Hot melt extrusion technology for improved dissolution, solubility and "spring-parachute" processes of amorphous self-micellizing solid dispersions containing BCS II drugs indomethacin and fenofibrate: Profiles and mechanisms.

Many strategies have been employed to improve oral drug delivery. One such approach involves the use of supersaturable delivery systems such as amorphous self-micellizing solid dispersions (SmSDs). SmSDs have attracted more attention recently, but little is known regarding the impact of production methods on profiles and internal mechanisms of final SmSDs in spite of its importance. In this study, amorphous SmSDs containing self-micellizing Soluplus® and BCS II drug (either indomethacin (IND) or fenofibrate (FEN)) were generated using various methods: solvent evaporation (SOL), freeze-drying (FD), microwave radiation-quench cooling (MQC), and hot melt extrusion (HME). Microscopic morphology, amorphous state, thermal behavior, dissolution/solubility, and "spring-parachute" data were used to assemble physicochemical profiles for SmSD systems prepared using each method. Analysis of intermolecular interactions, solubilization, and crystallization inhibition further uncovered internal mechanisms explaining observed physicochemical properties. Generally, SmSD/IND and SmSD/FEN systems generated using HME exhibited superior dissolution, solubility, and spring-parachute profiles. The superior advantages of HME-generated SmSD/IND systems were attributed to relatively stronger intermolecular interactions than observed in SmSD/IND systems fabricated using other methods. Moreover, self-micellizing Soluplus® carrier was able to solubilize IND or FEN and suppress drug crystallization from a supersaturated state, which seemed to be an important mechanism for the properties enhancement caused by SmSD/FENHME. This knowledge should be useful for guiding further development of self-micellizing solid dispersions and for gaining deeper understanding of how HME technology can improve supersaturable drug delivery based on SmSDs strategy.

Untargeted metabolomics approach (UPLC-Q-TOF-MS) explores the biomarkers of serum and urine in overweight/obese young men.

BACKGROUND AND OBJECTIVES: Obesity is linked to metabolic diseases characterized by insulin resistance, such as diabetes and cardiovascular disease. In this study, we investigated the metabolic disorders of uncomplicated obesity to identify early alterations in biological systems. METHODS AND STUDY DESIGN: Metabolic differences between overweight/obese (n=36) and normal-weight (n=35) young Chinese men without known metabolic disorders were assessed. Metabolic profiling of the serum and urine was performed using ultra-performance liquidchromatography quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Partial least squares discriminant analysis (PLS-DA) was undertaken to reveal and classify the differences between the two groups. RESULTS: Compared to normal-weight men, obese men had higher levels of the serum metabolites phenylalanine, Phe-Phe, and L-tryptophan, whereas those of p-cresol sulfate and p-cresol were less in obesity. Urinary metabolites phenylacetamide, L-glutamine, phenylacetylglutamine, indoxyl sulfate, p-cresol, and p-cresol sulfate were greater in obese men. CONCLUSIONS: These findings indicate that disorders involving aromatic amino acids and the tricarboxylic acid cycle (TCA) have microbiomic involvement in the uncomplicated phase of obesity.

Visual field impairment predicts recurrent stroke after acute posterior circulation stroke and transient ischemic attack.

AIMS: To evaluate whether visual field impairment (VFI) can predict stroke recurrence in patients with vertebral-basilar (VB) stroke. METHODS: A total of 326 patients were eligible for a VFI evaluation within 1 week of stroke onset. One-year follow-up data were obtained after VB stroke and other vascular events. All predictors were determined using Cox regression models. RESULTS: The overall incidence of recurrent VB stroke and transient ischemic attack (TIA) was 29% (n = 92). After multivariate adjustment, severe and moderate VFI were predictors of recurrent VB stroke and TIA. CONCLUSIONS: VFI is an independent predictor of recurrent VB stroke and TIA.

Oxidative damage of mitochondrial respiratory chain in different organs of a rat model of diet-induced obesity.

