bluuebunny/crossref_metadata_2025 huggingface dataset:
Diabetes mellitus and subjects' ageing: a study on the ATP content and ATP‐related enzyme activities in human erythrocytes
Authors: RABINI R. A. , PETRUZZI E. , STAFFOLANI R. , TESEI M. , FUMELLI P. , PAZZAGLI M. , MAZZANTI L.
Published: November 2003

Na+/K+‐ and Ca2+‐ATPase are the major ATP‐dependent membrane‐bound enzymes that regulate the cation transmembrane gradient which is altered both in red blood cell (RBC) senescence and in RBCs of diabetic patients. In an attempt to clarify the possible connection between diabetes mellitus and ageing, we investigated the relationship between RBC ATP content, Na+/K+‐ATPase, Ca2+‐ATPase activities and ageing in healthy, insulin‐dependent (IDDM) and non‐insulin‐dependent (NIDDM) subjects. A significant correlation was found (r = −0.82; P < 0.001) between RBC ATP content and subject's age only in the control group. A significant reduction in Na+/K+‐ATPase activity was observed in the older group (C2) of control subjects, in comparison with the younger (C1) one. In both IDDM and NIDDM subjects, the enzymatic activity was significantly decreased when compared with healthy subjects of similar age (P < 0.001). A significant negative correlation was found between age and enzymatic activity in healthy subjects (r = −0.60; P < 0.001). No difference was observed in the RBC membrane Ca2+‐ATPase activity between younger (C1) and older (C2) healthy subjects. Ca2+‐ATPase activity was significantly increased both in IDDM patients compared with C1 (P < 0.001) and in NIDDM patients compared with C2 (P < 0.001). The present data indicate that ageing causes a reduction in the erythrocyte ATP content in both healthy and diabetic subjects. In diabetic patients Na+/K+‐ATPase activity decreases independently of age.
Effects of high‐altitude chronic hypoxia on platelet α2‐receptors in man
Authors: ZACCARIA M. , BOREA P. A. , OPOCHER G. , PONCHIA A. , VARANI K. , FRACCAROLLO D. , SCANDELLARI C.
Published: November 2003

During chronic high‐altitude (HA) exposure, basal and exercise‐induced noradrenaline (NA) increases do not parallel blood pressure (BP) changes observed; unlike β‐adrenergic receptors, to our knowledge no data are available on α‐receptors. We studied platelet α2‐ and leucocyte β‐receptors and basal catecholamine levels in 11 trained climbers before and after they had spent a 15‐day period at a height of over 4400 m. In six of the climbers we also evaluated catecholamines after maximal bicycle ergometer exercise. After chronic high‐altitude exposure, a significant decrease was found in platelet α2‐receptor density and affinity [Bmax from 92.6 ± 6.7 to 54.6 ± 4.2 fmol mg−1 protein (P < 0.001) and KD from 1.271 ± 0.034 to 1.724 ± 0.077 nmol L−1 (P < 0.05)], although no changes to β‐receptors were observed. No changes were found in basal pre‐ and post‐expedition NA and adrenaline (A), and there was only a slight decrease in post‐expedition NA after maximal exercise. Our results suggest that prolonged exposure to hypoxia induces a down‐regulation of α2‐receptors, which may be a contributory factor in the regulation of the physiological vascular response to acclimatization.
Menopause‐associated changes in plasma lipids, insulin‐like growth factor I and blood pressure: a longitudinal study
Authors: POEHLMAN E. T. , TOTH M. J. , ADES P. A. , ROSEN C. J.
Published: November 2003

We examined the effects of the menopause transition on plasma lipids, insulin‐like growth factor I (IGF‐I) and blood pressure. An initial cohort of 38, non‐smoking, healthy premenopausal women (44–48 years) were examined at baseline and after a 6‐year follow‐up period. At follow‐up, 18 women had spontaneously stopped menstruating, whereas 17 women remained premenopausal. Women who experienced natural menopause showed a greater decline in high‐density lipoproteins (−5 ± 4 mg dL−1 vs. −1 ± 3 mg dL−1; P < 0.01) and a greater increase in low‐density lipoproteins (13 ± 12 vs. 5 ± 10 mg dL−1; P < 0.05) and fasting triglycerides (14 ± 15 vs. 5 ± 11 mg dL−1; P < 0.05) than women who remained premenopausal. No menopause effect was noted for total cholesterol. We noted a greater decline in IGF‐I levels in women who experienced a natural menopause (−21 ± 11 ng mL−1) than women who remained postmenopausal (−4 ± 10 ng mL−1). Systolic blood pressure increased in postmenopausal (13 ± 10 mmHg) compared with premenopausal women (5 ± 4 mmHg; P < 0.01), whereas no menopause effect was noted for diastolic blood pressure. The increase in the waist‐to‐hip ratio was related to a decrease in high‐density lipoprotein (r = −0.49; P − 0.05) and increase in low‐density lipoproteins (r = 0.48; P < 0.05). The decline in IGF‐I was related to the decline in reported leisure time physical activity (0.44; P < 0.05). We conclude that the natural menopause transition is associated with a worsening of the lipid profile and decline in IGF‐I, which might be mitigated by deleterious changes in body fat distribution and physical activity.
Cytokine profiles in bronchoalveolar lavage fluid and blood in HIV‐seropositive patients with Pneumocystis carinii pneumonia
Authors: PERENBOOM R. M. , SAUERWEIN R. W. , BECKERS P. , VAN SCHIJNDEL A. C. H. W. , VAN STEENWIJK R. P. , BORLEFFS J. C. C. , VAN LEUSEN R. , VAN DER MEER J. W. M.
Published: November 2003

