N-acetylglucosamine-phosphatidylinositol de-N-acetylase as a novel target for probing potential inhibitor against Leishmania donovani.

Leishmania donavani is the causative agent of leishmaniasis, responsible for social and economic disruption, especially in developing countries. Lack of effective drugs with few side effects have necessitated the discovery of newer therapeutic solutions for leishmaniasis. Glycophosphatidylinositol (GPI) synthesis plays a vital role in protozoan cell membranes structural formation and antigenic modification. Hence, any disruption in its biosynthesis can prove fatal to the parasitic protozoans. N-acetylglucosamine-phosphatidylinositol de-N-acetylase (NAGP-deacetylase) is an enzyme from the GPI biosynthetic pathway that catalyzes the deacetylation of N-acetylglucosaminylphosphatidylinositol to glucosaminylphosphatidylinositol, a step essential for the proper functioning of the enzyme. In the quest for novel scaffolds as anti-leishmaniasis agents, we have executed in silico virtual screening, density function theory, molecular dynamics and MM-GBSA based energy calculations with a natural product library and a diverse library set from Chembridge database. Two compounds, 14671 and 4610, were identified at the enzyme's active site and interacted with catalytic residues, Asp43, Asp44, His41, His147, His 150, Arg80 and Arg231. Both molecules exhibited stable conformation in their protein-ligand complexes with binding free energies for compound-14671 and compound-4610 of -54 ± 4 and -50 ± 4 kcal/mol, respectively. These scaffolds can be incorporated in future synthetic determinations, focusing on developing druggable inhibitor support, increasing potency, and introducing species selectivity.Communicated by Ramaswamy H. Sarma.

Genome-wide identification of carbapenem-resistant Gram-negative bacterial (CR-GNB) isolates retrieved from hospitalized patients in Bihar, India.

Carbapenemase-producing clinical isolates are becoming more common over the world, posing a severe public health danger, particularly in developing nations like India. Carbapenem-resistant Gram-negative bacterial (CR-GNB) infection has become a fast-expanding global threat with limited antibiotic choice and significant mortality. This study aimed to highlight the carbapenem-resistance among clinical isolates of hospital admitted patients in Bihar, India. A cross-sectional study was conducted with 101 clinical isolates of Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. All GNB isolates were tested for their antimicrobial susceptibility using Kirby-Bauer disc diffusion method. Double disc synergy test / modified Hodge test (DDST/MHT) were used to detect carbapenemase production by these isolates. Subsequently, these isolates were evaluated for carbapenem-resistance genes using whole-genome sequencing method. The overall percentage of carbapenem-resistance among GNB was (17/101) 16.8%. The genomic analysis of antimicrobial-resistance (AMR) demonstrates a significantly high prevalence of blaCTX-M followed by blaSHV, blaTEM, blaOXA, and blaNDM ß-lactam or carbapenem resistance genes among clinical isolates of GNB. Co-occurrence of blaNDM with other beta-lactamase-encoding genes was found in 70.6% of carbapenemase-producing isolates. Our study highlights the mechanism of carbapenem-resistance to curb the overwhelming threat posed by the emergence of drug-resistance in India.

Identification and structural studies of natural inhibitors against SARS-CoV-2 viral RNA methyltransferase (NSP16).

