Post Ingestion Research Articles

Impact of reducing the threshold for acetylcysteine treatment in acute paracetamol poisoning: The recent United Kingdom experience

Background. On 3 September 2012, the licensed indication for acetylcysteine was changed in the United Kingdom (UK) so that all patients with a plasma paracetamol concentration above a “100 mg/L” (4 h post ingestion) nomogram treatment line after an acute paracetamol (acetaminophen) overdose should be treated. This is a lower threshold than that used in the United States, Canada, Australia, and New Zealand. Here we report the impact of this change in the UK on the management of patients with acute overdose in different paracetamol concentration ranges. Methods. This is a cohort study, consisting of a retrospective analysis conducted on prospectively collected audit data in three UK hospitals. Following appropriate ethical and data protection authority approval, data for patients presenting within 24 h of an acute timed single paracetamol overdose were extracted. Numbers of admissions and use of antidote in relation to different paracetamol concentration bands (< 100 mg/L; 100–149 mg/L; 150–199 mg/L; and ≥ 200 mg/L at 4 h) were analyzed for one-year periods before and after the change. Results. Comparing the year before with the year after the change, there was no change in the numbers of patients presenting to hospital within 24 h of acute timed paracetamol overdose (1246 before and 1251 after), but more patients were admitted (759 before and 849 after) and treated with acetylcysteine (389 before and 539 after). Of the 150 additional patients treated with acetylcysteine in the year following the change, 114 (76%, 95% CI: 68.4–82.6) were in the 100–149 group and 9 (6.0%, 95% CI: 2.8–11.1) in the 150–199 group. Conclusions. Changes to national guidelines for managing paracetamol poisoning in the UK have increased the numbers of patients with acute overdose treated with acetylcysteine, with most additional treatments occurring in patients in the 100–149 mg/L dose range, a group at low risk of hepatotoxicity and higher risk of adverse reactions.

The effect of caffeine ingestion on functional performance in older adults.

Caffeine is a widely used nutritional supplement which has been shown to enhance both physical and cognitive performance in younger adults. However, few studies have assessed the effect of caffeine ingestion on performance, particularly functional performance in older adults. The present study aims to assess the effect of acute caffeine ingestion on functional performance, manual dexterity and readiness to invest effort in older adults. 19 apparently healthy, volunteers (10 females and 9 males aged 61-79; 66 ± 2 years) performed tests of functional fitness and manual dexterity post ingestion of caffeine (3mg*kg-1) or placebo in a randomised order. Pre and 60 minutes post ingestion, participants also completed measures of readiness to invest physical (RTIPE) and mental (RTIME) effort. A series of repeated measures ANOVAS indicated enhanced performance in the following functional fitness tests; arm curls (P = .04), 8 foot up and go (P = .007), six minute walk (P = .016). Manual dexterity was also improved in the presence of caffeine (P = .001). RTIME increased (P = .015) pre to post ingestion in the caffeine condition but not in the placebo condition. There were no significant main effects or interactions for RTIPE or gender in any analysis (all P > .05). The results of this study suggest that acute caffeine ingestion positively enhances functional performance, manual dexterity and readiness to invest effort in apparently healthy older adults.

Successful treatment of cardiogenic shock with an intraaortic balloon pump following aluminium phosphide poisoning

Aluminium phosphide (AlP) is a highly toxic pesticide that inhibits cytochrome oxidase c and causes oxidative stress. Death results from refractory cardiogenic shock due to myocardial dysfunction. There is very little information regarding extracorporeal life support in severe AlP poisoning. Although several therapies are available, none are curative. We report on the use of an intra-aortic balloon pump (IABP) in a 24-year-old woman brought to our hospital after an intentional ingestion of a tablet of AlP (3 g), which caused refractory AlP-induced cardiogenic shock and acute respiratory distress syndrome (ARDS). The patient underwent gastric lavage with potassium permanganate, received sodium bicarbonate intravenously, and was admitted to the intensive care unit. Echocardiography at 36 h post ingestion showed a left ventricular ejection fraction (LVEF) of <20 %. An IABP was inserted and the patient’s vital signs stabilised. After eight days, the IABP was removed and on day 20, the patient’s LVEF increased to 50 %. IABP was successfully used and may improve future prognoses for severely poisoned AlP patients with refractory cardiogenic shock. We encourage clinical toxicologists to examine this new treatment.

