Subcellular ROS Signaling in Cardiovascular Disease

This review discusses recent findings that have challenged the long-held dogma in the field that reduction in reaction oxygen species (ROS) would improve clinical outcome in the patients with cardiovascular disease (CVD). Attempts will be made to shed light on the differential spatial and temporal roles of subcellular ROS in vascular endothelium in health and disease. Recent findings demonstrating that above-physiological levels of endothelial cell (EC)-specific NADPH oxidase-derived ROS in vivo exert beneficial effects on vascular endothelium will be discussed. The paradoxical roles of ROS in CVD suggest that subcellular sources and types of ROS may play crucial roles in the prevention, development, and progression of CVD. A better understanding of the precise mechanisms by which subcellular ROS modulate cardiovascular health and functions will certainly better prepare us with effective treatment modalities for CVD

Identifying receptors for neuropeptides and peptide hormones: challenges and recent progress

Intercellular signaling events mediated by neuropeptides and peptide hormones represent important targets for both basic science and drug discovery. For many bioactive peptides, the protein receptors that transmit information across the receiving cell membrane are not known, severely limiting these signaling pathways as potential therapeutic targets. Identifying the receptor(s) for a given peptide of interest is complicated by several factors. Most notably, cell-cell signaling peptides are generated through dynamic biosynthetic pathways, can act on many different families of receptor proteins, and can participate in complex ligand-receptor interactions that extend beyond a simple one-to-one archetype. Here, we discuss recent methodological advances to identify signaling partners for bioactive peptides. Recent advancements have centered on methods to identify candidate receptors via transcript expression, methods to match peptide- peptidereceptor pairs through high throughput screening, and methods to capture direct ligand-receptor interactions using chemical probes. Future applications of the receptor identification approaches discussed here, as well as technical advancements to address their limitations, promises to lead to a greater understanding of how cells communicate to deliver complex physiologies. Importantly, such advancements will likely provide novel targets for treatment of a number of human diseases within the central nervous and endocrine systems

Antibiotic susceptibility patterns of Helicobacter pylori and triple therapy in a high-prevalence area

This study aims to determine primary Helicobacter pylori resistance and its effect on eradication of the organism. Ninety-two Patients with dyspeptic symptoms were enrolled. H. pylori was cultured and antibiotic sensitivity was determined by the Epsilometer test (Etest) for clarithromycin (CLR), amoxicillin (AMX) and metronidazole (MTR). 23S ribosomal RNA (rRNA) point mutations associated with clarithromycin resistance were also detected. Patients were treated with omeprazole (40 mg daily), CLR (500 mg) and AMX (1g twice a day) for 14 days. A (14)C-urea breath test ((14)C-UBT) was repeated four weeks after completion of treatment to confirm eradication. Triple therapy failure was seen in 30(33%) Patients. The resistance rates were: CLR 33% (30/92), MTR 48% (44192) and AMX (2/92). Clarithromycin resistance (CLR-R) was present in the 16-39 age group in 21 (47%) (P=0.007) compared to nine (19%)in the 40-79 age group. CLR resistance was seen in 30 H. pylori isolates, 20 (67%) from Patients with non-ulcer dyspepsia (NUD), six (20%) with gastric ulcer (GU) and four (13%) with duodenal ulcer (DU). Triple therapy failure was associated with CLR-R in 28 (93%) (

17β-Estradiol dysregulates innate immune responses to Pseudomonas aeruginosa respiratory infection and is modulated by estrogen receptor antagonism

