Short Time Course Research Articles

The effect of exposure duration on visual acuity for letter optotypes and gratings.

This study compared the effects of exposure duration on letter and grating targets in a visual acuity (VA) task and determined if the broadband nature of letters accounts for their temporal summation characteristics. Log MAR (minimum angle of resolution) VA of five individuals (ages 25-36) was measured with a set of tumbling E optotypes for durations of 24 ms to 1s. The Es were either unfiltered or low-pass filtered to determine the object frequencies (cycles per letter; cplE) mediating VA. The retinal frequencies mediating VA for the unfiltered E (cycles per degree; cpdE) were derived from the ratio of cplE to MAR. Values of cpdE were compared to threshold retinal frequency obtained with band-limited Es and gratings to further evaluate the effects of stimulus bandwidth. Both log MAR and log cplE for the unfiltered E decreased as duration increased up to approximately 260 ms, and were constant thereafter. VA also improved for gratings and band-pass filtered Es, but over a shorter time course (approximately 150 ms). The effect of duration on VA for the broadband E, Gabor, and band-pass filtered E was similar when the object frequencies mediating VA were included in the definition of VA by converting to cpdE. The results indicate that the pattern of temporal integration for the tumbling E is related to its broadband nature. Band-pass filtered letters can simplify the interpretation of VA because the object frequency information mediating VA is known exactly and is independent of duration and letter size.

Different stressors induce differential responses of the CRH-stress system in the gilthead sea bream (Sparus aurata)

The hypothalamus–pituitary-interrenal (HPI) axis, involved in the regulation of the neuroendocrine stress responses, presents important players such as corticotropin-releasing hormone (CRH, generally considered as the initiator of this pathway) and CRH-binding protein (CRH-BP, considered as an antagonist of CRH function). CRH and CRH-BP full-length cDNA sequences were obtained from Sparus aurata by screening a brain cDNA library, and their phylogenetic analysis as well as their roles during acute and chronic stress responses were assessed. mRNA expression levels and plasma cortisol concentrations were measured by RT qPCR and ELISA, respectively, in S. aurata juveniles submitted to: i) different environmental salinities in a short-time course response; and ii) food deprivation during 21days. In addition, osmoregulatory and metabolic parameters in plasma corroborated a clear reorganization depending on the stress source/period. Salinity transfer induced stress as indicated by enhanced plasma cortisol levels, as well as by up-regulated CRH and down-regulated CRH-BP expression values. On the other hand, food deprivation did not affect both expression levels, although plasma cortisol concentrations were enhanced. These results suggest that different stressors are handled through different stress pathways in S. aurata.

Speech intelligibility can improve rapidly during exposure to a novel acoustic environment

In natural listening environments, the background noises and the acoustic spaces they occupy can vary greatly, both in their characteristics and in their impact on speech intelligibility. It has been suggested that listeners build up a statistical representation of ongoing noises; however, listeners can move around a room or move from one room to another, constantly changing both the background noises and the reverberation around them. If listeners are to make use of such statistics to aid in speech intelligibility, they must engage in a constant adaptation. We asked normal and hearing-impaired listeners to identify in real-time a stream of random target words in a contiguous series of novel acoustic environments lasting 13 s each, thus measuring the extent and time-course of changes in speech intelligibility that listeners experience in a new environment. The results from our task demonstrate that most listeners experience a rapid increase in speech intelligibility over several seconds of exposure to certain acoustic environments, but not to others. This suggests that there are classes or types of noises and reverberations that can be adapted to over a short time course and others that cannot. [Work supported by the MRC and the CSO.]

An Interesting Case of Disappearing Murmur

Cardiovascular manifestations in a patient with congestive heart failure, which disappeared in short course of time, ignited the idea to think of unusuality from common rheumatic heart disease (RHD). Cardiac events that reversed within 2 days of admission in a chronic alcoholic, whose diagnosis puzzled us, are presented here. A retrospective conclusion of wet beri-beri is made, as all the haemodynamic sequelae vanished with thiamine replacement.

