In order to investigate the beneficial effects of 0.5 or 1.0 g/kg Korean garlic juice against the embryotoxicity of 20 mg/kg methylmercury chloride (MMC, CH3HgCl), pregnant Fisher 344 rats were simultaneously orally administered on day 7 of gestation. On day 20 of gestation the dams were laparotomized under ether anesthesia, and the fetuses were removed and examined for toxicity of methylmercury. Garlic juice depressed the toxicity in terms of some parameters. In the case of simultaneous treatment with 0.1 g/kg garlic juice and MMC, rates of increase were 17.5% in maternal body weight, 13.2% and 41.9% in fetal and litters' weight respectively, and 37.0% in fetal survival rate. Decreasing rates were 10.0% in maternal death rate, and 6.9% and 31.3% in pre- and post-implantation loss respectively. Decreasing rates of mercury levels in dams were 67.2% in liver, 57.6% in brain, 47.2% in kidney, 42.1% in spleen and 40.9% in blood. As well, decreasing rates of mercury level in fetuses were 54.9% in all body burden, 55.9% in liver, 46.7% in kidney and 37% in brain, respectively. The number of fetal ossification centers were reduced by 23.8% to 58.0% following simultaneous treatment with 1.0 g/kg garlic juice. These findings indicated that garlic juice effectively inhibited the embryotoxicity of methylmercury in pregnant Fischer 344 rats.
Animal ; Body Weight/drug effects ; Embryo/drug effects* ; Embryo Loss/prevention & control ; Embryo Loss/chemically induced ; Female ; Fetal Weight/drug effects ; Garlic* ; Methylmercury Compounds/toxicity* ; Methylmercury Compounds/pharmacokinetics ; Osteogenesis/drug effects ; Pregnancy ; Rats ; Rats, Inbred F344 ; Tissue Distribution

OBJECTIVEChronic lead (Pb) exposure during development is known to produce learning deficits. Nitric oxide participates in the synaptic mechanisms involved in certain forms of learning and memory. This study was designed to clarify whether Pb-induced impairment in learning and memory was associated with the changes of nitric oxide levels in mice brains.

METHODSSixty Balb/c mice aged 10 days were chosen. A model of lead exposure was established by drinking 0.025%, 0.05%, 0.075% lead acetate, respectively for 8 weeks. The controls were orally given distilled water. The ability to learn and memorize was examined by open field test, T-water maze test. In parallel with the behavioral data, NO level of hippocampus tissue was detected by biochemical assay.

RESULTSCompared with control groups, (1) the weight of 0.075% group was significantly reduced (P<0.05); (2) The number of times in mice attaining the required standards in T-water maze test was lower in 0.075% group (P<0.01). No significant difference was found between experimental and control groups in open field test (P>0.05); (3) NO level of mouse hippocampus tissue was decreased in 0.075% group (P<0.01).

CONCLUSIONSThe findings suggest that decreased hippocampus NO level may contribute to the Pb-induced deficits in learning and memory processes.

Animals ; Dose-Response Relationship, Drug ; Hippocampus ; drug effects ; metabolism ; Memory ; drug effects ; physiology ; Mice ; Mice, Inbred BALB C ; Nitric Oxide ; metabolism ; Organometallic Compounds ; toxicity ; Weight Loss

To investigate the effects of cigarette smoking in different manners on acute lung injury in rats.The commercially available cigarettes with tar of 1,5, 11 mg were smoked in Canada depth smoking (health canada method, HCM) manner, and those with tar of 11 mg were also smoked in international standard (ISO) smoking manner. Rats were fixed and exposed to mainstream in a manner of nose-mouth exposure. After 28 days, the bronchoalveolar lavage fluids from left lung were collected for counting and classification of inflammatory cells and determination of pro-inflammatory cytokines IL-1β and TNF-α. The right lungs were subjected to histological examination and determination of myeloperoxidase (MPO) and superoxide dismutase (SOD) activities and glutathione, reactive oxygen species (ROS) and malondialdehyde (MDA) levels.In both HCM and ISO manners, the degree of lung injury was closely related to the tar content of cigarettes, and significant decrease in the body weight of rats was observed after smoking for one week. In a HCM manner, smoking with cigarette of 11 mg tar resulted in robust infiltration of macrophages, lymphocytes and neutrophils into lungs, significant increase in IL-1β and TNF-α levels and MPO activities, and significant decrease in GSH levels and SOD activities and increase in ROS and MDA levels (all<0.05). Smoking with cigarette of 5 mg tar led to moderate increase in IL-1β and TNF-α levels, and MPO activities (all<0.05), and moderate decrease in GSH levels and SOD activities and increase of ROS and MDA levels (all<0.05). However, smoking with cigarette of 1 mg tar affected neither inflammatory cell infiltration nor IL-1β and TNF-α levels.Cigarette smoking in nose-mouth exposure manner can induce acute lung injury in rats; and the degree of lung injury is closely related to the content of tar and other hazards in cigarettes.
Acute Lung Injury ; etiology ; pathology ; physiopathology ; Animals ; Bronchoalveolar Lavage Fluid ; chemistry ; cytology ; Chemotaxis, Leukocyte ; drug effects ; Glutathione ; analysis ; drug effects ; Interleukin-1beta ; analysis ; drug effects ; Lung ; chemistry ; pathology ; Lymphocytes ; drug effects ; pathology ; Macrophages ; drug effects ; pathology ; Male ; Malondialdehyde ; analysis ; Neutrophil Infiltration ; drug effects ; Neutrophils ; drug effects ; pathology ; Peroxidase ; analysis ; drug effects ; Rats ; Reactive Oxygen Species ; analysis ; Smoking ; adverse effects ; Superoxide Dismutase ; analysis ; drug effects ; Tobacco Products ; adverse effects ; classification ; Tumor Necrosis Factor-alpha ; analysis ; drug effects ; Weight Loss ; drug effects

