Unimpaired thermogenic response to noradrenaline in genetic (ob/ob) and hypothalamic (MSG) obese mice

1984 ◽  
Vol 4 (4) ◽  
pp. 343-349 ◽  
Author(s):  
A. G. Duloo ◽  
D. S. Miller
Keyword(s):  
Metabolic Rate ◽  
Room Temperature ◽  
Low Dose ◽  
Monosodium Glutamate ◽  
Whole Body ◽  
High Dose ◽  
Obese Mice ◽  
Subcutaneous Injections ◽  
Noradrenaline Administration ◽  
Thermogenic Response

The thermogenic response to noradrenaline administration was investigated at 25° in two models of obese mice (genetic ob/ob obesity of the ‘QEC’ strain and monosodium-glutamate-induced obesity) and in their respective lean littermates. Subcutaneous injections of a low dose of noradrenaline (I00 μg/kg body wt.) eJevated metabolic rate by about 3096 in both obese models but not in their respective lean counterparts. In contrast, the increase in metabolic rate after injections of a high dose of noradrenaline (600 μg/kg body wt.) was of a similar magnitude in both lean and obese animals: metabolic rate was increased by 70–80%. These results indicate that the overall whole body thermogenic capacity is unimpaired at room temperature in this ‘QEC’ strain of ob/ob mice and in the hypothalamic damaged obese mice. Obesity in these models is therefore not associated with a reduced ability to respond to noradrenaline but could rather be due to a failure to release noradrenaline.

A New Hafnium-Beryllium System Prioduced by Ion Implantation and Annealing Techniques

1983 ◽  
Vol 27 ◽  
Author(s):  
J.C. Soares ◽  
A.A. Melo ◽  
M.F. DA Silva ◽  
E.J. Alves ◽  
K. Freitag ◽  
...  
Keyword(s):  
Ion Implantation ◽  
Single Crystals ◽  
Room Temperature ◽  
Low Dose ◽  
Correlation Method ◽  
High Dose ◽  
Tetrahedral Sites ◽  
Time Differential ◽  
Before And After ◽  
Beryllium Foil

ABSTRACTLow and high dose hafnium imolanted beryllium samoles have been prepared at room temperature by ion implantation of beryllium commercial foils and single crystals. These samples have been studied before and after annealing with the time differential perturbed angular correlation method (TDPAC) and with Rutherford backscattering and channeling techniques. A new metastable system has been discovered in TDPAC-measurements in a low dose hafnium implanted beryllium foil annealed at 500°C. Channeling measurements show that the hafnium atoms after annealing, are in the regular tetrahedral sites but dislocated from the previous position occupied after implantation. The formation of this system is connected with the redistribution of oxygen in a thin layer under the surface. This effect does not take place precisely at the same temperature in foils and in single crystals.

scholarly journals Selective regulation of cellular and secreted multimeric adiponectin by antidiabetic therapies in humans

2009 ◽  
Vol 297 (3) ◽  
pp. E767-E773 ◽  
Author(s):  
Susan A. Phillips ◽  
Jacqueline Kung ◽  
Theodore P. Ciaraldi ◽  
Charles Choe ◽  
Louis Christiansen ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Low Dose ◽  
Whole Body ◽  
Serum Adiponectin ◽  
High Dose ◽  
Hmw Adiponectin ◽  
Dose Combination ◽  
Cell Expression ◽  
The Impact

Adiponectin, an insulin-sensitizing factor secreted from adipose tissue, is decreased in individuals with type 2 diabetes (T2D) and increased in response to thiazolidinedione (TZD) therapy. Changes in its secretion and assembly into higher-order forms affect insulin sensitivity. To determine the relative potency of TZDs on intra-adipocyte multimerization and secretion of adiponectin, we assessed the impact of in vivo low- or high-dose rosiglitazone treatment alone or combined with metformin in subjects with T2D. T2D subjects received high-dose rosiglitazone (8 mg/day), high-dose metformin (2,000 mg/day), or low-dose combination rosiglitazone-metformin therapy (4 mg + 1,000 mg/day) for 4 mo. All subjects were then switched to high-dose rosiglitazone-metformin combination therapy (8 mg + 2,000 mg/day) for another 4 mo. Low-dose rosiglitazone increased serum adiponectin, whereas the high dose increased both adipocyte content and serum adiponectin levels. TZDs selectively increased the percentage of circulating adiponectin in the potent, high-molecular-weight (HMW) form. No TZD effects were evident on multimer distribution in the cell. Expression of the chaperone protein ERp44, which retains adiponectin within the cell, was decreased by TZD treatment. No changes occurred in Ero1-Lα expression. Metformin had no effect on any of these measures. Increases in adiponectin correlated with improvements in insulin sensitivity. In vivo, TZDs have apparent dose-dependent effects on cellular and secreted adiponectin. TZD-mediated improvements in whole body insulin sensitivity are associated with increases in circulating but not cellular levels of the HMW adiponectin multimer. Finally, TZDs promote the selective secretion of HMW adiponectin, potentially, in part, through decreasing the expression of the adiponectin-retaining protein ERp44.

