PREVALENCE OF DIDANOSINE-RELATED RETINAL TOXICITY AT AN URBAN ACADEMIC CENTER AS DIAGNOSED WITH ULTRA-WIDEFIELD IMAGING.

PURPOSE: Antiretroviral therapy has revolutionized HIV treatment with didanosine (DDI) as a pioneering drug. However, DDI has been associated with retinal toxicity, characterized by peripheral chorioretinal degeneration with macular sparing. Despite its clinical recognition, the prevalence and risk factors for didanosine-induced retinopathy are not well described. METHODS: This retrospective case series analyzed 127 DDI-treated patients at Weill Cornell Medicine Department of Ophthalmology. Inclusion criteria included at least 6 months of DDI use and available ultra-widefield imaging. Patients were categorized as affected or unaffected based on retinal imaging assessed by two reviewers. The affected group was further divided into "probable" or "possible" retinopathy. Patient demographics, DDI usage characteristics, and imaging findings were analyzed with statistical comparisons drawn between affected and unaffected cohorts. RESULTS: Of the 127 patients, 9 (7%) showed signs of didanosine-induced retinal toxicity. On average, the affected group was older compared with the unaffected group (65.1 vs. 56.5 years, P = 0.025), with lower BMI (23.2 vs. 27.4, P = 0.04), and older at the start of the treatment (51.6 vs. 40.8 years, P = 0.026). Mild phenotypes with peripheral pigmentary changes were also identified using ultra-widefield imaging. CONCLUSION: This pioneering academic study highlighted a notable prevalence of DDI-induced retinal toxicity. Statistical analysis demonstrated age, BMI, and age at treatment initiation as potential risk factors. Ultra-widefield autofluorescence emerged as a valuable tool in detecting and delineating findings. Follow-up studies are needed to determine the necessity of regular screening for individuals on or with a history of didanosine use.

Elucidating the effect of dietary neem (Azadirachta indica) on growth performance, haemato-biochemical, immunonological response, and anti-pathogenic capacity of Nile tilapia juveniles.

This investigation attempts to evaluate the effect of diet additives via aqueous or ethanolic herbal extracts from Azadirachta indica leaves on Nile tilapia, Oreochromis niloticus. Five dietary categories were assigned to the fish: the first category (N1, with no extract) was kept under control conditions; two categories contained aqueous extract (N2 (1.0 g/kg) and N3 (2.0 g/kg); and two categories contained ethanolic extract, N4 (1.0 g/kg) and N5 (2.0 g/kg), with each group being fed for 60 days. After the feeding trial, Aeromonas hydrophila was injected intraperitoneally into fish for 14 days; fish mortality was recorded during this period. The results showed that the fish-fed dietary A. indica significantly improved growth performance and intestinal health (digestive enzymes and intestinal morphology), especially in the N4 and N5 categories. However, N4 and N5 categories demonstrated a significant decrease in AST and ALT activities and an increase in total protein, serum albumin, globulin, growth hormone (GH), leptin hormone (LEP), hemoglobin, white blood cells, and hematocrit (P < 0.05) in comparison with the control category (N1). Compared to the control category, the N4 and N5 categories have revealed a significant reduction in MDA activity and improvements in immunological activities (lysozyme, complement C3, and nitric oxide) and antioxidant enzymes (CAT, SOD, and GPX). Moreover, in tilapia-fed A. indica, the expression of IL-8, IL-1ß, and Nf-κb genes was downregulated partially in the N4 and N5 categories than the control category. In contrast, the lysozyme, C3, GPX, and CAT genes were upregulated partially at N4 and N5 compared to the control category. Following the bacterial challenge, fish in the N4 and N5 categories also displayed the lowest fish mortality compared to the control category. The ethanolic extract displayed a more potent resistance against the parasite Cichlidogyrus tilapia in vitro than the aqueous and control categories, partially at 2 g/L. According to these findings, an ethanolic neem extract (2.0 g/kg feed) activates the immune system and antioxidant response in Nile tilapia fingerlings, improving growth and fish resistance to parasitic and bacterial infections.

