A Randomized, Double-Blind, Placebo-Controlled Trial Evaluating the Effect of Topical Urea for Secondary Prophylaxis of Hand Foot Skin Reaction in Renal Cell Cancer Patients on Sunitinib Therapy.

INTRODUCTION: Hand foot skin reaction (HFSR) is a common dose-limiting adverse effect of multi kinase inhibitors (MKI) whose mechanism is not fully understood, and the prophylaxis is inadequate. OBJECTIVE: In this pilot study, a double-blind, randomized placebo-controlled trial was conducted to evaluate the effect of topical urea in secondary prevention of sunitinib-induced HFSR in renal cell cancer patients. METHODS: Out of 55 screened patients, 14 were randomized to receive topical urea or placebo for four weeks. The association of HFSR with drug levels of sunitinib and its metabolite (n-desethyl sunitinib), genetic polymorphism of VEGFR2 gene, quality of life (QOL) and biochemical markers was also assessed. RESULTS: The results showed that urea-based cream was not superior to placebo (P = .075). There was no change in the QOL in both the groups. Single nucleotide polymorphism was checked for two nucleotides rs1870377 and rs2305948 located in VEGFR2 gene on chromosome 4. SNP (variant T > A) at rs1870377 was associated with appearance of new HFSR as compared to the wild type, although the association was not statistically significant (OR 0.714). There was no statistically significant difference between mean plasma levels of sunitinib and N-desethyl sunitinib in urea arm as compared to placebo arm as compared to placebo. The best fit population pharmacokinetic model for sunitinib was one compartment model with first order absorption and linear elimination. The median (IQR) of population parameters calculated from the population pharmacokinetics model for Ka, V and Cl was 0.22 (0.21-0.24) h-1, 4.4 (4.09-4.47) L, 0.049 (0.042-0.12) L/hr, respectively. CONCLUSION: The study suggested that the urea-based cream was not superior to placebo in decreasing the appearance of new HFSR in renal cancer patients receiving 4:2 regimen of sunitinib.

Impact of Topical Cyclosporine-A or Topical Chloroquine on Post-LASIK Ocular Surface Stability - A Randomized Controlled Trial.

PURPOSE: To compare effect of topical cyclosporine-A 0.05% (CsA) and chloroquine phosphate 0.03% (CHQ) as an adjunct to standard therapy in maintaining post-laser assisted in situ keratomileusis (LASIK) ocular surface stability. METHODS: Randomized controlled trial on 100 eyes undergoing femtosecond-LASIK randomized into three groups: 33 eyes in Group I (Standard Treatment group), 34 eyes in Group II (CsA group) and 33 eyes in Group III (CHQ group). Standard treatment included topical moxifloxacin, topical prednisolone and carboxymethyl cellulose. Group II received topical CsA 0.05% twice daily for three months and group III received topical CHQ 0.03% twice daily for three months in addition to standard treatment. Primary outcome measure was change in ocular surface disease index (OSDI) at 6 months. Secondary outcome measures were tear break up time (TBUT), Schirmer-I score, tear film osmolarity, tear film MMP-9 and visual acuity. Follow-up was performed at postoperative 1, 3 and 6 months. RESULTS: At 6 months, OSDI score, MMP-9, tear osmolarity, TBUT and Schirmer score were significantly better in both CsA and CHQ groups as compared with controls (p < 0.001). OSDI, Tear osmolarity, TBUT, MMP-9 levels were comparable in CsA and CHQ group (p > 0.05). In CsA group, tear film MMP-9 levels at 6 months were comparable to preoperative baseline (p = 0.09). There was no significant change in the Schirmer score from baseline in the CsA group; in addition, the Schirmer score was significantly better than the CHQ group at 6 months (p = 0.02). Visual acuity was comparable in all three groups. Adverse effects including burning sensation, stinging, pain and redness were reported by ten patients (CsA group- 3, CHQ group-7; p = 0.28). CONCLUSION: Both CsA and CHQ are useful adjuncts to standard therapy in maintaining ocular surface stability after refractive surgery. Cyclosporine A has more potent and sustained anti-inflammatory effect with less ocular irritative effects.

Comparative evaluation of once-daily and twice-daily dosing of topical bromfenac 0.09%: aqueous pharmacokinetics and clinical efficacy study.

