bluuebunny/crossref_metadata_2025 huggingface dataset:
Postischaemic interrelations between energy metabolism and functional recovery of protected canine kidneys
Authors: KEHRER G. , BLECH M. , KALLERHOFF M. , LANGHEINRICH M. , BRETSCHNEIDER H.‐J.
Published: March 2008

Abstract. Following renal ischaemia under effective protection glomerular filtration starts at a time when renal high‐energy phosphates are resynthesized. The present investigation was carried out to examine the interdependence of the two processes. Therefore, canine kidneys were protected with sodium poor and nominally Ca2+ free buffered solutions. After different times of ischaemia and reperfusion the glomerular filtration rates (GFR) were determined and afterwards tissue specimens were excised for the determination of high‐energy phosphates. Both the GFR and the renal energy content were higher with shorter ischaemia periods or longer reperfusion. As a rule there was a correlation between GFR and ATP, both probably mainly signifying the degree of preservation of proximal nephron sites, as the interrelation between the GFR and the renal SAN (ATP+ADP+AMP) content also signifies. However, with the addition of aspartate to the protective solution it could be demonstrated that the GFR also can rise without a concomitant increase of ATP. Under certain conditions an increase of GFR can even be associated with a lowering of the renal ATP content.
Low levels of serum type III procollagen aminoterminal propeptide confirmed type III collagen deficiency in patients without typical clinical symptoms of Ehlers‐Danlos type IV
Authors: DYNE K. M. , ZANABONI G. , ANNONI G. , AGOSTINI M. P. DE , CETTA G.
Published: March 2008

Abstract. Biochemical analysis of skin samples revealed that the content of type III collagen was greatly reduced in several subjects with joint hyper‐mobility, stretchability and bruisability of skin. When cultured dermal fibroblasts were found to secrete decreased amounts of type III procollagen into medium (about 30–45% the normal amount) and serum type III procollagen aminopropeptide levels were significantly lower than normal values (P < 0.001).

The abnormalities in type III procollagen are in keeping with Ehlers‐Danlos type IV although the clinical findings in our patients are not normally associated with this disorder. The results illustrate the clinical heterogeneity of Ehlers‐Danlos type IV and the importance of biochemical analysis, such as determination of type III procollagen aminopropeptide levels, to check type III collagen metabolism especially if there is no family history and if correct diagnosis is not reliable by clinical examination alone.
Unconjugated serum bile acids as a marker of small intestinal bacterial overgrowth
Authors: MASCLEE A. , TANGERMAN A. , SCHAIK A. VAN , VAN DER HOEK E. W. , VAN TONGEREN J. H. M.
Published: March 2008

Abstract. Non‐invasive methods to detect small intestinal bacterial overgrowth often lack specificity in patients who have undergone an ileal resection or have an accelerated intestinal transit. Since elevated serum unconjugated bile acid levels have been found in patients with clinical signs of bacterial overgrowth, we studied the clinical value of unconjugated serum bile acids as a marker of small intestinal bacterial overgrowth. Patients with culture‐proven bacterial overgrowth had significantly elevated fasting unconjugated serum bile acid levels (median and range: 4.5; 1.4–21.5 μmol l‐1) as compared to healthy subjects (0.9; 0.3–1.7 μmol l‐1, P < 0.005), to persons with an accelerated intestinal transit (1.0; 0.3–1.9 μmol l‐1, P < 0.005) and to persons who have undergone an ileal resection (2.1; 0.7–3.6 μmol l‐1P < 0.005). The same was true 30 and 60 min after ingestion of a Lundh meal. Serum unconjugated bile acid levels above 4 μmol l‐1 were found in eight of 10 patients with culture‐proven small intestinal bacterial overgrowth whereas serum levels above 4 μmol l‐1 were found in none of the patients from the three control groups. These results suggest that determination of unconjugated serum bile acids is of clinical value in the evaluation of patients suspected of small intestine bacterial overgrowth.
Leukotriene B4 metabolism in neutrophils of patients with chronic granulomatous disease: phorbol myristate acetate decreases endogenous leukotriene B4via NADPH oxidase‐dependent mechanism
Authors: HAMASAKI T. , SAKANO T. , KOBAYASHI M. , SAKURA N. , UEDA K. , USUI T.
Published: March 2008

Abstract. We studied the effect of phorbol myristate acetate (PMA) on endogenous leukotriene B4 (LTB4) metabolism of calcium ionophore A23187‐stimulated human neutrophils. Preincubation of normal neutrophils with PMA significantly suppressed the recovery of endogenous LTB4 induced by A23187. PMA did not suppress the recovery of LTB4 produced by neutrophils from patients with chronic granulomatous disease (CGD), which is known to be defective in NADPH oxidase activation to produce reactive oxygen species (ROS). PMA inhibited the formation of ω‐oxidation products of LTB4, but enhanced arachidonic acid release in normal and CGD neutrophils. Furthermore, 5‐lipoxygenase activity of 10000 times g supernatants from normal neutrophils pretreated with PMA was equivalent to that of the controls. Decrease in LTB4 recovery was not attributed to the suppression of the intracellular Ca2+ increase. Thus, it is suggested that reactive oxygen species (ROS) produced by PMA may directly affect endogenous LTB4 and convert it into metabolite(s) distinct from ω‐oxidation products.
Evidence for immunological differences between circulating and thyroid tissue‐derived thyroglobulin in men
Authors: SCHULZ R. , BETHÄUSER H. , STEMPKA L. , HEILIG B. , MOLL A. , HÜFNER M.
Published: March 2008

Abstract. The expression of six antigenic epitopes on plasma Tg and tissue‐derived Tg was investigated using mouse mabs in immunoradiometric assays. The sensitivity of the assays ranged between 0.5 and 1.5 μg 1‐1. Plasma thyroglobulin of 15 normal individuals and 18 patients with metastatic, differentiated thyroid cancer was analysed. Whereas five monoclonals produced values comparable to the conventional RIA system, the monoclonal antibody Tg 158 did not detect any Tg in the normal individuals and only low levels in two of the cancer patients with the highest Tg levels.