Elucidating the Environmental and Health Risks of Trace Element Pollution in Red Sea Fish from Nuweiba City, Aqaba Gulf, Egypt.

Trace element bioaccumulation in marine organisms is a rising international issue due to possible health concerns for humans. Thirteen trace elements were analyzed in the sediment, water, and muscular tissue of Red Sea fish. Additionally, the average daily intake (EDI), the cancer risk (CR), the hazard index (HI), and the target hazard quotient (THQ) of those elements have been taken into consideration when evaluating any possible health concerns related to their consumption. All species presented quantifiable values in muscle for all the analyzed elements (arsenic (As), lead (Pb), copper (Cu), aluminum (Al), boron (B), iron (Fe), barium (Ba), manganese (Mn), nickel (Ni), cadmium (Cd), chromium (Cr), zinc (Zn), and mercury (Hg), except for Cd and Hg, being Fe and Zn the most accumulated elements in all species. Conversely, in water samples, most elements were undeleted except for aluminum, boron, iron, and zinc. All Red Sea fish, however, had concentrations of Zn, Ni, Fe, Cu, and Mn below the upper limit allowed, although most species had higher levels of As, Cr, and Pb (0.48 ± 0.83-5.10 ± 0.79, 1.97 ± 0.46-5.25 ± 0.67 and 2.12 ± 1.01-6.83 ± 0.93 µg/g, respectively).The studied Red Sea fish showed contamination degrees (CD) of Mn, Cu, Fe, Ni, Zn, and Pb were ≤ 1, indicating minimal contamination, with As and Cr showing higher contamination degrees. However, the pollution index values (MPI-elements) can be represented according to ascending order: Lethrinus ramak < Cephalopholis hemistiktos < Pagellus affinis < Trachurus japonicus < Cheilinus lunulatus < Siganus luridus < Parupeneus forsskali < Caesio suevica. The study found that edible tissues are safe for human consumption, with HI values for children and adults less than ten, indicating negligible non-cancer hazards. However, fish consumption presents health risks due to chromium, lead, and arsenic, with THQ values several times greater than 1, and CR-Ni, CR-Cr, and CR-As values exceeding the acceptable 10-4 value in all studied species. This study provides critical insights into trace element contamination in marine fish species, highlighting the need for ongoing monitoring and proactive measures to ensure safe marine fish consumption in the Aqaba Gulf.

Prevalence of Age-Related Macular Degeneration in Patients with Chronic Exposure to P2X7R Inhibitors.

PURPOSE: P2X7 receptor (P2X7R) is a purinergic cation channel whose activation has been linked with age-related macular degeneration (ARMD). Several nucleoside reverse transcriptase inhibitors, zidovudine (AZT), lamivudine (3TC) and abacavir (ABC), have been shown to inhibit P2X7R and improve outcomes in animal models of ARMD. Our aim is to investigate the association between chronic AZT, 3TC, and ABC therapy and ARMD in a clinical setting. METHODS: This is a retrospective cohort study comparing 445 patients with HIV and confirmed usage of AZT, 3TC, and ABC against 200 patients with HIV without usage of AZT, 3TC, and ABC and 445 non-HIV infected patients. Fundus examination and spectral domain optical coherence tomography (SD-ODT) were used to measure prevalence of early-intermediate stage ARMD, geographic atrophy, and exudative ARMD. RESULTS: There was no statistically significant difference in the prevalence of early-intermediate stage ARMD between the HIV infected patients with a history of AZT, 3TC, and ABC use and the HIV infected patients without AZT, 3TC, and ABC use (p = 0.887). There was also no statistically significant difference in the prevalence of geographical atrophy (p = 0.062) and exudative AMD (p > 0.999) between the HIV infected patients with a history of AZT, 3TC, and ABC use and non-HIV infected patients. CONCLUSION: We did not find an effect of P2X7R inhibiting antiretrovirals usage on early-intermediate stage ARMD, geographical atrophy, or exudative ARMD. Studies with larger cohort and more rigorous medication history are needed to assess the effects on geographical atrophy or exudative ARMD.

