Fulltext search in archive

Valerian is used to treat sleeping disorders, restlessness and anxiety, but it seems only to work when taken over long periods (several weeks). Some studies have demonstrated that valerian extracts interact with the GABA and benzodiazepine receptors. Valerian is also used traditionally to treat gastrointestinal pain and spastic colitis. There are no long term safety studies. Valerian contains over 150 chemical constituents and many of them are physiologically active, mainly pyridine alkaloids, some organic acids and terpenes, especially the so called valepotriates, esterified iridoid-monoterpenes. As valepotriates may be potential mutagens, valerian should only be used after consultation with a physician. Valerian medication is sometimes recommended as first line treatment when the benefit-risk relation requires it and is often indicated as transition medication during the discontinuation processes involving bromazepam, clonazepam and diazepam, among others.

Natural products with antidiabetic activities provide important sources for the development of new drugs in the treatment of diabetes mellitus. This present work focuses on the antidiabetic activity of a hydro-methanolic (2:3) extract of the sepals of Salmalia malabarica on the blood glucose, the carbohydrade metabolic enzyme, oxidative stress, glycated haemoglobin and transaminase activity in streptozotocin (STZ) induced diabetic rats. Diabetic rats show a significant diminution in the activities of hexokinase, glucose-6-phosphate dehydrogenase and an elevation in the activity of glucose-6-phosphatase in the liver and skeletal muscle. Administration of hydro-methanolic extract of the sepals of Salmalia malabarica to diabetic rats resulted in a significant recovery in the parameters concerned. In the liver and kidney, the activities of catalase (CAT) and peroxidase (Px) were decreased significantly and levels of conjugated diene (CD) and thio-barbituric acid reactive substance (TBARS) were increased significantly in diabetic rats which recovered significantly after administration of hydro-methanolic extract of S. malabarica. Serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) activities which are increased in diabetes were restored by the extract. Glycated haemoglobin (HbA_1C) levels were resettled significantly in the extract treated group compared to the diabetic group. The antidiabetic activity of the extract was supported after a comparison with glibenclamide, a standard antidiabetic drug.

As part of a scientific appraisal of some of the folkloric and ethnomedical uses of Calotropis gigantea L. (Family: Asclepiadaceae), the present study was designed to evaluate the antitumour activity of the Calotropis gigantea flower against Ehrlich's ascites carcinoma (EAC) by using a crude ethyl acetate extract from the flower of Calotropis gigantea (designated as EECF) in Swiss mice. EECF was administered intraperitoneally at doses of 50, 100 and 200 mg/kg body weight. Bleomycin (0.3 mg/kg) was used as a positive control. EECF treatment significantly decreased both viable tumour cells and body weight gain induced by the tumour burden and prolonged survival time. The haematological and biochemical (glucose, cholesterol, triglyceride, blood urea, ALP, SGPT and SGOT) parameters altered during tumour progression, were also significantly restored in EECF-treated mice. Among the three doses tested, the highest dose was the most potent and comparable with the standard drug bleomycin (0.3 mg/kg). In conclusion, EECF from the Calotropis gigantea flower has a potent inhibitory effect against EAC cells in a dose dependent manner.

The applications of gas plasma and plasma modified materials in the emerging fields of medicine such as dentistry, drug delivery, and tissue engineering are reviewed. Plasma sterilization of both living and non-living objects is safe, fast and efficient; for example plasma sterilization of medical equipment quickly removes microorganisms with no damage to the tiny delicate parts of the equipment and in dentistry it offers a non-toxic, painless bacterial inactivation of tissues from a dental cavity. Devices that generate plasma inside the root canal of a tooth give better killing efficiency against bacteria without causing any harm to the surrounding tissues. Plasma modified materials fulfill the requirements for bioactivity in medicine; for example, the inclusion of antimicrobial agents (metal nano particles, antimicrobial peptides, enzymes, etc.) in plasma modified materials (polymeric, metallic, etc.) alters them to produce superior antibacterial biomedical devices with a longer active life. Thin polymer films or coating on surfaces with different plasma processes improves the adherence, controlled loading and release of drug molecules. Surface functionalization by plasma treatment stimulates cell adhesion, cell growth and the spread of tissue development. Plasma applications are already contributing significantly to the changing face of medicine and future trends are discussed in this paper.