In contrast, dilutions of extracts of three different euthyroid goitre samples and three different samples of differentiated thyroid cancer revealed no difference in the antigenic expression of all six epitopes, including the Tg 158 epitope. Papain digestion of purified Tg resulted in a 76 kD fragment which showed immuno‐reactivity for Tg 158 as well as for Tg 11. No interference of the binding of Tg 158 by T3, T4 or DIT could be detected.

We conclude that the monoclonal antibody Tg 158 detects an epitope which is present in thyroid tissue‐derived Tg but not in circulating thyroglobulin. This antibody might be useful for the investigation of the secretory process of thyroglobulin from the thyrocytes into the circulation.
Lovastatin reduces postprandial lipoprotein levels in hypercholesterolaemic patients with mild hypertriglyceridaemia
Authors: WEINTRAUB M. S. , EISENBERG S. , BRESLOW J. L.
Published: March 2008

Abstract. Drugs that inhibit cholesterol synthesis have recently been released for lowering LDL‐cholesterol levels. The current study examines the effect of one of these drugs, lovastatin, alone and in combination with cholestyramine on postprandial fat metabolism in five patients with severely elevated LDL‐cholesterol and normal triglyceride levels (< 1.8 mmol 1‐1) and in five patients with similarly elevated LDL‐cholesterol and mildly elevated triglyceride levels (1.8 to 2.7 mmoll‐1). In the group of patients with normal triglyceride levels, neither lovastatin alone nor in combination with cholestyramine had any effect on postprandial lipoprotein levels, while profoundly decreasing LDL‐cholesterol levels. This provides evidence that LDL and postprandial lipoproteins are cleared by different mechanisms. In the group of five patients with mildly elevated triglyceride levels, in addition to LDL‐cholesterol lowering, lovastatin significantly lowered VLDL‐cholesterol, fasting triglyceride and postprandial lipoprotein levels. Thus in patients with mild hypertriglyceridaemia, lovastatin may have another favourable effect on the lipoprotein system in addition to LDL‐cholesterol lowering.
Metabolism of chylomicrons in subjects with dysbetalipoproteinaemia (type III hyperlipoproteinaemia)
Authors: HAFFNER S. M. , KUSHWAHA R. S. , HAZZARD W. R.
Published: March 2008

Abstract. These studies were conducted to investigate whether subjects with dysbetalipoproteinaemia (type III hyperlipoproteinaemia) can catabolize chylomicrons normally and if chylomicron catabolism is related to the triglyceride pool size. Iodinated postprandial plasma chylomicrons were injected into subjects with dysbetalipoproteinaemia (n= 7), subjects with endogenous hypertriglyceridaemia (n=4), and normal subjects (n= 5). The subjects with dysbetalipoproteinaemia had VLDL‐cholesterol/total triglyceride ratios greater than 0.35 and were deficient in isoapoE‐3 and isoapoE‐4. The decay of radioactivity in chylomicron apoB was measured and residence times (RT) were calculated by measuring the area under the radioactivity decay curve. The mean RT for chylomicron apoB in subjects with dysbetalipoproteinaemia was 17.4 ± 3.5 h, which was significantly longer than in both subjects with endogenous hypertriglyceridaemia (4.8 ± 2.1 h) and also in normal subjects (5.9 ± 1.6 h). There was no significant correlation between chylomicron apoB RT and triglyceride levels in subjects with dysbetalipoproteinaemia or in other subjects. Thus, chylomicron apoB catabolism is retarded in subjects with dysbetalipoproteinaemia. The slow removal of chylomicron apoB in subjects with dysbetalipoproteinaemia does not seem to be attributable to an increased triglyceride pool size.
Degradation of vasoactive intestinal peptide by isolated, ventilated, and perfused rat lungs
Authors: BERNHARD W. , BOTHE‐SANDTFORT E. , KOOP H. , CASSEL W. , WICHERT P. VON
Published: March 2008

Abstract. The degradation of vasoactive intestinal peptide (VIP) was studied using an isolated perfused rat lung model. 125iodine labelled VIP (125I‐VIP) was used as a tracer. VIP was cleared from the perfusate by a single lung passage up to concentrations of 1 nmol 1‐1. The clearance rate was decreased at higher concentrations of VIP. VIP was taken up by the lung tissue and the cleavage products were re‐extruded into the perfusate. The time delay of re‐extrusion was increased at starting concentrations of VIP exceeding 1 nmol 1‐1 and in the presence of the lysosomal inhibitor chloroquine. After a bolus of 9 pmol or 40 nmol 125I‐VIP into the pulmonary artery catheter 6.3 pmol or 2920 pmol, respectively, were bound by the lung. Most of the radioactive material was extruded within 25 min and consisted of low molecular weight 125I‐labelled degradation products.

We conclude that the receptors for VIP in the alveolar capillaries are of high affinity and capacity to extract VIP from the circulation and that lysosomes may be involved in the degradation. The degradation products are of low molecular weight.
Treatment of endemic goitre due to iodine deficiency with iodine, levothyroxine or both: results of a multicentre trial
Authors: HINTZE G. , EMRICH D. , KÖBBERLING J.
Published: March 2008

Abstract. Preliminary clinical studies and recent in vitro investigations suggest that iodine administration may be an effective alternative in the treatment of the diffuse euthyroid goitre of iodine deficiency. Therefore a 12‐month multicentre study was initiated in which 166 patients were randomly assigned to take either 150 μg levothyroxine day‐1 (group A, n= 61), 400 μg iodine day‐1 (group B, n= 50), or a combination of 75 μg levothyroxine and 200 μg iodine day‐1 (group C, n= 55) for 8 months with follow‐up examinations at 4 and 8 months as well as 4 months after cessation of treatment. Initially, thyroid volume, as determined by ultrasound, was not significantly different in the three groups.