Concentrations and ex vivo production of interleukin 1β (IL‐1), tumour necrosis α (TNF), interleukin 6 (IL‐6), interleukin‐1 receptor antagonist (IL‐1RA) and TNF soluble receptors (sTNF‐receptors, P55 and P75) were measured in bronchoalveolar lavage (BAL) fluid and blood in 23 HIV‐seropositive (HIV+) patients with Pneumocystis carinii pneumonia (PCP) and compared with values found in healthy HIV‐seronegative (HIV−) controls and asymptomatic HIV+ subjects. Concentrations of the proinflammatory cytokine IL‐1β were increased in BAL fluid of HIV+ patients with PCP (184 ± 47 pg mL−1) compared with undetectable levels in healthy control subjects (P = 0.0001). In plasma of these patients higher concentrations of the anti‐inflammatory cytokine IL‐1RA were found during acute PCP than after recovery (2.1 ± 0.7 vs. 0.5 ± 0.2 ng mL−1, P = 0.01). No correlations could be found between cytokine concentrations and clinical severity of the infection. Corticosteroid treatment did not influence cytokine concentrations in BAL or blood, nor did it suppress the production in alveolar cells. In whole‐blood cultures, however, lipopolysaccharide (LPS)‐stimulated production was significantly suppressed for IL‐1 (1.3 vs. 5.5 ng mL−1, P = 0.009) and for IL‐6 (0.6 vs. 2.5 ng mL−1, P = 0.01). The overall data show that in HIV+ patients with PCP (similar to what we had found previously in HIV− patients with PCP) proinflammatory cytokines are more prominently present in BAL, whereas anti‐inflammatory reaction is predominant in the circulation.
Clinical results of long‐term slow‐release lanreotide treatment of acromegaly
Authors: GIUSTI M. , CICCARELLI E. , DALLABONZANA D. , DELITALA G. , FAGLIA G. , LIUZZI A. , GUSSONI G. , GIORDANO DISEM G.
Published: November 2003

Medical therapy is frequently needed to normalize growth hormone/insulin‐like growth factor I secretion in acromegaly. The aim of this study was to determine the long‐term effects of the slow‐release (SR) somatostatin analogue lanreotide in 57 acromegalic patients. SR lanreotide (30 mg) was given every 14 days for 12 months. In 33% of patients, the drug dosage was raised to 60 mg and/or the time interval was shortened to 10 days. Two months of clinical evaluation followed drug discontinuation in 47 out of 48 (84%) patients who com‐pleted the 12‐month period. A drug‐related decrease in GH/IGF‐I levels was observed. Basal GH/IGF‐I levels were significantly (P < 0.001) reduced at 12 months. IGF‐I was normalized in 35% of patients and GH levels were < 5 μg L−1 in 54%. There was a clinical improvement in patients complaining of joint pain, rachialgias, headache, digital paraesthesias and hyperhidrosis. Soft‐tissue changes were documented by significant (P < 0.001) decreases in finger size. In 52 (91%) patients without overt diabetes, a slight but significant increase in integrated glycaemia (P < 0.001) was noted, while integrated insulin levels were reduced (P < 0.001). Of 33 (58%) patients with normal basal ultrasound examination of the gall bladder, three (9%) had developed asymptomatic gall stones or biliary sludge after 12 months. Adverse events were generally mild. They frequently (52%) occurred after the first SR lanreotide administration; only 28% were recurrent and 20% appeared for the first time during therapy. SR lanreotide is an effective treatment in most unselected acromegalic patients. Tolerance towards the drug is high. Subjective benefits seem to override the simple biochemical control of the disease. Glucose homeostasis more than the incidence of gall stones seems to require monitoring on therapy. SR lanreotide is clearly advantageous in improving patient compliance with medical treatment for acromegaly.
Impaired arterial but not venous responsiveness to nitroglycerin in non‐insulin‐dependent diabetes mellitus
Authors: HUVERS F. C. , SCHAPER N. C. , HOUBEN A. J. H. M. , HOFSTRA L. , KITSLAAR P. J. E. H. M. , DE LEEUW P. W. , NIEUWENHUIJZEN KRUSEMAN A. C.
Published: November 2003

In earlier studies, the response of the arterioles to nitroglycerin (NTG) was found to be impaired in non‐insulin‐dependent diabetes mellitus (NIDDM) patients. NTG has major therapeutic effects in reducing cardiac after‐ and preload. Thus, the vasorelaxing efficacy of a therapeutic dose of 0.4 mg of NTG sublingually (s.l.) was evaluated in the conduit femoral artery and large veins of normotensive, normoalbuminuric NIDDM patients. After NTG, the increase in the femoral artery diameter was significantly lower in the NIDDM patients than in control subjects: 0.49 (0.29–0.79) vs. 0.75 (0.47–1.00) mm respectively (median, interquartile ranges). NTG resulted in an increase of pulse wave transit time in the aorta in control subjects but not in the NIDDM patients: from 64 (60–73) to 70 (63–80) ms, P < 0.02; and from 62 (53–69) to 66 (51–72) ms, P = NS, respectively. The reduction in the venous tone of the forearm to NTG was similar in both groups. These results suggest that the response to NTG is impaired in the arterial system but not in the venous system in well‐regulated NIDDM patients without diabetic complications.
The effect of vitamin C in high doses on plasma and biliary lipid composition in patients with cholesterol gallstones: prolongation of the nucleation time
Authors: GUSTAFSSON U. , WANG F.‐H. , AXELSON M. , KALLNER A. , SAHLIN S. , EINARSSON K.
Published: November 2003

