Anti-Helicobacter pylori potential of artemisinin and its derivatives.

The antimalarial drug artemisinin from Artemisia annua demonstrated remarkably strong activity against Helicobacter pylori, the pathogen responsible for peptic ulcer diseases. In an effort to develop a novel antimicrobial chemotherapeutic agent containing such a sesquiterpene lactone endoperoxide, a series of analogues (2 natural and 15 semisynthetic molecules), including eight newly synthesized compounds, were investigated against clinical and standard strains of H. pylori. The antimicrobial spectrum against 10 H. pylori strains and a few other bacterial and fungal strains indicated specificity against the ulcer causing organism. Of five promising molecules, a newly synthesized ether derivative ß-artecyclopropylmether was found to be the most potent compound, which exhibited MIC range, MIC(90), and minimum bactericidal concentration range values of 0.25 to 1.0 µg/ml, 1.0 µg/ml, and 1 to 16 µg/ml, respectively, against both resistant and sensitive strains of H. pylori. The molecule demonstrated strong bactericidal kinetics with extensive morphological degeneration, retained functional efficacy at stomach acidic pH unlike clarithromycin, did not elicit drug resistance unlike metronidazole, and imparted sensitivity to resistant strains. It is not cytotoxic and exhibits in vivo potentiality to reduce the H. pylori burden in a chronic infection model. Thus, ß-artecyclopropylmether could be a lead candidate for anti-H. pylori therapeutics. Since the recurrence of gastroduodenal ulcers is believed to be mainly due to antibiotic resistance of the commensal organism H. pylori, development of a candidate drug from this finding is warranted.

Interplay of potassium channel, gastric parietal cell and proton pump in gastrointestinal physiology, pathology and pharmacology.

Gastric acid secretion plays a pivotal role in the physiology of gastrointestinal tract. The functioning of the system encompasses a P2 ATPase pump (which shuttles electroneutral function at low pH) along with different voltage sensitive/neutral ion channels, cytosolic proteins, acid sensor receptors as well hormonal regulators. The increased acid secretion is a pathological marker of several diseases like peptic ulcer, gastroesophageal reflux disease (GERD), chronic gastritis, and the bug Helicobacter pylori (H. pylori) has also a critical role, which altogether affects the patient's quality of life. This review comprehensively described the nature of potassium ion channel and its mediators, the different clinical strategy to control acid rebound, and some basic experimental observations performed to study the interplay of ion channels, pumps, as well as mediators during acid secretion. Different aspects of regulation of gastric acid secretion have been focused either in terms of physiology of secretion or molecular interactions. The importance of H pylori infection and its treatment has also been discussed. Furthermore, the relevance of calcium signaling during acid secretion has been reviewed. The entire theme will make anyone understand in detail the gastric secretion machinery in general.

Dependence of Exchange Bias on Interparticle Interactions in Co/CoO Core/Shell Nanostructures.

This article reports the dependence of exchange bias (EB) effect on interparticle interactions in nanocrystalline Co/CoO core/shell structures, synthesized using the conventional sol-gel technique. Analysis via powder X-Ray diffraction (PXRD) studies and transmission electron microscope (TEM) images confirm the presence of crystalline phases of core/shell Co/CoO with average particle size ≈ 18 nm. Volume fraction (φ) is varied (from 20% to 1%) by the introduction of a stoichiometric amount of non-magnetic amorphous silica matrix (SiO2) which leads to a change in interparticle interaction (separation). The influence of exchange and dipolar interactions on the EB effect, caused by the variation in interparticle interaction (separation) is studied for a series of Co/CoO core/shell nanoparticle systems. Studies of thermal variation of magnetization (M-T) and magnetic hysteresis loops (M-H) for the series point towards strong dependence of magnetic properties on dipolar interaction in concentrated assemblies whereas individual nanoparticle response is dominant in isolated nanoparticle systems. The analysis of the EB effect reveals a monotonic increase of coercivity (HC) and EB field (HE) with increasing volume fraction. When the nanoparticles are close enough and the interparticle interaction is significant, collective behavior leads to an increase in the effective antiferromagnetic (AFM) CoO shell thickness which results in high HC and HE. Moreover, in concentrated assemblies, the dipolar field superposes to the local exchange field and enhances the EB effect contributing as an additional source of unidirectional anisotropy.

Bone modeling in bromocriptine-treated pregnant and lactating rats: possible osteoregulatory role of prolactin in lactation.

