Drugs Under Experimental and Clinical Research

The metabolic syndrome is strongly associated with insulin resistance and has been recognized as a cluster of risk factors for cardiovascular diseases such as visceral obesity, hypertension, diabetes and dyslipidemia. Recently, insulin resistance in the absence of overt diabetes or the metabolic syndrome itself has been shown to be associated with endothelial dysfunction, one of the initial steps in the process of atherosclerosis. In the present article we review the molecular mechanisms by which the metabolic syndrome causes endothelial dysfunction and subsequently promotes atherosclerosis...

This study aimed to define the pharmacokinetics of nifedipine following oral administration of a new extended-release formulation. Twelve healthy volunteers of both sexes, aged 39 +/- 4 years, were treated with a single oral tablet of a new extended-release formulation containing 40 mg of nifedipine. Samples of venous blood were taken before dosing, after 30 min and at 1, 2, 4, 8, 12, 16, 20 and 24 h after administration. Nifedipine concentration was measured by means of a high-performance liquid chromatography method...

The pool of different carnitine derivatives is formed by carnitine, acetylcarnitine, propionylcarnitine and isovalerylcarnitine. Isovalerylcarnitine is a compound performing activities that differ from those of the other carnitine esters. Its activity on proteolytic enzymes and on the calpain system has been demonstrated in the past. Both the calpain and the caspase systems belong to the protease family and lead to cytochrome activation and apoptosis. The two systems can interact to promote apoptosis. In view of this proapoptotic activity of isovalerylcarnitine, studies were carried out to ascertain whether this carnitine derivative influences cell-reaction processes associated with apoptosis...

D-004 is a lipid extract obtained from Cuban royal palm (Rosytonea regia) fruits, consisting of a mixture of fatty acids and esters. D-004 has shown protective effects on prostate hyperplasia induced by testosterone in rodents. We report the results of two studies investigating the acute and subchronic oral toxicity of D004 in rats. Oral acute toxicity of D-004 (2,000 mg/kg) was investigated in Sprague Dawley rats according to the acute toxic class method, and the results showed that D-004 oral acute toxicity was practically absent, being defined as unclassified...

Recently, it has become indispensable for anti-aging active ingredients to provide a visible and immediate smoothing antiwrinkle effect. In Quercus suber, suberin is the most important structural component of cork cell walls. Studies have shown that suberin is made up mostly of hydroxycarboxylic acids and that it is endowed with many special mechanical and chemical properties that evoke a possible smoothing effect on the surface of the skin. Therefore, we were interested in investigating the effect of this cork extract on the skin's surface in a double-blind clinical study...

It is well known that topical tacrolimus is safe and effective in the treatment of atopic dermatitis (AD) patients. Tacrolimus is primarily an immunosuppressive agent without any antistaphylococcal effects. Thus colonization of Staphylococcus aureus on the skin of patients treated with this agent might be increased. The purpose of this study was to determine the effect of tacrolimus on S. aureus colonization in patients with AD and to compare the results with clinical severity and skin barrier function. We enrolled 65 patients with moderate to severe AD...

Chondroitin sulfate (CS) and 500-730 kDa hyaluronic acid (HA) are symptomatic slow-acting drugs for the treatment of osteoarthritis (OA). In addition, a growing body of evidence suggests a role for CS and this specific HA as modifiers of the course of OA. The therapeutic efficacy of CS and HA lies in their different mechanisms of action. Stromelysin-1 (metalloprotease-3 [MMP-3]) is a cartilage proteolytic enzyme, which induces cartilage destruction and acts as a mediator of the inflammatory response. However, there are few studies evaluating the in vitro effect of CS and HA on MMP-3 synthesis in human chondrocyte cultures from OA patients...

We studied the effect of the anticancer drug Ukrain on Lewis carcinoma in C57BL/6 mice. A marked progressive anticancer and antimetastatic effect was observed. On day 33 of tumor development, the tumor growth inhibition and metastases inhibition index were 71.5% and 73.1%, respectively. The antimetastatic effect of the drug manifested as a decrease in both number and volume of lung metastases. This finding demonstrates that treatment with Ukrain in Lewis carcinoma-bearing mice not only prevents the formation of new metastases but also inhibits the growth of existing ones...

Adult rats were treated subcutaneously for 10 days with capsaicin, and their food intake and body weight were recorded for almost 6 weeks after stopping the treatment. The animals were exposed to different ambient temperatures: Ta (22, 32, 35, 10 and 22 degrees C). In the capsaicin-treated group a persistent increase in food intake and a reduction of body weight were observed when the animals were exposed to the lowest Ta of 10 degrees C. Starting from this temperature, food intake remained significantly higher than in controls until the end of the experiment at a Ta of 22 degrees C...

Diabetic nephropathy is a leading cause of end-stage renal disease in industrialized countries. Although the molecular mechanisms for the development and progression of diabetic nephropathy are not fully understood, the formation of advanced glycation end products (AGEs) and activation of the renin-angiotensin system (RAS) have been considered to be the main factors participating in the pathogenesis of diabetic nephropathy. However, functional cross-talk between AGEs and the RAS remains to be elucidated. In this study, we examined the effects of oral administration of olmesartan medoxomil, a newly developed angiotensin II type 1 receptor antagonist, on renal damage in AGE-treated rats...