OBJECTIVETo investigate acrylamide (ACR)-induced subacute neurotoxic effects on the central nervous system (CNS) at the synapse level in rats.

METHODSThirty-six Sprague Dawley (SD) rats were randomized into three groups, (1) a 30 mg/kg ACR-treated group, (2) a 50 mg/kg ACR-treated group, and (3) a normal saline (NS)-treated control group. Body weight and neurological changes were recorded each day. At the end of the test, cerebral cortex and cerebellum tissues were harvested and viewed using light and electron microscopy. Additionally, the expression of Synapsin I and P-Synapsin I in the cerebral cortex and cerebellum were investigated.

RESULTSThe 50 mg/kg ACR-treated rats showed a significant reduction in body weight compared with untreated individuals (P < 0.05). Rats exposed to ACR showed a significant increase in gait scores compared with the NS control group (P < 0.05). Histological examination indicated neuronal structural damage in the 50 mg/kg ACR treatment group. The active zone distance (AZD) and the nearest neighbor distance (NND) of synaptic vesicles in the cerebral cortex and cerebellum were increased in both the 30 mg/kg and 50 mg/kg ACR treatment groups. The ratio of the distribution of synaptic vesicles in the readily releasable pool (RRP) was decreased. Furthermore, the expression levels of Synapsin I and P-Synapsin I in the cerebral cortex and cerebellum were decreased in both the 30 mg/kg and 50 mg/kg ACR treatment groups.

CONCLUSIONSubacute ACR exposure contributes to neuropathy in the rat CNS. Functional damage of synaptic proteins and vesicles may be a mechanism of ACR neurotoxicity.

Acrylamide ; toxicity ; Animals ; Cerebellum ; cytology ; drug effects ; Cerebral Cortex ; cytology ; drug effects ; Drug Administration Schedule ; Gait ; Gene Expression Regulation ; drug effects ; Male ; Neurons ; drug effects ; Neurotoxicity Syndromes ; pathology ; Rats ; Rats, Sprague-Dawley ; Synapses ; drug effects ; Synapsins ; genetics ; metabolism ; Synaptic Vesicles ; drug effects ; physiology ; Weight Loss ; drug effects

