Synthesis of new 9-glycosyl-4,9-dihydropyrano [3,4-b]indole-1(3H)-ones as antibacterial agents

A series of new 9-glycosyl-4,9-dihydropyrano[3,4-b]indole-1(3H)-ones 3 was synthesized in moderate to low yields. 4,9-Dihydropyrano[3,4-b]indole-1(3H)-ones (1) were coupled with different acetobromoglycopyranoses 2 in refluxing toluene in the presence of silver oxide to afford one coupling product of the respective N-glycosides. α-L-Arabinopyranosides 3j and 3m were the most active glycosides among the tested compounds against certain Gram positive and Gram negative bacterial strains.     

Progesterone-induced Acrosome Exocytosis Requires Sequential Involvement of Calcium-independent Phospholipase A2β (iPLA2β) and Group X Secreted Phospholipase A2 (sPLA2)

Phospholipase A₂ (PLA₂) activity has been shown to be involved in the sperm acrosome reaction (AR), but the molecular identity of PLA₂ isoforms has remained elusive. Here, we have tested the role of two intracellular (iPLA₂β and cytosolic PLA₂α) and one secreted (group X) PLA₂s in spontaneous and progesterone (P4)-induced AR by using a set of specific inhibitors and knock-out mice. iPLA₂β is critical for spontaneous AR, whereas both iPLA₂β and group X secreted PLA₂ are involved in P4-induced AR. Cytosolic PLA₂α is dispensable in both types of AR. P4-induced AR spreads over 30 min in the mouse, and kinetic analyses suggest the presence of different sperm subpopulations, using distinct PLA₂ pathways to achieve AR. At low P4 concentration (2 μm), sperm undergoing early AR (0–5 min post-P4) rely on iPLA₂β, whereas sperm undergoing late AR (20–30 min post-P4) rely on group X secreted PLA₂. Moreover, the role of PLA₂s in AR depends on P4 concentration, with the PLA₂s being key actors at low physiological P4 concentrations (≤2 μm) but not at higher P4 concentrations (∼10 μm).     

Incidence of Echinococcus granulosus in Domestic Dogs in Palestine as Revealed by Copro-PCR

Hydatidosis or echinococcosisis considered a neglected zoonotic disease despite its high burden in the livestock industry and the high risk of infection by humans in endemic areas. In a cross-sectional study we estimated the copro-Incidence and also genotyped Echinococcus granulosus isolates from domestic dogs using polymerase chain reaction (PCR). Medical archives in nine major hospitals in Palestine were reviewed to determine incidence of E. granulosus infection detected in humans during surgery. Faecal samples were collected from 93 domestic dogs in three districts with the highest number of human cases: Al-Khalil (Hebron), Tubas and Jenin. Genomic DNA was extracted from dog faecal samples and amplified by PCR targeting the repeat DNA sequence (EgG1 Hae III) followed by sequencing of five positive samples. Genotyping was determined by sequencing and BLAST searching of mitochondrial cytochrome c oxidase subunit (CO1). The incidence of E. granulosus infection detected in humans at surgery was 1.2 per 100,000 in the West Bank and 1.0 per 100,000 in Gaza Strip. Seventeen of 93 domestic dogs (18%) were positive, based upon comparison with the Echinococcus DNA control. The five sequenced samples were confirmed to be E. granulosus. Successfully genotyped sample belonged to E.granulosus sensu stricto (formerly G1-G3 complex, sheep strain). For domestic dogs, age group (13-24 months) and sex were identified as two risk factors for contracting E. granulosus. The study identified the high incidence of E. granulosus sensu stricto in dogs in Palestine.     

