bluuebunny/crossref_metadata_2025 huggingface dataset:
Studies on lipoprotein metabolism in a family with jejunal chylomicron retention
Authors: NEMETH A. , MYRDAL U. , VERESS B. , RUDLING M. , BERGLUND L. , ANGELIN B.
Published: March 2008

Abstract. We describe two siblings with fat malab‐sorption and jejunal chylomicron retention. Plasma lipoproteins were studied in the patients and their first‐degree relatives. The patients were a 14‐year‐old girl and her 8‐year‐old brother. Compared to healthy controls, they both had low fasting plasma concentrations of plasma total, HDL, and LDL cholesterol, as well as of apolipoproteins A‐I and B. No increase in plasma lipoprotein levels or detectable apo B‐48 was observed following an oral fat load. Histological studies of jejunal biopsy specimens obtained during fasting and 1 h postprandially showed severe steatosis, and an apparent block of chylomicron secretion from the endoplasmic reticulum into the Golgi apparatus was observed by electron microscopy. Liver biopsy specimens showed moderate steatosis and ultrastruc‐tural changes similar to those in the enterocytes. One healthy sister had a normal plasma lipoprotein pattern, and showed increased plasma triglyceride levels as well as the presence of apo B‐48 following an oral fat load. Both parents had normal plasma total cholesterol levels, but clearly reduced fasting concentrations of HDL cholesterol and apo A‐I. At least in this family, determination of plasma apo A‐I levels might thus prove useful in the identification of heterozygotes.
Hydroxylation of collagen type I: evidence that both lysyl and prolyl residues are overhydroxylated in osteogenesis imperfecta
Authors: LEHMANN H. W. , RIMEK D. , BODO M. , BRENNER R. E. , VETTER U. , WÖRSDÖRFER O. , KARBOWSKI A. , MÜLLER P. K.
Published: March 2008

Abstract. The composition of the collagens secreted into the media of fibroblast cultures of 39 patients with osteogenesis imperfecta (OI) was the same in controls and OI cultures. An abnormal migration pattern of collagens upon SDS‐PAGE was evident in one third of the cultures investigated. Lysyl and prolyl hydroxylation of HPLC‐purified α 1(1) chains was elevated in about 60% of cultures. The degree of hydroxylation was highest in the lethal forms. The extent of lysyl and prolyl hydroxylation showed a strong correlation (r= 0.74,P < 0.001). While high levels of hydroxylation are frequently observed in OI patients, a direct correlation between lysyl or prolyl hydroxylation and fracture rate or growth retardation could not be established.
PC: PS liposomes induce a recruitment of neutrophils and the release of TNFa in the lungs of mice sensitized with Saccharopolyspora rectivirgula
Authors: BELLEMARE F. , ISRAEL‐ASSAYAG E. , CORMIER Y.
Published: March 2008

Abstract. The aim of this study was to verify the effectof nasally instilled liposomes (L) or dexamethasone‐containing L (Ldexa) on normal or inflamed lung tissue. Three groups of mice were studied. Group I was given saline instillations for 3 weeks prior to the instillation with liposomes. In groups I1 and 111 lunginflammation was induced by repeated instillations of Saccharopolyspora rectivirgula before the instillation of liposomes (group 11) or liposomes containing dexamethasone (group 111). Animals from all groups were killed at regular time intervals for up to 48 h after the instillation of liposomes. The total cell count in bronchoalveolar lavage fluid did not differ signifi‐ cantly between groups I and 11. However, in group I11 it decreased rapidly from 6.2 to 2.8 × 105 cells mL‐ within 2 h. Differential counts did not change in group I, but in group I1 a transient neutrophilia was observed 180 min after the instillation of liposomes. In group 111, the instillation of dexamethasone‐containing liposomes depleted all neutrophils and lymphocytes after 4h. No TNFa was found in samples of lavage fluid from any of the groups at time 0. In group I, liposomes induced the production of 0.03 ngmL‐l of TNFa in the 1 h sample only. In group 11, TNFa peaked to 1 ngmL‐1 at 1 h and had decreased to 0.35 ngmL‐1 by 3 h. In group 111, TNFa peaked at 1 h, but only reached a level of 0.1 ng mL‐1. It is concluded that liposomes cause few acute inflammatory effects when instilled in normal lungs, although in the presence of an underlying inflammation these lipids can induce a further neutrophilic response and the release of TNFa. However, this response and the underlying inflammation are inhibited by the incorporation of dexamethasone into the liposomes.
The influence of local skin heating and reactive hyperaemia on skin blood flow abnormalities in patients with reflex sympathetic dystrophy (RSD)
Authors: KURVERS H. A. J. M. , JACOBS M. J. H. M. , BEUK R. J. , WILDENBERG F. A. J. M. VAN DEN , KITSLAAR P. J. E. H. M. , SLAAF D. W. , RENEMAN R. S.
Published: March 2008

Abstract. Skin blood flow in reflex sympathetic dystrophy (RSD) patients has been reported to develop from an increase at an early stage to a decrease at later stages. So far, it remains unclear whether these abnormalities are solely of microcirculatory origin, and result from functional vasospasm or structural vessel wall changes. Eighty‐seven RSD patients were categorized as follows: stage I in case of a stationary warmth sensation; stage II in case of an intermittent warmth and cold sensation; and stage III in case of a stationary cold sensation. Laser Doppler flowmetry (LDF) was used as a measure of total skin blood flow and transcutaneous oximetry (TCPO2) as a measure of vascular reactivity in the more superficial skin layers. Local skin heating and reactive hyperaemia were used to study the relative reserve capacity of skin microvessels. Finapres was used to assess digital arterial pressures. As compared to healthy volunteers (n=16), LDF under control conditions demonstrated an increase in skin blood flow at stage I (P<0.01). A decrease in skin blood flow under control conditions was seen at stages II (P<0.05) and III (P<0.05), but the relative flow reserve capacity, as measured with LDF, was not impaired at these stages. Regression analysis did not show a relation between LDF parameters and duration of the syndrome. TCPO2 revealed no differences between patient groups and controls. Regression analysis did not demonstrate a relation between TCPO2 parameters and duration of the syndrome. Digital systolic blood pressures were increased at stages II (P<0.05) and III (p<0.001). These findings indicate that abnormalities in skin blood flow, as observed in RSD patients, are of microcirculatory origin. The observed decrease in skin blood flow at stages II and III most likely results from functional vasospasm rather than from structural vessel wall changes.
Diagnostic value of C‐reactive protein measurement does not justify replacement of the erythrocyte sedimentation rate in daily general practice
Authors: DINANT G. J. , KOCK C. A. DE , WERSCH J. W. J. VAN
Published: March 2008