PURPOSE: To evaluate aqueous pharmacokinetics of topical bromfenac 0.09% and compare clinical outcomes of once- and twice-daily dosing in phacoemulsification. SETTING: Dr. R.P. Center for Ophthalmic Sciences, AIIMS, New Delhi, India. DESIGN: Prospective interventional study. METHODS: In phase I, single-drop aqueous pharmacokinetics of topical bromfenac was estimated at 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 12 hours, and 24 hours using liquid chromatography mass spectrometry in 60 eyes. In phase II, 45 eyes undergoing phacoemulsification were enrolled: group I (control, n = 15), group II (once-daily bromfenac, n = 14), and group III (twice-daily bromfenac, n = 16). Intraoperative pupillary miosis, postoperative anterior chamber (AC) flare, Summed Ocular Inflammation Score (SOIS), central macular thickness (CMT), and pain scores were assessed. Follow-up was performed at 1 day, 7 days, 28 days, and 90 days postoperatively. RESULTS: Half-life of topical bromfenac was 3.6 hours, mean residence time 5.5 hours, and peak concentration (63.73 ng/mL) achieved after 2 hours. Aqueous concentration was more than inhibitory concentration (IC50) at 12 hours but not at 24 hours. Cumulative effect was observed with repeated dosing with aqueous levels more than IC50 in once-daily and twice-daily groups at 5 days. Significant intraoperative miosis was observed in group I. Pain score, AC flare, and SOIS were significantly more in group I (P < .001) and comparable in groups II and III at all timepoints. CMT was comparable in all groups; no case developed cystoid macular edema. CONCLUSIONS: Single-dose topical bromfenac did not maintain therapeutic aqueous concentration over 24 hours; however, cumulative effect was observed with repeated dosing. Clinical efficacy of once-daily and twice-daily dosing was comparable.

Tear inflammatory mediators and protein in eyes of post allogenic hematopoeitic stem cell transplant patients.

AIM: To analyze tear cytokines levels and their correlation to ocular surface parameters in allogenic hematopoietic stem cell transplants (allo-HSCT) patients. METHODS: Prospective longitudinal study of allo-HSCT patients and controls for ocular surface evaluation (OSDI, TBUT, Schirmer's test, staining scores), tear biochemical analysis for protein, cytokines [IL-10, IL-12, IL-2, IL-4, IL-6, IL-17, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, VEGF], MMPs [MMP 2, 9, 7, 13, 10 and chemokine (IL-8)], & VEGF on three consecutive follow up visits (at three monthly interval) was done. RESULTS: Of 24 post allo-HSCT patients (19 males, 5 females) & 12 controls (mean age 34.3 + 5.8 years) enrolled, 20 patients [mean age 33.4 + 7.77 years; mean time of recruitment of 5.2 + 2.12 months following alloHSCT] who completed three consecutive follow up visits were included for analysis. Ocular GVHD (oGVHD) was seen in 8 patients (33.3%). Tears biochemical analysis showed elevated levels of interferon γ, IL 6, IL 8, IL 10, IL 12AP70, IL 17A, MMP 9 and VEGF in oGVHD eyes as compared to non-oGVHD & control eyes. Non-oGVHD eyes showed elevated tear MMP 7 and MMP 9 as compared to healthy controls. Tear protein levels were significantly decreased in oGVHD eyes and were equivocal in nonGVHD and control eyes. TBUT and ocular staining scores to correlate best with tear interleukins and MMPs. CONCLUSION: Evaluation of levels of tear VEGF, total protein & MMP 9 can be of significance in identifying oGVHD in post alloHSCT patients.

Antiproliferative activity of marine stingray Dasyatis sephen venom on human cervical carcinoma cell line.

