The neuroprotective efficacy of α-crystallin against acute inflammation in mice

Acute inflammation activates macrophages or monocytes and subsequently releases several inflammatory cytokines and reactive oxygen and nitrogen species. These proinflammatory cytokines activate astrocytes and trigger neurodegenerative diseases. In this work, we chose to address the mechanistic aspects of alpha-crystallin's protective function in inflammation-triggered neurotoxicity in mice. Alpha-crystallin, a lens structural protein, comprising alpha-A and alpha-B subunits is an ubiquitous molecular chaperone, which have been shown to reduce reactive oxygen species (ROS) production and enhance cellular glutathione level in the acute inflammation-induced mice. Results show that the proinflammatory cytokines such as interleukin-1alpha (IL-1alpha) and tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) were significantly high (P<0.05) in the plasma, liver, cortex and hippocampus of inflammation-induced mice when compared to control. Alpha-crystallin pretreatment prevents inflammation-induced cytokines and NO production. In addition, a significant (P<0.05) reduction of dopamine (DA), 5-hydroxytryptamine (5-HT) and norepinephrine (NE) was also observed in the inflammation-induced mice. Nevertheless, their metabolites, such as 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-HIAA) increased significantly (P<0.05) as compared to control. The results indicate that alpha-crystallin pretreatment controls the inflammation-induced DA, 5-HT and NE catabolism and suggest that alpha-crystallin has the potential to act as an anti-inflammatory agent in the neuroprotective processes.     

Migration of Plasticizers from Polyethylene Terephthalate and Low-Density Polyethylene Casing into Bottled Water: A Case Study From India

Mineral bottled water packed in three polymers viz., virgin polyethylene terephthalate (PET), recycled PET, and low-density polyethylene (LDPE) were investigated for the occurrence, migration, and health risk of phthalic acid esters (PAEs) at 25 °C, 35 °C, and 45 °C. The average concentration of six USEPA priority PAEs in refrigerated water samples was highest in recycled PET> LDPE > virgin PET. The highest leaching was seen at 45 °C after 2 days for LDPE water packets with ∑₆PAEs amounting to 64,300 ng/L. Similarly, for recycled PET, the highest migration was seen at 45 °C after seven days (3,800 µg/L). Bis 2-ethyl hexyl phthalate (DEHP) and di-n-butyl phthalate (DnBP) were the predominant plasticizers from PET bottles and LDPE water packets, respectively. Predicted concentration after three weeks based on best fit obtained through the polynomial model for PET bottles was seen higher than the recommended limit suggested by USEPA (6 µg/L) and WHO (8 µg/L).

     

Implementation of Intraoperative Ultrasound Localization for Breast-Conserving Surgery in a Large,Integrated Health Care System is Feasible and Effective

Annals of Surgical Oncology - Intraoperative ultrasound (IUS) localization for breast cancer is a noninvasive localization technique. In 2015, an IUS program for breast-conserving surgery (BCS) was...     

Acute right heart syndrome: Rescue treatment with inhaled nitric oxide

Acute right heart syndrome is a common occurrence in intensive care units and is associated with a poor prognosis. There is lack of understanding of the involved pathophysiology, standard diagnostic protocols and treatment guidelines. Management goals include ensuring adequate right ventricle (RV) filling, maximizing RV contraction and reducing RV afterload. We describe a 39-year-old female with acute decompensated right heart failure secondary to multiple causes. She was managed with inhaled nitric oxide. Her condition improved, which was evident by a decrease in her pulmonary artery systolic pressure on serial echocardiography, decreased requirement of vasopressors and successful weaning from the ventilator.     

A Novel and Rapid Method to Determine Doxycycline in Human Plasma by Liquid Chromatography Tandem Mass Spectrometry

A simple, rapid, specific and sensitive liquid chromatography tandem mass spectrometric method has been developed and validated for the determination of doxycycline from the human plasma. Doxycycline is extracted from human plasma by solid phase extraction. Demeclocycline was used as an internal standard. Detection was performed at transitions of 444.800→428.200 for doxycycline and 464.700→448.100 for demeclocycline using mass spectrometry. Chromatographic separation of analyte and internal standard were carried out using a reverse phase C18, column at 0.500 ml/min flow. The assay of doxycycline is linear over the range of 0.055-7.612 μg/ml, with a precision <14.83%, regression coefficient (r²)=0.9961 and the limit of quantification in plasma for doxycycline was 0.055 μg/ml. Mean extraction recovery obtained was 95.55%. Samples are stable at room temperature for 6 h, processed samples were stable at least for 30.20 h and also stable at three freeze-thaw cycles. The method has been used to perform pharmacokinetic and bioequivalence studies in human plasma.     

