Prolonged exposure of pancreatic beta cells to raised glucose concentrations results in increased cellular content of islet amyloid polypeptide precursors

Summary Most non-insulin dependent diabetic patients have amyloid deposits in their pancreatic islets. It is not known whether chronic hyperglycaemia contributes to the formation of amyloid fibrils from the islet amyloid polypeptide that is produced by the pancreatic beta cells. Since islet amyloid exhibits islet amyloid polypeptide precursors immunoreactivity, we examined whether sustained in vitro exposure to raised glucose increases the abundance of these precursors in human beta cells. After 6 days stimulation with 20 mmol/l glucose the cellular content of insulin but not islet amyloid polypeptide was decreased leading to an increase in the ratio of the latter over insulin (3.0 ± 0.6 vs 1.8 ± 0.3 after 6 mmol/l glucose culture, p < 0.05). Similar changes occurred in rat beta cells cultured for 3 days in the presence of 20 mmol/1 glucose plus 3-isobutyl-1-methylxanthine. Western blot analysis of cellular islet amyloid polypeptide after prolonged exposure to high glucose indicated the presence of higher proportions of its precursor- and intermediate forms. In human beta cells cultured in 20 mmol/l glucose, the major form corresponds to an intermediate species which exhibits an immunoreactivity for the N-flanking peptide, as is also the case in islet amyloid. We concluded that prolonged in vitro exposure of beta cells to raised glucose concentrations increases the relative proportion of islet amyloid polypeptide over insulin, as well as of its precursors over the mature form of islet amyloid polypeptide. [Diabetologia (1999) 42: 188–194] Received: 1 April 1998 and in final revised form: 13 October 1998     

Paraproteinaemia plus osteolytic lesions in typical hairy-cell leukaemia

Most cases of hairy-cell leukaemia (HCL) involve proliferations of neoplastic B lymphocytes. In rare cases, M-proteins or osteolytic lesions have been documented in patients with HCL. In this study two patients with typical HCL are reported in whom both paraproteinaemia and osteolytic lesions of the femoral neck developed. In one of the patients the production of the M-protein by hairy cells could be established. In the other patient, at autopsy no signs of myeloma were found. The hairy cells from inside the osteolytic lesion had the same immunological phenotype as hairy cells from the peripheral blood, the spleen, and other parts of the bone marrow. These cases once more confirm the B-cell nature of many cases of HCL, and show that hairy cells can have functional capacities usually attributed to much more mature B lymphocytes, i.e. plasma cells.     

Associations Between Environmental Characteristics and Active Commuting to School Among Children: a Cross-sectional Study

Background

Active commuting to school can contribute to active living among children, and environmental characteristics might be related to transportation mode to school.

Purpose

The purpose of this study is to explore the association between physical and social environmental characteristics in the home, neighborhood, and school environment and walking and bicycling to school.

Method

Data were collected among parents (n?=?5,963) of children of primary schools in four Dutch cities. Parents reported mode of transportation to school, and individual, home environmental, neighborhood, and school environmental characteristics. Social as well as physical characteristics were included for the home and neighborhood environment. Multilevel multinomial logistic regression analyses were conducted to quantify the association between environmental characteristics and walking and bicycling to school.

Results

Three quarter of all children usually commute to school by active transportation, but age and distance from home to school were important prerequisites. Besides home environmental characteristics, lower neighborhood socioeconomic status was negatively associated with walking [odds ratio (OR)?=?0.51] and bicycling (OR?=?0.86). Perceived social safety was positively related to walking and bicycling (OR?=?1.04 for both), as was perceived social cohesion (OR?=?1.04 and 1.02 for walking and bicycling). Living in the city center was positively associated with walking (OR?=?1.91), whereas living in a city green neighborhood was negatively associated with walking and bicycling (OR?=?0.48 and 0.76, respectively). Traffic safety as perceived by school boards was positively associated with bicycling (OR?=?1.25).

Conclusion

This study shows that there is a relation between several characteristics in the home, neighborhood, and school environment and walking and bicycling to school among Dutch primary school children. Especially the social neighborhood characteristics were related to active commuting. Therefore, apart from providing a physical infrastructure that facilitates safe and convenient active commuting to school, policy makers should be aware of opportunities to facilitate active commuting by social initiatives in local communities.     

4D-CT angiography differentiating arteriovenous fistula subtypes

Objective and methods

In the diagnostic work-up of patients suspected of a dural arteriovenous fistula (dAVF), imaging has a key role in order to diagnose the dAVF, assess its bleeding risk and choose optimal treatment strategy. Digital subtraction angiography (DSA) is the gold standard for the most detailed image of a dAVF. Nowadays four-dimensional CT angiography (4D-CTA) could possibly be an additional first-line tool in the work-up of a patient suspected of a dAVF. We describe three cases clinically suspected of a dAVF which had a diagnostic work-up with 4D-CTA as well as DSA. We evaluated the angioarchitecture of the dAVF both on 4D-CTA and DSA, with emphasis on the patterns of venous drainage as this is important in assessing the bleeding risk of a dAVF.

Results and conclusion

4D-CTA identified the dAVF, revealed its angioarchitecture and correctly differentiated different patterns of venous drainage (Borden type I, II and III) as confirmed on DSA. Although DSA has the advantage of higher spatial and temporal resolution, 4D-CTA seems to be a new useful non-invasive tool in the diagnostic work-up of a patient suspected of a dAVF.     

The effect of submicron fat droplets in a drink on satiety,food intake,and cholecystokinin in healthy volunteers

Purpose

Small fat droplets infused into the gut reduce food intake and hunger more than bigger ones, at levels as low as 6 g, and these effects are hypothesized to occur via satiety hormones such as cholecystokinin. It is, however, unknown whether the effect of droplet size would persist after oral consumption. It is also unknown whether an even smaller droplet size can affect hunger and food intake and at what minimum amount of fat. Therefore, the aim of the study was to test the effect of very fine fat droplets on satiety and food intake in two different quantities.

Methods

In a balanced-order 4-way crossover design, 24 volunteers consumed a fat-free meal replacement drink with either 5 or 9 g oil (rapeseed) and either 3 or 0.1 μm droplet size. Appetite scores and plasma cholecystokinin levels (in n = 12 subset) were measured for 180 min, when food intake was assessed during an ad libitum meal. Data were analyzed by ANCOVA, followed by Dunnett’s test and paired t test. The behavior of the emulsions was also characterized in a simulated gastrointestinal model.

Results

Despite faster in vitro lipolysis of the smallest droplets, neither droplet size nor fat amount affected satiety or food intake. From t = 45–150 min, cholecystokinin response was 50 % higher (P < 0.05) after the 0.1 versus 3 μm, but only with 9 g fat.

Conclusion

When this particular fat at these amounts is delivered in a meal replacement drink, droplet size does not influence appetite or food intake. This effect is independent of the amount of fat or plasma cholecystokinin changes.