scholarly journals Dose-Dependent Effects of Central Leptin Gene Therapy on Genes That Regulate Body Weight and Appetite in the Hypothalamus

2001 ◽  
Vol 4 (2) ◽  
pp. 139-145 ◽  
Author(s):  
Harveen Dhillon ◽  
Satya P Kalra ◽  
Pushpa S Kalra
1966 ◽  
Vol 15 (03/04) ◽  
pp. 349-364 ◽  
Author(s):  
A.H Özge ◽  
H.C Rowsell ◽  
H.G Downie ◽  
J.F Mustard

SummaryThe addition of trace amounts of adrenaline to whole blood in plasma in vitro increased factor VIII, factor IX and whole plasma activity in the thromboplastin generation test. This was dose dependent.Adrenaline infusions less than 22 (μg/kg body weight in normal dogs accelerated clotting, increased factor IX, factor VIII and whole plasma activity in the thromboplastin generation test and caused a fall in blood pH. In a factor IX deficient dog, there was no increase in factor IX activity. After adrenaline infusions, however, the other changes occurred and were of the same order of magnitude as in the normal. Adrenaline in doses greater than 22 μg/kg body weight did not produce as great an effect on clotting in normal or factor IX deficient dogs. The platelet count in the peripheral blood was increased following the infusion of all doses of adrenaline. These observations suggest that the accelerating effect of adrenaline on clotting is not mediated through increase in activity of a specific clotting factor.


2021 ◽  
pp. 089719002110215
Author(s):  
Sara A. Atyia ◽  
Keaton S. Smetana ◽  
Minh C. Tong ◽  
Molly J. Thompson ◽  
Kari M. Cape ◽  
...  

Background: Dexmedetomidine is a highly selective α2-adrenoreceptor agonist that produces dose-dependent sedation, anxiolysis, and analgesia without respiratory depression. Due to these ideal sedative properties, there has been increased interest in utilizing dexmedetomidine as a first-line sedative for critically ill patients requiring light sedation. Objective: To evaluate the ability to achieve goal intensive care unit (ICU) sedation before and after an institutional change of dosing from actual (ABW) to adjusted (AdjBW) body weight in obese patients on dexmedetomidine. Methods: This study included patients ≥ 18 years old, admitted to a surgical or medical ICU, required dexmedetomidine for at least 8 hours as a single continuous infusion sedative, and weighed ≥ 120% of ideal body weight. Percentage of RASS measurements within goal range (−1 to +1) during the first 48 hours after initiation of dexmedetomidine as the sole sedative agent or until discontinuation dosed on ABW compared to AdjBW was evaluated. Results: 100 patients were included in the ABW cohort and 100 in the AdjBW cohort. The median dosing weight was significantly higher in the ABW group (95.9 [78.9-119.5] vs 82.2 [72.1-89.8] kg; p = 0.001). There was no statistical difference in percent of RASS measurements in goal range (61.5% vs 69.6%, p = 0.267) in patients that received dexmedetomidine dosed based on ABW versus AdjBW. Conclusion: Dosing dexmedetomidine using AdjBW in obese critically ill patients for ongoing ICU sedation resulted in no statistical difference in the percent of RASS measurements within goal when compared to ABW dosing. Further studies are warranted.


2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Nilutpal Sharma Bora ◽  
Partha Sarathi Bairy ◽  
Abdus Salam ◽  
Bibhuti Bhusan Kakoti

Abstract Background Garcinia lanceifolia Roxb. has been used by many ethnic communities of Northeast India to mitigate various disorders like dyspepsia, ulcers, diabetes, etc. However, a robust scientific study on its antidiabetic and antiulcer potential is unavailable till date. The aim of this present study is to scientifically validate if the antidiabetic and antiulcer effects reported by the ethnic tribes of Assam has any scientific value or not. The effects were tested in adult Wistar albino rats using approved animal models for preclinical testing of pharmacological activities. Results The hydroalcoholic extract of the bark of Garcinia lanceifolia Roxb. was prepared and its LD50 was calculated. The LD50 was determined to be greater than 5000 mg/kg body weight. The extract at doses of 250 mg/kg body weight and 500 mg/kg body weight was found to exhibit a very potent dose-dependent antidiabetic activity. The results were backed by a battery of test including analysis of serum levels of blood glucose, lipid profiles, in vivo antioxidant enzymes, and histopathological studies. Evidence of dose-dependent antiulcer activity of the extract was backed by robust scientific data. It was found that HAEGL induced a significant dose-dependent increase in the ulcer index in both alcohol-induced and acetic acid-induced ulcer models, which was evident from the macroscopic observation of the inner lining of the gastric mucosa and the histological evaluation of the extracted stomach. Conclusion The results suggested that the bark of Garcinia lanceifolia (Roxb.) has significant antidiabetic and antiulcer potential. Further studies with respect to the development herbal dosage forms and its safety evaluation are required.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xuewen Wu ◽  
Li Zhang ◽  
Yihui Li ◽  
Wenjuan Zhang ◽  
Jianjun Wang ◽  
...  

