Occult left ventricular dysfunction diagnosed by myocardial performance index in patients with limb girdle muscle dystrophy: A case control study

The myocardial performance index (MPI) was assessed in 30 patients with limb girdle muscle dystrophy (LGMD) with a normal left ventricular ejection fraction (greater than 50%), as well as in 30 age- and sex-matched healthy adults with a left ventricular ejection fraction greater than 50%. MPIs derived by pulsed-wave Doppler and tissue Doppler were also compared. The MPI was 0.37±0.09 in the LGMD patients and 0.29±0.09 in the control group (P=0.003). These data show that patients with LGMD have occult cardiac dysfunction as evidenced by a higher MPI than the controls. There was good agreement between the MPIs measured by pulsed-wave Doppler and tissue Doppler methods in these patients.     

A study of communication pathways in methionyl- tRNA synthetase by molecular dynamics simulations and structure network analysis

The enzymes of the family of tRNA synthetases perform their functions with high precision by synchronously recognizing the anticodon region and the aminoacylation region, which are separated by approximately 70 A in space. This precision in function is brought about by establishing good communication paths between the two regions. We have modeled the structure of the complex consisting of Escherichia coli methionyl-tRNA synthetase (MetRS), tRNA, and the activated methionine. Molecular dynamics simulations have been performed on the modeled structure to obtain the equilibrated structure of the complex and the cross-correlations between the residues in MetRS have been evaluated. Furthermore, the network analysis on these simulated structures has been carried out to elucidate the paths of communication between the activation site and the anticodon recognition site. This study has provided the detailed paths of communication, which are consistent with experimental results. Similar studies also have been carried out on the complexes (MetRS + activated methonine) and (MetRS + tRNA) along with ligand-free native enzyme. A comparison of the paths derived from the four simulations clearly has shown that the communication path is strongly correlated and unique to the enzyme complex, which is bound to both the tRNA and the activated methionine. The details of the method of our investigation and the biological implications of the results are presented in this article. The method developed here also could be used to investigate any protein system where the function takes place through long-distance communication.     

Formulation and evaluation of acyclovir microcapsules using bakers yeast

ObjectiveTo formulate and evaluate acyclovir microcapsules using bakers yeast.MethodsAcyclovir, pretreated yeast and deionised water were taken at a volumetric ratio of 1:2:4 respectively. This suspension was agitated in a magnetic stirrer at 25°C, 30°C, 35°C, and 40°C for 4 hours. The suspension was then centrifuged for 10 minutes at 2 000 rpm. The supernatant solution was decanted and the cells were washed 5 times with deionised water. Then the suspended drug entrapped yeast cells were dried in a lyophillizer for 48 hours. The yield was noted.ResultsThe first four formulations were done with 200 mg of the drug, followed by 400 mg for the next four formulations and 800 mg the last four formulations. SEM showed that the surface of the microcapsules was intact, with no burst characteristics. FTIR showed no interaction between acyclovir and the cell wall. DSC showed that the peak was within the standard values. The mean particle size for all the samples was 8 μm in diameter. The dissolution studies were done for all the twelve samples and showed a Fickian model of diffusion.ConclusionsFrom the results it is inferred that the samples prepared at 40°C (FY-4, FY-8, FY-12) show better entrapment and release. So these samples are formulated in the form of a suspension and compared with marketed acyclovir suspension using HPLC technique. The formulated suspensions with FY-4, FY-8 and FY-12 shows drug content in accordance with the standards of the pharmacopoeial limits.     

Talon cusp: an overview with case reports of 3 clinical variants.

Talon cusp is a dental anomaly, which is present as an accessory cusp and is seen both in the deciduous and permanent dentition. It may occur unilaterally or bilaterally and has been reported mostly in maxillary teeth, with a few cases occurring in the mandible. Talon cusp is usually asymptomatic; however, there are many clinical problems associated with it. Talon cusp is clinically manifested in three forms: talon, semi-talon and trace talon. In this article, we present four case reports of talon cusp with an overview of different clinical variants of talon cusp, classification, etiopathogenesis, associated syndromes, clinical problems, and treatment modalities.     

Structural Basis for Complementary and Alternative Medicine: Phytochemical Interaction with Non-Structural Protein 2 Protease—A Reverse Engineering Strategy

Objective: To understand the druggability of the bioactive compounds from traditional herbal formulations "Nilavembu Kudineer" and "Swasthya Raksha Amruta Peya" to heal chikungunya virus (CHIKV) infection. Methods: The efficiency of twenty novel chemical entities from "Nilavembu Kudineer" and "Swasthya Raksha Amruta Peya" to inhibit CHIKV infection in silico were evaluated. Ligands were prepared using Ligprep module of Schr?dinger. Active site was identified using SiteMap program. Grid box was generated using receptor grid generation wizard. Molecular docking was carried out using Grid Based Ligand Docking with Energetics (GLIDE) program. Results: Molecular docking studies showed that among twenty compounds, andrographoside, deoxyandrographoside, neoandrographolide, 14-deoxy-11-oxoandrographolide, butoxone and oleanolic acid showed GLIDE extra precision (XP) score of –9.10, –8.72, –8.25, –7.38, –7.28 and –7.01, respectively which were greater than or comparable with chloroquine (reference compound) XP score (–7.08) and were found to interact with the key residues GLU 1043, LYS 1045, GLY 1176, LEU 1203, HIS 1222 and LYS 1239 which were characteristic functional unit crucial for replication of CHIKV. Conclusion: The binding affinity and the binding mode of chemical entities taken from herbal formulations with non-structural protein 2 protease were understood and our study provided a novel strategy in the development and design of drugs for CHIKV infection.     