Implementation of a Teleophthalmology Screening Program for Diabetic Retinopathy in New York City.

Purpose: To examine the implementation of a teleophthalmology program for diabetic retinopathy (DR) screening at a metropolitan hospital system and identify the challenges that the clinical teams encountered using the program. Methods: The study was conducted in 2 parts. The first was a pilot retrospective chart review of 300 consecutive patients screened for DR by the teleophthalmology screening program. The baseline variables, DR capture rate and staging, and continuity of care for those diagnosed with DR were analyzed. The second was a web-based survey identifying the barriers encountered by 36 physicians and clinical staff as they participated in the teleophthalmology screening program. Results: Part 1: Of the patients evaluated, 57 (19.0%) were diagnosed with DR; 42 (73.7%) had mild nonproliferative DR (NPDR), 7 (12.3%) had moderate NPDR, none had severe NPDR, and 8 (14.0%) had PDR. Thirty-one patients (54.4%) with retinopathy diagnoses were referred for an in-person follow-up at the clinic while the rest continued monitoring via the program. Of this subset, 22 (71.0%) completed the follow-up visit. Part 2: The survey respondents comprised 28 physicians (77.8%), 6 licensed nurse practitioners (16.7%), and 2 medical assistants (5.6%). Twenty-two providers (71.0%) preferred initiating referrals for in-person annual examinations over teleophthalmology screening referrals. The most common barriers described were related to workflow interruption, time constraints, and staff shortages. Conclusions: The teleophthalmology DR screening program allowed identification of early or absent DR at clinics in an urban setting (New York City). The findings suggest areas for targeted improvement in the screening program to better complement internal referral practices' workflows.

Heavy Metals Assessment and Health Risk to Consumers of Two Commercial Fish Species from Polyculture Fishponds in El-Sharkia and Kafr El-Sheikh, Egypt: Physiological and Biochemical Study.

Metal pollution is a major environmental concern worldwide, especially in Egypt. The aquaculture industry uses widespread artificial feeds to stimulate fish production, leading to metal accumulation in the aquatic environment. Heavy metal concentrations (HMCs) in sediments, water, and tissues were studied to study the effect of pollution levels on heamatological, and biochemical, immunological aspects of farmed fish as well as on human health. Results declared that the HMC levels in the water and sediment were significantly different between El-Sharkia and Kafr El-Sheikh fishponds (T-test, p < 0.05). This was supported by the metal pollution index in the water and sediment, indicating that El-Sharkia fishponds (ES fishponds) were more contaminated than Kafr El-Sheikh fishponds (KES fishponds). Also, HMCs in fish tissues were significantly increased in fish cultivated in ES fishponds than in KES fishponds. Haematological, immunological, and biochemical alterations of Bolti (Oreochromis niloticus) and Topara (Chelon ramada) fish were significantly different within the different fish species as well as the different fishponds. From the human health perspective, the THQ-HMC and HI-HMC associated with the consumption of muscle suggest a safe non-carcinogenic risk to human health. In contrast, cadmium poses a cancer risk to children who consume the muscular tissue of Bolti fish from ES fishponds, which should be regarded as a warning sign based on data indices and a human health perspective. In order to minimise HMC pollution in the aquaculture sector, it is advisable to take possible assessments and carry out continuous monitoring considering international WHO/FAO assessments.

Heavy Metal Levels and Cancer Risk Assessments of the Commercial Denis, Sparus aurata Collected from Bardawil Lake and Private Fish Farm Waters as a Cultured Source, Egypt.