Hemodialysis clearance of glyphosate following a life-threatening ingestion of glyphosate-surfactant herbicide

Context. Ingestion of glyphosate-surfactant herbicides (GlySH) can result in acute kidney injury, electrolyte abnormalities, acidosis, cardiovascular collapse, and death. In severe toxicity, the use of hemodialysis is reported, but largely unsupported by kinetic analysis. We report the dialysis clearance of glyphosate following a suicidal ingestion of a glyphosate-containing herbicide. Case details. A 62-year-old man was brought to the emergency department (ED) 8.5 h after drinking a bottle of commercial herbicide containing a 41% solution of glyphosate isopropylamine, in polyoxyethyleneamine (POEA) surfactant and water. He was bradycardic and obtunded with respiratory depression necessitating intubation and mechanical ventilation. Initial laboratory results were significant for the following: pH, 7.11; PCO2, 64 mmHg; PO2, 48 mmHg; potassium, 7.8 mEq/L; Cr 3.3, mg/dL; bicarbonate, 22 mEq/L; anion gap, 18 mEq/L; and lactate, 7.5 mmol/L. Acidosis and hyperkalemia persisted despite ventilation and fluid resuscitation. The patient underwent hemodialysis 16 h post ingestion, after which he demonstrated resolution of acidosis and hyperkalemia, and improvement in clinical status. Serum glyphosate concentrations were drawn prior to, during, and after hemodialysis. The extraction ratio and hemodialysis clearance were calculated to be 91.8% and 97.5 mL/min, respectively. Discussion. We demonstrate the successful clearance of glyphosate using hemodialysis, with corresponding clinical improvement in a patient with several poor prognostic factors (advanced age, large volume ingested, and impaired consciousness). The effects of hemodialysis on the surfactant compound are unknown. Hemodialysis can be considered when severe acidosis and acute kidney injury complicate ingestion of glyphosate-containing products.

Antidote removal during haemodialysis for massive acetaminophen overdose

Context. Haemodialysis is sometimes used for patients with massive acetaminophen overdose when signs of “mitochondrial paralysis” (lactic acidosis, altered mental status, hypothermia and hyperglycaemia) are present. The role of haemodialysis is debated, in part because the evidence base is weak and the endogenous clearance of acetaminophen is high. There is also concern because the antidote acetylcysteine is also dialyzable. We prospectively measured serum acetylcysteine concentrations during haemodialysis in three such cases. Case details. Three adults each presented comatose and acidemic 10 to ˜ 18 h after ingesting > 1000mg/kg of acetaminophen. Two were hypothermic and hyperglycaemic. Serum lactate concentrations ranged from 7 mM to 12.5 mM. All three were intubated, and initial acetaminophen concentrations were as high as 5980 μM (900 μg/mL). An intravenous loading dose of 150 mg/kg acetylcysteine was initiated between 10.8 and ˜ 18 h post ingestion, and additional doses were empirically administered during haemodialysis to compensate for possible antidote removal. A single run of 3–4 h of haemodialysis removed 10–20 g of acetaminophen (48–80% of remaining body burden), reduced serum acetaminophen concentrations by 56–84% (total clearance 3.4–7.8 mL/kg/min), accelerated native acetaminophen clearance (mean elimination half-life 580 min pre-dialysis, 120 min during and 340 min post-dialysis) and corrected acidemia. Extraction ratios of acetylcysteine across the dialysis circuit ranged from 73% to 87% (dialysance 3.0 to 5.3 mL/kg/min). All three patients recovered fully, and none developed coagulopathy or other signs of liver failure. Discussion. When massive acetaminophen ingestion is accompanied by coma and lactic acidosis, emergency haemodialysis can result in rapid biochemical improvement. As expected, haemodialysis more than doubles the clearance of both acetaminophen and acetylcysteine. Because acetylcysteine dosing is largely empirical, we recommend doubling the dose during haemodialysis, with an additional half-load when dialysis exceeds 6 h.