The evolving role of lymphadenectomy for bladder cancer: why,when, and how

Radical cystectomy (RC) represents a standard treatment for non-metastatic muscle-invasive and select high-risk non-muscle invasive bladder cancer. Lymphadenectomy performed at time of RC identifies nodal metastases in up to 25% of patients despite normal imaging. There has been an increasing utilization of pelvic lymph node dissection (PLND) with RC since 1950, and in fact lymph node dissection is now recommended in contemporary National Comprehensive Cancer Network (NCCN) guidelines. Benefits of removing of nodal disease include improved staging, guidance for adjuvant treatment, and potentially improved oncologic outcomes. Advantages of dissection have been suggested among both node-negative and node-positive patients. Numerous studies have attempted to define the optimal dissection characteristics of lymphadenectomy with regard to nodal yield and anatomic boundaries of dissection. The ideal extent of lymphadenectomy remains uncertain due to the retrospective and non-randomized nature of the majority of existing reports, which are thereby limited by significant confounding and selection bias. Two randomized controlled trials have investigated this issue, one of which LEA AUO AB 25/02 recently reported its outcomes, demonstrating no significant improvement in 5-year outcomes with an extended dissection. Meanwhile, the Southwest Oncology Group 1011 trial has completed enrollment and data are maturing. While current data preclude definitive recommendations, herein we review the why, when, and how to perform a PLND for bladder cancer.     

Inguinal lymph node dissection for penile cancer: a contemporary review

Penile cancer is an uncommon disease associated with significant psychological and physical morbidity. Penile cancer has an expectable pattern of spread in a stepwise fashion, from inguinal to pelvic lymph nodes (PLN) then distant spread. Patients with penile cancer have variable survival, with patients with a low burden of nodal metastatic disease having lasting survival with surgical management, however patients with a large amount of locoregional metastatic disease having a worse prognosis. The current management options for patients with metastatic lymph node disease in penile cancer aims to reduce the morbidity associated with radical inguinal lymph node (ILN) surgery with appropriate risk stratification to optimise oncological control of the disease. This article describes current challenges in managing the inguinal region in patients with penile squamous cell carcinoma (SCC).     

Endoscopic diagnosis and treatment of pancreatic cysts

Pancreatic cystic neoplasms have emerged as an important new opportunity for many disciplines to participate in the diagnosis and management of early pancreatic neoplasia. With an increase in an understanding of these lesions and their potential for malignant transformation, there has been a dramatic increase in the frequency of diagnosis. We critically examined the literature on diagnostic methods for pancreatic cystic lesions over the past 5 years. The methods of endoscopic pancreatic pseudocyst drainage and clinical outcomes are also discussed. Morphologic studies of cystic lesions using cross-sectional imaging or endoscopic ultrasound have a low diagnostic rate. Cyst fluid analysis with the use of tumor markers (eg, carcinoembryonic antigen) increases the accuracy of diagnosis. The management of cystic lesions is heavily dependent on the type of cyst, the neoplastic potential, and the risk of surgery. The traditional therapy is pancreatic resection and not cyst enucleation. In contrast to cystic neoplasms, pseudocysts are localized collections of inflammatory fluid that mimic cystic neoplasms. The fluid collections arise from chronic pancreatitis and ductal leaks. Because pseudocysts have no neoplastic potential, they can be drained rather than resected. Drainage can be safely accomplished with external catheters or endoscopically with internal catheters. As we learn more about the pathophysiology of the various cystic lesions, treatment will be tailored to the specific cyst lesion. Endoscopic ultrasound has an important role in the characterization of pancreatic cystic lesions and helps in selection of the optimal treatment modality.