Vitamin C deficiency in guinea pigs leads to cholesterol supersaturation of bile and formation of cholesterol gallstones. It has been suggested that there may also exist an association between vitamin C and cholesterol gallstones in man, but such a relationship has not been studied in gallstone patients. In order to study the possible effects of vitamin C on gallstone disease in humans, plasma lipid levels, hepatic cholesterol metabolism, biliary lipid composition, cholesterol saturation and nucleation time of gallbladder bile were analysed in 16 consecutive gallstone patients, who were planned for laparoscopic cholecystectomy and were treated with vitamin C (500 mg, four times a day) for 2 weeks before surgery. The plasma concentration of vitamin C increased by 42% in the treatment group. The concentrations of plasma lipids did not differ before and after vitamin C treatment; nor did the plasma levels of lathosterol and 7α‐hydroxy‐4‐cholesten‐3‐one, reflecting cholesterol and bile acid synthesis respectively. The relative concentrations of cholesterol, bile acids and cholesterol concentration of bile did not differ significantly between the two groups, but the relative concentration of phospholipids was slightly higher in the treated group. The bile acid composition was changed; the percentage of cholic acid being lower and those of deoxycholic acid, ursodeoxycholic acid and lithocholic acid higher in the vitamin C‐treated patients compared with the untreated group. The nucleation time was significantly longer in the treatment group (7 days) compared with the untreated group (2 days). Our findings indicate that vitamin C supplementation may also influence the conditions for cholesterol gallstone formation in humans.
Carbonic anhydrase II in the cerebrospinal fluid: its value as a disease marker
Authors: PARKKILA A.‐K. , PARKKILA S. , REUNANEN M. , NIEMELÄ O. , TUISKU S. , RAUTAKORPI I. , RAJANIEMI H.
Published: November 2003

Carbonic anhydrase (CA) II is the predominant CA isoenzyme in the brain of mammals. We have recently developed a dual‐label time‐resolved immunofluorometric assay to quantify minute amounts of CA I and II in the cerebrospinal fluid (CSF). The present study was aimed at elucidating the clinical value of such measurements in the case of neurological disorders. Lumbar CSF samples were obtained from 111 patients suffering from various neurological diseases and from 97 control patients with no specific signs of central nervous system diseases. The highest CA II concentrations were found in patients with brain infarction (median 66.5 μg L−1, n = 20), whereas the control patients had markedly lower values (median 7.8 μg L−1, n = 97). Relative to a reference range calculated from the control material (10.2 ± 17.2 μgL −1), the sensitivity of CA II measurement in differentiating brain infarction was 100%. Patients with transient ischaemic attack (median 11.2 μg L−1, n = 9), multiple sclerosis (median 14.7 μg L−1, n = 18) or epilepsy (median 20.3 μg L−1, n = 17) usually had CA II concentrations within the normal range, but those with central nervous system infection (n = 14), dementia (n = 19) or trigeminal neuralgia (n = ;6) tended to have higher CA II levels in their CSF, the median values being 39.1 μg L−1, 45.5 μg L−1 and 44.0 μg L−1 respectively. The findings indicate that the concentration of CA II in the CSF marks disease activity in patients with brain damage. This finding could provide a basis for further studies estimating the value of CA II measurement as a new laboratory marker of diseases affecting the brain.
Response of myocardial cellular energy metabolism to variation of buffer composition during open‐chest experimental cardiopulmonary resuscitation in the pig
Authors: WIKLUND L. , RONQUIST G. , ROOMANS G. M. , RUBERTSSON S. , WALDENSTRÖM A.
Published: November 2003

The aim of the present study was to investigate possible relationships in piglets between myocardial energy‐related metabolites and intracellular electrolytes during open‐chest cardiopulmonary resuscitation (OCCPR) supplemented by the administration of alkaline buffers with varying sodium content. Our hypothesis was that an increasing myocardial intracellular sodium content would decrease the intracellular energy stores. In addition to haemodynamics, acid–base and blood gas variables were analysed, and myocardial biopsies were collected before and during OCCPR as well as after the return of spontaneous circulation. After a period of 4 min of untreated ventricular fibrillation (VF), 25 piglets were randomly allocated to one of four groups: OCCPR with normal saline (n = 5); OCCPR with sodium bicarbonate (SB) (n = 7); OCCPR with Tris buffer mixture (TBM) (n = 7); and a totally untreated control group (n = 6). The results showed that 4 min of untreated VF almost eradicated creatine phosphate (CrP) and that the ATP/ADP ratio decreased to 1.5–2.0. During OCCPR with normal saline, the myocardial content of CrP increased, whereas lactate, ATP and ADP levelled off and AMP decreased, causing an increased ATP/ADP ratio. The adenosine and inosine contents increased, whereas inosine monophosphate was unchanged at a low level, the adenosine and inosine contents being inversely correlated with the total content of adenine nucleotides. In both buffered groups, the increase in most energy‐related metabolites (CrP, ATP, ADP, AMP and the ATP/ADP quotient) was less and in lactate more pronounced than in the group not being buffered, with no difference between the groups receiving SB or TBM. Although the intracellular potassium content was unaltered, the sodium, chloride and calcium concentrations increased, more so in the group receiving SB. The intracellular content of sodium was correlated with that of calcium. Thus, buffering increased the myocardial AMP degradation during OCCPR by increasing the flux via the 5′‐nucleotidase reaction, and SB increased the intracellular contents of sodium and calcium to a greater extent than did TBM.
Smoking cessation improves insulin sensitivity in healthy middle‐aged men
Authors: ELIASSON B. , ATTVALL S. , TASKINEN M.‐R. , SMITH U.
Published: November 2003

Cigarette smokers have recently been shown to exhibit insulin resistance, dyslipidaemia and markers of the insulin resistance syndrome (IRS). The aim of this study was to examine the effects of smoking cessation on insulin sensitivity and IRS. Forty male, non‐obese healthy smokers participated in this open parallel study with 8 weeks of follow‐up. Seventeen subjects were able to stop smoking, while 23 subjects continued to smoke and served as a controls group. Anthropometric and metabolic data were measured. Degree of insulin sensitivity was determined with the euglycaemic hyperinsulinaemic clamp technique. Smoking cessation increased insulin sensitivity and improved the lipoprotein profile in spite of a modest increase in body weight. Initial smoking habits correlated positively with the increase in BMI as well as the improvements in the metabolic variables after smoking cessation. These data support the view that smoking causes insulin resistance and IRS, and also demonstrate that the beneficial metabolic effects of smoking cessation override the effects of an accompanying modest increase in body weight.
Effects of aerobic exercise training and yoga on the baroreflex in healthy elderly persons
Authors: BOWMAN A. J. , CLAYTON R. H. , MURRAY A. , REED J. W. , SUBHAN M. M. F. , FORD G. A.
Published: November 2003

