Chemistry

There has been an increase in cases of high cholesterol and high blood pressure in people worldwide. This is due to poor diets consisting of high processed sugar, fats and sugar content, as well as lifestyle that encourage little physical exercise. This study investigated the effects of ethanolic extract and aqueous extract of Morus alba leaves on blood glucose, cholesterol levels on twelve randomly selected rabbits which were fed on commercial rabbit pellets. The weights of rabbits were also analyzed to determine if they were affected by M. alba leaf extract. The rabbits were divided into four groups, Group I (Control) was not administered with any ethanolic extract of M. alba leaves, Group II was administered with ethanolic crude extract of M. alba leaves at a dose of 1ml/kg, Group III were administered with the normal saline dilution plus ethanolic crude extract of M. alba leaves and Group IV were administered with aqueous extract of M. alba . Oral administration of the extract w...

Models of the active transport of neurotransmitters in synaptic vesicles were constructed. The models were used to determine the resting potential at membranes of synaptic vesicles: 40 mV (monoamines and acetylcholine) and À40 mV (glutamate). The potential at the membrane of a synaptic vesicle was almost absent for the transport of GABA and glycine. The neurotransmitter concentration of a cell was 0.1-18 mM at the concentration of neurotransmitters in a vesicle equal to 0.5 M. This result is in qualitative agreement with the relevant experimental data.

A model of the active transport of ions through internal membranes of mitochondria is proposed. If concentrations of ions in a cell are known, this model allows calculating concentrations of all main ions (H + , Ca +2 , K + , Mg 2+ , Na + , Cl -) in the mitochondrion matrix and the resting potential across the membrane. The theoretical values satisfactorily agree with available experimental data on the concentrations and the potentials, including different operating regimes of the adenosine triphosphate (ATP) synthetase (the main regime, short circuiting or ATP synthetase blocking). The active transport of Mg 2+ ions in exchange for protons was assumed. In accordance with the model, the ATP synthetase operation is possible only if the stoichiometric coefficient of protons is 3.

Free radical-promoted conjugate addition of activated bromo compounds to a,b-unsaturated ketones and reactive a,bunsaturated esters has been described using titanocene(III) chloride (Cp 2 TiCl) as the radical initiator. Cp 2 TiCl was prepared in situ from commercially available Cp 2 TiCl 2 and activated zinc dust in THF.

Oxidative stress plays a crucial role in the pathogenesis of atherosclerosis by promoting endothelial dysfunction and impairing vascular relaxation. Flavonoids are largely investigated for their biological properties and particularly for their scavenging and antioxidant properties. In the current study, we evaluated the clastogenicity of the chalcone plicatin B in peripheral human lymphocytes (whole blood and pure lymphocytes) as well as its antioxidant activity and its ability to contrast dysfunction on human microvascular endothelial cells (HMEC-1) exposed to hydrogen peroxide. We measured in the cell culture medium the levels of 8-isoprostane, NO x , ET-1, and ICAM-1, as well as the expression of e-NOS, prepro-ET-1, and ICAM-1. In conclusion, our results demonstrate that the chalcone plicatin B (1-10 μM) may represent a good candidate for the prevention of atherosclerosis, as it consistently reduces the oxidative/ inflammatory process and is not genotoxic to human lymphocytes.

The present study was performed to assess and compare a therapeutic efficacy of obidoxime, HI-6, BI-6 and HS-6 administered in equimolar doses and combined with atropine in cyclosarin-poisoned mice and rats. It was demonstrated that all the therapeutic regimens tested, were able to decrease the cyclosarin-induced toxicity significantly -at least 1.5 times. Higher therapeutic ratios, almost three times, were achieved in rats in comparison with mice. The highest therapeutic ratio was achieved for therapeutic regimen consisting of HI-6 and atropine in both mice and rats. Obidoxime was the least effective oxime in the treatment of cyclosarin intoxication. The BI-6 oxime was significantly more efficacious than obidoxime (in both mice and rats) and HS-6 (in rats) but its effectiveness did not reach the efficacy of HI-6.

Acetylcholinesterase (AChE) inhibitors represent standard treatment of Alzheimer´s disease. Cholesterol plays an important role in Alzheimer´s disease development. Because cholesterol synthesis may be inhibited by statins or bisphosphonates, we hypothesized that these drugs might possibly have an influence on cholinesterases. Moreover, we also evaluated if the cholesterol-lowering agents that cross the blood-brain barrier (e.g. simvastatin) should be more effective than those which do not (e.g. atorvastatin). Four groups of rats were orally administered simvastatin, atorvastatin, alendronate or vehicle for seven days. Thereafter, blood samples were taken and the basal ganglia, septum, frontal cortex, and hippocampus were isolated from brains for measurement of acetylcholinesterase activity. In the blood, activities of neither acetyl-nor butyrylcholinesterase were influenced by any of the applied drugs. In the brain, no significant changes in AChE activity were observed after administration of atorvastatin. Both simvastatin and alendronate significantly suppressed the activity of AChE in the frontal cortex. In conclusion, our results confirmed the hypothesis that cholesterol-modifying drugs modulate AChE activity and it is more reasonable to use a blood-brain barrier penetrating drug.