PURPOSE: Mitochondrial dysfunction plays an important role in the development of obesity and obesity-associated metabolic diseases. METHODS: In this study, we dynamically observed the characteristics of mitochondrial damage in a rat model of diet-induced obesity (DIO). From the 2nd to the 10th week, animals were killed every 2 weeks and the heart, liver, kidney, and testicular tissues were harvested. Mitochondria were isolated and the activities of respiratory chain complexes I, II, III, and IV as well as the 8-Hydroxy-2-deoxy Guanosine content were determined. Reactive oxygen species and malondialdehyde were measured. RESULTS: Mitochondrial damages were observed in the heart and liver of DIO and DR rats, and the damages occurred later in DR group than that in DIO group. The mitochondrial membrane potential of heart and liver decreased in DIO and DR groups. The activity of the heart mitochondria complexes I, III, and IV (composing NADH oxidative respiratory) was higher in the early stage of DIO and lower in the end of week 10. The higher activity of the liver complexes I, III, and IV was found until the end of week 10 in DIO and DR groups, accompanied with enhanced oxidative stress. Besides, mitochondrial DNA damages were observed in all tissues. CONCLUSION: In DIO rats, the heart mitochondrial dysfunction occurred first and the liver presented the strongest compensatory ability against oxidative stress.

Intelligent "Peptide-Gathering Mechanical Arm" Tames Wild "Trojan-Horse" Peptides for the Controlled Delivery of Cancer Nanotherapeutics.

Cell-penetrating peptides (CPPs), also called "Trojan-Horse" peptides, have been used for facilitating intracellular delivery of numerous diverse cargoes and even nanocarriers. However, the lack of targeting specificity ("wildness" or nonselectivity) of CPP-nanocarriers remains an intractable challenge for many in vivo applications. In this work, we used an intelligent "peptide-gathering mechanical arm" (Int PMA) to curb CPPs' wildness and enhance the selectivity of R9-liposome-based cargo delivery for tumor targeting. The peptide NGR, serving as a cell-targeting peptide for anchoring, and peptide PLGLAG, serving as a substrate peptide for deanchoring, were embedded in the Int PMA motif. The Int PMA construct was designed to be sensitive to tumor microenvironmental stimuli, including aminopeptidase N (CD13) and matrix metalloproteinases (MMP-2/9). Moreover, Int PMA could be specifically recognized by tumor tissues via CD13-mediated anchoring and released for cell entry by MMP-2/9-mediated deanchoring. To test the Int PMA design, a series of experiments were conducted in vitro and in vivo. Functional conjugates Int PMA-R9-poly(ethylene glycol) (PEG)2000-distearoylphosphatidyl-ethanolamine (DSPE) and R9-PEG2000-DSPE were synthesized by Michael addition reaction and were characterized by thin-layer chromatography and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. The Int PMA-R9-modified doxorubicin-loaded liposomes (Int PMA-R9-Lip-DOX) exhibited a proper particle diameter (approximately 155 nm) with in vitro sustained release characteristics. Cleavage assay showed that Int PMA-R9 peptide molecules could be cleaved by MMP-2/9 for completion of deanchoring. Flow cytometry and confocal microscopy studies indicated that Int PMA-R9-Lip-DOX can respond to both endogenous and exogenous stimuli in the presence/absence of excess MMP-2/9 and MMP-2/9 inhibitor (GM6001) and effectively function under competitive receptor-binding conditions. Moreover, Int PMA-R9-Lip-DOX generated more significant subcellular dispersions that were especially evident within endoplasmic reticulum (ER) and Golgi apparatus. Notably, Int PMA-R9-Lip-DOX could induce enhanced apoptosis, during which caspase 3/7 might be activated. In addition, Int PMA-R9-Lip-DOX displayed enhanced in vitro and in vivo antitumor efficacy versus "wild" R9-Lip-DOX. On the basis of investigations at the molecular level, cellular level, and animals' level, the control of Int PMA was effective and promoted selective delivery of R9-liposome cargo to the target site and reduced nonspecific uptake. This Int PMA-controlled strategy based on aminopeptidase-guided anchoring and protease-triggered deanchoring effectively curbed the wildness of CPPs and bolstered their effectiveness for in vivo delivery of nanotherapeutics. The specific nanocarrier delivery system used here could be adapted using a variety of intelligent designs based on combinations of multifunctional peptides that would specifically and preferentially bind to tumors versus nontumor tissues for tumor-localized accumulation in vivo. Thus, CPPs have a strong advantage for the development of intelligent nanomedicines for targeted tumor therapy.