scholarly journals 2,4-dinitrophenol downregulates genes for diabetes and fatty liver in obese mice

2015 ◽  
Author(s):  
Qian Gao ◽  
Jiang He ◽  
Tao Liao ◽  
Qing-Ping Zeng
Keyword(s):  
Fatty Liver ◽  
High Fat Diet ◽  
Low Dose ◽  
Dependent Diabetes Mellitus ◽  
High Dose ◽  
Low Grade ◽  
Obese Mice ◽  
Nonalcoholic Fatty Liver ◽  
Mitochondrial Uncoupler ◽  
Anti Inflammation

Whether obesity is a disease or a risk factor of chronic diseases including diabetes and fatty liver remains debating. We report here that a high-fat diet (HFD) alone or HFD and intramuscular injection of mice with a high dose (1.2 mg/kg) of lipopolysaccharide (LPS) induces the peripheral noninflammatory obesity. In contrast, HFD and intraperitoneal injection of mice with a low dose (0.25 mg/kg) of LPS induces the visceral low-grade inflammatory obesity. While the noninsulin dependent diabetes mellitus (NIDDM)- and nonalcoholic fatty liver disease (NAFLD)-related genes are globally upregulated in HFD+low-dose LPS mice, NIDDM and NAFLD genes are not extensively upregulated in HFD+high-dose LPS mice. The mitochondrial uncoupler 2,4-dinitrophenol (DNP) was found to exert a weight-reducing effect in obese mice by downregulating NF-κB-primed inflammatory response accompanying with NIDDM and NAFLD genes, thereby abrogating inflammatory hepatic injury. In conclusion, visceral low-grade inflammatory obesity that predisposes NIDDM and NAFLD can be ameliorated by DNP via anti-inflammation.

scholarly journals Study of the Long-Term and Dose Dependent Effects of Methylphenidate and Monosodium Glutamate on the Hormonal Alterations of the Pituitary-Testicular Axis and Sperm Analysis in Adolescence Rats

2017 ◽  
Vol 74 (1) ◽  
pp. 75
Author(s):  
Azad ABDOLLAHZADEH ◽  
Davoud KIANIFARD ◽  
Gholamreza VAFAEI SAIAH
Keyword(s):  
Reproductive System ◽  
Low Dose ◽  
Sperm Count ◽  
Monosodium Glutamate ◽  
Normal Function ◽  
High Dose ◽  
Sperm Analysis ◽  
Testicular Weight ◽  
Dose Dependent

Methylphenidate is one of the most common medications that used for maintaining alertness and improving of attention which, may lead to increase of the risk of substance abuse in some cases. Monosodium glutamate is a food additive which has toxic effects on human and animal’s tissues.  Due to the various side effects of methylphenidate and monosodium glutamate on the reproductive system, the aim of this study was to evaluate the long-term and dose dependent effects of these compounds on the reproductive system during adolescence through hormonal and sperm analysis. Low and high dose of methylphenidate and monosodium glutamate was administrated to adolescent rats for 60 days. Body and testicular weight measurement, pituitary gonadotropins and testosterone levels assays and sperm analysis was performed on euthanized animals. The results showed that, high dose of methylphenidate and low dose of monosodium glutamate and/or combination form of these two compounds have more effects on body and testicular weight alterations. Low dose of methylphenidate with high dose of monosodium glutamate influenced some alterations in follicle stimulating hormone. The distinct use of methylphenidate and monosodium glutamate led to slight elevation in sperm count but simultaneous use of these compounds led to significant elevation of sperm count. The administration of these compounds had negative effect on sperm motility and viability. It has been concluded that, coadministration of methylphenidate and monosodium glutamate through the influence of brain-pituitary-testicular axis and induction of some hormonal alterations may lead to changes in normal function of reproductive system

scholarly journals An Investigation Into the Beneficial Effects of High-Dose Interferon beta 1-a, Compared to Low-Dose Interferon Beta 1-a (the base therapeutic regimen) in moderate to severe COVID-19

