Assessment of minimum inhibitory concentration to vancomycin, tigecycline, linezolid, daptomycin, ceftaroline and mupirocin against methicillin resistant Staphylococcus aureus clinical isolates by antibiotic gradient strips

Background: Staphylococcus aureus infections are one of the most common and serious hospital-acquired infections seen in developing countries. Methicillin resistant Staphylococcus aureus (MRSA) is an important human pathogen and normally colonized in body parts including skin, nose, perineum and throat. MRSA is resistant not only to all β-lactam groups but also other antibiotics including aminoglycosides, tetracycline and macrolides. In the present study the efficacy of agents used in the management of MRSA infections was determined by antibiotic gradient testing. Methods: A total of 60 clinical isolates of MRSA strains were collected from various diagnostic labs in central Kerala. Clinical isolates were reconfirmed as MRSA by gram staining, yellow-coloured colonies on mannitol salt Agar (MSA). Antibiotic susceptibility testing was done by disc diffusion method as recommended by CLSI guidelines. S. aureus isolates resistant to cefoxitin (30 µg) was identified as MRSA. Antibiotic gradient testing was performed to determine the MIC of vancomycin, tigecycline, linezolid, daptomycin, ceftaroline and mupirocin against MRSA isolates. Results: All the 60 MRSA isolates tested were sensitive to vancomycin, tigecycline, linezolid, daptomycin, ceftaroline and mupirocin (100%) and none of the MRSA isolates show resistance.  Conclusions: Results of present study indicates that these agents may be used alongside vancomycin in management of infection caused by MRSA

An Open Label, Randomized, Parallel Efficacy, Active Controlled Clinical Study to Compare the Efficacy of Nirgundi Patra and Erandamuladi Niruha Basti in Yoga Basti Pattern in Gridhrasi (Sciatica)

It is estimated that Low back pain afflicts nearly two thirds of the Indian population at some point in their life. Erandamuladi Niruha Basti is a widely practiced and proven formulation that is used in Gridhrasi (Sciatica). It contains more than 20 ingredients, which can be a daunting task for an ayurvedic practitioner in a clinic to procure. Hence the literary search was done with a view to find out other effective formulations which were preferably single drug formulations. Nirgundi patra Kashaya was mentioned by acharya Chakrapanidatta in Vatavyadhi Adhikarana of Chakradatta. Nirgundi itself has anti-inflammatory and analgesic properties, so this Kashaya was selected as a Basti to be compared with Erandamuladi Niruha Basti in Yoga Basti pattern. 30 patients were randomized into two groups, Group A and Group B based on a set of inclusion and exclusion criteria. Group A was given Nirgundi Patra Kashaya Niruha and Murchita Tila Taila Anuvasana and Group B patients were given Erandamuladi Niruha and Murchita Tila Taila Anuvasana. Objective and Subjective parameters were evaluated before the start of the treatment and at the end of the treatment. The parameters were evaluated using relevant statistical tests. The result showed that even though all the patients had relief after the treatment, he percentage of relief was more across all parameters in case of Group B. This showed that, Nirgundi patra Kashaya was effective in the treatment of Gridhrasi in Basti formulation, but, Erandamuladi Niruha Basti produced much significant relief

Structural compromise of disallowed conformations in peptide and protein structures

Using a data set of 454 crystal structures of peptides and 80 crystal structures of non-homologous proteins solved at ultra high resolution of 1.2 Å or better we have analyzed the occurrence of disallowed Ramachandran (φ, ψ) angles. Out of 1492 and 13508 non-glycyl residues in peptides and proteins respectively 12 and 76 residues in the two datasets adopt clearly disallowed combinations of Ramachandran angles. These examples include a number of conformational points which are far away from any of the allowed regions in the Ramachandran map. According to the Ramachandran map a given (φ, ψ) combination is considered disallowed when two non-bonded atoms in a system of two-linked peptide units with ideal geometry are prohibitively proximal in space. However, analysis of the disallowed conformations in peptide and protein structures reveals that none of the observations of disallowed conformations in the crystal structures correspond to a short contact between non-bonded atoms. A further analysis of deviations of bond lengths and angles, from the ideal peptide geometry, at the residue positions of disallowed conformations in the crystal structures suggest that individual bond lengths and angles are all within acceptable limits. Thus, it appears that the rare tolerance of disallowed conformations is possible by gentle and acceptable deviations in a number of bond lengths and angles, from ideal geometry, over a series of bonds resulting in a net gross effect of acceptable non-bonded inter-atomic distances