Bioavailability of epicatechin and effects on nitric oxide metabolites of an apple flavanol‐rich extract supplemented beverage compared to a whole apple puree: a randomized, placebo‐controlled, crossover trial

Flavanol-rich foods are known to exert beneficial effects on cardiovascular health. The biological effects depend on bioavailability of flavanols which may be influenced by food matrix and dose ingested. We compared the bioavailability and dose-response of epicatechin from whole apple and an epicatechin-rich extract, and the effects on plasma and urinary nitric oxide (NO) metabolites. In a randomized, placebo-controlled, crossover trial, subjects consumed drinks containing 70 and 140 mg epicatechin from an apple extract and an apple puree containing 70 mg epicatechin. Blood and urine samples were collected for 24 h post ingestion. Maximum plasma concentration, AUC(0-24 h) , absorption and urinary excretion were all significantly higher after ingestion of both epicatechin drinks compared with apple puree (p < 0.05). Time to maximum plasma concentration was significantly later for the puree compared with the drinks (p < 0.01). Epicatechin bioavailability was >2-fold higher after ingestion of the 140 mg epicatechin drink compared to the 70 mg epicatechin drink (p < 0.05). Excretion of NO metabolites was higher for all test products compared with placebo, which was significant for the high dose drink (p = 0.016). Oral bioavailability of apple epicatechin increases at higher doses, is reduced by whole apple matrix and has the potential to increase NO bioavailability.

Effects of Inclusion of Two Probiotic Strains Isolated From ?Sha?a?, a Maize-Based Traditionally Fermented Beverage on Lipid Metabolism of Rabbits fed a Cholesterol-Enriched Diet

The objective of this study was to assess the in vitro probiotic potential of Lactobacillus plantarum Lp10S and Lp11S isolated from Sha'a and evaluate their effects on lipid metabolism of hypercholesterolaemic rabbits. The strains were tested in vitro for their acid and bile tolerance, capability to remove cholesterol from MRS broth and to deconjugate bile salts. For in vivo studies, Lactobacillus plantarum Lp10S and Lp11S were administered to rabbits fed on cholesterol-enriched diet (standard diet+2×0.02 g of pure cholesterol per day per rabbit) at a dose of 2×10 8 CFU per day per rabbit for each strain; the treatment lasted seven weeks and one week post ingestion period was observed. Serum lipids were analyzed during the experiment. The results revealed that strains Lactobacillus plantarum Lp10S and Lp11S tolerated well low pH and bile salts, expressed bile salt hydrolase activity and have ability to assimilate cholesterol in vitro. The results also showed that diets including Lactobacillus plantarum Lp10S and Lp11S significantly lowered serum total cholesterol, (VLDL+IDL+LDL)-cholesterol and triglycerides levels of hypercholesterolaemic rabbits. In addition, HDL-cholesterol level significantly increased and the atherosclerosis index was significantly lowered. The present results indicate the probiotic potential of Lactobacillus plantarum Lp10S and Lp11S strains as well as their in vivo cholesterol-lowering properties that may be useful for their application as health-promoting bacteria.

Absorption, distribution, metabolism and elimination of a stable isotope‐labelled anthocyanin in Humans

Evidence suggests anthocyanins beneficially affect cardiovascular health; yet their absorption, distribution, metabolism and elimination (ADME) is poorly understood. We characterised the ADME of a13C‐labeled anthocyanin in humans. 8 male participants consumed 500 mg of labeled cyanidin‐3‐glucoside. Serum, urine, feces and breath collected over 48 h were analysed using isotoperatio mass spectrometry and liquid chromatography‐tandem mass spectrometry. 43.9 ± 25.9% of 13C was recovered in the urine, breath and feces, with a calculated relative bioavailability of 12.3 ± 1.3%. Metabolites were identified as degradation products (protocatechuic acid and phloroglucinaldehyde), phenolic, hippuric, phenylacetic and phenylpropenoic acids. Maximum rates of 13C absorption were achieved 30 min post ingestion (32.5 ± 14.2 μg/mL/h), while 13C‐labeled metabolites collectively peaked (6.0 ± 2.1 μmol/L) in the serum at 10.2 ± 4.1 h; with the total phase II conjugates of protocatechuic acid reaching 2.3 ± 0.1 μmol/L at 13.4 ± 2.5 h. The half‐lives for metabolites ranged between 12.4 ± 4.2 h for the phenolic degradation products to 51.6 ± 22.5 h for ferulic acid. Our data suggest that anthocyanins are more bioavailable than previously perceived and their metabolites are still present in the circulation after 48 h. Research support: UK Biotechnology and Biological Sciences Research Council (BBSRC‐DRINC; BB/H004963/1).

