Drug utilization study in neonatal intensive care unit at tertiary care hospital.

OBJECTIVE: Neonates are more susceptible to drug interactions and adverse effects, and special care should be taken when prescribing medication to them. This study aimed to investigate drug usage in the neonatal intensive care unit of a tertiary care hospital. METHODS: This prospective observational study was conducted on 98 patients at the Apollo tertiary care hospital (Bannerghatta, Bangalore, India) in a period of 6 months. The most common indications for neonatal intensive care unit admission, average number of drugs per patient, the most frequently used medication, distribution of patients based on the birth procedure, and possible drug interactions were collected from patient profiles. RESULTS: Among the patients, 52% were males and 48% were females. Notably, 38% of patients were preterm, 60% were term, and only 2% were post-term. Also, 80.6% were born by cesarean section and 19.4% were born by normal vaginal delivery. The highest mean of drug use was in the patient of 1,000-1,500 g (8.06 per patient). Preterm was the most frequent indication for admission in neonatal intensive care unit, followed by hyperbilirubinemia and then respiratory distress syndrome. The most frequently used medication was vitamin K (99%) and antibiotics followed by dextrose. In different types of antibiotics, amikacin (41%), cefoperazone+sulbactam (35%), cephalosporin (1%), ceftriaxone (0.7%), and amoxicillin (0.3%) were commonly administered. There were some possible interactions, such as aminoglycoside with furosemide and calcium gluconate. CONCLUSION: Premature birth and resulting low birth weight were the main reasons for drug prescription. High administration of antibiotics is probably an area of concern and should be seriously considered.

Drug utilization study in neonatal intensive care unit at tertiary care hospital

SUMMARY OBJECTIVE: Neonates are more susceptible to drug interactions and adverse effects, and special care should be taken when prescribing medication to them. This study aimed to investigate drug usage in the neonatal intensive care unit of a tertiary care hospital. METHODS: This prospective observational study was conducted on 98 patients at the Apollo tertiary care hospital (Bannerghatta, Bangalore, India) in a period of 6 months. The most common indications for neonatal intensive care unit admission, average number of drugs per patient, the most frequently used medication, distribution of patients based on the birth procedure, and possible drug interactions were collected from patient profiles. RESULTS: Among the patients, 52% were males and 48% were females. Notably, 38% of patients were preterm, 60% were term, and only 2% were post-term. Also, 80.6% were born by cesarean section and 19.4% were born by normal vaginal delivery. The highest mean of drug use was in the patient of 1,000-1,500 g (8.06 per patient). Preterm was the most frequent indication for admission in neonatal intensive care unit, followed by hyperbilirubinemia and then respiratory distress syndrome. The most frequently used medication was vitamin K (99%) and antibiotics followed by dextrose. In different types of antibiotics, amikacin (41%), cefoperazone+sulbactam (35%), cephalosporin (1%), ceftriaxone (0.7%), and amoxicillin (0.3%) were commonly administered. There were some possible interactions, such as aminoglycoside with furosemide and calcium gluconate. CONCLUSION: Premature birth and resulting low birth weight were the main reasons for drug prescription. High administration of antibiotics is probably an area of concern and should be seriously considered.

Decades-old renin inhibitors are still struggling to find a niche in antihypertensive therapy. A fleeting look at the old and the promising new molecules.

Hypertension is a diverse illness interlinked with cerebral, cardiovascular (CVS) and renal abnormalities. Presently, the malady is being treated by focusing on Renin- angiotensin system (RAS), voltage-gated calcium channels, peripheral vasodilators, renal and sympathetic nervous systems. Cardiovascular and renal abnormalities are associated with the overactivation of RAS, which can be constrained by angiotensin- converting enzyme inhibitors (ACEIs), angiotensin II (Ang-II) -AT1 receptor blockers (ARBs) and renin inhibitors. The latter is a new player in the old system. The renin catalyzes the conversion of angiotensinogen to Angiotensin I (Ang-I). This can be overcome by inhibiting renin, a preliminary step, eventually hinders the occurrence of the cascade of events in the RAS. Various peptidomimetics, the first-generation renin inhibitors developed six decades ago have limited drug-like properties as they suffered from poor intestinal absorption, high liver first-pass metabolism and low oral bioavailability. The development of chemically diverse molecules from peptides to nonpeptides expanded the horizon to achieving direct renin inhibition. Aliskiren, a blockbuster drug that emerged as a clinical candidate and got approved by the US FDA in 2007 was developed by molecular modeling studies. Aliskiren indicated superior to average efficacy and with minor adverse effects relative to other RAS inhibitors. However, its therapeutic use is limited by poor oral bioavailability of less than 2% that is similar to first-generation peptidic compounds. In this review, we present the development of direct renin inhibitors (DRIs) from peptidic to nonpeptidics that lead to the birth of aliskiren, its place in the treatment of cardiovascular diseases and its limitations.