High titer antisera against the protective antigen (PA) from Bacillus anthracis were generated immunizing Balb/c mice two times intraperitoneally with PA in combination with lipopeptide adjuvant P3CSK4. The sera were able to protect the mouse macrophage cell line J774A.1 from an anthrax toxin challenge. We also tested the blood of anthrax vaccine-immunized persons for PA- and lethal factor (LF)-specific antibodies. An increased titer was found after three immunizations, and the sera were also able to protect the mouse macrophage cell line from a toxin challenge...

The objective of the study was to investigate possible changes in cefazolin serum levels induced by cardiopulmonary bypass (CPB). Six cardiac male patients who underwent cardiac surgery requiring CPB took part in the study. Cefazolin 2 g was intravenously infused over 60 min before anesthesia and blood samples were taken at appropriate times after drug administration (0, 0.25, 0.5, 1, 4, 6, 8 h), 2 min before and 5 min after the beginning and 2 min before and 5 min after the end of CPB. Drug serum concentrations were determined by means of a microbiological method...

We used two approaches for studying the relationships between wine consumption, wine composition and cancer In the first approach, a transgenic mouse model of human neurofibromatosis, combined with the use of well-defined, chemically purified diets, showed that red wine contains nonalcoholic components that can delay tumor onset. In additional studies, catechin, the main monomeric polyphenol of red wine, delayed tumor onset in this mouse model in a positive, linear relationship when incorporated into the diet at levels of 0...

There is a growing body of evidence that dihydropyridine-based calcium antagonists (DHPs) improve endothelial function, thus slowing the development and progression of atherosclerosis. We have previously shown that nifedipine, one of the most popular DHPs, inhibits tumor necrosis factor-alpha (TNF-alpha)-induced reactive oxygen species generation and subsequent monocyte chemoattractant protein-1 (MCP-1) expression in human umbilical vein endothelial cells (HUVEC). However, the molecular mechanism underlying this phenomenon remains to be elucidated...

Rheumatoid arthritis (RA) is a disease that is still insufficiently controlled by current treatments. Methotrexate (M7X), a small molecular weight compound, has been the gold standard in the treatment of RA. It has several anti-inflammatory activities, but their contribution to its antiarthritic effects has not yet been established. We conducted a rat adjuvant arthritis study, in which we investigated the effect of MTX on local cytokine and chemokine production in arthritic paws. Our data demonstrate that MTX was able to significantly suppress cytokine and chemokine release in the inflamed joints in a dose-dependent fashion, accompanied by amelioration of the disease as indicated by reduced paw swelling and arthritic scores...

HESA-A, a marine compound, has been shown to exhibit antihepatic cancer, antitumor and anti-Parkinson effects. The hepatoprotective potential of HESA-A pretreatment at doses of 125 mg and 250 mg per day orally for a period of 40 days was evaluated against thioacetamide-induced liver damage in rabbits. Biochemical parameters such as serum glutamate oxaloacetate transaminase and lactate dehydrogenase in serum were estimated to assess liver function and lipid peroxidation products (malondialdehyde [MDA]) and the antierythrocyte lysis effect of plasma for measurement of antioxidant potential capacity...

The hepatoprotective activity of an ethanolic extract of Commiphora opobalsamum ("Balessan") was investigated in rats by inducing hepatotoxicity with carbon tetrachloride:liquid paraffin (1:1). This extract has been shown to possess significant protective effect by lowering serum transaminase levels (serum glutamate oxaloacetate transaminase and serum glutamate pyruvate transaminase), alkaline phosphatase and bilirubin. Pretreatment with an extract of Balessan prevented the prolongation of the barbiturate sleeping time associated with carbon tetrachloride-induced liver damage in mice...

Nonsteroidal anti-inflammatory drugs (NSAIDs) and Helicobacter pylori (H. pylori) are major factors in gastritis and peptic ulcer However, the role of NSAIDs and H. pylori infection in dyspepsia remains unclear. Gastric adaptive relaxation may be related to the pathogenesis of functional dyspepsia because the response is often disturbed in dyspeptic patients. In this study, we investigated the effects of indomethacin or H. pylori water extracts on gastric adaptive relaxation. This experiment was performed using the modified method of Desai et al...

Benign prostatic hyperplasia (BPH) is the noncancerous, uncontrolled growth of prostate gland cells and stroma that can cause difficulty urinating. Fruit lipid extracts from saw palmetto, a palm from the Arecaceae family, are used for BPH management. The Cuban royal palm, Roystonea regia, is also a member of the Arecaceae family and therefore it was appropriate to investigate the protective effects of Roystonea regia fruit lipid extracts on prostatic hyperplasia. The aim of this study was to investigate whether D-004, a lipid extract from Roystonea regia fruits, prevented testosterone-induced PH in castrated and intact rodents...

The aim of the present study was to investigate the potential antihypertensive effects of extracts of the flavonoid-rich Iranian flower, Crataegus curvisepala Lind., a member of the Rosaceae family. The hydroalcoholic extract of the leaves and flowers were studied in a double-blind, placebo-controlled clinical trial to determine its effects. A total of 92 men and women with primary mild hypertension, aged 40-60 years, were selected and divided randomly into two groups, receiving either hydroalcoholic extract of C...