In all three groups, during treatment a significant and comparable mean decrease in goitre size was documented (‐32.1% in group A, ‐37.3% in group B, ‐38.7% in group C). After cessation of treatment in group A mean thyroid volume again increased to near the baseline value (‐12.0% compared to the initial investigation), while the therapeutic effect was sustained in group B (‐32.5%). In group C, only a slight rebound effect was observed (‐26.3%vs baseline volume). Total thyroxine (T4) increased sharply and significantly in group A from 7.8 ± 1.9 to 10.9 ± 2.8 μg dl‐1 after 8 months (P<0.001), but only slightly, although significantly in group B (from 7.8±1.5 μg dl‐1 to 8.9 ± 1.6 μg dl‐1; P<0±02). Striking differences between the three groups were evident in the changes of basal and thyrotropin releasing hormone (TRH) stimulated thyrotropin (TSH). After 8 months a sharp and significant decrease of TSH occurred in group A (from 1.2±0.53 to 0.4±0.74 μU ml‐1; P<0001) and in group C (from 1.2 ± 0.97 to 0.5±0.56 μ ml‐1; P<0.001). In group B, TSH was also significantly lower (from 1.3 ± 1.04 to 0.9 ± 0.72 μUml‐1;P<0.02), but remained significantly higher compared to group A and group C. Similar changes were observed when the TSH after TRH administration was calculated. After cessation of treatment, the values for basal TSH and TRH‐stimulated TSH in the three groups were not significantly different from each other. They had increased to the initial values.

Our data clearly show that iodine alone (400 μg day‐1) or a combination of 75 μg levothyroxine and 200 μg iodine day‐1 are at least equally as effective for goitre reduction as levothyroxine alone (150 μg day‐1) and offers the further benefit of a sustained effect after cessation of therapy.
The effect of cytomegalovirus infection on the adherence of polymorphonuclear leucocytes to endothelial cells
Authors: SPAN ANGELIQUE H. M. , BOVEN C. P. A. VAN , BRUGGEMAN CATHRIEN A.
Published: March 2008

Abstract. Adherence of polymorphonuclear leucocytes (PMN) to the endothelial lining of blood vessels is an essential component of the inflammatory response. In this study the effect of cytomegalovirus (CMV) infection on the adherence of PMNs has been examined using an in vitro model system.

Human umbilical venous endothelial cells (HUVEC) were grown on fibronectin‐coated plastics. CMV infection of HUVEC resulted in the appearance of viral antigens in a small percentage of the cells. At 24 h post‐infection when no virus‐induced cytopathic effect could be observed in the cell monolayers, the adherence of PMNs was significantly increased. The virus‐induced adherence effect was cell bound and could not be induced by soluble components in the medium of the virus‐infected cells. The augmentation of the PMN adherence to CMV‐infected endothelium was sensitive to tunicamycin suggesting that the virus infection induces the expression of glycoproteins on the HUVEC membranes which are responsible for the PMN adherence.

Thus CMV infection of the endothelium results in an increased adherence of PMNs. In the in vivo situation systemic viral infection can potentially lead to infection of blood vessel endothelium and thus can induce a damage of endothelium. This phenomenon could play a role in the atherogenesis process.
Low protein alimentation normalizes renal haemodynamic response to acute protein ingestion in type 1 diabetic children
Authors: CASTELLINO P. , SANTO N. G. DE , CAPASSO G. , ANASTASIO P. , COPPOLA S. , CAPODICASA G. , PERNA A. , TORELLA R. , SALVATORE T. , GIORDANO C.
Published: March 2008

Abstract. The effect of an acute protein load (2 g kg‐1bodyweight [BW]) was studied in nine type 1 diabetic children. Patients were maintained on two different dietary regimens. In study one, patients were on a high protein diet providing from 2.7 to 1.8 g of protein/kg of BW per day. In study two, patients were reevaluated after three weeks of a diet providing from 1.0 to 1.2 g kg‐1 of BW per day of protein. In study one (High Protein Diet), we failed to observe any rise in GFR and RPF following the protein meal (137 ± 21 basal vs. 110±14 and 472±93 basal vs. 494±93 ml/1.73 m2 of SA min‐1 at 60 min.

This is in contrast with results from seven age matched controls consuming a free diet, which showed a significant rise in both GFR and RPF.

In study two (low protein diet), basal GFR was significantly reduced. However after the protein load, both GFR (92±11 vs. 126±18 ml/1.73 m2 of SA min‐1) and RPF (467±83 vs. 705±102 ml/1.73 m2 min‐1) rose significantly (P<0.05 vs. basal). The data indicate that:

1 short term protein restriction reduces significantly GFR in type 1 diabetic children;

2 diabetic children maintained on an high protein intake show an altered haemodynamic response to protein ingestion;

3 a normal response to protein ingestion can be restored by short term dietary protein restriction.
Recent developments in the chemistry of gastrointestinal peptides
Authors: MUTT V.
Published: March 2008

Abstract. Work carried out in different laboratories has shown that the peptide pattern of the intestinal tissue is very complex and that some of the peptides are identical to those found in the central nervous system. The best studied of the peptides are of a hormonal nature, but recently evidence has been obtained that others may primarily act as antibiotics. In addition, peptides have been isolated that are fragments of some well‐known proteins that have not been viewed as being prohormones. Whether the latter peptides only represent transient degradation products of the proteins or whether, at least some of them, have a physiologically meaningful selective function of their own is not yet clear.
Feedback regulation of pancreatic exocrine secretion in animal and man
Authors: FÖLSCH U. R.
Published: March 2008

Abstract. This chapter focuses on studies dealing with the feedback mechanism of pancreatic exocrine secretion in animal and man. Clear evidence is presented that this feedback mechanism is working in the rat and the pig and that this feedback is mediated in the rat by the gastrointestinal hormones pancreozymin (enzyme secretion) and secretin (volume and bicarbonate secretion). Two novel peptides have been described—the ‘CCK‐releasing peptide’ originating from the small intestinal mucosa, and the ‘monitor peptide’ cose‐creted together with the enzymes in the pancreatic juice—to account for the stimulation of pancreatic enzyme secretion by the release of CCK. A similar feedback regulation of pancreatic secretion is working in man. It remains as yet controversial whether the feedback in humans is regulated via hormonal or neural pathways. It is also a matter of debate whether this feedback regulation of pancreatic enzyme secretion could be utilized for therapeutic aims in the treatment of pain in patients with chronic pancreatitis.
Role of bile acids in the control of pancreatic secretion and CCK release
Authors: KOOP I.
Published: March 2008

