ABSTRACT
The role of mitochondrial ROS in signalling muscle adaptations to exercise training has not been explored in detail. We investigated the effect of supplementation with the mitochondria-targeted antioxidant MitoQ on a) the skeletal muscle mitochondrial and antioxidant gene transcriptional response to acute high-intensity exercise and b) skeletal muscle mitochondrial content and function following exercise training. In a randomised, double-blind, placebo-controlled, parallel design study, 23 untrained men (age: 44 ± 7 years, VO2peak: 39.6 ± 7.9 ml/kg/min) were randomised to receive either MitoQ (20 mg/d) or a placebo for 10 days before completing a bout of high-intensity interval exercise (cycle ergometer, 10 × 60 s at VO2peak workload with 75 s rest). Blood samples and vastus lateralis muscle biopsies were collected before exercise and immediately and 3 h after exercise. Participants then completed high-intensity interval training (HIIT; 3 sessions per week for 3 weeks) and another blood sample and muscle biopsy were collected. There was no effect of acute exercise or MitoQ on systemic (plasma protein carbonyls and reduced glutathione) or skeletal muscle (mtDNA damage and 4-HNE) oxidative stress biomarkers. Acute exercise-induced increases in skeletal muscle peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α) mRNA expression were augmented in the MitoQ group. Despite this, training-induced increases in skeletal muscle mitochondrial content were similar between groups. HIIT-induced increases in VO2peak and 20 km time trial performance were also similar between groups while training-induced increases in peak power achieved during the VO2peak test were augmented in the MitoQ group. These data suggest that training-induced increases in peak power are enhanced following MitoQ supplementation, which may be related to the augmentation of skeletal muscle PGC1α expression following acute exercise. However, these effects do not appear to be related to an effect of MitoQ supplementation on exercise-induced oxidative stress or training-induced mitochondrial biogenesis in skeletal muscle.
Subject(s)
Antioxidants , Exercise , Organophosphorus Compounds/pharmacology , Ubiquinone/analogs & derivatives , Adult , Antioxidants/metabolism , Dietary Supplements , Exercise/physiology , Humans , Male , Middle Aged , Mitochondria/metabolism , Muscle, Skeletal/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Ubiquinone/pharmacologyABSTRACT
PURPOSE: We compared urinary tract infection (UTI) symptom resolution rates at 7-10 days in symptomatic women randomized to treatment based on standard urine culture (SUC) versus expanded quantitative urine culture (EQUC) results. MATERIALS AND METHODS: Women ≥18 years old who responded "yes" to "do you feel you have a UTI?" agreed to urethral catheterization and followup. Symptoms were assessed using the validated UTI Symptom Assessment (UTISA) questionnaire. Culture method was randomized 2:1 (SUC:EQUC); antibiotics were prescribed to women with positive cultures. The primary outcome, UTI symptom resolution, was determined 7-10 days following enrollment on all participants regardless of treatment. RESULTS: Demographic data were similar between groups. Of the SUC and EQUC groups 63% and 74% had positive cultures (p=0.10), respectively. Of participants with positive cultures 97% received antibiotics. Primary outcome data were provided by 215 of 225 participants (SUC 143 [95%], EQUC 72 [97%]). At the primary outcome assessment, 64% and 69% in the SUC and EQUC groups, respectively, reported UTI symptom resolution (p=0.46); UTISA scores improved from baseline in the EQUC arm compared to the SUC arm (p=0.04). In the subset of women predominated by non-Escherichia coli (76), there was a trend toward more symptom resolution in the EQUC arm (21%, p=0.08). CONCLUSIONS: Symptom resolution was similar for the overall population (E. coli and non-E. coli) of women treated for UTI symptoms based on SUC or EQUC. Although the sample size limits conclusions regarding the utility of EQUC in women with non-E. coli uropathogens, the detected trend indicates that this understudied clinical subset warrants further study.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacteriological Techniques/methods , Bacteriuria/drug therapy , Aged , Aged, 80 and over , Anti-Bacterial Agents/pharmacology , Bacteriuria/diagnosis , Bacteriuria/microbiology , Bacteriuria/urine , Female , Humans , Microbial Sensitivity Tests/methods , Middle Aged , Self Report , Treatment OutcomeABSTRACT
This work examined the phosphorus (P) removal from the synthetic pretreated swine wastewater using lab-scale horizontal sub-surface flow constructed wetlands (HSSF-CWs). White hard clam (Meretrix lyrata) shells (WHC) and Paspalum atratum were utilized as substrate and plant, respectively. The focus was placed on treatment performance, removal mechanisms and lifespan of the HSSF-CWs. Results indicated that WHC-based HSSF-CW with P. atratum exhibited a high P removal (89.9%). The mean P efluent concentration and P removal rate were 1.34 ± 0.95 mg/L and 0.32 ± 0.03 g/m2/d, respectively. The mass balance study showed that media sorption was the dominant P removal pathway (77.5%), followed by microbial assimilation (14.5%), plant uptake (5.4%), and other processes (2.6%). It was estimated the WHC-based bed could work effectively for approximately 2.84 years. This WHC-based HSSF-CWs technology will therefore pave the way for recycling Ca-rich waste materials as media in HSSF-CWs to enhance P-rich wastewater purification.