Heavy metal pollution of natural and cultivated habitats may be caused by agricultural, industrial, and human activities. Fish living in these habitats easily accumulate metals in their organs; for food safety and human health, the heavy metals in fish flesh are of major concern due to the harmful nature of these pollutants even in low quantities. In this study, metals (Iron, Fe; Lead, Pb; Cadmium, Cd; Nickel, Ni; Copper, Cu and Zinc, Zn) in the muscle, liver, intestine, and gill of gilthead seabream (Sparus aurata, Denis is local name) were monitored to determine the contamination levels and to investigate the protective impact of cooking methods on the reduction or mitigation of metal levels. Although the Denis samples exhibited relatively low Pb and Cd levels, most fish samples had elevated levels of Fe and Zn. The examined metals accumulated at the highest level in the liver and gills compared to the other organs. Results showed that cooking methods had a considerable effect on concentrations of metals. However, the levels of metal in S. aurata from various sources were reduced significantly (P < 0.05) by frying, microwave, and grilling cooking, which was ordered in the following sequence as microwave cooking < grilling < frying. The consumption of Denis fish from different sources (wild and cultured) has no negative effects on health, according to a study of health hazards based on indices of carcinogenic and non-carcinogenic. The metal results indicated that different fish sources (wild and cultured) could be acceptable for human consumption. Data hypothesized a positive impact of awareness among the native community.

Primary and secondary focal choroidal excavation morphologic phenotypes, associated ocular disorders and prognostic implications.

AIMS: To characterise and classify the morphological, clinical and tomographic characteristics of focal choroidal excavation (FCE) lesions to determine their prognostic implications. METHODS: 36 eyes with FCE (32 patients) underwent multimodal imaging, including spectral domain optical coherence tomography and fundus autofluorescence. FCE lesions were classified into three subtypes: (1) type 1: myopic (central choroidal thickness: <100 µm), (2) type 2: suspected congenital (central choroidal thickness: 100-200 µm, without associated chorioretinal pathology) and (3) type 3: secondary or acquired (central choroidal thickness: >200 µm, with associated chorioretinal pathology). RESULTS: 80.6% of eyes were followed longitudinally (26.8±18.8 months). There were 9 type 1 FCEs (myopic), 8 type 2 FCEs (U-shaped, congenital) and 19 type 3 FCEs (V-shaped, secondary). Type 2 FCEs trended towards larger maximum widths (p=0.0563). Type 3 FCEs were associated with central serous chorioretinopathy or pachyvessels (47.4%), but were also seen in pattern dystrophy, geographic atrophy, inactive choroiditis, torpedo maculopathy and adult-onset vitelliform dystrophy. Choroidal neovascular membranes (CNVMs) were more prevalent in type 3 FCE (41.2% compared with 11.1% for type 1 FCE, p=0.251, and 0% for type 2 FCE, p=0.043). CONCLUSIONS: The FCE types, stratified by central choroidal thickness, demonstrated distinct morphological characteristics and associated findings. The classification scheme held prognostic implications as type 3 FCE with V shapes were associated with other chorioretinal conditions and were more likely to develop CNVM.

Bioaccumulation, Biosedimentation, and Health Hazards of Elements in Crayfish, Procambarus clarkii from El-Rahawi Drain and El-Qanatir in the River Nile, Egypt.

Elements accumulation in crayfish is proportional to the increase in bioavailability (direct contact) with the surrounding water, sediment, and feeding. Five heavy metals (Cu, Cr, Mn, Ni, and Ag) and lithium (Li) were analyzed in the sediment, water, and crayfish tissues. Elements (heavy metals and lithium) concentrations in sediment, water, and crayfish tissues showed significant differences between the two sampling stations (El-Qanatir and El-Rahawi drain). However, the levels of elements in crayfish tissues were arranged in declining order as hepatopancreas > gills > exoskeleton > muscles for Cu and Cr; hepatopancreas > exoskeleton > gills > muscles for Ni and Ag; and exoskeleton > gills > hepatopancreas > muscles for Li and Mn. The human health hazard evaluation of heavy metals and lithium exposure via edible tissue consumption was assessed for both children and adult consumers. The target hazard quotient THQ values of crayfish edible tissues (less than 1) will not impose any health implications for consumers who ingest edible tissues in sufficient quantities. Furthermore, the hazard index (HI) values reported for children and adult consumers were lower than one, indicating non-carcinogenic and carcinogenic hazards, suggesting that crayfish edible tissues are safe for human ingestion. This evidence also found that Procambarus clarkii could be a good bio-indicator organism for monitoring potentially metals in aquatic systems.

