Exosomes: Emerging implementation of nanotechnology for detecting and managing novel corona virus- SARS-CoV-2

The spread of SARS-CoV-2 as an emerging novel coronavirus disease (COVID-19) had progressed as a worldwide pandemic since the end of 2019. COVID-19 affects firstly lungs tissues which are known for their very slow regeneration. Afterwards, enormous cytokine stimulation occurs in the infected cells immediately after a lung infection which necessitates good management to save patients. Exosomes are extracellular vesicles of nanometric size released by reticulocytes on maturation and are known to m...     

Copy number variations in DCC/18q and ERBB2/17q are associated with disease‐free survival in microsatellite stable colon cancer

We conducted a prospective study to assess the prognostic impact of selected copy number variations (CNVs) in Stage II–III microsatellite stable (MSS) colon cancer. A total of 401 patients were included from 01/2004 to 01/2009. The CNVs in 8 selected target genes, DCC/18q, EGFR/7p, TP53/17p, BLK/8p, MYC/8q, APC/5q, ERBB2/17q and STK6/20q, were detected using a quantitative multiplex polymerase chain reaction of short fluorescent fragment (QMPSF) method. The primary end‐point was the impact of the CNVs on the 4‐year disease‐free survival (DFS). The recurrence rate at 4 years was 20.9%, corresponding to 14% Stage II patients versus 31% Stage III patients (p < 0.0001). The 4‐year DFS was significantly decreased in patients with a loss at DCC/18q (p = 0.012) and a gain at ERBB2/17q (p = 0.041). The multivariate analysis demonstrated that Stage III, a loss at DCC/18q and a gain at ERBB2/17q were independent factors associated with DFS. A combination of DCC/18q and ERBB2/17q was also associated with relapse, with the hazard ratio increasing from 1 to 2.4 (95% confidence interval (CI), 1.5–4.1) and 3.1 (95% CI, 1.2–8.4) in the presence of 0, 1 or 2 alterations, respectively (p = 0.0013). CNVs in DCC/18q and ERBB2/17q are significantly associated with DFS in Stage II–III MSS colon cancer.     

Three-dimensional analysis of 61 human endolymphatic ducts and sacs in ears with and without Menière's disease

We used light microscopy and computerized graphic reconstruction techniques to examine the endolymphatic duct and sac in 20 pairs of bones from patients with Menière's disease and 21 bones from controls. The diameters of the endolymphatic duct and the proximal portion of the vestibular aqueduct were significantly smaller in Menière's disease ears than in controls. Graphic reconstructions showed the Menière's sacs to be smaller and to have fewer tubular epithelial structures in the intraosseous portion than in the control ears. The median volume of the sac in the Menière's disease side was substantially lower than in the contralateral ear. The width of the external aperture of the vestibular aqueduct was significantly smaller in Menière's disease ears than in controls. These findings indicate that the size not only of the vestibular aqueduct but also of the sac is reduced in Menière's disease. The results may suggest that the endolymphatic sac is pathologically changed in Menière's disease and that a reduced resorptive capacity of a small endolymphatic sac could result in endolymphatic hydrops.     

Clinical Relevance of Alternative Endpoints in Colorectal Cancer First-Line Therapy With Bevacizumab: A Retrospective Study

Background

We studied the relationship between intermediate criteria and overall survival (OS) in metastatic colorectal cancer (mCRC) patients who received first-line chemotherapy with bevacizumab.

Familial amyloidotic polyneuropathy with muscle, vitreous, leptomeningeal, and cardiac involvement: Phenotypic, pathological, and MRI description

Familial amyloidotic polyneuropathy (FAN type 1) is a rare systemic disease that causes severe and disabling peripheral neuropathy. We describe the phenotypic, radiological, and pathological characteristics of a patient with familial amyloid polyneuropathy type 1 who had evidence of motor-sensory-autonomic neuropathy, ocular vitreous deposits, diffuse leptomeningeal involvement, and hypertrophic cardiomyopathy. Muscle involvement, an infrequently reported feature, was also observed. Early recognition of the disease has significant therapeutic implications.     

Bronchiolitis obliterans with organized pneumonia: a rare complication of primary Gougerot-Sjögren syndrome

INTRODUCTION: Bronchiolitis obliterans organizing pneumonia (BOOP) is characterized by plugs of granulation tissue in bronchioles, alveolar ducts and alveoli. This pulmonary disorder has been reported in some cases in relation to drug consumption (D-penicillamine, amiodarone), with bacterial or viral infections (Mycoplasma pneumoniae, HIV), and with systemic diseases, such as rheumatoid arthritis. To our knowledge, only three cases of association BOOP-Sj?gren's syndrome have been reported. EXEGESIS: We report three new cases of BOOP. These patients presented a primary Sj?gren's syndrome without clinical or biological abnormalities suggestive of other autoimmune diseases. Initial presentation was an acute pulmonary disorder mimicking a bacterial pneumonia. Two patients had cutaneous vasculitis and the third vasculitic neuropathy. Corticosteroid therapy was begun and was quickly successful. None of the patients presented a relapse of BOOP. CONCLUSION: The incidence of BOOP is probably underestimated in patients with primary Sj?gren's syndrome without cutaneous vasculitis. In case of pneumonia with antibiotic resistance, an immunological mechanism should be considered.     

Metabolism,oral bioavailability and pharmacokinetics of chemopreventive kaempferol in rats

The purpose of this study was to compare the hepatic and small intestinal metabolism, and to examine bioavailability and gastro‐intestinal first‐pass effects, of kaempferol in rats. Liver and small intestinal microsomes fortified with either NADPH or UDPGA were incubated with varying concentrations of kaempferol for up to 120 min. Based on the values of the kinetic constants (K_m and V_max), the propensity for UDPGA‐dependent conjugation compared with NADPH‐dependent oxidative metabolism was higher for both hepatic and small intestinal microsomes. Male Sprague‐Dawley rats were administered kaempferol intravenously (i.v.) (10, 25 mg/kg) or orally (100, 250 mg/kg). Gastro‐intestinal first‐pass effects were observed by collecting portal blood after oral administration of 100 mg/kg kaempferol. Pharmacokinetic parameters were obtained by non‐compartmental analysis using WinNonlin. After i.v. administration, the plasma concentration–time profiles for 10 and 25 mg/kg were consistent with high clearance (～3 L/hr/kg) and large volumes of distribution (8–12 L/hr/kg). The disposition was characterized by a terminal half‐life value of 3–4 h. After oral administration the plasma concentration–time profiles demonstrated fairly rapid absorption (t_max～1–2 h). The area under the curve (AUC) values after i.v. and oral doses increased approximately proportional to the dose. The bioavailability (F) was poor at ～2%. Analysis of portal plasma after oral administration revealed low to moderate absorption. Taken together, the low F of kaempferol is attributed in part to extensive first‐pass metabolism by glucuronidation and other metabolic pathways in the gut and in the liver. Copyright © 2009 John Wiley & Sons, Ltd.