Vertical sleeve gastrectomy (VSG) is becoming more and more popular among the world. Despite its dramatic efficacy, however, the mechanism of VSG remains largely undetermined. This study aimed to test interferon (IFN)-γ secretion n of mesenteric lymph nodes in obese mice (ob/ob mice), a model of VSG, and its relationship with farnesoid X receptor (FXR) expression in the liver and small intestine, and to investigate the weight loss mechanism of VSG. The wild type (WT) mice and ob/ob mice were divided into four groups: A (WT+Sham), B (WT+VSG), C (ob/ob+Sham), and D (ob/ob+VSG). Body weight values were monitored. The IFN-γ expression in mesenteric lymph nodes of ob/ob mice pre- and post-operation was detected by flow cytometry (FCM). The FXR expression in the liver and small intestine was detected by Western blotting. The mouse AML-12 liver cells were stimulated with IFN-γ at different concentrations in vitro. The changes of FXR expression were also examined. The results showed that the body weight of ob/ob mice was significantly declined from (40.6±2.7) g to (27.5±3.8) g on the 30th day after VSG (P<0.05). At the same time, VSG induced a higher level secretion of IFN-γ in mesenteric lymph nodes of ob/ob mice than that pre-operation (P<0.05). The FXR expression levels in the liver and small intestine after VSG were respectively 0.97±0.07 and 0.84±0.07 fold of GAPDH, which were significantly higher than pre-operative levels of 0.50±0.06 and 0.48±0.06 respectively (P<0.05). After the stimulation of AML-12 liver cells in vitro by different concentrations of IFN-γ (0, 10, 25, 50, 100, and 200 ng/mL), the relative FXR expression levels were 0.22±0.04, 0.31±0.04, 0.39±0.05, 0.38±0.05, 0.56±0.06, and 0.35±0.05, respectively, suggesting IFN-γ could distinctly promote the FXR expression in a dose-dependent manner in comparison to those cells without IFN-γ stimulation (P<0.05). It was concluded that VSG induces a weight loss in ob/ob mice by increasing IFN-γ secretion of mesenteric lymph nodes, which then increases the FXR expression of the liver and small intestine.
Animals ; Body Weight ; Cell Line ; Gastrectomy ; methods ; Gene Expression ; Hepatocytes ; cytology ; drug effects ; metabolism ; Interferon-gamma ; biosynthesis ; pharmacology ; secretion ; Intestine, Small ; drug effects ; metabolism ; Liver ; drug effects ; metabolism ; Lymph Nodes ; drug effects ; metabolism ; Mesentery ; drug effects ; metabolism ; Mice ; Mice, Obese ; Obesity ; metabolism ; pathology ; surgery ; Receptors, Cytoplasmic and Nuclear ; agonists ; genetics ; metabolism ; Weight Loss

OBJECTIVES: Gentamicin is a potent aminoglycoside antibiotic. Ototoxicity and nephrotoxicity are the main side effects which restrict the use of gentamicin. Garlic with its intrinsic antioxidant activity may prove beneficial in prevention from ototoxicity. S-allylmercaptocysteine (SAMC), diallyl disulfide (DD), and S-allylcysteine (SAC) are three active compounds found in garlic. In this study, we investigated the effect of SAMC, DD, and SAC on the ototoxicity induced by gentamicin in rats, by using brainstem evoked response audiometry (BERA). METHODS: Thirty male Wistar rats with intact Preyer’s reflex initially weighing 220–260 g were randomly assigned to either the gentamicin injection with SAMC treatment group (Genta-w SAMC), DD treatment group (Genta-w DD), SAC treatment group (Genta-w SAC), gentamicin injection without any active compounds (AC) treatment groups (Genta-w/o AC), or control group (n=6 rats each group). Gentamicin was given 120-mg/kg body weight, intraperitoneally once daily for 25 days to subjects in all groups except the control group. SAMC 100-mg/kg, and DD 50-mg/kg body weight were given intragastrically, and SAC 250-mg/kg body weight was given intraperitoneally once daily to subjects in Genta-w SAMC, and Genta-w DD, and Genta-w SAC groups, respectively during the study. After 25 days hearing thresholds were evaluated by using BERA test. RESULTS: The mean amplitude of auditory thresholds (sensation level [SL]) measured by using BERA for the Genta-w SAMC, Genta-w DD, Genta-w SAC, Genta-w/o AC, and control groups were 22±8, 25±5, 30±9, 54±11, and 10±7 dB SL, respectively (mean±SD). The differences between every active compound group (Genta-w SAMC, Genta-w DD, and Genta-w SAC) and Genta-w/o AC were statistically significant (P<0.016). CONCLUSION: SAMC, DD, and SAC are derivative of garlic seems to attenuate aminoglycoside-induced hearing loss. The effect of SAMC and DD seems to be more prominent than that of SAC.
Animals ; Audiometry, Evoked Response ; Auditory Threshold ; Body Weight ; Brain Stem ; Drug-Related Side Effects and Adverse Reactions ; Garlic* ; Gentamicins* ; Hearing ; Hearing Loss ; Humans ; Male ; Rats ; Rats, Wistar ; Reflex