The objective of the experiment was to verify that HI-6 dimethanesulphonate (HI-6 DMS) is able to penetrate the skin in amounts sufficient to protect against organophosphate poisoning using a rat model. HI-6 2Cl is a major component of Transant, a transdermal patch, used as a protective agent against organophosphate intoxication in the Czech and Slovak armies, although there is little evidence that HI-6 would penetrate the skin in sufficient amounts. HI-6 DMS at a total amount of 127 mg or 635 mg was applied as a buffer solution on the Transant patch which was fixed on the back of the rat. Two, seven or twenty-four hours later, rats were sacrificed and blood samples were collected to determine the levels of HI-6 in plasma by HPLC on reversed phase with isocratic elution and UV/VIS detection. HI-6 was not detectable in plasma samples of animals exposed to 127 mg of HI-6 DMS. The highest levels of HI-6 (20.6 ± 18.8 ng/ml) were found in plasma of animals exposed to 635 mg of HI-6 DMS 2 hours after patch application, whereas after 7 or 24 hours the levels were very low. Based on these results, the ability of HI-6 DMS to penetrate the skin is discussed and some possibilities of improving the transdermal penetration are suggested.

Three decontamination solutions of β-cyclodextrines were prepared. Their abilities to decontamine rat skin contamined with nerve agent soman were tested. Decontamination efficacy of the tested cyclodextrine solutions was compared with the same decontamination means but without the cyclodextrines. The efficacy of tested decontaminants was evaluated by the assessment of the ID50 values. Two decontamination prescriptions with cyclodextrines (tetraborate buffer and tetraborate buffer with acetone) do not show significantly better decontamination efficacies in comparison with prescriptions without cyclodextrines. Only in case of aqueous solution of 2–aminoethanol the addition of β-cyclodextrine resulted in significant increase (32%) in decontamination efficacy.

The toxicity of cyclohexyl methylphosphonofluoridate (GF-agent; cyclosarin) and therapeutic efficacy of four oximes (trimedoxime, methoxime, obidoxime and HI-6) in combination with atropine or benactyzine (BNZ) was studied in mice. The oxime therapy combined with anticholinergic drug was administered intramusculary (i.m.) 1 or 2 min after i.m. GF-agent challenge. All the drugs were applied in dose of 20% of LD50. Obidoxime and trimedoxime that were combined with atropine were less effective than methoxime and HI-6 in combination with BNZ when applied 2 minutes after GF-agent poisoning. When the drugs were administered 1 min after GF-agent challenge already, in case of methoxime, the faster application of therapy resulted in significantly higher protective ratio, while for obidoxime the therapeutic effectivity did not depend significantly on the seasonableness of therapeutic intervention. The present findings show that all four combinations of oxime with anticholinergic drug decrease...

The present study was performed to assess and compare a therapeutic efficacy of obidoxime, HI-6, BI-6 and HS-6 administered in equimolar doses and combined with atropine in cyclosarin-poisoned mice and rats. It was demonstrated that all the therapeutic regimens tested, were able to decrease the cyclosarin-induced toxicity significantly -at least 1.5 times. Higher therapeutic ratios, almost three times, were achieved in rats in comparison with mice. The highest therapeutic ratio was achieved for therapeutic regimen consisting of HI-6 and atropine in both mice and rats. Obidoxime was the least effective oxime in the treatment of cyclosarin intoxication. The BI-6 oxime was significantly more efficacious than obidoxime (in both mice and rats) and HS-6 (in rats) but its effectiveness did not reach the efficacy of HI-6.

The mechanism of intoxication with organophosphorus compounds, including highly toxic nerve agents, is based on the irreversible inhibition of acetylcholinesterase that is followed by an accumulation of acetylcholine at peripheral and central cholinergic synapses, which in turn leads to the clinical manifestation of various signs and symptoms summarized as acute cholinergic crisis. Nerve agent poisoning is commonly treated using a

The mechanism of intoxication with organophosphorus compounds, including highly toxic nerve agents, is based on the formation of irreversibly inhibited acetylcholinesterase (AChE; EC 3.1.1.7) that could be followed by a generalized cholinergic crisis. Nerve agent poisoning is conventionally treated using a combination of a cholinolytic drug (atropine mostly) to counteract the accumulation of acetylcholine at muscarinic receptors and AChE reactivators (pralidoxime or obidoxime) to reactivate inhibited AChE. At the Department of Toxicology, the strategy of the development of new more potent AChE reactivators consists of several steps: description of the nerve agent intoxication mechanism on the molecular basis (molecular design), prediction of the biological active structure of AChE reactivators (artificial neural networks), their synthesis, in vitro evaluation of their potencies (potentiometric titration and Ellman's method), in vivo studies (therapeutic index, LD 50 of newly synthesized reactivators, reactivation in different tissues, neuroprotective efficacy).

Protection experiments were conducted using different doses of equine serum butyrylcholinesterase (Eq BuChE) as pretreatment in rats. Cholinesterase activities were determined in blood [whole blood, red blood cells (RBC) acetylcholinesterase (AChE), and plasma BuChE] before and after sarin inhalation exposure in untreated rats and those pretreated with Eq BuChE. Brain AChE activity was also determined in the frontal cortex, basal ganglia and pontomedullar areas following exposure. Dose-dependent increases in plasma BuChE activity and no changes in the RBC and brain AChE activities were demonstrated following i.p. injection of different amounts of Eq BuChE. Decreases in plasma BuChE activity and RBC and brain AChE activities were observed in control rats following sarin inhalation exposure. In rats pretreated with Eq BuChE this inhibition was lower than in control animals. These results demonstrate protective effects of Eq BuChE pretreatment in rats intoxicated with sublethal concent...

