OBJECTIVE: Sphingomyelin synthase (SMS) catalyzes the conversion of ceramide to sphingomyelin and sits at the crossroads of sphingolipid biosynthesis. SMS has 2 isoforms: SMS1 and SMS2. Although they have the same SMS activity, they are different enzymes with distinguishable subcellular localizations and cell expression patterns. It is conceivable that these ...

RationaleWe have previously demonstrated that the importance of endothelium-derived hyperpolarizing factor (EDHF) increases as the vessel size decreases and that endothelium-derived hydrogen peroxide (H(2)O(2)) is an EDHF in animals and humans, for which endothelial nitric oxide synthase (eNOS) is the major source. Recent studies have suggested the important role of ...

This study investigated the potential convulsive activity of ciprofloxacin in mice and the possible mechanism(s) of this activity. Intraperitoneal (i.p.) administration of ciprofloxacin into mice resulted in convulsive seizures in a dose-dependent manner. The clonic median convulsant dose (CD(50)) of ciprofloxacin in mice was increased by pretreatment with dizocilpine, alpha-lipoic ...

Systemic lupus erythematosus (SLE) patients display impaired endothelial nitric oxide synthase (eNOS) function required for normal vasodilatation. SLE patients express increased compensatory activity of inducible nitric oxide synthase (iNOS) generating excess nitric oxide that may result in inflammation. We examined the effects of genetic deletion of NOS2 and NOS3, encoding ...

Nitric oxide synthase 3 (NOS3) produces nitric oxide (NO) in endothelial cells, which stimulates cyclic guanosine monophosphate (cGMP) production and thereby mediates pulmonary vasodilation. Inhibition of cGMP enzymatic cleavage by sildenafil might be involved in lung growth stimulating processes in pulmonary hypoplasia. The aim of this study was to discover ...

Mice with endothelial nitric oxide synthase (eNOS) deletions have defined the crucial role of eNOS in vascular development, homeostasis, and pathology. However, cell specific eNOS function has not been determined, although an important role of eNOS has been suggested in multiple cell types. Here we have generated a floxed eNOS ...

Garlic has been widely recognized as a cardioprotective agent. However, the molecular mechanism of its cardioprotective effects is not well established. Here we hypothesized that aqueous garlic homogenate may mediate cardioprotection via nitric oxide (NO). Mice were fed with saline and aqueous garlic homogenate (250 and 500mgkg(-1)day(-1) orally) for 30days. ...

Testosterone is necessary for the development of male pattern baldness, known as androgenetic alopecia (AGA); yet, the mechanisms for decreased hair growth in this disorder are unclear. We show that prostaglandin D(2) synthase (PTGDS) is elevated at the mRNA and protein levels in bald scalp compared to haired scalp of ...

Inflammation is a critical component of atherosclerosis. IL-1 is a classic proinflammatory cytokine that has been linked to atherosclerosis. A clinical trial has been launched in which an antibody specific for IL-1β is being studied for its effects on cardiovascular events in patients with atherosclerosis. In this issue of the ...

Hepatorenal syndrome occurs in patients with advanced liver cirrhosis and is associated with functional renal impairment and poor prognosis. These patients present a challenge to physicians and management strategies. Although various pharmacological therapies are available, large randomized controlled trials are required to determine which treatment modality is most effective to ...

Introduction: Septic shock is highly lethal and its incidence is increasing. Although TNF-α plays a key role in sepsis pathogenesis, past efforts to therapeutically inhibit it had limited success. However, there is continued interest in such therapies and there are now ongoing Phase II sepsis trials testing the effects of ...

Fear conditioning, extinction, and renewal were evaluated in adult (6-month-old) and aging (17-month-old) male C57Bl/6 mice. Mice were subjected to five tone-shock trials and later exposed to 150 tone-alone trials. Thereafter, all mice showed little fear in the extinction context. Adult mice demonstrated return of fear in a distinct context ...

To obtain experiences and expert opinion on treatment of SSc patients with TNF-α antagonists. An investigation was carried out among the EUSTAR centres into their expertise on use of TNF-α antagonists. Assessment forms on the frequency of TNF-α inhibitor use were distributed to EULAR Scleroderma Trials and Research Group (EUSTAR) ...