AbstractMutations in voltage-gated potassium channel KCNE1 cause Jervell and Lange-Nielsen syndrome type 2 (JLNS2), resulting in congenital deafness and vestibular dysfunction. We conducted gene therapy by injecting viral vectors using the canalostomy approach in Kcne1−/− mice to treat both the hearing and vestibular symptoms. Results showed early treatment prevented collapse of the Reissner’s membrane and vestibular wall, retained the normal size of the semicircular canals, and prevented the degeneration of inner ear cells. In a dose-dependent manner, the treatment preserved auditory (16 out of 20 mice) and vestibular (20/20) functions in mice treated with the high-dosage for at least five months. In the low-dosage group, a subgroup of mice (13/20) showed improvements only in the vestibular functions. Results supported that highly efficient transduction is one of the key factors for achieving the efficacy and maintaining the long-term therapeutic effect. Secondary outcomes of treatment included improved birth and litter survival rates. Our results demonstrated that gene therapy via the canalostomy approach, which has been considered to be one of the more feasible delivery methods for human inner ear gene therapy, preserved auditory and vestibular functions in a dose-dependent manner in a mouse model of JLNS2.


2010 ◽  
Vol 29 (3) ◽  
pp. 313-317
Author(s):  
Waleed A. Al-Madani ◽  
Nikhat J. Siddiqi ◽  
Abdullah S. Alhomida ◽  
Haseeb A. Khan ◽  
Ibrahim A. Arif ◽  
...  

This investigation was aimed to study the effect of 2,3-dimercapto-1-propanesulfonic acid (DMPS) on mercuric chloride (HgCl2)-induced alterations in urinary excretion of various carnitine fractions including free carnitine (FC), acylcarnitine (AC), and total carnitine (TC). Different groups of Wistar male rats were treated with HgCl2 at the doses of 0.1, 0.5, 1.0, 2.0, and 3.0 mg/kg body weight, and the animals were sacrificed at 24 hours following HgCl2 injection. A separate batch of animals received HgCl2 (2 mg/kg) with or without DMPS (100 mg/kg) and sacrificed at 24 or 48 hours after dosing. Administration of HgCl2 resulted in statistically significant and dose-dependent increase in the urinary excretion of FC, AC, and TC in rats. However, the ratio of urinary AC:FC was significantly decreased by HgCl2. Pretreatment with DMPS offered statistically significant protection against HgCl2-induced alterations in various urinary carnitine fractions in rats.


2015 ◽  
Vol 227 (3) ◽  
pp. 129-141 ◽  
Author(s):  
Russell T Turner ◽  
Michael Dube ◽  
Adam J Branscum ◽  
Carmen P Wong ◽  
Dawn A Olson ◽  
...  

Excessive weight gain in adults is associated with a variety of negative health outcomes. Unfortunately, dieting, exercise, and pharmacological interventions have had limited long-term success in weight control and can result in detrimental side effects, including accelerating age-related cancellous bone loss. We investigated the efficacy of using hypothalamic leptin gene therapy as an alternative method for reducing weight in skeletally-mature (9 months old) female rats and determined the impact of leptin-induced weight loss on bone mass, density, and microarchitecture, and serum biomarkers of bone turnover (CTx and osteocalcin). Rats were implanted with cannulae in the 3rd ventricle of the hypothalamus and injected with either recombinant adeno-associated virus encoding the gene for rat leptin (rAAV-Leptin,n=7) or a control vector encoding green fluorescent protein (rAAV-GFP,n=10) and sacrificed 18 weeks later. A baseline control group (n=7) was sacrificed at vector administration. rAAV-Leptin-treated rats lost weight (−4±2%) while rAAV-GFP-treated rats gained weight (14±2%) during the study. At study termination, rAAV-Leptin-treated rats weighed 17% less than rAAV-GFP-treated rats and had lower abdominal white adipose tissue weight (−80%), serum leptin (−77%), and serum IGF1 (−34%). Cancellous bone volume fraction in distal femur metaphysis and epiphysis, and in lumbar vertebra tended to be lower (P<0.1) in rAAV-GFP-treated rats (13.5 months old) compared to baseline control rats (9 months old). Significant differences in cancellous bone or biomarkers of bone turnover were not detected between rAAV-Leptin and rAAV-GFP rats. In summary, rAAV-Leptin-treated rats maintained a lower body weight compared to baseline and rAAV-GFP-treated rats with minimal effects on bone mass, density, microarchitecture, or biochemical markers of bone turnover.


INDIAN DRUGS ◽  
2013 ◽  
Vol 50 (11) ◽  
pp. 34-38
Author(s):  
T. Shyam ◽  
◽  
S Ganapaty

Four compounds viz α-amyrin, β- amyrin, bauerenol and ellagic acid were isolated from the methanolic extract of Rotula aquatica roots. The structures of these compounds were elucidated on the basis of spectroscopic data analysis and chemical evidence. The extract was evaluated for hepatoprotective activity against carbon tetrachloride induced hepatotoxic model at a dose levels of 200,400 and 800 mg/ kg body weight and compared with that of the standard silymarin (25mg/kg body weight). It showed good hepatoprotective activity in a dose dependent manner. The extract was also screened for antimicrobial activity against various types of organisms like bacteria and fungi.


