The potential use of asparaginases has gained tremendous significance in the treatment of acute lymphoblastic leukemia (ALL). Earlier studies suggest L-asparaginases (L-ASP) extracted from Escherichia coli and Erwinia aroideae regulates L-asparagine (L-Asn) from the circulating blood. Prolonged exposure to these enzymes may lead to hypersensitivity reactions. So, it is important to find novel asparaginases with anti-cancer properties. The three-dimensional structure of L-ASP I from Vibrio campbellii was determined by homology modeling using EasyModeller v.4.0. The structure was validated with quality indexing tools and was deposited in Protein Model DataBase. Molecular docking was performed between L-ASP I and ligand substrate L-Asn to study enzyme-substrate interactions. Qualitative and quantitative analysis of L-ASP I enzyme was found to be reliable and stable with a significant protein quality factor (LG score: 7.129). The enzyme is a dimer, belongs to α/β class of proteins. The active sites comprises of N-glycosylation site and a catalytic triad (T14-S117-D92). The binding energy of the docked complex was calculated to be -7.45 kcal/mol. The amino acid T14 identified as a primary nucleophile essential for catalytic reaction. The enzyme L-ASP I of V. campbellii provides a detailed view of structure and functional aspects with ligand substrate L-Asn. This in silico investigation has explicitly demonstrated for the first time that cytosolic L-ASP Type I of V. campbellii to have a catalytic triad which was attributed only to periplasmic L-ASP Type II. Thus, L-ASP I can serve as anti-leukemic agent in the treatment, management and control of ALL.
C-terminal amidation is a common feature of wild type membrane disrupting antimicrobial peptides (AMPs). Empirical evidence suggests that this modification increases antimicrobial efficacy. However, the actual role of C-terminal amidation in the molecular mechanism of action of AMPs is not fully understood. Amidation alters two key properties simultaneously: the net charge and helicity of the peptide, both of which are implicated in the mechanism of action. However, the differences between the physicochemical properties of the carboxyl and amide moieties have been disregarded in former studies. In this study we assessed whether the difference in activity is only caused by changes in the helicity and overall charge of a peptide, i.e. whether the chemistry of the terminus is otherwise irrelevant. To do so, the membrane disrupting activity of a modified aurein 1.2 peptide was studied in which a secondary amide was formed with a terminal methyl group, instead of the primary amide as in the wild type peptide. Results of quartz crystal microbalance, dye leakage and circular dichroism experiments show that the activity of the modified peptide is substantially reduced compared to the wild type peptide, in particular that the modified peptide exhibited a much-reduced ability to bind to the membrane. Thus, the primary amide at the C-terminus is required to bind to the membrane, and a secondary amide cannot serve the same purpose. We hypothesize that this difference is related to the hydration state of the terminus. The lack of membrane binding ability of the modified peptide identifies the primary amide moiety at the C terminus as a specific membrane binding motif.
Rabab Mahmoud Ahmed, Amin R. Soliman, Ahmad Yousry, Khaled Marzouk and Farouk Faris
Background: Early intervention for septic shock is crucial to reduce mortality and improve outcome. There is still a great debate over the exact time of Therapeutic plasma exchange (TPE) administration in septic shock patients. This study aims to investigate the effect of early initiation (within 4 hours) of TPE in severe septic shock on hemodynamics & outcome.
Methods: We conducted a prospective, before-after case series study on 16 septic shock patients requiring high doses of vasopressors admitted in two ICUs from Cairo, Egypt. All of our patients received TPE within 4 hours of ICU admission. The fresh frozen plasma exchange volume = 1.5 x plasma volume.
Results: In the 16 patients included in the study, mean arterial pressure was significantly improved after the initial TPE (p>0.002) and Norepinephrine dose which significantly reduced post TPE (p<0.001).In addition, Norepinephrine dose to mean arterial pressure significantly improved (p<0.001). There was reduction of a net 6 hours fluid balances following the first TPE were observed in all the patients (p>0.03) by a mean of 757 ml. Systemic vascular resistance index was markedly improved post-TPE along with statistically improved cardiac index (p<0.01). Stroke volume variance was also significantly decreased after the TPE sessions (p<0.01). C-reactive protein significantly improved after TPE (P<0.01).
