The Putative Role of the Antiageing Protein Klotho in Cardiovascular and Renal Disease

Ageing is a multifactorial process often characterized by a progressive decline in physiological function(s). Ageing can and is often associated with an increased incidence of cardiovascular and renal disease. Klotho is a novel antiageing gene that encodes a protein with multiple pleiotropic functions including an emerging role in cardiorenal disease. Mice deficient for this gene display a phenotype of premature human ageing characterized by diffuse vascular calcification, altered calcium/phosphate metabolism, and shortened lifespan. Klotho is mainly expressed in the renal tubules but it also exists as circulating soluble form detectable in the blood, with systemic effects. Reduction in soluble Klotho has been associated with renal disease, hyperphosphataemia, increased oxidative stress, endothelial dysfunction, and diffuse vascular calcification. Conversely, overexpression of Klotho promotes cardiovascular-renal protection. The majority of the research on Klotho has been conducted in vitro and in animal studies but there is emerging data from human studies which suggest that Klotho may be a modifiable factor involved in the pathogenesis of cardiovascular and renal disease in at-risk populations. Further data is required to confirm if this novel protein can emerge as therapeutic tool that may be used to prevent or slow progression of cardiorenal disease

Critical appraisal of the differential effects of antihypertensive agents on arterial stiffness

Increased central arterial stiffness, involving accelerated vascular ageing of the aorta, is a powerful and independent risk factor for early mortality and provides prognostic information above and beyond traditional risk factors for cardiovascular disease (CVD). Central arterial stiffness is an important determinant of pulse pressure; therefore, any pathological increase may result in left ventricular hypertrophy and impaired coronary perfusion. Central artery stiffness can be assessed noninvasively by measurement of aortic pulse wave velocity, which is the gold standard for measurement of arterial stiffness. Earlier, it was believed that changes in arterial stiffness, which are primarily influenced by long-term pressure-dependent structural changes, may be slowed but not reversed by pharmacotherapy. Recent studies with drugs that inhibit the renin–angiotensin–aldosterone system, advanced glycation end products crosslink breakers, and endothelin antagonists suggest that blood pressure (BP)-independent reduction and reversal of arterial stiffness are feasible. We review the recent literature on the differential effect of antihypertensive agents either as monotherapy or combination therapy on arterial stiffness. Arterial stiffness is an emerging therapeutic target for CVD risk reduction; however, further clinical trials are required to confirm whether BP-independent changes in arterial stiffness directly translate to a reduction in CVD events

Clinical Use of Insulin Glargine 300 U/mL in Adults with Type 2 Diabetes : Hypothetical Case Studies

Type 2 diabetes (T2D) is a progressive disease, with many individuals eventually requiring basal insulin therapy to maintain glycaemic control. However, there exists considerable therapeutic inertia to the prompt initiation and optimal titration of basal insulin therapy due to barriers that include fear of injections, hypoglycaemia, weight gain, and burdensome regimens. Hypoglycaemia is thought to be a major barrier to optimal glycaemic control and is associated with significant morbidity and mortality. Newer second-generation basal insulin analogues provide comparable glycaemic control with lower risk of hypoglycaemia compared with first-generation basal insulin analogues. The present review article discusses clinical evidence for one such second-generation basal insulin analogue, insulin glargine 300 U/mL (Gla-300), in the context of hypothetical case studies that are representative of individuals who may attend routine clinical practice. These case studies discuss individualised treatment needs for people with T2D who are insulin-naive or pre-treated. Clinical characteristics such as older age, frequent nocturnal hypoglycaemia, and renal impairment, which are known risk factors for hypoglycaemia, are also considered.Peer reviewe

Early management after self-poisoning with an organophosphorus or carbamate pesticide – a treatment protocol for junior doctors

Severe organophosphorus or carbamate pesticide poisoning is an important clinical problem in many countries of the world. Unfortunately, little clinical research has been performed and little evidence exists with which to determine best therapy. A cohort study of acute pesticide poisoned patients was established in Sri Lanka during 2002; so far, more than 2000 pesticide poisoned patients have been treated. A protocol for the early management of severely ill, unconscious organophosphorus/carbamate-poisoned patients was developed for use by newly qualified doctors. It concentrates on the early stabilisation of patients and the individualised administration of atropine. We present it here as a guide for junior doctors in rural parts of the developing world who see the majority of such patients and as a working model around which to base research to improve patient outcome. Improved management of pesticide poisoning will result in a reduced number of suicides globally

The Spectrum of Intermediate Syndrome Following Acute Organophosphate Poisoning: A Prospective Cohort Study from Sri Lanka

Jayawardane and colleagues evaluate a cohort of 78 patients with organophosphate poisoning from Sri Lanka, and identify changes in repetitive nerve stimulation that precede, and may help predict, the onset of intermediate syndrome