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Biomedical subjects

I Chapman

Publications and source records attributed to I Chapman.

At least 19 recordsLinked to original sources

Effect of pramlintide on satiety and food intake in obese subjects and subjects with type 2 diabetes.

AIMS/HYPOTHESIS: Long-term trials in insulin-treated subjects with type 2 diabetes have shown that adjunctive treatment with the amylin analogue pramlintide reduces HbA(1)c levels and elicits weight loss. While amylin reduces food intake in rodents, pramlintide's effect on satiety and food intake in humans has not yet been assessed. METHODS: In this randomised, double-blind, placebo-controlled crossover study, 11 insulin-treated men with type 2 diabetes (age 60+/-9 years, BMI 28.9+/-4.8 kg/m(2)) and 15 non-diabetic obese men (age 41+/-21 years, BMI 34.4+/-4.5 kg/m(2)) underwent two standardised meal tests. After fasting overnight, subjects received single subcutaneous injections of either pramlintide (120 microg) or placebo, followed by a preload meal. After 1 h, subjects ate an ad libitum buffet meal. Energy intake and meal duration were measured, as were hunger ratings (using visual analogue scales), and plasma cholecystokinin, glucagon-like peptide-1 and peptide YY concentrations over time. RESULTS: Compared with placebo, pramlintide reduced energy intake in both the type 2 diabetes (Delta-202+/-64 kcal, -23+/-8%, p<0.01) and obese (Delta-170+/-68 kcal, -16+/-6%, p<0.02) groups, without affecting meal duration. Hunger and hormonal analyte profiles provided evidence that pramlintide may exert a primary satiogenic effect, independently of other anorexigenic gut peptides. CONCLUSIONS/INTERPRETATION: The results indicate that enhanced satiety and reduced food intake may explain the weight loss observed in long-term pramlintide trials.

Adult↗

The effects of drinks made from simple sugars on blood pressure in healthy older people.

The objective of the research was to determine the blood pressure (BP) lowering effects in older people of 50 g carbohydrate drinks with varying carbohydrate content using a randomised, cross-over study with ten (six females) healthy older subjects (mean age 72.20 (sem 1.50) years). BP, heart rate and glucometer-derived blood glucose levels were determined at baseline and following the ingestion of equal volumes (300 ml) of water and carbohydrate drinks with varying nutrient content (glucose, sucrose and fructose). A significant decline in BP over the first 60 min was seen following glucose (systolic BP (SBP) P<0.01, diastolic BP (DBP) P<0.01, mean arterial BP (MAP) P=0.03) and sucrose (SBP P<0.01, DBP P<0.01, MAP P<0.01) ingestion, although the decrease occurred earlier after glucose than sucrose ingestion (SBP 7.33 (sem 2.19) v. 21.00 (sem 4.30) min (P=0.03) and MAP 11.22 (sem 3.10) v. 17.00 (sem 3.78) min (P=0.03)). BP increased after water ingestion (SBP P=0.04, DBP P=0.18, MAP P=0.02) but did not change after fructose ingestion (SBP P=0.36, DBP P=0.81, MAP P=0.34). Post hoc analyses revealed that the BP (SBP, DBP and MAP) decrease following glucose and sucrose ingestion were similar but significantly greater than following fructose or water ingestion. Sucrose, which is used widely (table sugar), reduces BP as much as glucose. In contrast to this, fructose ingestion causes no change in BP. Further studies are required to determine if the substitution of glucose or sucrose with fructose may be beneficial in the medical management of older people with severe symptomatic postprandial hypotension.

Aged↗

Effects of oral fructose and glucose on plasma GLP-1 and appetite in normal subjects.