Novel CYP4V2 mutations associated with Bietti crystalline corneoretinal dystrophy in Chinese patients.

AIM: To analyze the CYP4V2 mutations in five unrelated Chinese patients with Bietti crystalline corneoretinal dystrophy (BCD) and to provide clinical features of these patients. BCD is a rare monogenic autosomal recessively inherited disorder characterized by the presence of crystals in the retina and retinal pigment epithelium atrophy. Mutations in the CYP4V2 gene have been found to be causative for BCD. METHODS: Ophthalmic examinations were carried out in the affected individuals. Peripheral blood samples were collected and genomic DNA was extracted. All exons and flanking intronic regions of the CYP4V2 gene were amplified with polymerase chain reaction and screened for mutations by direct DNA sequencing. One hundred control chromosomes were also screened to exclude nonpathogenic polymorphisms. RESULTS: Fundus examination revealed the presence of tiny yellowish-sparkling crystals at the posterior pole of the fundus and atrophy of the retinal pigment epithelium in all patients. Choroid neovascularization was noted in one patient. Five different CYP4V2 mutations were identified, including two missense mutations (p.F73L, p.R400H), two splice site mutations (c.802-8_810del17insGC, c.1091-2A>G), and one single base-pair deletion (p.T479TfsX7 or c.1437delC). The two splice site mutations were identified in three of the patients with BCD. Mutation p.T479TfsX7 was a novel mutation not observed in any of 100 ethnically matched control chromosomes. CONCLUSION: Mutation c.802-8_810del17insGC and c.1091-2A>G are common mutations in Chinese patients with BCD. Our results expand the allelic heterogeneity of BCD.

Effects of gastrointestinal motility on obesity.

BACKGROUND: Changes of gastrointestinal motility, which are important related to the food digestion and absorption in the gastrointestinal tract, may be one of the factors in obesity-formation. AIMS: The changes of gastrointestinal motility were explored in the rats from diet-induced obesity (DIO), diet-induced obese resistant (DR) or control (CON) by diet intervention. METHODS: After fed with a high fat diet (HFD), 100 male Sprague-Dawley rats were divided into DIO, DR and CON groups. The rats from DIO and DR groups were fed with HFD, and CON with a basic diet (BD) for 6 weeks. Body weight, energy intake, gastric emptying, intestinal transit, motility of isolated small intestine segments and colon's function were measured in this study. Expression of interstitial cells of Cajal (ICCs) and enteric nervous system (ENS) - choline acetyltransferase (ChAT), vasoactive intestinal peptides (VIP), substance P (SP) and NADPH-d histochemistry of nitric oxide synthase (NOS) were determined by immunohistochemistry. RESULTS: Body weight and intake energy in the DIO group were higher than those in the DR group (p < 0.05). Gastric emptying of DIO group rats (78.33 ± 4.95%) was significantly faster than that of DR group (51.79 ± 10.72%) (p < 0.01). The peak value of motility in rat's duodenum from the DR group was significantly higher than that in the DIO group (p < 0.05). In addition, the expression of interstitial cells of Cajal (ICC), choline acetyltransferase (ChAT), substance P (SP), vasoactive intestinal peptides (VIP) and neuronal nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) in the intestine of rats were significantly increased in the DIO group when compared to the DR group (p < 0.05). CONCLUSION: A faster gastric emptying, a weaker contraction of duodenum movement, and a stronger contraction and relaxation of ileum movement were found in the rats from the DIO group. It indicated that there has effect of gastrointestinal motility on obesity induced by HFD.

[Vitreal surgery and etiological diagnosis of bacterial endophthalmitis].