Elevating endogenous GABA levels with GAT-1 blockade modulates evoked but not induced responses in human visual cortex.

The electroencephalographic/magnetoencephalographic (EEG/MEG) signal is generated primarily by the summation of the postsynaptic currents of cortical principal cells. At a microcircuit level, these glutamatergic principal cells are reciprocally connected to GABAergic interneurons. Here we investigated the relative sensitivity of visual evoked and induced responses to altered levels of endogenous GABAergic inhibition. To do this, we pharmacologically manipulated the GABA system using tiagabine, which blocks the synaptic GABA transporter 1, and so increases endogenous GABA levels. In a single-blinded and placebo-controlled crossover study of 15 healthy participants, we administered either 15 mg of tiagabine or a placebo. We recorded whole-head MEG, while participants viewed a visual grating stimulus, before, 1, 3 and 5 h post tiagabine ingestion. Using beamformer source localization, we reconstructed responses from early visual cortices. Our results showed no change in either stimulus-induced gamma-band amplitude increases or stimulus-induced alpha amplitude decreases. However, the same data showed a 45% reduction in the evoked response component at ∼80 ms. These data demonstrate that, in early visual cortex the evoked response shows a greater sensitivity compared with induced oscillations to pharmacologically increased endogenous GABA levels. We suggest that previous studies correlating GABA concentrations as measured by magnetic resonance spectroscopy to gamma oscillation frequency may reflect underlying variations such as interneuron/inhibitory synapse density rather than functional synaptic GABA concentrations.

Staphylococcus aureusin the House Fly: Temporospatial Fate of Bacteria and Expression of the Antimicrobial Peptidedefensin

House flies disseminate numerous species of bacteria acquired during feeding and breeding activities in microbe-rich habitats. Previous house fly surveys have detected the pathogen Staphylococcus aureus Rosenbach 1884, which causes cutaneous and septic infections in mammals, and enterotoxic food poisoning. We assessed the fate of GFP-expressing S. aureus (GFP-S. aureus) in the house fly alimentary canal with microscopy and by culture of whole flies and excreta. Furthermore, the concurrent expression of the antimicrobial peptide gene defensin was measured in the crop, proventriculus, midgut, and fat body. As soon as 4 h postingestion (PI), GFP-S. aureus were visualized as cocci or diplococci in the hindgut and rectum of flies fed approximately equal 10(5) colony forming units. Bacteria persisted up to 6 h PI but significantly decreased. Excretion of viable GFP-S. aureus peaked at 2 h PI and, although significantly less, continued up to 4 h PI. defensin was highly upregulated locally in the alimentary canal and systemically in fat body at 2, 4, and 6 h PI making this study the first to report, to our knowledge, an epithelial and systemic response to a bacterium with lysine-type peptidoglycan in flies exposed via feeding. While flies harbored S. aureus for up to 6 h PI, the highest probability of vectoring biologically relevant amounts of bacteria occurred 0-2 h PI. The combined effects of excretion, digestion and antimicrobial effectors likely contribute to loss of ingested bacteria. Nonetheless, house flies are relevant vectors for S. aureus up to 2 h PI and environmental reservoirs up to 6 h PI.