2021 ◽  
Author(s):  
Ilad Alavi Darazam ◽  
Firouze Hatami ◽  
Mohammad Mahdi Rabiei ◽  
Mohamad Amin Pourhoseingholi ◽  
Minoosh Shabani ◽  
...  
Keyword(s):  
Regression Model ◽  
Low Dose ◽  
Interferon Beta ◽  
Cox Regression ◽  
Intervention Group ◽  
Control Group ◽  
P Value ◽  
High Dose ◽  
Cox Regression Model ◽  
Subcutaneous Injections

Abstract Introduction: Coronavirus disease 2019 (COVID-19) has been a serious obstacle in front of public health. Interferon-beta 1a (IFN-β 1a) has been used to treat patients with COVID-19. We aimed to compare the effectiveness of high dose IFN-β 1a compared to low dose IFN-β 1a (the base therapeutic regimen) in moderate to severe COVID-19 cases.Methods: In this randomized, controlled, and clinical trial, eligible patients with confirmed SARS-CoV-2 infections were randomly assigned to receive one of the two following therapeutic regimens: The intervention group was treated with high dose IFN-β 1a (Recigen) (Subcutaneous injections of 88μg (24,000 IU) on days 1, 3, 6) + lopinavir /ritonavir (Kaletra) and the control group was treated with low dose IFN-β 1a (Recigen) (Subcutaneous injections of 44μg (12,000 IU) on days 1, 3, 6) + lopinavir /ritonavir (Kaletra) (400mg/100 mg twice a day for 10 days, orally, in all two groups). Result:A total of 168 COVID- 19 confirmed patients underwent randomization; 83 were assigned to the intervention group and 85 were assigned to the control group. Median Time To Clinical Improvement (TTIC) for cases treated with low dose of IFN-β1a was shorter than that for cases treated with high dose of IFN-β1a (6 vs10 days; P=0.018). Hazard Ratio for TTCI in the Cox regression model was 1.56 (95% CI: 1.05-2.30, P-value=0.026). Due to differences between some baseline clinical factors between intervention and control group, we; therefore, performed an adjusted analysis by including spo2, D-dimer and CRP in Cox regression model. The model failed to reach a significant difference between two groups. The adjusted HR was 1.37 (95% CI: 0.88-2.12, P-value=0.16). No difference was observed in terms of mortality between two groups. ConclusionThe use of high-dose IFN-β 1a did not improve TTCI in hospitalized patients with moderate to severe COVID-19. Also, it has not any significant effect in mortality reduction compared with treating with low-dose IFN-β 1a.Trial registration: The trial was confirmed by the Ethics in Medical Research Committee of the Shahid Beheshti University of Medical Sciences. signed informed consents were obtained from all the participants or their legally authorized representatives. This trial has been registered as ClinicalTrials.gov, NCT04521400.

scholarly journals Biological Effects of Continuous Low-Dose-Rate Irradiation in Silkworms and Mice: Growth Promotion and Tumor Transplantability

Dose-Response ◽  
2018 ◽  
Vol 16 (4) ◽  
pp. 155932581881175 ◽  
Author(s):  
Masahiro Nakashima ◽  
Chikao Sugie ◽  
Zhen Wang ◽  
Takuhito Kondo ◽  
Yoshihiko Manabe ◽  
...  
Keyword(s):  
Body Weight ◽  
Dose Rate ◽  
Low Dose ◽  
Growth Promotion ◽  
High Dose Rate ◽  
Whole Body ◽  
High Dose ◽  
Silkworm Larvae ◽  
Low Dose Rate ◽  
Emt6 Tumor

A previous study showed that continuous low-dose-rate irradiation promoted the growth of silkworm larvae. This study aimed to confirm that finding, determine the optimal dose rate for growth promotion, and compare low- and high-dose-rate irradiation in silkworms, while also investigating the effects of the radiation-emitting sheet on growth and tumor transplantability in mice. Silkworm eggs were placed on low-dose-emitting sheets with 4 different dose rates (γ-ray rate: 1.7 -22.4 μSv/hour) or on control sheets. The other groups of silkworm larvae received single whole-body X-irradiation (0.1-50 Gy), and subsequent body weight changes were monitored. Starting at 3 weeks old, Balb/c mice were bred on the same sheets, and body weight change was measured. Seven weeks later, the mice were used to investigate the transplantability of EMT6 tumor cells cultured in vitro. The silkworms bred on the 13.4- and 22.4-μSv/hour sheets became larger than the control. Single 50-Gy irradiation suppressed the growth of silkworms. An increase in the time to EMT6 tumor development was observed in low-dose-rate-irradiated mice. This study confirmed growth promotion of silkworms by continuous low-dose radiation and demonstrated growth suppression at a high dose rate. Growth promotion was not observed in mice; further studies using higher dose-rate sheets may be warranted.

