Assessment of the physicochemical and sensory characteristics of fermented camel milk fortified with Cordia myxa and its biological effects against oxidative stress and hyperlipidemia in rats.

Natural feed additives and their potential benefits in production of safe and highly nutritious food have gained the attention of many researchers the last decades. Cordia myxa is a nutrient-dense food with various health benefits. Despite this fact, very limited studied investigated the physicochemical and sensory impacts of incorporation of fermented camel milk with Cordia myxa and its biological effects. The current study aimed to assess the physical, chemical, and sensory characteristics of fermented camel milk (FCM) fortified with 5, 10, and 15% Cordia myxa pulp. The study demonstrated that fortification of camel milk efficiently enhanced protein, total solids, ash, fiber, phenolic substance, and antioxidant activity. When compared to other treatments, FCM supplemented with 10% Cordia myxa pulp had the best sensory features. In addition, FCM fortified with 10% Cordia myxa pulp was investigated as a potential inhibitor of hypercholesterolemia agents in obese rats. Thirty-two male Wistar rats were split into two main groups including normal pellet group (n = 8) served as negative control group (G1) and a group of hyperlipidemic animals (n = 24) were feed on a high-fat diet (HFD). Hyperlipidemic rats group (n = 24) were then divided into three subgroups (8 per each); second group or positive control (G2) which include hyperlipidemic rats received distilled water (1 mL/day), the third group (G3) involved hyperlipidemic rats feed on FCM (10 g/day) and the fourth group (G4) included hyperlipidemic animals feed on 10 g/day FCM fortified with 10% of Cordia myxa pulp by oral treatment via an intestinal tube for another 4 weeks. In contrast to the positive control group, G4 treated with Cordia myxa showed a substantial decrease in malondialdehyde, LDL, cholesterol, triglycerides, AST, ALT, creatinine, and urea levels, while a significant increase in HDL, albumin, and total protein concentrations. The number of large adipocytes decreased while the number of small adipocytes increased after consumption of fortified FCM. The results indicated that fermented milk fortified with Cordia myxa pulp improved the functions of the liver and kidney in hyperlipidemic rats. These results demonstrated the protective effects of camel milk and Cordia myxa pulp against hyperlipidemia in rats.

Impairments in reinforcement learning do not explain enhanced habit formation in cocaine use disorder.

RATIONALE: Drug addiction has been suggested to develop through drug-induced changes in learning and memory processes. Whilst the initiation of drug use is typically goal-directed and hedonically motivated, over time, drug-taking may develop into a stimulus-driven habit, characterised by persistent use of the drug irrespective of the consequences. Converging lines of evidence suggest that stimulant drugs facilitate the transition of goal-directed into habitual drug-taking, but their contribution to goal-directed learning is less clear. Computational modelling may provide an elegant means for elucidating changes during instrumental learning that may explain enhanced habit formation. OBJECTIVES: We used formal reinforcement learning algorithms to deconstruct the process of appetitive instrumental learning and to explore potential associations between goal-directed and habitual actions in patients with cocaine use disorder (CUD). METHODS: We re-analysed appetitive instrumental learning data in 55 healthy control volunteers and 70 CUD patients by applying a reinforcement learning model within a hierarchical Bayesian framework. We used a regression model to determine the influence of learning parameters and variations in brain structure on subsequent habit formation. RESULTS: Poor instrumental learning performance in CUD patients was largely determined by difficulties with learning from feedback, as reflected by a significantly reduced learning rate. Subsequent formation of habitual response patterns was partly explained by group status and individual variation in reinforcement sensitivity. White matter integrity within goal-directed networks was only associated with performance parameters in controls but not in CUD patients. CONCLUSIONS: Our data indicate that impairments in reinforcement learning are insufficient to account for enhanced habitual responding in CUD.

Finding Novel Anti-carcinomas Compounds by Targeting SFRP4 Through Molecular Modeling, Docking and Dynamic Simulation Studies.

