Muscle wasting in chronic kidney disease: the role of the ubiquitin proteasome system and its clinical impact

Muscle wasting in chronic kidney disease (CKD) and other catabolic diseases (e.g. sepsis, diabetes, cancer) can occur despite adequate nutritional intake. It is now known that complications of these various disorders, including acidosis, insulin resistance, inflammation, and increased glucocorticoid and angiotensin II production, all activate the ubiquitin–proteasome system (UPS) to degrade muscle proteins. The initial step in this process is activation of caspase-3 to cleave the myofibril into its components (actin, myosin, troponin, and tropomyosin). Caspase-3 is required because the UPS minimally degrades the myofibril but rapidly degrades its component proteins. Caspase-3 activity is easily detected because it leaves a characteristic 14kD actin fragment in muscle samples. Preliminary evidence from several experimental models of catabolic diseases, as well as from studies in patients, indicates that this fragment could be a useful biomarker because it correlates well with the degree of muscle degradation in dialysis patients and in other catabolic conditions

Relationship Between Plasma Levels and the Anti-Neuropathic Pain Effect of Lamotrigine in Rats

The purpose of this study was to assess the concentration-analgesic effect on neuropathic pain relationship of lamotrigine (LMT) from the direct plasma studies and pharmacodynamic studies. Although the anticonvulsant drugs are used for neuropathy, their pharmacokinetic and pharmacodynamic correlation on the time course of the effect of two drugs was determined after oral administration in conjunction with their pharmacokinetics. Non-compartmental analysis was adopted to calculate pharmacokinetics of the drug. Neuropathic pain was induced by chronic constriction injury of sciatic nerve. This technique allows consecutive measurements of the paw withdrawal thresholds and paw withdrawal duration on hyperalgesia and allodynia, respectively. Increase in threshold and decrease in duration of paw withdrawals were used as analgesic effect against neuropathy. After administration of drug, pronounced reversal in pain could be observed from all the behavioral studies and pharmacokinetic-pharmacodynamic studies showed good correlation coefficient which indicated a positive correlation. Findings from the current, preclinical study showed good relation between pharmacokinetics and pharmacodynamics of anticonvulsants on neuropathy.Keywords: Lamotrigine, neuropathy, pharmacokinetics, pharmacodynamic

Use of systemic steroid after successful macular surgery in eyes with epiretinal membrane : a randomized, controlled clinical study

To evaluate the functional and morphological outcomes of postoperative systemic steroid therapy after successful macular surgery in eyes with macular edema due to idiopathic macular epiretinal membranes (ERMs)