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Biomedical subjects

W C Burns

Publications and source records attributed to W C Burns.

At least 19 recordsLinked to original sources
PubMed2006

Developmental expression of ACE2 in the SHR kidney: a role in hypertension?

The abnormal development of the intrarenal renin-angiotensin system (RAS) is thought contribute to adult-onset hypertension in the spontaneously hypertensive rat (SHR). Angiotensin-converting enzyme 2 (ACE2) is a novel enzyme with complementary actions to that of ACE. Recent studies have shown that ACE2 expression is reduced in the adult SHR. However, its regulation in pre-hypertensive animals is unknown. In this study, we examine the developmental expression of ACE2 in the rodent kidney and its temporal expression, as it relates to the development of hypertension in the SHR model. Kidneys from SHR and normotensive Wistar Kyoto (WKY) rats (n=8-12/group) at birth, 6 weeks of age, and adulthood (80 days) were examined. Gene expression and activity of ACE2 were determined by real-time reverse transcription-polymerase chain reaction and quenched fluorescence assays, respectively. Renal expression was localized by in situ hybridization and immunohistochemistry. The expression and ACE2 activity are significantly increased in the SHR kidney at birth. With the onset of hypertension, the tubular expression of ACE2 falls in SHR compared to WKY and remains reduced in the adult SHR kidney. Glomerular expression is paradoxically increased in the SHR glomerulus. The overall developmental pattern of ACE2 expression in the SHR kidney is also modified, with declining expression over the course of renal development. The developmental pattern of ACE2 expression in the SHR kidney is altered before the onset of hypertension, consistent with the key role of the RAS in the pathogenesis of adult-onset hypertension. Further research is required to distinguish the contribution of these changes to the development and progression of hypertension in this model.

Angiotensin-Converting Enzyme 2↗
PubMed2005

Tubular changes in early diabetic nephropathy.

Far from being bystanders in diabetic nephropathy, changes in the proximal tubule are important for the development of progressive diabetic kidney disease. The proximal tubule is uniquely susceptible to a variety of metabolic and hemodynamic factors associated with diabetes. Renal function and prognosis correlate better with structural lesions in the tubuli and cortical interstitium than with classical glomerular changes of diabetic nephropathy. The proximal tubules show a variety of poorly characterized changes, which have led to the notion that tubular damage represents a "final common pathway" for proteinuric renal injury. However, tubular hypertrophy, reduced organic ion transport, and other tubular changes reviewed in this paper, are already apparent before the onset of proteinuria in diabetes. Indeed, increased tubuloglomerular feedback and defective uptake and lysosomal processing may independently contribute to hyperfiltration and urinary protein loss, respectively. This finding does not mean that glomerular or vascular dysfunction do not contribute to progressive nephropathy. However, although subdividing the nephron for the purposes of analysis and scientific discovery may be useful, the interactions between tubule, glomerulus, and interstitium are likely key to the understanding of complex disorders such as diabetic nephropathy. From this "holonephric" point of view, an understanding of the changes in the diabetic tubule forms an important component to the understanding of kidney disease in diabetes.

Diabetic Nephropathies↗
PubMed2004

Identification of angiotensin converting enzyme 2 in the rodent retina.

PURPOSE: An active renin-angiotensin system has been found in the retina of rats and humans. Angiotensin-converting enzyme 2 (ACE2) is a recently discovered enzymatic homologue of Angiotensin-converting enzyme (ACE) that may be an important new component of the renin-angiotensin system (RAS). This study assesses the involvement of ACE2 in the normal and diabetic rodent retina and its modulation by ACE inhibition. METHODS: Sprague-Dawley rats were randomised into three groups, control, diabetes, and diabetes plus ramipril, with diabetes induced with the cell toxin streptozocin and the study run for 24 weeks. ACE2 and ACE gene levels were measured using quantitative real-time polymerase chain reaction (QRT-PCR), ACE2 protein expression was confirmed by Western blotting, and ACE and ACE2 catalytic activity were measured using specific activity assays in the rat retina. Localisation of ACE2 mRNA and protein were determined by in situ hybridisation and immunohistochemistry, respectively. RESULTS: ACE mRNA levels were decreased to approximately 50% in the diabetic retina, but ACE2 mRNA levels were not significantly changed. ACE but not ACE2 gene expression was influenced by ramipril treatment. Following immunostaining, both ACE2 and ACE protein were localised predominantly to the inner nuclear layer (INL) but also to photoreceptors. In the diabetic retina, ACE enzyme activity was decreased, whereas ACE2 enzyme activity was increased. CONCLUSIONS: This study has identified ACE2 gene and catalytically active protein in the rodent retina. In diabetes, the major changes were a decrease in ACE but an increase in ACE2 enzymatic activity. The ACE inhibitor ramipril did not reduce ACE2 enzymatic activity.

