Effect of geranylated dihydrochalcone from Artocarpus altilis leaves extract on Plasmodium falciparum ultrastructural changes and mitochondrial malate: Quinone oxidoreductase.

Nearly half of the world's population is at risk of being infected by Plasmodium falciparum, the pathogen of malaria. Increasing resistance to common antimalarial drugs has encouraged investigations to find compounds with different scaffolds. Extracts of Artocarpus altilis leaves have previously been reported to exhibit in vitro antimalarial activity against P. falciparum and in vivo activity against P. berghei. Despite these initial promising results, the active compound from A. altilis is yet to be identified. Here, we have identified 2-geranyl-2', 4', 3, 4-tetrahydroxy-dihydrochalcone (1) from A. altilis leaves as the active constituent of its antimalarial activity. Since natural chalcones have been reported to inhibit food vacuole and mitochondrial electron transport chain (ETC), the morphological changes in food vacuole and biochemical inhibition of ETC enzymes of (1) were investigated. In the presence of (1), intraerythrocytic asexual development was impaired, and according to the TEM analysis, this clearly affected the ultrastructure of food vacuoles. Amongst the ETC enzymes, (1) inhibited the mitochondrial malate: quinone oxidoreductase (PfMQO), and no inhibition could be observed on dihydroorotate dehydrogenase (DHODH) as well as bc1 complex activities. Our study suggests that (1) has a dual mechanism of action affecting the food vacuole and inhibition of PfMQO-related pathways in mitochondria.

Citrulline Malate Does Not Improve Muscle Recovery after Resistance Exercise in Untrained Young Adult Men.

The effects of citrulline malate (CM) on muscle recovery from resistance exercise remains unknown. We aimed to determine if citrulline malate supplementation improves muscle recovery after a single session of high-intensity resistance exercise (RE) in untrained young adult men. Nine young adult men (24.0 ± 3.3 years) participated in a double-blind crossover study in which they received 6 g of CM and placebo (PL) on two occasions, separated by a seven-day washout period. Each occasion consisted of a single session of high-intensity RE (0 h) and three subsequent fatigue tests sessions (at 24, 48, and 72 h) to assess the time course of muscle recovery. During the tests sessions, we assessed the following variables: number of maximum repetitions, electromyographic signal (i.e., root mean square (RMS) and median frequency (MF)), muscle soreness and perceived exertion, as well as blood levels of creatine kinase (CK), lactate, insulin, and testosterone:cortisol ratio. CK levels increased at 24 h post-exercise and remained elevate at 48 and 72 h, with no difference between CM and PL conditions. Muscle soreness increased at 24 h post-exercise, which progressively returned to baseline at 72 h in both conditions. Lactate levels increased immediately post-exercise and remained elevated at 24, 48, and 72 h in both conditions. No significant treatment × time interaction was found for all dependents variables (maximum repetitions, perceived exertion, CK, lactate, RMS, MF, and testosterone:cortisol ratio) during the recovery period. In conclusion, our data indicate that CM supplementation (single 6 g dose pre-workout) does not improve the muscle recovery process following a high-intensity RE session in untrained young adult men.

Acute citrulline malate supplementation improves upper- and lower-body submaximal weightlifting exercise performance in resistance-trained females.

PURPOSE: Citrulline malate (CM) is a nonessential amino acid that increases exercise performance in males. However, based on physiological differences between genders, these results cannot be extrapolated to females. Therefore, the purpose of this investigation was to evaluate effects of acute CM supplementation on upper- and lower-body weightlifting performance in resistance-trained females. METHODS: Fifteen females (23 ± 3 years) completed two randomized, double-blind trials consuming either CM (8 g dextrose + 8 g CM) or a placebo (8 g dextrose). One hour after supplement consumption, participants performed six sets each of upper- (i.e., bench press) and lower-body (i.e., leg press) exercises to failure at 80 % of previously established one-repetition maximum. Immediately after each set, repetitions completed, heart rate and rating of perceived exertion (RPE) were recorded. RESULTS: Repeated-measures analysis of variance indicated that subjects completed significantly (p = .045) more repetitions throughout upper-body exercise when consuming CM versus placebo (34.1 ± 5.7 vs. 32.9 ± 6.0, respectively). When consuming CM, similar significant (p = .03) improvements in total repetitions completed were observed for lower-body exercise (66.7 ± 30.5 vs. 55.13 ± 20.64, respectively). Overall RPE score was significantly lower (p = .02) in upper-body exercise when subjects consumed CM versus placebo (7.9 ± 0.3 and 8.6 ± 0.2, respectively). The supplement consumed exhibited no significant effects on heart rate at any time point. CONCLUSIONS: Acute CM supplementation in females increased upper- and lower-body resistance exercise performance and decreased RPE during upper-body exercise. These data indicate that athletes competing in sports with muscular endurance-based requirements may potentially improve performance by acutely supplementing CM.

