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Cell shape, adhesion, and motility are affected by Ca-regulated pathways, which depend on Ca-binding proteins. One such protein is calreticulin, a ubiquitous and major Ca-binding protein, resident in the ER of eukaryotic cells. In the lumen of the ER, calreticulin is a lectin-like chaperone, sharing this function with an ER-membrane protein, calnexin. Calreticulin also functions as an ER-lumenal Ca store and plays a central role in intracellular Ca homeostasis, including the regulation of store-operated Ca influx via plasma membrane and ER Ca channels. Calreticulin also affects processes outside of the ER; most notably, it modulates expression of several genes, some of them adhesion related, such as vinculin and fibronectin. Curiously, changes in the expression level of calreticulin strongly affect tyrosine phosphorylation of cellular proteins, which is known to affect many adhesion-related functions. Consequently, calreticulin affects cell adhesion via the regulation of expression of proteins important in adhesion, as well as via its effects on intracellular signalling pathways. One of the proteins differentially phosphorylated in a calreticulin-dependent manner is β-catenin, a structural component of cadherin-mediated adhesion complexes and a part of the Wnt signalling pathway. We suggest that the observed changes in cell adhesiveness may be due to calreticulin's influence on a signalling pathway from the ER, which includes the β-catenin/vinculin protein system. Differential expression of calreticulin may affect the phosphorylation status of β-catenin by either inhibition of specific phosphotyrosine kinase(s) or activation of phosphotyrosine phosphatase(s). This is likely to affect the balance between complexed and free β-catenin and impinge further down on the Wnt signalling. At present, the mechanism by which calreticulin affects gene expression can only be speculated upon, but our data indicate that calreticulin, via its effects on Ca release from the ER, may indirectly control the expression of several genes by interfering with calcineurin activity and the ability of the transcription factor, NFAT-3, to translocate to the nucleus. The activation of calcineurin depends on the sustained release of Ca from ER stores, which is dependent on calreticulin.
In summary, we propose that calreticulin may be a centrally located connector molecule in a signalling network in the lumen of the ER. Calreticulin is uniquely endowed for such regulation because it is a multifunctional protein that interacts with several other ER proteins in a Ca-dependent manner, suggesting that it may function as a signalling "toggle switch". We therefore hypothesize that calreticulin regulates gene expression by participating in an "ER-to-nucleus" signalling pathway, which parallels an "ER-to-cell surface" pathway based upon post-translational events.

The aim of this study is to summarize new findings on the most important recessive hereditary disorders in cattle. Important diseases in cattle breeding are: BLAD (Bovine Leukocyte Adhesion Deficiency), DUMPS (Deficiency of Uridine - 5-Monophosphate Synthase), MSUD (Maple Syrup Urine Disease), Bovine Citrullinaemia, and - not detected until 2000 - CVM (Complex Vertebral Malformation). Some of these disorders occur also in man. Thanks to the intensive exploitation of elite sires in artificial insemination, the risk of a fast spread world-wide of recessive hereditary defects is extremely high. In animals there are methods for the detection of heterozygotes like test mating, but they are inapplicable in man due to ethical considerations. Molecular genetic methods enable early diagnosis in man, and are useful in genetic counselling. In animals, the detection of heterozygotes enables their selection and therefore the control and prevention of the spread of recessive diseases in the population. The use of new molecular technologies promises quick progress in animal bioechnology.

Hyperlipidaemia is one of the major risk factors of cardiovascular complication in diabetes. A study was undertaken to evaluate the antihyperlipidaemic activity of pterostilbene. Oral administration of pterostilbene (40mg/kg bodyweight) to streptozotocin-nicotinamide induced diabetic rats for 6 weeks significantly reduced the elevated serum very low density lipoprotein (VLDL) and low density lipoprotein (LDL)-cholesterol levels and significantly increased the serum high-density lipoprotein (HDL)-cholesterol level. In addition, pterostilbene also significantly lowered the levels of triglycerides, phospholipids, free fatty acids and total cholesterol in the serum, liver and kidney of diabetic rats.