Omega-3 fatty acids in ileal effluent after consuming different foods containing microencapsulated fish oil powder – an ileostomy study

The intestinal absorption of omega-3 long chain polyunsaturated fatty acids (ω3 LCPUFA), [eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA)], after consuming fish oil gelatine capsules or different food products fortified with microencapsulated fish oil, was determined using human ileostomates. The total amount of ω3 LCPUFA consumed per dose of fish oil capsule was 266 mg while that for fortified orange juice, yoghurt and cereal bar was 284 mg per serving of food product. In a time course experiment ω3 LCPUFA was measured in ileal effluent over 24 h post ingestion. Only 0.58-0.73% of the total ω3 LCPUFA dose was recovered in the ileal effluent irrespective of whether the fish oil was delivered in a gelatine capsule or in the form of a microencapsulated powder incorporated into fortified foods. Excretion of ω3 LCPUFA was detected in the 2-18 h effluent collections with none detected at 0 h or 24 h. post ingestion. The transit time of the minimal amount of ω3 LCPUFA that remained in the ileal effluent was dependent on the method of delivery of the fish oil. The ω3 LCPUFA content in the ileal effluent peaked at 2-8 h and declined after 10 h after consumption of fish oil capsules and fortified orange juice. In contrast, two peaks in ω3 LCPUFA content were observed in the ileal effluent, first at 2-8 h and again at 14-16 h, after consumption of fortified yoghurt and cereal bar. The highest recovery of the small amount of ω3 LCPUFA in the ileal effluent at 14-16 h was obtained when fortified cereal bar was consumed. The results suggest that the delivery of fish oil through food products fortified with microencapsulated fish oil does not compromise the bioavailability of the ω3 LCPUFA as evidence by no statistical differences detected in the remaining portion of ω3 LCPUFA in the ileal effluent (p = 0.58). However, the food matrix in which the microencapsulated oil was delivered may alter the transit kinetics of the ω3 LCPUFA through the small intestine.

Effect of proanthocyanidin single oral dose on glucose tolerance in response oral maltose load in healthy women

Aim: The present study was designed to assess the effect of standardized proanthocyanidin on postprandial blood glucose level after maltose load in non diabetic females. Materials and Methods: Single oral dose (50 mg) of proanthocyanidin tablet was administered by non diabetic adult females thirty minutes before oral ingestion of maltose load (50 gm) using acarbose as comparator. Blood glucose was monitored before and 15, 30, 60, 120, and 180 min post ingestion of maltose. Results: The results showed considerable decrease in 30 and 60 min postprandial hyperglycemia due to the use of proanthocyanidin, while non significant decrease of AUC and delta AUC was obtained in both proanthocyanidin and acarbose groups compared with control. However, comparable results for 2 hr postprandial hyperglycemia were achieved by proanthocyanidin (41%) and acarbose (40%). Conclusion: single oral dose of proanthocyanidin attenuates hyperglycemia after maltose challenge in non-diabetic females and such effect was comparable to that produced by acarbose.

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Case Reports: Gastric decontamination in ingestion has been deemphasized in the recent past predicated on extensive evidence-based medicine review and guidelines. We describe a case of life-threatening ingestion complicated by a charcoal-medication gastric bezoar that was removed by EGD at 18 hours (h) post ingestion with subsequent abatement of symptoms. A 16-year-old female was found unresponsive with labored breathing and generalized seizures after an ingestion of an unknown quantity of bupropion and aripiprazole tablets. She was intubated by pre-hospital responders and at the outside hospital received 3L of crystalloid and dopamine and norepinephrine drips to maintain a MAP >60 torr. Seizures were controlled with lorazepam and phenytoin. Activated charcoal was delivered via NG tube. Benztropine was given for suspected extrapyramidal movements and dantrolene for increased temperature (T). At PICU admission, she was unresponsive with poor perfusion, BP 82/36, HR 153, T 38.1, SaO2 94% on FiO2 1.0 and PEEP 8 cm H2O. Exam was significant for 1+ pulses, 5mm minimally reactive pupils, no eye opening, weak corneal reflex, hyperreflexic lower extremity DTRs and marginal withdrawal to stimuli. ARDS and hypotension dominated the early course despite additional fluid resuscitation, dopamine, milrinone and norepinephrine. A T 41?C prompted neuromuscular blockade, midazolam and cyproheptadine for presumptive serotonin syndrome. At 18 h, EGD revealed a large intragastric mass of charcoal with intact and fragmented pills. Medication concretions were removed by endoscopy-directed high pressure lavage and additional extrication of 5 intact pills via a retrieval basket. Within 12 h the patient became euthermic with continued cardiopulmonary improvement allowing norepinephrine cessation at 40 h and extubation at 60 h. The patient recovered intact. This case illustrates the need to consider pharmacobezoars in ingestions with refractory toxicity and the potential role for delayed aggressive gut decontamination with EGD. Consideration criteria may also include delayed or recurrent toxicity, absorption characteristics, gastro-intestinal ileus, altered pharmacokinetics and radiologic findings.

