Eradication of Helicobacter pylori: a prospective comparative randomized trial of standard versus optimized quadruple therapy.

The treatment of Helicobacter pylori infection remains a challenge. None of the proposed treatment regimens has resulted in a 100% eradication rate. The aim of our study was to compare the rate of H. pylori eradication after standard or dose-optimized amoxicillin quadruple therapy. We conducted a prospective comparative study collating patients naive to any anti-H. pylori treatment and with chronic H. pylori infection documented by histological examination. Patients were randomly assigned to either standard quadruple therapy or optimized quadruple therapy. Eradication control was performed by urea breath test. Eighty-eight eligible patients were included with 44 in each group.There was no significant difference between the eradication rates of Qo-14 and Qs-14 neither in ITT (84 vs 70.4%; p = 0.127) nor in PP (82.1 vs 77.7%; p = 0.473). Compliance and tolerance appeared similar in each group.

H. pylori is a common bacterium that can cause several digestive infections, including gastric ulcers and gastric cancer. The aim of this study was to compare the rate of H. pylori eradication after a standard dose compared with a double dose of a specific therapy known as amoxicillin quadruple therapy. The results showed no significant difference between the eradication rates of standard or optimized quadruple therapy.

Possible mitigating effect of adropin on lung injury in diabetic rats: Targeting the role of Rho A/Rho-associated kinase pathway.

This study evaluated possible mitigating effect of adropin on lung injury in diabetic rats, targeting role of Rho A/Rho-associated kinase pathway. Rats were allocated into four groups: control, adropin, diabetic, and diabetic+adropin groups. At the termination of the experiment, serum fasting glucose, insulin and adropin levels and insulin resistance were calculated. Wet/dry ratio, histopathological, immunohistochemical analyses, and relative real time gene expression of lung tissue was determined. Interleukin-6, tumor necrosis factor alpha, malondialdehyde, 8-Oxo-2'-deoxyguanosine, reduced glutathione, superoxide dismutase, Bcl-2, BAX, myeloperoxidase, intracellular adhesion molecule-1, vascular cell adhesion molecule-1, and transforming growth factor-ß were determined in lung tissue. Adropin treatment in diabetic rats notably attenuated hyperglycemia and insulin resistance. Also, it mitigated diabetic lung injury via suppressing effect on Rho A/ROCK pathway, apoptosis, inflammatory reactions, oxidative stress, and fibrosis of lung tissue. Adropin can be considered as a promising therapeutic agent for treating diabetic lung injury.

[Endoscopic removal of intrauterine device perforating the sigmoid colon: case report]. / Retrait endoscopique d'un dispositif intra-utérin perforant le côlon sigmoïde: à propos d'un cas.

Intrauterine device (IUD) is the mainstay of family planning methods in developing countries. However, it is associated with severe complications such as bleeding, perforation and migration to adjacent organs. Although perforation of the uterus is not rare, migration to the sigmoid colon is exceptional. We here report a case of IUD migration into sigmoid colon; this was removed via low endoscopy. The study involved a 45-year-old woman using an IUD who presented with pelvic pain associated with a feeling of pelvic heaviness 6 years later of insertion. Clinical examination was without abnormalities, and computed tomography (CT) scan showed the IUD embedded in the sigmoid colon wall. Diagnostic and therapeutic laparoscopy was performed, which objectified IUD-related intestinal perforation. IUD was partially embedded in the sigmoid colon wall and couldn't be removed. The device was removed during colonoscopy by diathermy loop excision (15 mm in diameter).

Correlation between the intensity of Helicobacter pylori colonization and severity of gastritis: Results of a prospective study.

Helicobacter pylori infection is strongly associated with chronic gastritis and is probably the main course of chronic inflammation in the gastric mucosa. Gradually, H. pylori gastritis will result in gastric atrophy and intestinal metaplasia. Identifying the relationship between intensity of colonization and activity of gastritis helps the clinician in more effective treatment and post-treatment follow-ups. The aim of our work was to analyze the relationship between the density of H. pylori colonization of the gastric mucosa and the severity of histological parameters of gastritis (inflammation activity, gastric atrophy, and intestinal metaplasia). This was a prospective monocentric study conducted from January 2020 to December 2020, collecting patients naive to any anti-H. pylori treatment and having a chronic H. pylori infection documented by histological examination. Epidemiological, endoscopic, and anathomopathological data were collected. Ninety-seven patients with a mean age of 42.6 years [18-65 years] and a sex ratio of M/F = 0.64 were included. The density of H. pylori colonization was mild (+) in 43.3% of patients, moderate (++) in 47.4% of patients, and significant (+++) in 9.3% of patients. Nearly, ten per cent of patients had no gastritis, 33% had mild gastritis, 50.5% had moderate gastritis, and 6.2% had severe gastritis. Gastric atrophy and intestinal metaplasia were found in 44.3% and 10.3% of our population, respectively. Patients with mild H. pylori colonization rates had the highest level of mild activity (59.5%). There was a statistically significant association between the severity of H. pylori infection and gastritis activity (p < .001). Gastric atrophy was significantly associated with the intensity of H. pylori colonization (p = .049). No significant relationship was found between the intensity of colonization and metaplasia (p = .08). Our study shows that there is a statistically significant association between the density of H. pylori and histopathological findings including gastritis activity and intestinal atrophy.