Subject(s)
Bivalvia , Water Pollutants, Chemical , Animals , Longevity , Phosphorus , Swine , Waste Disposal, Fluid , Wastewater , WetlandsABSTRACT
This study presents the removal of phosphate from aqueous solution using a new silver nanoparticles-loaded tea activated carbon (AgNPs-TAC) material. In order to reduce costs, the tea activated carbon was produced from tea residue. Batch adsorption experiments were conducted to evaluate the effects of impregnation ratio of AgNPs and TAC, pH solution, contact time, initial phosphate concentration and dose of AgNPs-AC on removing phosphate from aqueous solution. Results show that the best conditions for phosphate adsorption occurred at the impregnation ratio AgNPs/TAC of 3% w/w, pH 3, and contact time lasting 150 min. The maximum adsorption capacity of phosphate on AgNPs-TAC determined by the Langmuir model was 13.62 mg/g at an initial phosphate concentration of 30 mg/L. The adsorption isotherm of phosphate on AgNPs-TAC fits well with both the Langmuir and Sips models. The adsorption kinetics data were also described well by the pseudo-first-order and pseudo-second-order models with high correlation coefficients of 0.978 and 0.966, respectively. The adsorption process was controlled by chemisorption through complexes and ligand exchange mechanisms. This study suggests that AgNPs-TAC is a promising, low cost adsorbent for phosphate removal from aqueous solution.
Subject(s)
Camellia sinensis/chemistry , Charcoal/chemistry , Environmental Restoration and Remediation/methods , Metal Nanoparticles/chemistry , Phosphates/chemistry , Silver/chemistry , Adsorption , Environmental Restoration and Remediation/instrumentation , Kinetics , Plant Leaves/chemistry , Plant Preparations/chemistry , Water Pollutants/chemistryABSTRACT
AIM: Peritoneal metastases from colorectal cancer confer the worst survival among all metastatic sites. The adoption of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) can offer selected patients with isolated colorectal peritoneal metastases (CRPM) a favourable long-term survival. There are numerous factors postulated to influence survival in patients undergoing CRS and HIPEC. The aim of this study was to identify the key perioperative prognostic factors that influence survival in patients undergoing CRS and HIPEC for isolated CRPM. METHOD: A systematic review and meta-analysis were conducted to evaluate prognostic factors influencing survival in patients undergoing CRS and HIPEC for isolated CRPM. RESULTS: Thirty-three studies fitted the inclusion criteria for the systematic review, with 25 studies included in the meta-analysis. On pooled analysis, incomplete cytoreduction, increasing peritoneal carcinoma index (PCI) and lymph node involvement were significantly associated with a worse survival. Additionally, a rectal primary [hazard ratio (HR) 1.93, 95% CI 1.10-3.37], adjuvant chemotherapy (HR 0.71, 95% CI 0.54-0.93) and perioperative grade III/IV morbidity (HR 1.59, 95% CI 1.17-2.16) were also found to significantly influence survival. Notably, tumour differentiation and signet ring cell histology did not influence survival on pooled analysis. CONCLUSION: This meta-analysis confirms that in patients undergoing CRS and HIPEC for isolated CRPM, incomplete cytoreduction, high PCI and lymph node involvement have a negative influence on survival. In addition, a rectal primary, adjuvant chemotherapy use and grade III/IV morbidity are important factors that also significantly influence survival.