BACKGROUND: Secreted Frizzled-Related Protein 4 (SFRP4) is a glycoprotein that acts as a competitor of both canonical and non-canonical Wnt pathways. SFRP4 is mostly expressed in ovary and plays a significant role as a target molecule to cure ovarian carcinoma. OBJECTIVE: Multiple chemical agonists are being used to cure ovary melanoma. We are interested in theoretically analyzing the compounds through computational approaches for their potential inhibitory effects against SFRP4. METHODS: Compounds were sketched in Chemsketch drawing tool and minimized through chimera tool. Because the crystal structure of SFRP4 is not available in Protein Data Bank, homology modeling approach was used to predict Three-Dimensional (3D) crystal structure of SFRP4. Moreover, multiple computational approaches such as molecular docking and Molecular Dynamic (MD) simulations along with various online tools were employed to screen the best inhibitor against ovary melanoma. RESULTS: The docking results showed that 1d and 1e compounds revealed significant binding energy values (-9.10 and -9.00 kcal/mol, respectively) compared with the standard drugs such as cis-platin and docetaxel (-3.30, -10.80 kcal/mol), respectively. Moreover, MD simulation results showed that 1d has little fluctuations throughout the simulation period as depicted by the root mean square deviation and root mean square fluctuation graphs. CONCLUSION: The present in-silico study provides a deeper insight into the structural attributes of 1d compound and its overall molecular interactions against SFRP4 and gives a hypothetical gateway to use this compound as a potential inhibitor against ovarian carcinoma.

Bivariate versus multivariate smart spectrophotometric calibration methods for the simultaneous determination of a quaternary mixture of mosapride, pantoprazole and their degradation products.

The ability of bivariate and multivariate spectrophotometric methods was demonstrated in the resolution of a quaternary mixture of mosapride, pantoprazole and their degradation products. The bivariate calibrations include bivariate spectrophotometric method (BSM) and H-point standard addition method (HPSAM), which were able to determine the two drugs, simultaneously, but not in the presence of their degradation products, the results showed that simultaneous determinations could be performed in the concentration ranges of 5.0-50.0 microg/ml for mosapride and 10.0-40.0 microg/ml for pantoprazole by bivariate spectrophotometric method and in the concentration ranges of 5.0-45.0 microg/ml for both drugs by H-point standard addition method. Moreover, the applied multivariate calibration methods were able for the determination of mosapride, pantoprazole and their degradation products using concentration residuals augmented classical least squares (CRACLS) and partial least squares (PLS). The proposed multivariate methods were applied to 17 synthetic samples in the concentration ranges of 3.0-12.0 microg/ml mosapride, 8.0-32.0 microg/ml pantoprazole, 1.5-6.0 microg/ml mosapride degradation products and 2.0-8.0 microg/ml pantoprazole degradation products. The proposed bivariate and multivariate calibration methods were successfully applied to the determination of mosapride and pantoprazole in their pharmaceutical preparations.

Oxidative stress and epididymal sperm transport, motility and morphological defects.

OBJECTIVES: Radical oxidative species (ROS) have an important effect on sperm quality and quantity. Oxidative stress (OS) occurs when production of potentially destructive reactive oxygen species (ROS) exceeds the body's own natural antioxidant defenses, resulting in cellular damage. OS is a common pathology seen in approximately half of all infertile men. Increased ROS generation and reduced antioxidant capacity is negatively correlated with sperm concentration and motility in infertile men. For the first time, we used a more stable and reliable sensitive carbonyl protein (CP) detection method to determine ROS in seminal plasma than measuring ROS directly to clarify the effect of OS on spermatozoa in terms of protein dysfunction. This is the first report to measure CP in seminal plasma as an indicator of OS. Furthermore, for the first time we correlated the results of CP measurement with light microscopy in combination with ultrastructural analysis by electron microscopy. MATERIAL AND METHODS: 20 patients with idiopathic oligoasthenoteratozoospermia (iOAT) and 10 fertile controls were enrolled in this study. CP values were measured by enzyme-linked immuno sorbent assay (ELISA) to detect the level of OS. Transmission electron microscope (TEM) was used to detect axonemal anomalies. RESULTS: Compared to fertile controls, statistically highly significant higher degrees of abnormal sperm parameters (P<0.001) could be found in iOAT patients. CP values were highly significantly elevated in iOAT patients than in normal controls (P<0.001). A statistically highly significant difference in different axonemal anomalies were found between iOAT patients and normal controls (P<0.001). CP values have been found to be positively correlated with different axonemal anomalies (absence of axoneme (r(2)=0.841), missing of central singlet tubules (r(2)=0.702) and missing of outer doublet tubules (r(2)=0.869). A statistically negative correlation were found between different axonemal anomalies (absent axoneme (r(2)=-0.780), missing of central singlet tubules (r(2)=-0.611), and missing of outer doublet tubules (r(2)=-0.738) and forward progressive sperm motility. CONCLUSION: High levels of CP can be measured in iOAT patients, indicating that OS could underlie the aetipopathogenesis of the syndrome. OS negatively affects flagellar axonemal structure with subsequent impairment of forward progressive sperm motility. This can put an attention for antioxidants as a therapy for iOAT syndrome and further research to find how to decrease ROS production.