It is unclear whether the age‐associated reduction in baroreflex sensitivity is modifiable by exercise training. The effects of aerobic exercise training and yoga, a non‐aerobic control intervention, on the baroreflex of elderly persons was determined. Baroreflex sensitivity was quantified by the α‐index, at high frequency (HF; 0.15–0.35 Hz, reflecting parasympathetic activity) and mid‐frequency (MF; 0.05–0.15 Hz, reflecting sympathetic activity as well), derived from spectral and cross‐spectral analysis of spontaneous fluctuations in heart rate and blood pressure. Twenty‐six (10 women) sedentary, healthy, normotensive elderly (mean 68 years, range 62–81 years) subjects were studied. Fourteen (4 women) of the sedentary elderly subjects completed 6 weeks of aerobic training, while the other 12 (6 women) subjects completed 6 weeks of yoga. Heart rate decreased following yoga (69 ± 8 vs. 61 ± 7 min−1, P < 0.05) but not aerobic training (66 ± 8 vs. 63 ± 9 min−1, P = 0.29). VO2 max increased by 11% following yoga (P < 0.01) and by 24% following aerobic training (P < 0.01). No significant change in αMF (6.5 ± 3.5 vs. 6.2 ± 3.0 ms mmHg−1, P = 0.69) or αHF (8.5 ± 4.7 vs. 8.9 ± 3.5 ms mmHg−1, P = 0.65) occurred after aerobic training. Following yoga, αHF (8.0 ± 3.6 vs. 11.5 ± 5.2 ms mmHg−1, P < 0.01) but not αMF (6.5 ± 3.0 vs. 7.6 ± 2.8 ms mmHg−1, P = 0.29) increased. Short‐duration aerobic training does not modify the α‐index at αMF or αHF in healthy normotensive elderly subjects. αHF but not αMF increased following yoga, suggesting that these parameters are measuring distinct aspects of the baroreflex that are separately modifiable.
No acute effects of smoking and nicotine nasal spray on lipolysis measured by subcutaneous microdialysis
Authors: ELIASSON B. , SMITH U. , LÖNNROTH P.
Published: November 2003

Smoking is associated with insulin resistance, dyslipidaemia and markers of the insulin resistance syndrome. This study investigated adipose tissue lipolysis in situ by subcutaneous microdialysis twice in 10 healthy, male smokers after smoking four cigarettes over 2 h and after the administration of an equal amount of nicotine given as nasal spray (NNS). Glucose and insulin levels, in situ lipolysis and adipose tissue blood flow were studied in the post‐absorptive state and after a 75‐g oral glucose tolerance test (OGTT). Post‐absorptively, acute smoking and NNS increased neither subcutaneous adipose tissue glycerol production nor plasma free fatty acid (FFA) or glycerol levels. After the OGTT, plasma insulin and lactate levels were significantly higher after smoking, whereas FFA levels were higher after NNS. Normal smoking or the administration of a normal dose of NNS caused only minor metabolic changes. Thus, it does not seem likely that increased lipolysis is an important contributor to the dyslipidaemia seen in smokers.
The effects of insulin on transport and metabolism of glucose in skeletal muscle from hyperthyroid and hypothyroid rats
Authors: DIMITRIADIS G. , PARRY‐BILLINGS M. , BEVAN S. , LEIGHTON B. , KRAUSE U. , PIVA T. , TEGOS K. , CHALLISS R. A. J. , WEGENER G. , NEWSHOLME E. A.
Published: November 2003

The effects of insulin on the rates of glucose disposal were studied in soleus muscles isolated from hyper‐ or hypothyroid rats. Treatment with triiodothyronine for 5 or 10 days decreased the sensitivity of glycogen synthesis but increased the sensitivity of lactate formation to insulin. The sensitivity of 3‐O methylglucose to insulin was increased only after 10 days of treatment and was accompanied by an increase in the sensitivity of 2‐deoxyglucose phosphorylation; however, 2‐deoxyglucose and glucose 6‐phosphate in response to insulin remained unaltered. In hypothyroidism, insulin‐stimulated rates of 3‐O‐methylglucose transport and 2‐deoxyglucose phosphorylation were decreased; however, at basal levels of insulin, 3‐O‐methylglucose transport was increased, while 2‐deoxyglucose phosphorylation was normal. In these muscles, the sensitivity of lactate formation to insulin was decreased; this defect was improved after incubation of the muscles with prostaglandin E2. The results suggest: (a) in hyperthyroidism, insulin‐stimulated rates of glucose utilization in muscle to form lactate are increased mainly because of a decrease in glycogen synthesis; when hyperthyroidism progresses in severity, increases in the sensitivity of glucose transport to insulin and in the activity of hexokinase may also be involved; (b) in hypothyroidism, the decrease in insulin‐stimulated rates of glucose utilization is caused by decreased rates of glycolysis; (c) prostaglandins may be involved in the changes in sensitivity of glucose utilization to insulin observed in muscle in altered thyroid states.
Study of biochemical substrate and role of metalloproteinases in fascia transversalis from hernial processes
Authors: BELLÓN J. M. , BUJÁN J. , HONDUVILLA N. G. , JURADO F. , GIMENO M. J. , TURNAY J. , OLMO N. , LIZARBE M. A.
Published: November 2003