Subject(s)
Colorectal Neoplasms , Hyperthermia, Induced , Peritoneal Neoplasms , Antineoplastic Combined Chemotherapy Protocols , Colorectal Neoplasms/drug therapy , Combined Modality Therapy , Cytoreduction Surgical Procedures , Humans , Hyperthermic Intraperitoneal Chemotherapy , Peritoneal Neoplasms/drug therapy , Prognosis , Survival RateABSTRACT
The biogeochemical cycling of phosphorus (P) in South and Southeast Asian floodplain and delta aquifers has received insufficient attention in research studies, even though dissolved orthophosphate (PO43-) in this region is closely linked with the widespread contamination of groundwater with toxic arsenic (As). The overarching aim of this study was to characterize the enrichment of P in anoxic groundwater and to provide insight into the biogeochemical mechanisms underlying its mobilization, subsurface transport, and microbial cycling. Detailed groundwater analyses and in situ experiments were conducted that focused on three representative field sites located in the Red River Delta (RRD) of Vietnam and the Bengal Delta Plain (BDP) in West Bengal, India. The results showed that the total concentrations of dissolved P (TDP) ranged from 0.03 to 1.50â¯mgâ¯L-1 in groundwater, with PO43- being the dominant P species. The highest concentrations occurred in anoxic sandy Holocene aquifers where PO43- was released into groundwater through the microbial degradation of organic carbon and the concomitant reductive dissolution of Fe(III)-(hydr)oxides. The mobilization of PO43- may still constitute an active process within shallow Holocene sediments. Furthermore, a sudden supply of organic carbon may rapidly decrease the redox potential, which causes an increase in TDP concentrations in groundwater, as demonstrated by a field experiment. Considering the subsurface transport of PO43-, Pleistocene aquifer sediments represented effective sinks; however, the enduring contact between oxic Pleistocene sediments and anoxic groundwater also changed the sediments PO43--sorption capacity over time. A stable isotope analysis of PO43--bound oxygen indicated the influences of intracellular microbial cycling as well as a specific PO43- source with a distinct isotopically heavy signal. Consequently, porous aquifers in Asian floodplain and delta regions proved to be ideal natural laboratories to study the biogeochemical cycling of P and its behavior in groundwater environments.
Subject(s)
Ecological and Environmental Phenomena , Environmental Monitoring , Groundwater/chemistry , Phosphorus/analysis , Water Pollutants, Chemical/analysis , Ecosystem , India , VietnamABSTRACT
Background: Few studies have examined the impact of local animal-source foods (ASFs) on the nutritional status of reproductive-age women in developing countries.Objective: We hypothesized that a midmorning snack of local ASF for 6 mo would reduce dietary micronutrient deficiencies [usual intake less than the estimated average requirement (EAR)] and improve blood biomarkers of iron, zinc, and vitamins A and B-12 status among nonpregnant, reproductive-age women in rural Vietnam.Methods: One hundred seventeen women, 18-30 y old, were randomly assigned to receive either an ASF (mean: 144 kcal, 8.9 mg Fe, 2.7 mg Zn, 1050 µg retinoic acid equivalent vitamin A, and 5.5 µg vitamin B-12) or a control snack (mean: 150 kcal, 2.0 mg Fe, 0.9 mg Zn, 0 µg retinoic acid equivalent vitamin A, and 0 µg vitamin B-12) 5 d/wk for 6 mo. Usual nutrient intakes were estimated by repeated 24-h dietary recalls. Blood samples were collected at baseline and 3 and 6 mo. Because of the relation between nutritional status and inflammation, serum C-reactive protein, α-1-acid-glycoprotein, and urinary tract infections (UTIs) were also monitored.Results: Eighty-nine women (47 in the ASF group and 42 controls) completed the study. In the ASF group, intakes of iron and vitamins A and B-12 below the EAR were eliminated, and the prevalence of a low zinc intake was reduced to 9.6% compared with 64.7% in controls (P < 0.001). At 6 mo, a modest increase (P < 0.05) in hemoglobin and iron status occurred in the ASF group compared with the control group, but plasma zinc, retinol, and serum vitamin B-12 concentrations did not differ. UTI relative risk was 3.9 (P < 0.05) among women assigned to the ASF group who had a low whole-body iron status at baseline.Conclusions: Adding a small amount of locally produced ASF to the diets of reproductive-age Vietnamese women improved micronutrient intakes and iron status. However, the increased UTI incidence in women in the ASF group with initially lower iron stores warrants further investigation.
