Hepatoprotective effect of combination of L-carnitine and magnesium-hydroxide in nonalcoholic fatty liver disease patients: a double-blinded randomized controlled pilot study.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) still has no accepted pharmacological therapy. Even though monotherapy of L-carnitine or magnesium supplementation exhibits an essential beneficial role in NAFLD treatment, and despite that new NAFLD treatment strategies focus on combination therapies, the combination of L-carnitine with magnesium has not yet been examined in NAFLD patients. We aimed to assess the efficacy of L-carnitine in combination with magnesium in NAFLD patients. PATIENTS AND METHODS: Double-blinded, randomized controlled trial with 22 NAFLD participants who were randomized to either control group receiving placebo for the first 8 weeks and an additional 8 weeks with CIRRHOS product (2 gr L-carnitine and 150 mg magnesium) or treatment group receiving CIRRHOS product for 16 weeks. Weight, serum aspartate aminotransferase (AST), alanine transaminase (ALT) and C-reactive protein (CRP) levels were measured monthly. Lipid profile and serum insulin levels were monitored at baseline and at week 16 of treatment. Shear-wave elastography was used to evaluate liver stiffness (LS). RESULTS: While AST and ALT levels decreased progressively over 16 weeks of treatment in the treatment group, AST and ALT levels of the control group were increased modestly or unaffected. AST and ALT levels of the treatment group decreased by 25% (p=0.9) and 20% (p=0.1) respectively, compared to AST and ALT levels at baseline. However, serum CRP levels, insulin levels, lipid profile and LS were not affected by treatment. CONCLUSIONS: Our findings suggest that L-carnitine with magnesium supplementation could be a potential therapy for NAFLD. However, further studies with a larger population and high-sensitivity diagnostic parameters for early stages of NAFLD are needed to elucidate L-carnitine and magnesium efficacy in NAFLD.

Effects of Food and Antacids on Pharmacokinetics and Pharmacodynamics of Lesinurad, a Selective Urate Reabsorption Inhibitor.

Two clinical studies were performed in healthy volunteers to investigate food and antacid effects on lesinurad, a novel selective uric acid reabsorption inhibitor approved for treatment of hyperuricemia associated with gout in combination with xanthine oxidase inhibitors. Study 1 evaluated a high-fat, high-calorie meal or high doses of antacids (3000 mg calcium carbonate or 1600 mg magnesium hydroxide/1600 mg aluminum hydroxide) on the pharmacokinetics (PK) and pharmacodynamics (PD) of 400 mg oral lesinurad. Study 2 evaluated low doses of antacids (1250 mg calcium carbonate or 800 mg magnesium hydroxide/800 mg aluminum hydroxide) on the PK and PD of 400 mg lesinurad. Food did not alter the plasma AUC of lesinurad and only reduced its Cmax by 18%. In the fasted conditions, high-dose calcium carbonate reduced the Cmax and AUC of lesinurad by 54% and 38%, respectively, whereas high-dose magnesium hydroxide/aluminum hydroxide reduced Cmax and AUC by 36% and 31%, respectively. Food enhanced the maximum serum urate (sUA)-lowering effect of lesinurad by approximately 20% despite reducing the Cmax of lesinurad. High-dose calcium carbonate decreased the urate-lowering effect approximately 20% in the first 6 hours, whereas high-dose magnesium hydroxide/aluminum hydroxide reduced the effect by 26%. Low-dose calcium carbonate or magnesium hydroxide/aluminum hydroxide in the presence of food did not significantly affect plasma lesinurad Cmax and AUC or the sUA lowering and renal handling of uric acid. In summary, study results suggest food did not meaningfully alter lesinurad PK and PD. High doses of antacids reduced lesinurad AUC up to 40% and reduced the lesinurad uric acid-lowering effect.

Anti-Helicobacter pylori and antiulcerogenic activity of Aframomum pruinosum seeds on indomethacin-induced gastric ulcer in rats.

