The role of epsilon phenotype in brain glucose consumption in Alzheimer’s disease

The aim of our study was to investigate the impact of the epsilon phenotype in brain glucose consumption in a population with Alzheimer’s disease. Statistical Parametric Mapping (SPM8) was used to investigate differences in brain glucose consumption (as detectable by means of 18F FDG-PET/CT) in the population examined. A total of 129 patients (72 females and 57 males) with a diagnosis of probable AD according to the NINCDS-ADRDA criteria underwent the PET/CT examination. The mean (SD) age of the patients was 70 (± 7) years; the mean Mini-Mental State Examination was 19(± 5.6). 59 expressed epsilon 4 phenotype (E4) and 70 expressed the epsilon 3 phenotype (E3). Cerebral spinal fluid amyloid, tau, and t-tau have been measured resulting equal to 367.4 (± 149.1), 584.7 (± 312.1), and 79.2(± 45.9) pg/ml, respectively. Patients with confirmed amyloid and Tau changes were classified as AD. Patients with amyloid changes but negative Tau, considered as high risk of AD, were classified as IAD. Age, sex, MMSE, scholarship, and CSF parameters were used as a covariate in the SPM analyses. We did not find significant differences in age, gender, and MMSE and CSF parameters among groups. In the analysis of the AD group as compared to AD-E3, AD-E4 subjects show a significant reduction of brain glucose consumption in inferior frontal gyrus bilaterally (BA 45, BA 47). In the analysis of the IAD group as compared to IAD-E3, IAD-E4 subjects show a significant reduction of brain glucose consumption in right in medial, middle, and superior frontal gyrus (BA10, BA11), and in left medial and middle frontal gyrus (BA10, BA11). The differences between IAD-E3 and AD-E3 and between IAD-E4 and AD-E4 (and vice versa analysis) resulted not significant. APO-e4 is related to a major involvement of the frontal cortex confirming its role of risk factor in AD, while APO-3 seems not related to a specific pattern, supporting the hypothesis of neutral/protective role in AD.     

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.      

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.