Abstract. In most species stimulated pancreatic enzyme secretion and CCK release are increased in the absence and inhibited in the presence of luminal bile acids. Changes in CCK release are almost unequivocal in all investigated species. With respect to enzyme secretion, physiological bile acid concentrations seem to be necessary to exert an inhibitory effect on stimulated enzyme output in humans. Bile acids administered in higher concentrations may enhance basal and stimulated pancreatic secretion. Furthermore, the chemical properties of different bile acids (i.e., hydroxylation, conjugation) seem to contribute to their stimulating effect on enzyme secretion as was observed in several species. The rank order of bile acids inhibiting stimulated enzyme secretion in humans is taurocholate taurodeoxycholate > taurocheno‐deoxycholate. On the other hand, chenodeoxycholic acid exerts the strongest stimulating effect on secretin release, which may account for the stimulating effect of this bile acid on exocrine pancreatic secretion.

The strongest candidate for the mediator role in bile‐acid‐induced changes of exocrine pancreatic secretion is CCK (at least in dogs and rats).

The CCK cell may be influenced either directly or indirectly.

In conclusion, bile acids modulate pancreatic enzyme secretion and CCK release. CCK is a major candidate for this regulatory role under physiological conditions.
Classification and histogenesis of gastroenteropancreatic endocrine tumours
Authors: SOLCIA E. , SESSA F. , RINDI G. , VILLANI L. , RIVA C. , BUFFA R. , CAPELLA C.
Published: March 2008

Abstract. A series of 267 gastroenteropancreatic endocrine tumours has been revised from the point of view of histopathologic diagnosis, hormonal profile and clinical behaviour. Results of this investigation, together with revised concepts on the histogenesis of gastroenteropancreatic endocrine growths, allowed to develop detailed classification systems which proved useful for precise tumour diagnosis and for clinico‐pathologic correlation, with special reference to tumour function, prognosis and therapy. Among 132 pancreatic growths, various types of islet cell tumours (61 cases), with (45 cases) or without (16 cases) hyperfunctional syndrome, were separated from different types of gut‐related (38 cases) and ‘ectopic’ (three cases) tumours, as well as from 25 non‐functioning, locally symptomatic tumours, three small cell carcinomas and two mixed endocrine‐exocrine tumours. Among 97 intestinal tumours, 39 argentaffin EC cell carcinoids, mostly from the appendix and ileum, were separated from 23 hindgut‐type carcinoids, mostly from the rectum, 22 gastrin cell tumours, mainly from the duodenal bulb, five somatostatin cell tumours, mostly from the periampullary region of the duodenum, and two gangliocytic paragangliomas. Among 38 gastric tumours, five small cell ‘neuroen‐docrine’ carcinomas were separated from three gastrin cell tumours and 30 argyrophil carcinoids, 27 of which arose in the body fundus, 16 associated with chronic atrophic gastritis and four with combined Zollinger Ellison/Multiple Endocrine Neoplasia Syndrome.
Altered collagen metabolism in osteogenesis imperfecta fibroblasts: a study on 33 patients with diverse forms
Authors: BRENNER R. E. , VETTER U. , NERLICH A. , WÖRSDORFER O. , TELLER W. M. , MÜLLER P. K.
Published: March 2008

Abstract. The pattern of collagen metabolism was analysed in fibroblast cultures from patients with diverse forms of osteogenesis imperfecta (OI). Generally, OI fibroblasts show an insufficient collagen synthesis which is most obvious in patients between 2 and 9 years of age during which period control fibroblasts have an elevated collagen synthesis. OI fibroblasts remain on a basal level except for fibroblasts from OI type IV patients which seem to approach normal levels. In addition, OI fibroblasts generally show a slightly increased degradation of newly synthesized collagen which again is most obvious between 2 and 9 years. These differences in collagen degradation, however, only contribute to a minor extent to the lack of net collagen synthesis during early childhood. No correlation could be found between the degree of overmodification of collagen and its degradation since fibroblasts of both OI type I and OI type II have an elevated degradation though only the latter ones produce overmodified collagen molecules. Pulse labelling of collagen with radioactivity labelled sugars was used to distinguish between normal collagen chains or CNBr‐derived peptides and those which were overmodified. In all three cases studied (OI II, OI III, OI IV) the entire triple helical domain of α 1(1) and α2(I) was overglycosylated. The amount of overmodification, however, was not uniform but rather unique for each patient studied. We assume that the molecular defects in the majority of OI cases may be located in the mechanisms operating on the control of both the age appropriate synthesis of collagen and its degree of post‐translational modification.
The effect of amino acid infusion on leg protein turnover assessed by L‐[15N]phenylalanine and L‐[1‐13C]leucine exchange
Authors: BENNET W. M. , CONNACHER A. A. , SCRIMGEOUR C. M. , RENNIE M. J.
Published: March 2008