ABSTRACT Females have a more severe clinical course than males in terms of several inflammatory lung conditions. Notably, females with cystic fibrosis (CF) suffer worse outcomes, particularly in the setting of Pseudomonas aeruginosa infection. Sex hormones have been implicated in experimental and clinical studies; however, immune mechanisms responsible for this sex-based disparity are unknown and the specific sex hormone target for therapeutic manipulation has not been identified. The objective of this study was to assess mechanisms behind the impact of female sex hormones on host immune responses to P. aeruginosa . We used wild-type and CF mice, which we hormone manipulated, inoculated with P. aeruginosa , and then examined for outcomes and inflammatory responses. Neutrophils isolated from mice and human subjects were tested for responses to P. aeruginosa . We found that female mice inoculated with P. aeruginosa died earlier and showed slower bacterial clearance than males ( P &lt; 0.0001). Ovariectomized females supplemented with 17β-estradiol succumbed to P. aeruginosa challenge earlier than progesterone- or vehicle-supplemented mice ( P = 0.0003). 17β-Estradiol-treated ovariectomized female mice demonstrated increased lung levels of inflammatory cytokines, and when rendered neutropenic the mortality difference was abrogated. Neutrophils treated with 17β-estradiol demonstrated an enhanced oxidative burst but decreased P. aeruginosa killing and earlier cell necrosis. The estrogen receptor (ER) antagonist ICI 182,780 improved survival in female mice infected with P. aeruginosa and restored neutrophil function. We concluded that ER antagonism rescues estrogen-mediated neutrophil dysfunction and improves survival in response to P. aeruginosa . ER-mediated processes may explain the sex-based mortality gap in CF and other inflammatory lung illnesses, and the ER blockade represents a rational therapeutic strategy. </jats:p

Risk factors associated with Helicobacter pylori infection treatment failure in a high prevalence area

Triple therapy is commonly used for the treatment of Helicobacter pylori infection. We determined risk factors associated with its failure in compliant Patients focusing on H. pylori density, virulence marker and 23S ribosomal RNA (rRNA) point mutations associated with clarithromycin resistance. H. pylori infection was diagnosed by (14)C urea breath test ((14)C UBT) and rapid urease test or histology. Triple therapy with esomeprazole 20 mg b.i.d., amoxicillin 1 g b.i.d. and clarithromycin 500 mg b.i.d. was prescribed for 10 days. 14C UBT was repeated 4 weeks after treatment. In total, 111 Patients [69 (62%) males] with a mean age of 46 +/- 16 years were enrolled. The mean age of treatment failure was 39 +/- 14 years compared to 48 +/- 16 years with eradication (P=0.002). Treatment failure was associated with younger mean age, point mutations in the 23S rRNA gene of H. pylori and vacA s1a and m1 when associated with cagA negativity

Carcinome spinocellulaire de la levre inferieure: Sur cicatrice de lupus erythemateux chronique

Epidermoïd carcinoma is the most common malignant tumor of the lips.They often develop on precancerous lesions. Leukoplasia is the most frequent precancerous lesion. We report a case of a 35 years old man, who suffered from discoid lupus erythematous since 20 years; and wasn't treatedfrom. He consulted for a squamous ulceration of the under lip, developed from one year. The biopsy concluded to an epidermoïd carcinoma.He was treated with surgical excision with reconstruction and homolateral triangular recovery.Keywords: Squamous cell carcinoma, epidermoïd carcinoma, discoid lupus erythematosus, precancerous lesion

Mucocele geante de l’enfant

Les mucocèles sont des formations pseudo kystiques expansives des sinus de la face. Elles sont souvent diagnostiquées tardivement du fait de l’absence de signes spécifiques. Le bilan radiologique basé sur la TDM et ou l’IRM est essentiel pour confirmer le diagnostic et établir le bilan d’extension. Nous rapportons le cas d’un enfant âgé de 4 ans et 6mois traité d’une mucocèle géante éthmoïdo- maxillaire.Mots clés : mucocèle ; enfant ; TDM ; IRM ; chirurgieMucoceles are pseudo-cystic expansive formations of the sinuses. They are often diagnosed lately because of the lack of specific signs. CT and MRI are essential for the diagnosis and to evaluate the extension.We report a case of child with ethmoide-maxillary mucocèle treated in our department.Key words: mucocele; child; CT; MRI; surger