With the increased production of new fixed combinations and cheaper generic drugs, the need for a single, sensitive and reliable analytical method is hugely evoked to cover the versatile and prerequisite tests of in-vitro and in-vivo bioequivalence studies. A new fixed dose combination, containing dutasteride (DUT) and silodosin (SLD), has been recently launched for relieving moderate and severe symptoms of benign prostatic hyperplasia. Consequently, this concurrent study was dedicated to present, for the first time, eco-friendly high-performance liquid chromatographic (HPLC) methods coupled with dual-mode detection, for the simultaneous quantification of both drugs in versatile real samples. The optimized chromatographic separation was achieved on a Waters XBridge® (150×4.6 mm, 5 μm) C18 analytical column with a mobile phase composed of methanol & phosphate buffer pH 6.0 at ratio (77: 23, v/v) and pumped at 1.0 mL/min flow rate. In the first HPLC method, drug quantification was performed at 245 nm achieving linearity range of 3–120 µg/mL, while the second one made good use of the unique features of both drugs in possessing native fluorescence for more sensitive linearity ranges (50–1000 ng/mL for DUT & 80–2500 ng/mL for SLD). Both methods were validated and successfully applied for assay dosage forms as well as testing content uniformity. In addition, the capability of the proposed HPLC-fluorometric method in detecting drugs in nano-gram scale paved the way not only for studying their dissolution behavior in various dissolution media but also analyzing spiked human plasma samples extracted by liquid-liquid extraction. Finally, sustainability of the proposed methods was clearly declared, in comparison to the official ones, via environmental, health and safety (EHS) tool and analytical greenness (AGREE) software.

AIMS: Depression is one of the common neurological comorbidities in patients with inflammatory bowel disease (IBD). The current study aimed to investigate the potential impact of niacin on colitis-induced depressive-like behavior in rats.

MATERIALS AND METHODS: Animals were given 5 % dextran sulfate sodium (DSS) in drinking water for one week to induce colitis. Niacin (80 mg/kg), with or without mepenzolate bromide (GPR109A blocker), was administered once per day throughout the experimental period. Rats were tested for behavioral changes using open field and forced swimming tests.

KEY FINDINGS: Niacin significantly ameliorated DSS-induced behavioral deficits and alleviated macroscopic and microscopic colonic inflammatory changes. It also augmented the hippocampal levels of ZO-1, occludin, and claudin-5 proteins, indicating the ability of niacin to restore the blood-brain barrier (BBB) integrity. Moreover, niacin decreased hippocampal IL-1ꞵ and NF-ĸB contents but increased GSH, Sirt-1, Nrf-2, HO-1 concentrations. All these beneficial effects were partially abolished by the co-administration of mepenzolate bromide.

SIGNIFICANCE: The neuroprotective effect of niacin against DSS-induced depressive-like behavior was partially mediated through GPR109A-mediated mechanisms. Such mechanisms are also involved in modulating neuronal oxidative stress and inflammation via Sirt-1/Nrf-2/HO-1 signaling pathways.

The large popularity and rapid technology of smartphones have opened new avenues for their integration into different analytical methodologies and drug quality monitoring as a portable, easily accessible, and user-friendly detector. Herein, a novel and portable smartphone-based high-performance thin layer chromatographic (HPTLC) approach is proposed for the simultaneous analysis of two urological drugs, alfuzosin and solifenacin, which treat benign prostatic hyperplasia accompanied by overactive bladder syndrome. First, chromatographic separation was accomplished using an ecofriendly mobile phase, then the developed plates were visualized using Dragendorff's reagent and photographed a smartphone's rear-facing camera fixed on a fabricated two-illumination-source chamber. The intensities of the drug spots were quantified using open-source image analysis software ImageJ over the concentration ranges of 2.0 to 30.0 μg per band for both drugs with acceptable results in ICH validation parameters. To improve the method's accuracy and reproducibility, various construction and shooting key parameters were investigated and optimized. Moreover, the study was extended to compare the obtained results with those of a benchtop densitometric method using a Camag TLC Scanner 3 at 215.0 nm; the densitometric method provided an additional assessment tool for peak purity and was capable of assaying lower drug concentrations over a linearity range of 0.2-8.0 μg per band for alfuzosin and 0.1-6.0 μg per band for solifenacin. The fast, simple, reliable, green merits of the proposed HPTLC/smartphone method suggest that it is an excellent platform for assaying marketed combined capsules and assuring their content uniformity. Moreover, the high sensitivity of the densitometric method was used, for the first time, to determine the residual content of the cited drugs on manufacturing equipment surfaces for cleaning validation. Finally, the environmental impact of the developed methods was evaluated based on green analytical chemistry principles.

PURPOSE OF REVIEW: Over the past few decades, cystinosis, a rare lysosomal storage disorder, has evolved into a treatable metabolic disease. The increasing understanding of its pathophysiology has made cystinosis a prototype disease, delivering new insights into several fundamental biochemical and cellular processes.