Cyclosarin (GF-agent; O-cyclohexylmethylfluorophosphonate) belongs to highly toxic organophosphorus compounds. Potential for exposure to chemical warfare organophosphosphorus nerve agents, such as cyclosarin exists on the battlefield, or in the civilian sector as a threat by a terrorist group, as well as an accident as part of current demilitarization efforts. Cyclosarin was not in a front of scientific interest for long time. The research interest was increased after Operation Desert Shield and Desert Storm with the possibility (later confirmed by the UN special commission) that cyclosarin constituted the Iraqi chemical agent inventory. In this study, the neurotoxicity of cyclosarin and therapeutic efficacy of three oximes as acetylcholinesterase reactivators in combination with atropine was studied in rats. The therapy was administered intramusculary (i.m.) 1 min after i.m. GF-agent challenge (1 LD 50 ). Testing of cyclosarin-induced neurotoxicity progress was carried out using the method of Functional observational battery (FOB). The experimental animals were observed at 24 h and 7 days following cyclosarin administration. The results were compared to the condition of control rats that received physiological solution instead of cyclosarin and treatment. All tested antidotal compounds induced neuroprotective efficacy, because decrease of neurotoxicity signs was recorded. There were no poisoned experimental group treated with atropine only, because our preliminary study showed no therapeutical effect of atropine alone. Cyclosarin caused a marked statistically significant change in most of the neurobehavioral parameters (FOB) at 24 h and 7 days after exposure, compared to the saline control group. Survival was 7/10 at 24 h and 5/10 at 7 days. Oxime (BI-6, HS-6 or HI-6) + atropine treatment caused a progressing recovery of the neurobehavioral disturbances caused by cyclosarin at 24 h and 7 days after exposure.

Oximes in combination with atropine, are an integral part of the treatment of acute intoxications with organophosphorus insecticides or with the nerve agents such as tabun, sarin, soman, cyclosarin or VX. Organophosphorus compounds are extremely potent inhibitors of the enzyme acetylcholinesterase (AChE, 3.1.1.7). The pharmacological action of oximes is multiple: they are able to reactivate the inhibited AChE, but they affect acetylcholine release in peripheral and central cholinergic synapses, allosterically modulate the muscarinic receptors in peripheral and central synapses and influence the nicotinic receptor associated ion-channels. In our study, we have determined the acute toxicity of different structures of oximes after intramuscular application in mice. The acute toxicity of oximes is crucial for the assesment of a dose applied as a treatment for organophosphorus intoxications. We have tested 7 oximes of different structures (HS-6, K033, BI-6, MMB-4, K048, HI-6 and obidoxime) and during experiment we have observed the intoxication process including typical signs of intoxication, and times of death. K033 was the most toxic oxime with LD 50 only 48 mg/kg, while the least toxic oxime -HI-6 has value of LD50 671 mg/kg. All the oximes tested were of bispyridinium type with different length or shape of the connecting chain and positions of oxime groups at the pyridinium rings. All these structure features play important role in biological activity of these compounds performed by their acute toxicity as well as by their reactivation potency.

Changes of acetylcholinesterase (AChE) activities in the hypophysis and brain (frontal cortex, hippocampus, medial septum and basal ganglia), and butyrylcholinesterase in plasma and liver following galanthamine (GAL) administration were studied in rats pretreated with l-carnitine (CAR). Following only GAL administration (10 mg/kg, i.m.), both cholinesterases (without clinical symptoms of GAL overdosage) were significantly inhibited. Pretreatment with CAR (3 consecutive days, 250 mg/kg, p.o.) followed by GAL administration showed higher AChE inhibition in comparison with single GAL administration. However, a statistically significant difference was observed for AChE in the hippocampus only. The activity of peripheral cholinesterases was not influenced by CAR pretreatment. Thus, pretreatment with CAR enhanced AChE inhibition in some brain parts of the rat following GAL administration.

Following repeated antidotal treatment of anaesthetized dogs (1 min with atropine, 10 min with atropine and obidoxime, 60 min with atropine and obidoxime) after the intoxication with soman, sarin and VX (1 × × × × × LD 50 , i.m.), the blood cholinesterases (erythrocyte, whole blood, plasma) were monitored and their reactivatability (whole blood) was determined. During this treatment, the activities of erythrocyte acetylcholinesterase (AChE), plasma butyrylcholinesterase (BuChE) and whole blood cholinesterases were monitored. Atropine and obidoxime did not affect cholinesterase activities in control animals, whereas administration of obidoxime to dogs intoxicated with nerve agent caused an increase in the cholinesterase activities. The sensitivity of cholinesterases decreased in the order erythrocyte AChE > > > > > whole blood cholinesterases > > > > > plasma BuChE, respectively. Following sarin intoxication, blood cholinesterases were increased after the obidoxime administration. Intoxication with VX showed a similar picture but reactivation after the obidoxime administration was greater. In soman intoxication, the picture of cholinesterase changes was similar during the first 30 min of treatment. Then the increase in AChE activity following obidoxime administration was not as high as in the case of sarin and VX intoxication. Thus, the reactivation efficacy of obidoxime during nerve agent intoxication indicates that its repeated administration could be easily monitored using the reactivation test.