The effects of non-ionic contrast medium on the hemorheology in vitro and in vivo

Contrast media are the commonly used agents in radiology. However, because of their characteristics of high osmolality, high viscosity, and chemical toxicity, the administrations of contrast media have been shown to cause adverse effects especially on hemorheology in short time course. The present study is to find the effects of a non-ionic contrast medium, iopromide, on the hemorheology in long time course both in vitro and in vivo. For in vitro treatment, human peripheral blood samples were incubated with contrast medium at 37°C for 0.5, 1 and 2 h. For in vivo study, about 15 ml of contrast medium was injected into rabbits and blood samples were collected at 0.5, 2, 6, and 24 h after the bolus injection. Hemorheological parameters were examined. Results showed that hematocrit adjusted whole blood viscosity increased significantly at 1 h after in vitro treatment of contrast medium, while it decreased at 0.5 h and remained low till 6 h after bolus injection. Ektacytometer showed that erythrocyte deformability decreased to the lowest level at 2 h in vitro and it dropped at 0.5 h and resumed to normal after 2 h in vivo. Erythrocyte small deformation indices were reduced by contrast medium in both in vitro and in vivo studies. Erythrocyte orientation index was also reduced in in vivo study. Erythrocyte electrophoresis rates at all time points decreased but osmotic fragility did not change in both studies. These impaired hemorheological parameters may disturb the microcirculation and cause adverse effects in patients with kidney diseases.

The toxic effect of manganese on the acetylcholinesterase activity in rat brains.

Manganese (Mn) is a naturally occurring element and an essential nutrient for humans and animals. However, exposure to high levels of Mn may cause neurotoxic effects. Accumulation of manganese damages central nervous system and causes Parkinson's disease-like syndrome called manganism. Mn neurotoxicity has been suggested to involve an imbalance between the DAergic and cholinergic systems. The pathological mechanisms associated with Mn neurotoxicity are poorly understood, but several reports have established it is mediated by changing of AChE activity that resulted in oxidative stress. Therefore we focused the effect of Mn in AChE activity in the rat's brain by MnCl2 injection intraperitoneally and analyzed their brains after time intervals. This study used different acute doses in short time course and different chronic doses at different exposing time to investigate which of them (exposing dose or time) is more important in Mn toxic effect. Results showed toxic effect of Mn is highly dose dependent and AChE activity in presence of chronic dose in 8 weeks reaches acute dose in only 2 days.

IL-17 and TNF Synergistically Modulate Cytokine Expression while Suppressing Melanogenesis: Potential Relevance to Psoriasis

Inflammation-associated pigmentation changes are extremely common, but the etiology behind this clinical observation remains elusive. Particularly, it is unclear how the myriad of cytokines known to be involved in inflammatory skin processes affect epidermal melanocytes. We sought to determine how IL-17 and TNF influence normal human melanocytes, as these two cytokines have been implicated in various skin diseases. IL-17 and TNF jointly stimulated broad inductions of cytokines , including melanoma mitogens CXCL1 and IL-8. Moreover, IL-17 and TNF synergistically inhibited pigmentation-related signaling and melanin production, and induced keratinocytes production of β-defensin 3, an antagonist for melanocortin-receptor 1. When analyzing psoriasis lesions that are known to over express IL-17 and TNF, we observed an increase in melanocyte number and a simultaneous decrease in pigmentation signaling. Furthermore, therapeutic neutralization of TNF and IL-17 with mAbs results in a rapid recovery of pigment gene expression in psoriasis lesions. These results demonstrate that IL-17 and TNF can impact both the growth and pigment production of melanocytes, which may contribute to the pigmentation changes associated with psoriasis. These findings may allow the development of novel therapeutics for pigmentary disorders and bring new insights into the immune milieu surrounding melanocytes and related neoplasms.

Selective and divided attention: Spatial orienting in a semantic classification task

Preliminary data from our lab using non-lexical stimuli (alphabet letters) suggests that auditory spatial attention may act as a filter with some spatial roll-off (seen in patterns of false alarms to targets in unattended spatial streams). The current project extends that research, examining the interaction between auditory spatial attention and lexical activation. In a semantic classification task, listeners respond to words of a target class only when they occur in designated spatial streams. Streams are temporally interleaved (in random spatial order) to minimize energetic masking. Given that tone-complex experiments suggest a short time course for exogenous spatial reorientations (at least 150 ms but less than 450 ms) [Roberts et al., J. Exp. Psychol. Human 35, 1178–1191 (2009)] when compared to lexical activation (~400 ms) [Pylkkänen et al., Brain Lang 81, 666–678 (2002)], we predict that the additional processing required for semantic classification could paradoxically reduce false alarms in spatial locations proximal to the target stream(s), by delaying the response decision beyond the temporal scope of the exogenous orienting response. We discuss findings in relation to models of exogenous/endogenous attention and lexical processing.