The root of Acanthopanax senticosus (also called Eleutherococcus senticosus or Siberian ginseng) has been used extensively in China, Russia and Japan as an adaptogen to fight against stress and fatigue. The present study was designed to ascertain the anti-fatigue property of Acanthopanax senticosus by load-weighted swimming test, sleep deprivation test, ...

Several vegetables have been shown to possess cytoprotective and antioxidant effects with various mechanisms of action. The aim of this study was to determine the antioxidant effects and mechanism underlying of Syzygium gratum, a dietary and herbal plant commonly found in the Southeast Asia. Additionally, its effects on the induction ...

Several meta-analyses indicate that there is an inverse genetic correlation between ethanol preference drinking and ethanol withdrawal severity, but limited work has characterized ethanol consumption in 1 genetic animal model, the Withdrawal Seizure-Prone (WSP) and-Resistant (WSR) mouse lines selected for severe or mild ethanol withdrawal, respectively. We determined whether line ...

Ethanol disturbs astroglial growth and differentiation and causes functional alterations. Furthermore, many signalling molecules produced by astrocytes contribute to these processes. The aim of the present study was to investigate the influence of ethanol and its primary metabolite, acetaldehyde, on TNF-alpha and IL-6 production in a rat cortical astrocyte primary ...

GABA is synthesized from glutamate by glutamate decarboxylase (GAD), which exists in two isoforms, that is, GAD65 and GAD67. In line with GAD65 being located in the GABAergic synapse, several studies have demonstrated that this isoform is important during sustained synaptic transmission. In contrast, the functional significance of GAD65 in ...

Voluntary oral ethanol consumption in rodents is generally limited by strong taste-aversion in these species. Historically, this has been overcome by combining ethanol with a sweetener, typically sucrose or saccharine, and then slowly 'fading' away the sweetener. While useful in most instances, this approach has not proven as successful for ...

CYP2A5 metabolizes xenobiotics and activates hepatocarcinogens, and induction occurs in response to hepatic damage and cellular stress. We evaluated whether ethanol can elevate CYP2A5 and whether CYP2E1 plays a role in the ethanol induction of CYP2A5. Wild-type (WT), CYP2E1 knockout (KO), and CYP2E1 knockin (KI) mice were fed ethanol for ...

The depressant and anticonvulsant activities of iso-6-cassine (ISO) from Senna spectabilis (0.5, 1.0 and 1.5mg/kg) injected by oral route in mice caused a significant decrease in the motor activity of animals when compared with the control group, up to 30days after the administration and at dose of 1.5mg/kg, it reduced ...

Alcohol-induced increases in nucleus accumbens glutamate actively regulate alcohol consumption, and the alcohol responsiveness of corticoaccumbens glutamate systems relates to genetic variance in alcohol reward. Here, we extend earlier data for inbred mouse strain differences in accumbens glutamate by examining for differences in basal and alcohol-induced changes in the striatal ...

Neurotensin receptors (NTS) regulate a variety of the biological functions of neurotensin (NT) in the central nervous system. Although NT and neurotensin receptors type 1 (NTS1) are implicated in some of the behavioral effects of ethanol, the functional roles of neurotensin receptors type 2 (NTS2) in ethanol intoxication and consumption ...

This study investigated the in vitro antioxidant activity of (E)-2-benzylidene-4-phenyl-1,3-diselenole (BPD), the anticonvulsant effect of BPD on seizures induced by pilocarpine (PC), pentylenetetrazole (PTZ) and 4-aminopyridine (4-AMP) and the mechanism involved. BPD antioxidant activity in vitro was investigated using sodium nitroprusside (SNP) and malonate-induced thiobarbituric acid reactive species (TBARS) and ...

Growth restriction, craniofacial dysmorphology, and central nervous system defects are the main diagnostic features of fetal alcohol syndrome. Studies in humans and mice have reported that the growth restriction can be prenatal or postnatal, but the underlying mechanisms remain unknown.We recently described a mouse model of moderate gestational ethanol exposure ...