Phytochemicals in fruits, vegetables, spices and traditional herbal medicinal plants have been found to play a protective role against many human chronic diseases including cancer and cardiovascular diseases. These diseases are associated with oxidative stress caused by excess of free radicals and other reactive oxygen species. Fractions rich in flavonoids obtained from S. hispida seeds were orally administered at three different doses of 20, 40 and 80 mg/kg BW to HFD fed rats. The antioxidant activity of a flavonoid-rich fraction was measured both in vitro and in vivo. The flavonoid-rich fraction effectively scavenged DPPH^* and ABTS^*+ radicals in vitro. Further, the results showed elevated activities of free radical-scavenging enzymes (SOD, CAT and GPx) and increased levels of non-enzymic antioxidants (GSH, vitamins C and E). TBARS and lipid hydroperoxides decreased significantly in flavonoid-rich fraction treated rats compared to HFD control. Among the doses used, 40 mg/kg BW dose showed maximum effect. Thus, the results indicate that a S. hispida seed flavonoid-rich fraction possesses free radical scavenging and antioxidant activity both in vitro and in vivo.

Free radicals are believed to play an important role in many pathological states. Consequently antioxidants are receiving increased attention in medicinal research. As part of studies of the biological effects of the antidotes against chemical warfare agents currently used in the Czech Armed Forces, eleven compounds were assayed for their free radical scavenging activity. An optimized PC-controlled sequential injection analysis (SIA) system with spectrophotometric detection was used for evaluation of the antioxidation activity of the antidotes. The automated method is based on the known reaction of 2,2'-diphenyl-1-picrylhydrazyl radical (DPPH) with antioxidants. Only the radical scavenging activity of the tested compound 2,3-dimercaptopropanol (BAL) was found to be weaker compared to the reference antioxidant acidum ascorbicum. Other tested antidotes did not possess any DPPH radical scavenging activity. The results obtained show that a correlation between the required biological activity (prophylaxis or treatment of intoxications by warfare agents) and possible antioxidation activity of the tested antidotes is doubtful.

A survey of the current knowledge on stem cells and cell proliferation in turbellarians is presented, with special focus on recent results obtained by the authors when studying cell kinetics and cultivating neoblasts from various species. Differentiated somatic cells do not divide in flatworms. In these animals neoblasts constitute a proliferative compartment. These cells are rather uniform when viewed through a light microscope, but constitute a heterogeneous population comprising actual stem cells, progenitors and early differentiation stages. Cell kinetics were monitored by the incorporation of 5-bromo-2'-deoxyuridine and by immunocytochemical staining for mitoses in the marine microturbellarians Macrostomum, Microstomum and Convolutriloba. Distribution patterns of proliferating cells within the body were documented, and a tentative interpretation of the differences observed is given. Correlations to the nervous system and the mode of reproduction seem to exist. To analyse neoblasts quantitatively and establish primary cultures, neoblasts from the freshwater planarians (triclads) Dugesia and Schmidtea were isolated, purified and subjected to various culture conditions, with the ultimate but not yet achieved goal of establishing a permanent stem cell line. The role of stem cells in flatworms is compared with the situation in mammals, with special focus on embryogenesis, germline and strategies of cell renewal.

Reactive forms of oxygen are released during normal respiration, by the oxidative burst of the macrophages in response to infection, and by a variety of exogenous environmental agents. Oxidative stress, caused by imbalance between the production of reactive forms of oxygen and their elimination, leads to oxidative damage of biomolecules. It is generally accepted that oxidative stress is involved either as cause or effect in a variety of human degenerative diseases. The antioxidant hypothesis proposes that natural antioxidants in fruit and vegetables scavenge free radicals before they can cause damage. To test the hypothesis a reliable biomarker for in vivo assessment of oxidative damage is needed which can be correlated with antioxidant levels on one hand and with disease on the other. Oxidative damage to lymphocyte DNA can be measured by the comet assay or by HPLC. This paper gives a brief review of the methods and their application both in in vitro and in in vivo studies dealing with mutagenesis and carcinogenesis. Molecular epidemiological studies in Slovakia concerning different disease states, aging and the role of diet, and antioxidant supplementation in prevention are reviewed as well.

Hibiscus sabdariffa (Linn) (family Malvaceae), is an annual dicotyledonous herbaceous shrub plant popularly known as 'Gongura' in Hindi or 'Pulicha keerai' in Tamil, which is an indigenous edible medicinal plant used in Ayurvedic Medicine in India, China and Thailand. We have investigated the influence of Hibiscus sabdariffa leaf extract (HSEt) on the levels of circulatory ammonia, urea, lipid peroxidation products such as TBARS (thiobarbituric acid and reactive substances), HP (hydroperoxides) and liver marker enzymes such as AST (aspartate transaminase), ALT (alanine transaminase) and ALP (alkaline phosphatase), for its hepatoprotective effect in ammonium chloride induced hyperammonemia. Ammonium chloride treated rats showed a significant increase in the levels of circulatory ammonia, urea, AST, ALT, ALP, TBARS and HP. These changes were significantly decreased in rats treated with HSEt and ammonium chloride. Our results indicate that HSEt offers hepatoprotection by influencing the levels of lipid peroxidation products and liver markers in experimental hyperammonemia and this could be due to its free radical scavenging property and the presence of natural antioxidants. The exact mechanism has to be still investigated and the isolation of active constituents is required.

