Intra-Operative Assessment of Sentinel Lymph Nodes in Breast Cancer

Lymph node status remains an important prognostic indicator for survival in breast cancer. Sentinel lymph node biopsy has become the standard method of assessment of clinically node negative breast cancers. Economic implications as well as patient related factors have lead to the development a number of intra-operative techniques. Review of the emerging trends in the last 4 years show that although routine histological examination remains the gold standard in most centres intra-operative assessment remains the most favourable, timely and cost-effective option to analyse sentinel nodes. Molecular techniques appear to be far more superior to other histological tests such as Frozen Section or Touch Imprint Cytology. Emerging research suggests that molecular techniques can be used to predict the presence of non sentinel node metastasis

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SENSITIVE SPECTROPHOTOMETRIC ASSAY OF MUSCARINIC RECEPTOR ANTAGONIST TOLTERODINE TARTRATE IN BULK DRUG AND PHARMACEUTICAL FORMULATIONS

Objective: Simple, sensitive, and accurate spectrophotometric methods have been developed for the assay of tolterodine tartrate (TOL) in bulk drugand pharmaceutical formulations.Methods: The proposed methods are based on oxidation reaction of TOL with a known excess of cerium(IV) ammonium sulfate as an oxidizing agentin acid medium followed by determination of unreacted oxidant by adding a fixed amount of dye, e.g., amaranth (AM), rhodamine 6G (Rh6G), andindigo carmine (IC) followed by measuring the absorbance at 520, 530, and 610 nm, respectively. The effect of experimental conditions was studiedand optimized.Results: The Beer's law was obeyed in the concentration ranges of 1.0-10, 1.0-12, and 0.5-9.0 μg/mL using AM, Rh6G, and IC dyes, respectively, witha correlation coefficient ≥0.9995. The calculated molar absorptivity values are 1.868×104, 1.008×104, and 1.623×104 L/mol/cm using AM, Rh6G, andIC dyes, respectively. The limits of detection and quantification were reported. Intraday and interday accuracy and precision of the methods have beenevaluated. No interference was observed from the additives.Conclusion: The proposed methods were successfully applied to the assay of TOL in tablets preparations, and the results were statistically comparedwith those of the reported method by applying Student's t-test and F-test. The reliability of the methods was further ascertained by performingrecovery studies using the standard addition method

POSSIBLE PROTECTIVE ROLE OF SODIUM SALICYLATE NANOEMULSION AND GINGER ON CISPLATIN‑INDUCED HEPATOTOXICITY IN RATS (BIOCHEMICAL AND HISTOPATHOLOGICAL STUDY)

Objective: To describe the preparation and characterization of nanoemulsion of sodium salicylate loaded butane tetracarboxylic acid (Bt-Sc-NPs). It also investigates the possible protective effects of Bt-Sc-NPs and\or medicinal plant ginger to evaluate the changes of liver functions, oxidative stress and histopathological investigations against cisplatin-induced hepatotoxicity. Methods: Serum was used to determine alanine aminotransferase (ALT), aspartate aminotransferase (AST), δ-glutamyl transferase (δGT), serum human laminin (LN) and tissue inhibitors of metalloproteinase1 (TIMP1). Liver tissue samples collected from the rats were used for the measurement of malondialdehyde (MDA), nitric oxide (NO) and paraoxonase 1 (PON1). Results: The beneficial effects of Bt-Sc-NPs with its anti-inflammatory effect and the medicinal ginger with its antioxidant effect were observed. Injection of rats with cisplatin significantly increased serum ALT, AST, ɤGT, TIMP1 and LN. It also increased cisplatin-induced oxidative stress by a significant elevation in liver MDA, NO content; however, a significant decrease of PON1 content. While protection with Bt-Sc-NPs or ginger significantly improved these parameters. In addition, combination of both Bt-Sc-NPs and ginger significantly induced a decrease in serum ALT, AST, ɤGT, TIMP1 and LN. It also reduced cisplatin-induced oxidative stress by the significant reduction in liver MDA, NO content and elevation of PON1 content much more than protection with Bt-Sc-NPs or ginger alone. Conclusion: Bt-Sc-NPs were synthesized using nanoemulsion with the help of homogenization and ultra-sonication waves. Combination with both of Bt-Sc-NPs and ginger showed a hepatoprotective role in ameliorating cisplatin‑induced hepatotoxicity due to their anti-inflammatory and antioxidant effects

