Preclinical study of vitamin D deficiency in the pathogenesis of metabolic syndrome in rats.

OBJECTIVE: To explore the impact of vitamin D deficiency (VD-) in the pathogenesis of metabolic syndrome (MetS). MATERIALS AND METHODS: Models of (VD-) and (MetS) were induced in male Wister rats by dividing into four groups, group-I for the development of (VD-) by intraperitoneal injection of paricalcitol for 3 weeks, group II for (MetS) model by adding 10% fructose to their drinking water for 8 weeks, the group III for induction of combined (VD- + MetS) and group-IV as a control. Ultimately, the parameters of (VD-) and (MetS) were assessed at zero time and after 8 weeks. RESULTS: Both (VD-) and (MetS) groups alone displayed a remarkable enhancement of blood pressure, glucose and insulin levels, triglycerides, cholesterol, and low-density lipoproteins with a reduction of high-density lipoproteins. Additionally, all distinguishing features of obesity were substantially increased. Nevertheless, the combined group (VD-+MetS) demonstrated an expeditious and substantial increase in all the aforesaid parameters compared to the (VD-) and (MetS) groups alone. CONCLUSIONS: The hallmark of this study, reinforces a new frontier of awareness of the deleterious effect of (VD-) on each component of (MetS). Eventually, supplementation of vitamin D can circumvent the elements of (MetS) and needs further validation by determination of (VD-) molecular pathway on the parameters of (MetS).

Evaluation of salivary thiobarbituric acid reactive substances, total protein, and pH in children with various degrees of early childhood caries: a case-control study.

PURPOSE: According to new studies, oxidative stress may play an important role in the beginning and progression of oral diseases. The aim of this study was the evaluation of thiobarbituric acid reactive substances (TBARS) as an indicator of lipid peroxidation, total protein, and pH of saliva in children with various degrees of early childhood caries in comparison with caries-free children. METHODS: This case-control study was carried out on 90 children 3-5 years old in three equal groups, including caries-free children (CF), early childhood caries (ECC), and severe early childhood caries (S-ECC) who were age- and sex matched. Saliva pH was measured using a paper pH meter and TBARS and total protein were measured by spectrophotometer methods and data were statistically analysed. RESULTS: TBARS and total protein levels in ECC and S-ECC groups were significantly higher than the CF group (p < 0.001), but pH was not significantly different between groups. There were no significant differences between ECC and S-ECC groups in any of the studied indicators. CONCLUSION: Considering the limitations of the present study, the results showing the higher salivary TBARS levels in the S-ECC and ECC groups compared to caries-free children, lead to the conclusion that oxidative stress could be considered as a risk factor for early childhood caries.

The heart in m.3243A>G carriers.

OBJECTIVES: Little is known about cardiac involvement in m.3243A>G variant carriers. Thus, this study aimed to assess type and frequency of cardiac disease in symptomatic and asymptomatic m.3243A>G carriers. METHODS: Systematic literature review. RESULTS: The m.3243A>G variant may manifest phenotypically as mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), maternally inherited diabetes and deafness (MIDD), myoclonic epilepsy with ragged red fiber (MERRF), Leigh syndrome, or MELAS/KSS (Kearns-Sayre syndrome) overlap. Only few systematic studies which prospectively investigated m.3243A>G carriers for cardiac involvement were found. Cardiac abnormalities reported in m.3243A>G carriers include myocardial abnormalities, arrhythmias, or conduction defects. Myocardial abnormalities include myocardial thickening, hypertrophic cardiomyopathy, dilated cardiomyopathy, noncompaction, myocardial fibrosis, systolic dysfunction, heart failure, or arterial hypertension. Arrhythmias reported in m.3243A>G carriers include paroxysmal supraventricular or ventricular arrhythmias, including sinus tachycardia, atrial fibrillation and nonsustained ventricular tachycardia, and sudden cardiac death. Conduction defects in this group of patients include Wolff-Parkinson-White syndrome and left/right bundle branch block. Asymptomatic m.3243A>G carriers usually do not develop clinical or subclinical cardiac disease. CONCLUSIONS: Cardiac involvement in m.3243A>G carriers has been only rarely systematically studied, which is perhaps why the incidence of cardiac diseases in MELAS is lower than would be expected. Myocardial abnormalities are much more frequent than arrhythmias or conduction defects. All symptomatic and asymptomatic m.3243A>G carriers should be systematically investigated for cardiac disease.

The international normalized ratio (INR): What reagent, what instrument? The assessment of the agreement between INR values according to different reagent/instrument combinations.