Subject(s)
Deficiency Diseases/diet therapy , Eggs , Iron , Meat , Snacks , Vitamin A , Vitamin B 12 , Adolescent , Adult , Anemia, Iron-Deficiency/blood , Anemia, Iron-Deficiency/diet therapy , Animals , Avitaminosis/blood , Avitaminosis/diet therapy , Deficiency Diseases/blood , Dietary Supplements , Female , Hemoglobins/metabolism , Humans , Iron/administration & dosage , Iron/blood , Iron Deficiencies , Micronutrients/administration & dosage , Micronutrients/blood , Micronutrients/deficiency , Nutritional Status , Rural Population , Vietnam , Vitamin A/administration & dosage , Vitamin A/blood , Vitamin A Deficiency/blood , Vitamin A Deficiency/diet therapy , Vitamin B 12/administration & dosage , Vitamin B 12/blood , Vitamin B 12 Deficiency/blood , Vitamin B 12 Deficiency/diet therapy , Vitamins/administration & dosage , Vitamins/blood , Young Adult , Zinc/administration & dosage , Zinc/blood , Zinc/deficiencyABSTRACT
PURPOSE: To determine the metabolic profiles of the translocator protein ligands PBR102 and PBR111 in rat and human microsomes and compare their in vivo binding and metabolite uptake in the brain of non-human primates (Papio hamadryas) using PET-CT. METHODS: In vitro metabolic profiles of PBR102 and PBR111 in rat and human liver microsomes were assessed by liquid chromatography-tandem mass spectrometry. [18F]PBR102 and [18F]PBR111 were prepared by nucleophilic substitution of their corresponding p-toluenesulfonyl precursors with [18F]fluoride. List mode PET-CT brain imaging with arterial blood sampling was performed in non-human primates. Blood plasma measurements and metabolite analysis, using solid-phase extraction, provided the metabolite profile and metabolite-corrected input functions for kinetic model fitting. Blocking and displacement PET-CT scans, using PK11195, were performed. RESULTS: Microsomal analyses identified the O-de-alkylated, hydroxylated and N-de-ethyl derivatives of PBR102 and PBR111 as the main metabolites. The O-de-alkylated compounds were the major metabolites in both species; human liver microsomes were less active than those from rat. Metabolic profiles in vivo in non-human primates and previously published rat experiments were consistent with the microsomal results. PET-CT studies showed that K1 was similar for baseline and blocking studies for both radiotracers; VT was reduced during the blocking study, suggesting low non-specific binding and lack of appreciable metabolite uptake in the brain. CONCLUSIONS: [18F]PBR102 and [18F]PBR111 have distinct metabolic profiles in rat and non-human primates. Radiometabolites contributed to non-specific binding and confounded in vivo brain analysis of [18F]PBR102 in rodents; the impact in primates was less pronounced. Both [18F]PBR102 and [18F]PBR111 are suitable for PET imaging of TSPO in vivo. In vitro metabolite studies can be used to predict in vivo radioligand metabolism and can assist in the design and development of better radioligands.
Subject(s)
Brain/metabolism , Imidazoles/pharmacokinetics , Molecular Imaging/methods , Positron-Emission Tomography/methods , Pyridines/pharmacokinetics , Receptors, GABA/metabolism , Animals , Brain/diagnostic imaging , Drug Evaluation, Preclinical/methods , Humans , Isotope Labeling/methods , Ligands , Male , Metabolic Clearance Rate , Organ Specificity , Papio , Radiopharmaceuticals/chemical synthesis , Radiopharmaceuticals/pharmacokinetics , Rats , Reproducibility of Results , Sensitivity and Specificity , Species Specificity , Tissue DistributionABSTRACT
A variety of new and earlier synthesized lupane, oleanane, ursane and dammarane triterpenoids have been investigated for their inhibitory activity against α-glucosidase. 2,3-Indole-21 ß-acetyl-20ß,28-epoxy-18α,19ßH-ursane and 3-oxo-3A-homo-3a-aza-20(S)-hydroxydammar-24(25)-ene were synthesized for the first time. The compounds 3, 4, 8-11 and 14 demonstrated strong in vitro inhibitory activity towards α-glucosidase with IC50 values of 37.5-115.1 µM. 3-Deoxy-3a-homo-3a-aza-28-cinnamoyloxy-20(29)-lupene, with an IC50 of 6.67 µM was 60-fold more active than the market drug acarbose.
