Structure and anomeric configuration of the 3,6-anhydro-osazone derivatives obtained from d-altro-2-heptulose phenylosazone

Dehydration of d-altro-2-heptulose phenylosazone with methanolic sulfuric acid afforded two 3,6-anhydro-osazone derivatives (2 and 3). Compound 3 was obtained as the preponderant isomer, with inversion at C-1 (C-3 of the starting osazone), and 2 was obtained without inversion. Refluxing of 3 with copper sulfate afforded the C-nucleoside analog, namely, 2-phenyl-4-β-d-ribofuranosyl-1,2,3-osotriazole (4). Acetylation of 4 afforded the tri-O-acetyl derivative 5. The anomeric configuration was determined by c.d. and n.m.r. spectroscopy. The mass spectra of compounds 2–5 are discussed.     

Sensitive spectrofluorimetric determination of the prokinetic drug prucalopride succinate based on supramolecular aggregation approach with evaluation of method greenness: application to content uniformity test

The prokinetic drug, prucalopride (PCP) succinate, was determined using a new spectrofluorimetric approach with a highly sensitive, rapid, and simple procedure. The method exploited the enhancement of the inherent native fluorescence of PCP by micellar aggregation with sodium lauryl sulfate (SLS) as an anionic surfactant. Different factors that could affect the fluorescence intensity were carefully studied in order to achieve the maximal fluorescence signal. Measurement of the enhanced fluorescence was done at 354 nm after the excitation at 276 nm. The fluorescence intensity–concentration plot was rectilinear in the concentration range of 50–600 ng/ml with detection and quantitation limits of 13.9 and 42.1 ng/ml, respectively. The method underwent validation according to the International Council for Harmonisation criteria in order to assess its analytical performance, and promising results were achieved that proved the validity and reliability of the method. Furthermore, the method was employed effectively for the analysis of the cited drug in commercial pharmaceutical tablets.     

3-β-d-erythrofuranosyl-1-phenylpyrazolo[3,4-b]quinoxaline,a new C-nucleoside analog

Dehydration of the hydroxyalkyl chain of 1-phenyl-3-(d-arabino-tetritol-1-yl)pyrazolo[3,4-b]quinoxaline gave the C-nucleoside 3-β-d-erythrofuranosyl-1-phenyl-pyrazolo[3,4-b]quinoxaline (2) in 82% yield. The structure, and the configuration at the anomeric carbon atom, of 2 were elucidated by periodate oxidation, c.d. and n.m.r. spectroscopy, and mass spectrometry. N.m.r.-spectral and c.d. studies revealed that, due to the large size of the heterocyclic base, compound 2 is formed by inversion in the configuration or C-1 of the side chain. The mechanism of the dehydrative cyclization with inversion is discussed.     

Design,synthesis, antibacterial activity and physicochemical parameters of novel N-4-piperazinyl derivatives of norfloxacin

We report herein the synthesis of some N-Mannich bases in addition to different N-4 substituents of norfloxacin. The antibacterial activities of the newly synthesized compounds were evaluated and correlated with their physicochemical properties. Results revealed that some of the tested compounds exhibited better inhibitory activities than the reference antibiotic norfloxacin against Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumonia and Staphylococcus aureus strains. Correlation results showed that there is no single physicochemical parameter that can determine the effect of N-4 piperazinyl group on the activity of these fluoroquinolones, where lipophilicity, molecular mass and electronic factors may influence the activity.     

Schistosoma haematobium (Egyptian strain): rate of development and effect of praziquantel treatment