Acetylcholinesterase activity in defined brain regions was determined using biochemical and histochemical methods 30 min after treating rats with sarin, soman or VX (0.5 × LD 50 ). Enzyme inhibition was high in the pontomedullar area and frontal cortex, but was low in the basal ganglia. Histochemical and biochemical results correlated well. Determination of the activity in defined brain structures was a more sensitive parameter than determination in whole brain homogenate where the activity was a "mean" of the activities in different structures. The pontomedullar area controls respiration, so that the special sensitivity of acetylcholinesterase to inhibition by nerve agents in this area is important for understanding the mechanism of death caused by nerve agents. Thus, acetylcholinesterase activity is the main parameter investigated in studies searching for target sites following nerve agent poisoning.

The aim of this work was the comparison of reactivation potency of four oxime acetylcholinesterase (AChE) reactivators (pralidoxime, HI-6, K027 and K033) on three resources of the enzyme (human, pig and rat brain homogenate) inhibited by nerve agent sarin. The results demonstrate remarkable differences in the reactivation of inhibited brain AChE, depending on the oxime and species.

We develop a uniform theory for the many-particle diffusion-control effects on the Michaelis-Menten scheme in solution, based on the Gopich-Szabo relaxation-time approximation (Gopich, I. V.; Szabo, A. J. Chem. Phys. 2002, 117, 507). We extend the many-particle simulation algorithm to the Michaelis-Menten case by utilizing the Green function previously derived for excited-state reversible geminate recombination with different lifetimes (Gopich, I. V.; Agmon, N. J. Chem. Phys. 2000, 110, 10433). Running the simulation for representative parameter sets in the time domain and under steady-state conditions, we find poor agreement with classical kinetics but excellent agreement with some of the modern theories for bimolecular diffusion-influenced reactions. Our simulation algorithm can be readily extended to the biologically interesting case of dense patches of membrane-bound enzymes. † Part of the "Attila Szabo Festschrift".

The authors obtain, in the Laplace transform space, the exact analytic solution for the Green function and survival probabilities for the excited-state diffusion-influenced reversible geminate reaction, A*+B⇄C*+D, with two different lifetimes and in the presence of an added quenching process. This extends a previous investigation by Popov and Agmon [J. Chem. Phys. 117, 5770 (2002)] of the ground-state reaction without quenching. The long-time asymptotic behavior of the survival probabilities is obtained in the time domain. It is found to be different from the equal-lifetime case. This paper also provides a useful short-time approximation for the kinetics.

The diffusion-influenced reversible geminate-pair recombination problem is solved exactly in one dimension, in the presence of a constant external field. As the field strength changes sign, the long time asymptotics of the components of the Green function solution show a primary kinetic transition, in which the equilibrium values are changed. At two other critical values of the external field the approach to equilibrium changes, from a t−3/2 power-law to exponential. At the three critical fields, asymptotic t−1/2 decay prevails.

We provide an analytic solution for diffusion-influenced geminate reaction with multiple (N) reversible binding sites (of which one may be irreversible). The solution obtained in the Laplace domain, for two different initial conditions, is valid for the case when the sites are overlapping spheres with no long-range interactions with the diffusing particle. The possibility to invert into the time domain is determined by a characteristic polynomial. When all its roots are distinct, it is possible to apply the Lagrange interpolation formula and obtain a partial-fraction expansion that can be termwise inverted. At long times the occupancy of all sites, and for all initial conditions, decays as t−3/2. The behavior at short times depends on the initial condition: when starting from contact, the binding probability rises as t1/2, but if the particle is initially bound to one of the sites, the occupancy of the others rises as t3/2. In between these two power laws we observe an intermediate-...

We obtained the exact Green functions, in the Laplace domain, for a diffusion‐influenced excited‐state reversible geminate ABCD reaction with two different lifetimes and quenching processes under a constant external field in one dimension. Analytic expressions for the survival probabilities of the initial and final states are obtained in the time domain at short and long times, respectively. The short‐time approximations obtained in this work are valid for ${t \char60 \left| K \right|^{ - 1} }$, where K depends on several parameters of the system. The analysis of the long‐time asymptotic behaviors reveals rather complex kinetic transitions dependent upon the field and lifetimes. We also find a destructive interplay leading to the reduction in the number of kinetic transitions similar to that found for the excited‐state geminate ABC reaction with an external field in one dimension.

We have tested four new bisquaternary pyridinium acetylcholinesterase (AChE; EC 3.1.1.7) reactivators – K005 (1,3–bis(2–hydroxyiminomethylpyridinium) propane dibromide), K033 (1,4–bis(2–hydroxyiminomethylpyridinium) butane dibromide), K027 (1–(4–hydroxyiminomethylpyridinium)-3–(4–carbamoylpyridinium) propane dibromide) and K048 (1–(4–hydroxyiminomethylpyridinium)-4–(4–carbamoylpyridinium) butane dibromide) as the potential reactivators of AChE inhibited by cyclosarin. Their reactivation potencies were studied using standard in vitro reactivation test. Rat brain homogenate was used as the source of the enzyme. Oxime K033 seems to be the most potent reactivator of cyclosarin-inhibited AChE. Its reactivation potency is significantly higher than the efficacy of all other tested AChE reactivators.

