Biomedical subjects

H J Wang

Publications and source records attributed to H J Wang.

At least 37 records · Page 2Linked to original sources

PubMed2001

Prognostic significance of circulating microsatellite markers in the plasma of melanoma patients.

PURPOSE: Multiple genetic alterations including loss of heterozygosity (LOH) occur commonly in melanoma tumors. We demonstrated previously free-circulating DNA microsatellites with LOH in the blood of melanoma patients. These LOH markers in plasma may be useful as surrogates for subclinical disease progression. The purpose of this study was to determine whether the presence of circulating tumor microsatellite markers in the preoperative blood from patients with melanoma has prognostic utility. EXPERIMENTAL DESIGN: Plasma was analyzed for the presence of LOH at six chromosome regions, which are common for allelic loss in melanoma tumors, in 57 patients undergoing surgical resection of all of the clinically apparent disease. RESULTS: LOH was detected in 32 of 57 patients (56%). Both LOH incidence and frequency correlated with advancing American Joint Committee on Cancer stage. In patients with American Joint Committee on Cancer stage III, the presence of LOH as an independent variable in preoperative plasma was significantly associated (P = 0.05) with an increased risk of death. Furthermore, LOH at microsatellite marker D1S228 in the plasma of patients with advanced disease correlated significantly (P = 0.0009) with a poorer survival after surgical resection. LOH commonly found in melanoma tumors can be successfully identified in the plasma of a patient, providing a potentially less invasive route for following genetic changes that serve as molecular surrogates for assessing subclinical disease progression. CONCLUSIONS: This study provides evidence that blood testing for circulating tumor genetic markers may provide valuable prognostic information and guide future therapy.

DNA, Neoplasm↗

PubMed2001

Nocistatin, a peptide reversing acute and chronic morphine tolerance.

It has been reported that intracerebroventricular (i.c.v.) injection of nociception/orphanin FQ (OFQ) can antagonize morphine analgesia, whereas i.c.v. OFQ antibody can reverse morphine tolerance. Nocistatin (NST) is a recently characterized neuropeptide possessing an antagonizing effect on OFQ. Here we examine whether i.c.v. NST would result in a reversal of morphine tolerance. The results showed that: (1) i.c.v. NST at doses of 0.005, 0.05, 0.5, 5 or 50 ng per rat produced a bell-shaped dose-dependent reversal of chronic morphine tolerance, with maximum response at 0.5 ng. (2) Acute morphine tolerance could also be reversed, albeit partially, by i.c.v. NST at 0.5 ng. (3) The reversal of acute and chronic morphine tolerance by NST was completely abolished when NST (0.5 ng) was co-injected with (8 microg) OFQ. Since OFQ and NST are derived from the same preprohormone, the profile of its splicing in the CNS may play an important role in determining the effectiveness of morphine analgesia.

Analgesics, Opioid↗

PubMed2001

Molecular staging of early colon cancer on the basis of sentinel node analysis: a multicenter phase II trial.

PURPOSE: Approximately 30% of patients with American Joint Committee on Cancer stage I or II colorectal cancer (CRC) develop systemic disease. We hypothesized that multimarker reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of sentinel lymph nodes (SNs) draining a primary CRC could detect micrometastases not detected by conventional histopathologic analysis. PATIENTS AND METHODS: In a multi-institutional study, 40 patients with primary CRC underwent dye-directed lymphatic mapping at the time of colon resection. Each dye-stained SN was tagged, and the tumor and regional nodes were resected en bloc. All lymph nodes were examined by conventional hematoxylin and eosin (HE) staining. In addition, each SN was cut into multiple sections for cytokeratin immunohistochemical (CK-IHC) staining and for RT-PCR and electrochemiluminescent detection of three markers: beta-chain human chorionic gonadotropin, hepatocyte growth factor receptor, and universal melanoma-associated antigen. Whenever possible, RT-PCR assay was also performed on primary tumor tissue. The detection sensitivity of individual markers was 10(-3) to 10(-4) microg of RNA and one to five tumor cells in 10(7) lymphocytes of healthy donors. RESULTS: One to three SNs were identified in each patient. An average of 15 nodes were removed from each CRC specimen. No nonsentinel (untagged) node contained evidence of tumor if all tagged (sentinel) nodes in the same specimen were histopathology tumor-negative. HE staining of SNs identified tumor in 10 patients (25%), and CK-IHC of SNs identified occult micrometastases in four patients (10%) whose SNs were negative by HE. Of the remaining 26 patients with no evidence of SN involvement by HE or CK-IHC, 12 (46%) had positive RT-PCR results. The number of markers expressed in each SN correlated (P <.04) with the T stage of the primary tumor. There was 79% concordance in marker expression for the respective pairs (n = 38) of primary tumor and histopathologically positive SNs, and 86% (12 of 14) concordance between RT-PCR positive and histopathologically positive SNs. CONCLUSION: Identification and focused examination of the SN is a novel method of staging CRC. CK-IHC and RT-PCR identified occult micrometastases in 53% of patients whose SNs were negative by conventional staging techniques. These ultrasensitive assays of the SN can identify patients who may be at high risk for recurrence of CRC and therefore are more likely to benefit from systemic adjuvant therapy.