VALIDATED SPECTROPHOTOMETRIC METHODS FOR DETERMINATION OF MONTELUKAST SODIUM IN PURE AND DOSAGE FORMS USING N-BROMOSUCCINIMIDE AND DYES

Objective: Simple, sensitive, precise, reproducible and validated spectrophotometric methods have been developed for the quantification of montelukast sodium as leukotriene receptor antagonist drug, in pure and dosage forms (tablets). Methods: The methods use N-bromosuccinimide (NBS) as an oxidant and three dyes, amaranth, methylene blue, and indigo carmine, as auxiliary reagents. The three methods are based on oxidation reaction of montelukast sodium with a known excess of N-bromosuccinimide (NBS) in acid medium, followed by determination of unreacted NBS by the reaction with a fixed amount of dyes, amaranth, methylene blue, and indigo carmine followed by the measurement of the absorbance at 520, 664 and 610 nm, respectively. Results: Under the optimum conditions, linear relationships with good correlation coefficients (0.9993-0.9996) were found over the concentration ranges of 0.5-10, 1.0-12 and 0.5-8.0 µg/ml with a limit of detection (LOD) of 0.15, 0.3 and 0.14 µg/ml using amaranth, methylene blue, and indigo carmine methods, respectively. Intra-day and inter-day accuracy and precision of the methods have been evaluated. No interference was observed from the common tablet excipients. Conclusion: The proposed methods were validated in accordance with ICH guidelines and successfully applied to the analysis of montelukast sodium in dosage forms (tablets). The reliability of the methods was further ascertained by performing recovery studies using the standard addition method. Statistical comparison of the results obtained by applying the proposed methods with those of the reported method by applying student’s t-test and F-test revealed good agreement

Sensitive spectrophotometric methods for determination of some organophosphorus pesticides in vegetable samples

Three rapid, simple, reproducible and sensitive spectrophotometric methods (A, B and C) are described for the determination of two organophosphorus pesticides, (malathion and dimethoate) in formulations and vegetable samples. The methods A and B involve the addition of an excess of Ce4+ into sulphuric acid medium and the determination of the unreacted oxidant by decreasing the red color of chromotrope 2R (C2R) at a suitable lmax = 528 nm for method A, or a decrease in the orange pink color of rhodamine 6G (Rh6G) at a suitable lmax = = 525 nm. The method C is based on the oxidation of malathion or dimethoate with the slight excess of N-bromosuccinimide (NBS) and the determination of unreacted oxidant by reacting it with amaranth dye (AM) in hydrochloric acid medium at a suitable lmax = 520 nm. A regression analysis of Beer-Lambert plots showed a good correlation in the concentration range of 0.1-4.2 μg mL−1. The apparent molar absorptivity, Sandell sensitivity, the detection and quantification limits were calculated. For more accurate analysis, Ringbom optimum concentration ranges are 0.25-4.0 μg mL−1. The developed methods were successfully applied to the determination of malathion, and dimethoate in their formulations and environmental vegetable samples

UTILITY OF CERTAIN σ AND π-ACCEPTORS FOR THE SPECTROPHOTOMETRIC DETERMINATION OF VORICONAZOL ANTIFUGAL DRUG IN PHARMACEUTICAL FORMULATION