The absorption of a photon by a hydroxy-aromatic photoacid triggers a cascade of events contributing to the overall phenomenon of intermolecular excited-state proton transfer. The fundamental steps involved were studied over the last 20 years using a combination of theoretical and experimental techniques. They are surveyed in this sequel in sequential order, from fast to slow. The excitation triggers an intramolecular charge transfer to the ring system, which is more prominent for the anionic base than the acid. The charge redistribution, in turn, triggers changes in hydrogen-bond strengths that set the stage for the proton-transfer step itself. This step is strongly influenced by the solvent, resulting in unusual dependence of the dissociation rate coefficient on water content, temperature, and isotopic substitution. The photolyzed proton can diffuse in the aqueous solution in a mechanism that involves collective changes in hydrogen-bonding. On longer times, it may recombine adiabatically with the excited base or quench it. The theory for these diffusion-influenced geminate reactions has been developed, showing nice agreement with experiment. Finally, the effect of inert salts, bases, and acids on these reactions is analyzed.

Novel solid lipid nanoparticles (SLNs) were developed to improve oral bioavailability of oxyresveratrol (OXY). The SLNs were prepared by a high speed homogenization technique, at an effective speed and time, using Compritol<sup>®</sup> 888 ATO (5% w/w) as the solid lipid. The appropriate weight proportions (0.3% w/w) of OXY affected the physicochemical properties of blank SLNs. The effects of surfactant types on the properties of the formulations such as particle size and entrapment efficacy were also investigated. Conclusively, Tween 80 combined with soy lecithin was the most appropriate surfactant to stabilize OXY-loaded SLNs. The mean particle size of the optimized formulation was 134.40 ± 0.57 nm. <em>In vitro</em> drug release study, the selected S2 formulation showed a retarded release profile for OXY with no initial burst release compared to OXY suspension in the simulated gastrointestinal fluids. Therefore, these SLNs could provide a suitable system t...

A supersaturatable self-microemulsifying drug delivery system (S-SMEDDS) with a reduced amount of surfactant and incorporation of a polymer precipitation inhibitor, Eudragit® E PO was developed. The optimized S-SMEDDS formulation (SS-15) consisted of 55% surfactants, 40% oils, and 5% Eudragit® E PO (curcumin at 44.4 mg/g of the formulation). The precipitation profiles from the supersaturation assay revealed that the curcumin S-SMEDDS performed as a better inhibitor of curcumin precipitation in simulated gastric fluid over a 240-min study than the normal curcumin SMEDDS and an aqueous curcumin suspension. In addition, the mean droplet size of the curcumin S-SMEDDS (21.6 ± 0.1 nm) was significantly smaller than the SMEDDS (28.1 ± 0.3 nm). The curcumin S-SMEDDS exhibited a threefold reduction of Caco-2 cell toxicity when compared to the curcumin SMEDDS because of the reduced toxic effect of the surfactant present in the SMEDDS formulation. In addition, the absorptive permeability acros...

Self-microemulsifying drug delivery systems (SMEDDS) containing two types (Tween80 ® and Labrasol ® ) and two levels (Low; 5% and High; 15%) of co-surfactants were formulated to evaluate the impact of surfactant phase on physical properties and oral absorption of oxyresveratrol (OXY). All formulations showed a very rapid release in the simulated gastric fluid (SGF) pH1.2. After dilution with different media, the microemulsion droplet sizes of the Tween80 ® -based (~26 to 36 nm) were smaller than that of the Labrasol ®based systems (~34 to 45 nm). Both systems with high levels of surfactant increased the Caco-2 cells permeability of OXY compared to those with low levels of surfactant (1.4-1.7 folds) and the unformulated OXY (1.9-2.0 folds). It was of interest, that there was a reduction (4.4-5.3 folds) in the efflux transport of OXY from both systems compared to the unformulated OXY. The results were in good agreement with the in vivo absorption studies of such OXY-formulations in rats. Significantly greater values of Cmax and AUC 0-10h (p<0.05) were obtained from the high levels of Tween80 ® -based (F r,0-10h 786.32%) compared to those from the Labrasol ® -based system (F r,0-10h 218.32%). These finding indicate the importance of formulation variables such as type and quantity of surfactant in the SMEDDS to enhance oral drug bioavailability.

The aim of this study was to develop and assess nanostructured lipid carriers (NLC) compared to solid lipid nanoparticles (SLN) for improving the oral bioavailability of oxyresveratrol (OXY). The OXY formulated as SLN (OXY-SLN) and NLC (OXY-NLC) were prepared by a high shear homogenization technique. The optimized OXY-NLC (NLC3) produced smaller nanoparticle sizes (96 ± 0.9 nm) than that of the OXY-SLN (108 ± 0.3 nm) with a homogeneous size distribution and a high zeta potential. The spherical NLC had a significantly higher efficiency for OXY entrapment (89 ± 0.1%) and a better stability than the SLN after storage for 12 months at 4 ± 2 • C according to parameters such as smaller particles, greater zeta potential and a higher loading capacity (p < 0.05). Differential scanning calorimetry (DSC) showed a less ordered crystalline structure of NLC than SLN. The accumulated drug in an amorphous state in the NLC was also confirmed by powder X-ray diffraction (PXRD). The in vitro release profiles of the OXY-NLC showed a more sustained release compared to the SLN and unformulated OXY. The in vivo pharmacokinetic profiles implied enterohepatic recycling of OXY in the Wistar rat. Meanwhile, the oral absorption pattern of OXY was modified by both types of lipid nanoparticles. The SLN and NLC increased the relative bioavailability of OXY to 125% and 177%, respectively, compared with unformulated OXY. These findings indicated that NLC could be used as a potential carrier to improve the oral bioavailability of OXY.