Degradation of microbial fluorescence biosignatures by solar ultraviolet radiation on Mars

AbstractRecent and proposed robotic missions to Mars are equipped with implements to expose or excavate fresh material from beneath the immediate surface. Once brought into the open, any organic molecules or potential biosignatures of present or past life will be exposed to the unfiltered solar ultraviolet (UV) radiation and face photolytic degradation over short time courses. The key question, then, is what is the window of opportunity for detection of recently exposed samples during robotic operations? Detection of autofluorescence has been proposed as a simple method for surveying or triaging samples for organic molecules. Using a Mars simulation chamber we conduct UV exposures on thin frozen layers of two model microorganisms, the radiation-resistant polyextremophile Deinococcus radiodurans and the cyanobacterium Synechocystis sp. PCC 6803. Excitation–emission matrices (EEMs) are generated of the full fluorescence response to quantify the change in signal of different cellular fluorophores over Martian equivalent time. Fluorescence of Deinococcus cells, protected by a high concentration of carotenoid pigments, was found to be relatively stable over 32 h of Martian UV irradiation, with around 90% of the initial signal remaining. By comparison, fluorescence from protein-bound tryptophan in Synechocystis is much more sensitive to UV photodegradation, declining to 50% after 64 h exposure. The signal most readily degraded by UV irradiation is fluorescence of the photosynthetic pigments – diminished to only 35% after 64 h. This sensitivity may be expected as the biological function of chlorophyll and phycocyanin is to optimize the harvesting of light energy and so they are readily photobleached. A significant increase in a ∼450 nm emission feature is interpreted as accumulation of fluorescent cellular degradation products from photolysis. Accounting for diurnal variation in Martian sunlight, this study calculates that frozen cellular biosignatures would remain detectable by fluorescence for at least several sols; offering a sufficient window for robotic exploration operations.

Use of the pentagastrin dog model to explore the food effects on formulations in early drug development

The ability to extrapolate dosage performance from in vitro to in vivo situations has an important role in early drug development. In parallel, the Beagle dog has come to represent a useful animal model for extrapolation to humans especially when drugs formulated for humans are to be tested. In this article, the pentagastrin-induced Beagle dog model was validated internally to show that in the colony the dogs were generally responsive to known doses of pentagastrin that produces effects similar to gastrin in the stomach, i.e., increasing gastric acid production and lowering gastric pH. The effect was observed with a short time course, maximum pH lowering was observed between 0.5 and 1h with return to baseline at 2–4h. The dog stomach pH is a better representative of the human fasted stomach with this pretreatment. The ultimate goal was to use these animals in a food effect studies to predict the behavior of formulations in humans. The results for 4 compounds were provided in the dog and a clear relationship between the effect of food in the dog and the effect of food in humans was observed. While the directionality (positive or negative) of the effect could be adequately predicted, the extent of the effect could not be predicted for all the tested formulations of the 4 compounds. The data will be used to generate a database of known compounds from which a correlation can be drawn to make future predictions using the pentagastrin dog model.

Disruption of persistent nociceptive behavior in rats with learning impairment.

Despite the subjective nature of pain experience with cognitive and affective dimensions, preclinical pain research has largely focused on its sensory dimension. Here, we examined the relationship between learning/memory and nociceptive behavior in rats with combined learning impairment and persistent nociception. Learning impairment was induced by bilateral hippocampal injection of a mixed Aβ solution, whereas persistent nociception produced in these rats by complete Freund’s adjuvant-induced ankle inflammation. Those rats with learning impairment showed a diminished development of thermal hyperalgesia and mechanical allodynia and a shorter time course of nociceptive behavior without alteration of their baseline nociceptive threshold. In rats with pre-established hyperalgesia and allodynia due to ankle inflammation, bilateral intra-hippocampal injection of cycloheximide (a protein synthesis inhibitor) promoted the earlier recovery of nociceptive behavior. Moreover, expression of Aβ, NR1 subunit of the N-methyl-D-aspartate receptor, and protein kinase Cγ was upregulated, whereas the choline acetyl transferase expression was downregulated, in the hippocampus, thalamus, amygdala, and/or spinal cord of rats with combined learning impairment and persistent nociception. The data indicate that learning impairment could disrupt the response to a state of persistent nociception, suggesting an important role for cognitive maladaptation in the mechanisms of chronic pain. These results also suggest that a preclinical model of combined learning impairment and persistent nociception may be useful to explore the brain mechanisms underlying the transition from acute to chronic pain.