Angiotensin-Converting Enzyme 2↗
PubMed2003

Superior renoprotective effects of combination therapy with ACE and AGE inhibition in the diabetic spontaneously hypertensive rat.

AIMS/HYPOTHESIS: Diabetic renal disease has been postulated to progress as a result of an interaction between metabolic and haemodynamic pathways. Our aim was to assess the functional, structural, molecular and cellular aspects of renal disease in an experimental model of diabetes with associated hypertension. METHOD: Streptozotocin-induced diabetic spontaneously hypertensive rats were randomised to no treatment, the ACE inhibitor, perindopril (2 mg/l), the AGE formation inhibitor, aminoguanidine (1 g/l) and a combination of both agents and were followed for 32 weeks. RESULTS: Diabetes was associated with a considerable increase in albumin excretion rate. Both aminoguanidine and perindopril retarded the increase in albuminuria, which was completely abrogated by combination therapy. Glomerulosclerosis and tubulointerstitial damage was reduced by both monotherapies with further renoprotection afforded by combination therapy in both cases. Combination therapy was also associated with a superior restoration in diabetes-induced nephrin protein depletion compared to either monotherapy. TGFbeta1 expression as assessed by in situ hybridisation was increased in the diabetic rats and reduced by perindopril and aminoguanidine. CONCLUSION/INTERPRETATION: These findings indicate that in the context of diabetes-related renal injury, blocking both the renin-angiotensin and advanced glycation pathways offers superior renoprotection and could be considered as a therapeutic strategy in the prevention and retardation of progressive-diabetic renal injury.

Albuminuria↗
PubMed2003

Renoprotective effects of vasopeptidase inhibition in an experimental model of diabetic nephropathy.

AIMS: Although ACE inhibitors slow progression of diabetic renal disease, the mortality and morbidity is still high. As other hormonal factors are involved, inhibition of vasopeptidases could further reduce progression. We studied dual inhibition of angiotensin converting enzyme and neutral endopeptidase in a model of progressive diabetic renal injury. The major endpoints were reductions in systemic blood pressure, albuminuria and renal structural injury. METHODS: Diabetic spontaneously hypertensive rats were treated with the ACE inhibitor perindopril (mg.kg(-1).day(-1)) or the vasopeptidase inhibitor omapatrilat at doses of 10 (oma10) and 40 (oma40) mg.kg(-1).day(-1) for 32 weeks. In vivo ACE and NEP inhibition was quantitated by in vitro autoradiography. Renal structural injury was assessed by measurement of the glomerulosclerotic (GS) index and tubulointerstitial area (TI). The expression of transforming growth factor beta, beta-inducible gene-h3 and nephrin were also quantitated. RESULTS: Despite a similar reduction in blood pressure by perindopril and oma10, greater attenuation of albuminuria was afforded by oma10, with a complete amelioration observed with oma40. Oma40 lead to a 33% reduction in renal NEP binding and this was associated with less albuminuria and prevention of GS, TI area and overexpression of TGFbeta and betaig-h3. Diabetes-associated reduction in nephrin expression was restored by both drugs. CONCLUSION/INTERPRETATION: These findings suggest that other vasoactive mechanisms in addition to angiotensin II are important in the prevention of diabetic nephropathy, and that vasopeptidase inhibition might confer an advantage over blockade of the RAS alone in the treatment of diabetic renal disease.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1993

Anatomic relationships in the shoulder impingement syndrome.

Impingement syndrome of the shoulder may be produced by compression of the subacromial structures against the coracoacromial arch. The anterior tip of the acromion, the coracoacromial ligament, and the coracoid process have been implicated as sources of impingement. Anatomic specimens were examined to determine the anatomic sites on the coracoacromial arch that result in compression of the subacromial structures during specific shoulder motions that are known to produce impingement pain. The relationships of the supraspinatus tendon, the biceps tendon, and the greater tuberosity of the humerus with the coracoacromial arch were demonstrated through various arcs of shoulder motion in autopsy subjects. Biceps tendon impingement occurred predominantly against the lateral free edge of the coracoacromial ligament. Impingement of the supraspinatus tendon and greater tuberosity was demonstrated primarily against the acromial end of the coracoacromial ligament and the anterior tip of the acromion during arcs of flexion and internal rotation. The coracoacromial ligament was stretched by the greater tuberosity passing beneath it. This may explain the formation of traction osteophytes on the anterior acromion in patients with chronic impingement symptoms.

Biomechanical Phenomena↗
PubMed1992

Mortality in Syrian hamsters infected with Paragonimus kellicotti.