Antigens, Neoplasm↗

PubMed2001

Ventral margin of the paracaval portion of human caudate lobe.

The topographic anatomy of the ventral margin of the caudate lobe of the human liver is still obscure. We hypothesized the existence of a "precaudate plane", as a flat or slightly curved plane defined by the ventral margins of both the ligamentum venosum and hilar plate. Using 61 cadaveric liver specimens, without great differences in external shape or significant variations in the hilar bifurcation, we examined whether the paracaval caudate branches (PCs) ran through the plane to the ventral side. In 22 of the 61 specimens (36.1%), the PC extended over the plane for less than 10 mm (10 specimens), for 10-20 mm (7 specimens), or for more than 20 mm (5 specimens). The ventral extension consistently included the dome-like area under the terminals of the middle and right hepatic veins. Therefore, the ventrally extended PCs often interdigitated with these veins and their tributaries. The ventral extension often reached the upper, diaphragmatic surface. However, several branches were too difficult to discriminate from the PC, especially those with morphologies intermediate between the PC and segmental portal branches to S4 or S2. We discuss how to identify and manage the ventrally extended PCs before and during surgery.

Aged↗

PubMed2001

The management of white phosphorus burns.

Phosphorus burns are a rarely encountered chemical burn, typically occurring in battle, industrial accidents, or from fireworks. Death may result even with minimal burn areas. Early recognition of affected areas and adequate resuscitation is crucial. Amongst our 2765 admissions between 1984 and 1998, 326 patients had chemical burns. Seven admissions were the result of phosphorus burns. Our treatment protocol comprises 1% copper sulfate solution for neutralization and identification of phosphorus particles, copious normal saline irrigation, keeping wounds moist with saline-soaked thick pads even during transportation, prompt debridement of affected areas, porcine skin coverage or skin grafts for acute wound management, as well as intensive monitoring of electrolytes and cardiac function in our burns center. Intravenous calcium gluconate is mandatory for correction of hypocalcemia. Of the seven, one patient died from inhalation injury and the others were scheduled for sequential surgical procedures for functional and cosmetic recovery. Cooling affected areas with tap water or normal saline, prompt removal of phosphorus particles with mechanical debridement, intensive monitoring, and maintenance of electrolyte balance are critical steps in initial management. Fluid resuscitation can be adjusted according to urine output. Early excision and skin autografts summarize our phosphorus burn treatment protocol.

Adolescent↗

PubMed2001

Implementation of a primary care physician network obesity management program.