Use of dicarboxylic acids and polyphenols to attenuate reticular pH drop and acute phase response in dairy heifers fed a high grain diet.

BACKGROUND: The aim of this study was to determine the ability of two feed additives, a fumarate-malate (FM) and a polyphenol-essential oil mixture (PM), in attenuating the drop of ruminal pH and the metabolic and immune response resulting from an excessively high grain diet. Six heifers were used in a 3 × 3 Latin square experiment and fed a low starch (LS) diet for 14 d, followed by a high starch (HS) diet for 8 d (NDF 33.6%, starch 30.0% DM). In the last 5 days of each period, barley meal was added to decrease rumen pH. During HS feeding all animals were randomly assigned to one of the following three dietary treatments: no supplement/control (CT), a daily dose of 60 g/d of FM, or 100 g/d of PM. Reticular pH was continuously recorded using wireless boluses. On d 21 of each period, rumen fluid was collected by rumenocentesis (1400 h), together with blood (0800 h) and fecal samples (0800, 1400, and 2100 h). RESULTS: The correlation coefficient of pH values obtained using the boluses and rumenocentesis was 0.83. Compared with CT and PM, the FM treatment led to a lower DMI. Nadir pH was lowest during CT (5.40, 5.69, and 5.62 for CT, FM and PM, respectively), confirming the effectiveness of both supplements in reducing the pH drop caused by high grain feeding. This result was confirmed by the highest average time spent daily below 5.6 pH (199, 16 and 18 min/d) and by the highest acetate to propionate ratio of the CT fed heifers. The PM decreased the concentrations of neutrophils (2.9, 3.2, and 2.8 10(9)/L) and acute phase proteins: SAA (37.1, 28.6 and 20.1 µg/mL), LBP (4.1, 3.8, and 2.9 µg/mL), and Hp (675, 695 and 601 µg/mL). Free lipopolysaccharides (LPS) were detected in blood and feces, but their concentrations were not affected by treatments, as the remaining blood variables. CONCLUSIONS: Data suggest that both additives could be useful in attenuating the effects of excessive grain feeding on rumen pH, but the PM supplement was more effective than FM in reducing the inflammatory response compared to CT.

An in-vitro assessment of erosive potential of a calcium-fortified fruit juice.

AIM: To evaluate and compare the in vitro pH, buffer capacity and calcium loss from tooth enamel before and after calcium fortification of a packaged fruit juice. METHODS: An approved brand of packaged mixed fruit juice was selected as a test drink on the basis of a pilot questionnaire. The test drink was fortified with 1,000 mg/l (0.1% w/v) of calcium citrate malate to obtain two test groups: Group 1: original beverage (serving as control) and Group 2: calcium-fortified drink. The pH and buffering capacity for the test drinks were measured before and after calcium fortification; 90 prepared enamel samples were divided and immersed into three test subgroups: (1) buffer solution pH 7 (positive control), (2) original fruit juice (negative control) and (3) calcium-fortified fruit juice for 3 min. Calcium loss from the enamel of immersed teeth was measured as a quantitative estimate of tooth mineral loss. RESULTS: After calcium fortification of the fruit juice the mean pH raised from 3.4 to 4.0 (p = 0.029), the mean buffer capacity decreased from 9.73 to 9.16 (p < 0.001) and the mean calcium loss from enamel specimens decreased from 3.5 to 0.26 mg/dl (p < 0.001). STATISTICS: To compare the change in mean pH and buffering capacity between the subject groups, t test was used, and to compare the calcium loss from enamel specimens, among the three subgroups, ANOVA was used. CONCLUSION: Calcium fortification of packaged fruit juice in vitro, improves its pH and buffering capacity. Consequently, the fortified juice causes significantly less mineral loss from human enamel. Fortifying juice with calcium may exert a significant protective potential against dental erosion particularly due to frequent exposure of acidic drinks.

Effect of intensive vs conventional insulin therapy on perioperative nutritional substrates metabolism in patients undergoing gastrectomy.