Trimedoxime is a bisquaternary oxime that is widely used in the treatment of organophosphorous poisoning caused by tabun and paraoxon. We tested its affinity to acetylcholinesterase (AChE), its mechanism of interaction and effect on the cholinergic system of the rat bladder. The half maximal inhibitory concentration (IC₅₀) of trimedoxime to recombinant AChE was found to be 82.0 mM ± 30.1 mM. This represents a weak inhibition. Its interaction with AChE seems to be very similar to obidoxime - one aromatic nucleus interacts with the peripheral anionic site and the other with the residues TYR337 and TYR341 inside the cavity. Also the oxime moiety is moving towards the catalytic triade ready for the reactivation of the inhibited AChE. In the organ bath experiment no significant effect of trimedoxime was observed on the contraction of the detrusor caused by the muscarinic agonist metacholine.

This experiment tested the reactivity of the cationic surfactant Resamin AE [N-(2-hydroxyethyl)-N-(2-hydroxy-4-oxa(C14/22-alkyl))-N,N-dimethylammonium chloride] with organophosphonate soman. It was confirmed that soman is incorporated in the micelle of Resamin AE and that the hydroxyl group or Resamin AE supports the hydrolysis of this organophosphonate. A further increase in reactivity was achieved by the addition of hydrogen peroxide into the reaction mixture. In contrast, if the concentration of neutral salts was increased, a decrease in the velocity of the hydrolysis was obtained. The hydrolytic efficacy of Resamin AE was also compared with that of hexadecyldimethyl-(2-hydroxyethyl)-ammonium bromide. Resamin AE appeared to be a more efficacious hydrolytic agent than other similar compounds due to its advantageous chemical structure.

Succinic acid monoethyl ester (EMS) was recently proposed as an insulinotropic agent for the treatment of non-insulin dependent diabetes mellitus. The present study investigated the effect of EMS and Metformin on dearrangement in glycoprotein levels in the streptozotocin-nicotinamide induced type 2 diabeteic model. Succinic acid monoethyl ester was administered intraperitoneally for 30 days to normal and diabetic rats. The effect of EMS on glucose, insulin, and plasma and tissue glycoproteins were studied. The effect of EMS was compared with Metformin, a reference drug. The levels of glucose, glycosylated haemoglobin and plasma glycoproteins containing hexose, hexosamine and fucose were increased significantly whereas the level of plasma insulin and haemoglobin were decreased significantly in diabetic rats. There was a significant decrease in the level of sialic acid and elevated levels of hexose, hexosamine and fucose in the liver and kidney of streptozotocin-nicotinamide diabetic rats. Administration of EMS to diabetic rats was followed by a decreased level of glucose, glycosylated haemoglobin and plasma glycoproteins. The levels of plasma insulin, haemoglobin and tissue sialic acid were increased whereas the levels of tissue hexose, hexosamine and fucose were near normal. The present study indicates that the EMS possesses a significantly beneficial effect on the glycoprotein moiety in addition to its antidiabetic effect.

Three potential reactivators of nerve agents-inhibited acetylcholinesterase: 2-[(hydroxyimino)phenylmethyl]-1-methylpyridinium iodide 3a, 2-[(hydroxyimino)pyridin-2-ylmethyl]-1-methylpyridinium iodide 3b and 2-[(1-hydroxyimino) ethyl]-1-methylpyridinium iodide 3c were synthesized. Their reactivation potency was examined using a standard in vitro reactivation test. A rat brain homogenate was used as the source of acetylcholinesterase. Their reactivation potency was compared with a currently used acetylcholinesterase reactivator - 2-PAM (pralidoxime) 4. All tested reactivators were less effective acetylcholinesterase reactivators compared to 2-PAM. In this study, we also tested the reactivation potency of the oxime 2-PAM against inhibition of acetylcholinesterase by sarin, cyclosarin, VX and tabun. Satisfactory results are shown only for the reactivation sarin- and VX-inhibited acetylcholinesterase.

