozygous for a nonsense mutation in exon 8 (c.923 G > A) predicted to cause a truncated protein of 307 amino acids (p.W308X), previously reported in ABL patients. CONCLUSIONS: We discovered a novel mutation in MTTP gene and we confirmed the diagnosis of abetalipoproteinemia in new Tunisian families. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/8134027928652779.

Effect of genetic polymorphism +294T/C in peroxisome proliferator-activated receptor delta on the risk of ischemic stroke in a Tunisian population.

PPARδ +294T/C polymorphism was investigated in diabetics, in normolipidemic healthy controls, in dyslipidemic and nondyslipidemic coronary artery disease patients but never in ischemic stroke patients. The aim of this study was to explore, for the first time, the relationship between the genetic polymorphism of PPARδ and the risk of ischemic stroke among patients with diabetes. The study group consisted of 196 patients with ischemic stroke and 192 controls. Plasma concentrations of total cholesterol, triglycerides, low-, and high-density lipoprotein did not differ significantly between subjects carrying the TT genotype and those carrying the CC/TC genotype in both ischemic stroke patients (with or without diabetes) and control groups. The +294C allele (CC + CT genotypes) as compared with TT genotypes was found to be higher in total ischemic stroke patients than in controls. On the other hand, no interaction between diabetes and PPAR +294T/C polymorphism on the risk of ischemic stroke was found (p = 0.089). The PPARδ +294T/C polymorphism was associated with the risk of ischemic stroke in Tunisian subjects. This polymorphism has no influence on plasma lipoprotein concentrations and body mass index either in healthy subjects or in ischemic stroke patients with or without diabetes both in males and females.