Conclusion: Early initiation of TPE in severe septic shock patients might improve hemodynamic measures.
Ziga Snoj, Andrew B. Gill, Leonardo Rundo, Nikita Sushentsev and Tristan Barrett
The accuracy of any radiation therapy delivery is limited by target organ translocation and distortion. Bladder filling is one of the recognised factors affecting prostate translocation and distortion. The purpose of our study was to evaluate the effect of bladder volume on prostate translocation and distortion by using detailed three-dimensional prostate delineation on MRI.
Patients and methods
Fifteen healthy male volunteers were recruited in this prospective, institutional review board-approved study. Each volunteer underwent 4 different drinking preparations prior to imaging, with MR images acquired pre- and post-void. MR images were co-registered by using bony landmarks and three-dimensional contouring was performed in order to assess the degree of prostate translocation and distortion. According to changes in bladder or rectum distention, subdivisions were made into bladder and rectal groups. Studies with concomitant change in both bladder and rectal volume were excluded.
Forty studies were included in the bladder volume study group and 8 in the rectal volume study group. The differences in rectal volumes yielded higher levels of translocation (p < 0.01) and distortion (p = 0.02) than differences in bladder volume. Moderate correlation of prostate translocation with bladder filling was shown (r = 0.64, p < 0.01). There was no important prostate translocation when bladder volume change was < 2-fold (p < 0.01). Moderate correlation of prostate distortion with bladder filling was shown (r = 0.61, p < 0.01).
Bladder volume has a minimal effect on prostate translocation and effect on prostate distortion is negligible. Prostate translocation may be minimalised if there is < 2-fold increase in the bladder volume.
Oryzaephilus surinamensis is one of the stored product insect that commonly found in Malaysia. The biological study through host range or food preferences of O. surinamensis is important for the development of sustainable management practice to control its infestation. The objective of this study was to identify the food preference of O. surinamensis to different plant products in relation to food type and moisture content. Twenty adult of O. surinamensis were exposed to three different group of food; dried fruits (date, raisin, apricot, fig), grain/cereals (rice, barley, oat grout, dried maize), and nuts (almond, ground nut, walnut, cashew nut) for 240h in laboratory Kulliyyah of Science, IIUM Kuantan. Moisture content in each food was also measured. It was found out that the most preferred food by O. surinamensis is oat groat of cereal grain group with medium level of moisture content. Further analysis on food moisture suggested that under current experimental conditions (temperature of 27℃ and 64% relative humidity within 240h of exposure), food moisture content does not affect pest infestation and distribution.
Objective: The objective of the study was to determine the differences in selected clinical variables and self-image in people with alcohol dependence differing in severity of physical, emotional and sexual abuse experienced before age 18.
Method: The study included 90 people with alcohol dependence. The following research tools were used: Early Trauma Inventory (ETI), Adjective Check List (ACL), MAST, SAAD, and a questionnaire designed by the authors. In order to identify groups with varying indices of physical, emotional and sexual childhood abuse, a cluster analysis method was used.
Results: Two groups of subjects with alcohol dependence were identified: Group 1 with high indices of physical, emotional and sexual childhood abuse and Group 2 with low indices. In terms of self-image the subjects in Group 1 compared to subjects in Group 2 were characterized by a lower self-esteem, self-acceptance, resistance to stress, less intense needs for achievement, endurance, order, nurturing others, interaction with opposite-sex partners, subordinations but more intense need for change. The age of alcohol use initiation and the onset of regular alcohol drinking was statistically significantly lower in Group 1. The severity of alcohol dependence was significantly lower in Group 2. The subjects in Group 1 significantly more frequently confirmed the history of a hereditary predisposition to alcohol dependence, suicidal ideation, suicide attempts and self-harm.
Discussion: The obtained results closely correspond to the data available in the literature.
Conclusions: An assessment of exposure to various forms of childhood abuse appears to be an indispensable element of collecting medical history of people with alcohol dependence.