Acute physiological effects of the commercially available weight loss/energy product, Fastin-XR®, in contrast with the individual effects of caffeine and acacia rigidula

Background The prevalence of overweight and obesity worldwide has resulted in the growth of over the counter weight loss products into one the largest categories of nutritional supplements. However, few commercial products have been properly examined in finished commercial form and seldom have been studied in comparison with individual active ingredients. The purpose of this study was to investigate the acute effects of the commercial weight loss/energy product, Fastin-XR ® (High-Tech Pharmaceuticals, Inc., Norcross, GA) on measures of metabolic and hemodynamic activity in comparison with the effects of caffeine and the effects of acacia rigidula. Methods Ten recreationally active men, 28.5 ± 5 years of age, voluntarily participated in this investigation. Study participants completed four 3-hour resting metabolic testing sessions in which four treatment conditions including Fastin-XR R (FAS), 300 mg caffeine anhydrous (CAF), 250 mg acacia rigidula extract (AC), and cellulose placebo condition (PL) were examined in randomized order. Physiological activity was determined in 15 minute intervals immediately prior to and 1hr, 2hrs, and 3 hrs following ingestion. Metabolic activity was determined with open flow spirometry (VO2000, Medgraphics, St. Paul, MN) with outcomes including oxygen consumption (VO2), respiratory exchange ratio (RER), minute ventilation (VE) and oxygen extraction (VO2/VE). Hemodynamic activity was examined by measurement of heart rate (HR) and blood pressures (SBP, DBP). Values of metabolic and hemodynamic variables were adjusted into change scores relative to baseline levels. Statistical analyses were conducted using a 4x3 ANOVA for repeated measures with the accepted level of significance set at p<0.05. Results The VO2 change scores for 1hr, 2hrs, and hrs post ingestion were significantly greater with FAS (22.1%, 19.3%, 16.5%) compared with P (-2.6%, -1.7%, -2.0%), C (9.9%, 8.5%, 3.5%) and with AC (12.0%, 9.3%, 12.5%). The AC condition produced significantly greater VO2 compared with PL at all three time points with CAF displaying values greater than PL at 1hr and 2hrs post ingestion. No significant main or interaction effects were detected in values of RER. The FAS condition produced significantly greater elevations in VE compared with PL at all three time points. Both CAF and AC produced significantly greater VE change scores than PL, at 1hr post ingestion. Values of VO2/VE were significantly reduced from baseline at 1hr and 2hrs post with FAS and were significantly lower at 1hr post with CAF while AC produced elevations in VO2/VE of 5%, 4%, 7%. The changes in HR were significantly greater with FAS than PL at 2hrs and 3hrs post (9.4 and 11.1bpm) while AC resulted in 2.5 and 4.1 bpm greater HR at 1hr and 2hrs post which were significantly greater than P. FAS produced significantly greater blood pressure changes at all three time points compared with PL (SBP↑33%, 26%, 19%; DBP↑26%, 10%, 15%). Changes in DBP were significantly greater than PL with CAF at 1hr (9.4%) and 2hrs (7.1%). Blood pressures were not significantly affected by AC.

The effects of elevated endogenous GABA levels on movement-related network oscillations

The EEG/MEG signal is generated primarily by the summation of the post-synaptic potentials of cortical principal cells. At a microcircuit level, these glutamatergic principal cells are reciprocally connected to GABAergic interneurons and cortical oscillations are thought to be dependent on the balance of excitation and inhibition between these cell types. To investigate the dependence of movement-related cortical oscillations on excitation-inhibition balance, we pharmacologically manipulated the GABA system using tiagabine, which blocks GABA Transporter 1(GAT-1), the GABA uptake transporter and increases endogenous GABA activity. In a blinded, placebo-controlled, crossover design, in 15 healthy participants we administered either 15mg of tiagabine or a placebo. We recorded whole-head magnetoencephalograms, while the participants performed a movement task, prior to, one hour post, three hour post and five hour post tiagabine ingestion. Using time-frequency analysis of beamformer source reconstructions, we quantified the baseline level of beta activity (15-30Hz), the post-movement beta rebound (PMBR), beta event-related desynchronisation (beta-ERD) and movement-related gamma synchronisation (MRGS) (60-90Hz). Our results demonstrated that tiagabine, and hence elevated endogenous GABA levels causes, an elevation of baseline beta power, enhanced beta-ERD and reduced PMBR, but no modulation of MRGS. Comparing our results to recent literature (Hall et al., 2011) we suggest that beta-ERD may be a GABAA receptor mediated process while PMBR may be GABAB receptor mediated.