Oral glucose is a potent stimulant of glucagon-like peptide-1 (GLP-1) secretion. The effect of oral fructose on GLP-1 secretion in humans is unknown. The aims of this study were to determine (i) whether oral fructose stimulates GLP-1 secretion and (ii) the comparative effects of oral glucose and fructose on appetite. On 3 separate days, 8 fasting healthy males received, in single-blind randomized order (i) 75 g glucose, (ii) 75 fructose, or (iii) 75 g glucose followed by 75 g fructose I h later. Venous glucose, insulin and GLP-1 were measured. Appetite was assessed by visual analog questionnaires and intake of a buffet meal. Whereas glucose and fructose both increased plasma glucose, insulin and GLP-1 (P < 0.000)] for all), the response to glucose was much greater (P < 0.005 for all). There was no increase in plasma GLP-1 when fructose was given after glucose. There was no difference in food intake after oral glucose or fructose. We conclude that oral fructose (75 g) stimulates GLP-1 (and insulin) secretion, but the response is less than that to 75 g glucose. These observations suggest that neither GLP-1 nor insulin play a major role in the regulation of satiation.

Adult↗

Effect of diet on the response to leptin in the marsupial Sminthopsis crassicaudata.

The aim of this study was to determine in the marsupial Sminthopsis crassicaudata 1) the effect of leptin on food intake, body fat stores, and metabolism and 2) whether leptin can prevent a diet-induced increase in adiposity. In response to 21 days of feeding with mealworms (2.99 kcal/g, 30% fat), body weight (P < 0. 0001) and tail width (P < 0.0001) increased, compared with control animals fed with laboratory diet (1.01 kcal/g, 20% fat). Subsequently, S. crassicaudata were randomly allocated to receive either laboratory diet or a choice between laboratory diet and mealworms. For 13 days, one-half of the animals in each dietary group received intraperitoneal human leptin (2.5 mg/kg twice daily), while the other one-half received phosphate-buffered saline. In animals receiving laboratory diet alone, leptin induced a decrease in body weight (P < 0.0001), tail width (P < 0.0001), and energy intake (P < 0.01). In animals receiving both laboratory diet and mealworms, leptin had no effect on body weight or tail width, although the proportion of laboratory diet eaten was reduced (P = 0. 0001), and there was a nonsignificant fall in overall energy intake (P = 0.07). We conclude that in S. crassicaudata, 1) a high-calorie, higher-fat diet induces an increase in adiposity and 2) leptin induces weight loss, but 3) an increase in dietary calories and fat content is associated with resistance to the actions of leptin.

Animals↗

[Sneddon syndrome new clinical and immunological data].

In 27 of 47 patients with Sneddon's syndrome (33 females, 14 males age 40 years) enzyme immunoassay has detected IgG-antibodies to prothrombin (aPT)--one of cofactor proteins responsible for binding of antiphospholipid antibodies (aPL) to phospholipids. Other aPL were also found: antibodies to cardiolipin (aCL), lupus anticoagulant (LA) in 14 and 27 patients, respectively. 37 (79%) patients had at least one of the studied aPL suggesting that such patients belong to patients with primary antiphospholipid syndrome. A correlation exists between aPT and LA: LA is detectable in 67% of aPT-positive patients compared to 45% of aPT-negative patients (p < 0.05). This is in agreement with the fact that prothrombin is a cofactor for most aPL registered as LA. Comparison of two subgroups of aPL patients different by dominant antigenic specificity (18 patients with aPT but free of ACL and 6 patients with aCP but free of aPT) demonstrated that the latter developed disorders of cerebral circulation, head ache, dementia and renal syndrome less frequently. aPT in Sneddon's syndrome seems to be a marker of comparatively low risk of thrombosis and less severe course of the disease.

Adolescent↗

Decreased glucose utilisation does not increase food intake in the marsupial Sminthopsis crassicaudata.

The marsupial Sminthopsis crassicaudata increases food intake following a fast. However, the role of metabolic fuel availability, in particular glucose, in the regulation of food intake in this animal is unknown. In this study, we have demonstrated that neither insulin-induced hypoglycaemia nor metabolic blockade of glucose utilisation with 2-deoxy-D-glucose effects food intake compared to saline-treated controls, suggesting that mechanisms other than glucose availability are important in the regulation of food intake in this marsupial. These data are discussed in the context of the role of glucoprivation in feeding in other mammals.