Albumin-induced plasma volume expansion: diurnal and temperature effects

1984 ◽  
Vol 56 (5) ◽  
pp. 1361-1368 ◽  
Author(s):  
R. W. Hubbard ◽  
W. T. Matthew ◽  
D. Horstman ◽  
R. Francesconi ◽  
M. Mager ◽  
...  
Keyword(s):  
Relative Humidity ◽  
Plasma Volume ◽  
Volume Expansion ◽  
Room Temperature ◽  
Low Dose ◽  
Rapid Expansion ◽  
High Dose ◽  
Heat Acclimatization ◽  
Plasma Volume Expansion ◽  
Reliable Procedure

To develop a reliable procedure for the acute expansion of plasma volume (PV), 26 male volunteers were randomly assigned to either a thermoneutral (25 degrees C and 40% relative humidity) or hot-dry (37 degrees C and 25% relative humidity) environment; subsequently each subject was seated for at least 1 h and then infused intravenously with either 100 or 200 ml of a 25% albumin solution or 0.9% saline. On the day before each infusion, PV was estimated by dye dilution using indocyanine green. Net percent change in PV (using hematocrit and hemoglobin values) was calculated at 1, 3, 6, 9, 12, and 24 h postinfusion. The PV of subjects residing in the heat after a 100-ml saline infusion increased significantly over 1-h values at 6, 9, and 12 h postinfusion but not at 24 h. The same trend, although not significant, was apparent at room temperature. The data suggest a slow isooncotic circadian pattern of PV expansion and contraction. The infusion of hyperoncotic albumin produced rapid expansion of plasma volume. With the low dose (25 g) at 1 h postinfusion, the expansion was 379 +/- 102 ml in the heat and 301 +/- 160 ml at room temperature. With the high dose (50 g) at 1 h postinfusion, the expansion was 479 +/- 84 ml in the heat and 427 +/- 147 ml at room temperature. The high dose produced an expansion that persisted for at least 9 h in subjects in either environment. The data suggest a mechanism for the retention of fluid during heat acclimatization and a useful procedure for plasma volume expansion in humans.

scholarly journals 2,4-dinitrophenol downregulates genes for diabetes and fatty liver in obese mice

2015 ◽  
Author(s):  
Qian Gao ◽  
Jiang He ◽  
Tao Liao ◽  
Qing-Ping Zeng
Keyword(s):  
Fatty Liver ◽  
High Fat Diet ◽  
Low Dose ◽  
Dependent Diabetes Mellitus ◽  
High Dose ◽  
Low Grade ◽  
Obese Mice ◽  
Nonalcoholic Fatty Liver ◽  
Mitochondrial Uncoupler ◽  
Anti Inflammation

Whether obesity is a disease or a risk factor of chronic diseases including diabetes and fatty liver remains debating. We report here that a high-fat diet (HFD) alone or HFD and intramuscular injection of mice with a high dose (1.2 mg/kg) of lipopolysaccharide (LPS) induces the peripheral noninflammatory obesity. In contrast, HFD and intraperitoneal injection of mice with a low dose (0.25 mg/kg) of LPS induces the visceral low-grade inflammatory obesity. While the noninsulin dependent diabetes mellitus (NIDDM)- and nonalcoholic fatty liver disease (NAFLD)-related genes are globally upregulated in HFD+low-dose LPS mice, NIDDM and NAFLD genes are not extensively upregulated in HFD+high-dose LPS mice. The mitochondrial uncoupler 2,4-dinitrophenol (DNP) was found to exert a weight-reducing effect in obese mice by downregulating NF-κB-primed inflammatory response accompanying with NIDDM and NAFLD genes, thereby abrogating inflammatory hepatic injury. In conclusion, visceral low-grade inflammatory obesity that predisposes NIDDM and NAFLD can be ameliorated by DNP via anti-inflammation.