WHAT IS KNOWN AND OBJECTIVE: The international normalized ratio (INR) is widely used to monitor patients on vitamin K antagonists. This study aimed to assess the agreement of INR values obtained with different thromboplastin/instrument combinations. MATERIAL AND METHODS: International normalized ratio was determined on plasmas from 330 patients undergoing antivitamin K treatment (with acenocoumarol), using two calibration methods and four reagent/instrument combinations: Both Neoplastine CI and Neoplastine CI Plus on STA-R instrument from Diagnostica STAGO, Asnières, France; and both Thromborel S and Innovin on SYSMEX 2100i instrument from Siemens Health Care Diagnostics, Marbung, Germany. The agreement analysis was done using the Bland-Altman plot and the Cohen Kappa coefficient. RESULTS: The mean of the differences between the INR values and the limits of agreement were -0.07 [-0.51 to 0.38] for the Neoplastine CI plus and Neoplastine CI reagents, -0.08 [-1.18 to 1.03] for the Thromborel S and Innovin reagents when the INR was calculated, -0.1 [-1.15 to 0.95] for the Thromborel S and Innovin reagents when the INR was directly calibrated and -0.1 [-0.7 to 0.5] for the Neoplastine CI plus and Thromborel S. Cohen's kappa coefficients were 0.94, 0.76, 0.85 and 0.82, respectively. NEW FINDINGS AND CONCLUSION: The agreement between the four reagent/instrument combinations was high enough to classify patients as inefficaciously or efficaciously anticoagulated. The data interpretation should always be related to the clinical purpose.

The evaluation of the relevance of thrombin generation and procoagulant activity in thrombotic risk assessment in BCR-ABL-negative myeloproliferative neoplasm patients.

INTRODUCTION: It has been recently suggested that microparticles (MP) play a role in the pathogenesis of thrombotic complications. This study aimed to assess the contribution of procoagulant activity expressed by circulating MP in thrombotic events in MPN patients. METHODS: Seventy-four MPN patients were enrolled in a trans-sectional study. The MP procoagulant activity was measured using two assays: (i) the thrombin generation (TG) assay used in different conditions with the addition of both tissue factor (TF) and phospholipids (PL) and with the addition of TF or PL alone and (ii) the PROCOAG-PPL assay. RESULTS: The mean age was 62 (26 men and 48 women). The prevalence of thrombotic events was 28%. When comparing patients with thrombosis to those without, age, sex, MPN type, cardiovascular risk factors, and history of thrombosis were not significantly associated with thrombosis. The JAK2 V617F mutation was significantly associated with thrombotic events (90% vs 67%; P=.04). Results from the TG assay and the PROCOAG-PPL assays did not demonstrate a significant association between the MP procoagulant activity and thrombotic events. CONCLUSION: The MP procoagulant activity did not predict thrombosis in MPN patients. The contribution of TG assay in the assessment of the thrombotic risk is still in debate.

[Hemovigilance: State 2007-2013 Tunis]. / Hémovigilance à Tunis (hôpital La Rabta) : bilan 2007­2013.

INTRODUCTION: Despite its lifesaving role, blood transfusion still has risks associated with it. Hemovigilance is a set of surveillance procedures of the transfusion chain intended to promote safe and effective use of blood components. This work aims to present a descriptive analysis of adverse reactions, which were notified over a period of 5 years (incidence and etiology); to identify malfunctions and to propose corrections. MATERIALS AND METHODS: All transfusion adverse reactions accidents reported to the blood bank of the hospital La Rabta (n=120) are explored (clinical and laboratory tests). RESULTS: The average age of patients with transfusion reaction was 51.2 years (25 days to 89 years). The transfusion accident rates ranged from 0.59 to 2.19 accidents/1000 labile blood products (LBP) distributed. The investigations were used to classify 71 % of accidents in different categories. The most prevalent reaction is the hemolytic reaction, n=24 (19.8 %), followed by allergic reactions, n=21 (17.5 %) and non-hemolytic feverish reaction, n=19 (15.8 %). Transfusion reactions of grade 1 severity were the most frequent (n=94); followed by those of grade 3 severity (n=16), accidents grade 4 (n=4) including two cases of acute pulmonary edema, one case of hyperkalemia, and the last case classified undetermined. CONCLUSION: These data are particularly rich in learning lessons. This study identified several levels failures: under-reporting of certain transfusion accidents, malfunctions at certain stages of the transfusion chain. In order to achieve an accurate statement of each transfusion reaction, it is important to plan in-service training.

Transverse translunate fracture-dislocation: A rare injury.

Perilunate fracture-dislocation is rare. We report the case of a 24-year-old male who fell from his motorcycle and presented with a transverse lunate fracture with perilunate ligament damage. The initial diagnosis based on X-rays was confirmed by CT scan. A dorsal approach was used to obtain good reduction, double screw fixation and ligament reinsertion protected by temporary K-wires. To the best of our knowledge, this is the first case of transverse lunate fracture within perilunate fracture-dislocation. The patient returned to normal activities after 6 months.