Abstract. The purpose of this paper was to establish the diagnostic value of the C‐reactive protein measurement (CRP) in patients attending their general practitioner (GP) with a new complaint for which the GP considers determination of the erythrocyte sedimentation rate (ESR) to be indicated. During 4 successive months in 1992, 11GPs in four general practice centres in the Netherlands identified patients indicated for the erythrocyte sedimentation rate. ESR and CRP were determined at the local hospital laboratory. One year later, an independent GP established the follow‐up diagnoses. By comparing the test results with the follow‐up diagnoses, using logistic regression analysis and Receiver Operating Characteristic curves, sensitivities, specificities, predictive values and odds ratios were established. In 396 patients the prevalence of inflammatory diseases and malignancies (‘pathology’) was found to be 26% in males and 15% in females. Both ESR and CRP were valuable in discriminating pathology from harmless, often self‐limiting diseases. The optimal upper limits of reference values (‘cut‐off points’) for ESR were found to be 31 mm in both males and females. At these cut‐off points, the diagnostic gains from positive and negative test results (positive predictive value minus prevalence, and negative predictive value minus 100% minus prevalence) were 45% and 4% for males and 30% and 2% for females. The optimal cut‐off point for CRP was found at 15mgL‐1in males and 34mgL‐1in females. The diagnostic gain from positive and negative test results were 18% and 9% in males and 25% and 4% in females. In daily general practice there is no reason to abandon ESR in favour of CRP. Only if a GP wants to be informed of the test result as quickly as possible, and the costs of ordering tests are Jess important, might CRP be reconsidered as a test.
Increased erythrocyte calcium pump activity in a kindred with familial benign hypercalcaemia
Authors: ESCOBALES N. , FARIÑAS C. A. , HADDOCK L.
Published: March 2008

Abstract. The hypothesis that a global defect in cellular calcium transport may be critical in the development of familial benign hypercalcaemia (FBH) was investigated. Nine hypercalcaemic patients from a kindred with FBH and nine normal subjects were evaluated. Our results indicate that calcium pump activity in the FBH kindred was significantly higher (28%, P < 0.005) when compared to normal subjects. These findings suggest that alterations in calcium pump activity in activity in target tissues may play a role in the development of FBH.
Dopaminergic and cholinergic control of argininevasopressin secretion in type I diabetic men
Authors: COIRO V. , VOLPI R. , CAPRETTI L. , COLLA R. , CAFFARRI G. , VESCOVI P. P. , CHIODERA P.
Published: March 2008

Abstract. Enhanced cholinergic and dopaminergic controls of anterior pituitary function have been described in insulin‐dependent diabetes mellitus (IDDM). In order to verify whether similar neurotransmitter alterations also affect the regulation of posterior pituitary hormone secretion, the argininevasopressin (AVP) responses to the dopaminergic agonist apomorphine and in a different occasion to physostigmine, an acetylcholinesterase inhibitor, were evaluated in normal (n=10) and type I diabetics (n= 16). In addition, a control test with normal saline was performed in all subjects. None of the diabetic patients were affected by neuropathy or other diabetic complications. They were divided into two groups according to the duration of their disease (less than 10 years: group 1, n= 8; more than 10 years: group 2, n= 8). Physostigmine (12.5 μg kg‐1) was infused intravenously over 10 min; apomorphine (60 μg kg‐1) was injected subcutaneously. Basal AVP concentrations were similar in all groups and remained constant during the control test. In contrast, both drugs induced significant increments in plasma AVP levels in the normal controls and diabetic subjects. However, physostigmine‐ and apomorphine‐induced AVP increments were twofold higher in diabetics than in control subjects. No significant differences were observed between diabetics of groups 1 and 2. No significant correlations between duration of diabetes and peak AVP responses to physostigmine or apomorphine were found within each group or when all diabetic subjects were considered together. These data indicate enhancement of both dopaminergic and cholinergic stimulatory regulations of AVP secretion in patients with uncomplicated IDDM, regardless of the duration of diabetes.
Serum laminin in Graves' disease
Authors: WENISCH C. , MYSKIW D. , NARZT E. , PRESTERL E. , GRANINGER W.
Published: March 2008

Abstract. We determined serum levels of laminin in 23 patients with Graves' disease (GD) and in 24 patients with toxic nodular goiter (TNG). Elevated levels of soluble laminin were observed in patients with GD prior to treatment (median concentration 1376 ng mL‐1 [range 712–2402]), compared to patients with TNG (median 442 ng mL‐1 [284–891]), and normal controls (median 492 ng mL‐1 [range 235–675], n= 26) respectively. In GD patients serum laminin levels decreased during thiamazole treatment and normalized within 8 weeks of therapy. There was no correlation between serum laminin levels and serum levels of thyroid hormones and/or auto‐antibodies, respectively. Whether serum laminin is a marker for alterations of extracellular matrix during GD and release of basement membrane components in the circulation and/or reflects an impaired clearance remains to be elucidated.
Gastric myoelectrical activity and gastrointestinal motility in patients with functional dyspepsia
Authors: JEBBINK H. J. A. , BERGE‐HENEGOUWEN G. P. VAN , BRUIJS P. P. M. , AKKERMANS L. M. A. , SMOUT A. J. P. M.
Published: March 2008

