L-arginine, tetrahydrobiopterin, nitric oxide and diabetes.

PURPOSE OF REVIEW: The endothelial isoform of nitric oxide synthase (eNOS) is constitutively expressed but dynamically regulated by a number of factors. Building our knowledge of this regulation is necessary to understand and modulate the bioavailability of nitric oxide, central to the cardiovascular complications of diabetes and other diseases. This review will focus on the eNOS substrate (L-arginine), its cofactor (tetrahydrobiopterin), and mechanisms related to the uncoupling of eNOS activity. RECENT FINDINGS: The global arginine bioavailability ratio has been proposed as a biomarker reflective of L-arginine availability, arginase activity, and citrulline cycling, as all of these processes impact eNOS activity. The failure of oral supplementation of tetrahydrobiopterin to recouple eNOS has emphasized the importance of the tetrahydrobiopterin to dihydrobiopterin ratio. Identification of transporters for biopterin species as well as signals that regulate endogenous arginine production have provided insight for alternative strategies to raise endothelial tetrahydrobiopterin levels while reducing dihydrobiopterin and alter eNOS activity. Finally, new information about redox regulation of eNOS itself may point to ways of controlling oxidative stress in the vasculature. SUMMARY: Restoring proper eNOS activity is key to ameliorating or preventing cardiovascular complications of diabetes. Continued investigation is needed to uncover new means for maintaining endothelial nitric oxide bioavailability.

The incidence of primary antibiotic resistance of Helicobacter pylori in Vietnam.

GOALS: To determine the susceptibility of Helicobacter pylori strains isolated from a Vietnamese population to 5 antibiotics. BACKGROUND: The incidence of antibiotic resistance in H. pylori infection is increasing worldwide and has become a leading cause for failure of treatment. Antibiotic susceptibility testing is very important to provide optimal regimens in a clinical setting. STUDY: We isolated 103 H. pylori strains from the gastric mucosa of H. pylori-infected patients from 2 areas in Vietnam (Ho Chi Minh and Hanoi) in 2008. Epsilometer test was used to determine the minimum inhibitory concentrations of amoxicillin, clarithromycin (CLR), metronidazole (MNZ), levofloxacin, and tetracycline. RESULTS: Among the 103 strains, the resistance rates were 0% (amoxicillin), 33% (CLR), 69.9% (MNZ), 18.4% (levofloxacin), and 5.8% (tetracycline). The resistant strains showed a high-level of resistance (≥ 256 µg/mL) to CLR, 23.5% (8/34), and MNZ, 29.1% (21/72). The resistance rate for CLR was significantly higher in Ho Chi Minh than in Hanoi (49% vs. 18.5%, P=0.001). Resistance to both CLR and MNZ was most commonly observed (24.3%). Two strains (1.9%) were resistant to 4 of the 5 antibiotics. No significant association was observed between antibiotic resistance rates and age, sex, or clinical outcomes of the patients. CONCLUSIONS: High incidence of resistance to CLR and MNZ suggests that standard triple therapies may not be useful as first-line treatment in Vietnam. Alternative strategies such as bismuth-based quadruple therapies or sequential therapy may be more effective in Vietnam.

Helicobacter pylori infection and gastroduodenal diseases in Vietnam: a cross-sectional, hospital-based study.

BACKGROUND: The rate of H. pylori infection in Vietnam is reportedly high, but the spectrum of H. pylori-associated gastroduodenal diseases has not been systematically investigated. Moreover, despite the similarities of ethnicity and diet, the age-standardized incidence rate of gastric cancer in the northern city of Hanoi is higher than that in the southern city of Ho Chi Minh, but the reason for this phenomenon is unknown. The virulence of Vietnamese H. pylori has also not been investigated in detail. METHODS: Individuals undergoing esophagogastroduodenoscopy were randomly recruited. H. pylori infection status was determined based on the combined results of culture, histology, immunohistochemistry, rapid urine test and serum ELISA. Peptic ulcer (PU) and gastroesophageal reflux disease was diagnosed by endoscopy, and chronic gastritis was determined histologically. H. pylori virulence factors were investigated by PCR and sequencing. RESULTS: Among the examined patients, 65.6% were infected with H. pylori. The prevalence of infection was significantly higher in those over 40 years of age than in those aged ≤40. Chronic gastritis was present in all H. pylori-infected individuals, 83.1% of whom had active gastritis, and 85.3% and 14.7% had atrophy and intestinal metaplasia, respectively. PU was present in 21% of infected patients, whereas its incidence was very low in non-infected individuals. The prevalence of PU was significantly higher in Hanoi than in Ho Chi Minh. The prevalence of vacA m1, which has been identified as an independent risk factor for PU in Vietnam, was significantly higher among H. pylori isolates from Hanoi than among those from Ho Chi Minh. CONCLUSIONS: H. pylori infection is common in Vietnam and is strongly associated with PU, active gastritis, atrophy and intestinal metaplasia. vacA m1 is associated with an increased risk for PU and might contribute to the difference in the prevalence of PU and gastric cancer between Hanoi and Ho Chi Minh.