Abstract. A stable isotope technique depending on the use of [15N]phenylalanine and [1‐13C]leucine to assess exchange was utilized to measure the components of protein turnover of the human leg and the effects of amino acid infusion. Eight healthy subjects (28.5 ±2.5 years) were studied when post‐absorptive in the basal state and again during infusion of a mixed amino acid solution (55 g 1−1, 1.52 ml kg−1 h−1). During the basal period leucine oxidation by the leg was 4.4 ± 2.0 nmol 100 g−1 min−1 and this increased threefold during amino acid infusion (13.6 ± 3.1 nmol 100 g−1 min−1, mean ± SEM, P=0.003). Amino acid infusion abolished the net negative balance between incorporation of leucine into, and release from, protein (basal, — 31.8 ± 5.8; during infusion, +3.1 ±7.1 nmol 100 g−1 P = 0.001). Phenylalanine exchange showed a similar pattern (basal, —13.7 ±1.8; during infusion, ‐0.8±3.0 nmol 100 g−1 min−1, P=0.003). Basal entry of leucine into leg protein (i.e. protein synthesis) was 70.0± 10.8 nmol 100 g−1 min−1 and this increased during amino acid infusion to 87.3 + 14.1 nmol 100 g−1 min−1 (P = 0.11). Phenylalanine entry to protein also increased with amino acid infusion (29.1±4.5 vs. 38.3± 5.8 nmol 100 g−1 min−1, P=0.09). Release from protein of leucine (101.8 ± 9.1 vs. 84.2±9.l nmol 100 g−1 min−1, P=0.21) and of phenylalanine (42.8 ± 4.2 vs. 39.1±4.2 nmol 100 g−1 min−1, P=0.50) was unchanged by amino acid infusion. The results suggest that, in the post‐absorptive state in man, infusion of mixed amino acids, without additional energy substrates; reverses negative amino acid balance by a mechanism which includes stimulation of muscle protein synthesis but which does not alter protein breakdown. Interpretation of the results obtained concurrently on whole‐body protein turnover suggests that the increase in muscle protein synthesis contributes substantially to the whole‐body increase, but the fall in whole‐body breakdown with exogenous amino acids is independent of changes in muscle.
Postpartum thyroid dysfunction and HLA status
Authors: KOLOGLU M. , FUNG H. , DARKE C. , RICHARDS C. J. , HALL R. , McGREGOR A. M.
Published: March 2008

Abstract. Nine‐hundred‐and‐one women presenting in an antenatal clinic at the 60th week of pregnancy were tested for antithyroid antibodies. A group of 113 antibody‐positive women and 108 antibody‐negative age‐matched controls were HLA typed and followed prospectively at 6‐weekly intervals through pregnancy and for 12 months postpartum. Forty‐five of the women developed biochemical evidence of postpartum thyroid dysfunction (PPTD) of whom 36 were antibody positive. Compared with a local control population (n = 600), and using multiplex analysis, there was a significant increase in the combinations HLA B8, DR3 and HLA Al, B8, DR3 from 22.5% to 40.0% (P<0.02) and from 18.6% to 35.6% (P<0.01) respectively in the women who developed PPTD. The well‐recognized association of these haplotypes with other organ‐specific autoimmune diseases provides further support for autoimmune events being implicated in the development of PPTD.
Congestive heart failure: involvement of perivascular peptides reflecting activity in sympathetic, parasympathetic and afferent fibres
Authors: EDVINSSON L. , EKMAN R. , HEDNER P. , VALDEMARSSON S.
Published: March 2008

Abstract. In controls and in patients suffering from congestive heart failure (CHF) the circulating levels of catecholamines, neuropeptide Y‐like immunoreacti‐vity (NPY‐LI), vasoactive intestinal peptide‐LI (VIP‐LI), substance P‐LI (SP‐LI) and calcitonin gene‐related peptide‐LI (CGRP‐LI) markers of sympathetic, parasympathetic and sensory nervous systems, respectively, have been examined. There was a significant rise in the levels of noradrenaline, NPY‐LI and SP‐LI already in moderate CHF (New York Heart Association Stage I and II). In patients with severe CHF (NYHA Stage III and IV) the circulating levels of noradrenaline, adrenaline, NPY‐LI and SP‐LI were significantly increased. CGRP‐LI was not altered, despite the fact that this peptide co‐exists in many tissues with SP. There was no change in VIP‐LI. The pathophysiological significance of this pattern of reaction of circulating catecholamines and neuropeptides is unclear; however, the rise in SP‐LI may be a reaction to counterbalance the vasoconstrictive effects of the activation of the sympatho‐adrenal system.
Haemodynamic and neurohumoral responses in elderly patients with postural hypotension
Authors: LYE M. , VARGAS E. , FARAGHER E. B. , DAVIES I. , GODDARD C.
Published: March 2008

Abstract. Haemodynamic and neurohumoral responses to head‐up tilt were measured in 28 elderly patients with postural hypotension (EPPH) and 12 healthy elderly subjects (HE). There were no differences in catecholamines between the groups and only noradrenaline increased on tilt (P< 0.001). Plasma renin activity and aldosterone were similar in HE and EPPH in the supine and tilt positions. In both groups vasopressin increases (P=0.032), and plasma volume decreases were the same (P=0.673). Supine EPPH had higher heart rates (P=0.019) but similar cardiac indices (P = 0.621). Both had similar changes on tilting (P=0.975 and P=0.341). Stroke volume decrease was higher in HE (35%) than EPPH (23%; P< 0.001). HE showed an increase in peripheral resistance on tilting with no change in EPPH (P=0.005). EPPH had larger coefficients of variation for all variables. The differences in haemodynamic responses and the similarity of neurohumoral responses during tilting suggest end‐organ failure in EPPH with individual variations. Postural hypotension in old age is not a single entity.
Tubular site of renal sodium retention in ascitic liver cirrhosis evaluated by lithium clearance
Authors: ANGELI P. , GATTA A. , CAREGARO L. , MENON F. , SACERDOTI D. , MERKEL C. , RONDANA M. , DE TONI R. , RUOL A.
Published: March 2008

Abstract. Renal tubular sodium handling was evaluated in 27 non‐azotemic cirrhotic patients with ascites and positive sodium balance and in 17 controls after at least 5 days of a constant sodium intake using the lithium clearance as an index of fluid delivery to the distal tubule. Plasma renin activity and plasma aldos‐terone were also evaluated. Sodium fractional excretion, filtered sodium load, absolute sodium distal delivery, lithium fractional excretion and absolute distal sodium reabsorption were significantly lower in cirrhotics than in controls (0.58 ± 0.11 vs. 1.29 ± 0.12%, < 0.001; 12529± 677 vs. 15707±796 μEq min−1 1.73 m−2 BSA, <0.005; 2384±135.2 vs. 3685±219.3 μEq min−1 1.73 m−2 BSA, < 0.001; 19.5±1.0 vs. 24.2±l.3%, < 0.01; 2299±127 vs. 3485±214 μEq min−1 1.73 m−2 BSA, <0.001, respectively). A correlation was found between lithium clearance and sodium clearance only in cirrhotic patients (r = 0.62; <0.01). Distal sodium reabsorption evaluated as a per cent of filtered sodium load was lower in cirrhotics than in controls (19.1 ±1.0 vs. 22.4±1.2%, <0.05) while distal sodium reabsorption evaluated as a per cent of sodium distal delivery was higher in cirrhotics than in controls (96.7 ± 0.4 vs. 94.4± 0.5%,< 0.005). In both groups a correlation was found between log plasma aldosterone and distal sodium reabsorption evaluated as a per cent of absolute sodium distal delivery (r = 0.61, <0.01 and r=0.52,<0.05 respectively).