OBJECTIVE: To evaluate the clinical effects of vitreal surgery and the importance of etiological diagnosis in the treatment for bacterial endophthalmitis. METHODS: Retrospective series case study. 20 cases (20 eyes) of bacterial endophthalmitis that were treated in Peking Union Hospital were enrolled. 14 eyes were post-traumatic endophthalmitis, and 6 eyes were postoperative endophthalmitis. Twenty cases of aged 3 to 83 years [mean (40.5 ± 23.9) years] were enrolled, including 12 male and 8 female patients. Pre-operative visual acuity: 2 cases were able to count fingers, 6 cases were able to perform hand movement, 11 cases had light perception, light projection were uncertain in all cases, and there was no light perception in 1 case. Hypopyon was seen in 13 eyes. Severe anterior chamber inflammatory reaction was seen in the other 7 eyes. The fundus could not be observed in all 20 eyes. B-Scan ultrasound examination indicated that all 20 eyes displayed moderate to severe vitreous opacity; proliferation and organization were apparent in 12 eyes, and retinal detachment in 2 eyes. Vitrectomy and intravitreal injection of antibiotics were performed in 18 eyes, and only intravitreal injection of antibiotics was administered in the other 2 eyes. At the beginning of operation, vitreous fluids were smeared and Gram stained. To eyes that showed a positive result in Gram staining, 1 mg of Vancomycin was injected into the vitreous cavity or added in the perfusion fluid (balanced salt solution, BSS) in the eyes. To eyes that showed a negative result in Gram staining, 2 mg or 4 mg of Ceftazidime was injected into the vitreous cavity or added in the perfusion fluid (BSS) in the eyes, respectively. Additionally, we examined the vitreous specimens and performed drug susceptibility testing of the bacteria cultured from the specimens. The antibiotics that the bacteria were susceptible to were chosen according to the drug sensitivity tests. The follow-up period is from 1 to 102 months (average 16.6 months). RESULTS: Thirteen eyes presented with a positive Gram staining result, and 3 eyes presented a negative result; the other 4 eyes were not infected. Bacteria were cultured in 15 eyes. The detection rate of pathogen was 75%. The result for 11 eyes was consistent with the smear results. The bacteria detected were Staphylococcus aureus in 3 eyes, Staphylococcus epidermidis in 3 eyes, and Bacillus spp in 2 eyes. Streptococcus pneumoniae, Streptococcus mitis, Plesiomonas, Pseudomonas cepacia, Klebsiella oxytoca, Loffi Acinetobacter and Pseudomonas fluorescens were detected in 1 eye. The remaining 5 eyes did not have bacterial growth. The intraocular infection of all 20 eyes was controlled, and the intraocular inflammation was relieved. The visual acuity was significantly elevated. Postoperative visual acuity achieved were ≥ 0.3 in 4 eyes, 0.1 to 0.2 in 4 eyes, 0.02 to 0.09 in 6 eyes, CF in 2 eyes, HM in 3 eyes and LP in 1 eye. The retinas of 17 eyes were normal, but recurrent retinal detachment occurred in the other 3 eyes, postoperatively. CONCLUSIONS: Vitrectomy combined with antibiotics and intravitreal injection of antibiotics were an effective treatment of bacterial endophthalmitis. We obtained the vitreous fluid smears at the beginning of surgery to quickly and accurately obtain etiological diagnoses by Gram staining. It is crucial to use etiological diagnosis to choose the susceptible antibiotics.

[Current status and progress of fungal endophthalmitis treatment].

Fungal endophthalmitis is a devastating infectious disease, with a poor visual prognosis and even possibility of eyeball enucleated. In recent years, the incidence of fungal endophthalmitis remarkably increased due to widely use of broad-spectrum antibiotics and corticosteroid hormone. This pose a challenge to ophthalmologists and their capacity of treating fungal endophthalmitis need to be improved. It is necessary to introduce the present status and progress in fungal endophthalmitis treatment focus on medications, surgery and its etiological examination, especially the use of newer antifungal agents, including voriconazole and liposomal amphotericin B.

[Ocular toxicity associated with drugs].

The clinical manifestation of ocular toxicity associated with drugs are various. The ocular toxic manifestations and the degree of impairment are different due to the variety, dose, and routes of exposure and so on. It is difficult to diagnose the cause of the toxicity. If we can't find the toxic factor immediately, stop the damage to the eyes, and treat in time, the patient's vision will be impaired or even lose. This article reviews ocular toxicity caused by drugs, including the variety of drugs, clinical manifestations, etiopathogenesis, diagnosis, treatment and prevention.

Meta-analysis of the relationship between obestatin and ghrelin levels and the ghrelin/obestatin ratio with respect to obesity.

