H. Ditschuneit

Pathogenetic Implications of Ultrastructural Findings in Campylobacter pylori Related Gastroduodenal Disease

There is now substantial evidence that Campylobacter pylori (Cp) is able to colonize the gastroduodenal mucosa and is responsible for active chronic gastritis, its role in duodenitis, gastric ulceration and duodenal ulceration is still under debate. Cp has a lot of characteristics which are prerequisites for a pathogen: the typical S-shape, the corkscrew-like movement and the powerful urease and protease enzymes. These features allow a rapid movement through the mucous layer to permit access to the apical membranes of the surface mucous cells. There they adhere directly to the membranes and induce several ultrastructural alterations: degeneration of microvilli, depletion of mucous granules and an increase in sialic-acid rich glycoproteins in the apical part of the cytoplasma. Cp weakens the tight-junction complex and is found between the cells and sometimes intracellularly. Cp is phagocytized by invading polymorphonuclear leukocytes and causes an intense inflammatory response. These observations clearly demonstrate pathological alterations which in the cellular level induced by Cp with the result of a disrupted mucosal barrier of the stomach and the duodenum.

Ultrastructural localization of urease ofHelicobacter pylori

Helicobacter pylori urease was characterized by means of an enzyme histochemical electron microscopic technique. Ultrastructural analysis revealed no urease activity in one strain; in sevenH. pylori strains (43.75%), urease activity was associated with the cell membrane. Eight strains (50.0%) showed reaction product located within the cytoplasm. Urease activity showed no correlation with localization of activity. Our results demonstrate thatH. pylori urease is not uniform in allH. pylori strains, and differences in activity and localization of urease activity may account for different virulence activities.

Enhanced weight loss with protein‐enriched meal replacements in subjects with the metabolic syndrome

The objective of this study was to investigate the effects of a protein‐rich diet in comparison with a conventional protein diet on weight loss, weight maintenance, and body composition in subjects with the metabolic syndrome.

Lovastatin alters blood rheology in primary hyperlipoproteinemia : dependence on lipoprotein(a) ?

As part of a randomized, single‐blind, comparative study evaluating the efficacy of lovastatin and bezafibrate retard in the treatment of primary hypercholesterolemia, hemor‐heologic parameters (whole blood viscosity, hematocrit, plasma viscosity, red blood cell aggregation and de for mobility, and fibrinogen) were studied in 35 patients. Whole blood viscosity and plasma viscosity improved significantly after 3 months of treatment with lovastatin, whereas other hemorheologic variables remained unchanged. Stratifying 24 patients by their lipoprotein Lp(a) levels showed that in those with low Lp(a) (≤ 25 mg/dL) high‐density lipoprotein cholesterol increased and red blood cell aggregation as well as deformability decreased considerably, whereas in the group with high Lp (a) levels (>25 mg/dL), the opposite behavior was observed. Treatment of primary hypercholesterolemia with lovastatin may not only reduce the risk for atherosclerotic complications by its pronounced decrease of low‐density lipoprotein cholesterol, but also may favorably alter blood rheology, and may decrease insudation of plasmatic components into the arterial wall and improve tissue perfusion, in particular on the microcirculatory level. The possible relevance of Lp(a) levels for the hemorheologic effects of lovastatin remains to be elucidated.

Comparison of different HMG-CoA reductase inhibitors

SummaryThe HMG-CoA reductase inhibitors have been shown to cause marked reduction of cholesterol and offer a new and effective approach to treatment of hyperlipoproteinemia. Three agents, pravastatin (P), lovastatin (L) and simvastatin (S), have been studied with reference to long-term lipid-lowering effect, tolerance and clinical safety. Following a dietary lead-in period of at least 6 weeks in every case, patients with primary hypercholesterolemia were enrolled from participants of short-term controlled studies which after completion were extended as open studies. Treatment was administered over 6 months with 20 mg S (84 patients), L (42 patients) or P (23 patients) twice daily. Total cholesterol was decreased with S by 30.2% of basal, with L by 25.5%, and with P by 28.2%. The decrease in apolipoprotein B was 28.4%, of basal, with S 16.4% and in P 19.2%. Triglycerides were lowered by 19.6% of basal with S by 17.4%, with L, and by 6.4% with HDL-cholesterol increased in the S group by 23% of basal, by 9.7% in the L group, and by 8.0% in the P group. No serious clinical or laboratory abnormalities were observed. In the S group headache (3.6% of patients), abdominal discomfort (2.4%), sleeping disturbances (3.6%), and muscle pain (2.4%) were reported. In the L group headache (7.1%), abdominal discomfort (4.8%), sleep disorders (4.8%), and muscle pain (4.8%) were observed. In the P group one patient complained of abdominal discomfort (8.7%) and one of sleep disorders (8.7%). Increases in CPK were observed in the S group (4.8% of patients) and in the L group (11.9%). Increases in SGPT was measured in the S group (3.6% of patients), in the L group (7.1 %) and in the P group (4.4% ). None of the patients had to stop therapy because of adverse events. Clinical experience suggest that simvastatin is the inhibitor with the highest efficacy regarding cholesterol lowering, whereas pravastatin seems to the inhibitor that is best tolerated. However, more data are required for comparison of the complete profiles of these three compounds.

