Evaluation of Acid-Suppressive Medications Prescribing and Usage in Central Hospitals in Abha Region, Saudi Arabia / Evaluación de la prescripción y uso de medicamentos supresores de ácido en hospitales centrales en la región de Abha, Arabia Saudita

Objective: The aim of this study was to study and assess the indications of acid suppressive drugs and to find out percentage of irrational prescriptions with acid suppressive drugs. Material/Methods: It is a prospective observational study conducted in the Armed Forces Hospitals Southern Region and Abha Maternity Hospital, both in Abha in Assir region (Saudi Arabia). The sample size of study was 185 patients. The case sheets of the patients' prescription order were reviewed for acid suppressive drugs prescription and relevant data was taken. Patients’ age above 18 were identified. The duration of study was 8 weeks, between May and June 2017. Results: Our results showed that the majority of the prescriptions of proton pump inhibitors (68.1%) were unjustifiable and that proton pump inhibitor was the most commonly prescribed acid suppressive drugs for the patients (97.8%). The frequency of prescribing for the autism spectrum disorders in our study was found to be higher in patients with an existing risk factor and was mostly recommended by physicians as concomitant medications (67.6%). The most common concomitant medications used with the proton pump inhibitors were non-steroidal anti-inflammatory drugs (29.2%) in which aspirin composed 13.5% of the non-steroidal anti-inflammatory drugs prescribed followed by antimicrobials (9.2%). Conclusion: Acid suppressive drugs are the most commonly prescribed drugs with no proper indications hence irrational. Based on the results of this study, creating awareness about reasonable use of acid suppressive drugs is a necessity

Objetivo: El objetivo de este estudio fue estudiar y evaluar las indicaciones de los medicamentos supresores de ácidos y averiguar el porcentaje de recetas irracionales con medicamentos supresores de ácidos. Material / Métodos: es un estudio observacional prospectivo realizado en los Hospitales de las Fuerzas Armadas del Sur y en el Hospital de Maternidad Abha, ambos en Abha en la región de Assir (Arabia Saudita). El tamaño muestral del estudio fue de 185 pacientes. Se revisaron las hojas de casos de orden de prescripción de los pacientes para la prescripción de medicamentos supresores de ácido y se tomaron los datos pertinentes. Se identificó la edad de los pacientes mayores de 18 años. La duración del estudio fue de 8 semanas, entre mayo y junio de 2017. Resultados: nuestros resultados mostraron que la mayoría de las prescripciones de inhibidores de la bomba de protones (68,1%) eran injustificables y que este era el fármaco supresor de ácido más comúnmente prescrito para los pacientes (97,8%). La frecuencia de prescripción para los trastornos del espectro autistas en nuestro estudio, fue mayor en pacientes con un factor de riesgo existente y fue recomendada principalmente por los médicos como medicamentos concomitantes (67,6%). Los medicamentos concomitantes más comunes que se usaron con los inhibidores de la bomba de protones fueron los antiinflamatorios no esteroideos (29.2%) en los cuales la aspirina supuso el 13,5% de los antiinflamatorios no esteroideos prescritos, seguidos por los antimicrobianos (9.2%). Conclusión: los medicamentos supresores de ácido son los medicamentos más comúnmente recetados sin indicaciones adecuadas, por lo que son irracionales. Basado en los resultados de este estudio, crear conciencia sobre el uso razonable de los medicamentos supresores del ácido es una necesidad

Inhibitory Effects of Nitrite on Acid Production in Dental Plaque in Children.

