Pulmonary Langerhans cell histiocytosis: emerging concepts in pathobiology,radiology, and clinical evolution of disease

Pulmonary Langerhans cell histiocytosis (PLCH) is an uncommon disorder of adult smokers associated with a significant morbidity. Arising from the aberrant accumulation of Langerhans and other immune cells, PLCH tends to cause a relatively isolated pulmonary involvement as compared to other forms of Langerhans cell (LC) and histiocytic disorders. Increased knowledge of cytokine triggers, dendritic cell trafficking, and clonality of LC populations in PLCH have resulted in an improved understanding of the pathobiology of PLCH. High-resolution CT (HRCT) of the chest has led to better appreciation of nodular and cystic radiographic abnormalities characteristic of the disease. Correlation of HRCT abnormalities with lung pathologic changes has led to an improved comprehension of clinical evolution of PLCH. Current clinical predictors for PLCH outcomes remain poor, although long-term follow-up and radiologic monitoring may help to define disease progression. This review discusses advances in PLCH emphasizing the etiopathologic bases of the disease and currently available radiologic modalities for monitoring disease progression.     

Treatment of gastrointestinal bleeding in left ventricular assist devices: A comprehensive review

Left ventricular assist devices(LVAD) are increasingly become common as life prolonging therapy in patients with advanced heart failure. Current devices are now used as definitive treatment in some patients given the improved durability of continuous flow pumps. Unfortunately, continuous flow LVADs are fraught with complications such as gastrointestinal(GI) bleeding that are primarily attributed to the formation of arteriovenous malformations. With frequent GI bleeding, antiplatelet and anticoagulation therapies are usually discontinued increasing the risk of life-threatening events. Small bowel bleeds account for 15%as the source and patients often undergo multiple endoscopic procedures.Treatment strategies include resuscitative measures and endoscopic therapies.Medical treatment is with octreotide. Novel treatment options include thalidomide, angiotensin converting enzyme inhibitors/angiotensin Ⅱ receptor blockers, estrogen-based hormonal therapies, doxycycline, desmopressin and bevacizumab. Current research has explored the mechanism of frequent GI bleeds in this population, including destruction of von Willebrand factor,upregulation of tissue factor, vascular endothelial growth factor, tumor necrosis factor-α, tumor growth factor-β, and angiopoetin-2, and downregulation of angiopoetin-1. In addition, healthcare resource utilization is only increasing in this patient population with higher admissions, readmissions, blood product utilization, and endoscopy. While some of the novel endoscopic and medical therapies for LVAD bleeds are still in their development stages, these tools will yet be crucial as the number of LVAD placements will likely only increase in the coming years.     

A Competent and Commercially Viable Process for the Synthesis of the Anti-Hypertensive Drug Olmesartan Medoxomil

Drug product purity and potency are of most significance in the regulatory market as we notice many recalled batches worldwide, particularly in the US and Japan. Olmesartan Medoxomil is an anti-hypertensive drug. The present invention relates to a process for the preparation of Olmesartan Medoxomil with 99.9% purity in an overall 62% yield. The synthesis includes three isolations and one purification with easy plant operations. This process describes the formation and control of each individual impurity in all stages. This process for Olmesartan Medoxomil and its intermediates is competent for industrial production in very short reaction time intervals with an appreciable yield and high purity.     

Synthesis of non-toxic,biocompatible, and colloidal stable silver nanoparticle using egg-white protein as capping and reducing agents for sustainable antibacterial application

For nearly a decade, silver nanoparticles (AgNPs) have been the most prevalent commercial nanomaterials products widely used in different biomedical applications due to their broad-spectrum antimicrobial activity. However, their poor long-term stability in different environments, namely, pH, ionic strength, and temperature, and cytotoxicity toward mammalian cells has restricted their more extensive applications. Hence, there is urgent need to develop highly biocompatible, non-toxic, and stable silver nanoparticles for wide-ranging environments and applications. In the present study, a simple, sustainable, cost-effective and green method has been developed to prepare highly stable aqueous colloidal silver nanoparticles (AgNPs-EW) using the ovalbumin, ovotransferrin, and ovomucoid of egg-white as reducing and capping agents accomplished under the irradiation of direct sunlight. Then, we evaluated the effects of freezing–drying (lyophilization) and freeze–thaw cycles on the stability of AgNPs-EW in aqueous solution under visual inspection, transmission electron microscopy, and absorbance spectroscopy. In addition, we studied the antibacterial activity against Salmonella typhimurium and Escherichia coli, carried out biocompatibility studies on chicken blood, and tested acute, chronic toxicity in Drosophila melanogaster. The results suggest that AgNPs-EW did not aggregate upon freeze-thawing and lyophilization, thus exhibiting remarkable stability. The antibacterial activity results showed that the AgNPs-EW had the highest antibacterial activity, and the minimum inhibitory concentration (MIC) of AgNPs-EW for E. Coli and S. typhimurium were 4 and 6 μg ml⁻¹, respectively. The biocompatibility study revealed that the AgNPs-EW did not induce any hemolytic effect or structural damage to the cell membranes of chicken erythrocytes up to a concentration of 12 μg ml⁻¹. Similarly, no acute and chronic toxicity was observed on melanization, fecundity, hatchability, viability, and the duration of development in the 1^st generation of Drosophila melanogaster at the concentration range of 10 mg L⁻¹ to 100 mg L⁻¹ of AgNPs-EW, and all the flies completed their full developmental cycle. Therefore, the present study successfully demonstrated the green and sustainable preparation of non-toxic AgNPs-EW having good biocompatibility, enhanced colloidal stability, and antibacterial activity. Hence, the synthesized AgNPs-EW could be used for the development of an antimicrobial formulation for controlling microbial infection.

For nearly a decade, silver nanoparticles (AgNPs) have been the most prevalent commercial nanomaterials products widely used in different biomedical applications due to their broad-spectrum antimicrobial activity.