Most primary care physicians do not treat obesity, citing lack of time, resources, insurance reimbursement, and knowledge of effective interventions as significant barriers. To address this need, a 10-minute intervention delivered by the primary care physician was coupled with individual dietary counseling sessions delivered by a registered dietitian via telephone with an automated calling system (House-Calls, Mobile, AL). Patients were seen for follow-up by their physician at weeks 4, 12, 24, 36 and 52. A total of 252 patients (202 women and 50 men) were referred by 18 primary care physicians to the program. The comorbid conditions reported for all patients at baseline included low back pain, 29% (n = 72); hypertension, 45% (n = 113); hypercholesterolemia, 41% (n = 104); type 2 diabetes, 10% (n = 26); and sleep apnea, 5% (n = 12). When offered a choice of meal plans based on foods or meal replacements, two-thirds of patients (n = 166) chose to use meal replacements (Ultra Slim-Fast; Slim-Fast Foods Co., West Palm Beach, FL) at least once daily. Baseline weights of subjects averaged 200 +/- 46 lb for women (n = 202) and 237 +/- 45 lb for men (n = 50). Patients completing 6 months in the program lost an average of 19.0 +/- 4.0 lb for women (n = 94) and 15.5 +/- 8.2 lb for men (n = 26). Physicians reported a high degree of satisfaction with the program, suggesting that a brief, effective physician-directed program with nutritionist support by telephone can be implemented in a busy primary care office.

Back Pain↗

PubMed2001

Liquid meal replacements and glycemic control in obese type 2 diabetes patients.

OBJECTIVE: Although weight management is an important component in the treatment of type 2 diabetes, there has been concern about the use of liquid meal replacements (MRs) in treating obese patients with type 2 diabetes because of the sugar content of the MRs. The goal of this study was to evaluate the safety and feasibility of using MRs for weight loss in obese patients with type 2 diabetes. RESEARCH METHODS AND PROCEDURES: Seventy-five subjects with type 2 diabetes, treated only with oral agents, were recruited for this 12-week clinical study. Subjects were randomized into three groups using either a MR containing lactose, fructose, and sucrose, a MR in which fructose and sucrose were replaced with oligosaccharides (sugar-free Slim-Fast), or an exchange diet plan (EDP) using the proportion of macronutrients recommended by the American Diabetes Association. RESULTS: Fifty-seven patients (41 MR and 16 EDP) finished the study. None developed serious adverse effects, including major hypoglycemic reactions. Weight losses in the MR 1 and MR 2 groups were comparable (6.4% and 6.7%, respectively) and greater than the weight loss in the EDP group (4.9%). Fasting glucose level was significantly reduced in the MR group compared with the EDP group (p = 0.012). There was a significant reduction in the MR group in total cholesterol and low-density lipoprotein cholesterol that was not seen in the EDP group. DISCUSSION: We have shown that liquid MRs are a safe and effective weight loss tool for obese subjects with type 2 diabetes, and can result in improvements in body weight, glucose, insulin, hemoglobin A1c and lipid levels.

Blood Glucose↗

PubMed2001

Molecular detection of metastatic melanoma cells in cerebrospinal fluid in melanoma patients.

Melanoma frequently metastasizes to the central nervous system (CNS). The diagnosis of CNS metastases typically is made following the onset of clinical symptoms. Thus, more sensitive diagnostic approaches are needed to identify subclinical CNS metastases. Currently, standard cytologic analysis of the cerebrospinal fluid (CSF) is limited by its poor sensitivity. A more sensitive assay was therefore developed using multiple reverse transcriptase-polymerase chain reaction (RT-PCR) markers. CSF was collected and assessed by RT-PCR for three known melanoma-associated markers (MAGE-3, MART-1, and tyrosinase) to detect occult metastatic melanoma cells in the CSF of 37 American Joint Committee on Cancer (AJCC) stage IV melanoma patients. Cytologic analysis of CSF was performed on all patients, and immunohistochemistry (IHC) analysis was performed on 33 CSF samples using anti-S100 and anti-HMB-45 antibodies. Only one patient (3%) had tumor-positive CSF cytology and IHC upon entry into the study, whereas 12 patients (32%) were positive for at least one RT-PCR marker. The correlation between CSF RT-PCR positivity of MART-1 and/or MAGE-3 and the development of CNS metastases at 3 mo was significant (p = 0.04). Fifteen of 37 patients (41%) had either positive MRI and/or positive RT-PCR results. Multimarker RT-PCR is more informative and sensitive than cytology/IHC in assessing the CSF of melanoma patients.

Adolescent↗

PubMed2001

Expression of hepatitis B virus X protein is closely correlated with the high periportal inflammatory activity of liver diseases.

