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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.

For the psychiatrist, lithium is an effective drug for both the treatment and prophylaxis of bipolar disorder. The molecular mechanisms underlying its therapeutic actions have not yet been fully explained. The effects of lithium on a number of enzymes and biological processes have been studied. Inositol monophosphatase and glycogen synthase kinase-3 (GSK-3) have been suggested as the relevant intracellular targets for lithium action. The discovery of the role of GSK-3, the Wnt signalling system, and the anti-apoptotic factor Bcl-2 has led to the suggestion that there could be a therapeutic use for lithium in neurodegenerative disorders, such as Alzheimer's disease.

Estrogen replacement therapy (ERT) engenders much debate since several studies contradict its efficacy as a palliative therapy for cognitive decline and neurodegenerative diseases. Signaling transduction pathways alter brain cell activity, survival, and morphology by facilitating transcription factor activation and protein production. The steroidal hormone estrogen and the anti-depressant drug lithium can interact also through these signaling transduction pathways resulting in transcription factor activation. The transcription factor cAMP response element binding protein (CREB) is affected by both estrogen and lithium, and CREB regulates genes involved in learning, memory and neuronal survival. CREB is activated upon phosphorylation at serine 133 by protein kinases and, estrogen and its receptors (ER) facilitate this phosphorylation. Glycogen synthase kinase-3beta (GSK-3β) attenuates CREB's transcriptional properties via subsequent phosphorylation of its serine 129, and lithium is known as a negative regulator of GSK-3β, thus facilitating CREB response element binding. Interestingly, ERα function and DNA-binding properties are facilitated by GSK-3β. In this review we include protein modeling depicting the interaction of CREB/GSK-3β and ERα/GSK-3β using I-TASSER and PatchDock web servers. Understanding the molecular pathways of estrogen will assist in identifying a palliative therapy for menopause-related dementia, and lithium may serve this purpose by acting as a selective estrogen-mediated signaling modulator.

The present study was carried out to investigate the hypoglycaemic effect of S-allyl cysteine (SAC), a garlic component, on some biochemical parameters of STZ induced diabetic rats. STZ induced diabetic rats were treated with SAC at two different doses (100 mg/kg b.w. and 150 mg/kg b.w.) for 45 days. Treatment with SAC significantly decreased the levels of blood glucose, glycosylated hemoglobin, blood urea, serum uric acid, serum creatinine, and diminished activities of pathophysiological enzymes such as aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP). The antihyperglycaemic nature of SAC is also evidenced from the improvement in the levels of plasma insulin and haemoglobin. Further, the results are comparable with glyclazide, an oral standard drug. A 150 mg/kg b.w. dose produced a better effect than a 100 mg dose. Thus, the present findings suggest that SAC may be considered as an effective therapeutic agent for the treatment of diabetes mellitus.

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.

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.

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.

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.

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.

Pentacyclic triterpenes are produced by arrangement of squalene epoxide. These compounds are extremely common and are found in most plants. There are at least 4000 known triterpenes. Many triterpenes occur freely but others occur as glycosides (saponins) or in special combined forms. Pentacyclic triterpenes have a wide spectrum of biological activities and some of them may be useful in medicine. The therapeutic potential of three pentacyclic triterpenes - lupeol, betuline and betulinic acid - is discussed in this paper. Betulinic acid especially is a very promising compound. This terpene seems to act by inducing apoptosis in cancer cells. Due to its apparent specificity for melanoma cells, betulinic acid seems to be a more promising anti-cancer substance than drugs like taxol.

3,5-Dialkoxy-4-hydroxy cinnamic acids 8a-g have been conveniently synthesized from methyl 4-benzyloxy-3,5-dihydroxybenzoate 4. In five steps, cinamic acids 8a-g having various alkoxy groups on C-3 and C-5 positions of the phenyl ring were obtained in 33-70 % overall yields. The antioxidant properties of the newly synthesized amides and the effects on lipid peroxidation in rat brain homogenate will be examined by thiobarbituric acid reactive substances (TBARS) assay and other methods.

The effect of nucleotides in the newborn is a determinant in this first stage of life, and their correct level in breastmilk is vital. We have designed a new method for the assay of nucleotides in milk by capillary electrophoresis (CE) after acid hydrolysis. Breastmilk samples were collected from healthy mothers (ages, 25-35 years) of one month lactation, and stored at -20 °C. The duplicated samples were dissociated by acidic hydrolysis (HClO₄) and the CE assay was performed in an uncoated fused-silica capillary using an alkaline (borate) electrophoretic separation system.
The method gave good recoveries of 5'-mononucleotides. Under the conditions used, the actual CE analysis time was less than 20 minutes. The physiologically and nutritionally important nucleotides were detected at concentrations of 387 μg/100ml for UMP-5P, 385.3 μg/100ml for AMP-5P, 67 μg/100ml for CMP-5P, 172 μg/100ml for TMP-5P and 315 μg/100ml for GMP-5P. Nucleotides are a significant nutrient in infant growth, and capillary electrophoresis is a sensitive and efficient tool for the assay of nucleotides with a purine or pyrimidine base in breastmilk.

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.

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.