PURPOSE: To assess the inhibitory effects of nitrite on plaque acidogenicity and its relationship with caries experience. MATERIALS AND METHODS: Plaque (2 µl) was collected from 76 children (age 5.8 ± 2.6 years, dmft 2.9 ± 3.5, DMTF 0.6 ± 1.4) and mixed with nitrite solution (final concentration = 0.63 mM) or distilled water (control). The initial pH (pH-0) of each sample was measured using a portable pH meter. The samples were incubated for 10 min, then their pH (pH-1) was measured again. Next, glucose (final concentration = 0.67%) was added to the samples, which were then incubated for a further 10 min before their pH was assessed for a third time (pH-2). RESULTS: The pH-0, pH-1, and pH-2 values of the control samples were 7.25 ± 0.16, 6.07 ± 0.44, and 5.11 ± 0.48, respectively, and those of the nitrite-treated samples were 7.26 ± 0.16, 6.37 ± 0.45, and 5.34 ± 0.48, respectively. The pH-1 and pH-2 values of the nitrite-treated samples were higher than those of the control samples (p < 0.005). Greater plaque acid production was associated with stronger inhibition of plaque acid production by nitrite (p < 0.005). No relationship was detected between the inhibition by nitrite and caries experience. CONCLUSIONS: Nitrite inhibited both endogenous and exogenous plaque acid production. Nitrite inhibited acid production more markedly in plaque that exhibited greater acid production, suggesting that nitrite might be effective at preventing caries, as it contributes to pH homeostasis in plaque by countering excess acidification.

LASS2 enhances chemosensitivity of breast cancer by counteracting acidic tumor microenvironment through inhibiting activity of V-ATPase proton pump.

A main obstacle to overcome during the treatment of tumors is drug resistance to chemotherapy; emerging studies indicate that a key factor contributing to this problem is the acidic tumor microenvironment. Here, we found that LASS2 expression was significantly lower in drug-resistant Michigan Cancer Foundation-7/adriamycin (MCF-7/ADR) human breast cancer cells than the drug-sensitive MCF-7 cells, and low expression of LASS2 was associated with poor prognosis in patients with breast cancer. Our results showed that the overexpression of LASS2 in MCF-7/ADR cells increased the chemosensitivity to multiple chemotherapeutic agents, including doxorubicin (Dox), whereas LASS2 knockdown in MCF-7 cells decreased the chemosensitivity. Cell-cycle analysis revealed a corresponding increase in apoptosis in the LASS2-overexpressing cells following Dox exposure, showing that the overexpression of LASS2 increased the susceptibility to Dox cytotoxicity. This effect was mediated by a significant increase in pHe (extracellular pH) and lysosomal pH, and more Dox entered the cells and stayed in the nuclei of cells. In nude mice, the combination of LASS2 overexpression and Dox significantly inhibited the growth of xenografts. Our findings suggest that LASS2 is involved in chemotherapeutic outcomes and low LASS2 expression may predict chemoresistance.

Divalent cations enhance fluoride binding to Streptococcus mutans and Streptococcus sanguinis cells and subsequently inhibit bacterial acid production.

One preventive effect of topical fluoride application is derived from the fact that fluoride can inhibit bacterial acid production. Furthermore, divalent cations such as Ca(2+) and Mg(2+) increase the binding of fluoride to bacterial cells. These findings suggest that exposure of oral bacteria to fluoride in the presence of divalent cations increases fluoride binding to bacterial cells and subsequently enhances fluoride-induced inhibition of bacterial acid production. This study investigated the effects of fluoride exposure (0-20,000 ppm F) in the presence of Ca(2+) or Mg(2+) prior to glucose challenge on pH fall ability by bacterial sugar fermentation, as well as fluoride binding to bacterial cells by exposure to fluoride, and fluoride release from bacterial cells during bacterial sugar fermentation, using caries-related bacteria, Streptococcus mutans and Streptococcus sanguinis. The pH fall by both streptococci was inhibited by exposure to over 250 ppm F in the presence of Ca(2+) (p < 0.01), whereas in the presence of Mg(2+), the pH fall by S. mutans and S. sanguinis was inhibited after exposure to over 250 and 950 ppm F, respectively (p < 0.05). The amounts of fluoride binding to and released from streptococcal cells increased with the concentration of fluoride the cells were exposed to in the presence of Mg(2+), but were high enough even after 250 ppm F exposure in the presence of Ca(2+). The enhanced inhibition of acid production in the presence of divalent cations is probably due to the improved efficiency of fluoride binding to bacterial cells being improved via these divalent cations.