Effect of Traditional Processing Methods on the Cultivated Fish Species, Egypt. Part I. Mineral and Heavy Metal Concentrations.

The study aimed to determine the effects of wet salting, dry salting, and smoking processing methods on the heavy metal and mineral concentrations in the cultivated fish species which collected from private fish farms at Kafr El-Sheikh Governorate, Egypt, during winter, 2017. The impacts of fish processing on mineral contents of the raw and processed fish were significantly different (P ≤ 0.05). The maximum level of metals in the raw and processed fish samples (wet salted, dry salted, and smoked fish) were recorded for iron ion and the minimum level determined for cadmium ion. However, the highest sequences of the minerals in the raw and processed samples were obtained in this order Na > K > P > Ca. Regarding to processing methods, significant decreases occurred in the minerals of Ca, K, and P, but smaller decrease in the heavy metals of Cd, Cu, Fe, Mg, Ni, and Zn in the wet salted grass carp. In the dry salted mullet, the changes in the minerals and heavy metals are relatively small. However, the greatest changes are on smoked grass carp; most of the minerals, including Ca, K and P, except Na, significantly increased. In heavy metals, Cu, Fe, and Zn, except Mg and Ni, also significant increased.

Choroidal Neovascularization and Macular Hemorrhage: Real-World Experience During the New York City COVID-19 Lockdown.

Purpose: This work reviews ocular, systemic, and demographic factors contributing to presentation of choroidal neovascular membrane (CNVM)-associated macular hemorrhage after the New York City coronavirus disease 2019 (COVID-19) lockdown. Methods: A retrospective, consecutive case series was conducted of all established patients presenting with macular hemorrhage between March 22, 2020, and August 10, 2020. Results: Fourteen patients (mean age 82.2 years) were evaluated. Ten patients had active CNVMs, 1 had an inactive lesion that was last injected 2 years prior, and 3 had new conversions from nonexudative age-related macular degeneration. In the actively treated CNVM group there was a delay in expected follow-up from 50.4 days to 125 days. Eight patients with previously active CNVM (73%) had a history of prior macular hemorrhage. Eight patients (57%) were on some form of antiplatelet or anticoagulation therapy. Twelve patients (86%) had COVID-19-specific risk factors besides age, and all but 1 patient (93%) delayed care without discussion with a physician. Ten patients (71%) had more than 1 week of symptoms prior to presentation. Twelve patients (86%) had signs of CNVM on prior optical coherence tomography. Conclusions: Adequate documentation of potential risks for hemorrhage (particularly prior hemorrhage or presence of subclinical type 1 CNVM), as well as COVID-19-specific risk factors, would aid triage of clinic appointments in future lockdowns. High-risk patients would likely benefit from direct physician communication discussing their individual risk profiles to alleviate anxiety over clinic visits and communicate their risk of severe vision loss.

Feasibility and Clinical Utility of Ultra-Widefield-Navigated Swept-Source Optical Coherence Tomography Imaging.

Purpose: This work aims to evaluate the clinical utility and feasibility of a novel scanning laser ophthalmoscope-based navigated ultra-widefield swept-source optical coherence tomography (UWF SS-OCT) imaging system. Methods: A retrospective, single-center, consecutive case series evaluated patients between September 2019 and October 2020 with UWF SS-OCT (modified Optos P200TxE, Optos PLC) as part of routine retinal care. The logistics of image acquisition, interpretability of images captured, nature of the peripheral abnormality, and clinical utility in management decisions were recorded. Results: Eighty-two eyes from 72 patients were included. Patients were aged 59.4 ± 17.1 years (range, 8-87 years). During imaging, 4.4 series of images were obtained in 4.1 minutes, with 86.4% of the image series deemed to be diagnostic of the peripheral pathology on blinded image review. The most common pathologic findings were chorioretinal scars (18 eyes). In 31 (38%) eyes, these images were meaningful in supporting clinical decision-making with definitive findings. Diagnoses imaged included retinal detachment combined with retinoschisis, retinal hole with overlying vitreous traction and subretinal fluid, vitreous inflammation overlying a peripheral scar, Coats disease, and peripheral retinal traction in sickle cell retinopathy. Conclusions: Navigated UWF SS-OCT imaging was clinically practical and provided high-quality characterization of peripheral retinal lesions for all eyes. Images directly contributed to management plans, including laser, injection or surgical treatment, for a clinically meaningful set of patients (38%). Future studies are needed to further assess the value of this imaging modality and its role in diagnosing, monitoring, and treating peripheral lesions.

