Saturable Leptin Transport Across the BBB Persists in EAE Mice

We have shown that mice with experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis, have upregulated leptin receptor expression in reactive astrocytes of the hippocampus, a region involved in sickness behavior. Leptin can exacerbate EAE when its serum concentration is high. Although leptin receptors in astrocytes modulate leptin transport across cultured endothelial cell monolayers, it is not known how leptin transport in EAE mice is regulated. Here, we determined brain and cervical spinal cord uptake of leptin in early and recovery stages of EAE, after either intravenous delivery or in situ brain perfusion of ¹²⁵I-leptin and the vascular marker ¹³¹I-albumin. While increased vascular space and general blood–brain barrier (BBB) permeability after EAE were expected, the specific saturable transport system for leptin crossing the BBB also persisted. Moreover, there was upregulation of leptin transport in hippocampus and cervical spinal cord in the early stage of EAE, shown by higher leptin uptake in these regions and by competitive inhibition with coadministered excess unlabeled leptin. We conclude that EAE induced a time- and region-specific increase of leptin transport. The results provide a link between circulating leptin and enhanced leptin signaling that may play a crucial role in disease progression.     

Potato lectin activates basophils and mast cells of atopic subjects by its interaction with core chitobiose of cell-bound non-specific immunoglobulin E

A major factor in non-allergic food hypersensitivity could be the interaction of dietary lectins with mast cells and basophils. Because immunoglobulin E (IgE) contains 10-12% carbohydrates, lectins can activate and degranulate these cells by cross-linking the glycans of cell-bound IgE. The present objective focuses on the effect of potato lectin (Solanum tuberosum agglutinin; STA) for its ability to release histamine from basophils in vitro and mast cells in vivo from non-atopic and atopic subjects. In this study, subjects were selected randomly based on case history and skin prick test responses with food, pollen and house dust mite extracts. Skin prick test (SPT) was performed with STA at 100 microg/ml concentration. Histamine release was performed using leucocytes from non-atopic and atopic subjects and rat peritoneal exudate cells. SPT on 110 atopic subjects using STA showed 39 subjects positive (35%); however, none showed STA-specific IgE; among 20 non-atopic subjects, none were positive by SPT. Maximal histamine release was found to be 65% in atopic subjects (n = 7) compared to 28% in non-atopic subjects (n = 5); the release was inhibited specifically by oligomers of N-acetylglucosamine and correlates well with serum total IgE levels (R(2) = 0.923). Binding of STA to N-linked glycoproteins (horseradish peroxidase, avidin and IgG) was positive by dot blot and binding assay. As potato lectin activates and degranulates both mast cells and basophils by interacting with the chitobiose core of IgE glycans, higher intake of potato may increase the clinical symptoms as a result of non-allergic food hypersensitivity in atopic subjects.     

Evaluating the preoperative breast cancer characteristics affecting the accuracy of axillary ultrasound staging

We evaluate the preoperative breast cancer (BC) characteristics that affect the diagnostic accuracy of axillary ultrasound (US) and determine the reliability of US in the different subgroups of BC patients. Axillary US assessments in women with invasive BC diagnosed between 2009 and 2016 in a single institution were retrospectively reviewed. The diagnostic accuracy of axillary US was obtained using surgical nodal histology as the gold standard. Preoperative breast tumor sonographic and histological factors affecting axillary US diagnostic accuracy were examined. Of the 605 newly diagnosed invasive BC cases reviewed, 251 (41.5%) had nodal metastases. Axillary US sensitivity was 75.7%, specificity 92.9%, positive predictive value 88.4%, negative predictive value 84.4%, and false‐negative rate 24.3%. Lower US sensitivity was seen with invasive lobular cancer (ILC) (P = .043), grade I/II, (P = .021), unifocal (P = .039), and smaller tumors (P < .001). US specificity was lower in grade III (P < .001), estrogen receptor (ER)‐negative (P < .001), progesterone receptor (PR)‐negative (P = .004), HER2‐positive (P = .015), triple‐negative (P = .001), and larger breast tumors (P < .001). US has moderate sensitivity and good specificity in detecting metastatic axillary lymph nodes. Based on preoperative cancer characteristics, US was less sensitive for nodal metastases from ILC, unifocal, lower grade, and smaller breast tumors. It was also less specific in grade III, ER‐negative, PR‐negative, HER2‐positive, triple‐negative, and larger breast tumors. Caution is suggested in interpreting the US axillary findings of patients with these preoperative tumor features.     

Chronic Pancreatitis with Benign Biliary Obstruction: Management Issues

Background

Benign biliary obstruction (BBO) is an important complication in patients with advanced chronic pancreatitis (CP). Its presentation varies from an incidental finding to overt jaundice. Thus it presents certain management issues. The present study was therefore performed to analyze the clinical presentation and management of biliary obstruction in patients with CP.

Methods

Retrospective analysis was performed from a prospectively collected database of 155 CP patients managed at our institute from October 2003 to June 2012.