P 79. Effects of brain derived neurotrophic factor polymorphism on cortical excitability measured by transcranial magnetic stimulation

Variation in the brain derived neurotrophic factor (BDNF) gene affects neural plasticity. With the commonly studied single nucleotide polymorphism (SNP) BDNF Val66Met, the Met allele is associated with reduced plasticity. However, little is known about the baseline excitability measures of rarer form Met/Met compared to other forms and the response to plasticity and metaplasticity protocols using transcranial magnetic stimulation (TMS). To investigate the effects of the BDNF Val66Met SNP on motor cortex excitability, inhibition, facilitation, plasticity and metaplasticity. From 177 healthy volunteers we selected 7 subjects with the rare (around 5–10% of population) Met/Met genotype and compared them to 9 age-and gender-matched Val allele carriers on various excitability measures using TMS. Motor threshold, recruitment curves, short and long interval intracortical inhibition (SICI and LICI), short interval intracortical facilitation (SICF) and time courses of these circuits were studied. Potentiation [high frequency rTMS and paired associative stimulation at 25 ms latency (PAS25)] and depression (low frequency rTMS and PAS10) protocols as well as interactions of these plasticity protocols (metaplasticity) were studied with sessions separated at least by a week (6 sessions in total). Met/Met subjects showed higher motor threshold (61.7 ± 8.6% stimulator output compared to 48.7 ± 9.5; p = 0.01), and less steep recruitment curves (significant main effects and interaction for BDNF genotype and TMS intensity). There was no significant difference between the groups in terms of intracortical inhibitory circuits, the time course and recruitment curves for SICI/LICI. There was a trend for reduced facilitation at the peaks (1.5, 3 and 4 ms) for SICF in Met/Met compared to non-Met/Met subjects. For plasticity protocols, there was significantly higher potentiation of MEP amplitude with high frequency rTMS (main effects of BDNF genotype) and a trend of greater MEP depression with PAS10 in non-Met/Met subjects. No difference was noted in the other plasticity and metaplasticity protocols. Met/Met subjects had higher motor threshold, less steep MEP recruitment curves and reduced peaks of SICF, implying lower cortical excitability compared to non-Met/Met genotypes. This decreased excitability in Met/Met subjects is associated with less potentiation induced by high frequency rTMS. Our study is ongoing and more subjects are being recruited to compare the three BDNF genotypes (Met/Met, Val/Met and Val/Val genotypes) of subjects. Support by Canadian Institutes of Health Research.

P28 Identification of a novel slow-releasing hydrogen sulfide donor for cancer therapy

It has previously been reported that hydrogen sulfide (H 2 S) exerts both pro- and anti-apoptotic activity in different cultured cells [1] , [2] , [3] . However, the precise effect and mechanism(s) involved remain unclear. We have previously reported that the slow-releasing H 2 S donor, GYY4137 [4] (morpholin-4-ium 4 methoxyphenyl(morpholino) phosphinodithioate) exerts anti-cancer activity both in vivo and in vitro [5] . In this report, GYY4137 showed a distinct anti-proliferative effect across a broad range of cancer cell lines but did not affect proliferation in normal cell lines. In contrast, NaHS, which releases large amounts of H 2 S over a short time course, failed to affect proliferation of either cancer or normal cell lines. This work raised the possibility that H 2 S donors, with differing H 2 S-releasing kinetics, may be of value to kill cancer (but not normal) cells. To this end, in preliminary compound screening tests, we examined a number of novel compounds all of which are GYY4137 analogues, for the ability to kill both cancer and normal cell lines. We also determined the H 2 S-releasing profiles of these compounds using the conventional methylene blue spectrophotometric assay to monitor H 2 S release. In the course of this study, we identified an additional, slow-releasing H 2 S donor, FW1010. FW1010 can slow release H 2 S more than GYY4137 over a few days. Incubation of either FW1010 or GYY4137 (400 μ M) in culture medium led to the generation of low concentrations of H 2 S over 6 days. Comparing FW1010 to GYY4137, FW1010 exhibited enhanced, concentration-dependent killing of different human cancer cell lines (e.g. MCF7, HepG2, U2OS, HL-60, MDA-MB-231, SKOV3, and OVCAR10) but had little or only minimal killing effect in a normal cell line (WI38).We propose that the ability of GYY4137 and FW1010 to kill cancer cells in vitro is likely due to their ability to release H2S slowly over a period of several days. The precise mechanism of action is not clear but measuring intracellular pH (pHi) by confocal microscopy we noted that FW1010 treatment caused a significant concentration-dependent, decline in intracellular pH in MCF7 cells and that this effect was greater than that of GYY4137 at identical concentrations. In contrast, neither GYY4137 nor FW1010 affected pHi in a normal cell line (i.e. WI38). Moreover, both GYY4137 and FW1010 significantly increased lactate release and glucose uptake in a concentration dependent manner in MCF7 (but not in W138) cells. FW1010 was more potent than GYY4137 in this regard. These experiments provide further evidence of the anti-cancer effect of GYY4137 in vitro and identify a new analogue of this compound with seemingly greater efficacy. Additional studies are ongoing to define further the possible mechanisms of action of both FW1010 and GYY4137.