The key to halting progression of CKD might be in the produce market, not in the pharmacy.

In vitro, experimental, and clinical work suggests that metabolic acidosis, either directly or indirectly, can promote the progression of chronic kidney disease (CKD). Goraya et al. demonstrate that both oral alkali supplementation and a diet rich in fruits and vegetables are equally effective at decreasing urinary excretion of markers of renal injury in patients with stage 2 CKD. Although this study is promising, the short duration and use of only urinary markers as a surrogate outcome weaken the conclusions.

Probing the efficacy of peptide-based inhibitors against acid- and zinc-promoted oligomerization of amyloid-ß peptide via single-oligomer spectroscopy.

One avenue for prevention and treatment of Alzheimer's disease involves inhibiting the aggregation of amyloid-ß peptide (Aß). Given the deleterious effects reported for Aß dimers and trimers, it is important to investigate inhibition of the earliest association steps. We have employed quantized photobleaching of dye-labeled Aß peptides to characterize four peptide-based inhibitors of fibrillogenesis and/or cytotoxicity, assessing their ability to inhibit association in the smallest oligomers (n=2-5). Inhibitors were tested at acidic pH and in the presence of zinc, conditions that may promote oligomerization in vivo. Distributions of peptide species were constructed by examining dozens of surface-tethered monomers and oligomers, one at a time. Results show that all four inhibitors shift the distribution of Aß species toward monomers; however, efficacies vary for each compound and sample environment. Collectively, these studies highlight promising design strategies for future oligomerization inhibitors, affording insight into oligomer structures and inhibition mechanisms in two physiologically significant environments.

Dietary acid reduction with fruits and vegetables or bicarbonate attenuates kidney injury in patients with a moderately reduced glomerular filtration rate due to hypertensive nephropathy.

The neutralization of dietary acid with sodium bicarbonate decreases kidney injury and slows the decline of the glomerular filtration rate (GFR) in animals and patients with chronic kidney disease. The sodium intake, however, could be problematic in patients with reduced GFR. As alkali-induced dietary protein decreased kidney injury in animals, we compared the efficacy of alkali-inducing fruits and vegetables with oral sodium bicarbonate to diminish kidney injury in patients with hypertensive nephropathy at stage 1 or 2 estimated GFR. All patients were evaluated 30 days after no intervention; daily oral sodium bicarbonate; or fruits and vegetables in amounts calculated to reduce dietary acid by half. All patients had 6 months of antihypertensive control by angiotensin-converting enzyme inhibition before and during these studies, and otherwise ate ad lib. Indices of kidney injury were not changed in the stage 1 group. By contrast, each treatment of stage 2 patients decreased urinary albumin, N-acetyl ß-D-glucosaminidase, and transforming growth factor ß from the controls to a similar extent. Thus, a reduction in dietary acid decreased kidney injury in patients with moderately reduced eGFR due to hypertensive nephropathy and that with fruits and vegetables was comparable to sodium bicarbonate. Fruits and vegetables appear to be an effective kidney protective adjunct to blood pressure reduction and angiotensin-converting enzyme inhibition in hypertensive and possibly other nephropathies.

Screening of protein kinase inhibitors identifies PKC inhibitors as inhibitors of osteoclastic acid secretion and bone resorption.