Hepatitis B virus X (HBx) protein is a multifunctional protein that exerts dual activity on cell proliferation and death. Although HBx is thought to be a major determinant that leads to hepatocellular carcinoma, its pathophysiological role in humans remains to be established. Attempts have been made to evaluate the role of HBx in liver specimens derived from patients with chronic B viral hepatitis and hepatocellular carcinoma. Among 25 paired liver specimens of hepatocellular carcinoma and corresponding nontumour liver tissues, HBx mRNA was hardly detected and was significantly lower than other HBV transcripts. An immunohistochemical study demonstrated that expression of HBx protein was also lower than other HBV gene products. Interestingly, however, expression of HBx protein changed with the progression of chronic hepatitis. HBx was expressed in 5.0% of patients with chronic hepatitis without cirrhosis but increased to 44.8% in chronic hepatitis with cirrhosis. In contrast, only one (3.7%) of 27 hepatocellular carcinomas showed HBx positivity whereas 29.6% of surrounding nontumour tissues was still HBx-positive. These results suggest that HBx may play a major role at the promotion stage of carcinogenesis. Noticeably, HBx-positive cells were preferentially localized in the periportal region of chronic hepatitis or periphery of cirrhotic nodules where high necroinflammatory activity was accompanied. We found a positive correlation between HBx expression and periportal inflammatory activity (P < 0.001). Thus, HBx may potentiate cell destruction and regeneration of liver that provide an opportunity for the accumulation of genetic mutations, which contribute to multistep hepatocarcinogenesis.

Carcinoma, Hepatocellular↗

PubMed2001

Salvage of completely degloved finger with a posterior interosseous free flap.

The use of a free posterior interosseous skin flap should be considered in a single digit degloving injury, especially when replantation of the avulsed skin or the use of skin from the second toe, transferred as a composite-tissue flap, is not feasible. The flap is thin and pliable. It allows early mobilisation with good recovery of joint motion and attains protective sensation of the finger.

Accidents, Occupational↗

PubMed2001

Disaster epidemiology and medical response in the Chi-Chi earthquake in Taiwan.

STUDY OBJECTIVE: We examine the mortality and morbidity associated with earthquakes in the Chi-Chi earthquake in Taiwan in 1999. METHODS: Crude casualty data were collected from the reports of the government, local health bureaus, and 97 hospitals. The demographic data from the annual report of the Department of Interior were also employed for data analysis. Cross tables showing incidence of deaths and injuries by age, sex, time, and geographic distribution were generated to compare the mortality among different subgroups. Multiple regression models were established to explore the risk factors related to the mortality caused by earthquakes. RESULTS: The following results were found: the mortality rate increased with proximity to the epicenter, mortality was higher among the elderly than among young people, 30% of the victims died from head injuries caused by the collapse of dwellings, and the peak of medical demand was 12 hours after the earthquake and significantly increased demand for care lasted as long as 3 days. Furthermore, the regression model indicated that 78.5% of the variation of locality-age-sex-specific mortality was explained by the intensity of the earthquake, age, population density, distance to epicenter, medical beds per 10,000 people, and physicians per 10,000 people. CONCLUSION: The results implied that fragile minorities, specifically the elderly and children, require special consideration and attention in regard to disaster rescue and emergency medical care allocation. Epidemiologic analysis can guide disaster response and preparation.

Adolescent↗

PubMed2001

Expression of porcine growth hormone gene in transgenic rabbits as reported by green fluorescent protein.

Sperm-mediated gene transfer was used to produce transgenic rabbits that expressed the porcine growth hormone gene under the control of a metallothionein promoter. The gene that encodes the selectable marker green fluorescent protein (GFP) was inserted downstream of the transgene. After lipofectin-mediated gene transfer into sperm cells and after subsequent in vitro fertilization using the transfected sperm cells, 32% of the cultured blastocysts exhibited bright green fluorescence when stimulated with blue light. Of the 74 adult rabbits and five fetal rabbits (age, gestational day 15), 2 fetuses and 29 rabbits were GFP-positive as indicated by PCR analysis. Southern blot analysis of their genomic DNA showed that 13 of 21 GFP-positive rabbits were transgenic. GFP expression was observed in different tissues of transgenic rabbits and the growth rate of four GFP-positive rabbits was greater than that of controls. PCR analysis showed that one of six F1 offspring was transgenic. These results suggest that lipofectin-mediated gene transfer into sperm cells can be used to efficiently produce transgenic rabbits.