This study investigates the development of the Egyptian strain of Schistosoma haematobium and the resultant immunohistopathology and biochemical changes in organs affected. In addition, the response of different developmental stages of S. haematobium worms to praziquantel (PZQ) was examined. Schistosoma haematobium-infected hamsters were classified into 4 groups and were treated at day 35, 55, 75, and 95 postinfection (PI), respectively. Each group was subdivided into 3 subgroups. Two of them were treated orally with PZQ (300 mg/kg or 500 mg/kg divided equally on 2 consecutive days), and the third group was left without treatment. Treated groups were killed 20 days posttreatment. Infection with S. haematobium became patent 73 days PI; tissue egg load and worm fecundity were higher at 95 days and maximal 115 days PI, with an oogram pattern comparable to that in Schistosoma mansoni infection. In the liver, small cellular granulomas were observed 75 days PI, with preponderance of CD4+ T-cell phenotypes. In the urinary bladder, only submucosal focal Brunn's-nest formation and angiogenesis without typical granulomas were observed. Ninety-five and 115 days PI, confluent granulomata with multiple eggs in the center were observed in the liver and urinary bladder, with a preponderance of CD8+ positive T cells in the liver and hyperplasia of the urinary bladder epithelium with cystitis cystica and papillae formation. One hundred percent worm eradication was recorded with the higher dose of PZQ in animals treated 75 and 95 days PI. In conclusion, in spite of the long prepatent period of the Egyptian strain of S. haematobium, sensitivity to PZQ was recorded soon after infection. Granulomata were similar to those of S. mansoni in the livers and urinary bladders, but they were confluent with multiple eggs in the centers, hyperplasia of the urinary bladder urothelium with cystitis cystica, papillae, and Brunn's-nest formation predictive of malignant changes with no hepatocyte dysplasia.     

Growth regulators influence the fatty acid profiles of in vitro induced jojoba somatic embryos

Inducing somatic embryogensis from jojoba [Simmondsia chinensis (Link) Schneider] explants to produce artificial seeds in the laboratory (in vitro) may prove highly profitable, as the seeds contain a characteristic liquid wax of economic importance in industry, nutrition and medicine. Thus, there is a need to examine the effect of the factors involved in the in vitro process on the quality and quantity of the synthesized fatty acids in comparison with those naturally produced in vivo. Immature zygotic embryos and mature leaf explants were cultured on Murashige and Skoog basal medium (MS) supplemented with various levels of 2,4-D, BA and sucrose. Embryogenic calluses developed from the zygotic embryos and leaf explants over a period of 2–4 weeks with the highest response at 0.4 μM 2,4-D, 2.2/4.4 μM BA and 117 mM sucrose (4%). Following induction, the zygotic embryo derived somatic embryos developed to the globular, heart, torpedo, and cotyledon stages. Direct somatic embryogenesis was observed with some of the zygotic embryo explants. Leaf-derived embryogenic calluses did not mature on any of the maturation/germination media examined up to 4 weeks of culture. Analysis of fatty acids indicated that the mature seeds are characterized with long chain saturated fatty acids C22:0 behenic Acid. The zygotic embryo-derived somatic embryos (SE-Z) and leaf-derived somatic embryos (SE-L) are characterized with the induction of the essential polyunsaturated fatty acid C18:2 (omega-6) linoleic acid, (omega-3) alpha-linolenic acid (ALA), with higher values of long chain saturated fatty acids C16:0 palmitic acid and monounsaturated fatty acid C18:1 oleic acid. These results indicate that manipulating the growth regulators in the induction media influenced the fatty acids synthesis and hence the fatty acids profile in jojoba somatic embryos.     

Babesia gibsoni: identification of an immunodominant, interspersed repeat antigen

In this report, an immunodominant antigen called BgIRA from Babesia gibsoni is identified and described. A highly repetitive antigen was screened from a cDNA library. The genomic BgIRA gene exists as single cope gene and contains 10 introns. BgIRA plays a dominant role in the immune response in dogs infected with B. gibsoni. The specificity and sensitivity of the rBgIRA in an ELISA indicated that this antigen might be useful in a diagnostic test.     