Apigenin is a member of the flavone family of flavonoids and possesses anti-inflammatory, free radical scavenging and anti-carcinogenic properties. Hydrogen peroxide, which is generated during oxidative stress, is known to damage proteins, nucleic acids and cell membranes and also has been implicated in cancer, ageing and several chronic neurogenerative diseases. The present study focuses on the protective effect of apigenin against genotoxic doses of hydrogen peroxide (H₂O₂) using sister chromatid exchanges (SCEs) and cytokinesis blocked micronucleus (CBMN) assay. The treatment with 50, 100 and 150 μM of H₂O₂ results in a significant dose dependent increase in the frequency of SCEs and MN. The treatment with 100 μM of H₂O₂ along with 5, 10 and 20 μM of apigenin results in a dose dependent significant decrease in the frequency of SCEs and MN on cultured human lymphocytes. A similar result was obtained with treatment with 150 μM of H₂O₂ along with 5, 10 and 20 μM of apigenin. The results of the present study suggest a protective effect of apigenin against hydrogen peroxide induced genotoxic damage on cultured human lymphocytes.

Nano-technology has entered the field of medicine in recent decades and many of the nanomaterials developed have already had a high impact on health care. Among nanomaterials, gold nanoparticles (GNPs) and gold quantum dots (QDs) are receiving significant attention because their unique physical, chemical and biological properties are quite different from the bulk of their counterparts. In this article, after a brief historical overview, the use of gold and nano-gold in medicine is reviewed, analyzed, and discussed. The review particularly deals with the use of GNPs and bio-conjugated GNPs in cancer treatment, drug or gene delivery, DNA detection, biomedical imaging including that of brain activity, enhancement of gene regulation, the detection of toxic metals, immuno-assays, disease detection and diagnostics, therapy and also the toxicity of gold and GNPs, etc. A number of novel applications of GNPs in medicine and perspectives of nano-gold use in medicine are also discussed.

The ability of the oxime HI-6 to reduce tabun-induced acute neurotoxic signs and symptoms was compared with the neuroprotective efficacy of two combinations of oximes (HI-6 + trimedoxime, HI-6 + K203) using a functional observational battery. Tabun-induced neurotoxicity and the neuroprotective effects of HI-6 alone, and HI-6 combined with trimedoxime or K203, in rats poisoned with tabun at a sublethal dose (200 μg/kg i.m.; 80% of LD₅₀ value), were monitored by the functional observational battery at 24 hours following tabun challenge. The results indicate that both oxime mixtures tested, combined with atropine are able to allow tabun-poisoned rats to survive for 24 hours following tabun challenge, while one non-treated tabun poisoned rat and one tabun-poisoned rat treated with the oxime HI-6 alone combined with atropine, died within 24 hours following tabun challenge. The oxime HI-6 alone, as well as both oxime mixtures combined with atropine, were able to decrease tabun-induced neurotoxicity in the case of sublethal poisonings, but they did not eliminate all tabun-induced acute neurotoxic signs and symptoms. Their ability to reduce tabun-induced acute neurotoxcicity was almost the same, regardless of type of antidotal treatment. Thus, the tested combinations of oximes were not able to increase the neuroprotective effectiveness of the antidotal treatment of acute tabun poisonings compared to the individual oxime.

Tea tree oil (TTO) is well known as an anti-microbial and immunomodulatory agent and the latter property was examined in this study. Male, C₅₇BI₁₀ x CBA/H (F1), mice were exposed to TTO vapour three times a day, for one week. During this period, half of the mice also received naltrexone (endogenous opioid receptor antagonist) in their drinking water. A day before the end of the TTO inhalation treatment a number of the mice were intra-peritoneally injected with Zymosan or PBS. Spleens and peritoneal exudates were collected 24 h after the injections. Cultured splenocytes were used in in vitro proliferation assays with PHA, and LPS mitogens and peritoneal leukocytes (PTLs) were used for cytofluorimetric ROS level measurement.
The results obtained confirmed the anti-inflammatory properties of TTO, expressed as an inhibition of the increase in the PTL number stimulated by Zymosan. This effect was reversed by naltrexone, suggesting that TTO acts via the endogenous opioid system. TTO also stopped the proliferation of splenocytes in response to mitogens and the activity of PTLs was equivalent to that seen in the control (without inflammation) groups.