Animals↗

PubMed2001

Reconstruction of burn scar of the upper extremities with artificial skin.

The management of upper-extremity burn contractures is a major challenge for plastic surgeons. After approval by the Food and Drug Administration, artificial skin (Integra) has been available in Taiwan since 1997. From January of 1997 to July of 1999, the authors applied artificial skin to 13 severely burned patients for the reconstruction of their upper extremities, resulting in an increased range of motion in the upper-extremity joints and improved skin quality. An additional benefit was the rapid reepithelialization of the donor sites. There were no complications of infection throughout the therapeutic course, and the overall results were satisfactory. During the 2-year study, scar condition was monitored between 8 and 24 months, and a good appearance and pliable skin were obtained according to the Vancouver Scar Scale. According to this evaluation of Oriental skin turgor, normal pigmentation was restored about 6 months after the resurfacing procedure. For patients with severe burns in whom there is insufficient available skin for a full-thickness skin graft or another appropriate flap for scar revision, Integra is an alternative. The two major concerns in dealing with artificial skin are (1) a 10- to 14-day waiting period for maturation of the neo-dermis, necessitating a two-stage operation, and (2) prevention of infection with antibiotics and meticulous wound care.

Adolescent↗

PubMed2001

Insulin-leptin-visceral fat relation during weight loss.

INTRODUCTION: The relation between insulin-leptin-visceral fat axis during weight loss has not been studied previously. AIMS: To evaluate the insulin, leptin, and abdominal adiposity relation during weight loss in patients with upper body obesity. METHODOLOGY: Twenty volunteers (7 men, 13 women) with mean age 50.6+/-6.3 (SD) and upper body obesity (weight 105.4+/-12.3 kg, BMI 35.9+/-2.5 kg/m2) were recruited. Participants were enrolled in a one-arm clinical study using a calorie-deficient diet and an escalating dose regimen of sibutramine, starting with 5 mg daily and increasing in 5-mg increments to 20 mg per day. Body weight, insulin, leptin, glucose, lipids, abdominal computed tomography (CT), and total body electrical conductance (TOBEC) were measured serially at weeks 0, 4, 8, 12, and 24. RESULTS: Eighteen patients completed the 6-month study: one man and one woman discontinued because of adverse events. With diet and sibutramine, body weight was significantly and continuously reduced throughout the 6-month study. There was a 16.0% (p = 0.0001) reduction in body weight (p < 0.001) and 22.5% (p = 0.0001) decrease in total body fat mass. Abdominal CT scans showed a 28.3% (p = 0.0001) reduction in total abdominal fat, a 26.0% (p = 0.0001) reduction in subcutaneous fat (p < 0.001), and a 31.0% (p = 0.0003) reduction in visceral fat (p < 0.001). There was a 32.0% (p = 0.0008) reduction in leptin levels and 37.9% (p = 0.0001) reduction in insulin levels between baseline and week 4, but no further significant reduction in leptin and insulin levels was observed for the duration of the study. There was a significant correlation between insulin and leptin concentrations throughout the study (p = 0.0001). Leptin was presented as a function of insulin measured at the same time. Significant associations between visceral abdominal fat, subcutaneous fat, and leptin were also observed. CONCLUSION: In this study, we found that leptin and insulin were related in weight loss. The data suggest that insulin may act as a strong regulator of leptin secretion during weight loss and that circulating leptin levels can be predicted by insulin level. Using sibutramine in conjunction with hypocaloric diet reduced body weight and decreased fat mass significantly. Visceral and subcutaneous abdominal fat depots were shown to decrease. Whether sibutramine exerts any selective reduction of visceral abdominal fat as opposed to total body fat mass will require further clinical investigation.

Adipose Tissue↗

PubMed2001

Insertional mutagenesis in the n-alkane-assimilating yeast Yarrowia lipolytica: generation of tagged mutations in genes involved in hydrophobic substrate utilization.