The recent construct of Self-leadership, which includes cognitive and behavioral strategies of managing oneself, has yet to be examined for associations with central personality dimensions such as the Big Five and their higher-order factors (Alpha, Beta). It was hypothesized that Self-leadership and its subfacets would be significantly correlated with all ...

A functional connection between the circadian timing system and alcohol consumption is suggested by multiple lines of converging evidence. Ethanol consumption perturbs physiological rhythms in hormone secretion, sleep, and body temperature; and conversely, genetic and environmental perturbations of the circadian system can alter alcohol intake. A fundamental property of the ...

Experience with stress situations during early development can have long-lasting effects on stress- and anxiety-related behaviors. Importantly, this can also favor drug self-administration. These studies examined the effects of chronic social isolation and/or variable stress experiences during early development on subsequent voluntary ethanol intake in adult male and female C57BL/6J ...

Alcoholic liver disease is mediated via activation of TLR4 signaling; MyD88-dependent and -independent signals are important contributors to injury in mouse models. Adiponectin, an anti-inflammatory adipokine, suppresses TLR4/MyD88-dependent responses via induction of heme oxygenase-1 (HO-1). Here we investigated the interactions between chronic ethanol, adiponectin, and HO-1 in regulation of TLR4/MyD88-independent ...

Selectively breeding lines of mice and rats to differ in alcohol intake has proven useful for defining which traits correlate with high alcohol drinking behavior, as well as for creating animal models of alcoholism. This study reports the derivation of two novel sets of selected lines, High Alcohol Preferring (HAP) ...

Brief, non-harmful seizures can activate endogenous protective programmes which render the brain resistant to damage caused by prolonged seizure episodes. Whether protection in epileptic tolerance is long-lasting or influences the subsequent development of epilepsy is uncertain. Presently, we investigated the relationship between hippocampal pathology, neuropeptide Y rearrangement and spontaneous seizures ...

Large-scale synchronous firing of neurons during seizures is modulated by electrotonic coupling between neurons via gap junctions. To explore roles for connexin36 (Cx36) gap junctions in seizures, we examined the seizure threshold of connexin36 knockout (Cx36KO) mice using a pentylenetetrazol (PTZ) model. Mice (2-3months old) with Cx36 wildtype (WT) or ...

Progesterone (P) is an endogenous anticonvulsant hormone. P is being evaluated as a treatment for epilepsy, traumatic brain injury, and other complex neurological conditions. Preclinical and clinical studies suggest that P appears to interrupt epileptogenic events. However, the potential disease-modifying effect of P in epileptogenic models is not widely investigated. ...

The aim of the study was to determine the influence of N-(ortho-carboxyanilinomethyl)-p-isopropoxyphenylsuccinimide [o-CAMIPPS], N-(meta-carboxyanilinomethyl)-p-isopropoxyphenylsuccinimide [m-CAMIPPS], and N-(para-carboxyanilinomethyl)-p-isopropoxyphenylsuccinimide [p-CAMIPPS] on the protective activity of four classical antiepileptic drugs (carbamazepine, phenobarbital, phenytoin and valproate) in the mouse maximal electroshock seizure model. The results indicate that all tested succinimide derivatives administered intraperitoneally at ...

Inbred long-sleep and short-sleep mice (ILS and ISS) were selectively bred for differential sensitivity to the sedative effects of ethanol. Lines of mice derived from these progenitors have been used to identify several quantitative trait loci (QTLs) mediating loss of the righting reflex due to ethanol (LORE). This study investigated ...

Cardiospermum halicacabum roots have been used traditionally for the treatment of epilepsy and anxiety disorders. The purpose of this study was to characterize the putative phytoconstituents present in the ethanolic root extract having anxiolytic activity using an elevated plus-maze (EPM) and light dark transition model. Control mice were orally treated ...

We describe a new cable-free, non-telemetric method for synchronized electrophysiological and video recordings of seizure activity in freely moving mice. The electrophysiological recordings were made by a head-mounted 4-channel data-logging device, allowing the mouse to move freely in its cage, and even to be moved from cage to cage under ...