Subject(s)
Glycoside Hydrolase Inhibitors/pharmacology , Triterpenes/pharmacology , Glycoside Hydrolase Inhibitors/chemistry , Inhibitory Concentration 50 , Molecular Structure , Oleanolic Acid/analogs & derivatives , Oleanolic Acid/chemistry , Oleanolic Acid/pharmacology , Triterpenes/chemical synthesis , Triterpenes/chemistry , alpha-Glucosidases , DammaranesABSTRACT
The enzyme arginase catalyses the divalent cation dependent hydrolysis of L-arginine to produce L-ornithine and urea. Two isoforms of arginases have been identified in mammalian (including human) cells. Moreover, some infectious pathogens (e.g. Leishmania) synthesize their own arginase. Work over the last decades has revealed that elevated arginase activity both decreases cellular availability in nitric oxide (NO) by competing with NO synthases (NOS) and increases concentration in L-ornithine, a precursor in the biosynthesis of polyamines which are important for cell differentiation and proliferation. From these data emerged the concept that selective arginase inhibitors might be a valuable strategy for treatment of various diseases associated with decreased NO and/or increased polyamines production. Consistent with this, recent research provides compelling evidence supporting the beneficial effects of arginase inhibitors in cardiovascular diseases (hypertension, ischemia reperfusion injury, atherosclerosis, diabetes mellitus), asthma, cancer, immunologically-mediated diseases or leishmaniasis. Despite active programs to identify potent arginase inhibitors, effective chemical compounds with reliable pharmacokinetics and toxicological properties are rare. The present review summarizes available data on the discovery of new arginase inhibitors from natural origin. Current knowledge on plant-derived compounds or extracts with arginase inhibitory properties as well as available data on structure-activity relationship (SAR) will be presented. Lastly, the present review will open up new prospects in order to improve the discovery of novel arginase inhibitors from natural sources.
Subject(s)
Arginase/antagonists & inhibitors , Enzyme Inhibitors/chemistry , Animals , Arginase/metabolism , Cell Survival/drug effects , Enzyme Inhibitors/metabolism , Humans , Leishmania/enzymology , Nitric Oxide Synthase/antagonists & inhibitors , Nitric Oxide Synthase/metabolism , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plants/chemistry , Plants/metabolism , Protozoan Proteins/antagonists & inhibitors , Protozoan Proteins/metabolism , Structure-Activity RelationshipABSTRACT
This study explores the potential of removing phosphorus from aqueous solutions and sewage by Zr(IV)-loaded okara (ZLO) in the fixed-bed column. Soybean residue (okara) was impregnated with 0.25M Zr(IV) solution to prepare active binding sites for phosphate. The effect of several factors, including flow rate, bed height, initial phosphorus concentration, pH and adsorbent particle size on the performance of ZLO was examined. The maximum dynamic adsorption capacity of ZLO for phosphorus was estimated to be 16.43mg/g. Breakthrough curve modeling indicated that Adams-Bohart model and Thomas model fitted the experimental data better than Yoon-Nelson model. After treatment with ZLO packed bed column, the effluent could meet the discharge standard for phosphorus in Australia. Successful desorption and regeneration were achieved with 0.2 NaOH and 0.1 HCl, respectively. The results prove that ZLO can be used as a promising phosphorus adsorbent in the dynamic adsorption system.
Subject(s)
Phosphates/chemistry , Sewage/chemistry , Water Pollutants, Chemical/chemistry , Zirconium/chemistry , Adsorption , Australia , Hydrogen-Ion Concentration , Kinetics , Phosphates/analysis , Phosphorus/analysis , Phosphorus/chemistry , Waste Disposal, Fluid , Water Pollutants, Chemical/analysisABSTRACT
While Cr(III) dietary supplements are widely consumed, some commercial supplements have yet to be structurally characterized. X-ray absorption spectroscopy and other spectroscopic methods were used to characterize Cr(III) nicotinato nutritional supplements that have long been used in complementary medicine. Different ratios of nicotinic acid and CrCl3·6H2O (trans-[CrCl2(OH2)4]Cl·2H2O) at different pH values gave a range of products. The local structures of Cr(III) nicotinato complexes obtained at pH 7 and of the patented complex were characterized by performing multiple-scattering analysis of their EXAFS spectra as well as EPR, UV-vis, and IR spectroscopies. For the first time, these complexes have been definitively characterized as nicotinato-bridged polymers of dihydroxido-bridged dinuclear Cr(III) cores. In the patented complex used in commercial preparations, each Cr is octahedral with an additional terminal O-bound nicotinato ligand, two bridging nicotinato (one O and one N bound), and an aqua ligand. The other species also have two or three bridging nicotinato ligands and an aqua and, in some cases, a terminal hydroxido ligand, which is dependent upon the stoichiometry of the reactants and the pH value of the solution in which they are prepared.