In the present investigation, we studied the effect of aqueous green tea extract (GTE), alcoholic turmeric extract (ATE), and water-soluble Chitosan (WSC), individually/or in mixture, on the testicular tissue content of total cholesterol (TC), triglycerides (TG), phospholipids (PL), and thiobarbituric acid reactive substance (TBARS), in addition to nitric oxide (NO) in obese rats.
The testicular weight of the obese rats was increased more significantly than control; TC, TG, PL, TBARS and NO were significantly higher in the obese group. GTE reduced testicular weight and significantly reduced other estimated parameter. ATE significantly increased testicular weight, with apparent peritesticular vascular congestion. It significantly decreased all other studied parameters. WSC significantly increased testicular weight, with significant reduction of all other parameters. The mixture of the three drugs non-significantly decreased testicular weight, and significantly decreased other parameters, except NO, which was significantly more elevated than the obese control. We concluded that obesity induced a significant increase in testicular weight, in addition to TC, TG, PL, TBARS and NO, in comparison to the normal control subjects. An efficient protection against obesity-induced changes was achieved by each individual drug, while the mixture of GTE, ATE and WSC showed less protective potential than each individual drug.We here recommend the use of GTE, ATE in treating obesity-related testicular dysfunction and suggest that attention should be paid to the possible effect of WSC on the bioavailability of other concomitantly-used drugs and suggest a pertinent clinical benefit of both GTE and ATE.

The composition of artherosclerotic plaque can be distingushed from the normal physical properties of tissues by the inflammatory mediators and the cells' remodelling arterial walls, and can therefore be demonstrated by imaging methods. Imaging of the vulnerable atherosclerotic plaque is now accepted as the main target in the diagnostics of imminent acute complications in atherosclerosis. Recent results of clinical trials (Ross's, CAPTIM, Prague) suggest facilitated intervention - primary angioplasty together with pre-hospital fibrinolysis during transportation - as the urgent therapeutical method of choice. This life-saving emergency treatment is considered to be invasive because of the angiography and intravascular ultrasonography.
Angiography ranges from digital subtraction angiography to three-dimensional imaging, together for example with the rotational acquisition of angiographic pictures. X-ray densitometry of the atherosclerotic plaque tissues is also a promising method for differentiation. In contrast, intravascular ultrasonography, by the direct use of varying frequencies, allows the differentiation of tissues, and the demonstration of their relationship by virtual histology. The plaques liable to rupture (unstable vulnerable plaques) contain a large lipid core covered by a thin fibroplastic cap layer with a number of macrophages and mastocytes, and it seems that they, the plaques, can be identified by a so called new "gold-standard" modality. The usefulness of invasive methods is not only in distinguishing pathological processes or the location and size of the atherosclerotic plaque and its calcified parts, but in attracting attention to the extent of its vulnerability. The response to therapy of the arterial wall can also be demonstrated.

The present study was designed to investigate the antihyperglycaemic effect of ethanolic extract of Cardiospermum halicacabum Linn. (Sapindaceae) leaves on normal and streptozotocin (STZ) diabetic rats. Diabetes was induced into male albino Wistar rats by intraperitonial administration of STZ. The Cardiospermum halicacabum leaf extract (CHE) was administered orally at three different doses to normal and STZ-diabetic rats for 45 days. The diabetic rats showed an increase in levels of blood glucose and glycosylated haemoglobin (HbA_1c) and a decrease in the levels of insulin and haemoglobin (Hb). In addition, diabetic rats showed a significant reduction in the activity of glucokinase and an elevation in the activities of gluconeogenic enzymes such as glucose-6-phosphatase and fructose-1, 6-bisphosphatase. Treatment with CHE significantly decreased plasma glucose and HbA_1c, and increased the levels of insulin and Hb. CHE administration to diabetic rats reversed these enzyme activities in a significant manner. Thus, the results show that CHE possesses an antihyperglycaemic activity and provide evidence for its traditional usage in the control of diabetes. The 200 mg dose of the extract produced a better effect than 50 or 100 mg doses.