BACKGROUND: Venoms comprise mixtures of numerous bioactive compounds that have a wide range of pharmacologic actions. Toxins from venomous animals have attracted the attention of researchers because of their affinity for primary sites responsible for lethality and their efficacy at extremely low concentrations. The venoms of marine stingrays have not been extensively studied and limited data is available on them. The present study aims to evaluate the antiproliferative and biochemical properties of the venom obtained from a species of marine stingray (Dasyatis sephen) on human cervical cancer cell line HeLa. METHODS: The antiproliferative effect of D. sephen venom was determined by MTT assay, and the oxidative stress was determined by lipid peroxidation method along with assessment of changes in the enzymatic and non-enzymatic antioxidant status. We observed intracellular reactive oxygen species (ROS) levels by DCFH-DA method, mitochondrial membrane potential alterations by rhodamine 123 staining and apoptotic morphological changes by acridine orange/ethidium bromide dual staining method. RESULTS: D. sephen venom enhances lipid peroxidative markers such as thiobarbituric acid reactive substance, conjugated diene, and lipid hydroperoxide in HeLa cell lines. Stingray venom enhances the ROS levels, which is evidenced by the increased 2-7-diacetyl dichlorofluorescein fluorescence. Further, D. sephen venom treatment altered the mitochondrial membrane potential in HeLa cells. Additionally, we observed increased apoptotic morphological changes in D. sephen venom-treated groups. CONCLUSIONS: Dasyatis sephen venom exhibits potent antiproliferative effect on HeLa cell line and upon further purification it could be a promising antiproliferative agent.

Antiproliferative activity of marine stingray Dasyatis sephenvenom on human cervical carcinoma cell line

BackgroundVenoms comprise mixtures of numerous bioactive compounds that have a wide range of pharmacologic actions. Toxins from venomous animals have attracted the attention of researchers because of their affinity for primary sites responsible for lethality and their efficacy at extremely low concentrations. The venoms of marine stingrays have not been extensively studied and limited data is available on them. The present study aims to evaluate the antiproliferative and biochemical properties of the venom obtained from a species of marine stingray (Dasyatis sephen) on human cervical cancer cell line HeLa.MethodsThe antiproliferative effect of D. sephen venom was determined by MTT assay, and the oxidative stress was determined by lipid peroxidation method along with assessment of changes in the enzymatic and non-enzymatic antioxidant status. We observed intracellular reactive oxygen species (ROS) levels by DCFH-DA method, mitochondrial membrane potential alterations by rhodamine 123 staining and apoptotic morphological changes by acridine orange/ethidium bromide dual staining method.ResultsD. sephen venom enhances lipid peroxidative markers such as thiobarbituric acid reactive substance, conjugated diene, and lipid hydroperoxide in HeLa cell lines. Stingray venom enhances the ROS levels, which is evidenced by the increased 2-7-diacetyl dichlorofluorescein fluorescence. Further, D. sephen venom treatment altered the mitochondrial membrane potential in HeLa cells. Additionally, we observed increased apoptotic morphological changes in D. sephen venom-treated groups. ConclusionsDasyatis sephen venom exhibits potent antiproliferative effect on HeLa cell line and upon further purification it could be a promising antiproliferative agent.(AU)

Antiproliferative activity of marine stingray Dasyatis sephenvenom on human cervical carcinoma cell line

Background Venoms comprise mixtures of numerous bioactive compounds that have a wide range of pharmacologic actions. Toxins from venomous animals have attracted the attention of researchers because of their affinity for primary sites responsible for lethality and their efficacy at extremely low concentrations. The venoms of marine stingrays have not been extensively studied and limited data is available on them. The present study aims to evaluate the antiproliferative and biochemical properties of the venom obtained from a species of marine stingray (Dasyatis sephen) on human cervical cancer cell line HeLa.MethodsThe antiproliferative effect of D. sephen venom was determined by MTT assay, and the oxidative stress was determined by lipid peroxidation method along with assessment of changes in the enzymatic and non-enzymatic antioxidant status. We observed intracellular reactive oxygen species (ROS) levels by DCFH-DA method, mitochondrial membrane potential alterations by rhodamine 123 staining and apoptotic morphological changes by acridine orange/ethidium bromide dual staining method.ResultsD. sephen venom enhances lipid peroxidative markers such as thiobarbituric acid reactive substance, conjugated diene, and lipid hydroperoxide in HeLa cell lines. Stingray venom enhances the ROS levels, which is evidenced by the increased 27-diacetyl dichlorofluorescein fluorescence. Further, D. sephen venom treatment altered the mitochondrial membrane potential in HeLa cells. Additionally, we observed increased apoptotic morphological changes in D. sephen venom-treated groups. ConclusionsDasyatis sephen venom exhibits potent antiproliferative effect on HeLa cell line and upon further purification it could be a promising antiproliferative agent.

