Current Drug Therapy - Volume 4, Issue 3, 2009

Prevention and treatment of pain in preterm and term neonates became major issues in neonatal care since the landmark observations of Anand et al. on the impact of (in) adequate analgesia on mortality and morbidity after surgery in preterm neonates. Safe and effective analgesia does require thorough understanding of maturational clinical pharmacology. In the current review we summarized the available data on both pharmacokinetics and -dynamics of analgesics of various potency (potent opioids, moderate potent opioids, non-selective cyclo-oxygenase inhibitors and acetaminophen) in neonates. The available information on developmental pharmacology in neonates has extended significantly, but we have to be aware that most studies focussed on aspects of pharmacokinetics, and not yet on aspects of pharmacodynamics. The currently available information on developmental pharmacology of analgesics in neonates still needs to be further integrated in a multimodal, approach to prevent and treat pain in the neonate.

After a long initial stage obscured by empirism and misconceptions, oxygen-ozonetherapy has now become a scientific discipline where the reactions between ozone and human blood are within the realm of orthodox biochemistry, physiology and pharmacology. Most of the basic mechanisms of action have been clarified and ozone can be considered a pro-drug, which almost instantaneously reacts with antioxidants and unsaturated fatty acids. These reactions generate the actual ozone messengers represented by either hydrogen peroxide as a fast acting compound or a variety of lipid oxidation products as late effectors. While ozone is totally consumed, micromolar amounts of these messengers are able to enhance the delivery of oxygen via erythrocyte activation, the immune system by a bland leukocyte stimulation and most of the remaining body cells by up-regulating the antioxidant system. The hazard of ozone toxicity has been dispelled by using the gas only within a dose range perfectly calibrated against the potent blood antioxidant capability. Ozonetherapy can be very useful in patients with chronic vascular disorders and ischemic problems and should be extensively used by official medicine. An extraordinary facet of ozone is its medical application versatility, as represented by several administration routes, and the minimal cost of this drug.

In order to investigate the protective role of cefepime plus amikacin (Potentox) reconstituted with solvent for injection vs cefepime and amikacin alone as well as potentox reconstituted with water for injection, the mice were fed standard pelleted diet and water ad libitum. The test room was air conditioned with temperature 23 ± 2oC, humidity 65± 5% and with artificial fluorescent light (10-14 hrs. of light and dark, respectively). Thirty Mus musculus mice (weighing 30 ± 5 g) were divided into five groups containing six mice in each group. Group- I Control (Normal Saline), Group-II cefepime (28.5 mg/Kg body weight/day), Group-III amikacin (7.14mg/Kg body weight/day), Group-IV cefepime plus amikacin reconstituted with water for injection (35.7mg/Kg body weight/day) and Group-V cefepime plus amikacin reconstituted with solvent for injection (35.7mg/Kg body weight/day). The level of antioxidant enzymes such as superoxide dismutase and catalase along with malonaldialdehyde (free radical mediated damage) and some extracellular levels namely creatinine, uric acid, serum glutamyl oxaloacetic transaminase and serum glutamyl pyruvic transaminase were also analyzed. In cefepime, amikacin and potentox reconstituted with water for injection treated groups, antioxidant enzyme activities were significantly decreased and the level of malonaldialdehyde as well as oxidant levels were significantly higher than those in the control group. Our results indicated that the protective effect of potentox reconstituted with solvent for injection increases the activity of antioxidant enzymes with the reduction of lipid peroxidation and oxidant level. These findings suggest that fixed dose combination of cefepime plus amikacin (Potentox) reconstituted with solvent for injection was found to be more effective and improve the activities of free radical scavenging enzymes.

Activated Cancer Therapy (ACT), also known as Sonodynamic Photodynamic Therapy (SPDT) is a novel therapeutic modality that utilises a non-toxic photosensitive agent with reported ultrasound-activated properties. SPDT has previously demonstrated significant tumour cell inhibition in animal studies. There has been much research into the efficacy of photodynamic therapy and development in understanding of the underlying mechanism of tumour cytotoxicity. Synergistic ultrasound activation represents a promising development to activated sensitiser therapy, as photo-activation is limited by access and penetrance issues. Ultrasound has been demonstrated to activate a number of sono-sensitive agents allowing the possibility of non-invasive targeted treatment of deeper tumour sites than is currently achievable with photodynamic therapy. This case series of 115 patients with a variety of cancer diagnoses reports on experiences of this treatment over a 4 year period using sublingual administration of a new dual activation agent, Sonnelux-1, followed by a protocol of LED light and low-intensity ultrasound exposure. Initial clinical observation suggests SPDT is worthy of further investigation as an effective and well tolerated treatment for a wide variety of primary and metastatic tumours, including those refractory to chemotherapy.

Liver transplantation was approved for the treatment of decompensated cirrhosis in the United States in 1983. Hepatitis B and hepatitis C viruses are the leading causes of liver transplantation for viral hepatitis and hepatitis B is also an important cause of liver transplantation for fulminant liver failure (also called acute liver failure) due to either acute hepatitis B or an acute exacerbation of chronic hepatitis B. However, until the introduction of hepatitis B immunoglobulin and nucleoside/nucleotide analogues nearly twenty years ago, liver transplantation for hepatitis B was characterized by universal recurrence with a dismal prognosis. At present, liver transplantation for hepatitis B, regardless of whether for decompensated cirrhosis, hepatocellular carcinoma satisfying Milan criteria or acute liver failure has excellent outcomes with results comparable if not better to other liver transplant recipients. This article will review the management of patients with decompensated cirrhosis from HBV prior to liver transplantation, the use of hepatitis B positive donors and the prevention and management of hepatitis B after liver transplantation.

Atherosclerotic carotid artery disease is a well-defined risk factor for stroke, and other forms of cerebrovascular disease such as cognitive impairment. Research progress has advanced our understanding of the basic pathophysiology of atherosclerosis, and recent findings opened venues that could lead to the development of therapies and more individualized prophylactic treatment of cerebrovascular disease in general, and of carotid artery disease in particular. Emerging non-invasive imaging techniques show promising results to identify biological and molecular processes in vivo, offering potential benefits for identification of vulnerable atherosclerotic lesions and development of new therapies. In the present article we review current concepts in the pathophysiology of carotid artery atherosclerosis, specifically the role of select markers of endothelial dysfunction and extracellular matrix remodeling in atherosclerosis and carotid artery disease, as well as available non invasive diagnostic methods to assess pathologic events in carotid lesions and discuss the potential role of these processes as targets for the development of new therapies in cerebrovascular disease prevention.

This review addresses mainly the polyamine levels in various tissues and regional brain of (intact) rats treated with various types of anticancer drugs and those in diverse foods. Results indicate that the most effective combination therapy for cancer patients based on polyamine level is a polyamine-free diet coupled with drugs that reduce the amine in cancer-bearing host tissues.

Therapeutic angiogenesis, stimulated growth of new vasculature to compensate for tissue ischemia, has been studied in a number of clinical trials in patients with various ischemic vascular diseases. These clinical trials include growth factor protein and gene therapy, as well as cell therapy. However, almost randomized clinical trials using vascular endothelial growth factor and fibroblast growth factor families, delivered as either recombinant protein or gene therapy, have failed to demonstrate improvement in patients with coronary artery or peripheral artery disease until now. However, randomized clinical trials using bone marrow-derived cells demonstrated modest but some significant benefit in patients with myocardial infarction. This report reviews the current status of randomized clinical trials and some non-randomized clinical trials using these therapies, plus related potential problems.