Aerva lanata is prostrate or decumbent to erect herb. The objective of the present investigation was to study the antihyperglycaemic activity of alcoholic extract of A. lanata leaves (AL-alc) on serum glucose levels, and on the oral glucose tolerance test (OGTT) in alloxan induced diabetic mice. AL-alc (100, 200 and 400 mg/kg) and glyburide (10 mg/kg) were administered orally in alloxan (70 mg/kg, i.v.) induced diabetic mice. In AL-alc (400 mg/kg), the onset was 4 h, the peak effect was 6 h but the effect waned at 24 h. In the subacute study, repeated administration (once a day for 28 days) of the glyburide and AL-alc caused a significant reduction in the serum glucose level as compared to the vehicle treated group. AL-alc (400 mg/kg) treatment prevented a decrease in the body weight of the diabetic mice. In the OGTT, AL-alc (400 mg/kg) increased the glucose threshold at 60 min after the administration of glucose. The AL-alc (400 mg/kg) showed significantly more antihyperglycaemic activity than AL-alc (100 and 200 mg/kg).

The present study investigated the effect of the aqueous extract of Helicteres isora L. (Sterculiaceae) bark on oxidative stress in the heart of rats during diabetes. The aqueous extract of Helicteres isora bark (100 mg, 200 mg/kg body weight, b.w.) was screened for its antioxidant effect in streptozotocin (STZ) induced diabetic rats. An appreciable decrease in peroxidation products, thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD), and hydroperoxides (HP) was observed in the heart tissues of Helicteres isora (HI) treated diabetic rats. The decreased activities of key antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-tranferase (GST) and glutathione (GSH) in diabetic rats were brought back to near normal range upon HI treatment. Tolbutamide was used as the standard reference drug. These results suggest that HI possesses promising antioxidative activity in STZ diabetic rats.

Cyclooxygenase is the enzyme responsible for the production of prostaglandins (PGs). This cyclooxygenase exists in two isoforms: cyclooxygenase-1 (COX-1) and cyclooxygense-2 (COX-2). In humans and primates high levels of COX-2 are detected in the seminal vesicle. Further, the main source of PGs in the semen of these species is from the seminal vesicle. In rodents, the source of PGs in semen is from the vas deferens and abundant levels of COX-2 are detected. A direct relation is thought to exist between COX-2 levels and the source of PGs in semen. Moreover, the role of COX-1 and COX-2 in the seminal vesicle of rodents is obscure. The present study aims at localizing COX-1 and COX-2 in the seminal vesicle of mice. Immunohistochemical staining and COX activity assay revealed COX-1 as a dominant isoform in the mouse seminal vesicle. On treatment with nimesulide - a preferential COX-2 inhibitor - no change in staining intensity and COX activity was observed. The total PG levels also appeared to be unaltered following nimesulide treatment. This confirms that nimesulide had no effect on COX-1. The results presented here suggest COX-1 is the dominant isoform in the mouse seminal vesicle and is responsible for PG synthesis.

This study was designed to evaluate the effect of Terminalia chebula fruit extract on the levels of plasma and tissue glycoprotein components in streptozotocin-induced-diabetic rats. Oral administration of T. chebula fruit extract at a concentration of 200 mg/kg body weight for 30 days significantly reduced the levels of blood glucose, glycosylated hemoglobin, urea, and creatinine as well as fucose, hexose, hexosamine and sialic acid in the diabetic rats treated with the fruit extract. The observed decrease in the levels of plasma insulin and C-peptide in the diabetic rats was elevated to near normal by T. chebula fruit extract treatment. Histological observations made on the pancreatic tissue of control and experimental groups also revealed the beneficial effect of T. chebula fruit extract. The efficacy of the fruit extract was comparable with glibenclamide, a known hypoglycaemic drug.