Pathogenic RNA viruses are emerging as one of the major threats and posing challenges to human community. RNA viruses have an exceptionally shorter generation time and easy to adapt in host cells. The recent emergence of SARS-CoV-2, a long RNA virus, has shown us how difficult it is to overcome this kind of pandemic without understanding the viral infection and replication mechanisms. It is essential to comprehend replications of the viral genome, including RNA polymerization and the final capping process. The mRNAs of SARS-CoV-2 coronaviruses are protected at their 5'-ends by cap structure. The cap-like system plays a significant role in viral translational process, viral RNA stability, and scatting in detecting innate immune recognition in host cells. Two coronavirus enzymes, Nsp14 and Nsp16, critically help in the formation of capping and are considered as potential drug targets for antiviral therapy. Natural and herbal medicines have a past record of treating various acute respiratory diseases. In this work, we have exploited 56000 natural compounds to screen potential inhibitors against NSP16. In silico virtual screening, docking and Molecular Dynamics (MD) simulation studies were performed to understand how these potential inhibitors are bound to NSP16. We observed that the most highly screened compound binds to protein molecules with a high dock score, primarily through hydrophobic interactions and hydrogen bonding, as previously reported for NSP16. Compound-13 (2-hydroxy-N-({1-[2-hydroxy-1-(hydroxymethyl)ethyl]piperidin-3-yl}methyl)-5-methylbenzamide) and compound-51 (N-(2-isobutoxybenzyl)-N,2-dimethyl-2,8-diazaspiro[4.5]decane-3-carboxamide) occupied in active site along with good pharmokinetices properties. In conclusion, the selected compounds could be used as a novel therapeutic against SARS-CoV-2.Communicated by Ramaswamy H. Sarma.

Comparison of ocular pharmacokinetics of etoposide and its nanoemulsion after subtenon administration in rabbits.

Background Subtenon anticancer drugs are given as an adjunct to systemic chemotherapy for conditions like retinoblatoma. This study evaluated the ocular kinetics of nano-emulsion formulation of etoposide (NanoEt) and compared it with an equal dose of commercially available alcohol-based etoposide formulation in healthy rabbits. Methods A nanoemulsion formulation of NanoEt was developed and then evaluated for its ocular kinetics by subtenon administration in healthy rabbits. After the sterile subtenon administration of the drug, the eyes were enucleated after CO2 euthanasia at time intervals of 2 h, 6 h, 12 h, and 24 h, and ocular tissues, blood, and plasma were separated. The concentration of etoposide in the ocular tissues and blood was quantified using liquid chromatography tandem mass spectrometry (LC MS/MS). Results This study found that subtenon injection of NanoEt showed 24 times higher concentration in rabbit retina compared to an equal dose of conventional marketed formulation. Based on the ocular tissue bioavailability calculations (AUC0-24), the present study revealed that the formulation enhanced 90% ocular bioavailability of etoposide, when it was injected in the form of nano-emulsion in most of the tissues. Conclusions NanoEt has better bioavailability compared to the commercial alcohol-based formulation for subtenon injection. Low systemic exposure showed further advantage for its projected use in retinoblastoma (Rb) as an adjunct therapy. Further studies in Rb animal models are required to evaluate its safety and efficacy, for its clinical utility.

Influence of MDR1 and CYP3A5 genetic polymorphisms on trough levels and therapeutic response of imatinib in newly diagnosed patients with chronic myeloid leukemia.

Polymorphisms in genes coding for imatinib transporters and metabolizing enzymes may affect imatinib pharmacokinetics and clinical response. Aim of this study was to assess the influence of polymorphisms in MDR1 and CYP3A5 genes on imatinib trough levels, cytogenetic and molecular response in patients with CML. Newly diagnosed patients with chronic-phase CML started on imatinib therapy were enrolled and followed up prospectively for 24 months. The following single nucleotide polymorphisms were genotyped; C1236T, C3435T, G2677T/A in MDR1 gene and A6986G in CYP3A5 gene. Genotyping was done using PCR-RFLP method and validated by direct gene sequencing. Trough levels of imatinib were measured using LC-MS/MS. Cytogenetic response was assessed by conventional bone-marrow cytogenetics. Molecular response was assessed by qRTPCR using international scale. A total of 173 patients were included, out of which 71 patients were imatinib responders, while 102 were non-responders. Marked inter-individual variability in trough levels of imatinib was seen. Patients with GG genotype for CYP3A5-A6986G (P=0.016) and TT genotype for MDR1-C3435T (P=0.013) polymorphisms had significantly higher trough levels of imatinib. Patients with AA genotype for CYP3A5-A6986G [RR=1.448, 95% CI (1.126, 1.860), P=0.029] and CC genotype for MDR1-C1236T [RR=1.397, 95% CI (1.066, 1.831), P=0.06] &MDR1-C3435T [RR=1.508, 95% CI (1.186, 1.917), P=0.018] polymorphisms were at high risk for failure of imatinib therapy. Patients with CGC haplotype for MDR1 polymorphisms had significantly lower imatinib trough levels and were at a higher risk of imatinib failure [RR=1.547, 95% CI (1.324, 1.808), P<0.001]. GG vs. non-GG genotype for CYP3A5-A6986G [adjusted OR: 0.246; 95% CI (0.116, 0.519); P<0.001] and TT vs. non-TT genotype for MDR1-C1236T [adjusted OR: 0.270; 95% CI (0.110, 0.659); P=0.004] &MDR1-C3435T [adjusted OR: 0.289; 95% CI (0.135, 0.615); P=0.001] polymorphisms were independent factors predicting imatinib response in multivariate analysis. To conclude, MDR1 and CYP3A5 genetic polymorphisms significantly influence plasma trough levels and therapeutic response of imatinib in patients with CML. Genotyping of these polymorphisms could be of value to individualize the therapy and optimize the clinical outcomes.