Utility of the trough plasma imatinib level monitoring at two time points in patients with the chronic myeloid leukemia-chronic phase.

INTRODUCTION: Plasma imatinib levels vary widely in patients with the chronic myeloid leukemia-chronic phase, and studies have shown improved hematological, cytogenetic, and molecular responses in patients with the higher trough imatinib levels. MATERIALS AND METHODS: We analyzed 50 consecutive patients with the chronic myeloid leukemia-chronic phase and performed plasma imatinib levels at 1 month and 12 months and correlated them with complete hematological response at 3 months and molecular response at 12 months, respectively. RESULTS: Trough plasma imatinib levels at 1 month correlated well with complete hematological response at 3 months (P = 0.007) and levels at 12 months correlated with molecular response at 12 months (P = 0.04). Compliance to imatinib also significantly correlated with imatinib levels at 1 month (P = 0.0008) and imatinib levels at 12 months (P = 0.0002). CONCLUSION: Plasma imatinib levels may be of benefit in patients not achieving desired response at defined time intervals. The plasma level monitoring also helps in the assessment of drug compliance.

Randomized Controlled Trial in Advance Stage Breast Cancer Patients for the Effectiveness on Stress Marker and Pain through Sudarshan Kriya and Pranayam.

OBJECTIVE: The objective of this study is to examine the effect of a cognitive, behavioral stress management module of Sudarshan Kriya (SK) and P on levels of serum cortisol and pain among the women suffering from advanced stage breast cancer. MATERIALS AND METHODS: Participants (n = 147) were screened and randomized to receive standard care (n = 69) versus standard along with SK and Pranayam (P) intervention (n = 78) imparted in one 18 hrs workshop spread during 3 days. Participants were expected to practice it at home 20 min daily as adjuvant to standard pharmacological treatment for pain. RESULTS: There was a significant difference in blood cortisol levels after 3 months of practice of SK and P. Mean blood levels in the intervention arm were 341.2 ng/ml against 549.2 ng/ml in the control arm (P ≤ 0.002). Pain perception in comparison to control arm reduced by 3 points in SK and P arm on 0-10 verbal scale of pain. CONCLUSION: SK and P is an effective intervention in reducing stress and pain among advance stage patients of breast cancer.

Risk factors for gallbladder cancer: a case-control study.

Risk factors for gallbladder cancer (GBC) except gallstones are not well known. The objective was to study the risk factors for GBC. In a case-control study, 200 patients with GBC, 200 healthy controls and 200 gallstones patients as diseased controls were included prospectively. The risk factors studied were related to socioeconomic profile, life style, reproduction, diet and bile acids. On comparing GBC patients (mean age 51.7 years; 130 females) with healthy controls, risk factors were chemical exposure [odd ratios (OR): 7.0 (2.7-18.2); p < 0.001)], family history of gallstones [OR: 5.3 (1.5-18.9); p < 0.01)], tobacco [OR: 4.1 (1.8-9.7); p < 0.001)], fried foods [OR: 3.1 (1.7-5.6); p < 0.001], joint family [OR: 3.2 (1.7-6.2); p < 0.001], long interval between meals [OR: 1.4 (1.2-1.6); p < 0.001] and residence in Gangetic belt [OR: 3.3 (1.8-6.2); p < 0.001]. On comparing GBC cases with gallstone controls, risk factors were female gender [OR: 2.4 (1.3-4.3); p = 0.004], residence in Gangetic belt [OR: 2.3 (1.2-4.4); p = 0.012], fried foods [OR: 2.5 (1.4-4.4); p < 0.001], diabetes [OR: 2.7 (1.2-6.4); p = 0.02)], tobacco [OR 3.8 (1.7-8.1); p < 0.001)] and joint family [OR: 2.1 (1.2-3.4); p = 0.004]. The ratio of secondary to primary bile acids was significantly higher in GBC cases than gallstone controls (20.8 vs. 0.44). Fried foods, tobacco, chemical exposure, family history of gallstones, residence in Gangetic belt and secondary bile acids were significant risk factors for GBC.

