Titrimetric determination of acetylenic hypnotics using organic brominating agents

A titrimetric method is described for the determination of three acetylenic hypnotics, namely ethchlorvynol, ethinamate, and methylpentynol carbamate, in bulk and in dosage forms. The method involves the use of either 1,3-dibromo-5,5-dimethylhydantoin (DBH),N-bromosuccinimide (NBS) orN-bromophthalimide (NBP) as titrants. A known excess volume of the reagent is added and, after the specified time, the residual reagent is determined iodometrically. This procedure permits semimicro determination (1–15 mg) of the drug. The procedure has been successfully applied to pharmaceutical dosage forms; the results agree well with those given by compendial methods. The stoichiometry of the reaction has been assessed and an explanation of the reaction pathway is presented.     

Asynchronous adenoid cystic carcinoma of the prostate and transitional cell carcinoma of the urinary bladder

Histologic variants of prostatic carcinoma are readily recognized. In this report, we describe a rare variant, adenoid cystic carcinoma, in a 75-year-old man previously diagnosed to have transitional cell carcinoma of the urinary bladder. The diagnosis of adenoid cystic carcinoma was made by the characteristic microscopic features of the tumor morphologically and immunohistochemically. Two months later he was found to have metastatic disease. The patient's treatment consisted of chemotherapy in combination with prednisone and hormonal therapy. Five and a half months after diagnosis, he died with metastatic disease. Making this case unique is the asynchronous occurrence of this variant with transitional cell carcinoma of the urinary bladder, which has never been reported in the literature. We discussed the histopathologic and immunohistochemical features of adenoid cystic carcinoma of the prostate with review of literature.     

Influence of Temik (Aldicarb) on herbicide persistence in cultivated cotton field soil under field conditions

Summary The effect of the insecticide Temik on the persistence of the herbicides Cotoran and Cobex was investigated in cultivated cotton fields. Temik was applied to the soil which had also been treated with Gotoran or Cobex. Residues were determined at 15 day-intervals for four months. Temik was found to inhibit the degradation of both compounds as long as it persisted. As Temik disappeared the degradation of Cotoran and Cobex increased, attaining after the 15th day the rates shown by Cotoran and Cobex when applied in isolation.     

The effects of vascular occlusion on the human inner ear

Occlusion of the anterior vestibular artery has resulted in severe degeneration and new bone formation limited to the utricle, saccule, and superior and lateral semicircular canals. Depriving the inner ear of its main blood supply, i.e. the internal auditory artery, has resulted in severe degeneration and ossification of the entire membranous labyrinth, except the endolymphatic duct and sac. A more severe cochlear sclerosis was seen when both arterial and venous blood supplies to the cochlea were occluded. The implications of these findings on the etiology and management of inner ear disorders are emphasized.     

Neoadjuvant chemotherapy followed by concurrent chemo-radiation therapy in locally advanced nasopharyngeal carcinoma

PURPOSE: To evaluate the efficacy and outcomes of neoadjuvant cisplatinum and epirubicin chemotherapy followed by concurrent cisplatinum chemotherapy with radiotherapy in patients with locally advanced nasopharyngeal carcinoma. METHODS AND MATERIALS: One hundred ten patients (80 male, 30 female) with locally advanced nasopharyngeal carcinoma, staged according to the 1997 International Union Against Cancer/American Joint Committee on Cancer classification system as IIB (n = 9), III (n = 20), IVA (n = 32), and IVB (n = 49), World Health Organization types II (n = 25) and III (n = 85), were included in this protocol between January 1998 and July 2000 at King Faisal Specialist Hospital and Research Centre. Patients underwent two cycles of induction chemotherapy with cisplatinum 100 mg/m(2) and epirubicin 70 mg/m(2) on Days 1 and 21, followed by a radical course of radiotherapy (6,600 cGy in 6.5 weeks, 200 cGy/fraction) starting on Day 42, with three cycles of concurrent cisplatinum 25 mg/m(2) for 4 days on Days 42, 63, and 84. RESULTS: Of 110 patients included in this study, intracranial extension was present in 32 (29%), and nodal stage was N3 in 49 (45%). Complete remission and partial remission were achieved in 87 patients (79%) and 23 patients (21%), respectively. At a median follow-up for surviving patients of 37 months (22-55 months), 49 of 110 patients (44%) had failed treatment: 12 with local, 9 with regional nodes, 4 locoregional, 5 locoregional plus distant areas, and 19 with distant metastases. At the time of writing, 34 patients had died; all deaths were related to the patients' cancer except for 1 patient with treatment-related toxicity. Three-year actuarial overall survival, relapse-free survival, locoregional control, and distant metastasis-free survival rates were 89%, 78%, 88%, and 89% for patients with stage IIB; 71%, 70%, 89%, and 74% for stage III; 68%, 49%, 61%, and 77% for stage IVA; and 70%, 45%, 60%, and 69% for stage IVB, respectively. One patient received only one induction cycle; all others received two cycles; however, 9 of them required 20% reduction in the second cycle dose. Ninety patients (82%) completed two or more concurrent cycles of cisplatinum. Rates of Grade 3 and 4 reactions after induction chemotherapy were as follows: anemia 1% and 0%, leukopenia 8% and 4%, nausea 27% and 0%, vomiting 25% and 0%, and infection 4% and 4%, respectively. Acute Grade 3 and 4 reactions were also observed during chemoradiotherapy: anemia 1% and 0%, leukopenia 31% and 4%, nausea 35% and 0%, vomiting 26% and 2%, infection in 4% and 2%, mucositis in 49% and 0%, and skin reaction in 39% and 0%, respectively. CONCLUSIONS: Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy is a safe and effective method of treatment for locally advanced nasopharyngeal carcinoma. Further investigations in prospective studies are required to evaluate this regimen.     