Results

Among 43 (28 %) CP patients with biliary obstruction, 3 patients had evidence of malignancy on follow-up examination and were excluded from the final analysis. The various presentations include chronic nonprogressive elevation of serum alkaline phosphatase (SAP) (n = 15), a progressive increase in SAP with episodes of jaundice (n = 17), and persistent jaundice (n = 8). Of 15 patients with chronic nonprogressive elevation of SAP, 5 were managed conservatively, and the remaining 10 underwent only a pancreatic drainage procedure. During a median follow-up of 41 months (range 11–90 months), none of the 15 patients developed complications related to biliary obstruction. All patients with progressive increase in SAP levels and persistent jaundice underwent the biliary drainage procedure [choledochojejunostomy (CDJ, n = 20) and choledochoduodenostomy (CDD, n = 3)]. During a median follow-up of 30 months (range 10–89 months), two patients died of unrelated causes and two patients had an asymptomatic elevation of SAP.

Conclusions

BBO is common in patients with CP; however, biliary drainage is not indicated for chronic nonprogressive elevation of SAP. In patients with a progressive increase in SAP or persistent jaundice, both CDJ and CDD provide effective biliary drainage.     

Current Data Do Not Support Routine Use of Patient-Specific Instrumentation in Total Knee Arthroplasty

The purpose of this systematic review and meta-analysis is to compare patient-specific instrumentation (PSI) versus standard instrumentation for total knee arthroplasty (TKA) with regard to coronal and sagittal alignment, operative time, intraoperative blood loss, and cost. A systematic query in search of relevant studies was performed, and the data published in these studies were extracted and aggregated. In regard to coronal alignment, PSI demonstrated improved accuracy in femorotibial angle (FTA) (P = 0.0003), while standard instrumentation demonstrated improved accuracy in hip-knee-ankle angle (HKA) (P = 0.02). Importantly, there were no differences between treatment groups in the percentages of FTA or HKA outliers (>3 degrees from target alignment) (P = 0.7). Sagittal alignment, operative time, intraoperative blood loss, and cost were also similar between groups (P > 0.1 for all comparisons).     

A clinical profile of patients with Parkinson's disease and psychosis

Aims:

The aim of the study was to study the clinical profile of the patients with Parkinson''s disease (PD) and psychosis.

Settings and Design:

This was a prospective, cross sectional, hospital-based study done at the Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, India from September 2009 to January 2011. All patients with PD, diagnosed by United Kingdom PD Society Brain Bank criteria, having with features of psychosis as diagnosed by the neuropsychiatric inventory (NPI) were included. Patients without a caregiver who could validate the patient''s symptoms were excluded.

Results:

A total of 40 patients (5 women, 35 men) with PD with psychosis (mean age: 54.2 ± 11.5 years, mean duration of illness: 6.5 ± 4.5 years, and mean duration of psychosis: 4.3 ± 4.3 years) were included in the study. The Global NPI score was 19.1 ± 11.5. Majority of the patients had pure hallucinations (85%), while the rest had either pure delusions (7.5%) or a combination of delusions and hallucinations (7.5%). In those with hallucinations, visual hallucinations were the commonest (60%) (pure only in 22.5%), followed by auditory (45%), minor hallucinations (45%), and tactile (20%). Only one person reported having olfactory hallucinations (2.5%). Loss of insight was most often observed during the visual hallucinations (52%), followed by tactile (44.4%), auditory (38.9 %), and minor hallucinations (33.3%).

Conclusions:

In patients with PD and psychosis, pure hallucinations are common and visual hallucinations are the commonest among the hallucinations. A large proportion of patients have minor hallucinations, which need to be recognized early for effective and early management. The limitations of the study were small sample size, use of a single scale to assess psychosis and subjective assessment of insight.     

Effect of ovarian sex hormones on non-steroidal anti-inflammatory drug-induced gastric lesions in female rats

Objective:

The objective of the following study is to investigate the effect of ovarian sex hormones on gastric ulcer in female rats.

Materials and Methods:

Female rats were treated daily with estrogen (0.05 and 0.1 mg/kg), progesterone (2.0 and 5.0 mg/kg), combined estrogen (0.05 mg/kg) and progesterone (2.0 mg/kg), ranitidine (30 mg/kg) or vehicle for 7 days. Ulcers were induced with aspirin on 7^th day. Four hours later, animals were sacrificed and stomach were removed for macroscopic and biochemical examination.

Results:

Estrogen in 0.05 and 0.1 doses showed 32% and 18% of ulcer inhibition, respectively, progesterone 09% and 14% inhibition in 2.0 and 5.0 mg/kg doses, respectively, whereas combined estrogen and progesterone showed 23% and ranitidine showed 60% inhibition. However, the inhibition attained and the stomach malondialdehyde and glutathione levels in sex hormone treated groups were not statistically significant when compared to control group.

Conclusion:

At the tested doses, these ovarian sex hormones neither worsen nor protect against aspirin-induced gastric lesions in female rats.KEY WORDS: Estrogen, progesterone, ulcer, glutathione, malondialdehyde