Abstract. The aim of our study was to examine the prevalence of gastric myoelectrical disturbances in relation to gastrointestinal motility abnormalities in patients with functional dyspepsia, using simultaneous electrogastrography and antroduodenojejunal manometry. We carried out electrogastrography in 20 patients with functional dyspepsia and in 20 healthy volunteers. In 10 of these patients and in 10 of the volunteers antroduodenojejunal manometry was performed simultaneously. Apart from a higher postprandial power content of the 3 cycles per minute (cpm) component in the patients (1263 ± 317 and 393 ± 101 μV2, respectively; P= 0.016), no differences in the electrogastrographic variables were found between the groups. In the manometric part of the study, postprandial antral hypoactivity was not a prominent finding. Instead, small intestinal hyper‐activity was found in the dyspeptic patients, with both a higher frequency and amplitude of the contractions (P < 0.05). This hyperactivity often consisted of bursts, which were significantly more frequent in patients than in control subjects (total duration of burst activity 25.6 ± 6.4 and 6.0 ± l.7 min, respectively; P= 0.013). A positive correlation was found between the frequency of the gastric electrical control activity and the antral contraction frequency (P= 0.006), between the power content of the electrographic signal and the antral contraction amplitude (P= 0.025), and between the postprandial/fasting electrographic power ratio and the antral motility index (P= 0.007). In conclusion, gastric myoelectrical activity is minimally disturbed in patients with functional dyspepsia. Motor abnormalities, especially small intestinal hyperactivity, are more likely to play a prominent role in the genesis of dyspeptic symptoms.
Aminophylline: could it act as an antioxidant in vivo?
Authors: LAPENNA D. , GIOIA S. DE , MEZZETTI A. , CIOFANI G. , FESTI D. , CUCCURULLO F.
Published: March 2008

Abstract. Potential antioxidant properties of aminophylline and theophylline were investigated. We have found that these drugs, though ineffective against superoxide anion and hydrogen peroxide, are scavengers of hydroxyl radical (OH·). Indeed, second‐order rate constants (k) of aminophylline and theophylline with OH· are about 1.9 times 1010 mol‐1 s‐1 and 4.5 times 109 mol‐1 s‐1, respectively. Ethylenediamine, which is present in the aminophylline molecule, significantly contributes to this marked OH· scavenging activity, since it is characterized by a high k value, i.e. about 8 times 109 mol‐1 s‐1. However, when using therapeutically relevant concentrations of the methylxanthines (9 and 13 μmL‐1), significant antioxidant effects against OH·‐induced oxidant injury are evident only with aminophylline. Although all three substances can apparently bind and inactivate iron, only aminophylline is effective at 9 and 13 μgmL‐1; also this action is favoured by ethylenediamine. Moreover, therapeutic concentrations of aminophylline, but not of theophylline, are capable of antagonizing hypochlorous acid (HOC1); this effect is entirely due to the presence of ethylenediamine. Oxidant species, such as OH· and HOC1, have been implicated in the pathophysiology of asthma; it could be hypothesized, therefore, that some therapeutic effects of aminophylline may be related to its antioxidant properties, which are partly or totally attributable to ethylenediamine, depending on the chemical identity of the prooxidant antagonized (e.g. iron/OH· or HOC1). Aminophylline antioxidant capacity should be taken into account when investigating the lung epithelial lining fluid antioxidant capacity and oxidative stress indices in humans.
Alzheimer amyloid β‐peptides exhibit ionophore‐like properties in human erythrocytes
Authors: ENGSTRÖM I. , RONQUIST G. , PETTERSSON L. , WALDENSTRÖM A.
Published: March 2008

Abstract. There is growing evidence that the amyloid β‐peptide (β1_40) is involved in the aetiology of Alzheimer's disease also implicating an altered calcium homeostasis of affected cells. Beta1_40 has been proposed to form calcium channels in synthetic bilayer membranes [1]. We wanted to investigate in the present study whether β1‐40 (or fragments thereof) could act as ionophores in a biological membrane like the one in human erythrocytes. Incubation of the cells for 2h and 4h at 37°C together with 6μmolL‐1 of β1‐40 or of fragments β1_28and β25‐35, resulted in a significantly decreased energy charge qualitatively similar to the one obtained by a known calcium ionophore (A 23187, 0.05μmolL‐1). Moreover, β1_40 and its two fragments induced a significant alteration of 45Ca permeability in human red blood cells of the same type as the one achieved by the calcium ionophore. The ionophoric action of β1_40 and its two fragments may lead to an increase of the intracellular calcium ion concentration, in turn resulting in enhanced Ca2+‐ATPase activity and a decrease in energy charge. This may be valid also for neuronal plasma membranes and could, therefore, be a possible aetiological mechanism in Alzheimer's disease.
Body composition and serum lipids in female runners: influence of exercise level and menstrual bleeding pattern
Authors: HETLAND M. L. , HAARBO J. , CHRISTIANSEN C.
Published: March 2008

Abstract. The impact of running and menstrual disturbances on regional and total body fat distribution and serum lipids was investigated in 205 women. Body composition was measured by dual‐energy X‐ray absorptiometry. The total fat mass in the elite runners was approximately half of the normally active's (7.3 [0.48] kg vs. 14.3 [0.49] kg, P< 0.001) (mean [SEM]). The difference was most pronounced in the abdomen (fat percentage 9.7 [0.85]% vs. 22.0 [0.88]%, P<0.001). The elite runners tended to have a more favourable lipid profile than the normally active (NS). A significant relation was found between lipoproteins and body fatness. In comparison with the regularly menstruating runners (n= 93), the 13 runners with amenorrhea tended to have less body fat and slightly less favourable lipid profiles (NS). In conclusion, regular exercise was associated with a low abdominal fat percentage, which may affect cardiovascular risk beneficially. Running‐associated menstrual dysfunctions were not significantly related to a specific body composition or serum lipid profile.
Microdialysis assessment of adipose tissue metabolism in post‐absorptive obese NIDDM subjects
Authors: JANSSON P.‐A. , SMITH U. , LÖNNROTH P.
Published: March 2008

