Gene expression of LDL receptor, HMG-CoA reductase, and cholesterol-7 alpha-hydroxylase in chronic renal failure

BACKGROUND: Chronic renal failure (CRF) is associated with an atherogenic lipid profile and an increased risk of ischaemic cardiovascular disease. The associated hyperlipidaemia is reportedly ameliorated by erythropoietin (Epo) therapy. According to a recent report, rats studied 3 weeks after 5/6 nephrectomy and fed a high- protein diet exhibited increased activities of hepatic HMG-CoA reductase (HMG-CoAR) and cholesterol 7 alpha-hydroxylase (Ch-7 alpha- H), despite normal corresponding mRNA values. DESIGN AND METHODS: This study was designed to examine the effects of naturally progressing CRF of longer duration as well as those of Epo therapy on gene expressions of the key factors involved in hepatic cholesterol metabolism, i.e., LDL receptor (LDLR), HMG-CoAR, and Ch-7 alpha-H. Sprague-Dawley rats were randomized to the CRF group (5/6 nephrectomy), Epo-treated CRF group (given Epo 150 U/kg/twice weekly) and sham-operated, placebo- treated normal controls. They were allowed free access to regular rat chow and studied 6 weeks after surgery. Liver mRNAs and protein mass or activities of the above factors were studied. RESULTS: Plasma cholesterol concentration was significantly increased in the CRF group (P < 0.001) and was modestly lowered (P < 0.05) by Epo therapy. However, microsomal cholesterol concentration and LDLR, HMG-CoAR, and Ch-7 alpha-H mRNA as well as HMG-CoAR activity, and Ch-7 alpha-H and LDLR protein mass measurements were virtually identical in the three groups. Thus, hepatic LDLR, HMG-CoAR, and Ch-7 alpha-H mRNA and protein measurements in rats with CRF were similar to those of the normal control group representing an inappropriate response to the associated hypercholesterolemia. Epo therapy led to partial amelioration of CRF- associated hypercholesterolaemia with no discernible effect on hepatic tissue expression of the above factors.      

Interstitial nephritis related to nonsteroidal anti-inflammatory agents and beta-lactam antibiotics: a comparative study of the interstitial infiltrates using monoclonal antibodies

Acute interstitial nephritis (AIN) is a common pattern of renal injury induced by therapeutic agents. In order to characterize the types of mononuclear leukocytes infiltrating the kidney in drug-induced interstitial nephritis, a panel of monoclonal antibodies (Leu1, Leu3a, OKT8, OKM1, Leu14, OKT17, IL-2) was applied to cryostat sections of 13 renal biopsies (five non-steroidal anti-inflammatory agents (NSAID) (Group I); five beta-lactam antibiotics (Group II), 3 miscellaneous (Group III]. The majority of infiltrating mononuclear leukocytes were Leu1-positive T cells (71.7 +/- 18.7%), followed by monocytes (15.2 +/- 7.7%) and B cells (7.4 +/- 9.1%). Leu3a/OKT8 ratio was 0.954 +/- 0.341. Rare cells reacted with antibody to the interleukin-2 receptor (1.4 +/- 1.2%). No statistically significant differences could be found in the percentages of T lymphocytes, B lymphocytes, monocytes, activated (IL-2+) T cells or Leu3a/OKT8 (helper/suppressor) ratios in the three groups. In Group II, the following pathologic correlations were seen: Leu3a/OKT8 versus interstitial inflammation (R = -0.848), percent Leu3a versus interstitial inflammation (R = -0.818), percent OKT17 versus tubulitis (R = 0.785), percent Leu14 versus tubular atrophy (R = -0.891), and interstitial edema (R = 0.965). Our findings support a role for cellular immune mechanisms in the pathogenesis of AIN related to both NSAIDs and beta-lactam antibiotics.     

Haemoptysis in healthy children due to unsuspected foreign body

Abstract: Haemoptysis in otherwise healthy children is an uncommon event. Two cases of massive haemoptysis, subsequently requiring lobectomy, are discussed. In each case, foreign vegetable matter was identified despite previously normal bronchoscopy and minimal changes on chest radiograph.     

Non-invasive detection of fecal protein kinase C betaII and zeta messenger RNA: putative biomarkers for colon cancer

We have developed a non-invasive method utilizing feces, containing sloughed colonocytes, as a sensitive technique for detecting diagnostic colonic biomarkers. In this study, we used the rat colon carcinogenesis model to determine if changes in fecal protein kinase C (PKC) expression have predictive value in monitoring the neoplastic process. Weanling rats were injected with saline or azoxymethane (AOM) and 36 weeks later fecal samples and mucosa were collected, poly A+ RNA isolated, and quantitative RT-PCR performed using primers to PKC betaII and zeta. Fecal PKC betaII and zeta mRNA levels were altered by the presence of a tumor, with tumor-bearing animals having a 3-fold higher (P < 0.05) PKC betaII expression as compared with animals without tumors. In addition, AOM-injection increased mucosal PKC betaII mRNA expression compared with saline controls. No effect of tumor incidence on mucosal PKC betaII expression was observed. In contrast, fecal PKC zeta expression was 2.5-fold lower (P < 0.05) in animals injected with azoxymethane versus saline. Since tumor incidence exerts a reciprocal effect on fecal PKC betaII and zeta mRNA expression, data were also expressed as the ratio between PKC betaII and zeta. The isozyme ratio was strongly related to tumor incidence, i.e. ratio for animals with tumors was 2.18 +/- 1.25, animals without tumors was 0.50 +/- 0.16, P = 0.025. We demonstrate that the expression of fecal PKC betaII and zeta may serve as a noninvasive marker for development of colon tumors. A sensitive technique for the detection of colon cancer is of importance since early diagnosis can substantially reduce mortality.