The phentermine, an appetite suppressant, has been widely applied in Korea since 2004. However, there have been relatively few reports about the efficacy and the safety of phentermine in Korea. The aim of this study is to verify the effect of phentermine on weight reduction and the safety in Korean patients. This randomized, double-blind, placebo- controlled study had been performed between February and July, 2005, in Seoul on 68 relatively healthy obese adults whose body mass index was 25 kg/m2 or greater. They received phentermine-HCl 37.5 mg or placebo once daily with behavioral therapy for obesity. The primary endpoints were the changes of body weight and waist circumference from the baseline in the intention-to-treat population. Mean decrease of both body weight and waist circumference in phentermine-treated subjects were significantly greater than that of placebo group (weight: -6.7 +/- 2.5 kg, p < 0.001; waist circumference: -6.2 +/- 3.5 cm, p < 0.001). Significant number of subjects in phentermine group accomplished weight reduction of 5% or greater from the baseline and 10% or more (p < 0.001). There were no significant differences in systolic and diastolic blood pressure between the groups (p = 0.122 for systolic BP; p = 0.219 for diastolic BP). Dry mouth and insomnia were the only statistically significant adverse events that occurred more frequently in phentermine group. Most side effects of phentermine were mild to moderate in intensity. Short-term phentermine administration induced significant weight reduction and reduction of waist circumference without clinically problematic adverse events on relatively healthy Korean obese people.
Weight Loss/*drug effects ; Risk Factors ; Phentermine/administration & dosage/adverse effects/*therapeutic use ; Obesity/*drug therapy ; Male ; Korea ; Humans ; Female ; Double-Blind Method ; Appetite Depressants/administration & dosage/adverse effects/*therapeutic use ; Adult

OBJECTIVETopiramate is a new broad-spectrum anti-epileptic drug. Decreased body weight and appetite are common side effects of topiramate. The side effect affects the growth and development in children greatly. Little is known about the mechanisms of topiramate-induced weight loss and decreased appetite in children with epilepsy in China and abroad. galanin is one of factors that affect appetite. It is a neuroendocrine peptide and play an important role in the control of appetite and body weight in the mechanism of hormone release. The purpose of this study was to explore the mechanism of topiramate-induced weight loss in children with epilepsy and the relation of weight loss with change of galanin, thereby to provide evidences for improvement of quality of life, compliance to treatment and reduce side effects of growth and development in children with epilepsy.

METHODSTotally 61 patients with especial epilepsy were enrolled into this study and the disease was defined by clinical manifestations and electroencephalography (EEG). Among them 32 cases had generalized seizures and 29 had local seizures. Sixteen normal children were enrolled as control group. The patients' age ranged from 0.5 to 14 (4.76 +/- 4.05) years and the patients were instructed to take 0.5 - 1 mg/kg of topiramate per day, with 0.5 - 1 mg/kg every 3 - 5 d increased to maximum of 3 - 8 mg/kg per day. Patients continued receiving the doses for 4 months. All patients' serum galanin levels and body height and weight and hepatic function were detected before and after antiepileptic drugs treatment. The galanin was detected by using radioimmunoassay.

RESULTSAfter treatment with topiramate (61 cases) for 4 months, plasma galanin [(22.01 +/- 8.12) pg/ml] declined as compared with baseline [(26.56 +/- 9.35) pg/ml, t = 2.85, P < 0.01] in children with epilepsy. Twenty-two of 61 patients lost weight, their plasma galanin concentration was significantly lower [(26.51 +/- 10.00) pg/ml vs. (20.45 +/- 8.09) pg/ml, t = 2.91, P < 0.01], but there was no significant change in the weight-gained patients (39/61) and control group (n = 16). In children with epilepsy, the mean value of body weight decreased as compared with the pre-treatment values, but the difference was not significant; however, the body-mass index (BMI) was significantly lower than that obtained before treatment (t = 8.628, P < 0.01). Eighteen of 22 patients who lost weight had decreased appetite, but only five of 39 patients who gained weight showed decreased appetite (chi(2) = 28.50, P < 0.001). The mean value of plasma galanin declined after treatment in patients (23 cases) with decreased appetite [(18.35 +/- 7.80) pg/ml vs. (27.28 +/- 6.90) pg/ml, t = 4.84, P < 0.001]; while plasma galanin did not change significantly after treatment in patients (38 cases) without decreased appetite [(24.23 +/- 7.66) pg/ml vs. (26.12 +/- 5.49) pg/ml, t = 1.04, P > 0.05].

CONCLUSIONTopiramate treatment may lower the body weight and reduce appetite in part of children with epilepsy which may be mediated by the reduced plasma galanin level.

Adolescent ; Anticonvulsants ; therapeutic use ; Appetite ; drug effects ; Case-Control Studies ; Child ; Child, Preschool ; Epilepsy ; drug therapy ; Female ; Fructose ; analogs & derivatives ; therapeutic use ; Galanin ; blood ; Humans ; Infant ; Male ; Weight Loss ; drug effects

OBJECTIVETo investigate activation of brown adipose tissue (BAT) stimulated by medium-chain triglyceride (MCT).