CONTEXT: Peptic ulcer is one of the most common diseases affecting mankind. Although there are many products used for its treatment, most of these products produce severe adverse reactions requiring the search for novel compounds. Some Afromomum species are used traditionally to cure acute gastritis. OBJECTIVE: To evaluate the antiulcer activity of the methanol extract of Aframomum pruinosum Gagnepain (Zingiberaceae) seeds against two major etiologic agents of peptic ulcer disease; Helicobacter pylori and non-steroidal anti-inflammatory drugs. MATERIALS AND METHODS: The anti-Helicobacter activity of A. pruinosum was evaluated using the broth microdilution method. After oral administration of indomethacin (5 mg/kg) for 5 consecutive days, gastric ulcerated animals were divided into control group and five other groups: three groups that recieved respectively 125, 250 and 500 mg/kg of plant extract, the fourth group received Maalox (50 mg/kg) and the fifth group, Misoprostol (100 µg/kg), respectively, for 5 days. Ulcer areas, gastric mucus content and nitric oxide gastric levels of animals were assessed 24 h after this treatment. RESULTS: A. pruinosum extract shows a moderate anti-Helicobacter activity with an MIC value of 128 µg/mL. A. pruinosum extract, like Misoprostol and Maalox, markedly reduces the % of ulcerated area from 8.15 ± 0.33 to 1.71 ± 0.44% (500 mg/kg). It also increased significantly mucus and NO gastric production with respective values of 4.44 ± 1.35 and 965.81 ± 106.74 µmol/g (500 mg/kg). DISCUSSION AND CONCLUSION: These findings suggest that A. pruinosum methanol extract possesses antiulcer properties as ascertained by the comparative decreases in ulcer areas, increase of mucus and NO gastric production.

Uranium in well drinking water of Kabul, Afghanistan and its effective, low-cost depuration using Mg-Fe based hydrotalcite-like compounds.

Toxic elements in drinking water have great effects on human health. However, there is very limited information about toxic elements in drinking water in Afghanistan. In this study, levels of 10 elements (chromium, nickel, copper, arsenic, cadmium, antimony, barium, mercury, lead and uranium) in 227 well drinking water samples in Kabul, Afghanistan were examined for the first time. Chromium (in 0.9% of the 227 samples), arsenic (7.0%) and uranium (19.4%) exceeded the values in WHO health-based guidelines for drinking-water quality. Maximum chromium, arsenic and uranium levels in the water samples were 1.3-, 10.4- and 17.2-fold higher than the values in the guidelines, respectively. We next focused on uranium, which is the most seriously polluted element among the 10 elements. Mean ± SD (138.0 ± 1.4) of the 238U/235U isotopic ratio in the water samples was in the range of previously reported ratios for natural source uranium. We then examined the effect of our originally developed magnesium (Mg)-iron (Fe)-based hydrotalcite-like compounds (MF-HT) on adsorption for uranium. All of the uranium-polluted well water samples from Kabul (mean ± SD = 190.4 ± 113.9 µg/L; n = 11) could be remediated up to 1.2 ± 1.7 µg/L by 1% weight of our MF-HT within 60 s at very low cost (<0.001 cents/day/family) in theory. Thus, we demonstrated not only elevated levels of some toxic elements including natural source uranium but also an effective depurative for uranium in well drinking water from Kabul. Since our depurative is effective for remediation of arsenic as shown in our previous studies, its practical use in Kabul may be encouraged.

Enhancing anaerobic digestion of waste activated sludge by the combined use of NaOH and Mg(OH)2: Performance evaluation and mechanism study.

In this study, the combination treatment of NaOH and Mg(OH)2 was applied to anaerobic digestion of waste activated sludge (WAS) for simultaneously enhancement of volatile fatty acids (VFAs) production, nutrients removal and sludge dewaterability. The maximum VFAs production (461mg COD/g VSS) was obtained at the NaOH/Mg(OH)2 ratio of 75:25, which was much higher than that of the blank or sole NaOH. Moreover, nutrients removal and sludge dewaterability were improved by the combined using of NaOH and Mg(OH)2. Mechanism investigations revealed that the presence of Mg(OH)2 could maintain alkaline environment, which contributed to inhibit the activity of methanogens. Also, the bridging between Mg(2+) and extracellular polymeric substances (EPS) plays an important role in the solubilization and dewatering of sludge. High-throughput sequencing analysis demonstrated that the abundance of bacteria involved in sludge hydrolysis and VFAs accumulation was greatly enriched with the mixtures of NaOH and Mg(OH)2.