Objective: Studies were carried out, for the first time, to investigate the charge-transfer reactions of voriconazole antifungal drug (VOR) as n-electron donor with the σ-acceptor iodine (I2) and various Ï€-acceptors: 7,7,8,8-tetracyanoquinodimethane (TCNQ); 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and p-chloranilic acid (p-CLA).Methods: The formation of the colored charge-transfer complexes were utilized in the development of simple, rapid and accurate spectrophotometric methods for the analysis of voriconazole in pure form as well as in its pharmaceutical formulation (tablets). Different variables affecting the reactions were studied and optimized.Results: Under the optimum reaction conditions, linear relationships with good correlation coefficients (0.9994–0.9999) were found between the absorbance and the concentration of voriconazole in the range of 2.0–120 μg mL−1. For more accurate analysis, Ringbom optimum concentration range was found to be between 4.0-110 μg mL-1. The limits of detection ranged from 0.36 to 1.23 μg mL−1andthe limits of quantification ranged from 1.20 to 4.10 μg mL−1. A Job's plot of the absorbance versus the molar ratio of voriconazole to each of acceptors under consideration indicated (1:1) ratio.Conclusion: The proposed methods were applied successfully for simultaneous determination of voriconazole in tablets with good accuracy and precision and without interferences from common additives. The results were compared favourably with the reported method.Â

GREEN VORTEX-ASSISTED IONIC LIQUID-BASED DISPERSIVE LIQUID-LIQUID MICROEXTRACTION FOR ENRICHMENT AND DETERMINATION OF CADMIUM AND LEAD IN WATER, VEGETABLES AND TOBACCO SAMPLES

Objective: An eco-friendly, simple and sensitive vortex-assisted ionic liquid-based dispersive liquid-liquid microextraction method (VA-IL-DLLµE) has been proposed to enrich and determine trace levels of cadmium (Cd2+ ) and lead (Pb2+ ) ions in water, vegetables and tobacco samples, prior to its FAAS determination. Methods: The proposed method based on utilization of ionic liquid (IL) (1-hexyl-3-methylimidazolium tris(pentafluoroethyl)trifluorophosphate [HMIM][FAP]) as an extraction solvent for both ions after the complexation with 4,5-dihydroxy-3-phenylazo-2,7-naphthalenedisulfonic acid, disodium salt (Chromotrope 2R) at pH 6.5. The impact of different analytical parameters on microextraction efficiency was optimized. Results: In the ranges of 1.0–300 and 2.0-400 μg/ml, the calibration graphs were linear. The limits of detection were 0.3 and 0.6 μg/ml for Cd2+ and Pb2+ ions, respectively. The preconcentration factor was 100. The relative standard deviation (RSD %)<3.0%, which indicates the proposed method has high precision. Conclusion: The proposed VA-IL-DLLµE method was developed and applied for the estimation of Cd2+ and Pb2+ ion content in various water, vegetables and tobacco samples, and satisfactory results were obtained. The obtained recovery values showed good agreement with the certified values

Photodynamic Therapy in Primary Breast Cancer

Photodynamic therapy (PDT) is a technique for producing localized necrosis with light after prior administration of a photosensitizing agent. This study investigates the nature, safety, and efficacy of PDT for image-guided treatment of primary breast cancer. We performed a phase I/IIa dose escalation study in 12 female patients with a new diagnosis of invasive ductal breast cancer and scheduled to undergo mastectomy as a first treatment. The photosensitizer verteporfin (0.4 mg/kg) was administered intravenously followed by exposure to escalating light doses (20, 30, 40, 50 J; 3 patients per dose) delivered via a laser fiber positioned interstitially under ultrasound guidance. MRI (magnetic resonance imaging) scans were performed prior to and 4 days after PDT. Histological examination of the excised tissue was performed. PDT was well tolerated, with no adverse events. PDT effects were detected by MRI in 7 patients and histology in 8 patients, increasing in extent with the delivered light dose, with good correlation between the 2 modalities. Histologically, there were distinctive features of PDT necrosis, in contrast to spontaneous necrosis. Apoptosis was detected in adjacent normal tissue. Median follow-up of 50 months revealed no adverse effects and outcomes no worse than a comparable control population. This study confirms a potential role for PDT in the management of early breast cancer