Helicobacter pylori Vacuolating Cytotoxin A Causes Anorexia and Anxiety via Hypothalamic Urocortin 1 in Mice.

Helicobacter pylori (Hp) infection is related to the pathogenesis of chronic gastric disorders and extragastric diseases. Here, we examined the anorexigenic and anxiogenic effects of Hp vacuolating cytotoxin A (VacA) through activation of hypothalamic urocortin1 (Ucn1). VacA was detected in the hypothalamus after peripheral administration and increased Ucn1 mRNA expression and c-Fos-positive cells in the hypothalamus but not in the nucleus tractus solitarius. c-Fos and Ucn1-double positive cells were detected. CRF1 and CRF2 receptor antagonists suppressed VacA-induced anxiety and anorexia, respectively. VacA activated single paraventricular nucleus neurons and A7r5 cells; this activation was inhibited by phospholipase C (PLC) and protein kinase C (PKC) inhibitors. VacA causes anorexia and anxiety through the intracellular PLC-PKC pathway, migrates across the blood-brain barrier, and activates the Ucn1-CRF receptor axis.

Negative Effect of Proton-pump Inhibitors (PPIs) on Helicobacter pylori Growth, Morphology, and Urease Test and Recovery after PPI Removal--An In vitro Study.

BACKGROUND: Proton-pump inhibitor (PPI) consumption does lead to false-negative results of Helicobacter pylori diagnostic tests such as biopsy culture and rapid urease test (RUT). MATERIALS AND METHODS: Helicobacter pylori isolates from 112 dyspeptic patients with (56.5%) or without (43.5%) PPI consumption were recruited for examining the negative effects of omeprazole (OMP), lansoprazole (LPZ), and pantoprazole (PAN) on H. pylori viability, morphology, and urease, in vitro. The effect of a sublethal concentration of OMP on bacterial features and their recovery after removal of OMP was also assessed. RESULTS: Of 112 culture-positive gastric biopsies, 87.5% were RUT positive and 12.5% RUT negative. There was a significant correlation between negative RUT results and PPI consumption (p < .05). OMP (minimum inhibitory concentration, MIC 32 µg/mL) and LPZ (MIC 8 µg/mL) inhibited the growth of 78.6% of H. pylori isolates. OMP and LPZ inhibited urease of 90.3% of isolates between 0 and 40 minutes and 54.4% between 20 and 40 minutes, respectively. PAN did not inhibit H. pylori growth and urease. Three 3-day (9 days) consecutive subcultures of H. pylori on brucella blood agar (BBA) supplemented with OMP resulted in reduced bacterial viability (1+), compared with control (4+), change of spiral morphology to coccoid, and reduction in pink color intensity in urea agar. Bacterial growth (1+), morphology, and urease test did not improve after the first 3-day and second 3-day (6 days) subcultures on BBA. However, relative recovery occurred after the third 3-day (9 days) subculture and complete recovery was observed after the fourth 3-day (12 days) subculture, as confluent growth (4+), 100% spiral cells, and strong urease test. CONCLUSION: Proton-pump Inhibitors exert transient negative effects on H. pylori viability, morphology, and urease test. Accordingly, cessation of PPI consumption at least 12 days before endoscopy could help avoiding false-negative results of H. pylori diagnostic tests.

Propiedades anti-Helicobacter pylori de los extractos de Psidium guajava y Coptis chinensis / Atividade anti-Helicobacter pylori de los extractos de Psidium guajava e Coptis chinensis / Anti-Helicobacter pylori activity of extracts of Psidium guajava and Coptis chinensis

Se postula y fundamenta Ia utilidad de una mezcIa de extractos de plantas medicinales con propiedades sinérgicas compuesta por Psidium guajava L. estandarizado en su contenido de heterósidos flavónicos y Coptis chinensis Franch., estandarizado en su contenido de aIcaIoides benzofenantridínicos, para eI desarroIIo de un fitomedicamento útiI para eI tratamiento y prevención de Ia gastritis crónica provocada por Helícobacter pylori. EI estudio explora eI potencial que tiene Ia mezcIa para inhibir eI crecimiento in vitro de diversas cepas clínicas de H. pylori resistentes a los antibióticos convencionales, así como, su acción protectora deI epiteIio gástrico, al impedir Ia adherencia de Ia bacteria alas celulas AGS en cultivo (AU)

Descreve-se e fundamenta-se a utilidade de uma associagáo de extratos de plantas medicinais com propriedades sinergicas composta por Psidium guajava L., extracto padronizado em glicósidos flavónicos e Coptis chinensis Franch, extracto padronizado em alcalóides benzofenantridínicos, para o desenvolvimento de um medicamento a base de plantas para o tratamento e prevençáo da gastrite crónica provocada por Helicobacter pylori. O estudo explora o potencial que tem esta associaçáo para inibir o crescimento in vitro de diversas estirpes clinicas de H. pylori resistentes aos antibióticos convencionais, assim como, a sua acçáo protectora do epitelio gástrico, ao impedir a aderencia das bacterias ás culturas celulares de AGS (AU)

It is described the synergistic properties of a mixture of Psidium guajava L., extract standardized in its content of flavone glycosides and Coptis chinensis Franch, extract standardized in its content of benzophenantridinic alkaloids, for developing a phytodrug for the treatment and prevention of chronic gastritis induced by Helicobacter pylori. The study explores the properties of this combination of extracts by inhibiting in vitro growth of antibiotic-resistant clinical H. pylori strains and preventing adherence of the bacteria to human AGS cell cultures (AU)

Activities of muscadine grape skin and polyphenolic constituents against Helicobacter pylori.