Abstract. Lactate and glycerol turnover is enhanced in obesity and NIDDM. To evaluate the influence of NIDDM on subcutaneous adipose tissue metabolism microdialysis combined with 133Xe clearance and measurements in arterialized plasma were carried out using samples of subcutaneous abdominal fat from nine obese NIDDM subjects (glucose, 7.9 ± 0.7 mmol L‐1) (mean±SEM) and nine obese non‐diabetic subjects (glucose, 4.9 ±0.1) matched for age, BMI and body fat. After an overnight fast arterialized plasma levels were 1145 ±110 vs. 876 ±59 μmol L‐1 (P<0.05) for lactate and 75±10 vs. 66 ±8 μmol L‐1 for glycerol in the diabetic and control group, respectively. The corresponding abdominal subcutaneous interstitial lactate and glycerol concentrations were 1278 ± 63 vs 1107 ±64 μmolL‐1 and 314 ±28 vs. 311 ± 17μmol L‐1, respectively. However, adipose tissue blood flow in the same region was lower in NIDDM subjects (1.5±0.2 vs 2.4±0.3 mL 100g‐1 min‐1) (P<0.05). Consequently, apparent subcutaneous lactate and glycerol release, estimated according to Fick, were not statistically different in the two groups (1.8 ±0.4 vs 2.4 ±0.8 and 2.1 ±0.4 vs 3.1 ±0.5 μmol kg‐1 min‐1 in NIDDM and control subjects, respectively). Thus, in the post‐absorptive state apparent lactate and glycerol release by the abdominal subcutaneous tissue in obese NIDDM subjects was similar to that in a matched group of obese non‐diabetic controls. The data suggest that no primary defect is evident in adipose tissue metabolism in well controlled NIDDM subjects.
Key metabolite kinetics in human skeletal muscle during ischaemia and reperfusion: measurement by microdialysis
Authors: MÜLLER M. , SCHMID R. , NIESZPAUR‐LOS M. , FASSOLT A. , LÖNNROTH P. , FASCHING P. , EICHLER H. G.
Published: March 2008

Abstract. The tissue kinetics of key metabolites of ischaemic and postischaemic tissue damage were studied in the intercellular space of human skeletal muscle by microdialysis. In vivo microdialysis calibration experiments (n= 5) yielded the basal intercellular concentration of glucose in human skeletal muscle (3.6±0.6mM; mean±SD). The corresponding mean plasma glucose concentration was 4.3 ± 0.2 mM which was significantly higher. The time vs. concentration profiles of intercellular glucose (n= 7), lactate (n= 5), TxB2 (n= 6) and urea (n= 8) were characterized during a 20 min period of leg constriction. TxB2 increased exclusively during reperfusion in comparison to baseline (n= 6). Administration of 500 mg acetylsalicylic acid, 5–10min after onset of ischaemia blunted TxB2‐response to reperfusion (n= 4). It is concluded that intercellular muscle glucose concentration is less than that in plasma. Glucose uptake in skeletal muscle is rapid even under ischaemic conditions. Synthesis and release of TxB2 is not evident during ischaemia. TxB2 mediated reperfusion injury might be reduced by acetylsalicylic acid, even if administered after onset of ischaemia.
Studies in hypertriglyceridaemia, III: glucose tolerance, insulin sensitivity and indices of adipose tissue lipolysis in randomly selected non‐diabetic hypertriglyceridaemic Swedish men
Authors: ASPLUND‐CARLSON A.
Published: March 2008

Abstract. Hypertriglyceridaemia, insulin resistance and glucose intolerance are conditions associated with an increased risk of coronary heart disease. In this study we have examined randomly selected non‐diabetic hypertriglyceridaemic (HTG) males, 40–50 years (n= 65) and age‐matched normotriglyceridae‐mic (NTG) controls (n= 61). The (mean ± SD) insulin sensitivity index, as assessed by the Minimal Model method, was significantly lower in the HTG compared with the NTG group (3.69 ±2.96 vs. 6.29 ± 3.38 times 10‐4min‐1 per mUL‐1; P< 0.001). Thirty‐eight per cent of the HTG group was glucose intolerant, compared with 8% in the NTG group (X2= 13.16; P<0.001). The glucose intolerant HTG sub‐group had, when compared with the glucose tolerant one, significantly higher serum concentrations of apoB (1318±284 vs. 1094±312mgL‐1; P<0.01) and glycerol (84 ±26 vs. 65±22 nmolL‐1; P<0.01). Serum FFA concentrations were, irrespective of glucose tolerance/intolerance, higher in the HTG than in the NTG group. By logistic regression analysis with the HTG/NTG state as the dichotomous variable, it was found that neither a low insulin sensitivity, nor glucose intolerance were independently linked with the HTG state. Instead, the lower insulin sensitivity of the HTG group was related to their higher body mass index. The higher frequency of glucose intolerance in the HTG group was explained by their higher mean serum apoB concentration, when compared with the NTG group. In conclusion, this study of a randomly selected HTG group has confirmed the frequent coexistence of HTG, insulin resistance and glucose intolerance. The new important finding was that neither of these two latter conditions appear to be of direct pathogenetic importance for HTG.
Peroxides in human leucocytes in acute septic shock: a preliminary study of acute phase changes and mortality
Authors: LEAVER H. A. , YAP P. L. , ROGERS P. , WRIGHT I. , SMITH G. , WILLIAMS P. E. , FRANCE A. J. , CRAIG S. R. , WALKER W. S. , PRESCOTT R. J.
Published: March 2008