INTRODUCTION: The association between gastrointestinal hormones, obestatin and ghrelin, and obesity are controversial. Here, the authors summarize results of published works in this field by using meta-analysis. METHODS: Studies that evaluated these hormones and were published before December 2009 were collected from PubMed, HighWire Press and ProQuest Health and Medical Complete. Software Review Manager 4.2 was used (Cochrane Collaboration, Oxford, England). Differences between obese and normal weight (NW) groups were compared using fixed or random effects models based on heterogeneity. RESULTS: In obestatin group, 9 studies with 566 participants were included and had significant heterogeneity (I² = 98.6%, P < 0.01). Obestatin of NW groups was 64.19 pg/mL [95% confidence interval (CI) = 36.11-92.26, P < 0.01] higher than those of obese groups. In total ghrelin group, 21 studies with 1187 participants were included and had significant heterogeneity (I² = 97.9%, P < 0.01). Total ghrelin of NW groups was 145.53 pg/mL (95%CI = 109.59-181.47, P < 0.01) higher than those of obese groups. In active ghrelin group, 6 studies with 265 participants were included and had significant heterogeneity (I² = 98.10%, P < 0.01). Active ghrelin in NW groups was 53.22 pg/mL (95%CI = 25.92-80.53, P < 0.01) higher than those of obese groups. In ghrelin/obestatin group, 5 studies with 259 participants were included and had significant heterogeneity (I² = 94.2, P < 0.01). The ratios in NW groups were 2.49 pg/mL (95%CI = 0.03-4.9, P = 0.05) higher than those of obese groups but without significance. CONCLUSIONS: Obestatin, total and active ghrelin in NW groups were significantly higher than those of obese groups. Ghrelin/obestatin ratios in NW groups were also higher but without significance.

[Diagnosis and treatment of eye diseases associated with HIV infection and AIDS].

OBJECTIVE: To investigate the manifestations and treatment principles of ocular diseases associated with human immunodeficiency virus infection (HIV) and acquired immunodeficiency syndrome (AIDS). METHODS: It was a retrospective case series. One hundred and ten patients were recruited. Two hundred and twenty eyes underwent ophthalmologic examination that included vision acuity, anterior segment and fundus examinations with papillary dilation and fundus fluorescein angiography. CD(4)(+)T-lymphocyte was counted in peripheral blood of 110 patients. Intravitreal injection of ganciclovir 400 microg was performed in 4 eyes (2 patients) with cytomegalovirus (CMV) retinitis associated with AIDS. All statistical analyses were performed using SPSS 13.0 software. The association between the age, duration of HIV infection and HIV/AIDS related ocular manifestations was analyzed by Pearson Correlation Analysis. The association between the gender and HIV/AIDS related ocular manifestations was analyzed by Pearson Chi-Square test. For comparison of the CD(4)(+)T cells counts of the patients with normal fundus, HIV retinopathy, CMV retinitis, Kruskal-Wallis Test for Several Independent Samples was used. RESULTS: Baseline visual acuity: no light perception (NLP) 5 eyes; light perception (LP) to 0.04, 10 eyes; 0.05 to 0.2, 14 eyes; 0.3 to 0.7, 62 eyes and >/= 0.8, 129 eyes. Small grayish keratin precipitates or pigment keratin precipitates were present in 25 eyes, 22 eyes had positive aqueous flare, 4 eyes had posterior synechia of the iris, 28 eyes had cataract. HIV retinopathy was present in 34 eyes. Cotton-wool spots, retinal hemorrhages, and retinal microaneurysms were found in eyes with HIV retinopathy. CMV retinitis was present in 32 eyes. The fundus manifestations of CMV retinitis included retinal vasculitis; dense, full-thickness, yellow-white lesions along vascular distribution with irregular granules at the border, and hemorrhage on the retinal surface in 26 eyes. Late stage retinopathy was demonstrated in 3 eyes characterized as atrophic retina, sclerotic and attenuated vessels, and optic nerve atrophy. Retinal detachment was found in 3 eyes. The median of CD(4)(+)T-lymphocyte counts of the patients with normal fundus was 100.0/mm(3). The median of CD(4)(+)T-lymphocyte counts of the patients with HIV retinopathy was 41.0/mm(3). The median of CD(4)(+)T-lymphocyte counts of the patients with CMV retinitis was 18.0/mm(3). The difference of CD(4)(+)T-lymphocyte counts between patients with normal fundus and HIV retinopathy was statistically significant (chi(2) = 4.848, P = 0.028). The difference of CD(4)(+)T-lymphocyte counts between patients with normal fundus and CMV retinitis was statistically significant (chi(2) = 15.696, P = 0.000). The difference of CD(4)(+)T-lymphocyte counts between patients with CMV retinitis and HIV retinopathy was statistically significant (chi(2) = 4.860, P = 0.027). Four eyes (2 patients) with CMV retinitis underwent intravitreal injection of ganciclovir 400 microg. After intravitreal injection of ganciclovir, visual acuity was improved and fundus lesions disappeared in 4 eyes. CONCLUSIONS: HIV retinopathy is a common intraocular complication in HIV-infected patients. CMV retinitis is the severest intraocular complication in patients with AIDS. Highly active anti-retroviral therapy allows immune reconstitution. Intravitreal injection of ganciclovir can effectively control CMV retinitis and save the vision.