The present study was aimed to identify the antibacterial potential of biosynthesised silver nanoparticles using different plant parts (leaves, bark and root) of Avicenna marina mangrove plant. Of the selected three different parts, the leaf extract showed the maximum synthesis of silver nanoparticles. The in vitro antibacterial assay (100 lg disk -1 concentration) showed the results of maximum zone of inhibition with the E. coli (18.40 ± 0.97 mm), and minimum (10.87 ± 1.33 mm) zone of inhibition with S. aureus but the concentrations of MIC and MBC values ranged between 6.25 and 50.0 lg ml -1 between the selected bacterial strains. The FTIR results of most potent leaf extract-synthesized silver nanoparticles showed the promi-

A Pseudomonas aeruginosa was isolated from water sample from Industrial effluent and was tested for decolorization activity against commercially important dye of Methyl red. Percentage dye degradation by the isolated Pseudomonas aeruginosa was found to be 90%. The enzyme involved in degradation azoreductase was assayed and purified by anion-exchange chromatography. Total activity of the purified enzyme was 22.5U/mg. The enzyme gave a single band in the SDS-PAGE with a molecular weight of 29 kDa (approximately). The maximal azoreductase activity was observed at pH 7.0 and at 37°C. This activity was NADH dependent. Several metal ions inhibited the purified enzyme including Fe 2+ and Hg 2+ .

The present study was aimed to identify the antigenotoxic effect of bio-synthesised silver nanoparticles (SNP) of Ocimum sanctum leaf extract against cyclophosphamide (CP). We tested the antigenotoxic effect of bio-synthesized silver nanoparticles of O. sanctum leaf extract on human lymphocytes against CP by using chromosomal aberration assay (CAA). Silver nanoparticles was first synthesized from fresh leaf extract of O. sanctum and characterised. Their quality was checked by XRD technique and morphology by SEM. Three different doses of the bio-synthesised SNPs namely, 50, 100 and 200 ll/ml were selected and CP (100 lg/ml) was used as a positive control for CAA. CP administration to human lymphocytes culture caused reduction in mitotic index (MI) and increase in chromosomal damages. The three doses (50, 100 and 200 ll/ml) significantly (P \ 0.005) reduced the chromosomal damages by CP and there was increase in MI. The biological way of synthesising SNPs has advantages like cost effectiveness and eco-friendly. Also the bio-synthesised SNPs of O. sanctum leaf extract was found to be an powerful genoprotectant. Furthermore works are to be carried out in future to find the extract mechanism of its genoprotective nature.

Rubber production has been shown to be correlated positively with the pH of the cytosol of the latex cells (Table l), and negatively with t h e intravacuolar pH (Coupé and Lambert, 1977; Brzozowska-Hanover et al., 1979; Chréstin, 1985). Furthermore, a highly significant inverse relationship was demonstrated between the pH of the cytosolic compartment and the changes in intravacuolar pH (lutoidic pH), strongly suggesting the existence of vectorial He fluxes at the level of the lutoidic tonoplast (Table 1) (Brzozowska-Hanower et al., 1979; Chrkstin, 1985).

There is no significant difference between the ATPase present in the Hevea tonoplast of freshly isolated vacuoles and of lyophilized tonoplast vesicles (same k m value for MgA Tp 2 -, same pH-dependence, same effect of inhibitors, same effect of ionophores and protonophores). It is suggested that the components of the protonmotive force regulate the activity of the tonoplast H+-translocating ATPase. The consequences of such effects may be very important in the regulation of events linked to the compartmentation of solutes inside the plant cell.

We describe a new ultradian rhythm that occurs during the interphase of the cell cycle in a wide range of mammalian cells, including both primary and transformed cells. The rhythm was detected by holographic lens-free microscopy that follows the individual histories of the dry mass of thousands of live cells simultaneously, each at a resolution of five minutes. Importantly, the rhythm was observed in inherently heterogeneous cell populations, thus eliminating synchronization and labeling bias. The rhythm is independent of circadian rhythm, has a period of 4 hours and is temperature-compensated. We demonstrated that the 4 hr rhythm is suppressed by proteostasis disruptors and is detected only in proliferating cells, suggesting that it represents the periodic dynamics of protein mass in growing cells.Brief teaserWe have revealed a 4 hr rhythm in cell dry mass dynamics that seems to be general in proliferating mammalian cells.

The proximate compositions,some minerals,some vitamins and antinutrients contents of sweet Cassava (Manihot esculenta) and Black pepper (Piper nigrum) leaves were investigated on dried weight basis by employing the standard methods described by the Association of Official Analytical Chemists (AOAC, 1990)., Association of vitamin chemists (1987) and Harborne. (1973). The results showed that Sample A (sweet cassava leabes ) contained crude protein (11.70 ± 2.34%), Hexane extract (1.47 ± 0.1%), Ash content (1.90 ±0.1%), crude fibre (3.56 ± 0.14%), moisture (10.8 ± 0.00%) and carbohydrate (70.57 ± 0.45%).while Sample B(black pepper leaves ) contained crude protein (8.73±1.25%), Hexane extract (1.49 ± 0.1222%), Ash content (1.82 ± 0.141%), crude fibre (2.92 ± 0.141%), moisture (12.81 ± 0.00%) and carbohydrate (78.46 ± 1.25%). The results also revealed that Sample A contained potassium (155.75 ± 1.02 mg/100g), sodium (3.82 ± 0.14 mg/100g), calcium (2.47 ± 0.1 mg/100g), magnesium (75.28 ± ...