AIMS: To identify active phenolic constituents in muscadine grape skin (MGS) extracts and determine interactions among compounds while further exploring their anti-Helicobacter pylori potential in vitro. METHODS AND RESULTS: The inhibitory effects of quercetin and resveratrol, active polyphenols identified in MGS extracts, against H. pylori were investigated. Quercetin and resveratrol significantly (P < 0.05) reduced H. pylori counts regardless of pH with minimal bactericidal concentrations of 256 and 128 µg ml(-1), respectively. MGS extracts displayed the highest efficacy, suggesting additional unidentified compounds not determined in this study. Time-course viability experiments showed a dose-dependent anti-H. pylori response to quercetin and resveratrol. Interestingly, neither quercetin nor resveratrol affected H. pylori outer membrane (OM) integrity as determined by 1-N-phenylnaphthylamine (NPN) uptake assays. However, treatment with MGS extract did increase NPN uptake, indicating OM destabilization possibly by additional unknown components. Furthermore, quercetin was found to enter H. pylori as measured by HPLC supporting intracellular drug accumulation. CONCLUSIONS: Quercetin and resveratrol possess strong anti-H. pylori activity in vitro and are independent of pH. Our results also suggest that these compounds do not affect H. pylori OM integrity as previously hypothesized and that the primary antimicrobial activity of quercetin may be linked to interactions with intracellular components. SIGNIFICANCE AND IMPACT OF THE STUDY: The anti-H. pylori effects of quercetin and resveratrol suggest that these compounds may be useful in the dietary prevention and/or treatment of H. pylori infection.

Thermal degradation of allicin in garlic extracts and its implication on the inhibition of the in-vitro growth of Helicobacter pylori.

Allicin, the main active principle related to Allium sativum chemistry, is considered to be responsible for the bacteriostatic properties of garlic. The work described here has demonstrated the direct implication of the allicin present in solvent-free garlic extracts obtained with ethanol (ethanolic garlic extract, EGE) and acetone (acetonic garlic extract, AGE) in the inhibition of the in-vitro growth of Helicobacter pylori (Hp), the bacterium responsible for serious gastric diseases such as ulcers and even gastric cancer. The evolution of allicin concentration as a function of time and temperature has been the subject of a kinetic study. The reaction order, activation energy, and preexponential factor (in accordance with Arrhenius theory) have been determined for the decomposition process of allicin in these organic media. First-order decomposition, an activation energy of 97.4 kJ/mol, and an Arrhenius preexponential factor of 8.9 x 10(10) s(-1) have been determined for allicin in EGE. For allicin in AGE the kinetic order determined was 1.5, the activation energy 184.5 kJ/mol, and the preexponential factor 3.1 x 10(24) s(-1) (mg/L)(-0.5). The presence or absence of allicin in these garlic products was found to be crucial for the inhibition of the in-vitro growth of Hp, as demonstrated by microbiological analysis for AGE. A relationship has been identified between the effectiveness and durability of the anti-Hp properties shown by AGE and the allicin content of these products. The bacteriostatic properties were active for up to 10 months if the samples were maintained at 6 degrees C.

Allyl-thiosulfinates, the bacteriostatic compounds of garlic against Helicobacter pylori.

Allicin and allyl-methyl plus methyl-allyl thiosulfinate from acetonic garlic extracts (AGE) have been isolated by high-performance liquid chromatography. These compounds have shown inhibition of the in vitro growth of Helicobacter pylori (Hp), the bacterium responsible for serious gastric diseases such as ulcers and even gastric cancer. A chromatographic method was optimized and used to isolate these thiosulfinates. The method developed has allowed the isolation of natural thiosulfinates extracted from garlic by organic solvents and is an easy and cheap methodology that avoids complex synthesis and purification procedures. The capacity and effectiveness of isolated natural thiosulfinates have been tested, and this has enabled the identification of the main compounds responsible for the bacteriostatic activity shown by AGE origin of these kinds of organosulfur compounds along with ethanolic garlic extracts (EGE). Additionally, microbiological analyses have suggested that these compounds show a synergic effect on the inhibition of the in vitro growth of Hp. The results described here facilitate the process of obtaining garlic extracts with optimal bacteriostatic properties. The product is obtained in a way that avoids expensive purification methods and will allow the design of live tests with the aim of investigating the potential for the use of these garlic derivatives in the treatment of patients with Hp infections.

Enhancement of the growth of Helicobacter pylori in Brucella broth by hydrogen peroxide.

We found that a sub-lethal concentration of hydrogen peroxide (HPOx) enhanced the growth of Helicobacter pylori in Brucella broth supplemented with 10% fetal bovine serum (BB/FBS). The enhancement was evident at 0.1 mM HPOx and reached a maximun at 3.5 mM. The growth stimulation was dependent on the basal media used; when brain heart infusion broth (BHIB) was used instead of BB, the growth was not altered regardless of the presence or absence of HPOx. Furthermore, the growth in BHIB/FBS was comparable to that in BB/FBS plus 3.5 mM HPOx. This suggested that the enhancement of growth by HPOx resulted from the derepression of the inhibitory factor existing in BB by HPOx. The inhibitory substance seemed to be bisulfite salt since the bacteria grew to a similar extent in bisulfite-less Brucella broth (BLBB0)/FBS compared to the bacterial growth in BHIB/FBS and BB/FBS plus HPOx. These results indicate that the detoxification of bisulfite in BB can be easily achieved by simply adding HPOx to the medium, which causes the oxidation of bisulfite to bisulfate, a less-toxic compound to the bacterial growth. Since we also found that the morphology and cellular protein profile of BB/FBS-cultured bacteria were apparently different from those cultured in BLBB/FBS, we propose that the use of BB for primary isolation and cultivation of H. pylori should be limited on certain occasions, or if necessary, BB can be used after detoxification of the bisulfite by the addition of a low concentration of HPOx.