Author(s):  
Athesh K ◽  
Joshi G

Objective: To study the anti-obesity potential of aqueous rhizome extract of Acoruscalamus Linn. (AREAC)in high fat diet fed obese rats.Methods: Adult strain male Wistar rats used in this study were fed with High Fat Diet (HFD) for 60 days. For the treatment groups,AREAC was administered in a dose levels of100, 200 and 300 mg/kgbw, orally once a day along with HFD. Rats fed with normal pellet chow were served as normal control. The effect of AREAC on physical parameterssuch as body weight, organ weight, fat pad weights and various biochemical parameterslike serum glucose, insulin, leptin,lipid profile, liver markers, kidney markers and oxidative stress markers were analysed.In-vitro pancreatic lipase inhibition assay of AREAC was also studied.Results: Data of in-vivo studies revealedsignificant (p<0.05) reduction in percentage body weight gain, organ weights, fat pad weights and levels of serum glucose, insulin and leptin after treatment with AREAC in a dose dependent manner. Also, administration of AREAC significantly inhibited the increases in the concentrations of triglycerides, total cholesterol, LDL-cholesterol, VLDL-cholesterol, free-fatty acid and phospholipids in a dose dependent manner whereas, the level of HDL-cholesterol was found to be elevated on treatment. Moreover, on treatment with test drug,the elevated levels of serum liver and kidney markerssuch as AST, ALT, ALP, urea, creatinine were also brought back to near normalcy. Antioxidant status was found to be enhanced in liver tissues after treatment.In-vitro studies showed significant inhibition in the activity of pancreatic lipaseby AREAC.Conclusion: The data of the results obtained clearly depicted that AREAC was found to have pronounced anti-obesity activity particularly at the dose levels of 300 mg/kg bw.Key Words: Obesity, High Fat Diet, Leptin, AcoruscalamusLinn., Orlistat.  


2018 ◽  
Vol 12 (1) ◽  
pp. 11-14
Author(s):  
Sharmin Rahman ◽  
Mohammad Rezaul Quader ◽  
Md Ismail Khan

Background and objectives: Aegle marmelos (Bael), a medicinal plant, has been widely used indigenously to treat many diseases in Bangladesh and other countries. The present study was carried out to evaluate the efficacy of A. marmelos leaf to prevent ethanol induced gastric ulcer in a rat model.Methods: Thirty two Wister albino rats of either sex, weighing between 100-150g, were fed 200 mg/kg or 400 mg/kg aqueous extract of A. marmelos leaves one hour prior to oral administration of 90% ethanol (1 ml/200 gm body weight) to induce gastric ulcer. The animals were sacrificed after one hour and ulcer scores and index were determined. The protective efficacy of A. marmelos aqueous extract was expressed as percentage protection of ulcer.Results: Aqueous extract exhibited significant (p<0.05) dose dependent protection against gastric ulcer formation by ethanol in rat stomach. Percentage protection of ulcer with 200 mg/kg and 400 mg/kg of aqueous extract of A. marmelos leave were 19.3% and 37.2% respectively compared to standard anti-peptic ulcer drug omeprazole (50.4%).Conclusion: Thus, crude extracts of A. marmelos leave have been shown to have potential ability to prevent experimentally induced peptic ulcer formation in animal model.IMC J Med Sci 2018; 12(1): 11-14


2010 ◽  
Vol 38 (01) ◽  
pp. 65-73 ◽  
Author(s):  
Fa-Rong Yu ◽  
Ying Liu ◽  
Yong-Zhi Cui ◽  
Er-Qing Chan ◽  
Ming-Ren Xie ◽  
...  

The present study investigated the effects of a flavonoid extract from Cynomorium songaricum on the swimming endurance of rats by measuring changes of free radical scavenging enzymes, such as CuZn-SOD (copper, zinc-superoxide dismutase) and GSH-px (glutathione peroxidase), and body weights. Significant and dose-dependent antioxidant and anti-fatigue effects of flavonoids (rutin, catechin and isoquercitrin) on swimming rats were observed during 10 days of swimming exercise. After treatment with the flavonoid extract at doses of 0.5, 1.0, and 2.0 g/kg body weight, the CuZn-SOD and GSH-px activities in swimming rats were increased by 1.4%, 3.3%, 4.1% and 112.2%, 208.7%, 261.7%, respectively, while the levels of MDA (malondialdehyde) were decreased by 64.7%, 79.4%, and 86.4% respectively. Furthermore, the average body weight and the total swimming time were increased by 3.1%, 8.8%, 10.6%, and 7.7%, 34.5%, 61.5%, respectively. Our experimental results suggest that flavonoid supplementation could not only reduce free radical formation and scavenge free radicals, but also enhance endurance exercise performance by reducing muscle fatigue.


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