Chicken feathers: a complex substrate for the co-production of α-amylase and proteases by <Emphasis Type=Italic>B. licheniformis</Emphasis> NH1

This study is concerned with the co-production of alkaline proteases and thermostable α-amylase by some feather-degrading Bacillus strains: B. mojavensis A21, B. licheniformis NH1, B. subtilis A26, B. amyloliquefaciens An6 and B. pumilus A1. All strains produced both enzymes, except B. pumilus A1, which did not exhibit amylolytic activity. The best enzyme co-production was obtained by the NH1 strain when chicken feathers were used as nitrogen and carbon sources in the fermentation medium. The higher co-production of both enzymes by B. licheniformis NH1 strain was achieved in the presence of 7.5 g/l chicken feathers and 1 g/l yeast extract. Strong catabolic repression on protease and α-amylase production was observed with glucose. Addition of 0.5% glucose to the feather medium suppressed enzyme production by B. licheniformis NH1. The growth of B. licheniformis NH1 using chicken feathers as nitrogen and carbon sources resulted in its complete degradation after 24 h of incubation at 37°C. However, maximum protease and amylase activities were attained after 30 h and 48 h, respectively. Proteolytic activity profiles of NH1 enzymatic preparation grown on chicken feather or casein-based medium are different. As far as we know, this is the first contribution towards the co-production of α-amylase and proteases using keratinous waste. Strain NH1 shows potential use for biotechnological processes involving keratin hydrolysis and industrial α-amylase and proteases co-production. Thus, the utilization of chicken feathers may result in a cost-effective process suitable for large-scale production.     

Synthesis and anticancer activity of new [(Indolyl)pyrazolyl]-1,3,4-oxadiazole thioglycosides and acyclic nucleoside analogs

New [(Indolyl)pyrazolyl]-1,3,4-oxadiazole compounds and their derived thioglycosides as well as the corresponding sugar hydrazones were synthesized. The acyclo C-nucleoside analogs of the oxadiazoline base system were also prepared by reaction of acid hydrazides with aldehydo sugars followed by one pot process encompassing acetylation and cyclization of the synthesized hydrazones. The anticancer activity of the newly synthesized compounds was studied against colorectal carcinoma (HCT116), breast adenocarcinoma (MCF7) and prostate cancer (PC3) human tumor cell lines and a number of compounds showed moderate to high activities.     

Increased Levels of Sphingosylphosphorylcholine (SPC) in Plasma of Metabolic Syndrome Patients

Recent developments in lipid mass spectrometry enable extensive lipid class and species analysis in metabolic disorders such as diabesity and metabolic syndrome. The minor plasma lipid class sphingosylphosphorylcholine (SPC) was identified as a ligand for lipid sensitive G-protein coupled receptors playing a key role in cell growth, differentiation, motility, calcium signaling, tissue remodeling, vascular diseases and cancer. However, information about its role in diabesity patients is sparse. In this study, we analyzed plasma lipid species in patients at risk for diabesity and the metabolic syndrome and compared them with healthy controls. Our data show that SPC is significantly increased in plasma samples from metabolic syndrome patients but not in plasma from patients at risk for diabesity. Detailed SPC species analysis showed that the observed increase is due to a significant increase in all detected SPC subspecies. Moreover, a strong positive correlation is observed between total SPC and individual SPC species with both body mass index and the acute phase low grade inflammation marker soluble CD163 (sCD163). Collectively, our study provides new information on SPC plasma levels in metabolic syndrome and suggests new avenues for investigation.     

The natural antiviral and immune stimulant effects of Allium cepa essential oil onion extract against virulent Newcastle disease virus