The grape is one of the most valued conventional fruits, worldwide. Although most of the parts of the grapevine are useful, primarily, the grape is considered as a source of unique natural products not only for the development of valuable medicines against a number of diseases, but also for manufacturing various industrial products. Over the last few decades, apart from the chemistry of grape compounds, considerable progress has been made towards exploring the biological activities of various grape-derived constituents. Today, it is well established that in addition to serving as food, the grape is a major source of several phytochemicals. The main biologically active and well-characterized constituent from the grape is resveratrol, which is known for various medicinal properties in human diseases. This review discusses the roles of various grape-derived phytochemicals in relation to various diseases.

Ovim smo istraživanjem nastojali produbiti razumijevanje vrsnjackog nasilja među srednjoskolcima i provjeriti kako je povezano s doživljenim zlostavljanjem od strane roditelja, te koje su snage i poteskoce mladih povezane s pocinjenim i doživljenim vrsnjackim nasiljem. U istraživanju je sudjelovalo 558 ucenika i ucenica drugih razreda srednjih skola u Ogulinu, Velikoj Gorici, Zaboku i Oroslavju. Primijenjeni se instrumentarij sastojao od Upitnika socio-demografskih podataka, Skale vrsnjackog nasilja (Rimac i sur., 2012), Subskale zadovoljstva vlastitom obitelji iz Skale kvalitete obiteljskih interakcija (Vulic-Prtoric, 2004), Skale rjesavanja sukoba dijete-odrasli (Straus i sur., 1998) te Samoiskaza snaga i poteskoca djece/mladih (Goodman, 1997). Rezultati pokazuju kako svaki tjedan 37.8% ucenika doživljava barem jedan oblik vrsnjackog nasilja. Najzastupljenije je psihicko nasilje, narocito ogovaranje. Pocinjeno i doživljeno vrsnjacko nasilje su umjereno pozitivno povezani. Najvise ...

istraživanja pod nazivom Povezanost nasilja u obitelji, vršnjačkog nasilja i njihovih korelata kod srednjoškolaca te projekta Djeca, mladi, obitelji i socijalni razvoj Hrvatske (066-0661686-1431), koji je odobrilo i koji financira Ministarstvo znanosti, obrazovanja i sporta Republike Hrvatske. 167 Obiteljske i psihosocijalne odrednice vršnjačkoga nasilja među mladima Linda Rajhvajn Bulat, Marina Ajduković Studijski centar socijalnoga rada, Pravni fakultet Sveučilišta u Zagrebu Sažetak Ovim smo istraživanjem nastojali produbiti razumijevanje vršnjačkog nasilja među srednjoškolcima i provjeriti kako je povezano s doživljenim zlostavljanjem od strane roditelja, te koje su snage i poteškoće mladih povezane s počinjenim i doživljenim vršnjačkim nasiljem. U istraživanju je sudjelovalo 558 učenika i učenica drugih razreda srednjih škola u Ogulinu, Velikoj Gorici, Zaboku i Oroslavju. Primijenjeni se instrumentarij sastojao od Upitnika socio-demografskih podataka, Skale vršnjačkog nasilja (R...

ZnO/ZnAl2O4nanocomposite films were synthesised by ultrasonic spray pyrolysis (USP) by extracting Al2O(SO4)2oxide with zinc chloride hydrate in deionised water. The sample was then subjected to heat treatment at 650°C and 700°C for 1 h, which led to the formation of the spinel oxide (ZnAl2O4) and wurtzite (ZnO) phases. Al2(SO4)3·18H2O salt was transformed into aluminum oxide sulfate Al2O(SO4)2, which is an intermediary decomposition product, by calcination at 795°C for 3 h. The structures of the synthesised ZnO/ZnAl2O4films were confirmed by XRD, FTIR, and X-ray photoelectron spectroscopy (XPS). XPS spectra of the major Zn, Al, and O photoelectron lines and the major X-ray induced Zn LMM Auger lines for ZnO/ZnAl2O4are presented.

Background: Bruguiera gymnorrhiza L. (family Rhizophoraceae) is a true mangrove habitat in Indian Sunderban and traditionally uses for liver disorders. Objectives: The aim was to evaluate antioxidant and hepatoprotective actions of leave extract of B. gymnorrhiza L. Materials and Methods: Hydro-methanolic extract of mangrove leaves (BR) was standardized using spectrophotometric and high-performance thin layer chromatography methods. Radical scavenging activities were assessed in different in vitro methods, like 1,1-diphenyl-2-picrylhydrazyl, 2,2'-azino-bis-3-ethyl benzthiazoline-6-sulphonic acid + , superoxides, nitric oxides and hydroxyl radicals. Hepatoprotective efficacy of BR (125 mg/kg and 250 mg/kg, p.o) was measured in D-galactosamine (GalN) induced (200 mg/kg, i.p) hepatitis in Wistar rats. Silymarin (25 mg/kg, p.o) was used as known hepatoprotective agent. Results: Polyphenols such as gallic acid, quercetin, and coumarin obtained from BR exhibited powerful antioxidant properties. Moreover, it produced dose-dependent protection against GalN induced hepatitis in rats. It significantly reduced GalN induced elevation of enzymes (alanine transaminase, aspartate aminotransferase, and alkaline phosphatase) in serum and resist oxidative stress marked by lipid peroxides, glutathione, and catalase in hepatic parenchyma. Conclusions: Polyphenols rich B. gymnorrhiza L. leaves ameliorate hepatic tissue injury through its antioxidant effects.

