Role of high resolution computed tomography (HRCT) of the chest in the diagnosis of lymphangioleiomyomatosis (LAM) – A serial study of 15 patients

AbstractAim of workTo highlight the characteristic high resolution computed tomography (HRCT) findings in 15 patients diagnosed with lymphangioleiomyomatosis (LAM), narrowing the wide range of ILD and allowing accurate diagnosis preventing unnecessary interventional procedures.Patients and methods15 female patients ranged in age from 17 to 55years (mean age=40.33years). ILD was suspected based on clinical examination and chest radiographs. They were referred to do HRCT chest for further assessment. A 64 MSCT scanner was used.ResultsAll patients showed bilateral multiple cysts showing upper lobar predominance in 13.3% of cases and lower lobar one in 6.7%. The size of the cysts ranged from few mms to 3cm with variable wall thickness. Pneumothorax was reported in three patients and pulmonary hypertension in 15 cases.ConclusionHRCT is a valued diagnostic tool for diagnosis of LAM showing characteristic features for the disease

Simple Spectrophotometric Method for Determination of Paroxetine in Tablets Using 1,2-Naphthoquinone-4-Sulphonate as a Chromogenic Reagent

Simple and rapid spectrophotometric method has been developed and validated for the determination of paroxetine (PRX) in tablets. The proposed method was based on nucleophilic substitution reaction of PRX with 1,2-naphthoquinone-4-sulphonate (NQS) in an alkaline medium to form an orange-colored product of maximum absorption peak (λmax) at 488 nm. The stoichiometry and kinetics of the reaction were studied, and the reaction mechanism was postulated. Under the optimized reaction conditions, Beer's law correlating the absorbance (A) with PRX concentration (C) was obeyed in the range of 1–8 μg mL−1. The regression equation for the calibration data was: A = 0.0031 + 0.1609 C, with good correlation coefficients (0.9992). The molar absorptivity (ε) was 5.9 × 105 L mol−1 1 cm−1. The limits of detection and quantitation were 0.3 and 0.8 μg mL−1, respectively. The precision of the method was satisfactory; the values of relative standard deviations did not exceed 2%. The proposed method was successfully applied to the determination of PRX in its pharmaceutical tablets with good accuracy and precisions; the label claim percentage was 97.17 ± 1.06 %. The results obtained by the proposed method were comparable with those obtained by the official method

New Spectrophotometric and Fluorimetric Methods for Determination of Fluoxetine in Pharmaceutical Formulations

New simple and sensitive spectrophotometric and fluorimetric methods have been developed and validated for the determination of fluoxetine hydrochloride (FLX) in its pharmaceutical formulations. The spectrophotometric method was based on the reaction of FLX with 1,2-naphthoquinone-4-sulphonate (NQS) in an alkaline medium (pH 11) to form an orange-colored product that was measured at 490 nm. The fluorimetric method was based on the reaction of FLX with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) in an alkaline medium (pH 8) to form a highly fluorescent product that was measured at 545 nm after excitation at 490 nm. The variables affecting the reactions of FLX with both NQS and NBD-Cl were carefully studied and optimized. The kinetics of the reactions were investigated, and the reaction mechanisms were presented. Under the optimum reaction conditions, good linear relationships were found between the readings and the concentrations of FLX in the ranges of 0.3–6 and 0.035–0.5 μg mL−1 for the spectrophotometric and fluorimetric methods, respectively. The limits of detection were 0.1 and 0.01 μg mL−1 for the spectrophotometric and fluorimetric methods, respectively. Both methods were successfully applied to the determination of FLX in its pharmaceutical formulations

Open-array analysis of genetic variants in Egyptian patients with type 2 diabetes and obesity