Abstract. Peroxidation by peripheral blood leucocytes was measured in 15 patients in acute septic shock and 15 uninfected controls, using the probe dichloroflor‐escein. Mortality in septic subjects was 40%. In 14 of 15 patients from whom serial samples were analysed, periods of increased oxidative activity were detected. Increased peroxidation occurred early in the sequence of clinical changes, at the same time as increases in temperature, blood pressure and C‐reactive protein. Peak peroxide production preceded increases in acute phase reactants and changes in leucocyte distribution. Mean peroxide production in leucocytes from patients who died was significantly higher (P<0.001) than paired controls, and greater (P<0.05) than peroxide production in patients who survived. The in vitro oxidative response to endotoxin was upregulated in infected patients. This supports the hypothesis that systemic mediators and leucocyte‐derived reactive oxygen are involved in the vascular and organ damage associated with fatal septic shock.
Subcellular distribution of small GTP‐binding proteins in the intestinal cell line Caco‐2
Authors: STEIN J. , GERHARD R. , ZEUZEM S. , CASPARY W. F.
Published: March 2008

Abstract. The present study describes the subcellular distribution of low molecular weight GTP‐binding proteins in the human carcinoma cell line Caco‐2. Highly enriched subcellular fractions of basolateral and brush border membranes were prepared by differential density centrifugation and divalent cation precipitation. Small molecular weight GTP‐binding proteins were identified after SDS‐PAGE transfer to nitrocellulose using [α32P]‐labelled GTP. Smg‐proteins with molecular masses of 28, 27, 25 and 24 kDa were detectable in all fractions. Homo‐genate and brush border membrane fraction showed specific binding of [α32P] GTP to proteins of a molecular mass of 21 kDa, while in the membrane fractions (apical, basolateral) a high enrichment of 24 kDa smg‐proteins was detectable. Western blot analysis identified one of the 21 kDa proteins of the brush border membrane as rhoA. The homogenate of 4, 8, 11 and 14 days old Caco‐2 cells showed different [α32P]‐GTP binding to 21, 27 and 28 kDa proteins. In conclusion, this study is the first showing the presence and asymmetrical distribution of smg‐proteins among the various membrane components in the human carcinoma cell line Caco‐2.
Recurrent condylomata acuminata: how routine immediate and delayed hypersensitivity parameters might provide a clue to their immunopathogenesis
Authors: KYRIAKIS K. P. , BALAMOTIS A. K. , KATSAROU‐KATSARI A. , TOSCA A. D.
Published: March 2008

Abstract. In 30 male patients suffering from recurrent condylomata acuminata, immediate hypersensitivity parameters (total IgE, PTT and prick tests) and delayed hypersensitivity against seven recall antigens (multi test) were studied. Thirty healthy male volunteers, matched in age, were the controls. Significantly higher immediate hypersensitivity activity was shown in the patient group. Qualitative evaluation of delayed type hypersensitivity showed that controls had a positive test 16 times more often than patients. A rather homogeneous suppression of delayed type hypersensitivity was found in the patient group mainly as regards the presumably most common antigens vs. the control group. This suppression was proved to be related to disease duration. The hypothesis of a CD4+ Th‐2 lymphocyte predominance in recurrent condylomata, owed to longstanding or repetitive antigenic stimulation seems to adequately explain the findings of the present study.
Effect of danazol‐induced chronic hyperglucagonaemia on glucose tolerance and turnover
Authors: KOTZMANN H. , LINKESCH M. , LUDVIK B. , CLODI M. , LUGER A. , SCHERNTHANER G. , PRAGER R. , KLAUSER R.
Published: March 2008

Abstract. It has been shown that danazol (14‐ethinyl‐testosterone) induces hyperglucagonaemia. To investigate the effect of chronic glucagon excess on carbohydrate metabolism, we studied six patients before and after treatment with danazol for immuno‐thrombopenia. Glucose tolerance and insulin, C‐pep‐tide and glucagon secretion during an oral glucose tolerance test (oGTT) as well as peripheral and hepatic insulin sensitivity were determined by means of euglycaemic clamp technique (40mUm‐2 min‐1) before and after 3 months of danazol therapy. Overall glucose turnover (R2) was assessed radioisotopically. (1) Plasma glucagon levels rose significantly from 88 ±16 pgmL‐1 before to 683 ± 148pgmL‐1 after therapy (P < 0.01). (2) Glucose levels during an oGTT were not significantly different before and after therapy. Glucose‐stimulated insulin secretion at 60 and 120min and the area under the curve (AUC) for insulin during the oGTT. were significantly increased after danazol treatment compared with pre‐treatment values (P < 0.05), whereas glucagon secretion showed a similar decrease at both time points of investigation (NS). (3) Rd during steady state showed a significant decrease during the entire period of euglycaemic clamp following therapy (after 240min, 3.8 ±0.6 vs. 5.3 ±0.7 mg kg‐1 min‐1, P < 0.05). The decline in glucagon during the clamp was similar during steady state before and after therapy. (4) Basal hepatic glucose output did not differ significantly before and after therapy (1.74 ±0.41 vs. 1.45 ±0.22 mg kg‐1, NS), whereas hepatic glucose output during the clamp was significantly less suppressed after danazol therapy. The authors conclude that chronic glucagon excess leads to a decrease in peripheral and hepatic insulin action which is accompanied by an increase in insulin secretion.
An aldose reductase inhibitor, TAT, prevents electroretinographic abnormalities and ADP‐induced hyperaggregabiIity in streptozotocin‐induced diabetic rats
Authors: HOTTA N. , KOH N. , SAKAKIBARA F. , NAKAMURA J. , HAMADA Y. , HARA T. , TAKEUCHI N. , INUKAI S. , KASAMA N. , FUKASAWA H. , KAKUTA H.
Published: March 2008