Copy-number variation of the NPHP1 gene in patients with juvenile Nephronophthisis.

Objective: Juvenile nephronophthisis (NPHP) is an autosomal recessive cystic disease of the kidney. It represents the most frequent genetic cause of chronic renal failure in children. Methods: we investigated clinical and molecular features in two children with Juvenile nephronophthisis using firstly Multiplex ligation-dependent probe amplification (MLPA) and secondly multiplex PCR. Results: we report a homozygous NPHP1 deletion in two children. Conclusion: NPHP1 deletion analysis using diagnostic methods (e.g. MLPA, Multiplex PCR) should always be considered in patients with nephronophthisis, especially from consanguineous families. Our results provide insights into genotype-phenotype correlations in juvenile nephronophthisis that can be utilized in genetic counseling.

A novel de novo splicing mutation c.1444-2A>T in the TSC2 gene causes exon skipping and premature termination in a patient with tuberous sclerosis syndrome.

Tuberous sclerosis complex (TSC) syndrome is a neurocutaneous syndrome that affects the brain, skin, and kidneys that has an adverse impact on the patient's health and quality of life. There have been several recent advances that elucidate the genetic complex of this disorder that will help understand the basic neurobiology of this disorder. We report a Tunisian patient with clinical manifestations of TSC syndrome. We investigated the causative molecular defect in this patient using PCR followed by direct sequencing. Subsequently, in silico studies and mRNA analysis were performed to study the pathogenicity of the new variation found in the TSC2. Bioinformatics tools predicted that the novel mutation c.1444-2A>T have pathogenic effects on splicing machinery. RT-PCR followed by sequencing revealed that the mutation c.1444-2A>T generates two aberrant transcripts. The first, with exon 15 skipping, is responsible for the loss of 52 amino acids, which causes the production of an aberrant protein isoform. The second, with the inclusion of 122 nucleotides of intron 14, is responsible for the creation of new premature termination codons (TGA), which causes the production of a truncated TSC2 protein. This study highlighted the clinical features of a Tunisian patient with TSC syndrome and revealed a splicing mutation c.1444-2A>T within intron 14 of TSC2 gene, which is present for the first time using Sanger sequencing approach, as a disease-causing mutation in a Tunisian patient with TSC syndrome.

Mutational analysis in patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD): Identification of five mutations in the PKD1 gene.

Autosomal Dominant Polycystic Kidney Disease (ADPKD), the most frequent genetic disorder of the kidneys, is characterized by a typical presenting symptoms include cysts development in different organs and a non-cysts manifestations. ADPKD is caused by mutations in PKD1 or PKD2 genes. In this study, we aimed to search for molecular causative defects among PKD1 and PKD2 genes. Eighteen patients were diagnosed based on renal ultrasonography and renal/extra-renal manifestations. Then, Sanger sequencing was performed for PKD1 and PKD2 genes. Multiplex Ligation dependent Probe Amplification method (MLPA) methods was performed for both PKD genes. Mutational analysis of the PKD2 gene revealed the absence of variants and no deletions or duplications of both PKD genes were detected. But three novels mutations i.e. p.S463C exon 7; c. c.11156+2T>C IVS38 and c.8161-1G>A IVS22 and two previously reported c.1522T>C exon 7 and c.412C>T exon 4 mutations in the PKD1 gene were detected. Bioinformatics tools predicted that the novel variants have a pathogenic effects on splicing machinery, pre-mRNA secondary structure and stability and protein stability. Our results highlighted molecular features of Tunisian patients with ADPKD and revealed novel variations that can be utilized in clinical diagnosis and in the evaluation of living kidney donor. To the best of our knowledge, this is the first report of Autosomal Polycystic Kidney Disease in Tunisia.

