A bioassay-guided fractionation scheme for characterization of new antibacterial compounds from Prosopis cineraria aerial parts

Background and Objectives:Due to the importance of finding of new antibacterial agents, the antibacterial properties of Prosopis cinerariaaerial parts were investigated using a bioassay guided fractionation scheme. Materials and Methods:The organic extract was prepared via maceration in methanol, followed by the fractionation using n-hexane and ethyl acetate. The MICs of fractions were determined against some human pathogenic bacteria using broth micro-dilution assay. The primary characterization and identification of bioactive substance(s) was based on a bio-autograph- ical method using HPTLC and flash chromatography in parallel with agar overlay assays. Finally the exact mass of effective compound(s) was determined by LC-MS. Results:The best antibacterial activities were related to the ethyl acetate fraction. The effective antibacterial compound of the plant were 2 substances with molecular weight of 348 and 184 Dalton that inhibited the growth of assessed Gram positive bacteria with MIC values lower than 125 to 62.5 µg/ml synergistically. Conclusion: Further analysis using nuclear magnetic resonance could reveal the exact structure of these two antibacterial substances. These 2 effective antibacterial compounds could be applied as lead compound for synthesis of new antibacterial agents. © 2016, Tehran University of Medical Science. All Rights reserved

Early-infantile onset epilepsy and developmental delay caused by bi-allelic GAD1 variants

Gamma-aminobutyric acid (GABA) and glutamate are the most abundant amino acid neurotransmitters in the brain. GABA, an inhibitory neurotransmitter, is synthesized by glutamic acid decarboxylase (GAD). Its predominant isoform GAD67, contributes up to ∼90% of base-level GABA in the CNS, and is encoded by the GAD1 gene. Disruption of GAD1 results in an imbalance of inhibitory and excitatory neurotransmitters, and as Gad1−/− mice die neonatally of severe cleft palate, it has not been possible to determine any potential neurological dysfunction. Furthermore, little is known about the consequence of GAD1 disruption in humans. Here we present six affected individuals from six unrelated families, carrying bi-allelic GAD1 variants, presenting with developmental and epileptic encephalopathy, characterized by early-infantile onset epilepsy and hypotonia with additional variable non-CNS manifestations such as skeletal abnormalities, dysmorphic features and cleft palate. Our findings highlight an important role for GAD1 in seizure induction, neuronal and extraneuronal development, and introduce GAD1 as a new gene associated with developmental and epileptic encephalopathy

Chemotherapy in conjoint aging-tumor systems: some simple models for addressing coupled aging-cancer dynamics

Background In this paper we consider two approaches to examining the complex dynamics of conjoint aging-cancer cellular systems undergoing chemotherapeutic intervention. In particular, we focus on the effect of cells growing conjointly in a culture plate as a precursor to considering the larger multi-dimensional models of such systems. Tumor cell growth is considered from both the logistic and the Gompertzian case, while normal cell growth of fibroblasts (WI-38 human diploid fibroblasts) is considered as logistic only. Results We demonstrate, in a simple approach, how the interdependency of different cell types in a tumor, together with specifications of for treatment, can lead to different evolutionary patterns for normal and tumor cells during a course of therapy. Conclusions These results have significance for understanding appropriate pharmacotherapy for elderly patients who are also undergoing chemotherapy

Early-infantile onset epilepsy and developmental delay caused by bi-allelic GAD1 variants.

Gamma-aminobutyric acid (GABA) and glutamate are the most abundant amino acid neurotransmitters in the brain. GABA, an inhibitory neurotransmitter, is synthesized by glutamic acid decarboxylase (GAD). Its predominant isoform GAD67, contributes up to ∼90% of base-level GABA in the CNS, and is encoded by the GAD1 gene. Disruption of GAD1 results in an imbalance of inhibitory and excitatory neurotransmitters, and as Gad1-/- mice die neonatally of severe cleft palate, it has not been possible to determine any potential neurological dysfunction. Furthermore, little is known about the consequence of GAD1 disruption in humans. Here we present six affected individuals from six unrelated families, carrying bi-allelic GAD1 variants, presenting with developmental and epileptic encephalopathy, characterized by early-infantile onset epilepsy and hypotonia with additional variable non-CNS manifestations such as skeletal abnormalities, dysmorphic features and cleft palate. Our findings highlight an important role for GAD1 in seizure induction, neuronal and extraneuronal development, and introduce GAD1 as a new gene associated with developmental and epileptic encephalopathy

The pulsed ultrasound strategy effectively decreases the S. aureus population of chronic rhinosinusitis patients

