Analysis of MHC genes in a Tunisian isolate with autoimmune thyroid diseases: implication of TNF -308 gene polymorphism

Autoimmune thyroid diseases (AITDs), which include Hashimoto thyroiditis (HT), Graves' disease (GD) and primary idiopathic myxoedema (PIM), are recognized as multifactorial diseases. In this study, we have examined single and haplotypic genetic variation across the major histocompatibility complex (MHC) in a Tunisian isolate with a high prevalence of AITDs (62 patients: 32 with GD, 9 with HT and 21 with PIM). Genotyping was performed for HLA class I and II alleles as well as polymorphisms within tumor necrosis factor (TNF), lymphotoxin alpha (TLalpha) and heat shock protein (HSP70-02 and HSP70-hom) genes. Our results showed association of HLA-A2-B50-TNF 2 haplotype with AITDs (p = 0.045). Linkage analysis using Simwalk2 program has shown significant result with TNF -308 gene polymorphism (p = 0.03). The FBAT has given evidence for genetic association with TNF -308 and HLA-DR gene polymorphisms. TNF 2 allele was associated with GD (p = 0.0011), whereas TNF 1, HLA-DR11 and DR12 (p = 0.0039, p = 0.00089 and p = 0.0056, respectively) were rather implicated in HT pathogenesis. Results found by TDT-STDT have confirmed the involvement of the TNF -308 gene polymorphism in AITD pathogenesis (p < 10(-9)).     

LetterEvidence of Association between FKBP1B and Thyroid Autoimmune Disorders in a Large Tunisian Family

FKBP1B belongs to immunophilins superfamily and functions as a cytosolic receptor protein of FK506. The role of FKBP1B in the immunosuppressive pathway of FK506 is well established. Previously, we reported a strong evidence of linkage between D2S171 microsatellite marker (located in vicinity of FKBP1B gene) and susceptibility to autoimmune thyroid diseases (AITDs). In this study, we report linkage disequilibrium between the dimorphism (C/T) in the 3′ untranslated region (3′ UTR) of FKBP1B gene and susceptibility to AITDs.

DNAs were extracted from a large Tunisian family affected with Graves' disease (GD) and Hashimoto's thyroiditis (HT) and analysed by PCR–RFLP using DraIII restriction enzyme. Our results showed an excess of transmission of the allele C from heterozygous parents to affected offspring (transmission disequilibrium test (TDT)=4.76; p=0.012). This suggests a linkage disequilibrium of 3′ UTR (C/T) SNP with AITDs. Moreover, The FBAT analysis gives a significant association with the C allele under the recessive model (χ²=5.50; p=0.018). These results support the involvement of FKBP1B gene in the genetic susceptibility to the AITDs development in the studied family.     

Long-term predictors of death among Tunisian patients presenting fornon ST-elevation acute coronary syndrome

Background. Coronary artery disease is the leading cause of death in emerging countries. Contemporary data about clinical profile and prognosis in Tunisian patients presenting for non ST-elevation acute coronary syndrome (NSTE-ACS) are lacking. Aim. We sought to study the risk profile and 3-year mortality predictors in Tunisian patients presenting for NSTE-ACS in the contemporary setting. Methods. In this single center study, data about all consecutive patients presenting to our center for NSTE-ACS from April 2014 to July 2016 were extracted and outcomes exhaustively updated. 3-year mortality predictors were determined by multivariable survival analysis. Results. A total of 340 patients were included, of which 204 (61.8%) were male. Mean age was 63.6 ± 10.3 years. Prevalence of diabetes mellitus, hypertension and smoking was 57.3%, 62.4%, and 45.3%, respectively. In-hospital, 6, 12 and 36-month mortality rate was 2.3%, 3.2%, 7.1% and 15.2%, respectively. In multivariable survival analysis, independent predictors of death were age >75 (HR=5.45, 95% CI: 2.9-10.03, p<0.001), ST-segment deviation (HR=1.86, 95% CI: 1.04-3.33, p=0.036), anemia (HR=2.56, 95% CI: 1.41-4.67, p=0.002), left ventricular ejection fraction (LVEF) <40% (HR=3.5, 95% CI: 1.84-6.67, p<0.001) and a Global Registry of Acute Coronary Events (GRACE) score ≥140 (HR=2.38, 95% CI: 1.02-5.57, p=0.044) Conclusion. In Tunisian patients presenting for NSTE-ACS, long-term mortality was high. Advanced age, ST-segment deviation, anemia, LVEF <40% and a GRACE score ≥140 were independent long-term predictors of death.     