In the present study we have investigated the anticarcinogenic property of diallyl disulphide (DADS) on hepatic thiobarbituric acid reactive substances (TBARS) and antioxidants such as reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase in control, N-nitrosodiethylamine and diallyl disulphide treated rats. The levels of TBARS and activities of SOD and catalase were decreased in NDEA treated rats whereas GSH and GPx tended to increase in carcinogenic rats. Oral administration of DADS (60mg/kg body wt) tends to normalize these variables in liver. This clearly indicates that DADS could possess chemopreventive effects by modulating the oxidant-antioxidant status of the living system. However, the exact mechanism remains to be elucidated.

The biochemical and haematological parameters of nutritional interest were determined in the serum of opiate addicts in order to compare them with those obtained in healthy subjects. The blood of 106 opiate addicts in detoxification treatment (n=19) or in Methadone Maintenance Treatment Program (MMTP) (n=87) was studied. Opiate addicts presented lower levels in the number of red cells, cholesterol, albumin, retinol, α-tocopherol, folic acid, K and Se and higher levels in the number of leukocytes, GOT, GPT and Na, than the control group. The opiate addicts in MMTP had higher levels of glucose, triglycerides, Mg and P than the opiate addicts in the detoxification treatment and control groups. Significant correlations between the three vitamins (folic acid, retinal and α-tocopherol) were observed and the graphic representations suggest a biochemical differentiation between opiate addicts and healthy subjects. Factor analysis made it possible to select seven factors explaining 66.2% of the total variance, and representing the first and fourth factor, opiate addicts tended to separate from the control group.

Humic substances as part of humus-soil organic matter - are compounds arising from the physical, chemical and microbiological transformation (humification) of biomolecules. They are important because they constitute the most ubiquitous source of non-living organic material that nature knows. Approximately 80% of the total carbon in terrestrial media and 60% of the carbon dissolved in aquatic media are made up of humic substances. Humic substances have important roles in soil fertility, and are considered to have primal relevance for the stabilization of soil aggregates. They can be divided into three components according to their solubility: humic acids, fulvic acids and humin. Humic acids are the most explored group of humic substances. Beyond their relevance for life these substances have industrial applications in the development of absorbents to be used at the sources of metal-poisoning. Being natural substances, their purification process is cheaper than the synthesis of any other sorbent and, moreover, due to their high operability, they absorb more than the absorbents used to date, such as active charcoals or clays. The specific properties of humic acid products enable their application in industry, agriculture, environmental and biomedicine.

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.

Our research group has previously studied the role of melatonin in the immune system of birds and mice, finding that incubation with both pharmacological and physiological doses of melatonin augmented the activity of phagocytes from these animals, and that this activity was lowered in pinealectomized animals. Since melatonin is synthesized from the amino acid tryptophan, the aim of the present work was to determine whether the administration of tryptophan might affect the plasma levels of melatonin and the phagocytic activity of peritoneal macrophages over the course of a circadian cycle. The study animals were 14-week-old male Wistar rats. They were administered tryptophan orally in a daily single dose of 125 mg/kg at 19:00 h for 21 days. Prior to beginning this treatment, the circadian rhythms of plasma melatonin and phagocytic activity were evaluated under basal conditions over a 24-h period, taking blood and cell suspension samples each 2 hours during the light period (08:00-20:00) and each hour during the dark period (20:00-08:00), since it is during this latter period that the secretion of melatonin is maximum. The results showed that, under basal conditions, the rats' plasma melatonin levels and phagocytic activity peaked at 02:00. After the tryptophan administration, there were increases in plasma melatonin levels with respect to basal and control-group values, with a peak at 21:00, and in the phagocytic activity of the peritoneal macrophages, which peaked at 02:00. This suggests that the tryptophan administration stimulated melatonin synthesis, leading to increased and earlier peaking plasma levels of this hormone, and augmented the innate immune response carried out by the peritoneal macrophages as a result of the immunoregulatory action of melatonin.

The possibilities of MALDI-TOF mass spectrometric analysis of new neuro-protective peptide [G¹⁴]-humanin (HNG) and similar compounds are studied with the aim of finding optimal conditions for the determination of these peptides. Acidification and washing of HNG samples using 5% (v/v) formic acid is necessary to reach a detection limit similar to other peptides. The sensitivity of HNG determination is decreased in the oxidative environment as the peptide yields oxidation of methionine and cysteine forming several species, including a disulfide dimer. During Post-source Decay (PSD) it was found that intense cleavage between Asp and Leu in HNG reduces the possibility of detecting other fragments. Better sequence coverage is gained from shorter humanin-like peptides.

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.

A series of cyclic and acyclic aminophosphonates was synthesized for agrochemical application. The compounds differed in the substituents at the carbon, nitrogen and phosphorus atoms. Their potential biological activity was checked by studying their hemolytic potency, since hemolysis of erythrocytes by various compounds was found earlier to be a good indicator of their pesticidal efficiency. A series of hemolytic experiments permitted us to check the pesticidal efficiency of aminophosphonates and to determine what structural features of aminophosphonates are responsible for it.
Parallelly, we studied the hemolytic efficiency of binary mixtures of the aminophosphonates with the well-known herbicide 2,4-dichlorophenoxyacetic acid (2,4-D...) The aim was to check if potential biological efficiencies could be enhanced in comparison with those found for individual components due to interactions between aminophosphonates and 2,4-D. An analysis of the effects binary mixtures was carried out by constructing graphs for both components of binary mixtures that give the same hemolysis (the isobole method).