The aim of this study was to examine the fascia transversalis (FT) from patients with direct and indirect hernia in an attempt to identify possible differences between each type of hernia. FT samples were obtained from 36 patients presenting inguinal hernia (23 indirect hernia and 13 direct hernia) who underwent surgery. We have analysed the ultrastructure of the fascia surrounding the hernial lesions, the proline and lysine hydroxylation in the tissue, the type I–type III collagen ratio and the presence of metalloproteinases. We have not detected ultrastructural differences in the collagen fibrils from FT in direct and indirect hernias. However, the interfibrillar matrix was more abundant in direct hernias, showing abundant electron‐dense particles. No differences in proline hydroxylation were observed between each type of hernia. A small decrease in lysine hydroxylation was detected in patients with direct hernia. Enzyme‐linked immunosorbent assays (ELISAs) showed no statistically significant differences in the type I–type III collagen absorbance ratios. Immunohistochemistry revealed no differences in the expression of matrix metalloproteinase‐1. FT from patients presenting direct hernia showed a very strong staining vs. metalloproteinase‐2 when compared with that observed in indirect hernia.
Relationship between lipoprotein(a) phenotypes and albumin excretion rate in non‐insulin‐dependent diabetes mellitus: protective effect of ‘null’ phenotype?
Authors: HERNÁNDEZ C. , SIMÓ R. , CHACÓN P. , SEGARRA A. , LÓPEZ D. , MESA J.
Published: November 2003

The possible association between lipoprotein(a) [Lp(a)] and albumin excretion rate (AER) is a topic that generates conflicting views. In addition, Lp(a) phenotypes have not previously been considered as factors influencing AER. In order to clarify this issue, we studied 70 non‐insulin‐dependent diabetes mellitus (NIDDM) patients without clinically detectable macroangiopathy, 27 with microalbuminuria and 43 without it. Both groups were matched for the known variables that could influence AER and serum Lp(a) levels. Lp(a) was determined by enzyme‐linked immunosorbent assay (ELISA), and Lp(a) phenotypes were assessed by electrophoresis followed by immunoblotting. Lp(a) phenotypes were grouped as follows: ‘small’ (F, S1 and S2), ‘big’ (S3 and S4) and ‘null’. The NIDDM patients with microalbuminuria presented higher serum Lp(a) concentrations than the patients without it [15.7 mg dL−1 (95% CI 0.5–36.5) vs. 4.5 mg dL−1 (95% CI 0.1–18.5); P < 0.001] and a direct correlation between Lp(a) and AER was observed (r = 0.34; P < 0.01). AER was significantly different when Lp(a) phenotypes were considered [‘small’: median 19 μg min−1 (range 1–195); ‘big’: median 9.5 μg min−1 (range 1–186); ‘null’: 4 μg min−1 (range 1–9); P = 0.04]. None of the NIDDM patients with a ‘null’ phenotype showed an AER of > 10 μg min−1. In conclusion, this case–control study provides evidence that microalbuminuria is associated with high serum Lp(a) in NIDDM without clinically detectable macroangiopathy. Furthermore, NIDDM patients with a ‘null’ phenotype could be considered at low risk for the development of microalbuminuria.
Growth hormone improves cardiac function in rats with experimental myocardial infarction
Authors: ISGAARD J. , KUJACIC V. , JENNISCHE E. , HOLMÄNG A. , SUN X. Y. , HEDNER T. , HJALMARSON Å. , BENGTSSON B.‐Å.
Published: November 2003

Accumulating evidence suggests from experimental and clinical studies beneficial effects of growth hormone (GH) on contractility, although concomitant cardiac hypertrophy, generally considered to be a cardiovascular risk factor, has also been reported. In the present study, we combine a rat model with impaired cardiac performance after myocardial infarction (MI) with echocardiographic evaluation of GH effects on cardiac structure and function. We have used a rat model with ligation of the left coronary artery in normal, growing male rats resulting in subsequent impaired cardiac performance. After 6 weeks’ recovery, blind transthoracic echocardiography was performed to determine infarction size, cardiac geometry and performance. Rats with no signs of myocardial infarction were excluded from the study. After randomization, the rats were treated with daily s.c. injections of saline (n = 8) or recombinant human growth hormone (rhGH) (n = 6) at a dose of approximately 1 mg kg−1 body weight for 1 week. A new blind echocardiography examination was performed after treatment demonstrating a 13% increase in ejection fraction (EF) and a 50% increase in cardiac index in GH‐treated rats compared with control rats (P < 0.01). Moreover, GH caused a significant decrease in end‐systolic volume. There were no significant changes in left ventricular (LV) or interventricular wall thickness, LV dimensions, heart rate or diastolic function. No effects were seen on LV weight, cardiac insulin‐like growth factor (IGF) I, IGF‐I receptor and GH receptor mRNA content. GH in a physiological dose improves systolic function in an experimental model of heart failure without signs of hypertrophy, suggesting a potential role as a therapeutic agent in the treatment of heart failure and merits further investigation.
Effects of hemicolectomy on bile acid metabolism in relation to colon carcinogenesis in man
Authors: VAN GORKOM B. A. P. , CATS A. , VAN DER MEER R. , KUIPERS F. , VERSCHUEREN R. C. J. , MULDER N. H. , DE VRIES E. G. E. , KLEIBEUKER J. H.
Published: November 2003