Pro- and anti-inflammatory cytokines in post-infarction left ventricular remodeling.

OBJECTIVES: Acute myocardial infarction (MI) leads to molecular, structural, geometric and functional changes in the heart during a process known as ventricular remodeling. Myocardial infarction is followed by an inflammatory response in which pro- and anti-inflammatory cytokines play a crucial role, particularly in left ventricular remodeling. This study aimed at evaluating serum concentrations of interleukin-8 (IL8), tumor-necrosis-factor-alpha (TNFα) and interleukin-10 (IL10), pro- and anti-inflammatory cytokines, and at correlating them with left ventricular remodeling as assessed by echocardiographic parameters. METHODS: In a case-control study 30 MI patients were compared with 30 healthy controls. Serum concentrations of IL8, TNFα and IL10 were measured on day 2 and day 30 post-MI by chemiluminescence immunoassay and correlated with echocardiographic parameters. RESULTS: There was an increase of IL8, and TNFα together with a decrease of IL10 at both time points. IL8 was negatively correlated with the left ventricular end-diastolic diameter (LVEDD) and positively with left ventricular systolic volume. IL10 was negatively correlated with LVEDD and left atrial volume 30days post-MI. CONCLUSION: The increase of pro-inflammatory cytokines TNFα and IL8 was accompanied by decreased anti-inflammatory IL10. This imbalance between pro- and anti-inflammatory cytokines might contribute to the progression of left ventricular remodeling and may lead to heart failure.

Bishop Score vs. ultrasound cervical length in the prediction of cervical ripening success and vaginal delivery in nulliparous women.

AIM: The aim of this paper was to compare the predictive value of Bishop Score and sonographic measurement of cervical length for predicting cervical ripening success and vaginal delivery in nulliparous women with low Bishop Score. METHODS: A prospective observational study including 77 nulliparous pregnant women at exactly 41 weeks of gestation with a Bishop Score ≤ 5. Cervical measurement was performed by transvaginal ultrasonography and Bishop Score was determined by digital examination. All patients had cervical ripening with Prostaglandins prior to labor induction with oxytocin. RESULTS: Cervical ripening was successful in 63 patients (81%) and vaginal delivery occurred in 51 women (66.2%). Multiple logistic regression analysis demonstrated cervical length assessed by transvaginal sonography as the only independent predictor of successful cervical ripening and vaginal delivery. The best cut-off point was 34.6 for predicting successful cervical ripening and 32.5 mm for predicting vaginal delivery. The chance of vaginal delivery was 90% when initial cervical length was < 32.5 mm and 50% when cervical length was >32.5 mm. CONCLUSION: Compared with the Bishop score, ultrasound cervical length measurement is a better predictor of cervical ripening success and vaginal delivery in nulliparous women at 41 weeks of gestation with an unfavorable cervix.

Mitochondrial tRNA glutamine variant in hypertrophic cardiomyopathy.

BACKGROUND: Mitochondria play critical roles in both the life and death of cardiac myocytes. Pathogenic mitochondrial DNA (mtDNA) mutations leading to mitochondrial dysfunction can cause cardiomyopathies (CMPs). Our aim was to investigate the underlying mitochondrial defect in a patient with hypertrophic cardiomyopathy (hCMP). A detailed clinical and molecular genetic analysis was performed. PATIENTS AND METHODS: Total DNA was extracted from lymphocytes in a 14-year-old index male patient with hCMP, preexcitation syndrome, and severe ventricular arrhythmias. Direct sequencing of the PCR fragments was performed. To distinguish deleterious from functionally neutral variants, the ClustalW program, RNAfold software, and PolyPhen algorithm were applied, which predict the pathogenicity of a particular variant by using a set of empirical rules based on the nature of the mutation, the phylogenetic conservation of the variant, and the physicochemical property of the amino acid. RESULTS: The mutational analysis of mtDNA genes revealed four variants. The m.4395A>G transition (C6G) in the MT-TQ gene, which altered an evolutionary conserved nucleotide, with a conservation index of 85.7 % and affected a highly conserved U.G base pair in the secondary structure of MT-TQ. Additionally, the previously reported polymorphisms m.14757T>A, m.15236A>G, and m.15314G>A resulting in the replacement of amino acid residues in the MT-CYB gene were detected. CONCLUSION: The m.4395A>G variant was scored as possibly pathogenic and may exert a negative effect on heart function to generate hCMP.

Phenotypic abnormalities of peripheral blood mononuclear cells in patients with Behçet's disease and association with HLA-B51 expression.