Fabrication and Validation of Gyro-Dot-Optomotor Response Device using Gold Fish to Study Drugs Affecting Visual Perception.

An appropriate model to predict the effect of xenobiotics on the vision perception in neuropsychoharmacological studies is of great importance in drug development and toxicity studies. The present study valuated the effect of CNS stimulant, depressant and therapeutic agents known to have ocular toxicity on ptomotor response (OMR) using goldfish in a newly developed device. A digital light processing aided gyrating poly-chromatic dotted pattern-OMR (Gyro-dot-OMR) analyzer was developed and standardized for this study in our laboratory. Goldfishes were exposed to varying concentrations of caffeine and pentobarbitone sodium to evaluate the effect of CNS stimulation and depression on OMR in white light. Ethambutol induced ocular toxicity was evaluated by intravitreal injection into both eyes of goldfishes. They were subjected for polychromatic Gyro-dot-OMR in both clock and anticlockwise directions. At the low concentration (5, 10 and 20 ng/mL) caffeine exposed animals showed significant (p<0.05) stimulant effect and the EC(50) of caffeine in goldfish was found to be 4.806 ng/mL. In contrast, pentbbarbitone sodium treated fishes showed significant (p<0.05) depressant effect with increasing the concentration. Ethambutol toxicity was reflected by the color iscrimination in the Gyro-dot-OMR pattern. For the first time, this model proved the possibility of running Irwin profile test on goldfish using Gyro-dot-OMR. This model successfully predicted ethambutol induced toxicity with poor discrimination of red-green color. This model can be used for predicting toxicity of drugs affecting vision perception.

Evaluation of the Protective Effect of NMDA/Non-NMDA Receptor Antagonists Against Ethambutol Induced Retinal Toxicity Using ERG in Wistar Rats.

To study the protective effect of NMDA and non-NMDA receptor antagonists against ethambutol (EMB) induced retinal toxicity in Wistar rats using flash electroretinogram (ERG). Rats were randomized into four groups: Group-1 received vehicle. Group-2 received oral EMB (200 mg/kg/day). Group-3 and 4 were fed with oral EMB along with memantine (MEM) (1 mg/kg, ip) and trimetazidine (TMZ) (3mg/kg, ip) respectively. All treatments were continued up to 28 days. ERG was recorded at 0 and 21st day using green and white lights. Ethambutol and 2, 2' ethylene diimino dibutyric acid (EDBA) levels were quantified in rat body fluids and tissues using LC-MS/MS. A higher rate of rat mortality was observed between 21st and 28th day, 21st day considered for ERG recording among groups. Ethambutol did not cause any significant change in 'a'-wave amplitude of rat ERG but caused a predictable decrease in 'b'-wave amplitude of the rat ERG on the 21st day. Memantine treatment showed a significant (P=0.029) protection against the fall of 'b'-wave amplitude on 21st day. Interestingly, we found that plasma levels of EMB in memantine treated rats were significantly reduced when compared to the positive control group. Memantine reversed the effects of EMB on 'b'-wave of rat ERG suggests its protective role. We suggest MEM may be considered as a possible preventive treatment modality for EMB induced vision toxicity warranting further clinical investigations.