OBJECTIVE: Staphylococcus aureus with the ability of biofilm formation and the drug resistance acquisition is one of the most frequently isolated pathogens from chronic rhinosinusitis patients. Ultrasound as an alternative therapy is effectively able to kill the bacteria by cavitation in or on the bacterial cells and peroxide generation and hence improving antibiotic treatment efficacy. RESULTS: Staphylococcus aureus was detected in 4 and 6 out of 14 patients by phenotypic and qPCR assays, respectively. Four patients were completely resolved after pulsed ultrasound treatment. However, presence of the S. aureus was confirmed in three healthy controls by bacterial cultivation. Pulsed ultrasound have been quantitatively decreased the S. aureus population in chronic rhinosinusitis patients (p < 0.05). Further studies need to be investigated the effectiveness of pulsed ultrasound as an alternative course of CRS patient's treatment

An Assessment on the Particulars of the Nation's Best Cooperatives in 2008

It has been a promotional policy of the Ministry of Cooperatives to elect a number of cooperative societies annually for the purpose of further motivating cooperators nationwide.  Focusing on the particulars of the Nation's Best Cooperatives in 2008, the study traces them on a comparative basis in these cooperatives through three periods i.e. before 1991, during 1991-2001 and after 2001. To do so, the study has used the data regarding 351 best cooperatives elected in 2008, published by the Ministry of Cooperatives on the occasion of the 3rd Festival of Nation's Best Cooperatives. The Candidate cooperatives contest on six main criteria, with the pairs "employment size", "member satisfaction" and "entrepreneurship", "product quality" valued the highest and the lowest respectively.   Results suggest that the largest number of cooperatives has been registered after the year 1380. Ongoing membership decrease, increasing employment size and the most salient emphasis on education and training-stipulated by the 7th principle of the ICIS-are other significant facts revealed about these cooperatives

Antibacterial Components of Levisticum officinale Koch against Multidrug-resistant Mycobacterium tuberculosis

Background: A bioassay-guided fractionation technique was used to evaluate the active constituents of the perennial plant L. officinale W.D.J. Koch (Apiaceae) against multidrug resistant (MDR) Mycobacterium tuberculosis. Methods: Column chromatography was used to isolation of compounds from L. officinale and spectroscopic methods including 1D and 2D NMR (Nuclear magnetic resonance) and HRMS (high resolution mass spectrometry) were used to identification of the isolated compounds. Also, to evaluate antibacterial activity, minimum inhibitory concentration (MIC) was carried out by broth micro-dilution method. Finally, molecular docking (MD) was performed using the Schrodinger package to evaluate interactions between the active compounds and InhA protein. Results: Phytochemical analysis of the ethyl acetate extract of the plant roots led to isolation of bergapten (1), isogosferol (2), oxypeucedanin (3), oxypeucedanin hydrate (4), imperatorin (5), ferulic acid (6) and falcarindiol (7). Falcarindiol and oxypeucedanin indicated a moderate activity on MDR M. tuberculosis with MIC values of = 32 and 64 mu g/mL, respectively. Antibacterial activity of falcarindiol was also observed against S. aureus and methicillin-resistant S. aureus strains with the MIC values of 7.8 and 15.6 mu g/mL, respectively. The results of docking analysis showed a good affinity of oxypeucedanin (3) and falcarindiol (7) to InhA enzyme with docking score values of -7.764 and -7.703 kcal/mol, respectively. Conclusion: Finally, 7 compounds were isolated from L. officinale that compounds 2-6 report for the first time from this plant. On the basis of the molecular docking (MD) study, oxypeucedanin (3) and falcarindiol (7) as active compounds against M. tuberculosis may be proposed as potential inhibitors of 2-trans-enoyl-ACP reductase (InhA), a key enzyme involved in the biosynthesis of the mycobacterial cell wall. Moreover, antibacterial activity of falcarindiol against methicillin-resistant S. aureus (MRSA) was remarkable

Bacterial community of chronic rhinosinusitis patients and therapeutic ultrasound efficacy: clinical trial study

Background and Objectives: Bacterial involvement in chronic rhinosinusitis (CRS) condition made it difficult to treat using available antibiotic therapy. Therapeutic ultrasound was investigated here to evaluate bacterial diversity and quantity before and after continuous/pulsed ultrasound strategy compared to control patients. Materials and Methods: Totally, 34 CRS patients were studied in three groups, including continuous ultrasound, pulsed ultrasound and control. Bacterial culture and identification were done before and after treatment. Computed tomography scan (CT scan) and questionnaire scores were recorded two times before and after intervention. Results: The most prevalent bacterial isolates were non-hemolytic Streptococci (34 patients), coagulase-negative Staphylococcus (33 patients), Gram-negative cocci (26 patients), Staphylococcus aureus (19 patients), Streptococcus pneumoniae (five patients) and Streptococcus pyogenes (five patients). Both continuous and pulsed ultrasound could significantly reduce the quantity of bacterial isolates after treatment. CT scan and questionnaire results support the effectiveness of therapeutic ultrasound. Conclusion: The quantity of clinically important bacteria was significantly reduced using ultrasound treatment and recovery of patients was supported by CT scan and questionnaire scores. Alternative therapeutic ultrasound could be an effective procedure in CRS patients