Cobalamin and folic Acid status in relation to the etiopathogenesis of pancytopenia in adults at a tertiary care centre in north India.

Background. Pancytopenia has multiple etiologies like megaloblastic anemia, aplastic anemia, leukemia, and various infections. We investigated the clinical, etiological and hematological profile including bone marrow morphology of patients with pancytopenia in relation to their vitamin B12 and folic acid status at a tertiary care referral hospital in north India. Methods. A total of 140 consecutive patients with pancytopenia were selected from June 2007 to December 2008. Bone marrow examination and other tests were carried out as warranted, including serum cobalamin and folate assays using liquid chromatography mass spectroscopy (LC MS/MS). Results. The study population consisted of 92 males and 48 females with a mean age of 32.8 years. Megaloblastic anemia 60.7%, aplastic anemia (7.8%), and leukemia (9.2%) were common causes. Infectious causes (16.4% of all cases) included leishmaniasis, HIV-AIDS, malaria and tuberculosis. Severe cobalamin deficiency (B12 < 100 pg/mL) was seen in 81% of all patients including 91.6% of patients with MA. In contrast, only 7.14% of all pancytopenic patients were folate deficient. Folate deficiency (<5 ng/mL) was seen in just 5% MA patients. Combined cobalamin and folate deficiency was seen in 5 patients (3.51%). Conclusion. Cobalamin deficiency was found to be more common in our setting and is largely underdiagnosed in the age of folate supplementation. Infectious diseases like tuberculosis, leishmaniasis, and increasingly HIV are important and treatable causes of pancytopenia. This is in contrast with the developed nations where the bulk of disease is due to malignancy or marrow aplasia.

High concentration of adenosine in human visceral leishmaniasis despite increased ADA and decreased CD73.

Absence of an effective Th-1 response has been demonstrated as a major cause for the disease pathology among patients with visceral leishmaniasis (VL). Defining strategies to prevent the development of Th-2 response and/or initiate/activate effective Th-1 response may be of help to reduce the growing incidence of drug unresponsiveness. Adenosine, which is considered as an endogenous anti-inflammatory agent is generated in injured/inflamed tissues by the enzymatic catabolism of adenosine triphosphate (ATP), and it suppresses inflammatory responses of essentially all immune cells. The extracellular adenosine-producing pathway comprises two major enzymes CD39 (ATP → ADP → AMP) and CD73 (AMP → Adenosine). In contrast, the adenosine-degrading pathway contains only one major enzyme adenosine deaminase (ADA). Our study shows high concentration of adenosine in diseased condition, varying expression of enzyme involved in adenosine-producing (CD73↓) and adenosine-degrading (ADA↑) pathways. These are less studied in infections like VL but are very important in terms of endogenous regulation of immune response among patients.

Development, characterization and in vitro assessement of stearylamine-based lipid nanoparticles of paclitaxel.

The objective of the study was to design and evaluate a solid lipid nanoparticle (SLN) drug delivery system for delivery of paclitaxel. Components of the SLN were lipid (stearylamine) and surfactants (Pluronic F68 and Soya lecithin). The paclitaxel loaded nanoparticles were prepared by a modified solvent injection method. Experiments were carried out with excipients, where surfactants, lipid and drug molar ratios were varied to optimize the formulation characteristics. The in vitro drug release profile from the nanoparticles followed a diffusion controlled mechanism. The modified solvent injection method ensured high entrapment efficiency (approximately 75%), produced smaller, stable nanoparticles with a narrow size distribution and proved to be a reproducible and fast production method. The present study describes the feasibility and suitability of stearylamine based SLN produced using a mixture of surfactants to develop a clinically useful system with targeting potential for poorly soluble antineoplastic drugs.

Characterization and in vitro assessment of paclitaxel loaded lipid nanoparticles formulated using modified solvent injection technique.

