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Biomedical subjects

Richard Peterson

Publications and source records attributed to Richard Peterson.

6 recordsLinked to original sources

Effects of xenobiotics and steroids on renal and hepatic estrogen metabolism in lake trout.

Experiments were conducted to (1) elucidate the biochemical pathways of E2 metabolism in the lake trout (Salvelinus namaycush) kidney and liver, and (2) test the hypothesis that specific xenobiotics and endogenous steroids inhibit E2 metabolism by these tissues. Kidney and liver tissue fragments from immature lake trout were incubated in vitro in the presence of radiolabelled E2 plus various xenobiotics or steroids. E2 metabolites were identified by liquid chromatography/mass spectroscopy, and quantified by liquid scintillation spectroscopy. A major metabolite produced by both tissues was an unidentified hydroxylated estrogen metabolite (E2-OH) with a molecular mass of 288 that was not estriol (16-OH-E2), but possibly 7alpha-OH-E2 or 2-OH-E2 (catecholestrogen). Both tissues also produced estradiol-17-glucuronide (E2-17-G), estradiol-17-sulfate (E2-17-S), and estradiol-3-glucuronide (E2-3-G). Compared to the kidney, the liver produced half the amount of conjugated metabolites, but twofold more E2-OH. The following xenobiotics (at a concentration of 100 microM) inhibited the production of water-soluble (i.e., conjugated) E2 metabolites by both the kidney and liver: 4,4'-(OH)2-3,3',5,5'- tetrachlorobiphenyl (4,4'-OH-TCB), bisphenol A (BPA), tetrabromobisphenol A (TB-BPA), tetrachlorobisphenol A (TC-BPA), tribromophenol (TBP), trichlorophenol (TCP), and pentachlorophenol (PCP). The alkylphenols, 4-n-nonylphenol (NP), and 4-octylphenol (OP), and 2,2',4,4'-tetrabromodiphenyl ether (TBDE) had no significant effect on E2 metabolism by either tissue. Testosterone and 17alpha,20beta-dihydroxy-4-pregnen-3-one inhibited the production of conjugated E2 metabolites by both the kidney and liver. Cortisol and 11-ketotestosterone inhibited E2 metabolism by the liver only. The median inhibitory concentrations (IC50) for 4,4'-OH-TCB ranged from 7-32 microM in the kidney and 0.6-1.6 microM in the liver. For BPA, IC50's ranged from 40-108 microM in the kidney and 11-18 microM in the liver. Low doses (0.1 microM) of 4,4'-OH-TCB and BPA significantly increased estrogen metabolism in the kidney. The results suggest that certain estrogenic xenobiotics and endogenous steroids may inhibit the phase II conjugation of E2 by the kidney and liver of lake trout, and some of the known biological effects of these compounds are likely mediated, at least partially, by this mechanism of action.

Animals↗

Distributed neural representation of expected value.

Anticipated reward magnitude and probability comprise dual components of expected value (EV), a cornerstone of economic and psychological theory. However, the neural mechanisms that compute EV have not been characterized. Using event-related functional magnetic resonance imaging, we examined neural activation as subjects anticipated monetary gains and losses that varied in magnitude and probability. Group analyses indicated that, although the subcortical nucleus accumbens (NAcc) activated proportional to anticipated gain magnitude, the cortical mesial prefrontal cortex (MPFC) additionally activated according to anticipated gain probability. Individual difference analyses indicated that, although NAcc activation correlated with self-reported positive arousal, MPFC activation correlated with probability estimates. These findings suggest that mesolimbic brain regions support the computation of EV in an ascending and distributed manner: whereas subcortical regions represent an affective component, cortical regions also represent a probabilistic component, and, furthermore, may integrate the two.

Adult↗

(+)-Z-Bisdehydrodoisynolic acid ameliorates obesity and the metabolic syndrome in female ZDF rats.