Alpha1-macroglobulin: a potential obesity-related factor in serum.

BACKGROUND: The identification of factors related to obesity is very important for an early diagnosis of susceptibility to obesity and, accordingly, its prevention. The objective of the current study was to search for specific obesity-related factors in serum, as they can be measured non-invasively. MATERIAL/METHODS: Male Sprague-Dawley rats were fed a high-fat (HF) diet for eight weeks to generate obesity-prone (OP) and obesity-resistant (OR) rats. After blood sampling, serum proteome analysis was conducted using two-dimensional gel electrophoresis (2-DE) combined with mass spectrometry (MS). RESULTS: Apolipoprotein A-I (apo A-I), beta-actin, and vitamin D-binding protein (DBP) prepeptide were up-regulated in both the OP and OR rats. Two down-regulated haptoglobulins were observed in the OP and OR rats. Alpha1-macroglobulin (alpha1-M) and an unknown protein product were decreased in the OP rats compared with the OR rats. Alpha1-M was nearly undetectable in the OP rats from the 2-DE map and was further confirmed to be down-regulated by ELISA. CONCLUSIONS: The syntropic changes in the proteins apo A-I, beta-actin, DBP prepeptide, and haptoglobulin in the OP and OR rats might be a reflection of the HF diet. The unknown protein product should be isolated and identified. Alpha1-M is proved to be a potential serum factor related to obesity proneness and obesity resistance.

Post-weaning isocaloric hyper-soybean oil versus a hyper-carbohydrate diet reduces obesity in adult rats induced by a high-fat diet.

The aim of this study was to investigate the effects of a post-weaning isocaloric hyper-soybean oil diet on later obesity and explore the underlying mechanisms. In the present study, newborn male Wistar rats were weaned on d 24, divided into CON (control), HC and HSO groups. CON was assigned to AIN-93G diet (a hypercarbohydrate diet, for short HC diet) during the entire experiment. HC and HSO were fed with HC and isocaloric hyper-soybean oil (HSO) diet for 3 wk respectively, fed with HC diet for 2 wk successively, finally administrated high fat diet (HF) for 6 wk to induce obesity. On 3,5,11 wk, the body weight, body fat content, blood glucose, blood lipid, serum insulin and leptin levels and obesity-related gene (CPT-1, FAS, UCP2, UCP3) expression levels in rats were detected. It was shown that body weight, body fat content, blood glucose and blood lipid, serum insulin and leptin levels in HSO were down-regulated on 3 and 5 wk, therefore were significantly reduced on 11 wk vs. HC. The CPT-1, UCP2, UCP3 gene expressions were up-regulated but FAS were down-regulated persistently in HSO. The study indicated that an early isocaloric HSO diet may reduce later obesity risk and reduce blood lipid and glucose abnormalities in adulthood via persistently influencing insulin and leptin sensitivity and permanent regulation of obesity-related gene expressions.

[Effects of chromium and fish oil on the level of leptin and insulin in obese rats].

