Oral nifedipine and parenteral isoxsuprine in arresting preterm labor: A comparative study.

Objective: To compare the efficacy of oral nifedipine and parenteral isoxsuprine in arresting preterm labor. Considering the paucity of studies comparing these two agents, a comparative analysis is obligatory. Materials and methods: Eighty antenatal women in the gestational age range of 28-37 weeks, with regular uterine contractions, cervical dilatation ≤3 cm, and <50% cervical effacement, admitted with complaints of preterm labor pain were randomized to receive either 40 mg isoxsuprine or 20 mg nifedipine. Efficacy of the drugs was measured in terms of arrest of preterm labor, prolongation of pregnancy, and the days gained by infant before birth. Results: Isoxsuprine showed increased lowering of systolic blood pressure (SBP), diastolic blood pressure (DBP), and slightly higher maternal pulse rate, but higher fetal pulse rate post-administration in comparison to nifedipine (P < 0.05). Isoxsuprine was significantly associated with more side effects. Pregnancy was more prolonged in the nifedipine group (25 days) than in the isoxsuprine group (19 days) (P < 0.05). The birth weight of neonates in group B was more than that of neonates in group A (P < 0.05). At 5 min after birth, none of the neonates in group B had an Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) abnormal score <7, compared to neonates in group A. Majority of neonates in group A showed tachycardia and respiratory distress syndrome (RDS) (17.5% and 12.5%, respectively), compared to group B (12.5% and 7.5%, respectively). The overall success rate was better in group B (86.8%) compared to group A (80%). Conclusion: Nifedipine was slightly more effective in arresting preterm labor with fewer side effects, compared to isoxsuprine.

Understanding the riboflavin biosynthesis pathway for the development of antimicrobial agents.

Life on earth depends on the biosynthesis of riboflavin, which plays a vital role in biological electron transport processes. Higher mammals obtain riboflavin from dietary sources; however, various microorganisms, including Gram-negative pathogenic bacteria and yeast, lack an efficient riboflavin-uptake system and are dependent on endogenous riboflavin biosynthesis. Consequently, the inhibition of enzymes in the riboflavin biosynthesis pathway would allow selective toxicity to a pathogen and not the host. Thus, the riboflavin biosynthesis pathway is an attractive target for designing novel antimicrobial drugs, which are urgently needed to address the issue of multidrug resistance seen in various pathogens. The enzymes involved in riboflavin biosynthesis are lumazine synthase (LS) and riboflavin synthase (RS). Understanding the details of the mechanisms of the enzyme-catalyzed reactions and the structural changes that occur in the enzyme active sites during catalysis can facilitate the design and synthesis of suitable analogs that can specifically inhibit the relevant enzymes and stop the generation of riboflavin in pathogenic bacteria. The present review is the first compilation of the work that has been carried out over the last 25 years focusing on the design of inhibitors of the biosynthesis of riboflavin based on an understanding of the mechanisms of LS and RS. This review aimed to address the fundamental advances in our understanding of riboflavin biosynthesis as applied to the rational design of a novel class of inhibitors. These advances have been aided by X-ray structures of ligand-enzyme complexes, rotational-echo, double-resonance nuclear magnetic resonance spectroscopy, high-throughput screening, virtual screenings, and various mechanistic probes.

Design of heat shock-resistant surfaces to prevent protein aggregation: Enhanced chaperone activity of immobilized α-Crystallin.

α-Crystallin is a multimeric protein belonging to the family of small heat shock proteins, which function as molecular chaperones by resisting heat and oxidative stress induced aggregation of other proteins. We immobilized α-Crystallin on a self-assembled monolayer on glass surface and studied its activity in terms of the prevention of aggregation of aldolase. We discovered that playing with grafted protein density led to interesting variations in the chaperone activity of immobilized α-Crystallin. This result is in accordance with the hypothesis that dynamicity of subunits plays a vital role in the functioning of α-Crystallin and might be able to throw light on the structure-activity relationship. We showed that the chaperone activity of a certain number of immobilized α-Crystallins was superior compared to a solution containing an equivalent number of the protein and 10 times the number of the protein at temperatures >60 °C. The α-Crystallin grafted surfaces retained activity on reuse. This could also lead to the design of potent heat-shock resistant surfaces that can find wide applications in storage and shipping of protein based biopharmaceuticals.

Covalent immobilization of active lysozyme on Si/glass surface using alkoxy Fischer carbene complex on SAM.

A cross-metathesis reaction between an alkene terminated self-assembled monolayer (SAM) on glass/Si wafer and an alkene tethered Fischer carbene complex yielded a functionalized surface. Rapid aminolysis of the Fischer carbene moieties permit efficient anchoring of amine containing molecules on such a surface. Attachment of 1-pyrenemethylamine was thus monitored by ATR-IR spectroscopy and fluorescence microscopy. Similarly, BSA and lysozyme were individually grafted to such Fischer carbene modified surfaces using their pendant lysine residues. It has been demonstrated that the anchored lysozyme retains its bactericidal property.

Engineering bioactive surfaces with Fischer carbene complex: protein A on self-assembled monolayer for antibody sensing.

A Fischer carbene complex was grafted onto self-assembled monolayers (SAMs) on gold or glass by a copper-free "click" reaction. Pendant lysine residues of protein A obtained from Staphylococcus aureus rapidly reacted with the electrophilic metal complex on SAM effecting a covalent attachment of protein A with the surface. The protein A coated surface further led to bioaffinity immobilization of rabbit IgG in an oriented manner, a feature that also permits its purification from rabbit serum. Rabbit IgG could be removed from protein A coated surface by pH adjustment. The regenerated protein A surface was reused three times without loss of activity.