Exploring the binding affinities of p300 enzyme activators CTPB and CTB using docking method

364-369CREB binding protein (CBP) and E1A binding protein p300, also known as p300 are functionally related transcriptional co-activators (CoAs) and histone acetyltransferases (HATs). Some small molecules, which target HATs can activate or inhibit the p300 enzyme potently. Here, we report the binding affinities of two small molecules CTPB [N-(4-chloro- 3-trifluoromethyl-phenyl)-2-ethoxy-6-pentadecyl-benzamide] and CTB [N-(4-chloro-3-trifluoromethyl-phenyl)-2-ethoxy-benzamide] with p300 using docking method to obtain the insight of their interaction with p300. These small molecules bind to the enzyme, subsequently causing a structural change in the enzyme, which is responsible for the HAT activation. CTB exhibits higher binding affinity than CTPB, and their lowest docked energies are -7.72, -1.18 kcal/mol, respectively. In CTPB molecule, phenolic hydroxyl of Tyr1397 interacts with the non-polar atoms C(5E) and C(5F), and forms polar-non polar interactions. Similar interactions have also been observed in CTB. The residues Tyr1446 and Cys1438 interact with the non-pentadecyl atoms. Further, the docking study predicts a N-HO hydrogen bonding interaction between CTB and Leu1398, in which the HO contact distance is 2.06 Å. The long pentadecyl chain of CTPB reduces the formation of hydrogen bond with the p300. The H-bond interaction could be the key factor for the better activation of CTB.</span

Structural compromise of disallowed conformations in Peptide and protein structures

Using a data set of 454 crystal structures of peptides and 80 crystal structures of non-homologous proteins solved at ultra high resolution of 1.2 \AA or better we have analyzed the occurrence of disallowed Ramachandran (\Phi, \Psi) angles. Out of 1492 and 13508 non-glycyl residues in peptides and proteins respectively 12 and 76 residues in the two datasets adopt clearly disallowed combinations of Ramachandran angles. These examples include a number of conformational points which are far away from any of the allowed regions in the Ramachandran map. According to the Ramachandran map a given (\Phi, \Psi) combination is considered disallowed when two non-bonded atoms in a system of two-linked peptide units with ideal geometry are prohibitively proximal in space. However, analysis of the disallowed conformations in peptide and protein structures reveals that none of the observations of disallowed conformations in the crystal structures correspond to a short contact between non-bonded atoms. A further analysis of deviations of bond lengths and angles, from the ideal peptide geometry, at the residue positions of disallowed conformations in the crystal structures suggest that individual bond lengths and angles are all within acceptable limits. Thus, it appears that the rare tolerance of disallowed conformations is possible by gentle and acceptable deviations in a number of bond lengths and angles, from ideal geometry, over a series of bonds resulting in a net gross effect of acceptable non-bonded inter-atomic distances

Fuzzy Based Landsman Converter For Pumping Application

Fuzzy controlled landsman converter employed for pumping application is presented here. Landsman converter(LC) is designed using voltage multiplier cell which makes the converter from reduced switching voltages. The controller is designed with Fuzzy logic to derive constant voltage output irrespective of variation of input of the converter. The input to the converter is fed from solar panel(250W). The DC output voltage of converter is fed to the electrical machine to run for different pumping applications. The design of controller and converter is analyzed using MATLAB