RECENT FINDINGS: In this review, we aim to provide an overview of the latest advances in the pathogenetic, clinical, and therapeutic aspects of cystinosis.

SUMMARY: The development of alternative therapeutic monitoring strategies and new systemic and ocular cysteamine formulations might improve outcome of cystinosis patients in the near future. With the dawn of stem cell based therapy and new emerging gene-editing technologies, novel tools have become available in the search for a cure for cystinosis.

BACKGROUND: Many authors have described cytologic features in a variety of melanocytic lesions but, to our knowledge, a statistical analysis of sensitivity, specificity, and overall accuracy of these features alone or in combination has not been performed.

OBJECTIVE: We sought to determine the diagnostic value of nuclear and cytoplasmic characteristics in the diagnosis of melanocytic lesions via multivariate statistical analysis.

METHODS: This is a retrospective observational study conducted on 300 melanocytic lesions. We evaluated a series of distinctive features; subsequently a multivariate model was used to determine sensitivity and specificity.

RESULTS: Major features that favor a diagnosis of melanoma include: pleomorphism with enlarged nuclei, mitotic figures, notching/corrugation of the nuclear envelope, and peppered moth nucleus. Features with intermediate value include: solid hyperchromasia, vesicular nucleus with single round nucleolus, and nuclear/cytoplasmic ratio greater than 4:1.

LIMITATIONS: Limitations of this study include its retrospective nature, and the reliance on the original diagnostic classification of each neoplasm.

CONCLUSION: Our data suggest that some nuclear alterations have greater value in the diagnosis of benign and malignant melanocytic lesions.

BACKGROUND: Interpretation of Clark's nevi has generated debate over the years; although criteria have been proposed for grading morphological features of melanocytes, there is still confusion and variability in the assessment of these lesions.

METHODS: This is a retrospective observational study conducted on 100 Clark's nevi and 84 melanomas. A single expert dermatopathologist evaluated all blinded and randomized photomicrographs of both the Clark's nevi and melanomas for the presence of 14 cytologic features. Subsequently, a multivariate model was used to obtain sensitivity and specificity.

RESULTS: Clark's nevi showed a significantly higher frequency of absent-or-inconspicuous nucleoli over melanoma, whereas mitotic figures, pleomorphism, notching, multiple nucleoli, peppered moth nuclear pattern, flattened adjacent nuclei, prominent nucleoli and vesicular nucleus with rounded nucleoli were found significantly higher in frequency in melanomas.

CONCLUSION: Our data suggest that nuclear alterations are of value in the differentiation of atypical nevi from melanoma.

BACKGROUND: Interpretation of Clark's nevi has generated debate over the years; although criteria have been proposed for grading morphological features of melanocytes, there is still confusion and variability in the assessment of these lesions.

METHODS: This is a retrospective observational study conducted on 100 Clark's nevi and 84 melanomas. A single expert dermatopathologist evaluated all blinded and randomized photomicrographs of both the Clark's nevi and melanomas for the presence of 14 cytologic features. Subsequently, a multivariate model was used to obtain sensitivity and specificity.

RESULTS: Clark's nevi showed a significantly higher frequency of absent-or-inconspicuous nucleoli over melanoma, whereas mitotic figures, pleomorphism, notching, multiple nucleoli, peppered moth nuclear pattern, flattened adjacent nuclei, prominent nucleoli and vesicular nucleus with rounded nucleoli were found significantly higher in frequency in melanomas.

CONCLUSION: Our data suggest that nuclear alterations are of value in the differentiation of atypical nevi from melanoma.

OBJECTIVE: To describe demographic, genetic, and clinical characteristics of patients with neuronopathic Gaucher disease (NGD).

METHODS: All patients enrolled in the Neurological Outcomes Subregistry of the International Collaborative Gaucher Group (ICGG) Gaucher Registry as of June 2007 were identified.

RESULTS: The study cohort comprised 131 patients from 17 countries who were enrolled in the Neurological Outcomes Subregistry. The onset of neurological manifestations had occurred before 2 years of age in 47% (61 out of 131 patients), 2 years of age or older in 41% (54 out of 131), and could not be ascertained in the remaining 12% (16 out of 131). The most common manifestations were inability to look to the extreme up or down (45%, 55 out of 123), abnormally slow object tracking (43%, 53 out of 123), convergent squint (36%, 44 out of 121), and ataxia (15 to 20%, 18-27 out of 117). Seizures were reported in 19 out of 122 patients (16%), and myoclonic seizures were reported in 3 out of 121 patients (2%). The most common genotypes were L444P/L444P (76 out of 108, 70%), L444P/D409H (9 out of 108, 8%), D409H/D409H (8 out of 108, 7%), and L444P/rare allele (6 out of 108, 6%); full sequencing was not performed in all patients.

CONCLUSIONS: Neurological manifestations of GD often begin to appear before the age of 2 years. The most common neurological signs and manifestations are brainstem abnormalities and fine motor dysfunction. The most common genotype is L444P/L444P.