Cancer and different types of tumors are still the most resistant diseases to available therapeutic agents. Finding a highly effective anticancer drug is the first target and concern of thousands of drug designers. In our attempts to address this concern, a new pyrazine derivative, 1-(5-bromopyrazin-2yl)-1-[3-(trifuoromethyl)benzyl]urea (BPU), was designed via structural optimization and synthesized to investigate its anticancer/antitumor potential. The in-vitro anticancer properties of BPU were evaluated by MTT assay using selected cell lines, including the Jurkat, HeLa, and MCF-7 cells. The Jurkat cells were chosen to study the effect of BPU on cell cycle analysis using fow cytometry technique. BPU exhibited an effective cytotoxic ability in all the three cell lines assessed. It was found to be more prominent with the Jurkat cell line (IC 50 = 4.64 ± 0.08 µM). When it was subjected to cell cycle analysis, this compound effectively arrested cell cycle progression in the sub-G1 phase. Upon evaluating the antiangiogenic potential of BPU via the in-vivo/ex-vivo shell-less chick chorioallantoic membrane (CAM) assays, the compound demonstrated very significant findings, revealing a complementary supportive action for the compound to act as a potent anticancer agent through inhibiting blood vessel formation in tumor tissues. Moreover, the docking energy of BPU computationally scored -9.0 kcal/mol with the human matrix metalloproteinase 2 (MMP-2) and -7.8 kcal/mol with the human matrix metalloproteinase 9 (MMP-9), denoting promising binding results as compared to the existing drugs for cancer therapy. The molecular dynamics (MD) simulation outcomes showed that BPU could effectively bind to the previously-proposed catalytic sites of both MMP-2 and MMP-9 enzymes with relatively stable statuses and good inhibitory binding abilities and parameters. Our findings suggest that the compound BPU could be a promising anticancer agent since it effectively inhibited cell proliferation and can be selected for further in-vitro and in-vivo investigations. In addition, the current results can be extensively validated by conducting wet-lab analysis so as to develop novel and better derivatives of BPU for cancer therapy with much less side effects and higher activities.

Protein nutrition in ruminants encompasses providing the optimum ratio of rumen-degradable and undegradable protein to strike a balance between optimizing rumen efficiency and maximizing animal productivity. The present study aimed to enhance the rumen undegradable proteins of groundnut cake, guar korma, mustard cake, and sunflower meal, and were sprayed with 1 M malic acid (400 mL/kg feed sample) and subjected to heat treatment at 60, 100, 120, and 150°C. Modified in vitro gas production technique (IVGP) was used to determine the in vitro rumen degradable protein of treated and untreated feeds. The malic acid heat treatment was found to be effective in increasing the rumen bypass fraction of feeds at all temperatures, with the highest increase occurring at 150°C. Sunflower meal was shown to be the most resistant to MAH treatment with only about 30% decrease in rumen protein degradability at 150°C as compared to groundnut cake, guar korma, and mustard cake, where a significant reduction (64-70%) was evidenced. Acid detergent insoluble crude protein (ADICP) analysis of feeds treated at 120°C and 150°C for assessing the availability of bypass protein to the small intestine showed no significant (P>0.05) heat damage in groundnut cake, guar korma, and sunflower meal, and thus were considered useful in ruminant rations. However, mustard cake at 150°C was severely heat damaged (41.02%, ADICP) and was considered suitable for use only up to 120°C. Therefore, malic acid-heat treatment of oil cakes could be an effective technology to enhance rumen bypass protein sources for animals and to reduce environmental pollution through faecal and urinary nitrogen excretion.

Background: Traditionally, Portulaca oleracea Linn. is used for treating abscesses, dysentery and liver diseases. In addition, recent studies have reported its efficacy as an analgesic, as neuroprotective, anti-inflammatory, bronchodilatory, and anticancer agent, besides antioxidant, wound healing and other important pharmacological actions. Aim and Objective: For curing liver diseases, Chinese use juice from the fresh leaves of Portulaca oleracea Linn. Hence, to prove this claim, an in-vivo hepatoprotective study of extracts from Portulaca oleracea Linn. against carbon tetrachloride hepatotoxic rats was carried out. Methods: The in-vitro antioxidant activity by using 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay and hepatoprotective activity of extracts of Portulaca oleracea Linn. was assessed against the carbon tetrachloride-induced toxicity rat model. Results: The extracts of Portulaca oleracea Linn produced concentration-dependent percentage inhibition of 2,...

Hydroperoxides generated on lipid peroxidation are highly reactive compounds, tend to form free radicals, and their elevated levels indicate the deterioration of lipid samples. A good alternative to the classical methods for hydroperoxide monitoring are the electroanalytical methods (e.g., a catalytic electrode for their redox-transformation). For this purpose, a series of metal oxides—doped graphitic carbon nitride 2D nanomaterials—have been examined under mild conditions (pH = 7, room temperature) as catalysts for the electrochemical reduction of two water-soluble hydroperoxides: hydrogen peroxide and tert-butyl hydroperoxide. Composition of the electrode modifying phase has been optimized with respect to the catalyst load and binding polymer concentration. The resulting catalytic electrode has been characterized by impedance studies, cyclic voltammetry and chronoamperometry. Electrocatalytic effect of the Co-g-C3N4/Nafion modified electrode on the electrochemical reduction of bot...