The authors investigated whether cytosolic free calcium concentration ([Ca²⁺]c) plays a role in hydrogen peroxide-induced pancreatic acinar AR42J cells apoptosis. We analysed mitochondrial depolarization, [Ca²⁺]c determination and caspase-3 activity by fluorimetric methods, and cytochrome c release by subcellular fractionation and western blotting. The data shown that hydrogen peroxide, which causes a sustained [Ca²⁺]c increase, induces mitochondrial depolarization and cytochrome c release, and activation of caspase-3. Dimethyl-BAPTA loading did not affect hydrogen peroxide-evoked mitochondrial apoptosis, suggesting that these responses are independent of increases in [Ca²⁺]c. Treatment with thapsigargin, to induce extensive calcium store depletion and subsequent increases in [Ca²⁺]c, also stimulates mitochondrial depolarization cytochrome c release, and caspase-3 activation. Similar results were observed in AR42J cells loaded with dimethyl-BAPTA, suggesting that activation of apoptosis by thapsigargin does not require rises in [Ca²⁺]c. However, the blockade of mitochondrial calcium entry by pretreating with Ru360 showed protection against hydrogen peroxide- and thapsigargin-induced mitochondrial apoptosis. These results indicate that the apoptosis evoked by hydrogen peroxide and thapsigargin is mediated by mitochondrial calcium uptake.

Curcumin is the most active component of turmeric. It is believed that curcumin is a potent antioxidant and anti-inflammatory agent. Tetrahydrocurcumin (THC), one of the major metabolites of curcumin, exhibits many of the same physiological and pharmacological activities as curcumin and in some systems may exert greater antioxidant activity than curcumin. The aim of this study was to evaluate the effect of THC on the blood glucose, plasma insulin and fatty acid composition of the total lipids in the liver, kidney and brain of control and streptozotocin (STZ)-nicotinamide diabetic rats. The analysis of fatty acids showed that there was a significant increase in the concentrations of palmitic acid (16:1), stearic acid (18:0) and oleic acid (18:1) in the liver, kidney and brain, whereas the concentrations of linolenic acid (18:3) and arachidonic acid (20:4) were significantly decreased. Oral administration of the THC (80 mg/kg body weight) for 45 days to diabetic rats decreased the concentrations of fatty acids, viz., palmitic, stearic, and oleic acid, whereas linolenic and arachidonic acid were elevated. These results suggest that THC exhibits antidiabetic and antihyperlipidemic effects in STZ-nicotinamide induced diabetic rats. It also prevents the fatty acid changes produced during diabetes. The antidiabetic and antihyperlipidemic effects of THC are more potent than those of curcumin at the same dose. The results of the present study indicate that THC showed an antihyperlipidemic effect in addition to its antidiabetic effect in type 2 diabetic rats.

Cognitive impairment is a dramatically increasing problem affecting many individuals as well as the health system. As we have no causal treatment for the loss of memory, symptomatic treatment is needed. Influencing the ACh system is a generally accepted approach, although other therapeutic treatments are in various stages of development. The multiple target drug approach using hybrid compounds may be another optimized move forward for the treatment of cognitive disorders. Since the complex neuronal regulation is slowly being decoded, there is hope that ways will be found to stop neuronal loss and to generate new synapses.

The purpose of our study is to evaluate the protective effect of diphenyl dimethyl bicarboxylate (DDB) in combination with some antioxidants, namely vitamin C (V.C), vitamin E (V.E), and selenium (Se), in liver damage induced by carbon tetrachloride (0.2 ml/kg body weight). This was done by monitoring the liver total and fractional lactate dehydrogenase (LDH) activities. The results revealed a significant increase in the activity of liver total LDH activity in CCl4 - intoxicated rats with a significant increase in both LDH3 and 4 and a significant decrease in LDH5. LDH2 disappeared after CCl4 treatment and neither DDB nor its combinations could restore this permanent change. DDB alone significantly decreased the CCl4-raised total LDH and LDH4, but still far from the control and failed to correct LDH3 and 5 variations. A combination of DDB and V.C, V.E and Se showed the best corrective potential in both total LDH and LDH3 activities, without correcting the increased LDH4, nor the decreased LDH5 isoenzyme. Although this combination was previously reported to correct liver function disturbances, it seems that CCl4 and consequently hepatitis C may induce some irreversible, non-curable changes by DDB or even by additional antioxidants. Its clinical usefulness seems to be through different metabolic pathways, not including correction of LDH disturbances, which necessitates additional investigation for other adjunct medicines for treating liver fibrosis in clinical practice.

