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Biomedical subjects

B A Walsh

Publications and source records attributed to B A Walsh.

10 recordsLinked to original sources

Chronic estradiol treatment attenuates stiffening, glycoxidation, and permeability in rat carotid arteries.

Aging-related changes in vascular stiffening and permeability are associated with cardiovascular disease. We examined the interaction of estradiol on the aging process in vascular tissue from rats by assessing the changes in endothelial layer permeability, arterial compliance, and glycoxidative damage levels. We isolated carotid arteries from ovariectomized (OVX) rats that underwent 1 yr of estrogen treatment with subcutaneous pellets and a subsequent 1 mo of cessation of treatment. Endothelial layer permeability and arterial compliance were determined using quantitative fluorescence microscopy. Endothelial layer permeability was reduced with estradiol treatment (estrogen groups, 2.58 +/- 0.21 ng dextran x min(-1) x cm(-2) vs. nonestrogen groups, 4.01 +/- 0.30 ng dextran x min(-1) x cm(-2); P < 0.05). Additionally, arteries from animals treated with estradiol had an increased compliance index (estrogen groups, 82.9 +/- 3.8 mm2. Torr vs. nonestrogen groups, 69.3 +/- 3.2 mm2. Torr; P < 0.05). Estradiol treatment also reduced levels of pentosidine, which is a specific marker of glycoxidative damage (estrogen groups, 0.11 +/- 0.03 pmol pentosidine/nmol collagen vs. nonestrogen groups, 0.20 +/- 0.03 pmol pentosidine/nmol collagen; P < 0.05). These results indicate that estradiol has multiple chronic vasculoprotective effects on the artery wall to maintain normal vascular wall function.

Animals↗

17beta-estradiol acts separately on the LDL particle and artery wall to reduce LDL accumulation.

Estrogen replacement therapy has been shown to attenuate atherogenesis, although the mechanisms for this effect are incompletely defined. Previously, we showed that 17-beta estradiol (estradiol) attenuated oxidant stress-induced increases in vascular low density lipoprotein (LDL) accumulation. It was unclear whether estradiol's effect was imparted on the lipoprotein particle or the artery wall. To examine this, we chronically treated rats with the following sex hormones: low estradiol, high estradiol, progesterone, low estradiol + progesterone, placebo, or control. Carotid arteries (n = 8/group) were isolated and perfused with fluorescently labeled LDL. Rates of LDL accumulation were measured before and after treatment with 10 ng/ml tumor necrosis factor-alpha (TNF) using quantitative fluorescence microscopy. We observed a 50% decrease in basal LDL accumulation rates (P < 0.01) and a 25% decrease in endothelial layer permeability (P < 0.01) in arteries from estradiol-treated animals. There was no effect of hormone replacement on rate of TNF-induced LDL accumulation (P = 0.451), while incubation of LDL with 65 pg/ml estradiol attenuated the TNF effect (P < 0.01). These experiments suggest two independent mechanisms of anti-atherogenic protection by estradiol: 1) decreased endothelial layer permeability; and 2) incorporation of estradiol into the LDL particle and prevention of LDL binding to the artery wall.

Animals↗

17 beta-estradiol reduces glycoxidative damage in the artery wall.

Glycoxidative damage in the vasculature has been linked to atherosclerotic cardiovascular disease. Estrogens protect against the development and progression of atherosclerosis. Because estrogens are potent antioxidants that also effect glucose metabolism, part of their protection against atherosclerosis could be through attenuation of glycoxidative damage in the vascular wall. In this study, we tested the hypothesis that chronic estradiol administration is associated with decreased levels of glycoxidative damage in arterial walls. We harvested and examined iliac arteries from ovariectomized, 8-month-old rats that had been implanted for 6 months with 1 of the following subcutaneous hormone pellets: low estradiol (2.5 mg estradiol), high estradiol (25 mg estradiol), P4 (200 mg progesterone), low estradiol and P4, placebo (no hormone), or control (no implant). Using pentosidine as a biomarker of glycoxidative damage, we found that all vessels from rats receiving estradiol (low estradiol, high estradiol, and low estradiol+P4) exhibited a 50% reduction in glycoxidative damage compared with P4, placebo, and control vessels (P<0.05). Consistent with this finding, we observed that estradiol-treated rats had a 30% decrease in tissue levels of hydroperoxides, a marker of oxidative stress. Finally, estradiol-treated rats had a small, but significant, decrease in plasma glucose levels (P<0.01). In summary, we report the novel finding that chronic estrogen administration is associated with significant decreases in glycoxidative damage and oxidative stress in the arterial wall. It seems likely that these actions may constitute a mechanism by which estrogen attenuates the progression of atherosclerosis.

Animals↗

17beta-estradiol reduces tumor necrosis factor-alpha-mediated LDL accumulation in the artery wall.

