Dieulafoy's disease is a vascular anomaly characterized by the presence of a dysplastic artery that is related to an epithelial ulcer. The French surgeon Georges Dieulafoy first described it in 1898. Most frequently, it is a gastrointestinal condition, but occurrence in the bronchus has been reported in a few cases. The case of a 52-year-old man with massive hemoptysis, for which he underwent successful embolotherapy 10 years previously, is described. Over the next 10 years, he had several hospital admissions due to hemoptysis, and he underwent successful embolotherapy on each occasion. This case report underlines the importance of bronchial arteriography as the investigation of choice for massive hemoptysis.

The transfer coefficient (Kco) was significantly lower in diabetic patients with microangiopathy than in a matched group without this complication. This may reflect microangiopathy in the pulmonary circulation.Diabetic microangiopathy is a generalised abnormality of small blood vessels characterised by thickening of the capillary basal lamina. Postmortem studies have shown similar changes in the lungs of patients with diabetes, and its presence is associated with evidence of microangiopathy in other organs.'Previous studies of lung function in patients with diabetes have found various abnormalities, including reduced gas transfer,23 decreased elasticity,4 and airflow obstruction.5 The cause ofthese abnormalities is not clear. It has been suggested that the changes in elasticity and gas transfer are due in part to microangiopathy in the lungs, but they have not been shown to be associated with diabetic complications elsewhere.2 We have re-examined the relation between gas transfer and microangiopathic complications in patients with diabetes mellitus. MethodsNine subjects (six male) with diabetes with either proliferative retinopathy (eight) or maculopathy (one) were matched for age, sex, height, and smoking history with nine diabetic patients without these features. None of them currently smoked or had clinical evidence of unrelated cardiorespiratory disease, and none was taking drugs known to have effects on the lungs. All patients gave written informed consent after the purpose of the study had been explained.Spirometry was performed with a dry wedge spirometer (Vitalograph), and lung volumes were determined by a closed circuit helium dilution technique. The mean of three technically satisfactory measurements of single breath carbon monoxide gas transfer (TLCO; Morgan Transfertest machine, model C) was used in the analysis. The transfer coefficient (Kco-TLcO corrected for alveolar volume (VA)) was calculated. All patients answered the standard Medical Research Council questionnaire on respiratory symptoms and had blood samples taken for estimation of haemoglobin

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The authors in the current work suggested the potential repurposing of omarigliptin (OMR) for neurodegenerative diseases based on three new findings that support the preliminary finding of crossing BBB after a single dose study in the literature. The first finding is the positive results of the docking study with the crystal structures of A2A adenosine (A2AAR) and acetylcholine esterase (AChE) receptors. A2AAR is a member of non-dopaminergic GPCR superfamily receptor proteins and has essential role in regulation of glutamate and dopamine release in Parkinson’s disease while AChE plays a major role in Alzheimer’s disease as the primary enzyme responsible for the hydrolytic metabolism of the neurotransmitter acetylcholine into choline and acetate. Docking showed that OMR perfectly fits into A2AAR binding pocket forming a distinctive hydrogen bond with Threonine 256. Besides other non-polar interactions inside the pocket suggesting the future of the marketed anti-diabetic drug (that cross BBB) as a potential antiparkinsonian agent while OMR showed perfect fit inside AChE receptor binding site smoothly because of its optimum length and the two fluorine atoms that enables quite lean fitting. Moreover, a computational comparative study of OMR docking, other 12 DPP-4 inhibitors and 11 SGLT-2 inhibitors was carried out. Secondly, glucagon-like peptide-1 (GLP-1) concentration in rats’ brain tissue was determined by the authors using sandwich GLP-1 ELISA kit bio-analysis to ensure the effect of OMR after the multiple doses’ study. Brain GLP-1 concentration was elevated by 1.9-fold following oral multiple doses of OMR (5 mg/kg/day, p.o. for 28 days) as compared to the control group. The third finding is the enhanced BBB crossing of OMR after 28 days of multiple doses that had been studied using LC-MS/MS method with enhanced liquid–liquid extraction. A modified LC-MS/MS method was established for bioassay of OMR in rats’ plasma (10–3100 ng/mL) and rats’ brain tissue (15–2900 ng/mL) using liquid–liquid extraction. Alogliptin (ALP) was chosen as an internal standard (IS) due to its LogP value of 1.1, which is very close to the LogP of OMR. Extraction of OMR from samples of both rats’ plasma and rats’ brain tissue was effectively achieved with ethyl acetate as the extracting solvent after adding 1N sodium carbonate to enhance the drug migration, while choosing acetonitrile to be the diluent solvent for the IS to effectively decrease any emulsion between the layers in the stated method of extraction. Validation results were all pleasing including good stability studies with bias of value below 20%. Concentration of OMR in rats’ plasma were determined after 2 h of the latest dose from 28 days multiple doses, p.o, 5 mg/kg/day. It was found to be 1295.66 ± 684.63 ng/mL estimated from the bio-analysis regression equation. OMR passed through the BBB following oral administration and exhibited concentration of 543.56 ± 344.15 ng/g in brain tissue, taking in consideration the dilution factor of 10. The brain/plasma concentration ratio of 0.42 (543.56/1295.66) was used to illustrate the penetration power through the BBB after the multiple doses for 28 days. Results showed that OMR passed through the BBB more effectively in the multiple dose study as compared to the previously published single dose study by the authors. Thus, the present study suggests potential repositioning of OMR as antiparkinsonian agent that will be of interest for researchers interested in neurodegenerative diseases.

New HPLC-UV method (method A), for simultaneous determination of metformin (MET) and canagliflozin (CANA), was developed and compared to another novel UPLC-UV method (method B) in their tablet combination. Concerning method A, isocratic separation was done by C18 column (100 mm × 2.1 mm, 3 μm) using methanol and 0.03 M phosphate buffer (75 : 25, v/v) at pH 3.2 as a mobile phase. Meanwhile, chromatographic separation in method B was achieved via Hypersil® gold (50 mm × 2.1 mm, 1.9 μm). Mobile phase was methanol and 0.03 M phosphate buffer at ratio of 80 : 20  v/v. In both, detection was done at wavelength of 240 nm. Method A showed satisfactory linearity results over 1–50 μg·mL−1 and 0.5–100 μg·mL−1, while method B linearity was at 0.1–50 μg·mL−1 and 0.25–100 μg·mL−1 for CANA and MET, respectively. In terms of accuracy and precision, method A accuracy was 99.81 ± 0.73 and 99.37 ± 0.54, while method B gave accuracy of 99.47 ± 1.03 and 99.73 ± 0.89 for CANA and MET, respectively. For precision, the % RSD was found to be less than 2% for three concentrations analyzed three times. The two methods are convenient for quality laboratories, yet the UPLC method offered the advantage of shorter run times and higher sensitivity.

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