AIM: To investigate the effect of intensive vs conventional insulin therapy on perioperative nutritional substrates metabolism in patients undergoing radical distal gastrectomy. METHODS: Within 24 h of intensive care unit management, patients with gastric cancer were enrolled after written informed consent and randomized to the intensive insulin therapy (IIT) group to keep glucose levels from 4.4 to 6.1 mmol/L or the conventional insulin therapy (CIT) group to keep levels less than 10 mmol/L. Resting energy expenditure (REE), respiratory quotient (RQ), resting energy expenditure per kilogram (REE/kg), and the lipid oxidation rate were monitored by the indirect calorimeter of calcium citrate malate nutrition metabolism investigation system. The changes in body composition were analyzed by multi-frequency bioimpedance analysis. Blood fasting glucose and insulin concentration were measured for assessment of Homeostasis model assessment of insulin resistance. RESULTS: Sixty patients were enrolled. Compared with preoperative baseline, postoperative REE increased by over 22.15% and 11.07%; REE/kg rose up to 27.22 ± 1.33 kcal/kg and 24.72 ± 1.43 kcal/kg; RQ decreased to 0.759 ± 0.034 and 0.791 ± 0.037; the lipid oxidation ratio was up to 78.25% ± 17.74% and 67.13% ± 12.76% supported by parenteral nutrition solutions from 37.56% ± 11.64% at the baseline; the level of Ln-HOMA-IR went up dramatically (P < 0.05, respectively) on postoperative days 1 and 3 in the IIT group. Meanwhile the concentration of total protein, albumin and triglyceride declined significantly on postoperative days 1 and 3 compared with pre-operative levels (P < 0.05, respectively). Compared with the CIT group, IIT reduced the REE/kg level (27.22 ± 1.33 kcal/kg vs 29.97 ± 1.47 kcal/kg, P = 0.008; 24.72 ± 1.43 kcal/kg vs 25.66 ± 1.63 kcal/kg, P = 0.013); and decreased the Ln-HOMA-IR score (P = 0.019, 0.028) on postoperative days 1 and 3; IIT decreased the level of CRP on postoperative days 1 and 3 (P = 0.017, 0.006); the total protein and albumin concentrations in the IIT group were greater than those in the CIT group (P = 0.023, 0.009). Postoperative values of internal cell fluid (ICF), fat mass, protein mass (PM), muscle mass, free fat mass and body weight decreased obviously on postoperative 7th day compared with the preoperative baseline in the CIT group (P < 0.05, respectively). IIT reduced markedly consumption of fat mass, PM and ICF compared with CIT (P = 0.009 to 0.026). CONCLUSION: There were some benefits of IIT in decreasing the perioperative insulin resistance state, reducing energy expenditure and consumption of proteins and lipids tissue in patients undergoing gastrectomy.

Adverse effects of α-ketoglutarate/malate in a rat model of acute kidney injury.

Acute kidney injury (AKI) is the most common kidney disease in hospitalized patients with high mortality. Ischemia and reperfusion (I/R) is one of the major causes of AKI. The combination of α-ketoglutarate+malate (αKG/MAL) showed the ability to reduce hypoxia-induced damage to isolated proximal tubules. The present study utilizes a rat model of I/R-induced AKI accompanied by intensive biomonitoring to examine whether αKG/MAL provides protection in vivo. AKI was induced in male Sprague-Dawley rats by bilateral renal clamping (40 min) followed by reperfusion (240 min). αKG/MAL was infused continuously for 60 min before and 45 min after ischemia. Normoxic and I/R control groups received 0.9% NaCl solution. The effect of αKG/MAL was evaluated by biomonitoring, blood and plasma parameters, histopathology, and immunohistochemical staining for kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL), as well as by determination of tissue ATP and nonesterified fatty acid concentrations. Intravenous infusion of αKG/MAL at a cumulative dose of 1 mmol/kg each (146 mg/kg αKG and 134 mg/kg MAL) did not prevent I/R-induced increases in plasma creatinine, histopathological alterations, or cortical ATP depletion. On the contrary, the most notable adverse affect in animals receiving αKG/MAL was the decrease in mean arterial blood pressure, which was also accompanied by a reduction in heart rate. Supplementation with αKG/MAL, which is very protective against hypoxia-induced injury in isolated proximal tubules, does not protect against I/R-induced renal injury in vivo, possibly due to cardiovascular depressive effects.

The effect of nitric-oxide-related supplements on human performance.