Subject(s)
Chromium/chemistry , Dietary Supplements , Nicotinic Acids/chemistry , Organometallic Compounds/chemistry , Electron Spin Resonance Spectroscopy , Molecular Structure , Organometallic Compounds/chemical synthesis , Principal Component Analysis , Spectrophotometry, Infrared , Spectrophotometry, UltravioletABSTRACT
OBJECTIVE: Laryngeal cryptococcosis is a rare condition. In this report, we describe the findings for and treatment of a 58-year-old man with Cryptococcus gattii infection of the right vocal fold. METHOD: Case report and review of the relevant English language literature. RESULTS: The patient presented with persistent hoarseness of voice. Laryngoscopy demonstrated an irregular, red lesion on the right vocal fold. Histopathological examination identified cryptococcus. The patient was treated with oral fluconazole 400 mg/day for eight weeks. CONCLUSION: Laryngeal involvement by Cryptococcus gattii can result from prolonged inhaled corticosteroid therapy and proximity to eucalyptus trees. The clinical presentation, laryngoscopic findings and imaging results of laryngeal involvement may mimic a neoplasm. Histopathological examination can demonstrate the causative organism. Management consists of advice from an infectious disease specialist together with adequate treatment by antifungal agents.
Subject(s)
Antifungal Agents/therapeutic use , Cryptococcosis/diagnosis , Cryptococcus gattii , Fluconazole/therapeutic use , Laryngeal Diseases/diagnosis , Adrenal Cortex Hormones/adverse effects , Cryptococcosis/drug therapy , Diagnosis, Differential , Eucalyptus/adverse effects , Hoarseness/drug therapy , Hoarseness/microbiology , Humans , Inhalation Exposure/adverse effects , Laryngeal Diseases/drug therapy , Male , Middle Aged , Rare Diseases , Vocal Cords , VoiceABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Several Asian plants are known for their anti-diabetic properties and produce alkaloids and flavonoids that may stimulate insulin secretion. MATERIALS AND METHODS: Using Vietnamese plants (Nelumbo nucifera, Gynostemma pentaphyllum, Smilax glabra, and Stemona tuberosa), we extracted two alkaloids (neotuberostemonine, nuciferine) and four flavonoids (astilbin, engeletin, smitilbin, and 3,5,3'-trihydroxy-7,4'-dimethoxyflavone), and studied their insulin stimulatory effects. RESULTS: Nuciferine, extracted from Nelumbo nucifera, stimulated both phases of insulin secretion in isolated islets, whereas the other compounds had no effect. The effect of nuciferine was totally abolished by diazoxide and nimodipine, and diminished by protein kinase A and protein kinase C inhibition. Nuciferine and potassium had additive effects on insulin secretion. Nuciferine also stimulated insulin secretion in INS-1E cells at both 3.3 and 16.7 mM glucose concentrations. Compared with glibenclamide, nuciferine had a stronger effect on insulin secretion and less beta-cell toxicity. However, nuciferine did not compete with glibenclamide for binding to the sulfonylurea receptor. CONCLUSIONS: Among several compounds extracted from anti-diabetic plants, nuciferine was found to stimulate insulin secretion by closing potassium-adenosine triphosphate channels, explaining anti-diabetic effects of Nelumbo nucifera.
Subject(s)
Aporphines/pharmacology , Glyburide/pharmacology , Hypoglycemic Agents/pharmacology , Insulin-Secreting Cells/drug effects , Insulin/metabolism , Nelumbo/chemistry , Plant Extracts/pharmacology , ATP-Binding Cassette Transporters/metabolism , Animals , Antihypertensive Agents/pharmacology , Aporphines/adverse effects , Aporphines/isolation & purification , Cell Line , Cyclic AMP-Dependent Protein Kinases/pharmacology , Diazoxide/pharmacology , Glucose/pharmacology , Insulin Secretion , Insulin-Secreting Cells/metabolism , KATP Channels/metabolism , Mice , Nimodipine/pharmacology , Plant Extracts/adverse effects , Plant Extracts/chemistry , Potassium/pharmacology , Potassium Channels, Inwardly Rectifying/metabolism , Protein Kinase C/pharmacology , Receptors, Drug/metabolism , Sulfonylurea Receptors , VietnamABSTRACT
More than 400,000 primary hip and knee replacement surgeries are performed each year in the United States. From these procedures, approximately 0.5-3% will become infected and when considering revision surgeries, this rate has been found to increase significantly. Antibiotic-resistant bacterial infections are a growing problem in patient care. This in vitro research investigated the antimicrobial potential of the polymer released, broad spectrum, Cationic Steroidal Antimicrobial-13 (CSA-13) for challenges against 5 × 10(8) colony forming units (CFU) of methicillin-resistant Staphylococcus aureus (MRSA). It was hypothesized that a weight-to-weight (w/w) concentration of 18% CSA-13 in silicone would exhibit potent bactericidal potential when used as a controlled release device coating. When incorporated into a polymeric device coating, the 18% (w/w) broad-spectrum polymer released CSA-13 antimicrobial eliminated 5 × 10(8) CFU of MRSA within 8 h. In the future, these results will be utilized to develop a sheep model to assess CSA-13 for the prevention of perioperative device-related infections in vivo.