Background: Diabetes mellitus is considered a major public health problem worldwide. Susceptibility to diabetes is influenced by both genetic and environmental determinants.Aims/hypothesis: The aim of the present study was to test for 16 independent single nucleotide polymorphisms (SNPs) in established Type 2 diabetes (T2D) and obesity susceptibility loci by GWAS in a sample of Egyptian patients to find out if there is shared genetic background underlying both disease entities.Methods: Genotyping was performed using OpenArray protocol on the QuantStudioTM 12K Flex Real- Time PCR System. In the present case control study a custom array was designed to facilitate costeffective analysis of selected SNPs related to glycolysis, gluconeogenesis, inflammation, insulin signalling, and immune function.Results: Seven gene variants showed significant association with the risk of T2D patients including FCGRA2, STAT4, CELSR2, PPARG, EXT2 rs3740878, GCKR, PTGS1. Factors that significantly affect T2D were obesity (p < 0.001) and GCKR (p = 0.001) and PTGS1 (p = 0.001) gene variants. Gene variants that showed significant or borderline effect on obesity were MTHFD1, EXT2 rs3740878, GCKR and PTGS1 (p = 0.03, 0.017, 0.059, 0.006) respectively.Conclusions/interpretation: Overlapping genetic aspects should be considered and the presence of risk alleles of different genes together could contribute to the risk of T2D or obesity or both. The MTHFD1 and EXT2rs3740878 gene variants significantly affect obesity and not shared with T2D. Gene variants that showed combined effect on both disease entities were GCKR and PTGS1. These findings provide a basis for future studies on a larger scale. More stress on the risk gene variants that have a combined impact on both diabetes and obesity is recommended to improve risk prediction and preventive strategies

Tunable polymeric mixed micellar nanoassemblies of Lutrol F127/Gelucire 44/14 for oral delivery of praziquantel: a promising nanovector against hymenolepis nana in experimentally-infected rats

Hymenolepiasis represents a parasitic infection of common prevalence in pediatrics with intimidating impacts, particularly amongst immunocompromised patients. The present work aimed to snowball the curative outcomes of the current mainstay of hymenolepiasis chemotherapy, praziquantel (PRZ), through assembly of polymeric mixed micelles (PMMs). Such innovative nano-cargo could consolidate PRZ hydrosolubility, extend its circulation time and eventually upraise its bioavailability, thus accomplishing a nanoparadigm for hymenolepiasis tackling at lower dose levels. For consummating this goal, PRZ-PMMs were tailored via thin-film hydration technique integrating a binary system of Lutrol F127 and Gelucire 44/14. Box-Behnken design was planned for optimizing the nanoformulation variables employing Design-Expert® software. Also, in Hymenolepis nana-infected rats, the pharmacodynamics of the optimal micellar formulation versus the analogous crude PRZ suspension were scrutinized on the 1st and 3rd days after administration of a single oral dose (12.5 or 25 mg/kg). Moreover, in vitro ovicidal activity of the monitored formulations was estimated utilizing Fuchsin vital stain. Furthermore, the in vivo pharmacokinetics were assessed in rats. The optimum PRZ-PMMs disclosed conciliation between thermodynamic and kinetic stability, high entrapment efficiency (86.29%), spherical nanosized morphology (15.18 nm), and controlled-release characteristics over 24 h (78.22%). 1H NMR studies verified PRZ assimilation within the micellar core. Additionally, the in vivo results highlighted a significant boosted efficacy of PRZ-PMMs manifested by fecal eggs output and worm burden reduction, which was clearly evident at the lesser PRZ dose, besides a reversed effect for the intestinal histological disruptions. At 50 µg/mL, PRZ-PMMs increased the percent of non-viable eggs to 100% versus 47% for crude PRZ, whilst shell destruction and loss of embryo were only clear with the applied nano-cargo. Moreover, superior bioavailability by 3.43-fold with elongated residence time was measured for PRZ-PMMs compared to PRZ suspension. Practically, our results unravel the potential of PRZ-PMMs as an oral promising tolerable lower dose nanoplatform for more competent PRZ mass chemotherapy

Sodomy of Adolescent Males Presented to Pediatric Psychiatric Outpatient Clinic: A Case Series