Abstract. Rats with streptozotocin‐induced diabetes were oral given TAT, a potent aldose reductase inhibitor, at a dose of 10 rng kg‐1 day‐1or 40 mg kg‐1 day‐1 for 30 days. Prolongation of the peak latency of oscillatory potentials in the b‐wave of the electro‐retinogram (ERG), which is associated with retinal Müller cell dysfunction, was significantly improved by treatment with TAT as compared with untreated diabetic rats [Σ(O1+O2+ O3) was 106.8 ± 1.8 ms in normal controls (NC), 118.2 ±1. 1 ms in diabetic controls (DC) (P <0.001 vs. NC), 110.8 ±1.5ms with 10 mg kg‐1TAT (P< 0.001 vs. DC) and 111.4 ±1.6ms with 40 mg kg‐1 TAT (P<0.01 vs. DC)]. The improvement in ERG abnormalities in diabetic rats was accompanied by partial reduction of elevated sorbitol levels in the retina and erythro‐cytes, and by correction of platelet hyperaggregability. The authors' findings suggest that a better understanding of the mechanism by which TAT acts may provide new insights into the pathogenesis of hyper‐glycaemic retinal dysfunction and contribute to establishing effective therapy for diabetic retinopathy.
Transforming growth factor β1influences lysyl hydroxylation of collagen I and reduces steady‐state levels of lysyl hydroxylase mRNA in human osteoblast‐Iike celIs*
Authors: SEITZER U. , BÄTGE B. , ACIL Y. , MÜLLER P. K.
Published: March 2008

Abstract.Transforming growth factor β1(TGF‐β1) is an osteotropic growth factor that is found in substantial concentration in bone. The authors studied the influence of TGF‐β1on the modification of lysine residues of collagen I. The degree of lysyl hydroxylation and lysyl glycosylation of newly synthesized collagen as well as steady‐state levels of mRNA for both lysyl hydroxylase and collagens I and 111 were determined in human osteoblast‐like cellsin vitro. In normal human osteoblasts lysyl hydroxylation was decreased by TGF‐β1particularly in the collagen α2‐chain. This effect was paralleled by an increase in lysyl residues, whereas glycosylation was not affected. The mRNA for lysyl hydroxylase was reduced by one‐third under the influence of TGF‐β1. Additionally, the mRNAs for both procollagen I α‐chains were stimulated by TGF‐β1, whereas proα1 (111)‐mRNA showed a decrease. Changes in the local regulatory activity of TGF‐β1may play a role in matrix maturation such as collagen type production and lysyl hydroxylation, the latter being altered in various pathological conditions, e.g. in generalized osteopenia.
Is responsiveness to lovastatin in familial hypercholesterolaemia heterozygotes influenced by the specific mutation in the low‐density lipoprotein receptor gene?
Authors: LEREN T. P. , HJERMANN I.
Published: March 2008

Abstract. Lovastatin is one of the most commonly used lipid‐lowering drugs in familial hypercholesterolaemia (FH) heterozygotes. In order to study whether the response to lovastatin is influenced by the underlying mutation in the low‐density lipoprotein (LDL) receptor gene, the authors compared the response in 24 heterozygotes in whom the mutation has been classified and in 34 heterozygotes in whom the mutation has not been classified. Those possessing a classified mutation had significantly higher pre‐trial values of LDL‐cholesterol than those possessing an unclassified mutation. However, no difference was found in the response to lovastatin. Nor were there any differences in the response between subjects possessing one of the three different classified mutations. Furthermore, irrespective of whether or not the mutation had been classified, no difference in the response was found between subjects in the upper and lower quartile with respect to pre‐trial values of LDL‐cholesterol. The authors conclude that the response to lovastatin is independent of both the specific mutation in the LDL receptor gene and the actual cholesterol level in FH heterozygotes.
n‐3 Polyunsaturated fatty acids: update 1995
Authors: ENDRES S. , CATERINA R. DE , SCHMIDT E. B. , KRISTENSENJ S. D.
Published: March 2008

Abstract. Epidemiologic and biochemical studies have suggested an anti‐inflammatory effect of n‐3 fatty acids. Beneficial therapeutic effects reported from small patient groups need to be confirmed in large‐cohort controlled clinical trials. There is a growing number of clinical trials of n‐3 fatty acid supplementation in disease. Clinical benefits have been moderate in patients with rheumatoid arthritis and with arterial hypertension. Clearly negative results have been reported during the past 2 years for patients with lupus nephritis and for patients with psoriasis or with atopic dermatitis. Such trials have now been completed. For patients with coronary artery disease following coronary angioplasty, earlier results of a large meta‐analysis, could not be confirmed. For patients with IgA‐nephropathy and for patients following kidney transplantation, a clear benefit was seen in patients receiving fish oil. These promising results are currently pursued in follow‐up phase III clinical trials.
The myeloic related protein MRP8/14 (27E10 antigen)— usefulness as a potential marker for disease activity in ulcerative colitis and putative biological function
Authors: LÜGERING N. , STOLL R. , SCHMID K. W. , KUCHARZIK T. , STEIN H. , BURMEISTER G. , SORG C. , DOMSCHKE W.
Published: March 2008

