Low back pain--from definition to diagnosis

Low back pain is defined as pain and discomfort, localised below the costal margin and above the inferior gluteal folds, with or without leg pain. It is one of the most commonest cause of seeking physician office visits, secound cause of sick leave, and because of high direct and indirect costs it has great medical, social and economic impact for individual, family and society. Non-specific low back pain is defined as low back pain not attributed to recognisable, known specific pathology and specific low back pain which has known pathomorfological cause. For most patients with low back pain a thorough history taking and clinical examination are suffitient. Extended diagnostic analysis are needed in the case of nerve root pain/radicular pain and serious spinal pathology, respectively after identification of red flags. Moreover, great attention has to be achieved at psychosocial factors or so called yellow flags which increase the risk of developing chronic low back pain and long term disability (including work loss associated with low back pain).     

Significant further evidence to bolster the link between epoetin and strokes in chronic kidney disease and cancer

Erythropoiesis-stimulating agents (ESAs) have been used for about three decades in chronic kidney disease patients to treat the symptoms of anemia, avoid potentially hazardous blood-product transfusions, improve some facets of quality of life, and reduce cardiovascular risk. We review a new article in which this association between stroke and ESA use is examined in a different population in a different way, but with the same worrying findings as seen in the TREAT study.     

Phytoestrogens as inhibitors of the human progesterone metabolizing enzyme AKR1C1

Phytoestrogens are plant-derived, non-steroidal constituents of our diets. They can act as agonists or antagonists of estrogen receptors, and they can modulate the activities of the key enzymes in estrogen biosynthesis. Much less is known about their actions on the androgen and progesterone metabolizing enzymes. We have examined the inhibitory action of phytoestrogens on the key human progesterone-metabolizing enzyme, 20alpha-hydroxysteroid dehydrogenase (AKR1C1). This enzyme inactivates progesterone and the neuroactive 3alpha,5alpha-tetrahydroprogesterone, to form their less active counterparts, 20alpha-hydroxyprogesterone and 5alpha-pregnane-3alpha,20alpha-diol, respectively. We overexpressed recombinant human AKR1C1 in Escherichia coli, purified it to homogeneity, and examined the selected phytoestrogens as inhibitors of NADPH-dependent reduction of a common AKR substrate, 9,10-phenantrenequinone, and progesterone. The most potent inhibitors were 7-hydroxyflavone, 3,7-dihydroxyflavone and flavanone naringenin with IC(50) values in the low microM range. Docking of the flavones in the active site of AKR1C1 revealed their possible binding modes, in which they are sandwiched between the Leu308 and Trp227 of AKR1C1.     

Expression analysis of estrogen-metabolizing enzymes in human endometrial cancer

Estrogen-dependent endometrial cancer is related to unopposed and prolonged estrogen stimulation. We examined the expression of estrogen-metabolizing enzymes in correlation with the ERalpha and ERbeta estrogen receptors in human endometrial Ishikawa adenocarcinoma cells and in endometrial cancer specimens and adjacent normal endometrium from the same patients. Real-time PCR analysis revealed that both estrogen receptors and selected estrogen-metabolizing enzymes were expressed in the Ishikawa cells and in endometrial tissue. We detected higher expression of ERalpha than ERbeta, higher expression of sulfatase than sulfotransferase and low expression of aromatase in the Ishikawa cells and the tissue, as well as higher levels of type 2 17beta-hydroxysteroid dehydrogenase (17beta-HSD) in normal and diseased tissue than in the Ishikawa cells. When we compared the expression in endometrial cancer samples and in the adjacent normal endometrium, ERalpha and ERbeta, sulfatase and sulfotransferase were seen to be downregulated in the majority of the cancerous tissue specimens.     

Biosimilars: recent developments

Biopharmaceuticals are recombinant protein drugs which are produced by biotechnology. The availability of such molecules has revolutionised the way we treat many diseases. However, the patents for many originator biopharmaceuticals are expiring, and a new generation of follow-on molecules, termed “biosimilars”, are under development. Health care providers perceive biosimilars to be cheap replacements for originator drugs such as recombinant human erythropoietin and human growth hormone. However, concerns have been raised about the comparability of biosimilars with originator products especially in light of the complex manufacturing process required to produce biopharmaceuticals. The complexity of protein molecules renders it impossible to produce identical copies; this in turn raises questions on the safety of follow-on biosimilar products, particularly with respect to immunogenicity. This review briefly outlines the process of biopharmaceutical production, potential problems that can arise from their long-term use in patients, and the issues facing regulatory bodies as they look to institute guidelines for new biosimilar molecules.     

Sleep disorders: a systematic review of an emerging major clinical issue in renal patients

The prevalence of sleep disorders is significantly higher (up to 80%) in patients with chronic uremia compared to the general population. Sleep disorders appear even in the early stages of chronic kidney disease. These disturbances are complex, including difficulties in falling asleep and awakening, interrupted sleep, nightmares, restless legs syndrome, sleep apnea syndrome, etc. There are still disagreements on the major etiological factors of sleep disorders in the uremic patient. Older age, long dialysis vintage, alcohol and tobacco abuse and, particularly, the presence of significant comorbidities are major determinants of sleep disorders in dialysis patients. Proper assessment of sleep disorders in the renal population is still under investigation; recent studies have mostly addressed patients’ perception based on questionnaires. More precise polysomnographic assessments are less studied in renal patients. Sleep disorders significantly affect quality of life in dialysis patients. An accurate and early identification of such disturbances would lead to a significant improvement in quality of life, and probably also in outcome, in uremic patients. Sleep apnea syndrome is extremely frequent in dialysis patients, with obvious consequences for cardiovascular morbidity and mortality. Proper diagnosis and therapy of sleep apnea syndrome could significantly reduce cardiovascular risk. Although sleep quality improves after renal transplantation, allograft recipients still have significantly more sleep disorders than healthy individuals. Here, we review recent data on sleep disturbances in renal patients, focusing on the end-stage renal disease patient treated by dialysis.