BACKGROUND: Bone resorption is initiated by osteoclastic acidification of the resorption lacunae. This process is mediated by secretion of protons through the V-ATPase and chloride through the chloride antiporter ClC-7. To shed light on the intracellular signalling controlling extracellular acidification, we screened a protein kinase inhibitor library in human osteoclasts. METHODS: Human osteoclasts were generated from CD14+ monocytes. The effect of different kinase inhibitors on lysosomal acidification in human osteoclasts was investigated using acridine orange for different incubation times (45 minutes, 4 and 24 hours). The inhibitors were tested in an acid influx assay using microsomes isolated from human osteoclasts. Bone resorption by human osteoclasts on bone slices was measured by calcium release. Cell viability was measured using AlamarBlue. RESULTS: Of the 51 compounds investigated only few inhibitors were positive in both acidification and resorption assays. Rottlerin, GF109203X, Hypericin and Ro31-8220 inhibited acid influx in microsomes and bone resorption, while Sphingosine and Palmitoyl-DL-carnitine-Cl showed low levels of inhibition. Rottlerin inhibited lysosomal acidification in human osteoclasts potently. CONCLUSIONS: In conclusion, a group of inhibitors all indicated to inhibit PKC reduced acidification in human osteoclasts, and thereby bone resorption, indicating that acid secretion by osteoclasts may be specifically regulated by PKC in osteoclasts.

Cranberry polyphenols: potential benefits for dental caries and periodontal disease.

Over the past decade, cranberries and their molecular components have received increasing attention from researchers in human health. In particular, the properties of the high-molecular-weight polyphenols isolated from cranberries have shown promise with regard to dental caries and periodontal disease. These potential anticaries agents inhibit the production of organic acids and the formation of biofilms by cariogenic bacteria. In addition, cranberry polyphenols may reduce the inflammatory response, as well as the production and activity of proteolytic enzymes contributing to the destruction of the extracellular matrix in periodontal disease. The polyphenols of cranberries also interfere with various activities (including formation of biofilm and adhesion) of Porphyromonas gingivalis, the main etiologic agent in chronic periodontitis. This article summarizes the scientific evidence supporting the potential of cranberry polyphenols to prevent and/or treat diseases of the mouth.

Tetrahydrochromenoimidazoles as potassium-competitive acid blockers (P-CABs): structure-activity relationship of their antisecretory properties and their affinity toward the hERG channel.

Potassium-competitive acid blockers (P-CABs) constitute a new therapeutic option for the treatment of acid-related diseases that are widespread and constitute a significant economical burden. Enantiomerically pure tetrahydrochromenoimidazoles were prepared using the readily available candidate 4 (BYK 405879) as starting material or the Noyori asymmetric reduction of ketones as key reaction. A comprehensive SAR regarding the influence of the 5-carboxamide and the 8-aryl residue on in vitro activity, acid-suppression in the Ghosh Schild rat, and affinity toward the hERG channel was established. In addition, efficacy and duration of the antisecretory action was examined for the most promising target compounds by 24 h pH-metry in the fistula dog and a significantly different SAR was observed as compared to the Ghosh Schild rat. Several tetrahydrochromenoimidazoles were identified that possessed a comparable profile as the candidate 4.

Novel terpenoids, trichoderonic acids A and B isolated from Trichoderma virens, are selective inhibitors of family X DNA polymerases.

Trichoderonic acids A (1) and B (2), novel terpenoids, and (+)-heptelidic acid (3) isolated from cultures of a fungus, Trichoderma virens, and their structures were identified by spectroscopic analysis. These compounds selectively and competitively inhibited the activities of mammalian DNA polymerases beta, lambda (pols beta, lambda), and terminal deoxynucleotidyl transferase (TdT) in family X of pols, and compound 2 was a stronger inhibitor than compound 1 or 3. On the other hand, compounds 1-3 did not influence the activities of the other families (A-, B-, and the Y-families) of the mammalian pols tested, and showed no effect on the activities of plant pol alpha, fish pol delta, prokaryotic pol, or the other DNA metabolic enzymes tested. Compound 2 suppressed the growth of two human cancer cell lines, cervix carcinoma cells (HeLa) and breast carcinoma cells (MCF-7). The results suggest that these compounds identified inhibition among the families of mammalian pols.

Bioactivity-guided separation of anti-acidogenic substances against Streptococcus mutans UA 159 from Polygonum cuspidatum.