The ubiquitous polyamines putrescine, spermidine and spermine fulfil an array of physiological roles in man. In particular, their participation in cell growth and proliferation has been of great interest in relation to their roles in tumour growth and in wound healing. Both endogenous and dietary polyamines take part in such processes. The deprivation of exogenous polyamines emerges as a promising strategy in tumour therapy. Thus, reliable information on their content in foods is needed for dieticians. This review continues our previous comprehensive review on the topic, summarising data on the polyamine content in foods published from 2005 to April 2009. Some new data has appeared. Bovine, porcine and chicken liver, kidney, spleen and heart all have a high content of spermine; bovine liver also of spermidine. Losses of spermidine and spermine up to one half of their original levels occur during both cold and frozen storage and during various thermal treatments. Cultivated mushrooms were reported to contain very high levels of spermidine. Recent results have proved that polyamine content varies widely within a food item, and this complicates the application of available data for the controlled nutrition of patients.

Oxidative stress plays an important role in malignant transformation and is postulated to be associated with increased lipid peroxidation. The aim of this study was to determine the extent of lipid peroxidation with the antioxidant status in patients with gastric cancer. The study population consisted of fifty newly diagnosed gastric cancer patients and an equal number of age- and sex-matched healthy control subjects. Lipid peroxidation as evidenced by thiobarbutric acid reactive substances (TBARS), and also the status of enzymatic (superoxide dismutase - SOD, catalase - CAT, glutathione peroxidase - GPx, glutathione reductase - GR, glutathione S-transferase - GST) and non-enzymatic (reduced glutathione - GSH) antioxidants, were determined. Enhanced lipid peroxidation with concomitant depletion of antioxidants was observed in gastric cancer patients as compared to healthy control subjects. The present study highlights the occurrence of lipid peroxidation and possible breakdown of antioxidant status in patients with gastric carcinoma.

Nitric oxide is a gaseous substance which possesses many important physiological characteristics ranging from its action as a natural immune mechanism to endothelial control of blood pressure. However, it can also generate nitrogen reactive species (peroxynitrite and others), which are involved as a cause of or a consequence of many diseases. This article updates and summarizes the physiological and pathophysiological roles of nitric oxide.

The present study was undertaken to investigate the antihyperammonemic efficacy of the leaf extract of Pongamia pinnata, an indigenous plant used in Ayurvedic Medicine in India (PPEt), on blood ammonia, plasma urea, uric acid, non-protein nitrogen and serum creatinine in control and ammonium chloride induced hyperammonemic rats. The levels of blood ammonia, circulatory urea, uric acid, non-protein nitrogen and creatinine increased significantly in rats treated with ammonium chloride and decreased significantly in rats treated with PPEt and ammonium chloride. There were no significant changes in the body weights of the experimental animals when compared to controls. The antihyperammonemic effect of PPEt could be attributed to (1) its nephroprotective effect by means of detoxifying excess urea and creatinine, (2) its free radical scavenging property, and (3) its antioxidant property. The exact mechanism of antihyperammonemic effect PPEt has still to be investigated and isolation of the active constituents is required.

According to the free radical theory of aging, oxidative stress plays a key role in the senescent decline of the immune system, and therefore antioxidants may provide an effective therapy in order to protect the immune function against oxidative damage. Accordingly, the purpose of this study was to investigate the favourable effect of a diet supplemented with a glutathione precursor - namely the antioxidant N-acetylcysteine (NAC, 0.1% w/w) - on several functions of the leucocytes from prematurely-aging mice (PAM). In adult PAM, the immune functions studied showed values similar to those of older mice, and worse than those found in adult non prematurely-aging mice (NPAM). A short-term ingestion (4 weeks) of NAC, although unable to influence the NK activity, the IL-2 release or the glutathione content of the peritoneal leucocytes of PAM, resulted in an improvement of other very important leucocyte functions such as the lymphoproliferative response to the mitogen Con A, and IL-1β and TNFα release.