Validated spectrophotometric and chromatographic methods for analysis of the recently approved hepatitis C antiviral combination ledipasvir and sofosbuvir.

This work describes five simple and reliable spectrophotometric and chromatographic methods for analysis of hepatitis C antiviral binary mixture of ledipasvir (LPV) and sofosbuvir (SBV). Method I is based on the use of Amax and derivative spectrophotometry with the zero-crossing technique where LPV was determined using its Amax and 1D amplitudes at 324 and 338nm respectively, while SBV was determined by measuring the 1D amplitudes at 276nm. Method II involves the application of the ratio spectra derivative spectrophotometry. For LPV, 12µg/mL SBV was used as divisor and the 1DD amplitudes at 239.8nm were plotted against LPV concentrations; while by using 10µg/mL LPV, the amplitudes at 279.2nm were found proportional to SBV concentrations. Method III depends on ratio-difference measurement where the peak to trough amplitudes between 229.2 and 268.4nm were measured and correlated to LPV concentration. Similarly, the amplitudes between 268.6 and 229.2nm in the SBV ratio spectra were recorded. For method IV, the two compounds were separated using HPTLC sheets of silica gel and a mobile phase composed of chloroform-methanol (94:6) followed by densitometric measurement of LPV and SBV spots at 331 and 267nm respectively. Method V depends on HPLC-DAD. Effective chromatographic separation was achieved using Thermohypersil C8 column (4.6×250mm, 5µm) with a mobile phase consisting of 0.01M sodium dihydrogen phosphate (pH 2.5) and methanol (20:80) at a flow rate 1.2mL/min and detection at 332 and 262nm for LPV and SBV respectively. Analytical performance of the developed methods was validated according to the ICH guidelines with respect to linearity, ranges, precision, accuracy, detection and quantification limits. The validated methods were successfully applied to the simultaneous analysis of LPV and SBV in mixtures of different proportions and their combined tablet dosage form.

Validated stability-indicating HPLC-DAD method for determination of the recently approved hepatitis C antiviral agent daclatasvir.

A comprehensive stability indicating HPLC with diode array detection method was developed for the determination of the recently approved antiviral drug daclatasvir dihydrochloride (DCV) which is used for the treatment of chronic Hepatitis C Virus (HCV) genotype 3 infection. Effective chromatographic separation was achieved using Waters C8 column (4.6×250mm, 5µm particle size) with isocratic elution of the mobile phase composed of mixed phosphate buffer pH 2.5 and acetonitrile in the ratio of 75:25 (by volume). The mobile phase was pumped at a flow rate of 1.2mL/min, and quantification of DCV was based on measuring its peak areas at 306nm. DCV eluted at retention time 5.4min. Analytical performance of the proposed HPLC procedure was thoroughly validated with respect to system suitability, linearity, range, precision, accuracy, specificity, robustness, detection and quantification limits. The linearity range was 0.6-60µg/mL with correlation coefficient>0.99999. The drug was subjected to forced degradation conditions of neutral, acidic and alkaline hydrolysis, oxidation and thermal degradation. The proposed method proved to be stability-indicating by resolution of the drug from its forced-degradation products. The validated HPLC method was successfully applied to analysis of the cited drug in its tablets.