Cutting edge: alum adjuvant stimulates inflammatory dendritic cells through activation of the NALP3 inflammasome.

Adjuvants are vaccine additives that stimulate the immune system without having any specific antigenic effect of itself. In this study we show that alum adjuvant induces the release of IL-1beta from macrophages and dendritic cells and that this is abrogated in cells lacking various NALP3 inflammasome components. The NALP3 inflammasome is also required in vivo for the innate immune response to OVA in alum. The early production of IL-1beta and the influx of inflammatory cells into the peritoneal cavity is strongly reduced in NALP3-deficient mice. The activation of adaptive cellular immunity to OVA-alum is initiated by monocytic dendritic cell precursors that induce the expansion of Ag-specific T cells in a NALP3-dependent way. We propose that, in addition to TLR stimulators, agonists of the NALP3 inflammasome should also be considered as vaccine adjuvants.

Effect of an orally administered antacid agent containing aluminum hydroxide and magnesium hydroxide on abomasal luminal pH in clinically normal milk-fed calves.

OBJECTIVE: To determine the effects of a commercially available orally administered antacid agent containing aluminum hydroxide and magnesium hydroxide on abomasal luminal pH in clinically normal milk-fed calves. DESIGN: Randomized trial. ANIMALS: 5 male dairy calves. PROCEDURE: Throughout the study, calves were fed milk replacer at 7:30 AM and 7:30 PM. Cannulae for pH electrodes were placed in the abomasal body and pyloric antrum. Treatments consisted of oral administration of a high (50 ml) or low (25 ml) dose of the antacid agent and oral administration of milk replacer alone (control). Antacid was given at 7:30 AM, 3:30 PM, and 11:30 PM, and luminal pH was monitored continuously for 24 hours, beginning 15 minutes before administration of the first dose of antacid. RESULTS: Administration of the first dose of antacid at the time of the morning feeding resulted in an increase in mean abomasal body luminal pH of < 1 pH unit, whereas administration of the second and third doses of the antacid caused transient (< 3 hours) increases in mean luminal pH of approximately 1.5 (low dose) and 2.5 (high dose) pH units. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that clinically normal milk-fed calves given a commercially available antacid agent, PO, will have a transient increase in abomasal luminal pH. Such agents may, therefore, have a role in the treatment of abomasal ulceration in calves; however, the long-term effects of orally administered antacid agents in milk-fed calves and the clinical efficacy of such agents in treating abomasal ulceration remain to be determined.

Effect of acarbose and simultaneous antacid therapy on blood glucose.

In a single-centre, placebo-controlled, clinical study, the influence of an antacid containing magnesium hydroxide and aluminium hydroxide (Maalox 70; 10 ml) on the pharmacodynamics of the oral antidiabetic drug acarbose (Glucobay 100, Bay g 5421, CAS 56180; 100 mg) was tested in 24 healthy male volunteers. The drugs were given alone or in combination and were compared with placebo. Volunteers were randomized into four different treatment groups. The daily medication over 4 days was 1 x 1 placebo tablet, or 1 x 1 tablet containing 100 mg acarbose, or 1 x 1 tablet containing 100 mg acarbose plus 10 ml antacid suspension, or 1 x 1 placebo tablet plus 10 ml antacid suspension, interrupted by wash-out phases of 6-10 days between successive treatments. Efficacy was assessed on the basis of postprandial blood glucose and serum insulin levels after administration of 75 g sucrose, and was measured as maximal concentrations and 'area under the curve' (0-4 h). No influence of the antacid on the blood glucose and insulin-lowering effect of acarbose could be detected. Hence, there does not appear to be a significant interaction between acarbose and the antacid tested. Antacids similar to that tested do not need to be classified as a contraindication when used in combination with acarbose.

Acid secretory responses and parietal cell sensitivity following duodenal ulcer healing with omeprazole, sucralfate, and Maalox.