Bariatric surgery rapidly improves mitochondrial respiration in morbidly obese patients

Obesity and its attendant comorbidities are an emerging epidemic. Chronic metabolic inflammation (metainflammation) is thought to precipitate obesity-associated morbidities; however, its mechanistic progression is poorly understood. Moreover, although interventions such as diet, exercise, and bariatric surgery can control body weight, their effects on metainflammation are also poorly understood. Recently, metainflammation and the pathobiology of obesity have been linked to mitochondrial dysfunction. Herein we examined the effects of bariatric surgery on mitochondrial respiration as an index of resolving metainflammation in morbidly obese patients. This institutional review board-approved study involved morbidly obese patients (body mass index > 35 kg/m(2)) undergoing sleeve gastrectomy or Roux-en-Y gastric bypass. Mitochondrial respiration was assessed in peripheral blood monocytes and in skeletal muscle samples before surgery and at 12 weeks after surgery. Patient biometrics, homeostasis model assessment-estimated insulin resistance (HOMA-IR) score, C-reactive protein, and lipid profile were analyzed. Twenty patients were enrolled and showed an average percent excess body weight loss of 30.3% weight loss at 12 weeks after surgery. Average HOMA-IR score decreased from 3.0 to 1.2 in insulin-resistant patients. C-reactive protein, an index of metainflammation, showed a modest decrease. Lipid profile remained stable. Intriguingly, mitochondrial basal and maximal respiration rates in peripheral blood monocytes increased after surgery. Basal rates of skeletal muscle mitochondrial respiration were unchanged, but the maximal respiration rate trended toward an increase after surgery. Cellular and tissue mitochondrial respiration increased in a morbidly obese patient cohort after laparoscopic bariatric surgery. These changes were consistent in patients with postsurgical weight loss. Importantly, no significant changes or improvements occurred in canonical indices used to assess recovery after bariatric surgery over this short time course. Thus, increased mitochondrial respiration may represent a novel biomarker of early improvement and positive outcome after surgery in morbidly obese patients.

Differentiation from human pluripotent stem cells of cortical neurons of the superficial layers amenable to psychiatric disease modeling and high-throughput drug screening

Cortical neurons of the superficial layers (II-IV) represent a pivotal neuronal population involved in the higher cognitive functions of the human and are particularly affected by psychiatric diseases with developmental manifestations such as schizophrenia and autism. Differentiation protocols of human pluripotent stem cells (PSC) into cortical neurons have been achieved, opening the way to in vitro modeling of neuropsychiatric diseases. However, these protocols commonly result in the asynchronous production of neurons typical for the different layers of the cortex within an extended period of culture, thus precluding the analysis of specific subtypes of neurons in a standardized manner. Addressing this issue, we have successfully captured a stable population of self-renewing late cortical progenitors (LCPs) that synchronously and massively differentiate into glutamatergic cortical neurons of the upper layers. The short time course of differentiation into neurons of these progenitors has made them amenable to high-throughput assays. This has allowed us to analyze the capability of LCPs at differentiating into post mitotic neurons as well as extending and branching neurites in response to a collection of selected bioactive molecules. LCPs and cortical neurons of the upper layers were successfully produced from patient-derived-induced PSC, indicating that this system enables functional studies of individual-specific cortical neurons ex vivo for disease modeling and therapeutic purposes.