Metabolism of 14C-naphthalene in marine sediments.

Metabolism of 14C-naphthalene was studied in aerobic and anaerobic marine sediments from the Mumbai coast, India using a continuous flow-through system for 5 weeks. There was no volatilisation of naphthalene from anaerobic sediment. Naphthalene underwent more extensive mineralization in aerobic sediment (31.6% of the applied activity) than in anaerobic sediment (5% of the applied activity). No metabolite of naphthalene was present in sediments at the end of the incubation period.

Uptake of 14C-chlorpyrifos by clams.

The uptake of 14C-chlorpyrifos by clams (Katalysia opima) was studied to determine the bioaccumulation potential over a period of five days. Chlorpyrifos was applied to a model ecosystem in beakers at the rate of 3 mg l(-1) of seawater. Clams showed a maximum uptake of 14C-chlorpyrifos in the first 8 hours of exposure. Subsequently these residues decreased significantly and at the end of 5 days about 1.5% of the applied activity could be recovered from the clam samples. The half-life of chlorpyrifos in this marine water system was about a day. However, after 5 days about 28% of the applied 14C-activity was present in water. This may be significant and could possibly play a role in finding the residue of this insecticide in water bodies. Clams brought about rapid degradation of chlorpyrifos in the first 48 hours. The stabilised residues in water were reflected later in clams.

Degradation of 14C-carbofuran in soil using a continuous flow system.

14C-carbofuran underwent considerable mineralization (approximately 30% of the applied activity) in Vertisol soil under moist and flooded conditions during 60 days incubation. Bound residues were formed under both the conditions, the extent being more in moist soils (approximately 55% of the applied activity) than under flooded conditions (approximately 41% of the applied activity). 3-Keto carbofuran was the only significant metabolite observed under flooded conditions.

Monitoring of organochlorine pesticide residues in the Indian marine environment.

Organochlorine pesticide residues in sediment and fish samples collected from the east and west coasts of India are presented. HCH isomers and DDT and its metabolites are the predominantly identified compounds in most of the samples. Despite the higher quantity of consumption, HCH and DDT levels in fish in India were lower than those in temperate countries suggesting a lower accumulation in tropical fish, which could be due to rapid volatilization and degradation of these insecticides in the tropical environment. The predominance of alpha- and beta-HCH reflect the use of technical grade HCH in India. The high temperature in the tropics also enhances the elimination rate of chemicals in fish, as the biological half-lives of semivolatile compounds such as DDT are short at high temperature.

Bioremediation of DDT in soil by genetically improved strains of soil fungus Fusarium solani.

Bioremediation of DDT in soil by genetically improved recombinants of the soil fungus Fusarium solani was studied. The parent strains were isolated from soil enriched with DDD or DDE (immediate anaerobic and aerobic degradation products of DDT), as further degradation of these products are slow processes compared to the parent compound. These naturally occurring strains isolated from soil, however, are poor degraders of DDT and differed in their capability to degrade its metabolites such as DDD, DDE, DDOH and DBP and other organochlorine pesticides viz. kelthane and lindane. Synergistic effect was shown by some of these strains, when grown together in the medium containing DDD and kelthane under mixed culture condition. No synergism in DDE degradation was observed with the strains isolated from enriched soil. DDD-induced proteins extracted from individual culture filtrate (exo-enzyme) when subjected to SDS-Polyacrylamide Gel Electrophoresis (SDS-PAGE) showed complementary polypeptide bands in these strains i.e., each strain produced distinct DDD degrading polypeptide bands and the recombinant or hybrid strains produced all of the bands of the two parents and degraded DDD better than the parental strains. Recombinant hybrid strains with improved dehalogenase activity were raised by parasexual hybridisation of two such complementary isolates viz. isolate 1(P-1) and 4(P-2) showing highest complementation and are compatible for hyphal fusion inducing heterokaryosis. These strains are genetically characterised as Kel+Ben(R)DBP-Lin- and Kel-Ben(r)DBP+Lin+ respectively. Recombinants with mixed genotype, i.e., Kel+Ben(R)DBP+Lin+ showing superior degradation quality for DDT were selected for bioremediation study. Recombination was confirmed by polypeptide band analysis of DDD induced exo-proteins from culture filtrate using SDS-Polyacrylamide Gel Electrophoresis (PAGE) and RAPD (Random Amplified Polymorphic DNA) of genomic DNA using PCR (Polymerase Chain Reaction) technique. SDS-PAGE showed combination of DDD induced polypeptide bands characteristic of both the parents in the recombinants or the hybrids. PCR study showed the parent specific bands in the recombinant strains confirming gene transformation.