Mutations in codons 12 and 13 of K-ras exon 2 in colorectal tumors of Saudi Arabian patients: frequency, clincopathological associations, and clinical outcomes.

Mutations in codons 12/13 of K-ras exon 2 are associated with reduced benefit from anti-epidermal growth factor receptor antibody treatment for metastatic colorectal cancer (CRC). Here, we evaluated the frequency of K-ras mutations and their relationship with clinicopathological features and treatment outcomes in Saudi Arabian patients with CRC. The genetic status of K-ras was determined in 300 patients diagnosed with CRC. Clinical information was collected retrospectively. K-ras was wild-type in 58% and mutated in 42% of the tumors. Most mutations were at codon 12 (89%) and were associated with metastasis [odds ratio (OR) = 1.38 (95%CI = 1.14-1.67] and occurrence of >40 µg/L carcinoembryonic antigen (CEA) [OR = 1.33 (1.1-1.74)] during diagnosis. Patients in stages I-III of the disease with wild-type K-ras tumors had a median relapse free survival (RFS) of 29 months in contrast to 22 months for those with the mutated K-ras tumor (P = 0.0357). In multivariate analysis, only the stage of the disease significantly predicted RFS (P = 0.001). Patients in stage IV of CRC with the wild-type K-ras tumor did not reach the median overall survival (OS), whereas patients with the mutated K-ras tumor survived for 23.5 months (P = 0.044). CEA level >40 µg/L (P = 0.004) and status of K-ras (P = 0.044) were independent predictors of OS. This is the largest study investigating K-ras mutations in patients with CRC in the Middle East. Mutations were associated with advanced stage of CRC, higher serum CEA, shorter RFS and OS.

Validated spectrophotometric and chromatographic methods for simultaneous determination of ketorolac tromethamine and phenylephrine hydrochloride.

This work describes five simple and reliable spectrophotometric and chromatographic methods for analysis of the binary mixture of ketorolac tromethamine (KTR) and phenylephrine hydrochloride (PHE). Method I is based on the use of conventional Amax and derivative spectrophotometry with the zero-crossing technique where KTR was determined using its Amax and (1)D amplitudes at 323 and 341nm respectively, while PHE was determined by measuring the (1)D amplitudes at 248.5nm. Method II involves the application of the ratio spectra derivative spectrophotometry. For KTR, 12µg/mL PHE was used as a divisor and the (1)DD amplitudes at 265nm were plotted against KTR concentrations; while - by using 4µg/mL KTR as divisor - the (1)DD amplitudes at 243.5nm were found proportional to PHE concentrations. Method III depends on ratio-difference measurement where the peak to trough amplitudes between 260 and 284nm were measured and correlated to KTR concentration. Similarly, the peak to trough amplitudes between 235 and 260nm in the PHE ratio spectra were recorded. For method IV, the two compounds were separated using Merck HPTLC sheets of silica gel 60 F254 and a mobile phase composed of chloroform/methanol/ammonia (70:30:2, by volume) followed by densitometric measurement of KTR and PHE spots at 320 and 278nm respectively. Method V depends on HPLC-DAD. Effective chromatographic separation was achieved using Zorbax eclipse plus C8 column (4.6×250mm, 5µm) with a mobile phase consisting of 0.05M o-phosphoric acid and acetonitrile (50:50, by volume) at a flow rate 1mL/min and detection at 313 and 274nm for KTR and PHE respectively. Analytical performance of the developed methods was statistically validated according to the ICH guidelines with respect to linearity, ranges, precision, accuracy, detection and quantification limits. The validated spectrophotometric and chromatographic methods were successfully applied to the simultaneous analysis of KTR and PHE in synthetic mixtures of different proportions and laboratory-made ophthalmic solution.

Lapatinib-based therapy for women with advanced/metastatic HER2 positive breast cancer.