This study investigates the design and characterization of solid lipid nanoparticles (SLNs) containing paclitaxel fabricated by a modified solvent injection technique using stearic acid as lipid and stabilized by a mixture of surfactants, for future evaluation of this colloidal carrier system for the oral delivery of paclitaxel, devoid of the side effects of Cremophor EL. SLN formulations of paclitaxel stabilized by mixture of surfactants i.e. lecithin/poloxamer 188 were developed with smaller size and narrow size distribution. The paclitaxel-loaded SLNs exhibited spherical shape with smooth surface as analyzed by transmission electron microscopy (TEM). The average particle size obtained through this method was found to be approximately 113 nm. The zeta potential was between -32 and -39 mV with poloxamer 188. Encapsulation efficiencies of about 72.18 +/- 3.7 and 89.0 +/- 2.4% were achieved using 0.05 and 0.25 mmol of paclitaxel, respectively. Paclitaxel showed a sustained in vitro release profile and was found to follow Higuchi kinetic equations. In vitro cytotoxicity assay confirmed that paclitxel entrapped in SLNs showed higher cytotoxicity against cultured hepatocelluler carcinoma cells than paclitaxel alone. The modified solvent injection technique used in this research proved to be a simple, easily available and effective method to produce SLNs and could be used for controlled delivery of different lipophilic drugs for cancer chemotherapy.

Drug monitoring of imatinib levels in patients undergoing therapy for chronic myeloid leukaemia: comparing plasma levels of responders and non-responders.

PURPOSE: Imatinib mesylate is used as first line therapy in the treatment of chronic myeloid leukaemia. This study was designed to study the correlation of plasma levels of imatinib with response to the therapy. METHODS: A total of 40 chronic myeloid leukaemia patients in the chronic phase of the disease were recruited and placed into two groups of 20 patients: imatinib responders and imatinib non-responders, respectively. Each blood sample was taken 24 h after and immediately prior to taking a 400 mg oral dose of imatinib. Drug levels were detected by high-performance liquid chromatography. RESULTS: The mean plasma imatinib levels in the imatinib non-responders were significantly lower than those in the imatinib responders (0.70 vs. 2.34 microM, respectively; p = 0.002). CONCLUSIONS: Plasma levels of imatinib were correlated with response to the therapy, so routine monitoring of the therapeutic levels of the drug should be carried out specifically in treatment-resistant cases for determining dose escalation.

Vitreous and aqueous penetration of orally administered moxifloxacin in humans.

OBJECTIVE: To investigate the intraocular penetration of moxifloxacin into the aqueous and vitreous after oral administration in humans. METHODS: A prospective, nonrandomized study of 27 consecutive patients scheduled for elective parsplana vitrectomy surgery between 1 October and 31 December 2004 was carried out. Aqueous, vitreous, and serum samples were obtained and analysed after oral administration of a single 400 mg tablet of moxifloxacin a few hours before surgery. Assays were performed using high-performance liquid chromatography. RESULTS: Mean+/-SD moxifloxacin concentrations in the serum (n=27), aqueous (n=25), and vitreous (n=27) were 1.34+/-0.98, 0.21+/-0.21, and 0.09+/-0.09 microg/ml, respectively. The mean+/-SD sampling times after oral administration of the moxifloxacin tablet for serum, aqueous, and vitreous were 2.02+/-0.51, 1.53+/-0.45, and 1.55+/-0.46 h, respectively. The minimum inhibitory concentration for 90% of isolates (MIC90) was far exceeded in the aqueous for a wide spectrum of key pathogens, whereas it was not exceeded in the vitreous for several organisms. Of note, the MIC90 for Staphylococcus epidermidis was not exceeded in any of the samples. CONCLUSIONS: Orally administered moxifloxacin achieves measurable levels in the noninflammed human eye, with the aqueous levels effective against a variety of pathogens. However, the spectrum of coverage does not appropriately encompass the most common causative organisms in endophthalmitis, especially Staphylococcus epidermidis. Further studies are needed to precisely define the role of oral moxifloxacin in the treatment of or prophylaxis against intraocular infections.

Protection from ultraviolet radiation by spectacle lenses available in India: a comparative study.