Aging differentially affects human skeletal muscle amino acid transporter expression when essential amino acids are ingested after exercise

Amino acid transporters have been proposed as regulators of protein synthesis. The primary aim of this study was to determine whether amino acid transporter expression is increased in human muscle following resistance exercise (RE) coupled with essential amino acid (EAA) ingestion, and whether a differential response occurs with aging. Secondly, we aimed to compare this response to a previous study examining RE alone. Young (n=7, 30±2yr) and older men (n=6, 70±2yr) ingested EAA 1h after RE. Muscle biopsies were obtained at rest and 3 and 6h post exercise to examine amino acid transporter mRNA and protein expression. In both age groups, RE+EAA increased mRNA of L-type amino acid transporter 1 (LAT1)/solute linked carrier (SLC)7A5, sodium-coupled neutral amino acid transporter 2 (SNAT2)/SLC38A2, and cationic amino acid transporter 1/SLC7A1 (p<0.05). SNAT2 protein increased in young at 3 and 6h (p<0.05), whereas old maintained higher LAT1 protein (p<0.05). Compared to RE alone, RE+EAA enhanced amino acid transporter expression only in young (p<0.05). RE increases muscle amino acid transporter expression in young and older adults, however, post exercise EAA ingestion enhances amino acid transporter expression only in young indicating that aging may influence the function of specific amino acid transporters.

Correlation of paired toxic plasma and saliva paracetamol concentrations following deliberate self‐poisoning with paracetamol

• Paracetamol is commonly used in deliberate self poisoning (DSP) and this requires blood sampling to refine risk assessment. If saliva concentrations agreed with plasma concentrations, then this could support the development of non-invasive testing. Our pilot work supports this hypothesis, but was largely confined to nontoxic concentrations. • We found agreement between the indications for treatment of paracetamol DSP based on plasma and saliva paracetamol concentrations. Saliva may hold promise as a non-invasive method to risk stratify paracetamol poisoning. Paracetamol is commonly used in deliberate self poisoning (DSP) and requires blood sampling to refine risk assessment. We aimed to test the agreement between plasma and saliva paracetamol concentrations in the toxic range in DSP. Contemporaneous paired plasma and saliva paracetamol concentrations were measured. Saliva was collected using a Sarstedt Salivette® device and the concentration was measured using a colorimetric method. Fifty-six patients (44, 78% female) median age 26 years (IQR 20-41) were enrolled. The median reported paracetamol ingestion was 10 g (IQR 6-14). Specimens were collected at a median of 4 h (IQR 4-5.3) post ingestion. The median plasma and saliva paracetamol concentrations were 29 mg l(-1) (IQR 8-110) and 38 mg l(-1) (IQR 10-105) respectively [mean difference 8 mg l(-1) , 95% confidence interval (CI) 2, 14]. Lin's concordance correlation was 0.97 (95% CI 0.96, 0.98). There were 15 patients who were treated with N-acetylcysteine. Their median reported paracetamol ingestion was 14 g (IQR 10-23) and samples were collected at a median of 4 h post ingestion. The median plasma and saliva paracetamol concentrations were 167 mg l(-1) (IQR 110-200) and 170 mg l(-1) (IQR 103-210) respectively (mean difference 15 mg l(-1) , 95% CI -4, 35). Lin's concordance correlation was 0.94 (95% CI 0.88, 0.99). No patient needing treatment would have been missed using saliva concentrations only. The agreement between the indications for treatment of paracetamol DSP based on plasma and saliva paracetamol concentrations extends into the toxic range, but with slightly lower agreement. Saliva may hold promise as a non-invasive method to risk stratify paracetamol poisoning.