Platelet hyperaggregability is involved in the pathogenesis of type 2 diabetes mellitus. Thrombin-evoked platelet aggregation includes the activation of several intracellular pathways, including endogenous generation of reactive oxygen species (ROS), Ca²⁺ mobilization and protein tyrosine phosphorylation. Here we show that crude aqueous extract from Urtica dioica reduces thrombin-evoked aggregation in platelets from healthy donors and diabetics, in a concentration-dependent manner. U. dioica extract showed a potent antioxidant activity and prevented thrombin-evoked ROS generation in platelets from healthy and diabetic donors. Treatment with U. dioica extract reduced Ca²⁺ entry induced by thrombin or selective depletion of the two Ca²⁺ stores in platelets (without altering Ca²⁺ release), reduced protein tyrosine phosphorylation and reversed the abnormal Ca²⁺ mobilization and tyrosine phosphorylation in platelets from diabetics. We conclude that extract from U. dioica shows antiaggregant actions and might be used for the treatment and/or prevention of cardiovascular complications associated with type 2 diabetes mellitus.

Congenital abnormalities, various diseases and injuries may result in the degeneration of articular cartilage. Recently, stem cell therapy has offered new treatment possibilities for this condition. The aim of our study was to verify the chondrogenic differentiation potential of human bone marrow mesenchymal stem cells (BMSCs) and adipose tissue-derived mesenchymal stem cells (AMSCs) in vitro in the presence or absence of transforming growth factor beta (TGF-β1). Human BMSCs and AMSCs from healthy donors were collected during orthopaedic surgeries and expanded in vitro to obtain a sufficient quantity of cells; their chondrogenic differentiation was studied in the pellet culture system. Spontaneous chondrogenesis occurred in both BMSC and AMSC pellet cultures and was similar in both TGF-β1 treated and untreated pellet cultures. BMSC pellets contained more cells with a chondrogenic phenotype. The presence of TGF-β1 led to a decrease in the levels of collagen type I mRNA and to increased levels of collagen type II mRNA only in the BMSC pellet culture. Our results demonstrate that although both mesenchymal cell types can be used in cartilage tissue engineering, the chondrogenic potential of human BMSCs is higher than that of AMSCs.

Mushrooms are a low calorie food with very little fat and are highly suitable for obese persons. The objective of the present investigation was to study the interaction of aqueous extract of P. pulmonarius (called PP-aqu) with acarbose on serum glucose levels, and on the oral glucose tolerance test (OGTT) in alloxan induced diabetic mice. PP-aqu (500 mg/kg), acarbose (50 mg/kg) and their combination were administered orally in alloxan (70 mg/kg i.v.) induced diabetic mice. In the acute study, the serum glucose level was estimated at 0, 2, 4, 6 and 24 h after drug administration. The subacute study involved repeated administration of the drugs for 28 days, a serum glucose level estimation at 7, 14, 21 and 28 days and recording of the body weights of the mice. In the OGTT, D-glucose (2.5 g/kg) was administered in diabetic mice half an hour after pre-treatment with PP-aqu (500 mg/kg), acarbose (50 mg/kg) and their combination. Serum glucose levels were estimated 30 min prior to glucose administration and at 0, 30, 60 and 120 min after glucose loading. The antihyperglycaemic effects of PP-aqu and acarbose alone were similar; i.e. the onset was 2 h, the peak effect was 6 h but the effect waned at 24 h. The effect of the combination of PP-aqu with acarbose was however different, as serum glucose was lower at 24 h. In the subacute study, repeated administration (once a day for 28 days) of the acarbose, PP-aqu and combination caused a significant (P

The present study was undertaken to provide more information on the heterochromatin density in central and peripheral nuclear regions during "cell dedifferentiation" represented by blastic transformation of mature T lymphocytes. Heterochromatin was visualized using a simple cytochemical method for the demonstration of DNA followed by computer-assisted densitometry of digitised images. The results indicated that the blastic transformation was accompanied by a marked and significant decrease in the heterochromatin density at the nuclear membrane. Thus, this nuclear peripheral region seems to be important not only for cell differentiation but also dedifferentiation events. It is also interesting that the non-stimulated resting mature cells in the present study were characterized by less condensed heterochromatin at the nuclear membrane than differentiated granulocytic or erythrocytic precursors and apoptotic myeloblasts or leukemic B lymphocytes described in the previous study. However, in contrast to these cells, resting and mature T lymphocytes in the present study are known to revert to cycling blastic cells after PHA treatment. In addition, it is also known that nuclear peripheral regions with heterochromatin represent sites of chromosomal attachments as well as "together crowded replicons" and silent genes.

