Effect of Swimming at Low Temperature on Uncoupling Protein Gene Expression in Skeletal Muscle of Wistar Rats / Efecto de la Natación a Baja Temperatura sobre la Expresión del Gen de la Proteína de Desacoplamiento en el Músculo Esquelético de Ratas Wistar

SUMMARY: As the economy develops and living standards improve, overweight and obesity are increasingly prevalent. Currently, weight-loss medications are primarily administered orally or intravenously, which can result in poor targeting, low bioavailability, frequent administration, and high toxicity and side effects. The study aimed to address these challenges by preparing polylactic acid- polyethylene glycol staple fibers that carry the browning drug pioglitazone hydrochloride using electrostatic spinning and freeze-cutting techniques. Animal experiments were conducted to test the effectiveness of these fibers. Additionally, the study investigated the expression of uncoupling protein genes in rats exposed to different water temperatures by measuring changes in serum urea nitrogen and mRNA expression levels of skeletal muscle uncoupling protein genes. The physiological and genetic effects of low-temperature swimming exercise on changes in energy metabolism in rats were also analyzed at both the individual and molecular levels. The results revealed that serum urea nitrogen remained more stable in hypothermic swimming rats compared to rats in the swimming group. Furthermore, the study observed an induced up-regulation of uncoupling proteins in the skeletal muscle of Wistar rats in response to external temperature stimulation, and the expression of mRNA for skeletal muscle uncoupling proteins significantly increased as the temperature decreased. And the prepared short nanofibers also had a significant promotive effect on uncoupling protein gene, COX7A1, while suppressing the expression of lipogenic gene.

A medida que la economía se desarrolla y los niveles de vida mejoran, el sobrepeso y la obesidad son cada vez más frecuentes. Actualmente, los medicamentos para bajar de peso se administran principalmente por vía oral o intravenosa, lo que puede resultar en una mala focalización, baja biodisponibilidad, administración frecuente y alta toxicidad y efectos secundarios. El estudio tuvo como objetivo abordar estos desafíos mediante la preparación de fibras cortadas de ácido poliláctico y polietilenglicol que transportan el fármaco pardo clorhidrato de pioglitazona mediante técnicas de hilado electrostático y liofilización. Se realizaron experimentos con animales para probar la eficacia de estas fibras. Además, el estudio investigó la expresión de genes de proteínas desacopladoras en ratas expuestas a diferentes temperaturas del agua midiendo los cambios en el nitrógeno ureico sérico y los niveles de expresión de ARNm de genes de proteínas desacopladoras del músculo esquelético. También se analizaron los efectos fisiológicos y genéticos del ejercicio de natación a baja temperatura sobre los cambios en el metabolismo energético en ratas, tanto a nivel individual como molecular. Los resultados revelaron que el nitrógeno ureico sérico permaneció más estable en ratas nadadoras hipotérmicas en comparación con las ratas del grupo de natación. Además, el estudio observó una regulación positiva inducida de las proteínas desacopladoras en el músculo esquelético de ratas Wistar en respuesta a la estimulación de la temperatura externa, y la expresión de ARNm para las proteínas desacopladoras del músculo esquelético aumentó significativamente a medida que disminuía la temperatura. Además, las nanofibras cortas preparadas también tuvieron un efecto promotor significativo sobre el gen de la proteína de desacoplamiento, COX7A1, al tiempo que suprimieron la expresión del gen lipogénico.

Comparative study of efficacy and safety of compound pioglitazone hydrochloride glimepiride tablet and glimepiride tablet in treating type 2 diabetes mellitus / 重庆医学

