Hypertension in dialysis and kidney transplant patients

For the first time, the Canadian Hypertension Education Program has studied the evidence supporting blood pressure control in people requiring renal replacement therapy for end-stage kidney disease, including those on dialysis and with renal transplants. According to the Canadian Organ Replacement Registry’s 2008 annual report, there were an estimated 33,832 people with end-stage renal disease in Canada at the end of 2006, an increase of 69.7% since 1997. Of these, 20,465 were on dialysis and 13,367 were living with a functioning kidney transplant. Thus, it is becoming more likely that primary care practitioners will be helping to care for these complex patients. With the lack of large controlled clinical trials, the consensus recommendation based on interpretation of the existing literature is that blood pressure should be lowered to below 140/90 mmHg in hypertensive patients on renal replacement therapy and to below 130/80 mmHg for renal transplant patients with diabetes or chronic kidney disease.     

Stress, prefrontal cortex and environmental enrichment: studies on dopamine and acetylcholine release and working memory performance in rats

The aim of the present study was to investigate whether environmental enrichment changes the effects of acute stress on both the release of dopamine and acetylcholine in the prefrontal cortex (PFC) and working memory performance. Male Wistar rats (3 months of age) were housed in enriched or control conditions during 12 months. Behavioural testing was carried out to assess working memory performance in a delayed alternation task (water escape T-maze). Horizontal and vertical motor activity were also monitored in the open field. After behavioural testing (open field and water T-maze), animals were implanted with guide cannula in the PFC to perform microdialysis experiments and to monitor dopamine and acetylcholine extracellular concentrations. Handling stress (40min) produced similar increases of extracellular concentrations of dopamine in the PFC of both enriched and control animals. In contrast, handling stress increased significantly the extracellular concentrations of acetylcholine in the PFC of control, but not enriched, animals. Exposing animals to a lit open field during 10min significantly reduced working memory performance assessed immediately in the water T-maze just in control animals, though these effects were not significantly different between both groups of animals. Spontaneous motor activity in the open field was lower in enriched compared to control animals. These results suggest that environmental enrichment changes acetylcholine, but not dopamine, reactivity to stress in the PFC.     

A novel spinocerebellar ataxia type 15 family with involuntary movements and cognitive decline

Background and purpose: SCA15 is a recently identified spinocerebellar ataxia with pure cerebellar involvement. Here, we report a novel SCA15 Italian family with atypical clinical features. Methods: Three affected members from a three‐generation family segregating an autosomal dominant cerebellar ataxia underwent clinical examination and genetic tests for hereditary ataxia. Results: All affected members present with cognitive impairment and two of them with mild intermittent involuntary movements in association with the clinical hallmarks of SCA15 (gait ataxia, balance impairment, and dysarthria). Genetic tests detected a large deletion spanning ITPR1 and SUMF1 genes in affected members. Conclusion: Our findings help enlarging the clinical spectrum of SCA15.     

Effects of AT1 Receptor Antagonism With Candesartan on Endothelial Function in Patients With Hypertension and Coronary Artery Disease

Endothelial dysfunction is a major determinant of atherosclerosis and a negative prognostic factor in patients with coronary artery disease and hypertension. Recovery of endothelial dysfunction has been associated with improved prognosis in these patients. The aim of the present study was to verify whether antagonism of angiotensin II AT1 receptors with an angiotensin receptor blocker, candesartan, improved endothelial function in patients with hypertension, stable coronary artery disease, and endothelial dysfunction. We studied 26 patients who were receiving β-blockers with optimal blood pressure control, in a randomized, double blind study. Patients were randomized to placebo (n=13) or to candesartan 16 mg/d (n=13) for 2 months. Endothelial function was assessed by ultrasound using hyperemic flow-mediated dilation of the brachial artery. Mean arterial blood pressure was unchanged in both groups (from 93.3±9.2 to 93.2±17.3 mm Hg in the candesartan group and from 101.3±14.2 to 102.3±13.9 mm Hg in the placebo group; both P =ns). Maximal blood flow was similar between placebo and candesartan groups at baseline and at the end of the study, whereas flow-mediated dilation significantly increased in the candesartan group (from 5.27%±1.69% to 7.15%±2.67%; P =0.01) but remained unchanged in the placebo group (from 4.49%±1.97% to 5.88%±2.30%; P =ns). AT1 receptor antagonism with candesartan, in addition to β-blocker therapy, improves endothelial function in high-risk hypertensive patients.     

Melatonin as a potential therapeutic agent in psychiatric illness

The aim of this review was to summarize the potential use of melatonin in the treatment of mental disorders, specifically bipolar disorders, depression, and schizophrenia. To date, melatonin has been most commonly used in psychiatry because of its hypnotic, rhythm resynchronizing, and antioxidant actions. Here, we examine other properties of the melatonin including its anti‐inflammatory, antinociceptive, anxiolytic, and drug detoxification actions as well as its protective effects against neural loss. The brain is an intricate sensory and motor organ which receives information from both the external and internal environments. It transduces information into complex chemical and electrical signals which are transmitted throughout the central nervous system (CNS) and the organism. The pathogenesis of mental disorders remains ambiguous and neuroinflammation has been proposed as a causative agent. We consider the potential contributions of melatonin as therapeutic agent in CNS and during neuroinflammation in mental disorders. Copyright © 2009 John Wiley & Sons, Ltd.     

Intradermal hepatitis B vaccination in thalassaemia.

Fifty six children with thalassaemia, and 118 healthy subjects, who had all been immunised with an intramuscular injection of hepatitis B vaccine (HB-VAX) into the deltoid area three years previously, were given booster doses intradermally. All responders (good = hepatitis B surface (HBs) antibody titre greater than or equal to 10 U/l; poor = HBs antibody titre less than 10 U/l) showed pronounced increase in anti-HBs titre, in many cases above 1000 U/l. We also found positive HBs antibody response after further doses (two to four) at intervals of 15 days in non-responders (those patients who formerly had shown no HBs antibody titre after the conventional schedule of vaccination). The humoral response was always preceded by a delayed tissue hypersensitivity reaction. In conclusion, vaccine against hepatitis B virus given in low doses intradermally produces an effective immune response; it is a useful method of enhancing the antibody response in exposed patients, and of vaccinating those who do not respond initially.     

Regulation of lewis lung carcinoma invasion and metastasis by protein kinase A

Metastatic Lewis lung carcinoma (LLC-LN7) cells have increased protein kinase A (PKA) activity and are more invasive in vitro than are non-metastatic (LLC-C8) cells. To determine whether PKA mediates the in vitro invasiveness and in vivo metastatic capabilities of these tumor cells, the LLC variants were stably transfected to over-express the C_α subunit of PKA, and thus to have increased PKA activity, or to express a mutant cAMP-resistant PKA R_lα subunit which blocks PKA activation. Wild-type LLC-LN7 tumor cells were invasive in vitro and in vivo, recurred after tumor excision and metastasized to the lungs. However, they lost these properties after transfection to express the mutant R_lα that blocks PKA activation. The non-invasive, non-recurring and non-metastatic LLC-C8 cells gained the capacity to invade, to recur following tumor excision and to metastasize when transfected to express the PKA C_α subunit. © 1995 Wiley-Liss, Inc.