The lactogenic hormone prolactin (PRL) directly regulates osteoblast functions in vitro and modulates bone remodeling in nulliparous rats, but its osteoregulatory roles in pregnant and lactating rats with physiological hyperprolactinemia remained unclear. Herein, bone changes were investigated in rats treated with bromocriptine (Bromo), an inhibitor of pituitary PRL release, or Bromo+PRL at different reproductive phases, from mid-pregnancy to late lactation. PRL receptors were strongly expressed in osteoblasts lining bone trabeculae, indicating bone as a target of PRL actions. By using dual energy X-ray absorptiometry, we found a significant increase in bone mineral density in the femora and vertebrae of pregnant rats. Such pregnancy-induced bone gain was, however, PRL independent and may have resulted from the increased cortical thickness. Bone trabeculae were modestly changed during pregnancy as evaluated by bone histomorphometry. On the other hand, lactating rats, especially in late lactation, showed massive bone loss in bone trabeculae but not in cortical shells. Further study in Bromo- and Bromo+PRL-treated rats suggested that PRL contributed to decreases in trabecular bone volume and number and increases in trabecular separation and eroded surface, as well as a paradoxical increase in bone formation rate in late lactation. Uncoupling of trabecular bone formation and resorption was evident in lactating rats, with the latter being predominant. In conclusion, pregnancy mainly induced cortical bone gain, whereas lactation led to trabecular bone loss in both long bones and vertebrae. Although PRL was not responsible for the pregnancy-induced bone gain, it was an important regulator of bone modeling during lactation.

Detection and quantification of ppb level potassium in biological samples in the presence of high sodium by ion chromatographic method.

Employing a silica gel column modified with carboxyl groups and an eluent consisting of 4.0mM tartaric acid and 0.75mM dipicolinic acid in 2% acetone, an otherwise difficult quantification of K(+) at ppb level in presence of 6000ppm NaCl was achieved by incorporating 0.75mM 18-crown-6 ether in the mobile phase and subtracting the blank NaCl signal from each chromatogram. Optimized analytical conditions were established in terms of relative standard deviation (%) of retention time, peak area and calibration equations, and also by peak asymmetry factor. The net efflux of K(+) into the gastric lumen under in vitro conditions of acid secretion was investigated in Ussing chamber model. The effects of the physiological secretagogue histamine and the antisecretory agents cimetidine, omeprazole and SCH28080 were studied. The decline of K(+) efflux in presence of cimetidine, and the rise of the same in the presence of omeprazole and SCH28080 were conspicuously discernible, thereby validating the usefulness of ion chromatography based K(+) quantification method under biological experimental conditions.

Woodfordia fruticosa: traditional uses and recent findings.

Woodfordia fruticosa Kurz of the family Lythraceae is a plant of tropical and subtropical region with a long history of medicinal use. A wide range of chemical compounds including tannins (especially those of macrocyclic hydrolysable class), flavonoids, anthraquinone glycosides, and polyphenols have been isolated from this species in recent times. Extracts and metabolites of this plant, particularly those from flowers and leaves, possess useful pharmacological activities. A comprehensive account of the chemical constituents and the biological activities is presented and a critical appraisal of the ethnopharmacological issues is included in view of the many recent findings of importance on this plant.

On the potential of Tephrosia purpurea as anti-Helicobacter pylori agent.

AIM OF THE STUDY: Since Tephrosia purpurea (Linn.) Pers. (Fabaceae) has traditional use in curing different types of wounds including gastroduodenal ulcers, it was of interest to evaluate the in vitro anti-Helicobacter pylori activity profile of the plant extract and its fractions with a view to examining its therapeutic potential, if any. MATERIALS AND METHODS: Employing clinical isolates and standard strains of Helicobacter pylori, the extract and fractions were bioevaluated in terms of MIC and MBC values, acid stability, time-kill kinetics, drug resistance, and synergistic potential. RESULTS: The methanolic extract showed promising activity against clinical isolates and standard strains of Helicobacter pylori, including metronidazole-resistant strains. Fractionation of the extract revealed the n-hexane and chloroform fractions to possess marked activity. The extract and the less polar fractions remained functionally active in acidic condition similar to stomach environment, exhibited consistent bacteriostatic activity during repeated exposure, and demonstrated synergism, complete or partial, even with antibiotic-resistant strains. CONCLUSION: Apolar fractions of Tephrosia purpurea may have therapeutic potential in combating Helicobacter pylori mediated gastroduodenal disorders.