Fifty broiler chicks were divided into five groups to study the antiviral and immune-stimulant effect of Allium cepa essential oils (ACEO). The effect of Allium cepa essential oils administration single or combined with NVD vaccine in broilers, more than one parameter was studied in this study i.e., the clinical symptoms that appeared on the chicks after the experimental infection with velogenic Newcastle disease virus, postmortem lesions, pathological lesions scoring, mortality rate (MR), and viral shedding, birds immunity was assessed by HI test and protection percent post-challenge with vNDV. Our result showed that mild clinical signs, lesion scoring, decreased viral shedding in ACEO treated groups 3 (G 3) more than control groups post-challenge with vNDV. Delayed onset of mild clinical signs in G3 followed by complete recovery 7th-day post-challenge (DPC). Low MR (40 and 0%) and high protection percent (100 and 60%) in ACEO treated G3 and G5, respectively. spleen, thymus, cecal tonsil, proventriculus, and cerebrum lesions scoring in G3 and G5 were significantly ((p ≤ 0.05).) lower than the control group, proving a decrease in NDV replication and effective antiviral activity of ACEO. HI titer significantly increased (p ≤ 0.05) In G3, G4 and G5 compared with control groups. There is no significant difference in HI titer in ACEO treated groups and vaccinated groups. In conclusion, oral administration of ACEO combined with NDV vaccines significantly reduces or eliminates lethal clinical signs, lesions, viral shedding, and enhances immune response and protection percent after vNDV challenge proving the natural antiviral and immune stimulant effect of ACEO onion extract. Implementing such a regime might aid NDV control in broiler flocks in endemic areas and reduce the epidemiological load of NDV in the environment.     

Liposomes as an ocular delivery system for acetazolamide: In vitro and in vivo studies

The purpose of this study was to formulate topically effective controlled release ophthalmic acetazolamide liposomal formulations. Reverse-phase evaporation and lipid film hydration methods were used for the preparation of reversephase evaporation (REVs) and multilamellar (MLVs) acetazolamide liposomes consisting of egg phosphatidylcholine (PC) and cholesterol (CH) in the molar ratios of (7∶2), (7∶4), (7∶6), and (7∶7) with or without stearylamine (SA) or dicetyl phosphate (DP) as positive and negative charge inducers, respectively. The prepared liposomes were evaluated for their entrapment efficiency and in vitro release. Multilamellar liposomes entrapped greater amounts of drug than REVs liposomes. Drug loading was increased by increasing CH content as well as by inclusion of SA. Drug release rate showed an order of negatively charged > neutral > positively charged liposomes, which is the reverse of the data of drug loading efficiency. Physical stability study indicated that approximately 89%, 77%, and 69% of acetazolamide was retained in positive, negative, and neutral MLVs liposomal formulations up to a period of 3 months at 4°C. The intraocular pressure (IOP)-lowering activity of selected acetazolamide liposomal formulations was determined and compared with that of plain liposomes and acetazolamide solution. Multilamellar acetazolamide liposomes revealed more prolonged effect than REVs liposomes. The positively charged and neutral liposomes exhibited greater lowering in IOP and a more prolonged effect than the negatively charged ones. The positive multilamellar liposomes composed of PC:CH:SA (7:4:1) molar ratio showed the maximal response, which reached a value of −7.8±1.04 mmHg after 3 hours of topical administration. Published: January 5, 2007     

Effects of garlic on Schistosoma mansoni harbored in albino mice: Molecular characterization of the host and parasite

Garlic has been used for its health benefits for thousands of years. Modern research confirmed many of the healing properties of garlic, including its antiparasitic activity. This study was designed to evaluate the antischistosomal action of garlic through detecting the changes in DNA profile of Schistosoma mansoni worms and the infected mouse. Forty mice were subcutaneously infected with ~ 200 Schistosoma mansoni cercariae/mouse. Infected mice were divided into four equal groups: non-treated, prophylactic, therapeutic, and continuously-treated. Non-infected control and garlic-treated groups were assigned for the sake of comparison. Garlic extract (50 mg/kg bw/mouse) was given orally, day after day, at a fixed daytime. Seven weeks post-infection, adult schistosomes were recovered by perfusion and the livers of the mice were excised out and were processed for DNA extraction and Random Amplification of Polymorphic DNA-Polymerase Chain Reaction (RAPD-PCR). The results showed that garlic exerted no major changes in the genome of schistosomes. Nevertheless, that schistosomal infection induced genetic alterations in the DNA of mice, and garlic was able to ameliorate such alterations to a great extent.