Altered anesthetic requirements and carbon dioxide setpoint in chronic airway obstruction

Accidental ingestion of a foreign body into either tracheobronchial tree or esophagus is not an uncommon occurrence. However, there is limited literature available on sequelae of post foreign body ingestion--carbon dioxide set point and apneic threshold due to chronic respiratory acidosis. We report a case of chronic airway obstruction in a 14-month-old boy with prior history of battery ingestion and share our experience in the management.

Determination of cranberry proanthocyanidin A2 in human plasma and urine using LC‐MS/MS

A‐type proanthocyanidins (PAC) exhibit anti‐adhesion activity against uropathogenic Escherichia coli in vitro, putatively protecting against urinary tract infections. However, data on PAC bioavailability in humans has not been established due to lack of a method for their quantification. We conducted a single‐dose pharmacokinetic study to quantify PAC A2 (A2) in urine and plasma of 10 healthy adults. Fasted subjects consumed 237 mL low‐calorie, low‐sugar 54% cranberry juice cocktail (CJC). Blood and urine samples were collected at specified intervals before and up to 24 h following CJC consumption. Prior to LC‐MS/MS analysis of urinary A2, liquid‐liquid extraction using ethyl acetate and solid phase extraction (SPE) were sequentially employed to extract A2 and minimize matrix‐induced MS signal depression. A2 was extracted from plasma using SPE only. The limit of quantitation (LOQ) for A2 was 1.25 ng/mL in urine and 2.5 ng/mL in plasma. The recovery rate of A2 spiked into urine was 12%. The intra‐ and inter‐assay CV for A2 spiked into urine were 9.8% and 10.6%, respectively. The maximal concentration of A2 in urine was 24.4 ng/mg creatinine at 11.0 h post ingestion, while A2 was detected in plasma at concentrations below the LOQ. This study demonstrates for the first time the bioavailability of A2 following CJC consumption. The detected A2 in urine may be derived from the beverage and via metabolism by gut microflora.

A Finished Dietary Supplement Stimulates Lipolysis and Metabolic Rate in Young Men and Women

Background:Dietary supplements are often marketed to increase lipolysis and thermogenesis, with the proposed end result being weight loss and body fat reduction. It was the purpose of the present investigation to study the acute effects of a weight/fat loss supplement within a sample of healthy human subjects.Methods:Twelve subjects (men 24.8 ± 4.3 yrs; women 22.8 ± 0.4 yrs) ingested a dietary supplement (OxyELITE Pro™) or a placebo, on two separate days in a double-blind, cross-over design. Blood samples were collected immediately before ingestion, and at 60 and 120 minutes post ingestion, and analyzed for plasma glycerol and free fatty acids (FFA). Breath samples were collected immediately before ingestion and at 30, 60, 90, and 120 minutes post ingestion, for a measure of kilocalorie expenditure using indirect calorimetry. Area under the curve (AUC) was calculated. Heart rate and blood pressure were recorded at all times and rate pressure product (RPP) was calculated.Results:AUC was greater for supplement compared to placebo for glycerol (22.74 ± 1.98 μg · mL−1 · 2 hr−1 vs. 15.76 ± 1.36 μg · mL−1 · 2 hr−1; P = 0.001), FFA (1.62 ± 0.07 mmol · L−1· 2 hr−1 vs. 0.78 ± 0.12 mmol · L−1 · 2 hr−1; P < 0.0001), and kilocalorie expenditure (149 ± 7 kcal · 2 hr−1 vs. 122 ± 8 kcal · 2 hr−1; P = 0.005). Heart rate (P = 0.02), systolic blood pressure (P < 0.0001), and RPP (P = 0.002) were higher for supplement compared to placebo.Conclusion:Ingestion of OxyELITE Pro™ resulted in an increase in blood markers of lipolysis, as well as metabolic rate, during a two-hour post ingestion time period. An increase in hemodynamic variables was also observed. These findings are in reference to a sample of healthy men and women who were naïve to treatment with the dietary supplement. Additional work is needed to determine if the acute changes observed here would persist with chronic use of the supplement and possibly lead to weight/body fat loss over time.