Screening of antiangiogenic potential of twenty two marine invertebrate extracts of phylum Mollusca from South East Coast of India.

OBJECTIVE: To evaluate the antiangiogenic potential of twenty two marine invertebrate species of Phylum Mollusca from south east coast of India. METHODS: Live specimens of molluscan species were collected and their methanolic extracts were evaluated for preliminary antiangiogenic activity using the in ovo chick chorio-allantoic membrane assay. The extracts were further evaluated for in vivo antiangiogenic activity using chemical cautery induced corneal neovascularization assay in rats and oxygen induced retinopathy assay in rat pups. RESULTS: In the chick chorio-allantoic membrane assay, four methanolic extracts of marine molluscan species viz. Meretrix meretrix, Meretrix casta, Telescopium telescopium and Bursa crumena methanolic extracts exhibited noticeable antiangiogenic activity at the tested concentration of 200 µg whereby they significantly inhibited the VEGF induced proliferation of new blood vessels. Among these four extracts, the methanolic extract of Meretrix casta exhibited relatively higher degree of antiangiogenic activity with an inhibitiory percentage (64.63%) of the VEGF induced neovascularization followed by the methanolic extracts of Telescopium telescopium (62.02%), Bursa crumena (60.48%) and Meretrix meretrix (47.01%). These four methanolic extracts were further evaluated for in vivo antiangiogenic activity whereby the methanolic extract of Telescopium telescopium exhibited most noticeable inhibition (42.58%) of the corneal neovascularization in rats in comparison to the sham treated group, and also exhibited most noticeable inhibition (31.31%) of the oxygen induced retinal neovascularization in rat pups in comparison to the hyperoxia group that was observed for considerable retinal neovascularization. CONCLUSIONS: The significant antiangiogenic activity evinced by the extract of Telescopium telescopium merits further investigation for ocular neovascular diseases.

Role of organic cation transporters in the ocular disposition of its intravenously injected substrate in rabbits: implications for ocular drug therapy.

The present study was conducted to test the hypothesis; OCT may be active from blood-to-vitreous for the uptake of its substrates. Ocular uptake of Tetraethylammonium (TEA) across blood ocular barriers and the tissue distribution was evaluated in vivo in New Zealand albino rabbits after intravenous administration. Quinidine (blocker) pretreatment resulted in a significant (p < 0.05) reduction in the Area Under the Curve (AUC) of TEA in vitreous (4.2 fold) and aqueous humor (1.8 fold) as compared to the control group which supports the role of OCT in uptake transport of its substrate across Blood ocular barrier. The blockade of OCT also affected the elimination of its substrate resulting in increased plasma levels. In most of the tissues, OCT are functionally present from apical to basolateral. The gene expression studies also showed the presence of OCT1, OCTN1 and OCTN2 in various ocular tissues studied. The present findings suggest that OCT are functionally active in blood ocular barriers and involved in the transport of its substrate from blood-to-vitreous humor.

Evaluation of pharmacological activities and assessment of intraocular penetration of an ayurvedic polyherbal eye drop (Itone™) in experimental models.