Animals↗

Food intake and food choice: the role of the endogenous opioid peptides in the marsupial Sminthopsis crassicaudata.

Endogenous opioid peptides activate food seeking behaviour and influence macronutrient choice in a number of animal species and previous studies have suggested that the palatability of food is strongly modulated by the opioid feeding system. The effect of opioid peptides on appetite and food choice in marsupials has not been evaluated. The aim of these studies was to determine the effect of mu, delta and K opioid receptors on food intake and food choice in the marsupial Sminthopsis crassicaudata. When offered a choice of mealworms or laboratory diet after 24 h food deprivation, S. crassicaudata ate predominantly mealworms. After a 24 h fast, adult male S. crassicaudata were injected peripherally with opioid receptor antagonists or saline. Animals were re-fed with either their laboratory diet alone, or a choice of laboratory diet and mealworms. In animals re-fed with laboratory diet alone, naloxone at doses of 15 and 10 mg/kg produced a 31% (P < 0.05) and 38% (P < 0.05) respectively reduction in food intake in the first 30 min after laboratory diet was re-introduced, but lower doses had no effect. The selective delta antagonist naltrindole at 20 mg/kg resulted in a 65% (P < 0.01) reduction in food intake compared to controls between 30 and 60 min. The selective kappa opioid antagonist nor-binaltorphimine had no effect on the intake of laboratory diet. In animals offered a choice of laboratory diet and mealworms, naloxone doses of 1, 5, 10, 15 and 20 mg/kg significantly decreased intake in the first 0.5 h after re-feeding, due to a preferential suppression of the intake of mealworms. Naltrindole and nor-binaltorphimine had no effect on food choice. These studies demonstrate that endogenous opioid peptides influence both food intake and choice in S. crassicaudata and that the role of the opioid feeding system is in part modulated by food palatability. In S. crassicaudata these effects appear to occur predominantly by a mu opioid receptor mechanism.

Animals↗

Identification of brown fat and mechanisms for energy balance in the marsupial, Sminthopsis crassicaudata.

The presence of brown adipose tissue (BAT) in marsupials is controversial because attempts to identify mitochondrial uncoupling protein (UCP) have been unsuccessful. Sminthopsis crassicaudata is a small nocturnal marsupial with an interscapular pad of adipose tissue. Electron microscopy revealed this tissue to have characteristics typical of BAT. GDP binding and UCP detection by immunoblot confirmed BAT. Expression of UCP was increased by cold exposure. When animals were placed from 28 to 15 degrees C, body temperature (Tb) decreased by 1.7 degrees C within 30 min and a further 1.0 degree C by 90 min (P < 0.001) before stabilizing at these lower levels. When animals were returned to 28 degrees C, Tb increased within 30 min (P < 0.001) and returned to basal by 120 min. When animals were maintained at 15 degrees C with ad libitum food for 12 days, Tb (P < 0.05), tail width (P < 0.04), and O2 consumption (P < 0.01) all decreased. The respiratory quotient increased (P < 0.001), indicating a change from fat to carbohydrate utilization. Food intake was unchanged, and body weight increased on day 1 (P < 0.01) before returning to baseline on day 3, remaining stable thereafter. These data suggest that although BAT is present in the marsupial S. crassicaudata, it may not be necessary for thermogenesis, at least in the short term. S. crassicaudata utilizes a plasticity in Tb and a change in substrate utilization to maintain energy balance and body composition without the need for an increase in metabolic rate or food consumption and without the need for torpor.

Acclimatization↗

Human recombinant lymphokines and cytokines induce pulmonary eosinophilia in the guinea pig which is inhibited by ketotifen and AH 21-132.