Tagged mutants affected in the degradation of hydrophobic compounds (HC) were generated by insertion of a zeta-URA3 mutagenesis cassette (MTC) into the genome of a zeta-free and ura3 deletion-containing strain of Yarrowia lipolytica. MTC integration occurred predominantly at random by nonhomologous recombination. A total of 8,600 Ura(+) transformants were tested by replica plating for (i) growth on minimal media with alkanes of different chain lengths (decane, dodecane, and hexadecane), oleic acid, tributyrin, or ethanol as the C source and (ii) colonial defects on different glucose-containing media (YPD, YNBD, and YNBcas). A total of 257 mutants were obtained, of which about 70 were affected in HC degradation, representing different types of non-alkane-utilizing (Alk(-)) mutants (phenotypic classes alkA to alkE) and tributyrin degradation mutants. Among Alk(-) mutants, growth defects depending on the alkane chain length were observed (alkAa to alkAc). Furthermore, mutants defective in yeast-hypha transition and ethanol utilization and selected auxotrophic mutants were isolated. Flanking borders of the integrated MTC were sequenced to identify the disrupted genes. Sequence analysis indicated that the MTC was integrated in the LEU1 locus in N083, a leucine-auxotrophic mutant, in the isocitrate dehydrogenase gene of N156 (alkE leaky), in the thioredoxin reductase gene in N040 (alkAc), and in a peroxine gene (PEX14) in N078 (alkD). This indicates that MTC integration is a powerful tool for generating and analyzing tagged mutants in Y. lipolytica.

Alkanes↗

PubMed2001

Synergistic neutrophil elastase-cytokine interaction degrades collagen in three-dimensional culture.

Proteolytic degradation of extracellular matrix is thought to play an important role in many lung disorders. In the current study, human lung fibroblasts were cast into type I collagen gels and floated in medium containing elastase, cytomix (combination of tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma), or both. After 5 days, gel collagen content was determined by measuring hydroxyproline. Elastase alone did not result in collagen degradation, but in the presence of fibroblasts, elastase reduced hydroxyproline content to 75.2% (P < 0.01), whereas cytomix alone resulted in reduction of hydroxyproline content to 93% (P < 0.05). The combination of elastase and cytomix reduced hydroxyproline content to 5.2% (P < 0.01). alpha(1)-Proteinase inhibitor blocked this synergy. Gelatin zymography and Western blot revealed that matrix metalloproteinase (MMP)-1, -3, and -9 were induced by cytomix and activated in the presence of elastase. Tissue inhibitor of metalloproteinase (TIMP)-1 and -2 were also induced by cytomix but were cleaved by elastase. We conclude that a synergistic interaction between cytomix and elastase, mediated through cytokine induction of MMP production and elastase-induced activation of latent MMPs and degradation of TIMPs, can result in a dramatic augmentation of collagen degradation. These findings support the notion that interaction among inflammatory mediators secreted by mononuclear cells and neutrophils can induce tissue cells to degrade extracellular matrix. Such a mechanism may contribute to the protease-anti-protease imbalance in emphysema.

Animals↗

PubMed2001

Contraction of fibroblast-containing collagen gels: initial collagen concentration regulates the degree of contraction and cell survival.