METHODS30 Male C57BL/6J obese mice induced by fed high fat diet (HFD) were divided into 2 groups, and fed another HFD with 2% MCT or long-chain triglyceride (LCT) respectively for 12 weeks. Body weight, blood biochemical variables, interscapular brown fat tissue (IBAT) mass, expressions of mRNA and protein of beta 3-adrenergic receptors (β3-AR), uncoupling protein-1 (UCP1), hormone sensitive lipase (HSL), protein kinase A (PKA), and adipose triglyceride lipase (ATGL) in IBAT were measured.

RESULTSSignificant decrease in body weight and body fat mass was observed in MCT group as compared with LCT group (P<0.05) after 12 weeks. Greater increases in IBAT mass was observed in MCT group than in LCT group (P<0.05). Blood TG, TC, LDL-C in MCT group were decreased significantly, meanwhile blood HDL-C, ratio of HDL-C/LDL-C and norepinephrine were increased markedly. Expressions of mRNA and protein of β3-AR, UCP1, PKA, HSL, ATGL in BAT were greater in MCT group than in LCT group (P<0.05).

CONCLUSIONOur results suggest that MCT stimulated the activation of BAT, possible via norepinephrine pathway, which might partially contribute to reduction of the body fat mass in obese mice fed high fat diet.

Adipose Tissue, Brown ; drug effects ; Adiposity ; drug effects ; Animals ; Dietary Fats ; administration & dosage ; pharmacology ; Ion Channels ; genetics ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mitochondrial Proteins ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Triglycerides ; chemistry ; pharmacology ; Uncoupling Protein 1 ; Weight Loss

BACKGROUNDIncretin-based therapies provide additional options for treating type 2 diabetes. We aimed to evaluate the efficacy and tolerability of exenatide monotherapy in obese patients with type 2 diabetes.

METHODSA 26-week, metformin controlled, parallel-group study was conducted among antidiabetic drug-naive obese patients aged > 18 years, and with type 2 diabetes. Participating patients were randomly assigned to receive exenatide or metformin treatments.

RESULTSFifty-nine patients (age (50.5 ± 8.6) years, body mass index (BMI) (30.2 ± 1.6) kg/m(2), and hemoglobin A1C (HbA(1C) (8.2 ± 1.2)%) were enrolled in the study. Glucose control and weight reduction improved in both groups receiving treatment. HbA(1C) and oral glucose tolerance test (OGTT) 2 hour glycemia reduction with exenatide was superior to that obtained with metformin ((-2.10 ± 1.79)% vs. (-1.66 ± 1.38)%, (-5.11 ± 2.68) mmol/L vs. (-2.80 ± 2.70) mmol/L, P < 0.05). Fast plasma glucose (FPG) reduction was not significantly different between the two groups ((-1.8 ± 2.0) mmol/L vs. (-1.6 ± 1.7) mmol/L, P > 0.05). Patients treated with exenatide achieved HbA(1C) of < 7% (97% of patients) and < 6.5% (79%) at end-point, vs. 93% and 73% with metformin (P > 0.05). Greater weight reduction was also achieved with exenatide ((-5.80 ± 3.66) kg) than with metformin ((-3.81 ± 1.38) kg, P < 0.01). Homeostasis model assessment of beta-cell function (HOMA-B) was not significantly increased, but the insulinogenic index and HOMA for insulin sensitivity (HOMA-S) were greatly improved in the exenatide group (P < 0.05). Nausea was the most common adverse effect in exenatide treatment (30% vs. 8%; P < 0.05), but most cases were of mild to moderate intensity. One case in the exenatide group was withdrawn early because of severe nausea. Hypoglycemia events were often observed during the first 4 weeks, with 12% of patients in the exenatide and 3.2% in metformin groups, respectively (P < 0.05). No incidents of severe hypoglycemia were reported.

CONCLUSIONSExenatide demonstrated more beneficial effects on HbA(1C), weight reduction and insulin resistance during 26 weeks of treatment, but there were more hypoglycemic events and mild-to-moderate nausea compared with metformin. These results suggested that exenatide monotherapy may provide a viable treatment option in newly developed type 2 diabetes.

Adult ; Diabetes Mellitus, Type 2 ; blood ; drug therapy ; Female ; Glycated Hemoglobin A ; metabolism ; Humans ; Hypoglycemia ; chemically induced ; Hypoglycemic Agents ; adverse effects ; therapeutic use ; Insulin Resistance ; Male ; Metformin ; adverse effects ; therapeutic use ; Middle Aged ; Nausea ; chemically induced ; Obesity ; blood ; drug therapy ; Peptides ; adverse effects ; therapeutic use ; Venoms ; adverse effects ; therapeutic use ; Weight Loss ; drug effects