Nitric oxide (NO) has led a revolution in physiology and pharmacology research during the last two decades. This labile molecule plays an important role in many functions in the body regulating vasodilatation, blood flow, mitochondrial respiration and platelet function. Currently, it is known that NO synthesis occurs via at least two physiological pathways: NO synthase (NOS) dependent and NOS independent. In the former, L-arginine is the main precursor. It is widely recognized that this amino acid is oxidized to NO by the action of the NOS enzymes. Additionally, L-citrulline has been indicated to be a secondary NO donor in the NOS-dependent pathway, since it can be converted to L-arginine. Nitrate and nitrite are the main substrates to produce NO via the NOS-independent pathway. These anions can be reduced in vivo to NO and other bioactive nitrogen oxides. Other molecules, such as the dietary supplement glycine propionyl-L-carnitine (GPLC), have also been suggested to increase levels of NO, although the physiological mechanisms remain to be elucidated. The interest in all these molecules has increased in many fields of research. In relation with exercise physiology, it has been suggested that an increase in NO production may enhance oxygen and nutrient delivery to active muscles, thus improving tolerance to physical exercise and recovery mechanisms. Several studies using NO donors have assessed this hypothesis in a healthy, trained population. However, the conclusions from these studies showed several discrepancies. While some reported that dietary supplementation with NO donors induced benefits in exercise performance, others did not find any positive effect. In this regard, training status of the subjects seems to be an important factor linked to the ergogenic effect of NO supplementation. Studies involving untrained or moderately trained healthy subjects showed that NO donors could improve tolerance to aerobic and anaerobic exercise. However, when highly trained subjects were supplemented, no positive effect on performance was indicated. In addition, all this evidence is mainly based on a young male population. Further research in elderly and female subjects is needed to determine whether NO supplements can induce benefit in exercise capacity when the NO metabolism is impaired by age and/or estrogen status.

Effect of organic acids and mannanoligosaccharide on excretion of Salmonella typhimurium in experimentally infected growing pigs.

The effect of organic acids and mannanoligosaccharide addition to the diet was assessed in pigs orally inoculated with Salmonella typhimurium. Forty-six growers were distributed among four treatments: Basal Diet (BD); BD+encapsulated organic acids; BD+free organic acids; BD+mannanoligosaccharide. Seroconversion was monitored, and feces and tissue samples were tested for Salmonella isolation. No treatment prevented the carrier state, but a tendency of lower fecal excretion was observed in the group treated with mannanoligosaccharide.

1-methylmalate from camu-camu (Myrciaria dubia) suppressed D-galactosamine-induced liver injury in rats.

To evaluate the protective effects of fruit juices against D-galactosamine (GalN)-induced liver injury, lyophilized fruit juices (total 12 kinds) were fed to rats for 7 d, and then we evoked liver injury by injecting GalN. The juice of camu-camu (Myrciaria dubia) significantly suppressed GalN-induced liver injury when the magnitude of liver injury was assessed by plasma alanine aminotransferase and aspartate aminotransferase activities, although some other juices (acerola, dragon fruit, shekwasha, and star fruit) also tended to have suppressive effects. An active compound was isolated from camu-camu juice by solvent fractionation and silica gel column chromatography. The structure was determined to be 1-methylmalate. On the other hand, malate, 1,4-dimethylmalate, citrate, and tartrate had no significant effect on GalN-induced liver injury. It is suggested that 1-methylmalate might be a rather specific compound among organic acids and their derivatives in fruit juices in suppressing GalN-induced liver injury.

Managing the patient presenting with xerostomia: a review.

AIMS: Patients complaining of a dry mouth can present themselves to various clinicians such as the primary care physician, dentists, otolaryngologists and/or oral surgeons. The aim of our review is to provide a systematic method of assessing and managing these patients based on current best evidence published in the literature. METHODS: A literature search was performed on 20th April 2009 using MEDLINE and EMBASE using the terms dry mouth and xerostomia in combination with diagnosis, management, investigations and treatment. RESULTS: There appears to be little correlation between patient symptoms and objectives tests of salivary flow. Therefore clinical management should be based on patient symptoms. There is good evidence to support that xerostomia is commonly associated with anticholinergic drugs, and altering such agents plays an important role in the management of these patients. In patients with residual salivary gland function, the use of salivary stimulants appears to be more beneficial than salivary substitutes. CONCLUSION: Xerostomia can be debilitating and primarily affects the middle aged and elderly population. The most common causes of xerostomia include medications with anticholinergic properties, dehydration, diabetes and radiotherapy for head and neck cancer. Treatment of xerostomia essentially involves addressing the cause followed by salivary substitutes and/or salivary stimulants.

Calcium and vitamin D supplements reduce tooth loss in the elderly.