Bile acids are probably important in colon carcinogenesis. Regional differences in bile acid metabolism within the colon were studied to illuminate the preferential distal occurrence of colon cancer in Western countries. Faeces (24 h) were collected for bile acid measurement from 25 patients with hemicolectomy (nine left and 16 right) and 17 adenoma patients with an intact colon (control subjects). Duodenal bile and cytolytic and alkaline phosphatase activity of faecal water were also studied. The median percentage of deoxycholic acid (DCA) was lower in the hemicolectomy groups [left 48% (range 38–57%), right 45% (2–62%) vs. control subjects 59% (38–70%), P < 0.05]. In duodenal bile, the proportion of DCA in left [4% (1–25%)] was lower than in the patients with right hemicolectomy [19% (0–69%)] and control subjects [24% (7–50%)], P < 0.05. Faecal concentration of protonated DCA was higher in those with right hemicolectomy (0.101 μmol g−1) than in those with left hemicolectomy (0.048 μmol g−1), which coincided with a higher cytolytic [right 49% (3–93%), left 2% (1–37%)] and alkaline phosphatase activity [right 6.7 U mL−1 (1.2–40.1 U mL−1), left (2.0 U mL−1 (1–25.7 U mL−1), both P < 0.02]. These findings suggest differences in bile acid metabolism between the proximal and distal colon that may contribute to the disparity in cancer risk.
Stimulation of arginine vasopressin secretion by a small increase in blood ionized calcium in normal men
Authors: CHIODERA P. , VOLPI R. , CAPRETTI L. , CAFFARRI G. , PILLA S. , COIRO V.
Published: November 2003

Evidence has been provided for an increase in baseline serum corticotrophin (ACTH) levels in response to a rise in circulating ionized calcium (Cai) levels within the physiological range. In order to establish whether small Cai increments are also able to modify the basal secretion of arginine vasopressin (AVP), we infused calcium gluconate through an intravenous infusion pump in eight healthy male subjects (25–31 years old). Serum Cai, ACTH and AVP concentrations were measured every 10 min over an infusion period lasting 90 min. A significant progressive rise in serum Cai (baseline: 42 ± 0.9 mg dL−1; 90 min: 47.2 ± 0.9 mg dL−1, P < 0.001), ACTH (baseline: 30.7 ± 1.3 pg mL−1; mean peak at 80 min: 37.4 ± 2.4 pg mL−1, P < 0.01) and AVP levels (baseline: 2.1 ± 0.6 pg mL−1; mean peak at 80 min: 3.2 ± 0.5 pg mL−1, P < 0.01) was observed during calcium infusion. Furthermore, a significant positive correlation (r = 0.71; P < 0.001) was observed between ACTH and AVP responses to calcium infusion at 60, 70, 80 and 90 min. These data demonstrate that AVP secretion is stimulated by a slight rapid increase in serum Cai levels even though absolute serum Cai levels remain within the normal range. In addition, the positive correlation between Cai‐induced ACTH and AVP increments suggests that AVP plays a releasing role on ACTH secretion during calcium infusion.
Thrombosis triggered by severe arterial lesions is inhibited by oral administration of a glycoprotein IIb/IIIa antagonist
Authors: BADIMON J. J. , MEYER B. , FEIGEN L. P. , BARON D. A. , CHESEBRO J. H. , FUSTER V. , BADIMON L.
Published: November 2003

Platelet aggregation and thrombosis play an important role in the onset of acute coronary events. Regardless of the stimulus for activation, platelet thrombus formation is ultimately regulated through the IIb/IIIa receptor complex. The effects of oral administration of xemilofiban, a non‐peptide mimetic of the RGDF sequence of the IIb/IIIa receptor complex, on thrombus formation were evaluated in a canine model. Xemilofiban significantly reduced platelet deposition on severely damaged arterial wall. Platelet deposition was reduced at both low (13 ± 1 from 56 ± 18 × 106 platelets cm−2; P < 0.05) and high (23 ± 2 from 111 ± 21 × 106 platelets cm−2; P < 0.01) shear rates. Platelet deposition was reduced to a monolayer as seen by electron microscopy (platelet–vessel wall interaction). Therefore, the availability of an orally active IIb/IIIa antagonist for chronic use may have significant value in preventing thrombus formation in those clinical situations associated with severe arterial injury, such as atherosclerotic plaque disruption.
Glucagon‐like peptide‐1 (GLP‐1): a trial of treatment in non‐insulin‐dependent diabetes mellitus
Authors: TODD J. F. , WILDING J. P. H. , EDWARDS C. M. B. , KHAN F. A. , GHATEI M. A. , BLOOM S. R.
Published: November 2003

Glucagon‐like peptide‐1 (7–36) amide (GLP‐1) is released from the gut into the circulation after meals and is the most potent physiological insulinotropic hormone in man. In contrast to presently available therapeutic agents for non‐insulin‐dependent diabetes mellitus (NIDDM), GLP‐1 has the advantages of both suppressing glucagon secretion and delaying gastric emptying. We report the first chronic study of subcutaneous (s/c) GLP‐1 treatment in NIDDM. Five patients with poorly controlled NIDDM were entered into a six‐week, double‐blind crossover trial. Each received three weeks treatment with s/c GLP‐1 40 nmol or saline, given three times a day immediately before meals. A standardized test meal was given at the beginning and end of each treatment period. GLP‐1 reduced plasma glucose area under the curve (AUC) following the standard test meal by 25% (AUC, 0–180 mins, GLP‐1 start of treatment 482.2 ± 38.2 vs. saline start of treatment 635.7 ± 45.4 mmol min L−1, F = 16.4, P < 0.02). The beneficial effect of GLP‐1 on plasma glucose concentration was fully maintained for the three‐week treatment period. Plasma glucagon levels were significantly lower for 60 min postprandially after GLP‐1 treatment. In this group of patients there was no significant increase in postprandial insulin levels with GLP–1. We have demonstrated a significant improvement in postprandial glycaemic control with s/c GLP‐1 treatment that was fully maintained over a three‐week treatment period. GLP‐1 improves glycaemic control even in the absence of an insulinotropic effect and is a potential treatment for NIDDM.
Western blotting of NC1 type IV collagen fragments in human plasma
Authors: WERLE E. , HAO L. , HASSLACHER C. , FIEHN W.
Published: November 2003