Acid secretory responses and parietal cell sensitivity (PCS) have been studied in 21 duodenal ulcer patients before and after successful treatment with omeprazole (n = 7), sucralfate (n = 7), or Maalox (n = 7). The second study was carried out 3 days after documented healing and withdrawal of treatment in the sucralfate- and Maalox-treated groups and 14 days after documented healing and withdrawal of treatment in the omeprazole-treated patients. Acid output (mmol/hour) was measured as basal secretion, and in response to 0.1 microgram/kg/hour pentagastrin (low-dose) and 6.0 micrograms/kg/hour pentagastrin (high-dose) stimulation. PCS was calculated as the ratio of low dose:high dose acid output (expressed as a percentage). Ulcer healing with sucralfate resulted in significant (p less than 0.05) decreases in low-dose acid output from 36.4% (13.2-51.0) (median [range]) to 8.4% (3.2-45.4) mmol/hour and PCS from 69.1% (44.9-91.4) to 22.0% (16.0-85.6), whereas no significant decreases in any of the measured parameters were noted following ulcer healing with Maalox. Ulcer healing with omeprazole resulted in significant (p less than 0.05) decreases in basal acid output from 6.3 (1.5-22.9) (median [range]) to 2.2 (0-6.9) mmol/hour, and low-dose acid output from 31.0 (6.0-58.0) to 23.0 (1.4-44.8) mmol/hour. These findings suggest that acid secretory responses following ulcer healing vary according to the therapeutic agent used.

Catalysis of the hydrolysis of phosphorylated pyridines by Mg(OH)+: a possible model for enzymatic phosphoryl transfer.

The second-order rate constants for reaction of the Mg2+ complexes of phosphorylated pyridine monoanions with Mg(OH)+ are 10(4)-10(6)-fold larger than the second-order rate constants for their reaction with water (25 degrees C, ionic strength 1.5). Of the 10(6)-fold rate enhancement with the phosphorylated 4-morpholinopyridine/Mg2 complex, approximately 10(4)-fold is attributed to the greater nucleophilicity of Mg(OH)+ compared with water. The remaining catalysis of approximately 10(2)-fold is attributed to induced intramolecularity from positioning of the hydroxide ion and phosphoryl group by the Mg2+ ions. This reaction may provide a model for the role of a metal ion in increasing the concentration of the anions of enolpyruvate and serine and holding the nucleophile in the correct position for phosphoryl transfer in the reactions catalyzed by pyruvate kinase and alkaline phosphatase, for example. Some mechanisms that can provide catalysis of phosphoryl transfer through a metaphosphate-like transition state are reviewed briefly.

Effect of antacid treatment on endogenous prostaglandin synthesis in human antral and duodenal mucosa.

Using 14C-labeled arachidonic acid as precursor for in vitro prostaglandin synthesis, the effect of an antacid containing Al (OH)3, Mg(OH)2 and CaCO3 on endogenous prostaglandin synthesis was investigated in antral and duodenal mucosa of healthy volunteers. After three weeks of treatment with a high-dose antacid, there was no detectable change in the total capacity of the mucosa for prostaglandin synthesis, but the prostaglandin profile was markedly altered. The relative amounts of PGE2 and PGF2 alpha synthesized by antral and duodenal mucosa increased at the expense of the prostaglandins A2/B2, thromboxane A2, and prostacyclin. In a short-term study, this change was not observed following a single antacid dose within 1 hr after application. It is concluded that long-term antacid treatment may alter the prostaglandin pattern formed by gastroduodenal mucosa and this may be related to its therapeutic effect.

Long-term use of magnesium hydroxide as a phosphate binder in patients on hemodialysis.