Induction of stable benomyl-tolerant phenotypic mutants of Trichoderma pseudokoningii MTCC 3011, and their evaluation for antagonistic and biocontrol potential.

Trichoderma pseudokoningii MTCC 3011 is a very useful strain for biological control of the plant pathogen Sclerotium rolfsii under post-harvest conditions. In the present investigation, several benomyl-tolerant phenotypic mutants of this strain have been generated using a two step mutagenesis-chemical followed by gamma irradiation. The mutants differed from the wild type strain in antibiotic and disease control potential. Some of the mutants are superior to the wild type in biocontrol potential on S. rolfsii.

Studies on degradation of 14C-DDT in the marine environment.

Degradation of 14C-DDT was studied in a marine ecosystem for 60 days and in marine sediments under moist and flooded conditions using a continuous flow system for a period of 130 days. 14C-DDT residues were recovered in sediments of the marine ecosystem at uniform level of 60-65% of the applied 14C-activity throughout the incubation period. DDD was a major metabolite in sediments while DDMU was a major metabolite in clams. Clams brought about substantial degradation of DDT. However, 14C-residues recovered form clams are not suggestive of significant bioaccumulation. In the continuous flow experiment, under both moist and flooded conditions, DDT underwent degradation and about 22% of the applied 14C-activity was recovered as volatiles under both conditions. In sediments, extractable 14C-residues accounted for about 30 and 19% under moist and flooded conditions, respectively. DDT was the major compound in extractable residues as identified by TLC-autoradiographic procedures. More bound residues were formed under flooded than under moist conditions.

Studies on degradation of 14C-chlorpyrifos in the marine environment.

Degradation of 14C-chlorpyrifos was studied in a marine ecosystem for 60 days and in marine sediment under moist and flooded conditions using a continuous flow system allowing a total 14C-mass balance for a period of 40 days. In the marine ecosystem, 14C-chlorpyrifos underwent rapid degradation and very little (1-2%) 14C-residues of the applied activity were detected after two months in sediments. Clams were major component of the ecosystem and played a significant role in degradation of the insecticide. In the continuous flow system chlorpyrifos did not undergo substantial mineralization. Volatilization accounted for 0.8-1% loss during first ten days of application. The amounts of extractable 14C-activity were higher in flooded sediments than in moist sediment. More bound residues were formed under moist conditions. TCP (3,5,6-trichloro-2-pyridinol) was the major degradation product formed under both moist and flooded conditions, its formation being higher in the latter conditions. These studies underline the role of clams in degradation of chlorpyrifos and lack of microbial degradation. In absence of clams, chlorpyrifos underwent abiotic degradation in marine sediment with formation of bound residues.

Novel polypeptides induced by the insecticide lindane (gamma-hexachlorocyclohexane) are required for its biodegradation by a Sphingomonas paucimobilis strain.

When exposed to the potent insecticide gamma-hexachlorocyclohexane or lindane, a Sphingomonas paucimobilis strain rapidly synthesized 7 novel polypeptides and concomitantly gained the ability to degrade lindane. Synthesis of these proteins was switched-off subsequent to the disappearance of lindane from the medium. Treatments which induced the synthesis of identical proteins also conferred on cells the ability to degrade lindane. In contrast, cells blocked in protein synthesis could not be induced to degrade lindane. The close correspondence observed between expression of lindane-induced proteins and gamma-hexachlorocyclohexane catabolism strongly implicates these novel proteins in lindane biodegradation.

Degradation of pentachlorophenol (PCP) in aerobic and anaerobic soil.

Aerobic and anaerobic degradation of 14C-labeled pentachlorophenol (PCP) was examined in nitrogen aerated, moist Hagerstown silty clay loam with or without cellulose amendments. In anaerobic soil, PCP reduced soil respiration in the presence of cellulose; volatilization losses accounted for only 0.5% of the PCP added to soil; no 14CO2 was detected; and organic solvent extractable radioactivity was the same from all treatments. Gas and thin-layer chromatographic analysis of the soil extracts showed the presence of pentachloroanisole in both aerobic and anaerobic soils. 2,3,5,6- and 2,3,4,5-tetrachlorophenols and 2,3,6-trichlorophenol were also detected as degradation products by gas chromatography after methylation. Further degradation of pentachloroanisole was examined in both aerobic and anaerobic soils.