Our study indicates that a decrease in filtered sodium load and an increase in proximal sodium reabsorption play a critical role in the impairment of renal sodium handling in non‐azotemic cirrhotic patients with ascites.
Mechanisms of hypercholesterolaemia in glycogen storage disease type I: defective metabolism of low density lipoprotein in cultured skin fibroblasts
Authors: LEVY E. , THIBAULT L. , ROY C. C. , LETARTE J. , LAMBERT M. , SEIDMAN E. G.
Published: March 2008

Abstract. Hyperlipidaemia is a feature of glycogen storage disease type I (GSD‐I) (Levy et al. [1]). High levels of LDL cholesterol (200 ± 25 mg dl‐1) and apo B (387 ± 44 mg dl‐1) were found in association with hypercholesterolaemia in GSD‐I. Related causative factors might be attributed to overproduction and/or delayed removal of LDL. In this study, a possible alteration in the clearance of LDL was examined. Using cultured fibroblasts for LDL receptor activity, the following observations were made:

1 GSD‐I fibroblasts revealed only a slight decrease in LDL binding (65 ± 7) when compared with controls (74 ± 4 ng mg‐1 protein), however, LDL internalization (382±24 vs. 570 ± 52 ng mg‐1 protein) and proteolytic degradation (2082±280 vs. 2916± 12.5 ng mg‐1 protein) were significantly affected (P<0.01).

2 Binding, internalization and proteolytic degradation of LDL from GSD‐I were compared with that of controls, and were found to be significantly lower (P<0.01).

3 Substitution of control lipoprotein‐deficient serum (LPDS) by GSD‐I LPDS further diminished the above processes (P<0.05).

Our results demonstrate that increased plasma cholesterol in GSD‐I is due to a decreased catabolism of LDL. The data suggest that the problem may well be multifactorial, due to diminished receptor expression, abnormal LDL composition and impaired LDL receptor interaction due to a circulating inhibitory factor.
Tubular sodium handling in cirrhotic patients with ascites as analysed by the renal lithium clearance method
Authors: DIEZ J. , SIMON M. A. , ANTON F. , INDART F. J. , PRIETO J.
Published: March 2008

Abstract. The proximal and distal sodium reabsorption were calculated from lithium clearance in 21 healthy controls and 24 cirrhotic patients with ascites after 4 days under a sodium‐restricted diet. The values of fractional lithium clearance were lower in patients than in controls (7.37±0.87 vs. 18.13±1.76%, P< 0.001). Fractional proximal sodium reabsorption was increased in patients compared with controls (92.8±1.1 vs. 81.8± 1.7%, P<0.001). No differences were found in fractional distal sodium reabsorption between controls and patients (96.9 ± 0.8 vs. 98.6 ±0.1%). When patients were separated into two subgroups according to their sodium balance, it was found that fractional distal sodium reabsorption was increased in patients whose balance remained positive, compared with patients on a negative sodium balance (98.99 ±0.26 vs. 94.11 ± 1.50%, P<0.05). In addition, the natriuretic response to a specific dose of spirono‐lactone was higher in patients on positive sodium balance compared with patients on negative sodium balance (per cent increase in natriuresis after spirono‐lactone 300 mg day‐1: 355.24 ± 73.98 vs. 84.21 ± 15.8%, P<0.01). We conclude that proximal sodium reabsorption is increased in cirrhotics with ascites. In addition, distal sodium reabsorption is enhanced only in those patients which exhibit avid sodium retention.
The effect of pharmacological modification of gastric emptying and mouth‐to‐caecum transit time on the absorption of sugar probe marker molecules of intestinal permeability in normal man
Authors: BRUNETTO A. L. , PEARSON A. D. J. , GIBSON R. , BATEMAN D. N. , RASHID M. U. , LAKER M. F.
Published: March 2008

Abstract. The present study examined the hypothesis that altered motility of the gastrointestinal tract affects absorption of probe markers of intestinal permeability. Seven healthy subjects, aged 32–44 years, received saline, 600 μg atropine or 10 mg metoclopramide in randomized order at weekly intervals. After 10 min they ingested a test solution containing 5 g lactulose, 5 g mannitol and 2 g 3‐O‐methyl glucose in 100 ml tap water. The molarity of the solution was 542 mmol l‐1 and the dose administered was 80 ml m‐2 body surface area. Gastric emptying was measured by ultrasound, mouth‐to‐caecum transit time by breath hydrogen analysis and sugar concentrations by gas‐liquid chromatography. Gastric emptying half‐times (min) were [mean (95% confidence intervals)] 14.9 (11.4–18.5) after saline, 22 (18.7–25.2) after atropine and 10.3 (7.0 12.6) after metoclopramide (P< 0.002). Transit times (min) were 68.9 (52–85.2) after saline, 143 (126–159) after atropine and 38 (21.2–54.5) after metoclopramide; P<0.0001. Analysis of plasma levels of mannitol and 3‐O‐methyl glucose showed a significant within‐subject effect of drug with time (P<0.03). Urinary excretion of mannitol in the first 5 h after ingestion of the test solution was 1256 (974–1620) mg after saline, 1560 (1210–2013) mg after atropine and 955 (740–1232) mg after metoclopramide (P<0.03). There were no significant differences in lactulose and 3‐O‐methyl glucose urinary excretion between drug treatments. Gastric emptying time was significantly correlated with mannitol excretion (P< 0.003) and lactulose excretion (P<0.03). There were no significant differences in lactulose:mannitol excretion ratios between treatments.
Exercise‐induced changes in insulin‐like growth factors and their low molecular weight binding protein in healthy subjects and patients with growth hormone deficiency
Authors: BANG P. , BRANDT J. , DEGERBLAD M. , ENBERG G. , KAIJSER L. , THORÉN M. , HALL K.
Published: March 2008