A major pathway for chronic ethanol-induced liver injury is ethanol-induced oxidant stress. Several pathways contribute to mechanisms by which ethanol induces oxidant stress. Although some studies support a role for cytochrome P450 2E1 (CYP2E1), others do not. Most previous studies were conducted in the intragastric infusion model of ethanol administration. ...

The adolescent period is characterized by a specific sensitivity to the effects of alcohol, which is believed to contribute to the enhanced risks of alcohol dependence when drinking is initiated early during adolescence. In adolescent rodents, while the reduced sensitivity to the sedative effects of ethanol has been well characterized, ...

Persistent down-regulation in the expression of the hyperpolarization-activated HCN1 cation channel, a key determinant of intrinsic neuronal excitability, has been observed in febrile seizure, temporal lobe epilepsy, and generalized epilepsy animal models, as well as in patients with epilepsy. However, the role and importance of HCN1 down-regulation for seizure activity ...

Excitotoxicity plays a major role in various neurological disorders. In this study, we explored the behavioral and neurotoxic effects of intraventricular NMDA administration in mice. After NMDA injection, acute seizures were followed by impairments in locomotor activity, motor performance on a rotarod, and climbing ability. Mice killed 1 day after ...

Mutations of the LGI1 (leucine-rich, glioma-inactivated 1) gene underlie autosomal dominant lateral temporal lobe epilepsy, a focal idiopathic inherited epilepsy syndrome. The LGI1 gene encodes a protein secreted by neurons, one of the only non-ion channel genes implicated in idiopathic familial epilepsy. While mutations probably result in a loss of ...

Sepsis is a major cause of mortality worldwide. Acute or chonic ethanol exposure typically suppresses innate immunity and inflammation and increases the risk of mortality in patients with sepsis. The study described here was designed to address the mechanism(s) by which acute ethanol exposure alters the course of sepsis. Ethanol ...

Clinical and laboratory evidence suggests that alcohol consumption dysregulates immune function. Burn patients who consume alcohol before their injuries demonstrate higher rates of morbidity and mortality, including acute respiratory distress syndrome, than patients without alcohol at the time of injury. Our laboratory observed higher levels of proinflammatory cytokines and leukocyte ...

Berberine, an isoquinoline alkaloid is reported to modulate several neurotransmitter systems like N-methyl-D-aspartate, nitric oxide and serotonin, which modulate convulsions. In addition, it is suggested that Berberis vulgaris may be useful in treatment of convulsion and epilepsy. Therefore, the present study investigated the effects of berberine in pentylenetetrazole, maximal electroshock ...

OBJECTIVE: To determine the analgesic effect of ethanolic extract of Nigella sativa seeds on experimentally-induced pain in albino mice. STUDY DESIGN: Randomized controlled trial (RCT). PLACE AND DURATION OF STUDY: Physiology Department, Services Institute of Medical Sciences (SIMS), Lahore, from May to September, 2009. Methodology: The study was carried out ...

Calpains constitute a superfamily of Ca2+-dependent cysteine proteases, indispensable for various cellular processes. Among the 15 mammalian calpains, calpain 8/nCL-2 and calpain 9/nCL-4 are predominantly expressed in the gastrointestinal tract and are restricted to the gastric surface mucus (pit) cells in the stomach. Possible functions reported for calpain 8 are ...

Clinical and laboratory evidence suggests that alcohol consumption prior to burn injury leads to dysregulated immune function and subsequent higher rates of morbidity and mortality. Our laboratory previously observed higher levels of pro-inflammatory cytokines and leukocyte infiltration in the lungs of mice following ethanol and burn injury. To understand the ...

Ethanol exposure during early life has been shown to permanently alter the circadian expression of clock regulatory genes and the beta-endorphin precursor proopiomelanocortin (POMC) gene in the hypothalamus. Ethanol also alters the stress- and immune-regulatory functions of beta-endorphin neurons in laboratory rodents. Our aim was to determine whether the circadian ...

Pioglitazone, a peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist, is used in inflammatory brain diseases, and it was shown to protect against seizures in genetically epileptic mice. The present study, therefore, verified its potential antiepileptic effect in pentylenetetrazole (PTZ)-induced acute seizures and kindling in mice. Kindling was induced in male Swiss albino ...