PURPOSE: Oral bone and tooth loss are correlated with bone loss at nonoral sites. Calcium and vitamin D supplementation slow the rate of bone loss from various skeletal sites, but it is not known if intake of these nutrients affects oral bone and, in turn, tooth retention. SUBJECTS AND METHODS: Tooth loss was examined in 145 healthy subjects aged 65 years and older who completed a 3-year, randomized, placebo-controlled trial of the effect of calcium and vitamin D supplementation on bone loss from the hip, as well as a 2-year follow-up study after discontinuation of study supplements. Teeth were counted at 18 months and 5 years. A comprehensive oral examination at 5 years included assessment of caries, oral hygiene, and periodontal disease. The odds ratio (OR) and 95% confidence interval (CI) of tooth loss were estimated by stepwise multivariate logistic regression. Initial age (mean +/- SD) of subjects was 71 +/- 5 years, and the number of teeth remaining was 22 +/- 7. RESULTS: During the randomized trial, 11 of the 82 subjects (13%) taking supplements and 17 of the 63 subjects (27%) taking placebo lost one or more teeth (OR = 0.4; 95% CI: 0.2 to 0.9). During the 2-year follow-up period, 31 of the 77 subjects (40%) with total calcium intake of at least 1000 mg per day lost one or more teeth compared with 40 of the 68 subjects (59%) who consumed less (OR = 0.5; 95% CI: 0.2 to 0.9). CONCLUSION: These findings suggest that intake levels of calcium and vitamin D aimed at preventing osteoporosis have a beneficial effect on tooth retention.

Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older.

BACKGROUND: Inadequate dietary intake of calcium and vitamin D may contribute to the high prevalence of osteoporosis among older persons. METHODS: We studied the effects of three years of dietary supplementation with calcium and vitamin D on bone mineral density, biochemical measures of bone metabolism, and the incidence of nonvertebral fractures in 176 men and 213 women 65 years of age or older who were living at home. They received either 500 mg of calcium plus 700 IU of vitamin D3 (cholecalciferol) per day or placebo. Bone mineral density was measured by dual-energy x-ray absorptiometry, blood and urine were analyzed every six months, and cases of nonvertebral fracture were ascertained by means of interviews and verified with use of hospital records. RESULTS: The mean (+/-SD) changes in bone mineral density in the calcium-vitamin D and placebo groups were as follows: femoral neck, +0.50+/-4.80 and -0.70+/-5.03 percent, respectively (P=0.02); spine,+2.12+/-4.06 and +1.22+/-4.25 percent (P=0.04); and total body, +0.06+/-1.83 and -1.09+/-1.71 percent (P<0.001). The difference between the calcium-vitamin D and placebo groups was significant at all skeletal sites after one year, but it was significant only for total-body bone mineral density in the second and third years. Of 37 subjects who had nonvertebral fractures, 26 were in the placebo group and 11 were in the calcium-vitamin D group (P=0.02). CONCLUSIONS: In men and women 65 years of age or older who are living in the community, dietary supplementation with calcium and vitamin D moderately reduced bone loss measured in the femoral neck, spine, and total body over the three-year study period and reduced the incidence of nonvertebral fractures.

[The effect of metabolic agents on the antiarrhythmic activity of novocainamide and acetylnovocainamide]. / Vliianie metaboliticheskikh sredstv na antiaritmicheskuiu aktivnost' novokainamida i atsetilnovokainamida.

The effects of potassium malate and sodium succinate on the antiarrhythmic activity of novocainamide and acetylnovocainamide during modelling of chlor-calcium-induced arrhythmia as well as in disorders of cardiac rhythm during modelling of pituitrin-isadrine-induced myocardial infarction were studied. The metabolic agents were found to increase the effectiveness of acetylnovocainamide and the toxicity of novocainamide. To interpret the specific features of the mechanism of the anti-arrhythmic action of the compounds there was studied their ability to form complexes with components of biomembranes and ions of biometals.

[Use of malate and NAD for the correction of the blood supply and oxygen balance of the acutely ischemic myocardium]. / Primenenie malata i NAD dlia korrektsii krovoobrashcheniia i kislorodnogo balansa ostroishemizirovannogo miokarda.

The experiments on cats under the conditions of acute myocardial ischemia showed that malate (20 and 100 mg/kg) and NAD (0.2 and 2 mg/kg) are able of increasing the coronary blood flow against the background of insignificantly increased oxygen consumption by the heart. The combination of these drugs (malate 100 mg/kg + NAD 0.2 mg/kg) produces an increase in the coronary blood flow and a dramatic raise in cardiac oxygen consumption.