Abstract. Serum concentrations of insulin‐like growth factors 1 and 2 (IGF‐1 and IGF‐2), the low molecular weight form of IGF binding protein (IGFBP‐1), insulin, C‐peptide and GH were determined in six healthy subjects and four patients with GH deficiency during 30 min of moderate physical exercise on the cycle ergometer. The load corresponded to 60% of individual maximal oxygen uptake. IGF‐1 and IGF‐2 were determined by radioimmunoassays developed with antibodies isolated from immunized hens egg‐yolk after separation by automated acid gel filtration of serum samples prior to assay.

Significant increases in the serum concentrations (mean±SEM) of IGF‐1 (157±24 to 196 ± 29 μg l‐1, P<0.05) and IGF‐2 (451±37 to 678 ±85 μg 1‐1, P< 0.01) were seen in the healthy subjects after 10 min of exercise. The mean percentage increase was 26 ± 5% for IGF‐1 and 50± 11% for IGF‐2. No relation to the GH release was found. In GH‐deficient patients the mean IGF‐2 concentration rose 48 ± 17% from basal 216 ± 63 μg 1‐1 to a peak concentration of 324 ±115 μg 1‐1 (P<0.01) after 30 min, while the 38 ±20% rise of IGF‐1 from basal 36± 13 μg 1‐1 to a peak concentration of 55 ±27 μg 1‐1 was not significant. The serum IGFBP‐1 concentration did not change during exercise, while insulin and C‐peptide concentrations, as well as blood glucose, decreased in both healthy subjects and GH‐deficient patients.

In conclusion, exercise induced an increase in the serum concentrations of IGF‐1 and IGF‐2 independently of the GH response. It may be hypothesized that IGFs have a physiological role in the glucose transport into working muscles.
Galactose removal kinetics during hypoxia in perfused pig liver: reduction of Vmax, but not of intrinsic clearance Vmax/Km
Authors: KEIDING S. , JOHANSEN S. , TYGSTRUP N.
Published: March 2008

Abstract. The galactose elimination kinetics was examined in five perfused pig livers of 1.2 kg during hypoxia induced by administration of 2, 4 or 7% oxygen in the oxygenator instead of 20% as used in nine control experiments, previously published [1]. Galactose was given as four to five successive constant infusion rates so that successive steady‐state period with galactose concentrations from 0.04 to 5 mmol l‐1 were obtained in each experiment. From the relationship between the calculated elimination rate and the perfusate galactose concentration, values of the maximal elimination rate Vmax and the half saturation concentration Km were calculated. Both Vmax and Km were reduced by hypoxia: the lower the oxygen supply, the greater the reduction. Vmax was about 0.08 mmol min‐1 kg‐1 liver at 2% oxygen and about 0.18 mmol min‐1 kg‐1 liver at 4–7% oxygen; both being significantly lower than the value of 0.43 mmol min‐1 kg‐1 liver at 20% oxygen. Km was about 0.07 mmol l‐1 at 2% oxygen and 0.13 mmol 1‐1 at 7% oxygen; both significantly lower than the value of 0.23 mmol l‐1 at 20% oxygen. A nearly parallel reduction of liver ATP concentration and galactose Vmax indicates that the galactose Vmax may reflect the phosphorylation capacity of the liver cells. The Vmax/Km ratio (intrinsic hepatic clearance) was unchanged during hypoxia.
Cyclic nucleotide phosphodiesterases and methyltransferases in purified lymphocytes, monocytes and polymorphonuclear leucocytes from healthy donors and asthmatic patients
Authors: PRIGENT A. F. , FONLUPT P. , DUBOIS M. , NÉMOZ G. , TIMOUYASSE L. , PACHECO H. , PACHECO Y. , BIOT N. , PERRIN‐FAYOLLE M.
Published: March 2008

Abstract. Cyclic nucleotide phosphodiesterase and phospholipid N‐methyl‐transferase activities were simultaneously measured in purified polymorphonuclear cell‐, mononuclear cell‐, lymphocyte‐ and mono‐cyte‐homogenates from control subjects, from patients with atopic asthma and from patients with non‐atopic asthma. Whereas cyclic AMP and cyclic GMP phosphodiesterase activities were found to be about 10‐fold lower in polymorphonuclear than in mononuclear cells, phospholipid N‐methyltransferase proved to be rather similar in each cell type from control donors. Cyclic AMP phosphodiesterase and phospholipid N‐methyltransferase were significantly decreased in polymorphonuclear cells and monocytes from asthmatic patients compared with the control group while cyclic GMP phosphodiesterase was significantly impaired only in the monocyte subpopulation.
Castration inhibits glomerular hypertrophy and proteinuria in uninephrectomized male rats
Authors: GAFTER U. , BEN‐BASSAT M. , LEVI J.
Published: March 2008