Abstract. MRP8, MRP14 and their heterodimer MRP8/14 (27E10 antigen) are myeloic related proteins which have been shown to have a major role in inflammatory and immunological responses. In the present study monospecific antibodies against MRPs were used to investigate immunohistochemically the distribution of these proteins in routinely processed bowel tissues from 23 patients with ulcerative colitis (UC). MRP8, MRP14 and their heterocomplex MRP8/14 were demonstrated in the majority of granulocytes and macrophages in tissues of patients with active UC. Furthermore by employing the ELISA technique we measured MRP8/14 serum levels in 62 patients with UC and the results were compared with those for healthy controls. Disease activities were determined by established clinical activity indices. Serum MRP8/14 concentrations were significantly (P<0.0001) increased in patients with active ulcerative colitis. No enhancement of serum levels were found for MRP 14 and MRP8 alone, respectively. The follow‐up of individual patients with initially active disease showed a decrease of MRP8/14 serum levels in parallel with clinical improvement following the start of therapy. It is thus concluded that MRP8/14 accurately reflects the degree of disease activity in UC. Further, possible biological function of MRPs seems to be associated with the heterodimeric form (27E10 antigen) rather than with individual proteins. Our morphological results confirm the finding of enhanced MRP8/14 serum levels in patients with active UC.
Glutathione, glutathione utilizing enzymes and thioltransferase in platelets of insulin‐dependent diabetic patients: relation with platelet aggregation and with microangiopatic complications
Authors: SIMPLICIO P. DI , GIORGIO L. A. DE , CARDAIOLI E. , LECIS R. , MICELI M. , ROSSI R. , ANICHINI R. , MIAN M. , SEGHIERI G. , FRANCONI F.
Published: March 2008

Abstract. Reduced glutathione (GSH) and activity of GSH related enzymes play a key role in defence against oxygen free radicals, whose production is, as known, raised in patients affected by diabetes mellitus, and at the same time they may contribute to the process of platelet aggregation. The purpose of this study was to evaluate GSH levels and activity of glutathione peroxidase (GSH‐Px), glutathione reduc‐tase (GSSG‐Red), glutathione transferase (GSH‐Tr), glucose‐6‐phosphate‐dehydrogenase (G6PDH), and thioltransferase (TT) in platelets of insulin‐dependent diabetic patients in fair metabolic control (mean glycated haemoglobin: 6.5%), as related to presence of retinopathy, neuropathy or nephropathy and to platelet aggregation by arachidonic acid (AA)in vitro. Mean effective dose (ED50) of AA was on average significantly lower in the group of insulin‐dependent diabetic patients (0.41 ± 0.02mM (SEM),n= 46) as compared with that of control subjects strictly matched for age, sex and weight (0.77 ± 0.02, n= 51; P= 0.0001). Mean platelet GSH as well as the activity of GSH related enzymes expressed as geometric mean (95% confidence intervals) were similar in diabetic patients and in controls, except for GSSG‐Red whose activity was significantly higher in diabetic subjects (28.5 (14.4–57.5) mU 10‐9 platelets vs. 20.3 (8.7–56) mU 10‐9 platelets; P= 0.01). In the diabetic group TT was reduced when compared with healthy controls (3.8 (0.9–12.2) mU 10‐9 platelets vs. 6 (1.6–26.1) mU 10‐9 platelets; P = 004). Moreover TT was significantly reduced in diabetic patients with worse metabolic control or with increased urinary albumin excretion rate (AER ≤ 20 μg min‐1), while neither TT, GSH nor GSH related enzymes were significantly different in patients with retinopathy or neuropathy. In addition TT was significantly related to ED50 of AA (r= 0.51; P= 0.0003). In conclusion GSH is not modified in insulin‐dependent diabetic patients in fair metabolic control, probably due to an augmented GSSG‐Red activity. Diabetic status, increase in platelet aggregation, and raised urinary AER seem to be altogether associated with a selective reduction in platelet TT activity.
Renal and adrenal mechanisms in cyclosporine‐induced hyperkalaemia after renal transplantation
Authors: LAINE J. , HOLMBERG C.
Published: March 2008

Abstract. CsA associated hyperkalaemia was investigated in 24 renal transplant recipients 6 months after transplantation. 51Cr‐EDTA‐, PAH‐, lithium and sodium clearances, 24 h urinary creatinine and potassium excretions, plasma renin activity and aldosterone concentrations were measured. Transtubular potassium concentration gradient (TTKG) was calculated. An ACTH test was performed to document adrenal function. Eleven patients had hyperkalaemia. The TTKGs were low normal or reduced in both normo‐and hyperkalaemic patients implying inhibition of K+ secretion. The hyperkalaemic patients received more CsA (mean dose 21.3 vs. 9–7 mgkg‐1d‐1, P = 0.01), and had lower lithium clearances (mean 9.9 vs. 170 mLmin‐1 1.73m‐2, P <005). Adrenal function had no clear effect. Serum potassium concentration correlated with CsA dose (r=0.773, P<0.001) and inversely with lithium clearance (r = ‐0.568, P<0.01) suggesting that CsA induced decrease in distal tubular flow rate reduced K+ excretion. Hyperkalaemia was not fully explained by renal mechanisms.
Inhibition of ileal bile acid transport by cyclosporin A in rat
Authors: SAUER P. , KLÖTERS‐PLACHKY P. , STIEHL A.
Published: March 2008

Abstract. Chronic administration of cyclosporin A may induce cholestasis and this effect has been attributed to impaired hepatic bile salt synthesis, metabolism and transport. We investigated the effect of cyclosporin A on intestinal absorption of bile acids in the ileum of rat. Ileal bile acid absorption was measured by in vivo intestinal perfusion with cyclosporin A and the solvent Cremophor EL. During ileal perfusion with 25 μM glycocholic acid, the concentration of 2.8 mm cyclosporin A inhibited intestinal bile acid absorption on average by 34%. Additional experiments were performed with everted gut sacs of the distal ileum to evaluate active absorption. A dose and time dependent inhibition of the active intestinal absorption of bile acids was found, with a 50% transport inhibition at an average cyclosporin A concentration of 2.69mmolL‐'. Thus, cyclosporin A inhibits the active intestinal absorption of bile acids which may influence bile acid synthesis, turnover and secretion and may contribute to cyclosporin A induced cholestasis.
Determinants of insulin‐stimulated skeletal muscle glycogen metabolism in man
Authors: SCHALIN‐JÄNTTI C. , LAURILA E. , LÖFMAN M. , GROOP L. C.
Published: March 2008