BACKGROUND: The polyherbal eye drop (Itone™) is a mixture of aqueous distillates of nineteen traditionally used ingredients that sum up to impart potency to the formulation and make it a useful adjunct in various ocular pathologies. However, as there have been no controlled experimental studies accounting to the above claim, therefore, the present study was designed to evaluate the polyherbal formulation (PHF) for antiangiogenic, anti-inflammatory, anticataract, antioxidant and cytotoxicity in addition to the evaluation of intraocular penetration of PHF in rabbit eyes using LC-MS/MS. MATERIALS AND METHODS: Antiangiogenic activity of the PHF was evaluated using in ovo chick chorio-allantoic membrane (CAM) assay and in vivo cautery induced corneal neovascularization assay in rats. Anticataract potential was evaluated using steroid induced cataract in developing chick embryos, sodium selenite induced cataract in rat pups and galactose induced cataract in rats. The antioxidant activity was evaluated using di-phenyl picryl hydrazyl (DPPH) radical scavenging assay. Anti-inflammatory activity was evaluated in vitro using inhibition of LTB4 formation in human WBCs and in vivo using carrageenan induced paw edema assay in rats. The cytotoxicity was evaluated against HeLa cancer cell lines using (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Furthermore evaluation of the intraocular penetration of the PHF was carried out in rabbit eyes via aqueous humor paracentesis and further analysis using LC-MS/MS. RESULTS: PHF significantly inhibited VEGF induced proliferation of new blood vessels in CAM assay and inhibited the cautery induced corneal neovascularization in rats. Additionally, PHF showed noticeable delay in the progression of cataract in the selenite and galactose induced cataract models whereby the PHF treated lenses were graded for stages II and III respectively. However, the PHF did not show any anticataract activity in the hydrocortisone induced cataract model. Moreover, PHF exhibited anti-inflammatory activity whereby it showed 39.34% inhibition of LTB4 formation and significantly inhibited carrageenan induced paw edema in rats. Eight compounds of PHF viz. camphor, casticin, curcumin-II, quercetin, rosmarinic acid, γ-terpinene, ß-pinene and dipentene exhibited transcorneal penetration in rabbit eyes. CONCLUSION: The significant antiangiogenic and anti-inflammatory activities evinced by the PHF merits further investigation for ocular neovascular and inflammatory diseases in humans.

Evaluation of the functional importance of organic cation transporters on the ocular disposition of its intravitreally injected substrate in rabbits.

PURPOSE: To evaluate the functional role of organic cation transporters (OCT) and ocular tissue distribution of intravitreally injected OCT substrate tetraethylammonium (TEA) in presence of OCT blocker (quinidine). METHODS: New Zealand albino rabbits of either sex were used. Intravitreal quinidine pretreatment was made 30 min before the administration of TEA. Modulation of vitreous and ocular tissue kinetics of OCT substrate was evaluated with or without blocker pretreatment. Gamma scintigraphy was also performed to visualize the vitreous residence of (99m)Tc-labelled TEA in the presence and absence of blocker. RESULTS: Intravitreally injected quinidine did not significantly alter the ocular disposition of TEA. TEA showed less significant posterior elimination kinetics and slow anterior elimination which resulted in longer residence time of TEA in eye after intravitreal administration. CONCLUSIONS: Intravitreally injected OCT substrates may follow an anterior elimination pathway and prolonged residence time in vitreous humor. The present study shows that OCT may not be active from vitreous-to-blood route in the blood-retinal barrier.

Development of novel in silico model to predict corneal permeability for congeneric drugs: a QSPR approach.

This study was undertaken to determine in vivo permeability coefficients for fluoroquinolones and to assess its correlation with the permeability derived using reported models in the literature. Further, the aim was to develop novel QSPR model to predict corneal permeability for fluoroquinolones and test its suitability on other training sets. The in vivo permeability coefficient was determined using cassette dosing (N-in-One) approach for nine fluoroquinolones (norfloxacin, ciprofloxacin, lomefloxacin, ofloxacin, levofloxacin, sparfloxacin, pefloxacin, gatifloxacin, and moxifloxacin) in rabbits. The correlation between corneal permeability derived using in vivo studies with that derived from reported models was determined. Novel QSPR-based model was developed using in vivo corneal permeability along with other molecular descriptors. The suitability of developed model was tested on ß-blockers (n = 15). The model showed better prediction of corneal permeability for fluoroquinolones (r(2) > 0.9) as well as ß-blockers (r(2) > 0.6). The newly developed QSPR model based upon in vivo generated data was found suitable to predict corneal permeability for fluoroquinolones as well as other sets of compounds.

Development and validation of a highly sensitive LC-MS/MS method for organic cation transporter (OCT) substrate tetraethylammonium (TEA) in rabbits.