OBJECTIVES: The aim of this study was to separate the anti-acidogenic substances against Streptococcus mutans UA 159 from Polygonum cuspidatum. MATERIAL AND METHODS: The anti-acidogenic substances were separated by a series of liquid-liquid fractionations followed by normal-phase silica gel liquid chromatography, based on high-performance liquid chromatography and glycolytic pH-drop assay. The effectiveness of the separated substances on the acidogenicity of Streptococcus mutans UA 159 was examined using sodium fluoride as a positive control. The chemical composition and quantities of the components of the substances was also assessed by qualitative-quantitative chromatographic analysis. RESULTS: Among the substances separated from P. cuspidatum, F3 showed the strongest inhibitory effect on the acidogenicity of S. mutans UA 159 in a dose-dependent manner without displaying any bactericidal activity. F3 decreased the acidogenicity of S. mutans even at 12.5 microg ml(-1) (P < 0.05). F3 consisted mainly of resveratrol and emodin (C(14)H(12)O(3) and C(14)H(4)O(2)(OH)(3)CH(3), respectively), which made up approximately 60% of the weight of F3. CONCLUSION: F3 can be considered as a promising agent for controlling the acidogenicity of S. mutans and subsequent dental caries formation.

Survival of the acid-adapted Bacillus cereus in acidic environments.

In this study, the acid tolerance of Bacillus cereus 1-4-1 after adaptation at pH 5.5 for 1, 2 and 4 h was first determined. The survival of acid-adapted and non-adapted cells of B. cereus in phosphate buffer solution (PBS pH 4.0) containing various organic acids such as acetic, propionic, citric, lactic or tartaric acid as well as in a commercial acidic beverage of mixed fruits and vegetables (pH 3.7) was then examined. Results revealed that acid adaptation time influenced the increased tolerance of B. cereus in PBS (pH 4.0). The 2 h-adapted cells exhibited the highest acid tolerance in PBS. The presence of chloramphenicol during the acid adaptation reduced the extent of increased acid tolerance. Acid adaptation was also found to enhance the tolerance of the test organism in the presence of the various organic acids tested. While the extent of increased acid tolerance varied with the organic acid examined. Acid-adapted B. cereus cells exhibited the largest extent of increased tolerance, showing an increased survival of ca. 1000 folds, in the propionic acid-containing PBS. Additionally, a higher survival percentage was noted with the acid-adapted than the non-adapted cells of B. cereus in the acidic beverage stored at 4 or 25 degrees C.

Physiologic actions of zinc related to inhibition of acid and alkali production by oral streptococci in suspensions and biofilms.

Zinc is a known inhibitor of acid production by mutans streptococci. Our primary objective was to extend current knowledge of the physiologic bases for this inhibition and also for zinc inhibition of alkali production by Streptococcus rattus FA-1 and Streptococcus salivarius ATCC 13419. Zinc at concentrations as low as 0.01-0.1 mm not only inhibited acid production by cells of Streptococcus mutans GS-5 in suspensions or in biofilms but also sensitized glycolysis by intact cells to acidification. Zinc reversibly inhibited the F-ATPase of permeabilized cells of S. mutans with a 50% inhibitory concentration of about 1 mm for cells in suspensions. Zinc reversibly inhibited the phosphoenolpyruvate: sugar phosphotransferase system with 50% inhibition at about 0.3 mm ZnSO4, or about half that concentration when the zinc-citrate chelate was used. The reversibility of these inhibitory actions of zinc correlates with findings that it is mainly bacteriostatic rather than bactericidal. Zinc inhibited alkali production from arginine or urea and was a potent enzyme inhibitor for arginine deiminase of S. rattus FA-1 and for urease of S. salivarius. In addition, zinc citrate at high levels of 10-20 mm was weakly bactericidal.

Xylitol inhibition of acid production and growth of mutans Streptococci in the presence of various dietary sugars under strictly anaerobic conditions.