Estrogens have direct effects on the vascular wall that may prevent the development of atherosclerosis. In particular, estrogens, such as 17beta-estradiol (estradiol), are known to have potent antioxidant activity. Tumor necrosis factor-alpha (TNF) is found in human atheroma and produces oxygen-derived free radicals. These oxygen-derived free radicals may modify low density lipoproteins (LDL) and increase LDL binding in the artery wall. We asked: 1) does TNF increase LDL accumulation in the artery wall and 2) can the TNF-mediated increase in LDL accumulation be prevented by the antioxidant activity of estradiol? Carotid arteries from ovariectomized 3-month-old rats were removed and perfused with fluorescently labeled LDL and arterial LDL flux was measured using quantitative fluorescence microscopy. In six arteries, addition of TNF (10 ng/ml) to the perfusate resulted in a 2.3-fold increase in the rate of LDL accumulation (1.50 +/- 0.37 ng/min per cm2 vs. 3.38 +/- 0.48 ng/min per cm2; P < 0.01). Estradiol (65 pg/ml) and alpha-tocopherol (6 mg/L) both attenuated TNF-mediated LDL accumulation (P < 0.05), indicating that TNF may exert its effects on LDL accumulation through cellular production of oxygen-derived free radicals. These results support an antioxidant role for estradiol in the protection against LDL accumulation in the artery wall and subsequent progression of atherosclerosis.

Animals↗

Multidisciplinary management of altered body image in the patient with an ostomy.

Many clinical studies have found patients with ostomies to be a group facing multiple adjustment demands. One of these demands is coping with a significant change in body image. At the Medical College of Wisconsin, a team approach has been initiated; the ET nurse, the psychologist, and the surgeon deal with body image concerns together. Problems requiring counseling have included difficulty with personal acceptance, personal and social body-image disruption, sexual concerns, reduced self-care skills, and the management of surgical complications. This article represents a study employing a methology of selected case presentations. Cases were chosen to outline the types of problems encountered and were selected from referrals made for psychologic intervention by the surgeon and ET nurse. The patients included four women and three men, ranging in age from 22 to 79 years. Data were compiled by examining the records of the surgeon, ET nurse, and psychologist. The primary needs revolved around personal or social acceptance of altered body image. By addressing these needs in a straightforward, time-limited manner, postsurgical counseling was delivered effectively for these patients. In conclusion, we have demonstrated the multidisciplinary approach to be successful in facilitating adaptation to an altered body image.

Adult↗

Giant cell tumour of bone in a cat.

A domestic shorthaired cat had a firm, non-painful swelling of the left antebrachium. Radiographs showed an expansile, multiloculated lesion in the radius. The mass gradually enlarged over the following four and a half months and the animal became completely lame. The histological diagnosis was giant cell tumour of bone; this is a rare neoplasm of bone in veterinary patients. Giant cell tumour of bone should be considered in the differential diagnosis of bone lesions having an expansile, multiloculated radiographic appearance.

Animals↗

Potential role of helix-loop-helix proteins in cardiac gene expression.

Because helix-loop-helix (HLH) transcription factors appear to play an important role in mesodermal development, we have investigated the potential role of these factors in cardiac gene expression. HLH proteins interact with DNA at consensus "E-box" sites and may be tissue specific or more widely expressed. We have examined cardiac cells for expression and regulation of widely expressed factors Pan1/Pan2 and the inhibitor of differentiation (Id) by RNase protection analysis. The effect of MyoD, Id, and Pan1/Pan2 expression on skeletal and cardiac promoters in cardiac cells was examined by transient cotransfection studies. Our results indicate that neonatal ventricular cells are a functional HLH environment, because MyoD can activate a skeletal muscle-specific promoter in these cells. MyoD, however, has no effect on the expression of several genes that are expressed in cardiac cells. In addition, Id may be an early response gene for signal transduction in cardiac cells, because increases in Id mRNA occurred within 30 minutes of stimulation with serum or phenylephrine. Activities of three cardiac promoter elements in primary ventricular myocytes were not downregulated by Id. Surprisingly, expression of Pan1 and Pan2 exhibited a strong negative effect on cardiac expression of the myosin light chain-2 promoter.

Animals↗

Meeting the challenge of infection: a case study.

Infection is the most critical complication of cancer. A case study is presented that describes an adolescent with acute lymphocytic leukemia. He experienced multiple complications due to infection. Both new and standard therapies were required for the treatment and prevention of infections. A discussion of the rationale for various aspects of his care is presented.

Adolescent↗

Urostomy and urinary pH.

Significant variations of urinary pH can cause problems for all human beings, but these problems are magnified when an individual has a urostomy. Most significant stomal and peristomal complications are related to an alkaline urine including hyperkeratosis; stoma bleeding, incrustation, and ulceration; stoma stenosis; urinary tract infection; odor; and urinary calculi. Treatment of these conditions includes both external and internal measures. External methods of treatment involve keeping urine away from the stoma and the peristomal skin by use of a correctly fitting clean appliance and a night drainage system. Vinegar solution compresses can help to restore the acid mantle of the skin. Internal methods of treatment that are advocated in the literature include ingestion of cranberry juice and ascorbic acid to promote urine acidity. Increasing oral intake of fluids is the least risky method to promote the production of acidic, dilute urine, and results are equally effective.

Humans↗