Drug use pattern for emergency psychiatric conditions in a tertiary care hospital: A prospective observational study.

PURPOSE: Psychiatric emergencies (PEs) are defined as acute disturbances of thought, mood, behavior, or social relationships requiring immediate interventions. The common emergency psychiatrics are attempted suicide, severe anxiety, schizophrenia, acute psychosis, substance abuse, acute panic attacks, drug toxicities, and extrapyramidal reactions. Emergency physicians in the general hospital may face the challenge of assessing and managing patients in PEs. This study was conducted to evaluate the clinical pattern and drug use pattern for PEs at a tertiary care hospital. MATERIALS AND METHODS: This was a cross-sectional, observational study where patients presenting to emergency medical services of a tertiary care hospital were recruited after approval from Institutional Ethics Committee and written informed consent. Demographic details, diagnosis, medication details, cost of the treatment, and adherence to guidelines in the management of emergency psychiatric conditions were assessed using a validated questionnaire. Descriptive statistics was applied to analyze the data. RESULTS: In 110 patients, a total number of drugs prescribed were 463 (mean: 4.21 drugs/prescription). The most commonly used psychotropic drug in emergency setting was found to be risperidone (19.39%), followed by lorazepam (13.60%) and clonazepam (4.28%). The most common diagnoses were substance abuse (32.72%) and schizophrenia (21.81%). About 74.5% of the physicians prescribed drugs abiding by the standard guidelines. The average total cost incurred by patients was about Rs. 366. CONCLUSION: The most commonly used drugs in emergency treatment found in this study are risperidone, followed by lorazepam and haloperidol.

Practical challenges in conducting respiratory studies.

Respiratory studies are complex on account of specific therapeutic knowledge that is needed and various instruments that are used for the management of this condition. Monitoring a respiratory study requires knowledge of the specific disease and associated guidelines. The intent of this article is to help clinical research professionals understand the technicalities, challenges, and the nuances of performing respiratory studies.

Genotoxicity of different nanocarriers: possible modifications for the delivery of nucleic acids.

The prevention of cyto- and genotoxicity of nanocarriers is an important task in nanomedicine. In the present investigation, we, at the first time using similar experimental conditions, compared genotoxicity of nanocarriers with different composition, architecture, size, molecular weight and charge. Poly(ethylene glycol) polymers, neutral and cationic liposomes, micelles, poly(amindo amine) and poly(propyleneimine) dendrimers, quantum dots, mesoporous silica, and supermagnetic iron oxide (SPIO) nanoparticles were studied. All nanoparticles were used in non-cytotoxic concentrations. However, even in these concentrations, positively charged cationic liposomes, dendrimers, and SPIO nanoparticles induced genotoxicity leading to the significant formation of micronuclei in cells. Negatively charged and neutral nanocarriers were not genotoxic. A strong positive correlation was found between the number of formed micronuclei and the positive charge of nanocarriers. We proposed modifications of both types of dendrimers and SPIO nanoparticles that substantially decreased their genotoxicity and allowed for an efficient intracellular delivery of nucleic acids.

Multifunctional triblock Nanocarrier (PAMAM-PEG-PLL) for the efficient intracellular siRNA delivery and gene silencing.

A novel triblock poly(amido amine)-poly(ethylene glycol)-poly-l-lysine (PAMAM-PEG-PLL) nanocarrier was designed, synthesized, and evaluated for the delivery of siRNA. The design of the nanocarrier is unique and provides a solution to most of the common problems associated with the delivery and therapeutic applications of siRNA. Every component in the triblock nanocarrier plays a significant role and performs multiple functions: (1) tertiary amine groups in the PAMAM dendrimer work as a proton sponge and play a vital role in the endosomal escape and cytoplasmic delivery of siRNA; (2) PEG, a linker connecting PLL and PAMAM dendrimers renders nuclease stability and protects siRNA in human plasma; (3) PLL provides primary amines to form polyplexes with siRNA through electrostatic interaction and also acts as penetration enhancer; and (4) conjugation to PEG and PAMAM reduced toxicity of PLL and the entire triblock nanocarrier PAMAM-PEG-PLL. The data obtained show that the polyplexes resulted from the conjugation of siRNA, and the proposed nanocarriers were effectively taken up by cancer cells and induced the knock down of the target BCL2 gene. In addition, triblock nanocarrier/siRNA polyplexes showed excellent stability in human plasma.