Oxidative stress may cause free radical reactions to produce deleterious modifications in membranes, proteins, enzymes and DNA. Valproic acid is a major anti-epileptic drug with a broad spectrum of anti-epileptic activity. Chronic treatment with valproic acid can lead to elevated serum ammonia levels and specific oxidative metabolites of valproic acid have been associated with the drug's toxicity. The influence of sodium valproate treatment on lipid peroxidation and lipid profiles and the detoxifying effects of α-ketoglutarate on sodium valproate induced toxicity were studied in rats. The levels of thiobarbituric acid reactive substances, hydroperoxides and lipid profile variables (cholesterol, phospholipids, triglycerides and free fatty acids) were significantly increased in sodium valproate treated rats. Further, non-enzymic antioxidants (reduced glutathione) and the activities of the enzymic (superoxide dismutase, catalase, glutathione peroxidase) antioxidants were significantly decreased in sodium valproate treated rats. The levels were observed to be normal in α-KG + sodium valproate treated rats. These biochemical alterations during α-KG treatment could be due to (i) its ubiquitous collection of amino groups in body tissues, (ii) the participation of α-KG in non-enzymatic oxidative decarboxylation of the hydrogen peroxide decomposition process and (iii) its role in the metabolism of fats which could suppress oxygen radical generation and thus prevent lipid peroxidative damage.

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.

The circadian rhythms of the haemato-immune system seem to be synchronized by two clocks: the hypothalamic endogenous, and the exogenous which is based on environmental stimuli. The suprachiasmatic nucleus is not only a circadian clock, it also synchronizes peripheral oscillators and integrates light information through the retino-hypothalamic tract. The role of the "peripheral" clock genes in mature leucocytes still remains an unanswered question as well as the role of clock proteins in "non-clock" physiology. The circadian rhythms may be a basis for circannual variations, although the molecular bases of such rhythms remain a mystery. There are several hormones which have a significant impact on haematological characteristics; the finding of a lower superoxide release from granulocytes at higher melatonin levels opens up new research opportunities for melatonin therapy. Discrepancies between circadian changes in mRNAs and the appropriate protein participating in haemocoagulation and fibrinolysis may indicate that we do not know their control processes or their genetic background well, although this problem has now opened up a new area for pharmacological research. The endogenous clock facilitates an alternation in the immune system which counters external attacks in daytime and induces repair and development by night.

The goal of the present study was to investigate the daily amount of motor activity and the daily rhythm of tryptophan and serotonin in goats housed in individual boxes under a 12/12 light/dark cycle. We equipped six Girgentana breed goats with Actiwatch-Mini® (Cambridge Neurotechnology Ltd., UK), actigraphy-based data loggers that record a digitally integrated measure of motor activity. Also blood samples were collected at four-hour intervals over a 48 h period via an intravenous cannula inserted into the jugular vein. The concentration of tryptophan (TRP) and serotonin (5-HT) were assessed by the high-performance liquid chromatography (HPLC) method. Our results outline a diurnal pattern of motor activity and levels of tryptophan in the serum, and a nocturnal pattern of levels of serotonin in the serum, which underline the impact of endogenous serotoninergic activity on the behavioural aspects of the circadian response to light.

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.

Disruptions in sleep-wake patterns have been linked to a variety of health problems, including an increase risk for obesity, type II diabetes, and hypertension. The link to increased risk of malignancy and premature aging is less clear, however. This manuscript reviews current epidemiological and experimental evidence linking alterations in sleep-wake patterns to malignancy and premature aging. Epidemiological evidence suggests that alterations in sleep-wake patterns (e.g.; night-shift or rotating-shift work) are associated with increases in leukemia, endometrial, breast, prostate, and colorectal cancers. Excessive long or short sleep duration is associated with increased mortality. These observations are further supported by experimental animal model systems: Sleep deprivation causes death in Drosophila cycle⁰¹ mutants. Manipulations of light-dark cycle in rodents or mutations that knock out certain genes in the circadian pathway accelerate aging and neoplastic growth. Melatonin, the pineal hormonal signal of darkness appears to have evolved in part to protect against mutagenesis by synchronizing cellular proliferation, differentiation, and apoptosis to the circadian peaks and troughs of genotoxic stress. A model based on circadian-gating of sleep-wake cycles, therefore, links the circadian pathway to the mutational theories of senescence and neoplasia.