Traditional Arab culture hides male sexual abuse and considers it a shame. Instead of treating male victims of sexual assault, they are often stigmatized as homosexual individuals. Moreover, guardians of sexually abused boys are also negatively affected. They have to choose between reporting abuse to a legal authority with the risk of labeling their child or keeping a close eye on them to prevent further abuse. However, reporting abuse to healthcare authorities does take place. Disclosing sexual abuse in the privacy of a psychiatric clinic is often the only way for victims to be successfully treated for the psychological effects of such abuse

Greenness assessment of HPLC analytical methods with common detectors for assay of paracetamol and related materials in drug products and biological fluids

Abstract Paracetamol is one of the most widely consumed analgesic and antipyretic medications worldwide. It is frequently analyzed in many quality control (QC) laboratories in pharmaceutical companies, either in raw materials or drug products. It was reported that paracetamol self-toxicity often occurs, leading to the frequent analysis of paracetamol in toxicological centers in biological fluids. Green analytical chemistry (GAC) is growing to be a global philosophy; therefore, the high frequency of paracetamol analysis poses potential concerns. Chromatographic analytical methods used for the daily analysis of paracetamol could be a potential risk to the environment or the health of the analysts if not thoroughly considered. The presented study aims to establish greenness assessments of nine HPLC methods used to assay paracetamol in raw materials and drug products and twenty-one HPLC methods. The reason for selecting HPLC methods of analysis to be the core of the study is the known reproducibility, reliability and availability in most QC laboratories. The most commonly used metric systems for greenness evaluation are the Analytical GREEnness (AGREE), the eco-scale assessment (ESA) and the national environmental methods index (NEMI) which have been used in this comparative study. The greenest chromatographic method for the analysis of paracetamol in raw materials and drug products was introduced by Rao et al. (the obtained scores were ESA = 76 and AGREE = 0.62, while the greenest chromatographic method for the analysis of paracetamol in biological fluids was proposed by Modick et al.). The obtained scores were ESA = 85 and AGREE = 0.7. The NEMI tool proved to have limited performance compared to other metric systems, hence it could not be used alone. Accordingly, the collaboration of NEMI results with ESA and AGREE for greenness assessment is highly recommended to reach appropriate conclusions

New FTY720-docetaxel nanoparticle therapy overcomes FTY720-induced lymphopenia and inhibits metastatic breast tumour growth

Purpose: Combining molecular therapies with chemotherapy may offer an improved clinical outcome for chemoresistant tumours. Sphingosine-1-phosphate (S1P) receptor antagonist and sphingosine kinase 1 (SK1) inhibitor FTY720 (FTY) has promising anticancer properties, however, it causes systemic lymphopenia which impairs its use in cancer patients. In this study, we developed a nanoparticle (NP) combining docetaxel (DTX) and FTY for enhanced anticancer effect, targeted tumour delivery and reduced systemic toxicity. Methods: Docetaxel, FTY and glucosamine were covalently conjugated to poly(lactic-co-glycolic acid) (PLGA). NPs were characterised by dynamic light scattering and electron microscopy. The cellular uptake, cytotoxicity and in vivo antitumor efficacy of CNPs were evaluated. Results: We show for the first time that in triple negative breast cancer cells FTY provides chemosensitisation to DTX, allowing a four-fold reduction in the effective dose. We have encapsulated both drugs in PLGA complex NPs (CNPs), with narrow size distribution of ~ 100 nm and excellent cancer cell uptake providing sequential, sustained release of FTY and DTX. In triple negative breast cancer cells and mouse breast cancer models, CNPs had similar efficacy to systemic free therapies, but allowed an effective drug dose reduction. Application of CNPs has significantly reversed chemotherapy side effects such as weight loss, liver toxicity and, most notably, lymphopenia. Conclusions: We show for the first time the DTX chemosensitising effects of FTY in triple negative breast cancer. We further demonstrate that encapsulation of free drugs in CNPs can improve targeting, provide low off-target toxicity and most importantly reduce FTY-induced lymphopenia, offering potential therapeutic use of FTY in clinical cancer treatment