scholarly journals Interleukin-1 Receptor Antagonist Attenuates Regional Neuronal Cell Death and Cognitive Dysfunction after Experimental Brain Injury

1999 ◽  
Vol 19 (10) ◽  
pp. 1118-1125 ◽  
Author(s):  
Kristin L. Sanderson ◽  
Ramesh Raghupathi ◽  
Kathryn E. Saatman ◽  
David Martin ◽  
Gerald Miller ◽  
...  
Keyword(s):  
Brain Injury ◽  
Total Dose ◽  
Receptor Antagonist ◽  
Motor Function ◽  
Low Dose ◽  
Interleukin 1 ◽  
High Dose ◽  
Subcutaneous Injections ◽  
Fluid Percussion ◽  
Interleukin 1 Receptor Antagonist

The effect of systemic administration of human recombinant interleukin-1 receptor antagonist (rhIL-1ra) on behavioral outcome and histopathologic damage after lateral fluid-percussion brain injury of moderate severity was evaluated. In study 1, brain-injured Sprague Dawley rats received timed subcutaneous injections beginning 15 minutes after injury of either 100 mg/kg rhIL-1ra (high dose, total dose = 1900 mg/kg), 10 mg/kg rhIL-1ra (low dose, total dose = 190 mg/kg), or vehicle over 7 days. No effect of low-dose rhIL-1ra was observed in study 1. High-dose rhIL-1ra significantly attenuated posttraumatic neuronal loss in the injured hippocampal CA3 region ( P < 0.05), dentate hilus ( P < 0.05), and cortex ( P < 0.05) but impaired recovery of motor function at 7 days after trauma ( P < 0.05). In study 2, rats were pretrained to learn a visuospatial task in a Morris water maze, subjected to fluid-percussion brain injury or sham treatment, and randomly assigned to receive multiple subcutaneous injections at timed intervals of 100 mg/kg rhIL-1ra (total dose = 900 mg/kg) or vehicle over 42 hours, followed by continuous infusion of a lower concentration of rhIL-1ra (20 mg/kg/day, total dose = 100 mg/kg), or vehicle for 5 days using subcutaneously implanted osmotic minipumps. Postinjury administration of rhIL-1ra significantly attenuated cognitive deficits compared with vehicle-treated animals at 42 hours ( P < 0.05) but did not affect motor function at 48 hours, 1 week, and 2 weeks. These results suggest that inhibitors of cytokine pathways may be therapeutically useful for the treatment of brain trauma.

Marked depression of radiation-induced emesis in frogs following prior exposure to a brief dose of X-rays

2002 ◽  
Vol 80 (8) ◽  
pp. 828-832 ◽  
Author(s):  
Yukihisa Miyachi ◽  
Takahisa Koike ◽  
Kenzo Muroi ◽  
Tomoko Kanao ◽  
Taro Kawamoto ◽  
...  
Keyword(s):  
Low Dose ◽  
Lethal Dose ◽  
Prior Exposure ◽  
Whole Body ◽  
High Dose ◽  
X Rays ◽  
Sham Control ◽  
Toxic Dose ◽  
Acute Emesis ◽  
Radiation Induced

Acute emesis response to harmful doses of X-rays on frogs (Rana porosa porosa) was examined. Results showed that the number of radioemesis events following exposure to 0.85 Gy was slightly higher than in the sham control animals. The increase in emesis action became more pronounced when the total dose of radiation was raised to 2.5 Gy. Only 1 frog out of a total of 12 did not show vomiting following radiation, while no response was observed in sham control animals. Note that animals in which the low dose rate of radiation was applied to whole body did not display any changes in the emesis response relative to control animals. The present studies, and those by others, showed that a brief dose of X-rays prior to a second exposure to a sub-lethal dose might induce a tolerance to radiation. An additional experiment was conducted to examine whether a small conditioning dose could induce a depression of radioemesis (tolerance) following an exposure to high dose X-ray. With prior exposure to 0.3 Gy, only 1 frog out of a total of 5 frogs vomited as a result of radiation exposure. Suppression of the emetic response became significant when the pre-radiation dose was decreased to 0.1 Gy. On the contrary, increasing the small conditioning dose to 0.5 Gy resulted in a remarkable rise of radiation-induced emesis. This results indicate that exposure to the smaller dose of X-rays elicits a tolerance effect to toxic dose level of radiation.Key words: emesis, hormesis, low-dose X-rays, resistance, frog.

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