Subject(s)
Anti-Infective Agents/therapeutic use , Coated Materials, Biocompatible/pharmacology , Drug Resistance, Bacterial/drug effects , Methicillin-Resistant Staphylococcus aureus/drug effects , Polymers/chemistry , Staphylococcal Infections/drug therapy , Staphylococcal Infections/prevention & control , Anti-Infective Agents/pharmacology , Colony Count, Microbial , Methicillin-Resistant Staphylococcus aureus/growth & development , Microbial Sensitivity Tests , Porosity , Staphylococcal Infections/microbiology , Steroids/pharmacology , Steroids/therapeutic use , Time FactorsABSTRACT
In this study, soy protein isolate (SPI) (4%, v/w) was supplemented to the yogurt mix to increase the amount of biologically active isoflavone in yogurt (SY). The control yogurt was without any SPI supplementation (USY). The supplementation significantly (P < 0.05) increased the lactose metabolism by the yogurt starter including Lactobacillus delbrueckii ssp. bulgaricus ATCC 11842 (Lb 11842) and Streptococcus thermophilus ST 1342 (ST 1342) during the fermentation process by 4.7%. The starter produced more acetic acid and less lactic acid in SY than that in USY and altered the ratio of lactic and acetic acid during the entire storage period. The viability of both Lb 11842 and ST 1342 in SY was significantly (P < 0.05) lower than that in USY from 14 d of the storage period, however, their concentration still remained high (8.11 to 8.84 log CFU/g). The starter transformed 72.8% of total inactive isoflavone glycosides (IG) to active isoflavone aglycones (IA), increasing the IA content from 1.35 to 15.01 mg/100 g sample. During the storage period, IA concentration slowly rose from 15.02 to 15.51 mg/100 g sample.
Subject(s)
Dietary Supplements , Isoflavones/metabolism , Soybean Proteins/administration & dosage , Yogurt/analysis , Yogurt/microbiology , Acetic Acid/metabolism , Fermentation , Glycosides/metabolism , Lactic Acid/metabolism , Lactobacillus delbrueckii/metabolism , Lactose/metabolism , Streptococcus thermophilus/metabolismABSTRACT
This study compared the efficacy of two different injection sites for subconjunctival anaesthesia (SCA) in cataract surgery. One-hundred-and-three eyes of 99 consecutive patients undergoing routine cataract surgery were randomised to receive SCA either to the superior bulbar conjunctiva (n = 52) or the inferior bulbar conjunctiva (n = 51). Pain experienced during anaesthetic administration and at various stages of the perioperative period was assessed using a simplified scale. Assessment of subconjunctival haemorrhage and chemosis was made by the surgeon. The percentage of patients reporting any pain on administration of superior SCA was 46% compared to 67% with inferior SCA (P = 0.036). Moderate to severe pain on SCA injection was experienced by 15% and 18% of those in the superior and inferior SCA groups respectively. The cataract procedure was well tolerated in both groups. There was no difference between the groups for duration of surgery (P = 0.25), anaesthetic related complications including chemosis (P = 0.28), subconjunctival haemorrhage (P = 0.38) or intraoperative complications (P = 0.50). We found that subconjunctival anaesthesia is effective for routine cataract surgery. There was no difference in block efficacy between superiorly and inferiorly delivered SCA. However, superior SCA appeared to be less painful on injection compared to inferiorly delivered SCA.