Tetraethylammonium is widely used as a probe in organic cation transporters studies. A simple, highly sensitive, and specific method using direct protein precipitation was developed using Hydrophilic Interaction Liquid Chromatography coupled with positive electrospray ionization tandem mass spectrometry for the determination of tetraethylammonium (TEA) in rabbit plasma. Isocratic separation was achieved using a ZIC-HILIC column with acetonitrile and 5mM ammonium acetate in the ratio of 8:2 containing 0.1% formic acid. Acquisition was performed in multiple reaction monitoring mode with the transitions: m/z 130→100 and 130→86 for TEA and m/z 276.1→142.2 for internal standard (homatropine). This method was validated to determine selectivity, linearity, sensitivity, precision, accuracy, recovery and stability. A good linearity was found within a range of 1.53-784.6 ng/mL. The above method has been demonstrated for its capability to estimate the plasma levels of TEA after its topical instillation in rabbit eyes. This method provides an accurate, precise and sensitive tool for determining TEA levels for transporter studies.

Evidencing the modulation of P-glycoprotein at blood-ocular barriers using gamma scintigraphy.

PURPOSE: To evaluate the effect of P-glycoprotein modulation at blood-ocular barriers using gamma scintigraphy. METHODS: Ofloxacin, a fluoroquinolone, was selected as a substrate to study the drug efflux transporter (P-glycoprotein) modulation after labeling with Technetium ((99m)Tc) in rabbits. New Zealand albino rabbits were randomized into two groups of 4 each. Group I received labeled ofloxacin intravitreally (100 micro Ci) and Group II animals were given verapamil intravitreally 15 min before the labeled ofloxacin. Static imaging was done at predetermined time, and dynamic images were also taken after 30 min of intravitreal injection. RESULTS: The radio-chemical purity of labeled ofloxacin was found to be 90-95% with the labeling efficiency of 90%. The static anterior planar images of verapamil pre-treated group showed marginal increase in the uptake of labeled ofloxacin, and dynamic images showed less systemic pool as compared to its control. CONCLUSION: This study further confirms the findings of our laboratory regarding the involvement of P-glycoprotein in the intraocular disposition of susceptible drugs.

Evaluation of the modulation of P-glycoprotein (P-gp) on the intraocular disposition of its substrate in rabbits.

PURPOSE: To evaluate the functional role of P-gp and ocular tissue distribution of intravitreally injected Rhodamine-123 (Rho-123) in the presence of P-gp specific blocker (GF 120918) in normal as well as rifampicin-fed rabbits using microdialysis and direct sampling technique. METHODS: Intravitreal pharmacokinetics of Rho-123 were conducted in male New Zealand albino rabbits. Direct sampling and microdialysis were employed to study the disposition of Rho-123 in normal as well as rifampicin-fed conditions. Control animals received Rho-123 at the concentration of 350 ng in PBS (0.05 ml) intravitreally, and the blocker-treated group received GF 120918 intravenously at the dose of 3.5 mg/kg 30 min prior to intravitreal injection of Rho-123. In case of direct sampling, four eyes were enucleated at different time points, and ocular tissues and humors were stored at -86 degrees C until analysis by HPLC with fluorescence detection. RESULTS: In direct sampling, the blocker group showed significant increase (2.6 fold) in the mean vitreous concentration of Rho-123. Other tissues like ret-choroid, iris, and cornea also showed significant increase in their mean concentration. Microdialysis did not significantly predict the changes observed with direct sampling. Rifampicin-fed rabbits showed a vitreous pharmacokinetic profile comparable with non-fed (control) animals, and the pharmacokinetic parameters were unaffected by the blocker pretreatment. CONCLUSION: Intravenously injected blocker significantly altered the ocular disposition of intravitreally injected P-gp substrate. Rifampicin pretreatment did not upregulate P-gp transporters of the retina to the extent to affect the intravitreal kinetics of Rho-123 significantly.

Mycoplasma pneumoniae and central nervous system complications: a review.