In an attempt to find a small animal model for paragonimiasis, Syrian hamsters were infected with between 1 and 16 metacercariae of Paragonimus kellicotti. A definitive mortality dose-response was observed with 90% of all hamsters given 3 or more parasites succumbing to the infection within 35 days. Hamsters demonstrated acute pleuritis, reactive mesothelial hyperplasia, subpleural accumulations of reactive and mature plasma cells, neovascularization, fibrohistiocytic thickening with and without giant cells, raised fibroconnective tissue lesions, and granulomatous inflammation with hemorrhage. Perivascular plasmacytic (lymphocytic) infiltrate, multifocal bronchopneumonia, and parenchymal necrotizing suppurative granulomatous inflammation, hemorrhagic pneumonia, and diffuse sprinkling of eosinophils, neutrophils, and intraalveolar macrophages also were observed. The response observed here may represent a new small animal mortality model useful in the search for new compounds to treat early trematode infections.

Animals↗
PubMed1985

Sheath area in Brahman and grade Brahman calves and its association with preweaning growth traits.

Data from 439 Brahman (B) and grade Brahman (GB; 7/8 Brahman or more) calves born from 1970 through 1975 at the USDA Subtropical Agricultural Research Station were used to estimate least-squares means, heritabilities and genetic correlations for sheath area and preweaning growth traits. Grade Brahman calves weighed more (P less than .01) at birth and gained more (P less than .01) preweaning than B calves, although sheath areas were not different. Males exceeded (P less than .01) heifers in all preweaning growth traits and had larger (P less than .01) sheath areas. Heritabilities were: sheath area, .45 +/- .13; birth weight, .25 +/- .13; average daily gain, .38 +/- .15 and weaning weight, .35 +/- .15. Genetic correlations between sheath area and birth weight, average daily gain and weaning weight were .23 +/- .35, .58 +/- .25 and .52 +/- .27. These results suggest selection could be effective in reducing sheath area in B and B-derivative breeds, but would be antagonistic to preweaning growth traits. Because of relatively low phenotypic correlations between sheath area and preweaning growth rate (.27) and weaning weight (.29), continued emphasis on increasing growth rate or weaning weight could generally be maintained with careful attention to avoiding large sheath areas through independent culling level or index selection procedures.

Abdomen↗
PubMed1985

Genotype X environment interaction in Hereford cattle: IV. Postweaning traits of bulls.

Genotype X environment interactions for postweaning performance traits of bulls produced by different lines of Hereford cattle were investigated in the contrasting environments of Miles City, Montana and Brooksville, Florida. During Phase 1 of the study (1966 to 1973), the performance of bull progeny from two unrelated lines (M1 and F6 previously developed in Montana and Florida, respectively) was compared at each of the two experimental sites. During Phase 2 (1967 to 1974), performance of bulls from two related lines (M1 of Montana origin and F4 derived from an M1 foundation through selection in Florida) was compared at each of the two locations. The line X location interaction effect in Phase 1 was highly significant for weaning weights and average daily gain during the postweaning test, and for end-of-test weight, conformation score, condition score and forecannon circumference. The interaction effect in Phase 2 was highly significant for 205-d and end-of-test weights and significant for all other traits except end-of-test conformation score. These results, consistent with results for traits covered in other papers of the same series (reproductive traits, birth-to-weaning traits of bull and heifer calves combined, and postweaning traits of heifers), indicated the existence of economically important genotype X environment interactions in beef cattle. Results from the series of papers indicated that adaptation to local environment should receive consideration in planning breeding programs, performance tests and interregional transfers of beef cattle.

Animals↗
PubMed1983

Genotype X environment interaction in Hereford cattle: III. Postweaning trait of heifers.

The postweaning performance of heifers from contrasting lines of Hereford cattle was compared simultaneously at Miles City, Montana and at Brooksville, Florida in an experiment designed to evaluate the importance of genotype X environment interactions in beef cattle. During Phase 1 of the study (1964 to 1973), the performance of two unrelated lines, M1 and F6, was compared at the two locations. During Phase 2 (1967 to 1974), two related lines, M1 of Montana origin and F4 derived from M1 by selection in Florida, were compared at each of the two locations. The line X location interaction term was highly significant in either Phase 1, Phase 2 or both for weaning weight, daily gain from weaning to spring, spring yearling weight, daily gain from weaning to fall, fall yearling weight, yearling condition score, conformation score, wither height, body depth, body length, shoulder width, hook width and forecannon circumference. Daily gain of yearlings from spring to fall was the only objective measurement for which the interaction term was nonsignificant in both phases. These results, consistent with the results on performance to weaning age reported previously, indicate the existence of highly significant genotype X environment interactions in beef cattle. The results indicate that genetic adaptation to the local environment is important in beef cattle production and should be considered in designing breeding programs or performance testing procedures and in interregional transfer of breeding stock.

Animals↗