Genetic diversity within and among sinai populations of three Ballota species (Lamiaceae).

Ballota undulata, Ballota kaiseri, and Ballota saxatilis are very rare (and endemic--B. kaiseri), threatened species growing in St. Catherine Protectorate, southern Sinai, Egypt. They are subjected to a number of threats that have caused populations to decline in both number and size. For the long-term survival of these species, an appropriate conservation strategy for the maintenance of their genetic variation should be developed. This study measures genetic diversity within and among populations of these Ballota species and determines the conservation implications of the results. The genetic analyses demonstrated that the three Ballota species maintain relatively high levels of genetic diversity (He = 0.195-0.317) and that most of the their genetic diversity was found within populations (GST = 0.045-0.099). Indirect estimates of historical gene flow for B. undulata and B. saxatilis were relatively high (Nm(W) = 5.25 and 3.37, respectively) but suggest that there is somewhat less gene movement among B. kaiseri populations (Nm(W) = 2.29). The levels of genetic diversity maintained within populations of the three Ballota species indicate that an appropriate sampling design for ex situ safeguarding should capture the majority of the genetic diversity found within these taxa.

Determination of imipramine in presence of iminodibenzyl and in pharmaceutical dosage form.

Two spectrophotometric methods for the determination of imipramine in presence of iminodibenzyl as an impurity are described. The first method is a ratio-spectra first derivative spectrophotometry, the signals were measured at 240.2 nm for imipramine. Calibration graph was found linear in the range 5-30 microg ml(-1). The second method is based on the reaction of imipramine base, being an electron donor, with p-chloranilic acid, being pi acceptor, to form a purple colored charge transfer complex. The absorbance was measured at 520.5 nm without interference with iminodibenzyl. Both methods are rapid, simple and do not require any preliminary separation or treatment of the samples. Furthermore, the two methods were applied to pharmaceutical dosage form.

Determination of zolpidem hemitartrate by quantitative HPTLC and LC.

Two methods are described for the determination of zolpidem hemitartrate in presence of its degradation product. The first method was a TLC-UV densitometric one in which the mobile phase methanol: water (20:80) was used for developing the TLC plates. The R(f) of zolpidem hemitartrate was found to be 0.29+/-0.01 and that of its degradation product was 0.59+/-0.01. Linearity range was 0.5-4 microg/spot with mean recovery percentage (99.98+/-0.988)%. The second method was an HPLC method. HPLC was performed on a Bondapack C(18) column. The mobile phase was composed of a mixture of acetonitrile-0.01 M KH(2)PO(4) (40:60). The pH was adjusted to 3.5+/-0.1. Flow rate was 1.2 ml/min. Calibration graphs were linear in the range of 0.5-5 microg/ml with UV detection at 245 nm. Both methods have been successfully applied to pharmaceutical formulations. The results obtained were statistically compared with those obtained by applying the reported methods.

Stability-indicating methods for the determination of sumatriptan succinate.

Four stability-indicating methods were developed for the determination of sumatriptan succinate in the presence of its degradation products. The first method depends on the quantitative densitometric evaluation of thin-layer chromatography of sumatriptan succinate in the presence of its degradation products without any interference. Cyclohexane-dichloromethane-diethylamine (50:40:10 v/v/v) was used as a mobile phase and the chromatogram was scanned at 228 nm. This method determines sumatriptan succinate in the concentration range l-8 microg per spot with mean percentage recovery 100.52+/-1.23%. The second and third methods depend on the use of first-derivative (D(1)) and second-derivative (D(2)) spectrophotometry at 234 and 238 nm, respectively. These methods determine the drug in the concentration range 1.25-10 microg x ml(-1) with mean percentage recovery 99.91+/-1.01% and 99.96+/-1.13% for (D(1)) and (D(2)), respectively. The fourth method depends on the use of ratio derivative spectrophotometric technique. The amplitude in the first derivative of the ratio spectra at 235 nm was selected to determine the cited drug in the presence of its degradation products. Calibration graph is linear in the concentration range 1.25-10 microg x ml(-1) with mean percentage recovery 100.19+/-1.19%. The suggested methods were successfully applied for determining sumatriptan succinate in bulk powder, laboratory-prepared mixtures and pharmaceutical dosage forms (Imigran tablet) with good accuracy and precision. The results obtained by applying the proposed methods were statistically analyzed and compared with those obtained by the reported method.