Mycoplasma pneumoniae is a common cause of community-acquired pneumonia. Little is known about the extrapulmonary manifestations of this organism. Numerous central nervous system (CNS) manifestations have been described with M. pneumoniae. CNS involvement is probably the most common site of involvement in addition to the respiratory system. Up to 7% of patients hospitalized with M. pneumoniae may have CNS symptoms. Common CNS presentations include encephalitis, aseptic meningitis, polyradiculitis, cerebellar ataxia, and myelitis. The mechanism behind these CNS manifestations remains unclear. Direct invasion, neurotoxin production, or an immune-mediated mechanism has been proposed. Newer diagnostic techniques for the direct detection of the antigen and the microorganism are proving useful for the detection of extrapulmonary disease. This review comprehensively reviews the CNS complications that have been reported with M. pneumoniae.

Centbucridine, a newer topical anaesthetic compared with lignocaine: a randomized double masked single drop instillation clinical trial.

A randomized double-masked single drop instillation clinical trial was conducted on 60 healthy volunteers divided into 3 equal groups to compare the efficacies of centbucridine and lignocaine. One eye of each volunteer was instilled with a single drop of either 0.5% centbucridine hydrochloride, 1% centbucridine hydrochloride or 4% lignocaine hydrochloride, with the other eye as an unanaesthetized control-side effects, if any, were also recorded. The onset of anaesthesia assessed both objectively and subjectively, was quickest with lignocaine 4% (P < 0.001) followed by centbucridine 0.5% and 1%. However, the period of peak activity as well as the total duration of surface anaesthesia, and also the depth of analgesia, were significantly highest with 1% centbucridine, followed by 0.5% centbucridine and 4% lignocaine respectively. Minor side effects like burning sensations were longest with 1% centbucridine--no significant adverse effects, local or systemic, were observed. Prolonged surface anaesthetic and analgesic actions of centbucridine 1% may be advantages for longer duration ophthalmic microsurgeries.

Role of 0.02% polyhexamethylene biguanide and 1% povidone iodine in experimental Aspergillus keratitis.

PURPOSE: To determine the efficacy of 0.02% polyhexamethylene biguanide and 1% povidone iodine in experimental keratitis. METHODS: Aspergillus fumigatus keratitis was induced by corneal intrastromal injection of spores in 24 healthy rabbits that were randomly divided into four groups of six rabbits each. Drugs used were 5% natamycin (standard antifungal), 0.02% polyhexamethylene biguanide (PHMB) (test drug), 1% povidone iodine (test drug), and 0.5% hydroxypropylmethyl cellulose (HPMC) (control). RESULTS: The average healing times of the ulcer were 21.5 +/- 3.08 days with 5% natamycin, 27.8 +/- 2.28 days with 0.02% PHMB, 36.4 +/- 2.57 days with 1% povidone iodine, and 38.2 +/- 4.74 days with 0.5% HPMC. While no corneal perforations occurred with natamycin treatment, one perforation was noted with PHMB, three perforations were noted with povidone iodine, and five perforations were noted with controls. CONCLUSION: Polyhexamethylene biguanide (0.02%) is a moderately effective drug for experimental Aspergillus keratitis, but 1% povidone iodine is not effective.

Drug utilization study in dermatology in a tertiary hospital in Delhi.

The present study was undertaken to describe patterns of dermatological drug utilization in a tertiary hospital in Delhi by measuring WHO delineated drug use indicators. Six hundred and six prescriptions of dermatology out-patients were analyzed and the data collected were used to evaluate the following drug use indicators: average number of drug per prescription, average consultation time, percentage of drugs prescribed by generic name, percentage of encounters with an antibiotic prescribed, percentage of encounters with an injection prescribed and percentage of drug prescribed from the essential drugs list or formulary. The average number of drugs per prescription +/- SD was found to be 2.6 +/- 1.2, average consultation time +/- SD was 4.4 +/- 2.6 minutes, percentage of drug prescribed by generic name was 6.98, percentage of encounters with an antibiotic and injection prescribed were 46.86 and 6.76 respectively and 23% of the total drugs prescribed were from Delhi State Essential Drugs Formulary.