Collagen IV matrix of glomerular basement membrane may be involved in the development of various renal diseases, e.g. diabetic nephropathy. An immunoblotting method for the detection of the carboxy‐terminal non‐collagenous (NC1) domain of type IV collagen in plasma was developed. The high sensitivity down to the picogram range enabled characterization of NC1(IV) fragments in human blood for the first time. Both Western blotting and gel filtration chromatography coupled with an enzyme‐linked immunoassay surprisingly revealed that the NC1(IV)‐related components are bound to the fibrin clot forming during blood coagulation. About 40% of the NC1(IV) fragments in plasma had an apparent molecular mass higher than 340 000. Abnormal NC1(IV) immunoblot patterns were observed in about 50% of patients with insulin‐dependent (n = 20) and non‐insulin‐dependent (n = 20) diabetes mellitus compared with less than 7% in healthy control subjects (n = 30). There were no obvious associations between abnormal immunoblots and stage of nephropathy or glycaemic control in diabetic subjects.
Experimental hydatid disease of the liver
Authors: ŞAHIN M. , AYDIN A. , BÜLBÜLOĞLU E. , CIRALIK H.
Published: November 2003

Hydatid disease caused by Echinococcus granulosis is an endemic problem in many parts of the world and the liver is the most frequently involved organ. A suitable experimental model for hydatid disease of the liver, resembling naturally infected livers, is established in this study by injection of protoscolices via the mesenteric vein of the mice. This model can be used in assessment of the efficacy of various agents in treatment of hydatid disease of the liver.
Low‐density lipoprotein‐induced formation of nitric oxide by cultured vascular smooth muscle cells of the rat
Authors: LOCHER R. , SUTER P. M. , WEISSER B. , VETTER W.
Published: November 2003

There is evidence that low‐density lipoprotein (LDL) plays a crucial role in atherogenesis. On the cellular level, LDL has been shown to activate a number of mechanisms involved in atherogenesis and vasoconstriction. Local immoderate vasoconstriction is physiologically antagonized by nitric oxide, which is released from the endothelium. To find out whether LDL also influences the synthesis of nitric oxide in vascular smooth muscle cells, both the conversion of arginine to citrulline and the production of nitrite were determined as a measure of nitric oxide formation. After incubation of rat vascular smooth muscle cells with native LDL (25 μg mL−1) for 24 h, the production of both l‐[14C]‐citrulline [39 600 (3600) cpm mg−1 cell protein] and nitric oxide [2.95 (0.56) μmol L−1] were about twice and 1.5‐fold the amount of the corresonding values in untreated cells (mean ± SD, P < 0.05, n = 4). Oxidized LDL was less effective than the native form. The presence of the arginine analogue NG‐methyl‐l‐arginine reduced citrulline production dose‐dependently but augmented DNA synthesis, both induced by LDL. In addition, the lipoprotein caused a 1.6‐fold increase in cyclic GMP production following a 24‐h incubation [control = 10.9 (3.8) pmol mg−1 cell protein, P = 0.016]. The results suggest that native LDL might partly impair its atherogenic potential on the vasculature by stimulating the production by smooth muscle cells of both nitric oxide and cyclic GMP.
Chronic administration of propranolol improves vascular contractile responsiveness in portal hypertensive rats
Authors: HUANG Y.‐T. , LIN H.‐C. , TSAI J.‐F. , HOU M.‐C. , HONG C.‐Y.
Published: November 2003

Propranolol is used clinically as a prophylactic drug to prevent oesophageal variceal bleeding in cirrhotic patients with portal hypertension. Vascular hyporesponsiveness is a common characteristic of the portal hypertensive state. The present study aimed to investigate whether chronic administration of propranolol could improve vascular responsiveness in portal hypertensive rats. Portal hypertension was induced by partial portal vein ligation (PVL). Sham‐operated rats served as controls. There were four study groups: PVL–propranolol group (portal hypertensive rats receiving propranolol), PVL–vehicle group (portal hypertensive rats receiving saline), sham–propranolol group (sham‐operated rats receiving propranolol) and sham–vehicle group (sham‐operated rats receiving saline). Propranolol (30 mg kg−1 day−1) or saline was given for 9 days via gastric gavage starting 1 day before ligation and thereafter. Then, the superior mesenteric artery was removed from each group for contractile study after haemodynamic measurement. In portal hypertensive rats, propranolol significantly alleviated the hyperdynamic state, including portal pressure, cardiac index and total peripheral resistance in the treated group compared with the vehicle group. The maximal contractile responses to KCl and vasopressin in mesenteric artery were significantly greater in the sham–vehicle group than in the PVL–vehicle group. Long‐term propranolol treatment enhanced the contractile reactivity of mesenteric artery to KCl and vasopressin in PVL rats, and the contractile profiles were corrected towards those in sham‐treated animals. In contrast, propranolol treatment decreased heart rate, mean arterial pressure and cardiac index but did not alter the contractile responsiveness of sham‐operated rats These results showed that, in portal vein stenosed rats, long‐term treatment with propranolol improved arterial contractile reactivity together with portal pressure reduction. The propranolol effect on vascular reactivity is probably related to haemodynamic improvement, instead of a direct contractile effect on the vasculature.
Impaired gallbladder and gastric motility and pathological gastro‐oesophageal reflux in gallstone patients
Authors: PORTINCASA P. , DI CIAULA A. , PALMIERI V. , VELARDI A. , VANBERGE‐HENEGOUWEN G. P. , PALASCIANO G.
Published: November 2003