Objective To compare the efficacy and safety of compound pioglitazone hydrochloririe glimepiride tablet and glimepiride tablet in the treatment of type 2 diabetic mellitus(T2DM) for evaluating the effectiveness and safety of compound pioglitazone hydrochloride glimepiride tablet for treating T2DM.Methods The random,double-blind,double-dummy,positive drugs parallel control clinical study method was adopted.Thirty-three T2DM patients with poorly controlled blood glucose were randomly assigned to the test group(n=22) and control group(n=11) by the 2 ∶ 1 ratio.The test group was given compound pioglitazone hydrochloride glimepiride tablet,while the control group received glimepiride tablet.The treatment cycle was 12 weeks.The differences of FBG,HbA1c,FINS and HOMA-IR in the two groups were compared between before and after treatment.Moreover the changes of body mass,blood pressure and blood lipids as well as adverse events occurrence were compared between the two groups.Results Thirty-one cases finished the treatment follow up(21 cases in the test group and 10 cases in the control group);the decreased amplitudes of HbA1c levels after 12-week treatment in the test group and control group were (0.99 ± 1.87)％ and (-0.02 ± 0.90) ％ respectively,which of FPG were (0.94 ± 1.87) mmol/L and (0.37 ± 2.62) mmol/L respectively.The FPG and HbA1c levels after treatment in the test group were decreased compared with before treatment,the difference was statistically significant (P＜0.01).The change difference of FPG and HbA1c in the control group had no statistical difference(P＞0.05).FINS and HOMO-IR in the test group were significantly decreased before and after treatment,the difference was statistically significant (P＜0.01).The incidence rate of hypoglycemia had no statistically significant difference between the test group and control group.Conclusion The effectiveness of compound pioglitazone hydrochloride glimepiride tablet in treating T2 DM is superior to the single use of glimepiride,while the safety is equivalent to single use of glimepiride.

Identification of the related substances in pioglitazone hydrochloride by hyphenated LC-MS techniques / 中国药科大学学报

To identify the related substances in pioglitazone hydrochloride by hyphenated LC-MS techniques,an Ultimate XB-C18 (250 mm × 4.6 mm,5 μm) column was used for separation of the related substances with methanol and 0.1％ ammonium acetate buffer as the mobile phases in gradient elution.Electrospray positive ionization high resolution TOF/MS was used for the determination of the accurate mass and elemental composition of parent [M + H] + ions of the related substances,and triple quadrupole tandem mass spectrometry was employed for the product mass spectra determination.Eleven major related substances were detected and identified to be one synthesis intermediate,six by-products and four degradation products,by using LC-MS determination,spectra elucidation,and further synthetic process and stress degradation mechanisms analysis.The results are useful for pioglitazone hydrochloride manufacturing processes optimization and quality control.

Development of pioglitazone hydrochloride lipospheres by melt dispersion technique: Optimization and evaluation.

The objective of the present study was to develop and evaluate pioglitazone hydrochloride loaded lipospheres for treatment of diabetes. Pioglitazone hydrochloride lipospheres were formulated by using melt dispersion (homogenization) technique using compritol®888 ATO as lipid matrix and Phospholipon 90G (P 90G), PVA, Poloxamer 188 as surfactants. Formulation was optimized by using 32 full factorial design where entrapment efficiency and particle size were dependent variables and lipid and surfactant concentration were independent variables. Optimized formulation of pioglitazone hydrochloride (PLS 5) shows 79.69± 1.35% entrapment efficiency, 94.63± 2.10% drug content and particle size was found to be 23.74± 0.35μm with spherical shaped free flowing particles. In vitro release was carried out using dissolution apparatus in 0.1N HCl and optimized formulation shows 96.06 ± 0.54 % drug release within 8 hrs. which follows quasi-fickian type of transport and was characterized by the Korsmeyer- Peppas model. Formulation was stable at 5 oC ± 3 oC for two months. Developed liposphere formulation was able to sustain the drug release and entrap the pioglitazone hydrochloride drug at high level.

Preparation and in vitro Dissolution of Pioglitazone Hydrochloride Sustained-release Pellet Capsules / 中国药师

Objective:To prepare pioglitazone hydrochloride ( PGH) sustained-release pellet capsules and study the in vitro disso-lution. Methods:The preparation was prepared with a bottom spray fluidized bed, and the formula and technology were optimized by orthogonal test. Results:The method was simple and easy to operate, the reproducibility of the formula and technology was good, and the pellets had obvious sustained-release property. Conclusion:The formula and technology are easy and controllable, and the stability of sustained release pellets is good.