Voltammetric study of danazol and its determination in capsules and spiked biological fluids

The voltammetric behaviour of danazol DZ (antigonadotropin) was studied using cyclic voltammetry, direct current, differential pulse polarography (DPP) and alternating current polarography. Danazol exhibited irreversible cathodic waves over the pH range of 1-5 in Britton Robinson buffers. At pH 1 (the analytical pH), a well-defined wave with E1/2 of -1.04 V versus Ag/AgCl reference electrode was obtained. The diffusion current constant (Id) was 4.8+/-0.14 microA.L.m mole(-1) and the current-concentration plot was rectilinear over the range from 5 x 10(-6) to 1 x 10(-4) M with correlation coefficient (n = 11) of 0.995. The calculated detection limit was 1 x 10(-6) M using the DPP mode. The wave was characterized as being irreversible, diffusion-controlled although adsorption phenomenon played a limited role in the electrode process. The proposed method was applied to commercial capsules and the average percentage recovery was in agreement with that obtained by the official USP method. The method was extended to the in vitro determination of DZ in spiked human urine and plasma samples, the percentage recoveries were 96+/-4 and 97+/-5, respectively. A proposal of the electrode reaction was postulated.     

Voltammetric determination of montelukast sodium in dosage forms and human plasma

The voltammetric behaviour of montelukast (MKST) was studied using cyclic voltammetry, direct current (DCt), differential pulse polarography (DPP) and alternating current (ACt) polarography. MKST exhibited well-defined cathodic waves over the range pH range 1-5. No anodic waves were produced over the same pH range. At pH 1, the analytical pH; the diffusion current constant (Id) was 2.2+/-0.01 microA l mmol-1. The current concentration plot was rectilinear over the range 2-20 microg ml-1 with correlation coefficient (n=10) of 0.9943. The lower limit of detection (S/N=2) was 0.2 microg ml-1 (3.41x10(-7) M). The wave has been characterised as being diffusion-controlled, although adsorption phenomenon played a limited role in the electrode reaction. The proposed method was successfully applied to the determination of MKST in commercial tablets, and results were in agreement with those given with a reference HPLC method. The method was further extended to the in vitro determination of the drug in spiked human plasma. The mean % recovery (n=5) was 101.38+/-3.85. The number of electrons transferred in the reduction process could be accomplished and a proposal of the electrode reaction was proposed.     

Differential pulse cathodic voltammetric determination of floctafenine and metopimazine

A simple, rapid and sensitive voltammetric method for the determination of floctafenine (FFN) and metopimazine (MPZ) was developed. Well-defined cathodic waves were obtained for both drugs in Britton-Robinson buffer pH 9.0 using the differential-pulse mode at the hanging mercury drop electrode (HMDE). The current-concentration relationship was found to be linear over the ranges 0.4-3.6 and 0.4-2.4 microg ml(-1) for FFN and MPZ, respectively. The quantification of the two drugs in their pharmaceutical formulations was carried out using the proposed voltammetric method and compared with spectrophotometric analysis data. The mechanisms of the electrode reactions for the two drugs were proposed.     

Transforming growth factor beta cooperates with persephin for dopaminergic phenotype induction

The aim of the present study was to investigate the putative cooperative effects of transforming growth factor beta (TGF-beta) and glial cell line-derived neurotrophic factor (GDNF) family ligands in the differentiation of midbrain progenitors toward a dopaminergic phenotype. Therefore, a mouse midbrain embryonic day (E) 12 neurospheres culture was used as an experimental model. We show that neurturin and persephin (PSPN), but not GDNF, are capable of transient induction of dopaminergic neurons in vitro. This process, however, requires the presence of endogenous TGF-beta. In contrast, after 8 days in vitro GDNF rescued the TGF-beta neutralization-dependent loss of the TH-positive cells. In vivo, at E14.5, no apparent phenotype concerning dopaminergic neurons was observed in Tgf-beta2(-/-)/gdnf(-/-) double mutant mice. In vitro, combined TGF-beta/PSPN treatment achieved a yield of approximately 20% TH-positive cells that were less vulnerable against 1-methyl-4-phenyl pyridinium ion toxicity. The underlying TGF-beta/PSPN differentiation signaling is receptor-mediated, involving p38 mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways. These results indicate that phenotype induction and survival of fully differentiated neurons are accomplished through distinct pathways and individual factor requirement. TGF-beta is required for the induction of dopaminergic neurons, whereas GDNF is required for regulating and/or maintaining a differentiated neuronal phenotype. Moreover, this study suggests that the combination of TGF-beta with PSPN is a potent inductive cocktail for the generation of dopaminergic neurons that should be considered in tissue engineering and cell replacement therapies for Parkinson's disease.