OBJECTIVE: The putative selective estrogen receptor modulator (+)-Z-bisdehydrodoisynolic acid (Z-BDDA) has been found to improve cardiovascular risk in rodents. The objective of this study was to investigate the effectiveness of (+)-Z-BDDA compared with the antidiabetic drug, rosiglitazone, in treating obesity and risk factors associated with the metabolic syndrome. RESEARCH METHODS AND PROCEDURES: Female Zucker Diabetic Fatty rats were randomly assigned to three treatment groups for 29 weeks: control (C), 1.8 mg (+)-Z-BDDA/kg diet [control diet + (+)-Z-BDDA (CB)], or 100 mg rosiglitazone/kg diet [control diet + rosiglitazone (CR)]. At sacrifice, physiological, biochemical, and molecular parameters were examined. RESULTS: CB animals gained less weight and exhibited a decrease in total body lipids (p < 0.05) as compared with C or CR rats. Body weight and total body lipids were the highest in CR rats (p < 0.05). Liver weights in CB and CR rats were lower (p < 0.05) than in C rats, whereas kidney weights were lower in CB (p < 0.05) than in C and CR animals. Fasting plasma glucose was lower (p < 0.05) in the CB and CR animals when compared with C animals. C rats exhibited the highest concentration of total plasma cholesterol, and CR-treated rats exhibited the lowest concentration. Plasma triglycerides followed the same pattern as plasma cholesterol. Histomorphometry of heart vasculature revealed that CB and CR treatments produced a significant shift from small to large venules and arterioles compared with C (p < 0.05). Liver expression profiles of peroxisome proliferator-activated receptor (PPAR) alpha, PPARgamma, and PPAR-regulated genes revealed encouraging CB-induced effects. DISCUSSION: These results suggest that (+)-Z-BDDA may have applications in treating obesity and complications associated with the metabolic syndrome.

Animals↗

Gene expression and adiposity are modified by soy protein in male Zucker diabetic fatty rats.

It has earlier been demonstrated that soy protein diets ameliorate the diabetic phenotype in obese Zucker rats. In this study, we further investigated physiological changes related to adiposity in male Zucker diabetic fatty rats consuming soy-based diets and compared these diets with the insulin-sensitizing drug, rosiglitazone. Transcript abundance of known genes was assessed in the livers to identify potential molecular connections between soy diets and adiposity. Male Zucker diabetic fatty rats were assigned to casein (C) protein, low-isoflavone soy (LIS) protein, high-isoflavone soy (HIS) protein, or C + rosiglitazone (CR) diets. Compared with the C diet, the LIS diet decreased plasma lipids and increased body weight, but did not change liver weight or carcass adiposity. HIS decreased plasma lipids, liver weight, and body weight. CR decreased plasma lipids and increased carcass adiposity and body weight with no effect on liver weight. In LIS livers, 15 genes involved in signaling and lipid metabolism were up-regulated 2-fold or higher. In HIS livers, seven genes had a 2-fold or higher change in abundance. However, in CR livers, none of the genes was significantly changed compared with the C diet. There appears to be a distinct change in gene expression associated with soy diets as compared with C-based diets and rosiglitazone treatment.

Adipose Tissue↗

Hemicorporectomy for chronic pressure ulcer carcinoma: 7 years of follow-up.

Development of squamous cell carcinoma (Marjolin's ulcer), a well-known and rare complication of chronic ulcers, sinuses, chronic osteomyelitis and burn scars, may complicate chronic pressure ulcers. For several years, reports have suggested these cancers (pressure sore carcinoma, PSC) are highly fatal and aggressive, unlike other Marjolin's ulcers. A 39-year-old male, paraparetic from spina bifida, with history of chronic pressure sores and osteomyelitis of the pelvic bones underwent multiple resections. A descending colostomy was performed to avoid soiling of the perineum and decubitus ulcers. He developed squamous cell carcinoma in multiple pelvic areas. He was dependent on two daily visits by home care nurses for wound care. After negative workup for metastasis, as his only chance for cure he was offered hemicorporectomy, which was performed at the L4-L5 disc level. A prosthesis was applied 1 month after the surgery. As of November 2003, he remains disease-free after 7 years (90 months) from initial surgery. He is employed as a computer programmer, is self-dependent, and also drives. Aggressive treatment in select patients with PSC is essential and can lead to long-term disease control and increase in overall quality of life.

Adult↗