Exercise and Cardiac Preconditioning Against Ischemia Reperfusion Injury

Cardiovascular disease (CVD), including ischemia reperfusion (IR) injury, remains a major cause of morbidity and mortality in industrialized nations. Ongoing research is aimed at uncovering therapeutic interventions against IR injury. Regular exercise participation is recognized as an important lifestyle intervention in the prevention and treatment of CVD and IR injury. More recent understanding reveals that moderate intensity aerobic exercise is also an important experimental model for understanding the cellular mechanisms of cardioprotection against IR injury. An important discovery in this regard was the observation that one-to-several days of exercise will attenuate IR injury. This phenomenon has been observed in young and old hearts of both sexes. Due to the short time course of exercise induced protection, IR injury prevention must be mediated by acute biochemical alterations within the myocardium. Research over the last decade reveals that redundant mechanisms account for exercise induced cardioprotection against IR. While much is now known about exercise preconditioning against IR injury, many questions remain. Perhaps most pressing, is what mechanisms mediate cardioprotection in aged hearts and what sex-dependent differences exist. Given that that exercise preconditioning is a polygenic effect, it is likely that multiple mediators of exercise induced cardioprotection have yet to be uncovered. Also unknown, is whether post translational modifications due to exercise are responsible for IR injury prevention. This review will provide an overview the major mechanisms of IR injury and exercise preconditioning. The discussion highlights many promising avenues for further research and describes how exercise preconditioning may continue to be an important scientific paradigm in the translation of cardioprotection research to the clinic.

Molecular Biology Techniques Q&A

Molecular Biology Techniques Q&A

A Method to Construct Gene Regulatory Networks to Estimate and Calculate Time Delays

In general, the motive of this research is to infer gene regulatory network in order to clarify the basis consequences of biological process at the molecular level. Time course gene expression profiling dataset has been widely used in basic biological research, especially in transcription regulation studies since the microarray dataset is a short time course gene expression dataset and have lots of errors, missing value, and noise. In this research, R library is implemented in this method to construct gene regulatory which aims to estimate and calculate the time delays between genes and transcription factor. Time delay is the parameters of the modeled time delay linear regression models and a time lag during gene expression change of the regulator genes toward target gene expression. The constructed gene regulatory network provided information of time delays between expression change in regulator genes and its target gene which can be applied to investigate important time-related biological process in cells. The result of time delays and regulation patterns in gene regulatory network may contribute into biological research such as cell development, cell cycle, and cell differentiation in any of living cells.

Effects of growth hormone withdrawal in obese premenopausal women

We previously reported improved body composition and cardiovascular risk markers plus a small decrease in glucose tolerance with GH administration vs placebo for 6 months to abdominally obese premenopausal women. The objective of this study was to determine whether the effects of GH treatment on cardiovascular risk markers, body composition and glucose tolerance in obese women persist 6 months after GH withdrawal. Fifty abdominally obese premenopausal women completed a trial of rhGH vs placebo for 6 months; thirty-nine women completed a subsequent 6-month withdrawal observation period. IGF-I, body composition by CT, (1) H-MRS and DXA, serum cardiovascular risk markers, oral glucose tolerance test (OGTT). IGF-I standard deviation scores (SDS) within the GH group were -1.7 ± 0.1 (pretreatment),-0.1 ± 0.3 (after 6 months of GH) and -1.7 ± 0.1 (6 months post-GH withdrawal). Six months after GH withdrawal, total abdominal and subcutaneous adipose tissue, total fat, trunk fat, trunk/extremity fat, hsCRP, apoB, LDL, and tPA were higher than at the 6-month (GH discontinuation) timepoint (P ≤ 0.05). All body composition and cardiovascular risk markers that had improved with GH returned to baseline levels by 6 months after GH discontinuation, as did fasting and 2-h OGTT glucose levels. The effects of GH administration to abdominally obese premenopausal women have a short time-course. The beneficial effects on body composition and cardiovascular risk markers, and the side effect of altered glucose tolerance returned to pretreatment levels after GH withdrawal. There was no suppression of endogenous IGF-I levels, which returned to baseline after GH withdrawal.

Blood lactate concentration after exposure to conducted energy weapons (including TASER® devices): is it clinically relevant?

In previous studies, blood lactate concentration (BLac) consistently increased in anesthetized animals and in human subjects after exposures to TASER(®) conducted energy weapons (CEWs). Some have suggested the increased BLac would have detrimental consequences. In the current review, the following are evaluated: (a) the nature of muscle contractions due to CEWs, (b) general aspects of increased BLac, (c) previous studies of conventional neuromuscular electrical stimulation and CEW exposures, and (d) BLac in disease states. On the basis of these analyses, one can conclude that BLac, per se (independent of acidemia), would not be clinically relevant immediately after short-duration CEW applications, due to the short time course of any increase.