Proximal Gastric Motility Functions Are Normal in Severe Obesity

The role of altered gastric motor functions for the development of obesity is still unclear. In this study, we investigated whether severe obesity is related to gastric dysfunctions or to abnormal perception in response to distension. 31 obese patients and 20 healthy volunteers were studied using an electronic barostat. Basal gastric tone, gastric accommodation, and perception in response to distension were not altered in obese patients. The median minimal distending pressure, reflecting the intra-abdominal pressure, was significantly elevated in obese patients, being 12 versus 7 mm Hg, respectively (p < 0.0001). We conclude that the proximal gastric motility, including perception and accommodation in response to intragastric distension, is not impaired in severe obesity. Whether disturbances of gastric reflex relaxation in response to a meal are involved in the pathogenesis of obesity remains to be established.

Sympathetic modulation of lipolysis in subcutaneous adipose tissue: Effects of gender and energy restriction

To investigate the differences in the regulation of lipolysis between male and female obese subjects in vivo, we used an in situ microdialysis technique before and after 3 weeks of energy restriction. Using this method, we examined glycerol, glucose, and lactate responses after 5 minutes of epinephrine stimulation in the adipose tissues. Glycerol releases after the perfusion of phentolamine, orciprenaline, and propranolol were also studied. Sixteen subjects were studied (8 men, 8 women, 35 to 45 years of age, body mass index 38 to 50 kg/m2). In women, epinephrine provoked a greater glycerol release than in men in both abdominal and femoral regions (P < .05). In men and women there was a significant decrease in the concentration of glucose and a significant increase in lactate concentration after epinephrine stimulation (P < .001). After 3 weeks of energy restriction, glycerol release after epinephrine stimulation was greater in both sexes than that observed before energy restriction (P < .05). Both phentolamine and orciprenaline stimulated the release of glycerol (P < .01); phentolamine had a higher effect in women, while propranolol had no effect on glycerol release in both sexes. In summary, we have demonstrated that epinephrine provoked a greater lipolytic response in obese women in both abdominal and femoral adipose tissues. The lipolytic response was further enhanced after 3 weeks of energy restriction in each gender. The decrease in glucose concentration suggests that glucose may be reutilized for synthesis into new triacylglycerol. Knowledge about the sensitivity to lipolytic agents in subcutaneous adipose tissue may provide potential new approaches for modulating the lipolytic responses of subcutaneous adipose tissue differently in men and women.

Effects of moderate consumption of white wine on weight loss in overweight and obese subjects

BACKGROUND: Patients on dietary, weight-reducing treatment commonly are advised against alcohol consumption. In light of the widespread use of alcoholic beverages and the well-established benefits of light to moderate alcohol consumption in risk reduction, a revision of dietary treatment recommendations may be warranted.OBJECTIVE: To investigate whether daily consumption of moderate amounts of alcohol influences the effectiveness of an energy-restricted diet in overweight and obese subjects.DESIGN: A prospective randomized clinical trial was conducted, with a 3-months intervention period and two isocaloric dietary regimens containing 6.3 MJ (1500 kcal) each, one with 10% of energy from white wine and one with 10% of energy from grape juice. The trial was performed in obese subjects being recruited from the Obesity Outpatient Clinic at the University Hospital, Ulm, who all habitually consumed moderate amounts of alcohol. Out of 87 patients, 49 were eligible to participate and 40 completed the study (age 48.1±11.4 y, BMI 34.2±6.4 kg/m2). Efficacy parameters were body weight and biomarkers of good health.RESULTS: All subjects achieved significant body weight reduction. Weight loss in the grape juice group and white wine group was 3.75±0.46 and 4.73±0.53 kg, respectively. Percent body fat, waist circumference, blood pressure, blood glucose, insulin, triglycerides, and cholesterol were reduced. The antioxidant status was unchanged, as were liver enzyme activities and other safety parameters. There were no significant differences between the groups.CONCLUSIONS: An energy-restricted diet is effective in overweight and obese subjects used to drinking moderate amounts of alcohol. A diet with 10% of energy derived from white wine is as effective as an isocaloric diet with 10% of energy derived from grape juice.

Inhibition of human exocrine pancreatic secretion by the long‐acting somatostatin analogue octreotide (SMS 201‐995)

The new long‐acting somatostatin analogue octreotide (SMS 201–995) was investigated for its influence on segretatagogue‐stimulated human exocrine pancreatic secretion. Eighteen healthy volunteers participated in the study. During duodenal intubation with a background stimulation of either secretin 1 U.kg/h or secretin 1 U. kg/h + ceruletide, 120 ng.kg/h, octreotide was infused at doses of 5, 20 and 80 μg/h in a placebo‐controlled randomized double‐blind crossover trial. Duodenal juice samples were collected in 10‐min intervals, and amylase, trypsin, chymotrypsin, and bicarbonate were measured in the individual fractions.

Metformin inhibits catecholamine-stimulated lipolysis in obese, hyperinsulinemic, hypertensive subjects in subcutaneous adipose tissue: an in situ microdialysis study.

Aims Metformin has been reported to decrease the plasma concentrations of non‐esterified fatty acids in Type 2 diabetic subjects. This study investigated the effects of metformin on basal and catecholamine‐stimulated lipolysis in abdominal subcutaneous adipose tissue of obese, hyperinsulinaemic, hypertensive subjects.