BACKGROUND: Exposure to ultraviolet radiation (UVR) can result in several ocular ailments. We studied the UV absorption (UV-A and -B bands) in 20 lenses (11 hard resin and 9 glass) commonly available in India as uncut lenses for the purpose of prescription as well as non-prescription wear. METHODS: Using a UV-visible spectrophotometer (Thermo-Spectronic, UV-1 model, Thermo Electron Corporation, USA), the percentage transmittance was scanned between 190 and 400 nm, from which the results at 280, 320, 340, 360, 380 and 400 nm were analysed. RESULTS: At 360 nm (UV-A), 75% of the lenses studied failed to offer 95% protection as recommended by the United States Food and Drug Administration (US FDA). At 280 nm (UV-B), 35% of the lenses failed to offer 99% protection against UV-B. Hard resin lenses showed a higher degree of variation in protection from UV-A. CONCLUSIONS: Most of the lenses studied failed to meet the US FDA recommendations in terms of protection from UV-A. Glass lenses afforded better protection up to 320 nm compared with hard resin lenses. As the claims of lens manufacturers regarding UVR protection fall short of international standards, certification of UVR protection for different lenses should be introduced in India.

Intraocular ciprofloxacin levels after oral administration in silicone oil-filled eyes.

PURPOSE: To evaluate penetration of oral ciprofloxacin in the retro-silicone oil space fluid (RSOF) in silicone oil (SO)-filled eyes. METHODS: One dose of 750 mg ciprofloxacin was given to two groups of five patients with vitrectomized eyes with SO endotamponade, 4 hours (group I) and 8 hours (group II) before SO removal. In 10 vitrectomized eyes with SO endotamponade (group III) and another 10 patients scheduled for vitrectomy for the first time (group IV), two 750-mg doses every 12 hours, with the last dose 12 hours before surgery, were given. Blood samples were taken at the time of collection of RSOF samples in groups I, II, and III and of the vitreous in group IV. All samples were assayed for ciprofloxacin by high-performance liquid chromatography. RESULTS: The mean drug concentration in the RSOF was 0.34 +/- 0.09, 0.37 +/- 0.04, 0.84 +/- 0.29, and 0.44 +/- 0.11 micro g/mL in groups I, II, III, and IV respectively. The mean serum concentration was 1.29 +/- 0.63, 1.08 +/- 0.14, 1.93 +/- 0.84, and 1.34 +/- 0.55 micro g/mL in groups I, II, III, and IV respectively with no statistically significant difference between groups III and IV (P = 0.081). CONCLUSIONS: Antibiotic levels in the RSOF in SO-filled eyes after oral administration of ciprofloxacin in two 750-mg doses exceeded the minimal inhibitory concentration for 90% of isolates (MIC(90)) for most bacterial species and was higher than levels reached in the vitreous in nonvitrectomized eyes (P = 0.001).

Etoposide encapsulated in positively charged liposomes: pharmacokinetic studies in mice and formulation stability studies.

Etoposide is an antineoplastic agent which acts by forming a ternary complex with topoisomerase II and DNA, causing DNA breaks and cell death. In recent studies we have demonstrated that encapsulation in liposomes increases the antitumour efficacy and reduces the adverse effects associated with etoposide. The present study was thus conducted to evaluate whether encapsulation in cationic liposomes altered the pharmacokinetics of etoposide and to study the effect of cholesterol incorporation on the stability of the liposomes. Etoposide-encapsulated unilammellar liposomes were synthesized by thin film hydration followed by extrusion. The drug was administered to Swiss albino mice at a dose of 10 mg kg(-1). The concentration of the drug in plasma was analysed at different time points till 360 min after injection, using a h.p.l.c. method. The terbium chloride-dipicolinic acid interaction method was applied to study the stability of the formulation in mouse serum and also following storage at 0( composite function)C over a period of time. The effect of the free and liposomal drug on myelosuppression was evaluated at 10 mg m(-2)and 40 mg m(-2)dose levels by quantifying blood cell counts on day 15 and day 21 following a 5 day course of therapy. Encapsulation in cationic liposomes increased the area under the concentration vs time curve to 42.98 microghml(-1)from 24.18 microghml(-1)in the case of the free drug. Half-life (beta) was 58. 62 and 186 min in the case of free and liposomal etoposide, respectively. In the stability studies, incorporation of cholesterol progressively stabilized the formulation in serum. The use of sucrose at increasing concentrations as a cryoprotectant also increased the shelf stability of the formulation at 0( composite function)C. Toxicity studies using a dose of pure drug revealed that though myelosuppression was evident in both liposomal- and free drug-treated groups on day 15 it was reversed by day 21 following initiation of therapy. The present findings suggest that liposomes could serve as an alternative mode of delivery for etoposide.