New components of transdisciplinary spectra or known components in new variables in us, matching those around us, are being mapped. Their hardly trivial interactions associated with the good and bad around us - from religiosity to crime and war - are being rendered measurable, for the eventual development of countermeasures to the diseases of societies and nations. Internal cycles not only underlie life itself and underlie our evolving genetics at all levels of organization; they also constitute the essential control and reference information in all transdisciplinary science. In preparing for travel to Mars and other missions in space that may take more than a year, let us do what is immediately practicable. Transyears may have very small amplitudes yet are associated with sudden cardiac death in some terrestrial locations; if they should play a role in these electrical incidents of the heart, among others like myocardial infarction and stroke, they will jeopardize lengthy missions in extraterrestrial space, away from hospitals.
The likelihood of stroke or cardiac death can be immediately reduced by chronobiologically assessing blood pressure and heart rate variability and by optimizing the efficacy of timed treatment rather than relying on an unacceptable and often inaccurate spotcheck and treating by convenience rather than pertinence. Needed are: detection of nocturnal abnormality when medication may no longer be effective (or is too effective) neither seen during office visits by day; detection of circadian hyper-amplitude-tension (CHAT) associated with a risk of stroke and kidney disease greater than other risks (including "hypertension" when all risks are assessed concomitantly); detection of CHAT as high risk among normotensives who may not need anti-hypertensive medication; individualized inferential statistical testing to determine whether a drug or non-drug intervention such as autogenic training (relaxation) is effective and for how long (detecting any initial and later success or failure), some of which conditions otherwise are not found without chronobiology; individualization of treatment timing, since the same dose of the same medication can further lower the subject's blood pressure average and circadian amplitude when the timing of daily administration is optimized, as ascertained by sequential testing and parameter tests.
Thus, we save lives by monitoring and assessing, and if need be treating, vascular disease risk through chronobiologically interpreted 24-hour or preferably longer (24-hour/7-day) blood pressure and heart rate variability. Abnormalities in the variability of blood pressure and heart rate, impossible to find during a conventional office visit (the latter aiming at the fiction of a "true" blood pressure), can raise cardiovascular disease risk in the next six years from 4% to 100%.

Chronomic cardiovascular surveillance serves to recognise and treat any risk elevation as well as overt disease, and to ascertain whether treatment is effective and, if so, for how long treatment effects lasts, be it for lowering an increased risk and/or in surveilling the success or failure of treatment. A treatment-associated increase in circadian amplitude of blood pressure (BP) may induce iatrogenic overswinging, also dubbed CHAT ( circadian hyper- amplitude- tension), in some patients, thereby increasing cardiovascular disease risk unknowingly to care provider and receiver.

Tyrosine kinase (TK) activity in primary mononuclear blood cells (MNBC) derived from chronic myelogenous leukemia (CML) patients in the chronic phase as well as from healthy donors was measured by a sensitive time-resolved fluorescence method using the Delfia® Tyrosine Kinase kit. The level of phosphotyrosine was assessed in parallel by flow-cytometry. The experimental protocol for Delfia® was optimized using a K562 cell line. A large part (20 to 50%) of the fluorescence signal from K562 cells was sensitive to Imatinib mesylate, an inhibitor of Bcr-Abl tyrosine kinase, which is currently the leading drug in CML treatment. In primary MNBC, the direct contribution of Bcr-Abl itself to the signal was low. However, a 48h treatment of MNBC with 5 μM Imatinib resulted in a significant reduction of the observed TK activity (mean TK activity value: 56% of control) paralleled by a decrease in the phosphotyrosine level in the CML group. Modification of TK activity by Imatinib was observed also in the donor group. Imatinib mesylate thus probably affects cell signalization even in Bcr-Abl negative cells.