The most physiological processes that take place in the body have a circadian rhythm which is controlled by an internal biological clock located in the suprachiasmatic nucleus. The indole melatonin synthesized in the pineal gland, acts to synchronize these biological rhythms, and also it is synthesized and released following a circadian rhythm. The present study analyzed the levels of melatonin over a 24-hour period in Wistar rats in both basal and control conditions and after the oral administration of 125 mg/kg tryptophan, the amino acid that is the precursor of this indole, for 7 days. The levels of melatonin in the plasma and the pineal gland were measured by radioimmunoassay every hour during the night, and every 4 hours during the day. The results indicated that the tryptophan administration provoked raised levels of melatonin at all hours studied in both plasma and pineal. Of the chronobiological parameters studied, there were also increases in the values of the melatonin MESOR with respect to the values obtained in the basal and control groups (the respective increases being 45% and 52% in plasma, and 46% and 47% in the pineal), as well as an advanced acrophase with respect to the basal and control groups. In summary, our findings confirm that tryptophan intake one hour before lights-off increases melatonin levels in plasma and pineal over a 24-hour period, as well as advancing the peak of its synthesis.

This study was designed to evaluate the effect of chronic administration of quinine on the myocardium of Swiss albino mice. 20 or 30 mg quinine/kg b.w. were administered for 30 consecutive days, while the control mice received equal amounts of normal saline. The mice were sacrificed 24 hours after the last administration. Some of the hearts were excised and processed for light microscopic study while some were assayed for malondialdehyde (MDA) and catalase activities. The histological findings indicated that the treated sections of the heart were at variance with the control. The myocardium in the control section presents well organized myofibrils with long cylindrical mononucleated cells in contrast to a dose dependent distorted arrangement of myofibrils and scanty cellular components observed in the treated sections. There was a statistically significant decrement in the weight difference and relative percentage weight of the heart in a dose dependent manner just as the activities of MDA and catalase significantly increased in the treated groups. These findings indicate that chronic administration of quinine may have some deleterious effects on the heart of mice and by extension may affect its function.

The target of the present work was a study of the oxidation-reduction system of the organism damaged with ionizing radiation. The parameters chosen for examination were: the superoxide dismutase activity in erythrocytes, the concentration of reduced glutathione in erythrocytes, the activity of glutathione peroxidase in the total blood, the concentration of malondialdehyde in the blood plasma, and the antioxidant capacity of blood plasma. These parameters were monitored in four groups (patients after radiotherapy, volunteers whose blood was submitted to in vitro irradiation, employees of a nuclear power plant, and a group of healthy persons). A statistically significant decrease in the GSHPx activity was measured in patients after radiotherapy and in employees of the nuclear power plant. Results of processing the data obtained by the method of multidimensional analysis of variance suggest that the dynamics of the changes is comparable in the group of patients after radiotherapy and employees of the nuclear power plant on the one hand, and in the control group and group of healthy volunteers whose blood was subjected to in vitro irradiation, on the other. The study demonstrated changes concerning certain parameters of the oxidation-reduction system after the action of ionizing radiation.

Nitric oxide (NO) is a free radical endogenously produced by nitric oxide synthase. This molecule possesses many important functions in the mammalian organism. The role of NO in regulating cell death and proliferation is now widely recognized. In cultured primary hepatocytes both proapoptotic and antiapoptotic NO effects have been reported. However, most reports support its role in the inhibition of apoptosis. NO has been shown to suppress apoptosis in a model of inflammation and cholestasis, and inhibits spontaneous apoptosis. NO antiapoptotic function was exerted via inhibition of both activity and activation of caspases either directly by nitrosylation, or indirectly via an cGMP-dependent pathway. Both spontaneous and induced hepatocyte apoptosis can be determined by biochemical and morphological methods, which cover various aspects of the apoptotic process, and have a different specificity for detection of apoptotic cell death.

The protective and anticonvulsive efficacy of two prophylactic mixtures (PANPAL consisting of pyridostigmine, benactyzine, and trihexyphenidyle and pyridostigmine plus biperiden) administered prior to the administration of soman in a lethal dose (1.5 LD₅₀) with or without antidotal treatment (atropine + HI-6) was evaluated using rats as experimental animals. The pretreatment was applied 30 and 60 min before intoxication and the antidotal therapy was administered 1 min after soman poisoning. The anticonvulsive efficacy of both prophylactic combinations was determined using a seven degree scale. Non-treated soman-poisoned rats died within 10 min after soman challenge showing severe tremor, subconvulsions and generalized convulsions. More than 90% of pretreated animals survived for 24 hrs following soman poisoning and they were observed to be free from soman-induced toxic signs 24 hrs after soman administration. Our findings confirm that both prophylactic mixtures are able not only to protect experimental animals from the lethal effects of soman but also to eliminate most soman-induced toxic signs. Our results confirm that both prophylactic mixtures should be considered as a pretreatment for nerve agent poisoning, especially in the case of the threat of exposure to soman.

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.

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.