Association study of apoptosis gene polymorphisms in mitochondrial diabetes: A potential role in the pathogenicity of MD.

Mitochondrial diabetes (MD) is a heterogeneous disorder characterized by a chronic hyperglycemia and is maternally transmitted. Syndromic MD is a subgroup of MD including diabetic microangiopathy and macroangiopathy, in addition to extrapancreatic disorder. MD is caused by genetic mutations and deletions affecting mitochondrial DNA. This mitochondrial damage initiates apoptosis. In this study, we hypothesized that functional polymorphisms in genes involved in apoptotic pathway could be associated with the development of apoptosis in MD disease and increased its risk. Detection of apoptosis was confirmed on muscle biopsies taken from MD patients using the TUNEL method and the Cytochrome c protein expression level. We genotyped then 11 published SNPs from intrinsic and extrinsic apoptotic pathway and assessed the signification of these polymorphisms in 43 MD patients and 100 healthy controls. We found 10 selected polymorphisms (p53 (rs1042522 and rs17878362), BCL2 (rs2279115), BAX (rs1805419), BAK1 (rs210132 and rs2227925), CASP3 (rs1405937), CASP7 (rs2227310), CASP8 (rs1045485) and CASP10 (rs13006529)) with a potential apoptosis effect in MD patients compared to control population. Specifically, SNPs involved in the intrinsic pathway (p53, BCL2, BAK1 and CASP3) presented the highest risk of apoptosis. Our result proved that apoptosis initiated by mtDNA mutations, can be emphasized by a functional apoptotic polymorphisms associated with high expression of cytochrome c protein and more myofibers with apoptosis in syndromic MD subgroup compared with non-syndromic MD subgroup.

Whole mitochondrial genome screening of a family with maternally inherited diabetes and deafness (MIDD) associated with retinopathy: A putative haplotype associated to MIDD and a novel MT-CO2 m.8241T>G mutation.

Mitochondrial diseases are a clinically heterogeneous group of disorders that arise as a result of dysfunction of the mitochondrial respiratory chain. They can be caused by mutations in both nuclear and mitochondrial DNA. In fact, mitochondrial DNA (mtDNA) defects are known to be associated with a large spectrum of human diseases and patients might present wide range of clinical features with various combinations. Our study reported a Tunisian family with clinical features of maternally inherited diabetes and deafness (MIDD). Accordingly, we performed a whole mitochondrial genome mutational analysis, results revealed a haplotype composed by "A750G, A1438G, G8860A, T12705, T14766C and T16519C", in homoplasmic state, in the mother and transmitted to her daughter and her son. The patient with MIDD2 and retinopathy presented, in addition to this haplotype associated to the MIDD, two de novo variations including a novel one m.8241T>G (p. F219C) in MT-CO2 gene and a known one m.13276G>A (p. M314V) in MT-ND5 gene. The coexistence of these two mutations could explain the retinopathy observed in this patient.

A novel mutation MT-COIII m.9267G>C and MT-COI m.5913G>A mutation in mitochondrial genes in a Tunisian family with maternally inherited diabetes and deafness (MIDD) associated with severe nephropathy.

Mitochondrial diabetes (MD) is a heterogeneous disorder characterized by a chronic hyperglycemia, maternal transmission and its association with a bilateral hearing impairment. Several studies reported mutations in mitochondrial genes as potentially pathogenic for diabetes, since mitochondrial oxidative phosphorylation plays an important role in glucose-stimulated insulin secretion from beta cells. In the present report, we studied a Tunisian family with mitochondrial diabetes (MD) and deafness associated with nephropathy. The mutational analysis screening revealed the presence of a novel heteroplasmic mutation m.9276G>C in the mitochondrial COIII gene, detected in mtDNA extracted from leukocytes of a mother and her two daughters indicating that this mutation is maternally transmitted and suggest its implication in the observed phenotype. Bioinformatic tools showed that m.9267G>C mutation (p.A21P) is « deleterious ¼ and it can modify the function and the stability of the MT-COIII protein by affecting the assembly of mitochondrial COX subunits and the translocation of protons then reducing the activity of the respective OXPHOS complexes of ATP synthesis. The nonsynonymous mutation (p.A21P) has not been reported before, it is the first mutation described in the COXIII gene which is related to insulin dependent mitochondrial diabetes and deafness and could be specific to the Tunisian population. The m.9267G>C mutation was present with a nonsynonymous inherited mitochondrial homoplasmic variation MT-COI m.5913 G>A (D4N) responsible of high blood pressure, a clinical feature detected in all explored patients.