Subject(s)
Anesthesia, Local/methods , Cataract Extraction , Conjunctiva , Pain/classification , Aged , Female , Humans , In Vitro Techniques , Injections/adverse effects , Male , Pain/etiologyABSTRACT
AIMS: Chronic alcoholism is classically associated with major deficits in the visual and auditory processing of emotions. However, the crossmodal (auditory-visual) processing of emotional stimuli, which occurs most frequently in everyday life, has not yet been explored. The aim of this study was to explore crossmodal processing in alcoholism, and specifically the auditory-visual facilitation effect. METHODS: Twenty patients suffering from alcoholism, and 20 matched healthy controls had to detect the emotion (anger or happiness) displayed by auditory, visual or auditory-visual stimuli. The stimuli were designed to elicit a facilitation effect (namely, faster reaction times (RTs) for crossmodal condition than for unimodal ones). RTs and performance were recorded. RESULTS: While the control subjects elicited a significant facilitation effect, alcoholic individuals did not present this effect, as no significant differences between RTs according to the modality were shown. This lack of facilitation effect is the marker of an impaired auditory-visual processing. CONCLUSIONS: Crossmodal processing of complex social stimuli (such as faces and voices) is crucial for interpersonal relations. This first evidence for a crossmodal deficit in alcoholism contribute in explaining the contrast observed between experimental results describing, up to now, mild impairments in emotional facial expression (EFE) recognition in alcoholic subjects (e.g. Oscar-Berman et al.,1990), and the many clinical observations suggesting massive problems.
Subject(s)
Alcoholism/physiopathology , Alcoholism/psychology , Anger/physiology , Happiness , Social Facilitation , Acoustic Stimulation/methods , Adult , Facial Expression , Female , Humans , Male , Middle Aged , Photic Stimulation/methods , Pilot Projects , Reaction Time/physiologyABSTRACT
OBJECTIVE: To investigate whether improvements in cardiovascular risk factors, as observed in energy-balance conditions after exchanging carbohydrates (CHO) for monounsaturated (MUFA) fats, are also observed in energy-restricted conditions. DESIGN: Longitudinal, clinical intervention study using two types of energy-restricted diets (-30% of initial energy intake) with similar levels of saturated and polyunsaturated fats: a high CHO diet (55% of energy from CHOs, 10% from MUFAs) and a high MUFA diet (40% of energy from CHOs, 25% from MUFAs). SUBJECTS: A total of 32 overweight subjects (nine males, 23 females, BMI: 26-45 kg/m(2)). MEASUREMENTS: Body weight, serum lipids, fasting plasma insulin and phospholipid fatty acid composition of red blood cells were measured at baseline and after 8 weeks. Various oxidative status parameters (plasma lipid hydroperoxides, total plasma antioxidant capacity, plasma uric acid and vitamin E) and serum-induced smooth muscular cell (SMC) proliferation were also measured at these time points. RESULTS: Weight loss (1.1 kg/week over the first 4 weeks and 6.7 kg at week 8) was not significantly affected by the diet composition. Both diets reduced significantly total serum cholesterol, but the MUFA-rich diet showed better effects on fasting serum triacylglycerol (TG) than the CHO-rich diet: 1.18 vs 1.51 mmol/l for the MUFA-rich diet (after vs before, P<0.05) and 1.42 vs 1.62 for the CHO-rich diet. After 8 weeks, plasma vitamin E concentrations were positively associated with the oleic acid level of red blood cell phospholipids and showed opposite variations in both diets (increase with the MUFA-rich diet and decrease with the CHO-rich diet). Relative changes in SMC proliferation induced by sera were negatively associated with the ratio oleic:linoleic acid of red blood cell phospholipids and were significantly higher with the CHO-rich diet. CONCLUSIONS: The MUFA-rich diet showed better effects on serum TG than the CHO-rich diet, even with energy restriction and weight loss. The results suggest also a protective effect of oleic acid on oxidative stress and SMC proliferation, two other important cardiovascular risk factors.
Subject(s)
Dietary Carbohydrates/metabolism , Dietary Fats/metabolism , Fatty Acids, Monounsaturated/metabolism , Weight Loss/physiology , Animals , Blood Glucose/metabolism , Cells, Cultured , Cholesterol, HDL/metabolism , Cholesterol, LDL/metabolism , Fatty Acids, Unsaturated/metabolism , Female , Humans , Insulin/blood , Longitudinal Studies , Male , Myocytes, Smooth Muscle/metabolism , Rats , Rats, WistarABSTRACT
The development of precise connections in the mammalian brain proceeds through refinement of initially diffuse patterns, a process that occurs largely within critical developmental windows. To elucidate the molecular pathways that orchestrate these early periods of circuit remodeling, we have examined the role of a calcium- and cAMP-regulated transcriptional pathway. We show that there is a window of CRE/CREB-mediated gene expression in the developing thalamus, which precedes neocortical expression. In the LGN, this wave of gene expression occurs prior to visual experience, but requires retinal function. Mutant mice with reduced CREB expression show loss of refinement of retinogeniculate projections. These results suggest an important role of the CRE/CREB transcriptional pathway in the coordination of experience-independent circuit remodeling during forebrain development.