The long-term use of magnesium hydroxide [Mg(OH)2] as a phosphate binder was investigated in 18 patients on chronic hemodialysis. All patients received a basal treatment with oral calcium carbonate. Vitamin D supplements were not used. In period I each patient ingested aluminum hydroxide [Al(OH)3], in period II Mg(OH)2 and in period III Mg(OH)2 and Al(OH)3 together. During period II and III a dialysate devoid of Mg was used. Mg(OH)2 doses were adjusted to prevent severe hypermagnesemia and diarrhea. The mean dose of Mg(OH)2 in period II was 2.4 +/- 0.6 and in period III 2.6 +/- 1.2 g/day. Serum phosphate increased significantly in period II and fell again in period III. Despite a halving of the Al(OH)3 dose in period III, serum Al was similar in period I and period III (55.8 +/- 19.1 vs 57.1 +/- 27.3 microg/l). Parathyroid hormone (PTH) concentration fell in period II and decreased even further in period III. We conclude that oral Mg(OH)2 may reduce the required Al(OH)3 dose, however, without an effect on serum Al concentration. The observed suppression of parathyroid activity needs further study.

[Prostaglandin synthesis in stomach and duodenal mucosa of the human: effect of aspirin with and without antacid]. / Die Prostaglandinsynthese in Magen- und Duodenalmukosa des Menschen: Einfluss von Aspirin mit und ohne Antazidum.

A decreased PG E2 content in gastric mucosa of humans receiving a longterm antirheumatic therapy has been reported to be partially reversed after a one week treatment with an antacid (Reimann et al., Fortschr Med 102 [1984], 25-26). Therefore the effect of an Aspirin treatment of healthy volunteers with or without an antacid on the prostaglandin synthesis in gastric or duodenal mucosa was investigated. 14C-labelled arachidonic acid was used as substrate during in vitro incubation of the mucosal homogenate for determination of the endogenous formation of prostaglandins. Aspirin suppressed the total prostaglandin synthesis to less than 10% of control after one week treatment. The addition of a high dose antacid did not influence this inhibition, and no significant effect on the prostaglandin profile was detectable. It is concluded that antacids do not influence the suppression of the endogenous prostaglandin synthesis by NOSAC's, however another effect, eg a prolonged stability of PG E2 in a less acidic environment is more likely.

Response of milking cows fed a high concentrate, low roughage diet plus sodium bicarbonate, magnesium oxide, or magnesium hydroxide.

To determine the ability of mineral supplements to elevate depressed milk fat percent, we placed 42 Holstein cows in early to midlactation in seven blocks and assigned each to one of six treatments: control (25% corn silage and alfalfa haylage, 75% concentrate, mostly corn, dry matter); control plus magnesium oxide ground to pass a .425-mm sieve; control plus prilled magnesium oxide sieved to between 1.70 and .425 mm; control plus sodium bicarbonate; control plus reactive powdered magnesium oxide to pass a 45 microns sieve; and control plus powdered magnesium hydroxide. Sodium bicarbonate was 1% of diet as fed, magnesium oxide .5%, magnesium hydroxide .7% later reduced to .5%. Cows were fed control ration for 3 wk to induce milk fat depression, then were changed to treatment rations for 5 wk. Five cows (unblocked) were continued on each dietary treatment for a digestibility study after the feeding trial. All mineral supplements produced greater milk fat percent and yield of milk fat per day than control and all magnesium treatments produced greater milk fat percent than sodium bicarbonate. Magnesium oxide passing a .425-mm sieve produced the greatest increase of milk fat percent. Milk production was most for sodium bicarbonate treatment. Supplementation with magnesium increased ruminal magnesium concentration by factors of 1.26 to 3.75. Blood serum, urine, and fecal magnesium concentrations and fecal pH were more for cows fed magnesium than those fed sodium bicarbonate treatments. Kidney filtration ratios of element to creatinine increased for magnesium when diets were supplemented with magnesium and increased for phosphorus and sodium when diets were supplemented with sodium bicarbonate.

Calcium requirements in humans. Report of original data and a review.

Presently submitted and previously available data indicate that the recommended calcium requirement of 800 mg/day is inadequate for a large segment of the population, particularly the elderly. With an intake of 800 mg of calcium/day, calcium balance was only slightly positive, without consideration of dermal losses or other risk factors that may play a role in calcium bioavailability and calcium retention. A calcium intake of 1000-1200 mg/day is preferable, as calcium balance increased significantly when calcium intake was increased from 800 to 1200 mg/day; there was no further improvement in calcium balance on higher calcium intakes, up to 2300 mg/day.