Abstract. Renal mass reduction may lead to glomerular hypertrophy, proteinuria and focal glomerulo‐sclerosis (FGS) in humans and rats. In humans and rats, females are less susceptible than males to these phenomena. This study was undertaken to evaluate the effect of male rat castration on the pathogenesis of proteinuria and FGS. Urinary protein was measured in 60‐day‐old male and female rats. Uninephrectomy was performed in all rats, and castration in half of the males. After 180 days, proteinuria, glomerular filtration rate (GFR) and blood biochemistry were determined. Kidneys were resected, weighed and subjected to morphologic studies. Following uninephrectomy, male rats developed severe proteinuria:132.3 pM 40.9 mg 24 h‐1, most of which was accounted for by an albuminuria of 70.9 pM 19.3 mg 24 h‐1. In contrast, protein excretion in female and castrated male rats remained within normal limits: 8.0 pM 1.8 and 4.2 pM 0.5 mg 24 h‐1, respectively. Mean glomerular volume in male rats was 1.18 pM 0.08 times 106μm3; much higher than in female rats, 0.84 pM 0.04 times 106μm3, and castrated male rats, 0.87 pM 0.03 times 106μm3 (P<0.005). On light and electron microscopy, glomeruli of female and castrated male rats were completely normal. In contrast, in four of seven male rats, mild glomerular changes were observed. They consisted mainly of mesangial expansion, electron‐dense deposits and collapse of capillary loops. These data suggest that castration confers protection against the development of glomerular hypertrophy and proteinuria in uninephrectomized male rats. Endogenous testosterone may be associated with this development.,
Cellular targets and receptors for interleukin‐6 II. Characterization of IL‐6 binding and receptors in peripheral blood cells and macrophages
Authors: PETERSEN C. MUNCK , DAVIDSEN O. , MOESTRUP S. K. , SONNE O. , NYKJÆR A. , MØLLER B. K.
Published: March 2008

Abstract. Within 15 min, approximately 2–5% of 125I‐labelled interleukin‐6 (IL‐6) injected intravenously into rats was taken up by the spleen. As determined by light microscopic autoradiography, uptake was mainly (60%) accounted for by macrophages in the red pulp. 125I‐IL‐6 binding in rat peritoneal macrophages was quantitatively similar to that in cultured human monocytes and T‐cells. By comparison, IL‐6 binding to polymorphonuclear granulocytes and freshly isolated monocytes was low. Stimulation with antigen, but not with mitogen (PWM), induced receptor presentation in B‐cells, whereas antigen and mitogen downregulated the binding in T‐cells.

At 4 C, labelled IL‐6 bound to cells with a half‐time of about 1.5 h. Binding appeared reversible, but dissociation was slow and incomplete. The apparent Kd for IL‐6 binding was about 30 pmol 1‐1 in most cell types, however, values of approximately 120 pmol 1‐1 were obtained in polymorphonuclear granulocytes. At 37cC, 125I‐IL‐6 was rapidly internalized by T‐cells and monocyte‐macrophages, and after a lag time, TCA‐soluble radioactivity was released from the cells following a sigmoidal curve. Polyacrylamide gel electro‐phoresis of radiolabelled IL‐6 cross‐linked to its binding sites in T‐cells, yielded receptor‐ligand complexes with molar masses of 70–80 and 120–140 kg mo‐1. This would agree with a dimeric conformation of the IL‐6 receptor.,
Further studies on the mechanism of the natriuretic response to low‐dose dopamine in man: effect on lithium clearance and nephrogenic cAMP formation
Authors: SCHOORS D. F. , DUPONT A. G.
Published: March 2008

Abstract. The effect of intravenous infusion of low‐dose dopamine on electrolyte excretion, lithium clearance, nephrogenous cAMP formation and renal hae‐modynamics was investigated in healthy volunteers. Dopamine significantly increased the urine flow rate by 70.6% and urinary sodium excretion by 72%, but did not change creatinine clearance, PRA or plasma levels of AVP, ANP and cAMP. Renal plasma flow significantly increased by 48.6%; the glomerular filtration rate was not changed.

Lithium per se increased basal PRA, but had no effect on the increments of urine flow rate, sodium excretion and renal blood flow induced by dopamine. Dopamine significantly increased the fractional excretion of lithium (representing fractional excretion of sodium at the proximal level). The increase in urinary sodium excretion during dopamine infusion, significantly correlated with the increase in fractional excretion of lithium (r= 0.94; P <0.01) and the increase in nephrogenous cAMP formation (r= 0.96; P > 0.01). No correlation was found between the increase in urinary sodium excretion and the increase in renal blood flow.

In conclusion, this study confirms that low‐dose dopamine increases renal blood flow and urinary sodium excretion in healthy volunteers. This natriuretic response appears to be due to interaction with proximal tubular dopamine receptors, which are positively coupled to adenylate cyclase.,
Platelet aggregability in humans: contrasting in vivo and in vitro findings during sympatho‐adrenal activation and relationship to serum lipids
Authors: LARSSON P. T. , HJEMDAHL P. , OLSSON G. , ANGELIN B. , HORNSTRA G.
Published: March 2008

Abstract. Platelet aggregability was studied in 18 healthy volunteers during mental stress (a colour word test; CWT) and low‐ and high‐dose adrenaline infusions using an ex vivo technique (filtragometry) and conventional in vitro aggregometry. CWT and high‐dose adrenaline (3–4 nmol 1‐1 in plasma) shortened filtragometry readings, suggesting increased platelet aggregability in vivo. Low‐dose adrenaline had no effect despite higher adrenaline levels in plasma (0.9 nmol I‐1) than during CWT (0.4 nmol I‐1). Platelet sensitivity to ADP in vitro was reduced following CWT and further reduced following adrenaline infusions. In vitro, adrenaline (50 nmol I‐1) had little effect on platelet aggregation per se, but enhanced aggregability evoked by ADP (at ED50). Adrenaline potentiation of ADP‐induced aggregation was enhanced after CWT, but was not related to filtragometry responsiveness to stress in vivo. Serum LDL‐cholesterol levels were inversely correlated to filtragometry readings at rest, suggesting an adverse influence on platelet aggregability in vivo. HDL‐cholesterol levels were inversely correlated to platelet sensitivity to ADP in vitro, suggesting a positive influence. Thus, sympathp‐adre‐nal activation enhances platelet aggregability in vivo (as assessed by ex vivo filtragometry), but adrenaline alone cannot explain the pro‐aggregatory effect of mental stress. Serum lipoprotein alterations associated with increased risk for atherosclerosis seem to enhance platelet aggregability. The conventional in vitro technique may poorly reflect platelet aggregability in vivo.,