<Emphasis Type="Italic">Saccharomyces cerevisiae</Emphasis>, the Baker’s Yeast,suppresses the growth of Ehrlich carcinoma-bearing mice

This study was undertaken to evaluate the effectiveness and mechanisms of anti-tumor activity of Baker’s yeast, Saccharomyces cerevisiae, in immunocompetent mice. Swiss albino mice were inoculated intramuscularly in the right thigh with Ehrlich Ascites Carcinoma (EAC) cells. At day 8, mice bearing Solid Ehrlich Carcinoma tumor (SEC) were intratumorally (IT) injected with killed S. cerevisiae (10 × 10⁶ and 20 × 10⁶ cells) for 35 days. Histopathology of yeast-treated mice showed extensive tumor degeneration, apoptosis, and ischemic (coagulative) and liquefactive necrosis. These changes are associated with a tumor growth curve that demonstrates a significant antitumor response that peaked at 35 days. Yeast treatment (20 × 10⁶ cells) three times a week resulted in a significant decrease in tumor volume (TV) (67.1%, P < 0.01) as compared to PBS-treated mice. The effect was determined to be dependent on dose and frequency. Yeast administered three and two times per week induced significant decrease in TV as early as 9 and 25 days post-treatment, respectively. Administration of yeast significantly enhanced the recruitment of leukocytes, including macrophages, into the tumors and triggered apoptosis in SEC cells as determined by flow cytometry (78.6%, P < 0.01) at 20 × 10⁶ cells, as compared to PBS-treated mice (42.6%). In addition, yeast treatment elevated TNF-α and IFN-γ plasma levels and lowered the elevated IL-10 levels. No adverse side effects from the yeast treatment were observed, including feeding/drinking cycle and life activity patterns. Indeed, yeast-treated mice showed significant final body weight gain (+21.5%, P < 0.01) at day 35. These data may have clinical implications for the treatment of solid cancer with yeast, which is known to be safe for human consumption.     

Biosorption of lead(II), cadmium(II), copper(II) and nickel(II) by anaerobic granular biomass

Biosorption is potentially an attractive technology for treatment of wastewater for retaining heavy metals from dilute solutions. This study investigated the feasibility of anaerobic granules as a novel type of biosorbent, for lead, copper, cadmium, and nickel removal from aqueous solutions. Anaerobic sludge supplied from a wastewater treatment plant in the province of Quebec was used. Anaerobic granules are microbial aggregates with a strong, compact and porous structure and excellent settling ability. After treatment of the biomass with Ca ions, the cation exchange capacity of the biomass was approximately 111 meq/100 g of biomass dry weight which is comparable to the metal binding capacities of commercial ion exchange resins. This work investigated the equilibrium, batch dynamics for the biosorption process. Binding capacity experiments using viable biomass revealed a higher value than those for nonviable biomass. Binding capacity experiments using non-viable biomass treated with Ca revealed a high value of metals uptake. The solution initial pH value affected metal sorption. Over the pH range of 4.0-5.5, pH-related effects were not significant. Meanwhile, at lower pH values the uptake capacity decreased. Time dependency experiments for the metal ions uptake showed that adsorption equilibrium was reached almost 30 min after metal addition. It was found that the q(max) for Pb2+, Cd2+, Cu2+, and Ni2+ ions, were 255, 60, 55, and 26 mg/g respectively (1.23, 0.53, 0.87, and 0.44 mmol/g respectively). The data pertaining to the sorption dependence upon metal ion concentration could be fitted to a Langmiur isotherm model. Based on the results, the anaerobic granules treated with Ca appear to be a promising biosorbent for removal of heavy metals from wastewater due to its optimal uptake of heavy metals, its particulate shape, compact porous structure, excellent settling ability, and its high mechanical strength.     

New ultra-short acting hypnotic: synthesis, biological evaluation, and metabolic profile of ethyl 8-oxo-5,6,7,8-tetrahydro-thiazolo[3,2-a][1,3]diazepin-3-carboxylate (HIE-124)

Ethyl 8-oxo-5,6,7,8-tetrahydro-thiazolo[3,2-a][1,3]diazepin-3-carboxylate (HIE-124, 4) is a member of a new generation of ultra-short acting hypnotics. HIE-124 (4) exhibited potent in vivo activity with a rapid onset of action and a short duration of action, with no acute tolerance or noticeable side effects. The metabolic profile of 4 is also performed. HIE-124 (4) has the potential use as a preanesthetic medication, anesthesia inducer, and could be used with thiopental sodium to maintain anesthesia for longer duration.