[Stool behavior following the administration of antacids]. / Stuhlverhalten nach Gabe von Antazida.

The direct correlation between the dosage of magnesium in antacids and the appearance of partly massive diarrheas in ulcus-patients known from literature could be confirmed. The clinically relevant dosage of antacids of 420 mval NK/day, divided in six individual dosages, resulted in diarrheas from the second to fourth day in 32 percent of the test persons when antacid A with a high content of magnesium was administered. There was no hint for a constipating effect of Solugastril gel at these high dosages (= 12 individual doses). Indeed the application of an Al-Ca-antacid may result in a slight fecal impaction, however, at the same time also to an increase of stool frequency, which is similar to that obtained with antacid B having a lower content of magnesium. The antacid can be regarded as neutral concerning stool frequency and consistency in the majority of test persons. From all four tested antacids the triple-combination (Al, Mg, Ca), showed the least important deviations from the preceding norms concerning stool frequency and consistency. The triple-combination shows an absolutely neutral stool behaviour. Serum electrolytes remained in the normal range with the Al-Ca- and the Al-Mg-Ca-antacid; whereas after application of antacid. A with high magnesium content, important increases of magnesium could be observed after seven days already, which were also dealt with in the literature.

High dose of antacid (Mylanta II) reduces bioavailability of ranitidine.

To investigate the effect of antacid on the bioavailability and disposition of ranitidine six healthy volunteers were studied on two occasions one week apart. In the first study the received ranitidine 150 mg with 60 ml water, and in the second study they received ranitidine 150 mg plus 30 ml of an aluminium/magnesium hydroxide mixture (Mylanta II) and 30 ml water. Giving antacid reduced both the maximum plasma ranitidine concentration and the area under the curve by one-third; elimination of the drug was not changed. Thus giving a high dose of antacid significantly diminished the bioavailability of ranitidine.

Antacid therapy--changes in mineral metabolism.

Antacid ingestion may lead to side-effects related to their chemical composition. Aluminum hydroxide may cause the phosphate depletion syndrome even during short-term administration of high doses in patients at high risk, such as alcoholics. Long-term intake may lead to bone demineralization and to osteomalacia. Fluoride complexing in the gut and prevention of fluoride absorption may be an additional factor. The clinical relevance of aluminum absorption in patients with normal renal function is not clear. In contrast, in patients with renal failure, aluminum hydroxide ingestion may contribute to an increasing hyperaluminemia. Hyperaluminemia and tissue deposition of aluminum in these patients may contribute to the dialysis-associated encephalopathy. Magnesium hydroxide causes an alkalinization of the urine due to magnesium absorption and urinary excretion. Thus, in renal insufficiency, a life-threatening hypermagnesemia may develop if magnesium-aluminum-containing antacids are prescribed. The milk-alkali syndrome, rarely observed nowadays, may be caused by calcium carbonate- and sodium bicarbonate-containing antacids. Hypercalciuria and alkaluria predispose to nephrolithiasis. The possibility that these disturbances in mineral metabolism will develop in patients with normal renal function is unlikely unless there is an abuse of these "over the counter" antacids.

Effect of magnesium--aluminum hydroxide and kaolin--pectin on absorption of digoxin from tablets and capsules.

Twelve healthy fasting volunteers received two 0.2-mg digoxin capsules or tablets with 60 ml water, 60 ml Maalox, or 60 ml Kaopectate in a randomized, single-dose, six-way crossover study. Concentrations of digoxin in multiple plasma samples and in all urine collected during the 24 hours after each dose were determined by radioimmunoassay. Compared to the water treatment, administration of both tablets and capsules with Maalox or Kaopectate reduced the peak digoxin plasma concentrations but did not significantly influence the time of peak concentration. Neither Maalox nor Kaopectate influenced the area under the 24-hour plasma concentration--time curve for either tablets or capsules. However, 24-hour urinary recovery of digoxin from tablets tended to be reduced by Maalox and Kaopectate; this was not the case with capsules. Digoxin capsules may have an advantage over currently available tablets in clinical situations requiring digoxin coadministration with nonabsorbable gastrointestinal preparations.