Stability-indicating methods for the determination of doxazosin mezylate and celecoxib.

Two stability-indicating methods were developed for the determination of doxazosin mesylate (I) and celecoxib (II) in the presence of their degradation products. The first method depends on the use of first derivative spectrophotometry (D(1)) at 256, 269 nm for (I) and (II), respectively. This method determines (I) and (II) in concentration ranges of 0.8-12 and 1-20 microg ml(-1) with mean percentage accuracies of 99.21+/-0.88 and 99.59+/-1.67% for (I) and (II), respectively. The second method depends on the quantitative densitometric evaluation of thin-layer chromatography of (I) and (II) in the presence of their degradation products without any interference. Methylisobutyl ketone-glacial acetic acid-water (20:10:10) was used as a mobile phase for (I) and cyclohexane-dichloromethane-diethyleamine (50:40:10) for (II). The chromatograms were scanned at 248 and 253 nm for (I) and (II), respectively. This method determines (I) and (II) in concentration ranges of l-4 microg per spot for both drugs with mean percentage accuracies of 100.19+/-0.95 and 99.91+/-1.95% for (I) and (II), respectively. The suggested methods were used to determine doxazosin mesylate and celecoxib in bulk powder, laboratory-prepared mixtures and pharmaceutical dosage forms (cardura tablet and celebrex capsule). The results obtained by applying the proposed methods were statistically analysed and compared with those obtained by the reported methods.

Spectrophotometric methods for the determination of lansoprazole and pantoprazole sodium sesquihydrate.

Spectrophotometric procedures for determination of two irreversible proton pump inhibitors, lansoprazole (I) and pantoprazole sodium sesquihydrate (II) are presented. Two methods were based on charge transfer complexation reaction of these drugs, where they act as n-donors, with either pi acceptor 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and with sigma acceptor as iodine. A third method was also investigated depending on ternary complex formation with eosin and copper (II). The colored products were quantified spectrophotometrically using absorption bands at 457 nm for DDQ (method A) at 293 and 359 nm for iodine (method B) and at 549 nm using ternary complex formation (method C), for both drugs. The molar combining ratio and the optimum assay conditions were studied. These methods determined the lansoprazole in concentration ranges from 10 to 90, 1.48 to 6.65 and 3.69 to 16.61 microg ml(-1) with mean percentage recovery 99.63% for DDQ, 99.71%, 99.18% for iodine and 99.76% for ternary complex and with relative standard deviation 0.11, 0.24, 0.13 and 0.36%, respectively. For pantoprazole, the concentration ranges were 10-60, 17.7-141.6 and 4.3-25.9 microg ml(-1) with mean percentage recovery 99.51, 98.97, 99.84 and 99.46% and relative standard deviation 0.53, 1.21, 0.65, 0.81% for the three mentioned methods, respectively. Investigation of the formed complexes was made with respect to its composition, molar ratio of the reaction, association constant K(C)AD, molar absorptivity epsilon(lambda)AD and free energy change deltaG for methods (A) and (B). The proposed methods have been applied successfully to the analysis of the cited drugs either in pure form or in pharmaceutical formulations, with good accuracy and precision, compared statistically with those given by the reported methods. They are recommended for quality control and routine analysis.

Effects of industrial formulations of Bacillus thuringiensis on the biology of Musca domestica L. (Diptera : Muscidae).

The effects of two industrial formulations of Bacillus thuringiensis (Bactimos and Vectobac) on larval and adult stages of Musca domestica L. were assessed in the laboratory. Biocides concentrations of 0.4% to 2% were tested on larvae, while the concentrations of 1% and 2% were tested on adults and were given to the flies in their diet. Larval mortality ranged between 38% and 53% and between 55% and 71% for bactimos and Vectobac respectively. Pupation rates decreased from 91% in the control group down to 47% and 29% for Bactimos and Vectobac respectively. Moreover, adult emergence rates decreased 3-4 folds in groups treated with the highest biocide concentrations. The effect on adult mortality was relatively lower, as control adults showed 4% mortality whereas those treated with Bactimos and Vectobac experienced 17-28% and 32-44% mortality respectively. In addition, biocides treatment induced a dramatic decrease in female fecundity from 273 eggs/female in the control to 118-180 eggs/female treated siblings. These findings indicate that Bactimos and Vectobac possess both direct and indirect harmful effects on Musca domestica.