GPR109A mediates the effects of hippuric acid on regulating osteoclastogenesis and bone resorption in mice.

The G protein-coupled receptor 109 A (GPR109A) is robustly expressed in osteoclastic precursor macrophages. Previous studies suggested that GPR109A mediates effects of diet-derived phenolic acids such as hippuric acid (HA) and 3-(3-hydroxyphenyl) propionic acid (3-3-PPA) on promoting bone formation. However, the role of GPR109A in metabolic bone homeostasis and osteoclast differentiation has not been investigated. Using densitometric, bone histologic and molecular signaling analytic methods, we uncovered that bone mass and strength were significantly higher in tibia and spine of standard rodent diet weaned 4-week-old and 6-month-old GPR109A gene deletion (GPR109A-/-) mice, compared to their wild type controls. Osteoclast numbers in bone and in ex vivo bone marrow cell cultures were significantly decreased in GPR109A-/- mice compared to wild type controls. In accordance with these data, CTX-1 in bone marrow plasma and gene expression of bone resorption markers (TNFα, TRAP, Cathepsin K) were significantly decreased in GPR109A-/- mice, while on the other hand, P1NP was increased in serum from both male and female GPR109A-/- mice compared to their respective controls. GPR109A deletion led to suppressed Wnt/ß-catenin signaling in osteoclast precursors to inhibit osteoclast differentiation and activity. Indeed, HA and 3-3-PPA substantially inhibited RANKL-induced GPR109A expression and Wnt/ß-catenin signaling in osteoclast precursors and osteoclast differentiation. Resultantly, HA significantly inhibited bone resorption and increased bone mass in wild type mice, but had no additional effects on bone in GPR109A-/- mice compared with their respective untreated control mice. These results suggest an important role for GPR109A during osteoclast differentiation and bone resorption mediating effects of HA and 3-3-PPA on inhibiting bone resorption during skeletal development.

Nonantibiotic prevention and management of recurrent urinary tract infection.

Urinary tract infections (UTIs) are highly prevalent, lead to considerable patient morbidity, incur large financial costs to health-care systems and are one of the most common reasons for antibiotic use worldwide. The growing problem of antimicrobial resistance means that the search for nonantibiotic alternatives for the treatment and prevention of UTI is of critical importance. Potential nonantibiotic measures and treatments for UTIs include behavioural changes, dietary supplementation (such as Chinese herbal medicines and cranberry products), NSAIDs, probiotics, D-mannose, methenamine hippurate, estrogens, intravesical glycosaminoglycans, immunostimulants, vaccines and inoculation with less-pathogenic bacteria. Some of the results of trials of these approaches are promising; however, high-level evidence is required before firm recommendations for their use can be made. A combination of these agents might provide the optimal treatment to reduce recurrent UTI, and trials in specific population groups are required.

Sensibilidad antimicrobiana de cepas hipurato-negativas de Campylobacter spp. y de Helicobacter pullorum aisladas de enfermos con diarrea / Antimicrobial sensitivity of hippurate-negative Campylobacter and Helicobacter pullorum strains isolated from patients with diarrhea

El género Campylobacter, tanto C. jejuni como algunas especies hipurato-negativas y géneros relacionados, son la principal causa de gastroenteritis en nuestro entorno a lo largo de todo el año. El objetivo del presente estudio es determinar la sensibilidad de cepas hipurato negativas de Campylobacter spp. y de Helicobacter pullorum aislados de heces diarreicas humanas. Se estudiaron 39 cepas de Campylobacter coli, dos de C. lari y cinco de Helicobacter pullorum identificadas por espectrometría de masas MALDI-TOF. La sensibilidad a amoxicilina- clavulánico, eritromicina, azitromicina, gentamicina, ciprofloxacino, levofloxacino, tetraciclina, tigeciclina y cloranfenicol se determinó por E-test. La mayoría de las cepas de Campylobacter hipurato-negativos y H. pullorum estudiadas presentaron una elevada resistencia a las dos fluoroquinolonas probadas y a la tetraciclina. Por otro lado, todas las cepas fueron sensibles a amoxicilina-clavulánico, a tigeciclina y a cloranfenicol, mientras que la mayoría lo fueron a los macrólidos y a la gentamicina(AU)

C. jejuni as well as some hippurate-negative Campylobacter species and related diarrheagenic organisms, are the leading cause of gastroenteritis in our environment all throughout the year. The aim of the present study was to determine the sensitivity of hippurate-negative Campylobacter and Helicobacter pullorum strains isolated from the stools of patients with diarrhea. We tested 39 Campylobacter coli, two C. lari and five Helicobacter pullorum strains identified by mass spectrometry analysis. The sensitivity to amoxicillin-clavulanic acid, erytrhomycin, azithromycin, gentamicin, ciprofloxacin, levofloxacin, tetracycline, tigecycline and chloramphenicol was tested by E-test. Most hippurate-negative Campylobacter and H. pullorum isolates studied showed high resistance to tetracycline and to the two fluorquinolones tested. On the other side, all strains were sensitive to amoxicillin-clavulanic acid, tigecycline and chloramphenicol, while most of them were sensitive to both macrolides tested and to gentamicin(AU)

Spinal-injured neuropathic bladder antisepsis (SINBA) trial.

OBJECTIVE: To determine whether Methenamine Hippurate (MH) or cranberry tablets prevent urinary tract infections (UTI) in people with neuropathic bladder following spinal cord injury (SCI). STUDY DESIGN: Double-blind factorial-design randomized controlled trial (RCT) with 2 year recruitment period from November 2000 and 6 month follow-up. SETTING: In total, 543 eligible predominantly community dwelling patients were invited to participate in the study, of whom 305 (56%) agreed. METHODS: Eligible participants were people with SCI with neurogenic bladder and stable bladder management. All regimens were indistinguishable in appearance and taste. The dose of MH used was 1 g twice-daily. The dose of cranberry used was 800 mg twice-daily. The main outcome measure was the time to occurrence of a symptomatic UTI. RESULTS: Multivariate analysis revealed that patients randomized to MH did not have a significantly longer UTI-free period compared to placebo (HR 0.96, 95% CI: 0.68-1.35, P=0.75). Patients randomized to cranberry likewise did not have significantly longer UTI-free period compared to placebo (HR 0.93, 95% CI: 0.67-1.31, P=0.70). CONCLUSION: There is no benefit in the prevention of UTI from the addition of MH or cranberry tablets to the usual regimen of patients with neuropathic bladder following SCI.