Remodeling of extracellular matrix involves a number of steps including the recruitment, accumulation, and eventual apoptosis of parenchymal cells as well as the production, organization, and rearrangement of extracellular matrix produced by these cells. The culture of fibroblasts in three-dimensional gels made of type I collagen has been used as a model of tissue contraction which characterizes both wound repair and fibrosis. The current study was designed to determine the effect of initial collagen concentration on the ability of fibroblasts to contract collagen gels and on cell survival. Native type I collagen was extracted from rat tail tendons and used to prepare collagen gels with varying collagen concentrations (0.75-2.0 mg/ml). Human lung fibroblasts (HFL-1) were cast into the gels and cultured in Dulbecco modified Eagle medium with 0.1% fetal calf serum for 2 wk. The gel size, collagen content, and deoxyribonucleic acid (DNA) content were determined. Gels prepared with an initial concentration of 0.75 mg/ml contracted more rapidly and to a smaller final size than gels prepared from 2 mg/ml initial collagen concentration (final size 7.1 versus 36.4% of initial size, P < 0.01). There was no significant degradation of the collagen in the gels under either condition. Hence, the dramatically increased contraction of the lower density gels resulted in a higher final density (P < 0.01). Cell density was estimated from DNA content. In low initial density gels, the final DNA content was significantly less than that in higher initial density gels (0.73 versus 1.88 microg/gel, P < 0.05). This was accompanied by an increased percentage of apoptotic cells at day 14 (43.3 versus 34.1%, P < 0.05). If the gels were maintained in the attached state which largely prevents contraction, apoptosis was significantly reduced, suggesting that contraction rather than matrix composition was a requirement for the increased apoptosis. In summary, these findings indicate that the initial matrix composition can lead to differing outcomes during fibroblast-mediated wound contraction.

Apoptosis↗

PubMed2001

Comparison of the metabolic effects of metformin and troglitazone on fructose-induced insulin resistance in male Sprague-Dawley rats.

BACKGROUND AND PURPOSE: Insulin resistance is a hallmark of the development of type 2 diabetes. Metformin and troglitazone are oral antidiabetic agents used to reduce insulin resistance. The aim of this study was to compare the metabolic effects of these two drugs in fructose-induced insulin-resistant rodents. METHODS: Male Sprague-Dawley rats were allocated to receive one of the following four treatments for 6 weeks: normal rat chow (control group, n = 7), high-fructose diet (fructose group, n = 7), high-fructose diet plus metformin (metformin group, n = 8), or high-fructose diet plus troglitazone (troglitazone group, n = 8). Systolic blood pressure (SBP), insulin, free fatty acid (FFA), and triglyceride concentrations were measured as parameters of insulin resistance. Leptin concentration was also measured in the four groups. RESULTS: The fructose group developed significantly elevated SBP, hyperinsulinemia, and hypertriglyceridemia without significant change in body weight or leptin concentration compared with the control group. The metformin group had significantly reduced body weight (397.9 +/- 40.9 vs 470.1 +/- 59.6 g, p < 0.05), insulin concentration (14.8 +/- 10.5 vs 48.4 +/- 15.2 microU/mL, p < 0.05), triglyceride concentration (75.3 +/- 65.5 vs 250.1 +/- 95.7 mg/dL, p < 0.05), and leptin concentration (3.1 +/- 1.5 vs 6.9 +/- 2.0 ng/mL, p < 0.05) without significant change in SBP (147.8 +/- 5.8 vs 152.4 +/- 13.0 mm Hg, p > 0.05) compared with the fructose group. The troglitazone group had significantly reduced SBP (137.8 +/- 9.2 vs 152.4 +/- 13.0 mm Hg, p < 0.05), insulin concentration (15.0 +/- 13.6 vs 48.4 +/- 15.2 microU/mL, p < 0.05), FFA concentration (38.9 +/- 22.7 vs 78.7 +/- 24.6 mg/dL, p < 0.05), triglyceride concentration (67.6 +/- 32.4 vs 250.1 +/- 95.7 mg/dL, p < 0.05), and leptin concentration (4.4 +/- 2.0 vs 6.9 +/- 2.0 ng/mL, p < 0.05) without significant change in body weight (452.5 +/- 32.8 vs 470.1 +/- 59.6 g, p > 0.05) compared with the fructose group. The metabolic effects of metformin and troglitazone on insulin, FFA, triglyceride, and leptin concentrations were not significantly different. However, metformin treatment resulted in significantly lower body weight (397.9 +/- 40.9 vs 452.5 +/- 32.8 g) and troglitazone treatment in significantly lower SBP (137.8 +/- 9.2 vs 147.8 +/- 5.8 mm Hg) compared to the fructose group, after adjusting for basal values (p < 0.05). CONCLUSIONS: Both metformin and troglitazone were comparably effective in reducing insulin resistance. Metformin treatment caused body weight reduction but was not effective in reducing SBP. Troglitazone treatment lowered SBP but did not reduce body weight.

Animals↗