Subcutaneous or intraperitoneal injection of recombinant human granulocyte-macrophage colony-stimulating factor, interleukin 3, or mouse tumour necrosis factor alpha, but not recombinant human interferon gamma, platelet-derived growth factor, or transforming growth factor beta caused selective eosinophilia of the pulmonary airways in the guinea pig. Unlike responses to platelet-activating factor, there was no attendant detectable airway hyperreactivity, but in common with responses to platelet-activating factor, eosinophilia of the airways was prevented by pretreatment with ketotifen or AH21-132. Cytokines or lymphokines may contribute to pulmonary eosinophilia in diseases such as asthma.

Airway Resistance↗

Prevalence of genetic haemochromatosis among diabetic patients.

Since diabetes mellitus is a frequent manifestation of haemochromatosis the prevalence of the disease was investigated in 418 patients attending a diabetic clinic. 21 (5%) patients had a persistently high serum ferritin (men, over 400 micrograms/l; women, over 300 micrograms/l) and 5 of these had transferrin saturations consistently over 55%. Idiopathic haemochromatosis was confirmed by liver biopsy in 4 patients, all of whom had a hepatic iron index greater than 2.0. The prevalence rate of previously unrecognised idiopathic haemochromatosis was thus 9.6 per 1000 (general population prevalence 1 in 250), suggesting that screening of diabetic patients for this genetic disease may be more cost-effective than screening in the general population.

Adult↗

The effect of prophylactic anti-asthma drugs on PAF-induced airway hyperreactivity.

Intravenous injection of platelet activating factor (PAF) in anesthetized guinea pigs induces non-selective airway hyperreactivity. This response to PAF was reduced in a dose-dependent manner by systemic administration of established prophylactic anti-asthma drugs (ketotifen, cromoglycate, aminophylline and glucocorticosteroids) and by competitive antagonists of PAF. These inhibitory effects could not be accounted for by antagonism of histamine (H1), serotonin or peptidoleukotrienes receptors; parasympatholytic activity; cyclo-oxygenase or lipoxygenase inhibition; mast cell stabilization; or bronchodilatation. Infusion or injection of PAF to induce airway hyperreactivity in the guinea pig may provide a prospective test for prophylactic anti-asthma drugs.

Animals↗

Inhibition of PAF-induced eosinophil accumulation in pulmonary airways of guinea pigs by anti-asthma drugs.

Intraperitoneal (i.p.) injection of platelet activating factor (PAF) in guinea pigs caused a dose-related increase in the number of eosinophils recovered from bronchoalveolar lavage fluid (BALF). The prevalence of eosinophils in BALF had significantly increased within 1 hr of i.p. injection of PAF (10 micrograms/animal) and was maximal after 24 hr. Subcutaneous osmotic mini-pumps were used to administer drugs for 5 days prior to i.p. injection of PAF (10 micrograms/animal) and for the subsequent 24 hr. The percentage increase of eosinophils in BALF, due to PAF, was inhibited in animals treated with dexamethasone, aminophylline, cromoglycate, tranilast or ketotifen, but not in animals treated with oxatomide, azelastine, amlexanox, ibudilast or AA-861. These results suggest that inhibition of pulmonary eosinophilia may be a necessary property of prophylactic anti-asthma drugs and provide indirect evidence favoring a role for PAF in eosinophilia of asthma.

Animals↗

Congenital arteriovenous malformation rupturing into a true jejunal diverticulum.

Massive hemorrhage from the gastrointestinal tract of an elderly patient due to a hitherto unreported cause is described. A congenital arteriovenous malformation located in the submucosa of a true jejunal diverticulum ruptured into the lumen. Both selective angiographic demonstration and histologic documentation of the bleeding point are presented. The simultaneous presence of these two entities is probably not a coincidence and is discussed.

Aged↗

Mucinous hamartoma of the biliary dust system causing obstructive jaundice.

A unique case of obstructive jaundice due to a previously undescribed mucus-secreting hamartoma compressing the common bile duct is reported. The obstructing lesion was part of a diffuse hamartoma that originated within the walls of the intrahepatic bile ducts. Gross and microscopic findings are presented.

Bile Duct Neoplasms↗