OBJECTIVE: In order to study the effects of chromium and fish oil on the level of leptin and insulin in obese rats, 32 obese model rats were divided randomly into four groups: fish oil group (5 ml/kg bw), chromium group (3 mg/kg bw), fish oil + chromium group and high fat diet group. METHODS: In the end of the experiment (6 weeks) fats around kidney and spermary were weighted and blood samples were collected to determine the level leptin and insulin. RESULTS: The results showed that the level of leptin and insulin in experimental groups were lower than those in high fat diet group. The ratios of fats around kidney and/or around spermary to body weight in experimental groups were lower than those in high fat diet group. CONCLUSION: Chromium and fish oil possible depress the high level of leptin and insulin in obese model rats.

[Effects of different diet composition after weaning on the obesity in rats induced by high-energy diet].

OBJECTIVE: To explore the effects of different diet composition on the obesity in rats induced by high-fat diet after weaning. METHODS: Male Wistar rats weaned on 24 days were randomly divided into groups A, B and C and were assigned to high carbohydrate, i.e. basic diet, high protein, high non-saturated fat diets respectively for 3 weeks. Then all groups were fed with basic diet. After 2 weeks, rats from group A were randomly divided into groups A1 and A2, A1 was assigned to basic diet continuously and groups A2, B, C were fed with high-fat diet for 6 weeks. 8 rats from each group were sacrified at the end of different treatments to detect serum glucose, TG and hormones dynamicly. RESULTS: High nonsaturated fat diet after weaning significantly reduced the body weight, body fat content, increased the sensitiveness to insulin, the levels of glucagons, FT4, FT3, improved leptin resistance in rats fed with high-fat diet. High-protein diet also reduced body weight, body fat content and increase lipolysis in rats fed with high-fat diet, but blood glucose in which group was higher than in group A2. CONCLUSION: High non-saturated fat diet after weaning can significantly reduce the obesity of rats fed with high-fat diet.

[Expression of hormone-sensitive lipase mRNA in diet-induced obesity resistant rats].

OBJECTIVE: In order to explore the expression of hormone-sensitive lipase (HSL) mRNA in white adipose tissue of diet-induced obesity-resistant (DIO-R) rats. METHODS: Fifty male Sprague-dawley (SD) rats were randomly divided into control group and high-fat group and they were fed with basic diet and high-fat diet respectively for 13 weeks. DIO-R and DIO rats were selected according to their body weight and the quantity of energy intake, then observing changing of the body fat content, the level of serum growth hormone was determined by radioimmunoassay and the level of the HSL mRNA in white adipose tissue was determined by RT-PCR. RESULTS: The body fat content of DIO-R rats were lower than those of DIO rats (P < 0.05). The level of serum growth hormone of DIO-R rats were higher than those of DIO rats (P < 0.05). High fat diets increased the level of the HSL mRNA in DIO-R rats. CONCLUSION: Increasing expression of HSL in white adipose tissue may play a part of role in resisting diet-induced obesity of rats.

[Expression of uncoupling protein-2 mRNA in diet-induced obesity-resistant rats].

OBJECTIVE: To explore the expression of uncoupling protein-2 mRNA in brown adipose tissue, white adipose tissue and skeletal muscle of diet-induced obesity-resistant (DIO-R) rats. METHODS: Fifty male Sprague-Dawley (SD) rats were randomly divided into a control group and a high-fat group and fed with basic diet and high-fat diet respectively for 13 weeks. DIO-R and DIO rats were selected according to their body weight. The change of body weight and the intake of total calorie were observed. Reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the expression of UCP2 mRNA in rat. RESULTS: Body weight and total calorie intake in DIO-R rats (425.1 +/- 27.1) g, (31,693 +/- 946) kJ were significantly lower than those in DIO rats (489.7 +/- 20.5) g, (34,363 +/- 1465) kJ. The peak area of UCP2 mRNA in white adipose tissue in DIO-R rats was 352 +/- 30 and in DIO rats was 101 +/- 12. The peak areas of UCP2 mRNA in skeletal muscle in DIO-R and DIO rats were 130 +/- 15 and 170 +/- 12, respectively. The peak areas of UCP2 mRNA in brown adipose tissue of DIO and DIO-R rats were 124 +/- 14 and 147 +/- 19, respectively. CONCLUSION: The expression of UCP2 mRNA in white adipose tissue of DIO-R rats increased significantly. These results suggest that obesity-resistance was associated with a tissue-specific increase in UCP2 expression.