Abstract. To examine factors which influence skeletal muscle glycogen synthesis in man, we related insulin sensitivity measured by euglycaemic insulin clamp in 43 healthy males to muscle glycogen synthase (GS) activity, GS protein content (Western blot), glycogen concentrations and fibre composition. Insulin increased muscle glycogen content (P<0.05) and the change in glycogen content correlated with the GS protein content (r=0.90, P=0.01). GS protein concentration correlated inversely with age (r=‐0.69, P=0.04). Non‐oxidative glucose disposal was inversely related to per cent type 2B fibres (r=‐0.52, P< 005). The influence of age on these relationships was separately studied in young (n=12, age=26 ± 2 years) and elderly (n=15, age = 56 ± 2 years) males. Insulin increased GS activity significantly only in young subjects (from 17.8 ± 30 to 25.3 ± 3.2 nmol mg protein ' min‐1; P=0.015). GS activity and non‐oxidative glucose disposal correlated in young (r=0.69, P=001) but not in the elderly (r=0.064, P = 0.82) males, and this relationship was not influenced by the degree of obesity. In conclusion, muscle fibre type and GS activity are both determinants of muscle glycogen metabolism in healthy, normoglycae‐mic males. The close relationship between non‐oxidative glucose metabolism and GS activity in young males is altered in ageing.
Cellular processing of apolipoprotein B‐containing lipoproteins from young post‐infarction patients and healthy controls
Authors: TORNVALL P. , REGNSTRÖM J. , HAMSTEN A.
Published: March 2008

Abstract. 3‐Hydroxy‐3‐methylglutaryl‐coenzyme A (HMG‐CoA) reductase activity was measured in fibroblasts incubated with large (Sf >60) and small (Sf 20–60) very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and low density lipoprotein (LDL) particles, at similar protein concentrations, from young post‐infarction patients and healthy controls. The results showed that apolipoprotein (apo) B‐containing lipoproteins (VLDL, IDL, LDL) from patients suppressed HMG‐CoA reductase activity to a similar extent compared to apo B‐containing lipoproteins from controls. When all subjects taken together were grouped according to triglyceride levels, it was found that small VLDL from hypertriglyceridaemic individuals suppressed the HMG‐CoA reductase activity more than small VLDL from normotriglyceridaemic individuals. The opposite pattern was seen for LDL. The lipoprotein composition was related to the respective HMG‐CoA reductase activity. In addition to a positive association between the cholesterol content of small VLDL and LDL, and the inhibition of HMG‐CoA reductase activity, the apo C I and C II content of small VLDL and IDL was inversely related to the suppression of HMG‐CoA reductase activity. This study shows that the cellular processing of apo B‐containing lipoproteins in young post‐infarction patients and healthy controls is heterogeneous and dependent on the composition of the lipoprotein.
Elevated interleukin‐1β in the circulation of patients with essential hypertension before any drug therapy: a pilot study
Authors: DALEKOS G. N. , ELISAF M. S. , PAPAGALANIS N. , TZALLAS C. , SIAMOPOULO K. C.
Published: March 2008

Abstract. Immune system disturbances have been implicated in the pathogenesis of essential hypertension. The aim of this study was to determine the levels of the interleukin‐1β and soluble interleukin‐2 receptors in serum samples from 114 hypertensive patients before any drug therapy because there are no well‐established data regarding these immunologic mediators in essential hypertension. We found increased levels of interleukin‐1β in 59.6% of patients, while soluble interleukin‐2 receptors were not detected. The interleukin‐1β levels were significantly higher in patients than in healthy controls (P= 0.0001). We conclude that patients with essential hypertension have high levels of interleukin‐1β but not indicators of cellular immune activation in their sera. Further studies are in progress in order to confirm, explain and assess the clinical utility of the above findings.
Acute insulin administration does not affect plasma leptin levels in lean or obese subjects
Authors: MUSCELLI E. , CAMASTRA S. , MASONI A. , BALDI S. , SIRONI A. M. , NATALI A. , FERRANNINI E.
Published: March 2008

Abstract. Whether leptin levels are related to insulin sensitivity or subject to acute regulation by insulin is not known. In 12 obese [body mass index (BMI) = 34.0 ±1.5 kg m‐2] and 12 lean (BMI = 22.2 ±0.6 kg m‐2) non‐diabetic subjects, plasma leptin concentrations were measured in the fasting state and during 2 hours of euglycaemic hyperinsulinaemia (˜600 pmol L‐2). Fasting plasma leptin was significantly higher in obese (26.6 ±3.2) than in lean subjects (6.4 ±1.2 ng mL‐1, P= 0.0001), and in women (21.1 ±3.3) than in men (7.3 = 2.3 ng mL‐1, P= 0.01). In univariate analysis, fasting plasma leptin was strongly related to all anthropometric measures (body weight, fat mass, percent fat mass, waist and hip circumferences). In multiple regression, per cent adiposity, hip circumference and duration of obesity explained 90% of the variability in fasting leptin concentrations. Fasting and stimulated (OGTT) insulin levels, insulin sensitivity (22.6 ±1.9 vs 36.7 ±2.0 μmol min‐1 kg‐1 in lean and obese subjects, respectively, P < 0.0001), glucose area, and serum triglycerides were positively related to fasting plasma leptin concentrations; none of these associations, however, was statistically significant after adjusting for BMI. During the clamp, plasma leptin concentrations remained constant in both lean and obese subjects. We conclude that neither insulin levels nor sensitivity relate to leptin levels independently of fat mass, and that leptin is not subject to acute (2 hours) regulation by insulin in lean or obese humans.