Harris Manchester College

Objective: This study aimed to show the effect of high glucose concentrations in combination with a pharmaceutical analog of the Na+/H+ antiport inhibitor, cariporide, on scavenger receptor CD36 expression, cell adhesion, and cell migration of human monocytes derived from obese and normal individuals.Research Methods and Procedures: Monocytes were isolated from six healthy obese individuals and six healthy age- and sex-matched controls by use of whole blood Percoll sedimentation and plastic surface monocyte binding. The density of CD36 scavenger receptors on the surface of monocytes was assessed by the use of a fluorescent fluorescein isothiocyanate (FITC)-linked monoclonal antibody. Transmigration of monocytes through laminin-1–coated filters was performed on 5-μm pore Transwell culture inserts. Monocyte attachment to laminin was estimated by a solid phase assay.Results: High glucose concentrations caused an increase in monocytes from normal and obese individuals in the expression of CD36 receptors and positively influenced monocyte migration and adhesion to laminin. Cariporide together with glucose counteracted these effects. The effects of migration and adhesion of monocytes to laminin were specific to glucose, because the effect was significantly higher when monocytes were incubated in the presence of 20 mM of glucose than in the presence of 20 mM of fructose. Monocytes from obese subjects showed greater response than in normal to all of the studied effects, with the highest response in laminin attachment.Discussion: The data of this study suggest that cariporide counteracts atherosclerosis-related functions through Na+/H+ antiport inhibition in monocytes from both normal and obese individuals.

Monocyte–extracellular matrix interactions have been implicated in atherosclerosis pathophysiology. In the present study we evaluated the oxidation of laminin by monocytes derived from either diabetic patients or healthy volunteers. Moreover, reactive oxygen species production was measured. Monocyte attachment and migration through oxidized and non-oxidized laminin were also studied.Laminin oxidation was tested by a sensitive ELISA assay in isolated monocytes. ROS production was measured with fluorescent indicators. 35S-methionine was used for evaluating monocyte attachment. Monocyte migration through laminin was examined on transwells.Monocytes derived from patients with diabetes mellitus showed an increased ability to carbonylate and attach to laminin. Diabetic monocytes produced increased levels of ROS as compared to controls. Our results showed the involvement of the alpha2 integrin subunit in monocyte attachment to both native and oxidized laminin in control and diabetic monocytes.The results indicate a modified interaction between monocytes and laminin in diabetes.

BACKGROUND: Benign anorectal conditions are fairly common. Physicians of various specialties usually see patients with these conditions before being referred to colorectal specialists, frequently with an incorrect diagnosis.We sought to evaluate the effect of attending an outpatient colorectal clinic by medical students on the diagnostic accuracy of these conditions.
METHODS: Over a 1-year period, medical students were randomized into a group that attended the clinic, and one that did not. Both groups were shown images of six common benign anorectal conditions. The overall diagnostic accuracy as well as
the diagnostic accuracy for each one of these conditions was prospectively evaluated for both groups.
RESULTS: Nineteen students attended clinic and 17 did not. Overall diagnostic accuracy was 80.6% for students attending clinic and 43.1% for non-attending students. (p < 0.05) In the attending group, diagnostic accuracy was
significantly greater for prolapsed internal hemorrhoids (73.6% versus 35.2%, p < 0.05), thrombosed external hemorrhoid, (73.6% versus 17.6%, p < 0.05) fissure (100% versus 47%, p < 0.05), and anal tags (68.4% versus 11.7%, p < 0.05%).
CONCLUSION: Exposure to these conditions during surgical clerkships in medical school may help future specialists provide better care for patients with benign anorectal disorders.

Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance with onset or first recognition during pregnancy. Women with GDM and their offspring have an increased risk of developing type 2 diabetes mellitus in the future. The global incidence of GDM is difficult to estimate, due to lack of uniform diagnostic criteria. Various diagnostic criteria have been proposed. The benefit of treating GDM has also been controversial. The clinical significance of treating maternal hyperglycemia was made evident in the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study. The HAPO study demonstrated that there is a continuous association of maternal glucose levels with adverse pregnancy outcomes and served as the basis for a new set of diagnostic criteria, proposed in 2010 by the International Association of Diabetes and Pregnancy Groups (IADPSG). According to these criteria the diagnosis of GDM is made if there is at least one abnormal value (≥92, 180 and 153 mg/dl fo...