Pioglitazone hydrochloride improving learning and memory abilities in rats with type 2 diabetes via increasing amount of hippocampal cholinergic neurostimulating peptide in the hippocampus / 中华神经医学杂志

Objective To demonstrate the effect of Pioglitazone hydrochloride on spatial memory ability in diabetes rats via improving the level of hippocampal cholinergic neurostimulating peptide (HCNP) in the hippocampus tissues. Methods Twenty-four 12-week old male SD rats were equally randomized into control group (Con),diabetes group (DM),DM+Pioglitazone hydrochloride treatment group (DP).Rats of the DM and DP groups were fed with high fat diet,and rats of the DP group were also performed intragastric administration of 10 mg/(kg· d) Pioglitazone hydrochloride daily.Morris water maze test was performed on the rats enjoyed successful model making to detect their spatial memory ability; the level of HCNP precursor protein (HCNP-pp) was measured by Western blotting so as to measure the level of HCNP; and the relative mRNA contents of HCNP-pp, choline acetyltransferase (ChAT),muscarinic receptor 1 (M1R) and α7 type nicotinic receptor (α7NR) genes were measured by reverse transcription PCR. Results The escape latency in rats of the con and DP groups was significantly shortened as compared with that in the DM group (P＜0.05).As compared with that in the Con and DP groups, the relative amount of HCNP-pp in DM group was higher in protein and mRNA levels (P＜0.05); however,the relative amount of HCNP in the DM group was obviously lower than that in the Con and DP groups (P＜0.05).And the mRNA ChAT,M1R and α7NR levels in the Con and DP groups were significantly higher than those in the DM group (P＜0.05). Conclusion Pioglitazone hydrochloride can accelerate the lysis of HCNP-pp in the hippocampus to induce the increased level of HCNP,further making the cholinergic nerve receptors activation,which maybe one of the mechanisms to improve the ability of spatial memory in eldly rats with type 2 diabetes.

Simultaneous estimation of metformin hydrochloride, rosiglitazone and pioglitazone hydrochloride in the tablets dosage form.

A simple, specific, accurate and isocratic reversed phase liquid chromatographic method was developed and subsequently validated for the determination of metformin hydrochloride, rosiglitazone and pioglitazone hydrochloride. Separation was achieved with a Zorbax C8 column of 150×4.6 mm i.d. with 5 μm particle size and ammonium dihydrogen phosphate buffer adjusted to pH 3.0 using diluted ortho phosphoric acid and acetonitrile (65:35 v/v) as eluent at a constant flow rate of 0.7 ml per min. UV detection was performed at 215 nm. The retention time of metformin hydrochloride, rosiglitazone and pioglitazone hydrochloride were about 1.9, 3.4 and 6.7 min, respectively. This method is simple, rapid and selective and can be used for routine analysis of antidiabetic drugs in pharmaceutical preparation. It is a convenient method for separation and simultaneous determination of metformin hydrochloride, rosiglitazone and pioglitazone hydrochloride in pharmaceutical formulations.

Determination of Blood Concentration of Pioglitazone Hydrochloride by HPLC / 中国药房

OBJECTIVE:To establish the method of determining the blood concentration of pioglitazone hydrochloride. METHODS:Chromatographic column was based on Hypersil C l8 (150mm?4.6mm,5?m),the mobile phase consisted of ace-tonitrile-buffer phosphate(40∶60,V/V)with a flow rate at l.0ml/min,the detecting wavelength was229nm.The blood sample was extracted with dichlormethane.RESULTS:The linear concentration range was25～4000ng/ml(r=0.9998,n=8).The lowest detecting concentration was25ng/ml.The extracting recovery rate of high,medium and low concentrations were(73.33?1.22)%,(76.92?6.57)%and(84.50?3.40)%respectively,the method recovery which were(103.26?3.31)%,(97.31?9.07)%and(99.61?6.48)%respectively.The intra-day RSD