Impaired gallbladder motility is common in gallstone patients and might be associated with other gastrointestinal defects. Twenty patients with small stones in an opacified gallbladder at oral cholecystography and 20 healthy subjects homogeneous for sex, age and body size were studied by ultrasonography to assess gallbladder and gastric emptying simultaneously in response to a standard liquid meal (120 kcal, 11 g fat, 200 mL). The same subjects underwent ambulatory 24‐h gastro‐oesophageal pH monitoring. Dyspeptic symptoms were specifically investigated using a questionnaire. Gallstone patients had a significantly larger fasting (P < 0.05) and residual (P < 0.005) gallbladder volume with slower (P < 0.05) and less complete (anova, 0.001 < P < 0.05) gastric emptying than healthy control subjects. The speed of antral emptying was significantly correlated with the speed of gallbladder emptying (n = 40, r = + 0.31, P < 0.05). Pathological gastro‐oesophageal reflux was present in 75% and 15% of patients and control subjects respectively (P < 0.05). Overall, 95% of gallstone patients had abnormal pH profiles resulting from pathological gastro‐oesophageal reflux and/or prolonged gastric alkalinization. The speed of post‐prandial antral emptying was significantly correlated with the duration of the longest gastro‐oesophageal reflux episode (r = + 0.30, P < 0.03) and duodeno‐gastric reflux episode (r = + 0.80, P < 0.02). Best predictors for gastric alkalinization were the following indices of gallbladder function: large fasting volume (P = 0.03), large ejection volume (P = 0.009) and slower emptying (P = 0.032). Gallbladder and gastric motility were similar in patients with (n = 12) and without (n = 8) dyspeptic symptoms. Pathological gastro‐oesophageal reflux was found in 83% of dyspeptic patients and in 25% of patients without dyspepsia (P < 0.01). When reflux was present, it was significantly less in asymptomatic than in dyspeptic patients [time at pH < 4, median (range): 6.4% (3.2–22.6%) vs. 47.8% (2.1–87%), P < 0.05]. This study shows that a subgroup of gallstone patients with small—mainly asymptomatic—stones have impaired gallbladder and gastric motility as well as abnormal gastro‐oesophageal pH‐profiles. These findings point to the existence of multiple functional defects of the upper gastrointestinal tract in gallstone disease.
Decreased sensitivity to insulin‐like growth factor I in Turner's syndrome: a study of monocytes and T lymphocytes
Authors: Hochberg Z. , Aviram M. , Rubin D. , Pollack S.
Published: November 2003

Turner's syndrome is characterized, amongst other things, by growth retardation with high serum levels of insulin‐like growth factor 1 (IGF‐I) in relation to growth, by a tendency to autoimmune disease and by insulin resistance with hyperlipidaemia. Assuming a role for IGF‐I subresponsiveness in the last two features, the present study was designed to evaluate in patients with Turner's syndrome their monocyte/macrophage response to growth hormone (GH) and to IGF‐I with respect to low‐density lipoprotein (LDL) degradation and to the monocyte‐dependent lymphocyte proliferation. Nineteen patients with Turner's syndrome and puberty‐matched control subjects were studied. Monocytes were isolated from the blood of the patients and the control group, and cultured to develop into macrophages. The cells were then incubated with 125I‐labelled LDL (25 μg of protein mL−1) in the absence or presence of 50 ng mL−1 IGF‐I or GH, and cellular lipoprotein degradation was determined. GH and IGF‐I effects on T‐cell proliferation were measured in autologous mixed lymphocyte reaction (AMLR) and on interleukin 2 (IL‐2) secretion by blastoid T‐cell culture. Monocytes/macrophages degradation of LDL was lower in Turner's syndrome patients than in control subjects (P < 0.05). IGF‐I stimulated LDL degradation by 42 ± 8% in the control subjects and by only 16 ± 7% in Turner's syndrome patients (P < 0.05). Control lymphocyte proliferation in AMLR was significantly augmented by 50–100 ng mL−1 GH or IGF‐I. Lymphocytes derived from peripheral blood of Turner's syndrome patients remained almost unaffected by either GH or IGF‐I. Measurement of IL‐2 secretion by purified blastoid T lymphocytes revealed a significant augmentation by 100 ng mL−1 GH and by 50–100 ng mL−1 IGF‐I in control subjects, and almost no response in Turner's syndrome. Turner's syndrome is associated with decreased sensitivity of peripheral blood mononuclear cells to GH and to IGF‐I, as is evident by the reduction in LDL degradation, monocyte‐stimulated T‐lymphocyte proliferation and IL‐2 secretion by blastoid T cells.
Comparative effects of nitric oxide synthesis inhibition and catecholamine treatment in a rat model of endotoxin shock
Authors: NAVA E. , SALAZAR F. J.
Published: November 2003

Catecholamines and volume repletion are currently used for the treatment of septic shock. However, the prognosis of patients suffering from this condition is very poor. An overproduction of nitric oxide (NO) seems to be related to the hypotension and tissue damage of endotoxin shock. Thus, treatment with NO synthase inhibitors has been proposed. Using a rat model of septic shock we have studied the effects of noradrenaline or the NO synthase inhibitor, NG‐nitro‐l‐arginine methylester (l‐NMMA) on arterial pressure, tissue damage and NO production. Anaesthetized rats treated with Salmonella typhosa showed a decrease in blood pressure accompanied by an increase in the plasma concentration of cytosolic enzymes (transaminases and lactate dehydrogenase, markers of cell disruption) and nitrite plus nitrate (NO−2/NO−3, markers of NO production). A large proportion of these animals (40%) died before the end of the experiment. Co‐treatment with noradrenaline resulted in temporary maintenance of arterial pressure followed by a decline, despite the dose being increased progressively. No differences were observed in plasma cytosolic enzymes, NO−2/NO−3 or mortality compared with animals treated with lipopolysaccharide (LPS) alone. In contrast, administration of l‐NMMA (10 mg kg−1) to septic animals prevented the fall in blood pressure and death caused by endotoxin. This treatment markedly diminished cell disruption, as measured by the plasma levels of necrosis enzymes, and partially, but significantly, reduced the production of NO as assessed by plasma NO−2/NO−3. We conclude that tissue damage in septic shock is related to the overproduction of NO and not exclusively to the hypotension that follows this increased production. Thus, maintenance of blood pressure with catecholamines fails to improve cellular damage. Instead, partial inhibition of NO generation is sufficient to ameliorate the haemodynamic and tissue‐damaging effects of septic shock and improves survival in this model of endotoxaemia.