The aim of this study was to investigate the subclasses and the immunophenotypic profile of peripheral mononuclear cells in patients with Behçet's disease (BD) and to assess associations between the expression of HLA-B51 antigen and that of other cell markers. Thirty healthy volunteer blood donors and forty patients with BD were enrolled into this study. Phenotyping was performed using two color flow cytometry. HLA-B51 typing was performed using the complement dependent microlymphocytotoxicity assay. Unlike controls, patients with BD presented a modified immunophenotypic profile of lymphocytes. Compared to those in the remission phase, patients with active BD showed an increased mean of MFI ratio of CD56 on CD16+CD56+ cells (32.47 ± 14.26 versus 23.87 ± 10.3; p = 0.032), increased absolute numbers of CD4(-)CD8(bright) and CD4(+)CD8(+) cells (657.1 ± 463.6 cells/µL versus 319.24 ± 116.4 cells/µL; p = 0.017 and 40.77 ± 36.41 cells/µL versus 10.77 ± 9.78 cells/µL; p < 0.0001, respectively) and an elevated mean of MFI ratio of CD19 on B cells (252.3 ± 56.7 versus 205.67 ± 32.3; p = 0.021). However, expression of HLA-B51 was not associated with any specific immunophenotypic profile. In conclusion, abnormal immunophenotypic profile of peripheral lymphocytes was found in patients with BD, especially in active phase, reflecting an immune dysregulation. Moreover, HLA-B51 expression was not found to be related to the expression of other cell markers.

Comparison of total antioxidant capacity in saliva of children with severe early childhood caries and caries-free children.

Oxidative stress may play an important role in the onset and development of oral inflammatory and dental decay diseases. The aim of this study was to compare total antioxidant capacity (TAC) levels in the unstimulated whole saliva of children with severe early childhood caries (S-ECC) and caries-free children. In this case-control study, 80 children aged 3-5 years from nursery schools in Babol, northern Iran were the subjects of the study. The S-ECC group contained 40 children with dmfs ≥4 (age 3), ≥5 (age 4) or ≥6 (age 5) and the control group contained 40 caries-free children (dmfs = 0). Out of consideration for growth pattern and general health, the clinical examinations of the chosen children were conducted by a physician. These two groups were age and sex matched. TAC was measured by the FRAP (ferric-reducing antioxidant power) method and total protein in unstimulated whole saliva was evaluated spectrophotometrically. According to the normal distribution of data, statistical tests including the t test and Pearson's correlation test were used; p < 0.05 was considered significant in the difference between the two groups. TAC levels and salivary total protein increased in children with S-ECC compared with caries-free children (p = 0.025 and p = 0.033, respectively). Moreover, salivary TAC showed a significant positive correlation with total protein concentration and dmfs in the S-ECC group (p < 0.001, r = 0.685 and r = 0.902, respectively). The significant increment of salivary TAC in S-ECC may represent a compensatory mechanism against oxidative stress in S-ECC.

[Urinary disorders and metabolic syndrome: prospective study]. / Troubles vésicosphinctériens et syndrome métabolique: étude prospective.

OBJECTIVE: Metabolic syndrome (MS) risk factors are potentially implicated in the development of lower urinary tract symptoms (LUTS). The goals of this study were to analyze the prevalence of the LUTS in patients presenting with MS and to evaluate the correlation between the MS components and LUTS. METHODS: A prospective study was conducted on a group of 34 patients with MS according to the criteria of the NCEP ATP III. Urinary symptom profile (USP) questionnaire was used to evaluate LUTS. The physical examination included: weight, waist circumference, body mass index (BMI) and blood pressure looking for orthostatic hypotension. The following laboratory data were obtained: fasting blood sugar, postprandial glycemia, glycosylated hemoglobin (HbA1c), HDL-cholesterol, LDL-cholesterol, triglycerides and total cholesterol. RESULTS: The mean age was 56.2 years (±9.2). Twenty of the patients (58.8%) were females. All patients underwent diabetic and hypertension therapy. The mean BMI was 30.2±4.8 and waist circumference was 107.8±9.3 cm. USP total score was 8.3±6. Besides, 29 (85.2%) patients had overactive bladder symptom, and 13 (38.2%) patients presented with urinary stress incontinence. The overactive bladder USP score was significantly correlated with age, waist circumference, BMI and postprandial glycemia. The other parameters of MS were not correlated with urinary symptoms. CONCLUSION: The most frequent urinary symptom in the MS was overactive bladder symptoms and urinary incontinence. The components of MS that influenced the USP score were abdominal obesity and hyperglycemia. The hypothesis of a link between MS and overactive bladder in diabetic patients with MS is plausible.