Effectiveness of Antimicrobial Peptide Immobilization for Preventing Perioperative Cornea Implant-Associated Bacterial Infection

Titanium (Ti) is a promising candidate biomaterial for an artificial corneal skirt. Antimicrobial peptide (AMP) immobilization may improve the bactericidal effect of the Ti substrate. In this study, we tested the bactericidal efficacy of a functionalized Ti surface in a rabbit keratitis model. A corneal stromal pocket was created by a femtosecond laser. The Ti films were then inserted into the pocket, and Staphylococcus aureus or Pseudomonas aeruginosa was inoculated into the pocket above the implant films. The corneas with Ti-AMP implants were compared with the corneas implanted with unprotected Ti by slit lamp observation and anterior segment optical coherence tomography (AS-OCT). Inflammatory responses were evaluated by bacterium counting, hematoxylin-eosin staining, and immunostaining. There was a lower incidence and a lesser extent of infection on rabbit corneas with Ti-AMP implants than on those with unprotected Ti implants. The bactericidal effect of AMP against S. aureus was comparable to that of postoperative prophylactic antibiotic treatment; hence, SESB2V AMP bound to the Ti implant provided functional activity in vivo, but its efficacy was greater against S. aureus than against P. aeruginosa. This work suggests that SESB2V AMP can be successfully functionalized in a rabbit keratitis model to prevent perioperative corneal infection.     

A DNA primase specified by I-like plasmids.

An enzyme has been isolated from Escherichia coli strains harboring the I-like plasmid R64drd11, which is capable of initiating DNA synthesis on the circular, single-stranded DNA of phages phi X174, fd, and G4. In the conversion of these templates to duplex forms in vitro, the enzyme can substitute for the functions of E. coli dna B-dnaB-dnaC-dnaG proteins, E. coli RNA polymerase, and E. coli dnaG protein, respectively. The enzyme requires all four ribonucleoside triphosphates for optimal activity, although a combination of ATP, CTP, and GTP can almost completely satisfy the rNTP requirement. The enzyme appears to cooperate specifically with DNA polymerases III because single-stranded DNA-dependent synthesis takes place in extracts deficient in DNA polymerases I and II but not in extracts from a dnaZ mutant. Highly purified enzyme preparations consist mostly of two major polypeptides, Mr 140,000 and 180,000, when analyzed by sodium dodecyl sulfate gel electrophoresis. These polypeptides cosediment with the enzyme activity through a glycerol gradient with a sedimentation coefficient of 3.6 S. DNA priming activity in extracts of E. coli strains harboring the mutant plasmids R64drd11 or ColIdrd1, which are derepressed in functions of conjugational DNA transfer, severalfold higher than the activity from strains carrying the corresponding wild-type plasmid. This correlation suggests that the enzyme may play a role in conjugational DNA synthesis.     

Potent antifungal agents and use of nanocarriers to improve delivery to the infected site: A systematic review

There are four major classes of antifungals with the predominant mechanism of action being targeting of cell wall or cell membrane. As in other drugs, low solubility of these compounds has led to low bioavailability in target tissues. Enhanced drug dosages have effects such as toxicity, drug–drug interactions, and increased drug resistance by fungi. This article reviews the current state-of-the-art of antifungals, structure, mechanism of action, other usages, and toxic side effects. The emergence of nanoformulations to transport and uniformly release cargo at the target site is a boon in antifungal treatment. The article details research that lead to the development of nanoformulations of antifungals and potential advantages and avoidance of the lacunae characterizing conventional drugs. A range of nanoformulations based on liposomes, polymers are in various stages of research and their potential advantages have been brought out. It could be observed that under similar dosages, test models, and duration, nanoformulations provided enhanced activity, reduced toxicity, higher uptake and higher immunostimulatory effects. In most instances, the mechanism of antifungal activity of nanoformulations was similar to that of regular antifungal. There are possibilities of coupling multiple antifungals on the same nano-platform. Increased activity coupled with multiple mechanisms of action presents for nanoformulations a tremendous opportunity to overcome antifungal resistance. In the years to come, robust methods for the preparation of nanoformulations taking into account the repeatability and reproducibility in action, furthering the studies on nanoformulation toxicity and studies of human models are required before extensive use of nanoformulations as a prescribed drug.