BACKGROUND: Lapatinib alone or in combination with other agents, mostly capecitabine is used for patients with advanced/metastatic HER2 positive breast cancer (HER2(+)BC) after progression on trastuzumab based therapy. Here we report our experience with lapatinib based therapy in this setting. MATERIAL AND METHODS: 67 consecutive patients received lapatinib based therapy. 58 (86.6%) received lapatinib + capecitabine (LC), 7 (10.4%) with other agents and 2 (3.0%) as single agent lapatinib. Data was collected from patients' records retrospectively. RESULTS: Objective response to lapatinib based therapy in 64 evaluable patients was 64.0% in all patients and 64.0% in patients who received LC. Median progression free survival and overall survival were 10 and 27 months in all patients and 10 and 17 months in patients who received LC, respectively. 16 (24.0%) patients had dose delay > 1 week and/or dose reduction. CONCLUSION: Lapatinib based therapy is an effective treatment for women with advanced/metastatic HER2(+)BC after prior exposure to trastuzumab. It yields meaningful response rates, progression free and overall survival. Some patients require dose adjustments.

Isolation and Characterization of a Novel Imidacloprid-Degrading Mycobacterium sp. Strain MK6 from an Egyptian Soil.

Thus far, only a small number and types of bacteria with limited ability in degrading imidacloprid have been reported. Also, genes regulating imidacloprid (IMDA) degradation have yet to be discovered. To study this in more detail, an enrichment technique was used to isolate consortia and pure cultures of IMDA-degrading bacteria. Through this approach, we successfully isolated a novel bacterium capable of completely degrading IMDA as a sole nitrogen source. The bacterium was subsequently identified as Mycobacterium sp. strain MK6 by sequence analysis of its 16S rRNA gene (Genbank accession number KR052814 ). BLASTn searches indicated that 16S rRNA gene from Mycobacterium sp. strain MK6 was 99% identical to several Mycobacterium spp. Mycobacterium sp. strain MK6 transformed 99.7% added IMDA (150 µg mL(-1)) in <2 weeks (t1/2 = 1.6 days) to 6-chloronicotinic acid (6-CNA) as its major metabolite. Although the isolated strain and mixed bacterial consortia were able to degrade IMDA, they failed to grow further on 6-CNA, indicating a lack of IMDA mineralization to carbon dioxide. Small amounts of the desnitro-olefin and desnitro-degradates of IMDA were observed during the incubation but did not accumulate in culture medium.

Sorption-desorption of imidacloprid onto a lacustrine Egyptian soil and its clay and humic acid fractions.

Sorption-desorption of the insecticide imidacloprid 1-[(6-chloro-3-pyridinyl)-methyl]-N-nitro-2-imidazolidinimine onto a lacustrine sandy clay loam Egyptian soil and its clay and humic acid (HA) fractions was investigated in 24-h batch equilibrium experiments. Imidacloprid (IMDA) sorption-desorption isotherms onto the three sorbents were found to belong to a non-linear L-type and were best described by the Freundlich model. The value of the IMDA adsorption distribution coefficient, Kd(ads), varied according to its initial concentration and was ranged 40-84 for HA, 14-58 for clay and 1.85-4.15 for bulk soil. Freundlich sorption coefficient, Kf(ads), values were 63.0, 39.7 and 4.0 for HA, clay and bulk soil, respectively. The normalized soil Koc value for imidacloprid sorption was ∼800 indicating its slight mobility in soils. Nonlinear sorption isotherms were indicated by 1/n(ads) values <1 for all sorbents. Values of the hysteresis index (H) were <1, indicating the irreversibility of imidacloprid sorption process with all tested sorbents. Gibbs free energy (ΔG) values indicated a spontaneous and physicosorption process for IMDA and a more favorable sorption to HA than clay and soil. In conclusion, although the humic acid fraction showed the highest capacity and affinity for imidacloprid sorption, the clay fraction contributed to approximately 95% of soil-sorbed insecticide. Clay and humic acid fractions were found to be the major two factors controlling IMDA sorption in soils. The slight mobility of IMDA in soils and the hysteresis phenomenon associated with the irreversibility of its sorption onto, mainly, clay and organic matter of soils make its leachability unlikely to occur.