Non-thiol farnesyltransferase inhibitors: N-(4-aminoacylamino-3-benzoylphenyl)-3-[5-(4-nitrophenyl)-2 furyl]acrylic acid amides and their antimalarial activity

Water solubility was previously found to be essential for in vivo-antimalarial activity of a novel type of benzophenone-based farnesyltransferase inhibitors. Introduction of a alpha-amino group into the phenylacetic acid substructure provided more soluble compounds with high farnesyltransferase inhibitory activity. The in vitro-antimalarial activity was detrimentally influenced by this structural modification.     

Carcinoid tumors of the appendix. A report of 46 cases

Carcino?d tumors of the appendix are rare. The appendix constitutes the most frequent localization of these tumors. We studied of a retrospective way all cases that had an appendectomy in the service of general surgery of Sfax on a period of 7 years going from 1995 to 2001. During this period, 9584 patients had an appendectomy in our service. Among which, 46 cases (0.48%) of carcinoid tumor of the appendix have been diagnosed. In more than 95% of cases, patients were admitted due to acute appendicitis; but none of them had the signs of the carcinoid syndrome. The treatment was a simple appendectomy in 44 cases (95%). The right hemicolectomy was necessary in two cases, because of an invasion of the appendicular base in a case and a tumor greater than 2 cm in the other case. There is no reported case of lymph node or systemic metastasis. The authors discuss data in the literature and analyse the features of the clinical picture, diagnosis, and try to define a convenient attitude of treatment of these tumors.     

1]Benzofuro[3,2-b]pyridin-4-yl-amines - synthesis and investigation of activity against malaria

The ethyl 4-chlorobenzofuro[3,2-b]pyridine-3-carboxylate (2) reacted with the hydrochlorides of the mono- and bis-phenol Mannich bases 3 to yield the amodiaquine and pyronaridine analogues 4. The chloroquine analogue 6 was formed by melting 2 with the novaldiamine base (5) in phenol. The most active compound 4c inhibited the growth of the malaria parasite Plasmodium falciparum with an IC50 of 500 nM.     

1]Benzothieno[3,2-b]pyridin-4-yl-amine--synthesis and investigation of activity against malaria

The ethyl 4-chlorobenzothieno[3,2-b]pyridine-3-carboxylate (2) reacted with the hydrochlorides of the mono- and bis-phenol Mannich bases 6 to yield the amodiaquine and pyronaridine analogues 9. The chloroquine analogue 10 was formed by melting 2 with the novaldiamine base (7) in phenol. The stability of the 4-aminophenols 9 was investigated by anodic oxidation using the rotating platinum electrode by means of difference pulse voltammetry. The half wave potentials were measured giving E(1/2) approximately 1.05 V. Compound 9g displayed the highest activity against the growth of the malaria parasite Plasmodium falciparum. Testing against the chloroquine sensitive 3D7 and the chloroquine resistant Dd2 strain resulted in IC50 values of 150 nM and 210 nM, respectively. Surprisingly, the 3-carbinol 4 and the 3-chloromethyl derivative 5, synthesized from the 3-carboxylic acid ester 2, reacted with the phenol Mannich base 6a and the novaldiamine base (7), respectively, to yield the 4-pyridone 8.     

2-(Arylpropionylamino)- and 2-(arylacryloylamino)benzophenones: farnesyltransferase inhibition and antimalarial activity

Structural variation of the 2-acylamino moiety of some benzophenone farnesyltransferase inhibitors led to the para-trifluoromethylphenylpropionyl derivative with relatively low farnesyltransferase inhibition but considerable antimalarial activity and no cytotoxicity.