Enantioselective Wacker-type cyclization of 2-alkenyl-1,3-diketones promoted by Pd-SPRIX catalyst.

An enantioselective intramolecular Wacker-type cyclization of 2-alkenyl-1,3-diketones catalyzed by a Pd(II)-SPRIX complex was developed. The reaction proceeded in a 6-endo-trig mode to give the desired chromene derivatives with moderate to good enantioselectivity. Isomerization of C-C double bonds via a pi-allyl Pd intermediate was involved as the key step.

LHRH-targeted nanoparticles for cancer therapeutics.

Synthesis and evaluation of a novel cancer cell's receptor-targeted internally quaternized and surface neutral poly(amidoamine) (PAMAM) generation four dendrimer as well as PAMAM-paclitaxel conjugate are described. The advantages of developed nanocarriers include but are not limited to (1) internal cationic charges for the complexation with small interfering RNA or antisense oligonucleotides and their protection from the degradation in systemic circulation; (2) neutral-modified surface for low cytotoxicity of empty unloaded dendrimers; (3) efficient internalization by cancer cells; and (4) preferential accumulation in the tumor and the prevention of adverse side effects of chemotherapy.

Internally cationic polyamidoamine PAMAM-OH dendrimers for siRNA delivery: effect of the degree of quaternization and cancer targeting.

A novel cancer targeted, internally cationic and surface neutral polyamidoamine (PAMAM) dendrimer, was designed, synthesized, and evaluated as a nanocarrier for the targeted intracellular delivery of siRNA. The dendrimer contained a synthetic analog of Luteinizing hormone-releasing hormone as cancer targeting moiety. The proposed delivery system possesses the following advantages: (1) internal cationic charges for complexation with siRNA and enhanced siRNA protection; (2) low cytotoxicity; (3) lesser degree of quaternization offering free tertiary amines for potential proton sponge effect; and (4) targeting specifically to cancer cells for enhancing siRNA uptake and efficiency and potential limitation of adverse side effects of chemotherapy on healthy organs. Both nontargeted and targeted dendrimer-siRNA complexes formed compact nanometer size spherical particles, exhibited very low cytotoxicity even at the higher concentration, and efficiently penetrated cancer cells in vitro. However, only the targeted dendrimer-siRNA complex was able to substantially decrease the expression of a targeted BCL2 gene.

Surface-modified and internally cationic polyamidoamine dendrimers for efficient siRNA delivery.

A novel internally quaternized and surface-acetylated poly(amidoamine) generation four dendrimer (QPAMAM-NHAc) was synthesized and evaluated for intracellular delivery of siRNA. The proposed dendrimer as a nanocarrier possesses the following advantages: (1) modified neutral surface of the dendrimer for low cytotoxicity and enhanced cellular internalization; (2) existence of cationic charges inside the dendrimer (not on the outer surface) resulting in highly organized compact nanoparticles, which can potentially protect nucleic acids from degradation. The properties of this dendrimer were compared with PAMAM-NH 2 dendrimer, possessing surface charges, and with an internally quaternized charged and hydroxyl-terminated QPAMAM-OH dendrimer. Atomic force microscopy studies revealed that internally charged and surface neutral dendrimers, QPAMAM-OH and QPAMAM-NHAc, formed well-condensed, spherical particles (polyplexes) with siRNA, while PAMAM-NH 2 resulted in the formation of nanofibers. The modification of surface amine groups to amide significantly reduced cytotoxicity of dendrimers with QPAMAM-NHAc dendrimer showing the lowest toxicity. Confocal microscopy demonstrated enhanced cellular uptake and homogeneous intracellular distribution of siRNA delivered by the proposed QPAMAM-NHAc nanocarrier. The results clearly demonstrated distinct advantages of developed QPAMAM-NHAc/siRNA polyplexes over the existing nucleic acid dendrimeric carriers.

Recent developments on chiral ionic liquids: design, synthesis, and applications.

The recent progress in chiral ionic liquids with respect to their syntheses and applications in enantioselective reactions and chiral recognition is described. In addition to the conventional chiral ionic liquids derived from chiral natural products, a library of novel chiral spiro compounds, including spiro bis(pyridinium) and spiro bis(imidazolium) salt, is also described.

Design and synthesis of novel chiral spiro ionic liquids.

[reaction: see text] Novel chiral imidazolium salts have been synthesized as examples of chiral ionic liquids with a spiro skeleton. Effects of N-substituents and counteranions on the melting point of spiro imidazolium salts and their chiral discrimination abilities are described.