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.      

Excitability properties of medial forebrain bundle axons of A9 and A10 dopamine cells

A9 and A10 units identified as dopaminergic were recorded with extracellular micropipettes. The units were antidromically activated by electrical stimulation at the level of the preoptic area. The absolute refractory periods ranged from 1.2 to 2.5 ms. During the 2–8 ms of the relative refractory period, conduction was slower than normal by up to 1.5 ms. The time constant, C, of the strength-duration curve ranged from 0.4 to 0.6 ms. The current (I)-distance (D) relationship, tested by moving the stimulating electrode past the axon, was approximately parabolic (I = K D exp 2), with the constant of the equation, K, ranging from 900 to 2000 μA/mm exp 2, for 0.5 ms pulses. This relationship allows calculation of the radius of the field of dopamine axon excitation at any current. These high K values show that axons of dopamine cells cannot be activated unless high current densities are derivered, even when electrodes are placed near the axons. These data allow determination of the extent to which dopamine axons can be the directly activated substrates for behaviors, such as self-stimulation and circling, which are evoked by electrical stimulation of the medial forebrain bundle or internal capsule.     

Factors Related to Drop-outs by Borderline Patients : Treatment Contract and Therapeutic Alliance

High patient drop-out rates have traditionally interfered with both treatment and study of patients with borderline personality disorder (BPD). The authors tested hypotheses that an adequate treatment contract, a positive therapeutic alliance, and the severity of illness would all correlate with continuation of treatment versus drop-out in a BPD cohort receiving psychodynamic psychotherapy. Therapists' contributions to the contract and to the alliance correlated with the length of treatment. Patients' impulsivity was negatively related to length of treatment. This study supports the view that the therapist's technique plays a role in engaging the borderline patient to remain in treatment.     

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.      

Quality of life in chronic NSAID users: a comparison of the effect of omeprazole and misoprostol

OBJECTIVE: To compare the impact on quality of life (QoL) of omeprazole and misoprostol during healing, and omeprazole, misoprostol, and placebo during maintenance treatment in chronic NSAID users with NSAID-associated gastroduodenal lesions. METHODS: Validated baseline and follow-up QoL questionnaires were completed by 610 patients (healing: after 4/8 weeks; maintenance: after 6 months). RESULTS: Patients with arthritis being treated with NSAIDs have a poor QoL. Rheumatoid arthritis causes more joint problems and physical mobility limitations than osteoarthritis. Chronic NSAID use causes heartburn and dyspepsia. QoL improved on both treatments (about equally on two general QOL scales), but omeprazole relieved gastrointestinal symptoms more than misoprostol, particularly reflux, abdominal pain and indigestion symptoms. During maintenance, both treatments maintained QoL, but misoprostol induced diarrhoea. CONCLUSION: QoL in arthritis patients on chronic NSAID treatment is destroyed. Omeprazole is superior to misoprostol for relief and prevention of NSAID-associated gastrointestinal symptoms allowing continued NSAID treatment without compromising the patients' QoL.