The aim of this study was to investigate the inhibitory effect of xylitol on the growth of and acid production by mutans streptococci in the presence of various dietary sugars, and the relationship between the inhibition and the accumulation of xylitol 5-phosphate (X5P) under strictly anaerobic conditions like those in the deep layers of dental plaque. Xylitol retarded the growth of mutans streptococci in the presence of glucose (G), galactose (Gal), maltose (M), lactose (L) or sucrose (S) as an energy source, though the inhibition of growth on fructose (Fr) was small. Xylitol inhibited acid production by washed cells of Streptococci mutans from G, Gal, M, L or S (12-83% inhibition). S. mutans accumulated X5P intracellularly through activity of the phosphoenolpyruvate-xylitol phosphotransferase system (PEP-xylitol PTS) when they fermented these sugars in the presence of xylitol. However, in the presence of Fr, no inhibition of acid production was observed. In addition, the amounts of X5P during the fermentation of Fr were smaller than those of other sugars in spite of the presence of PEP-xylitol PTS activity. These results suggest that along with the intracellular accumulation of X5P, xylitol decreases the growth and acid production of mutans streptococci in the presence of various dietary sugars except Fr.

Functional evidence for intracellular acid extruders in human ventricular myocardium.

Intracellular pH (pH(i)) is a major homeostatic system within the cell. Changes in pH(i) exert great influence on cardiac contractility and rhythm. Both the housekeeping Na+ - H+ exchanger (NHE) and the Na+ - HCO3- symporter (NHS) have been confirmed as major transporters for the active acid extrusion mechanism in animal cardiomyocytes. However, whether the NHE and NHS functionally coexist in human ventricular cardiomyocytes remains unclear. We therefore examined the mechanism of pH(i) recovery following an NH4Cl-induced intracellular acidosis in the human ventricular myocardium. The pH(i) was monitored by microspectrofluorimetry by the use of intracellular 2',7'-bis(2-carboxyethyl)-5(6)-carboxy-fluorescein (BCECF)-fluorescence. HOE 694 (30 microM), a specific NHE inhibitor could block pH(i) recovery from induced intracellular acidosis completely in nominally HCO3- -free HEPES Tyrode solution, but it only partially inhibited the pH(i) recovery in 5% CO2/HCO3- Tyrode solution. In 5% CO2/HCO3- Tyrode solution, the addition of HOE 694 together with DIDS (an NHS inhibitor) or the removal of [Na+](o) could entirely inhibit the acid extrusion. We conclude for the first time that two different acid extruders, HCO3- -independent and -dependent, were most likely the NHE and NHS, respectively, that functionally coexisted in the human ventricular cardiomyocytes.

Invasion of HeLa cells by Enterococcus faecalis clinical isolates.

We examined the in vitro ability of Enterococcus faecalis clinical isolates to adhere to and to invade HeLa cells, suggested to be a valuable model system to study bacteria-directed endocytosis. Using a variety of compounds that act on eukaryotic cell structures, both microtubules and microfilaments were found to be involved in enterococcal entry into cells. Two distinct modes of interaction were observed: in one, a close proximity of bacteria with the cell membrane was observed, possibly leading to direct engulfment of the bacterial cell. In the other mode, cellular pseudopodal formation seemed to be stimulated by vicinity of bacterial cells; in some cases, such associations involved formation of clathrin-coated-like vesicles before internalizing enterococci. The above-mentioned experimental data together with the use of monodansylcadaverine, amiloride and NH4Cl, all involved in cytosol acidification and inhibition of receptor-mediated endocytosis (RME), led us to conclude that E. faecalis is internalized within HeLa cells by more than one invasion pathway. One, sensitive to amiloride, is most likely a macropinocytic, actin-dependent uptake mechanism, which determines the production of large smooth-membrane vacuoles engulfing enterococci. The other is RME, in which entry is dependent on both microfilament and microtubule structural integrity.