bluuebunny/crossref_metadata_2025 huggingface dataset:
The ontogeny and site of intestinal lipid and lipoprotein synthesis
Authors: MEHRAN M. , THIBAULT L. , RUSSO P. , GAROFALO C. , LEVY E.
Published: March 2008

Abstract. The developmental aspects of characteristic intestinal lipoprotein synthesis, chylomicrons (CM), very low density lipoproteins (VLDL) and high density lipoproteins (HDL), are unknown. Our objective was to determine the ontogeny of intestinal lipid and lipoprotein synthesis in both the jejunum and the ileum. Explants of the jejunum and the ileum from fetal (F) (18–19 days of gestation), suckling (S) (5 days old) and weaning (W) (23 days old) rats were cultured in the presence of [14C]‐oleic acid to examine lipid synthesis. The results indicate the following. (1) The incorporation of oleic acid is higher for the fetal explants. However, the efficiency of esterification of free fatty acids (FFA) into triglycerides (TG) in the jejunum increases with age (33% F, 37% S, 48% W) (P<0.05, by ANOVA). (2) The same profile is found at the ileal site for the incorporation of oleic acid. However, the capacity for the synthesis of TG is more intense at the suckling period (34% F, 54% S, 42% W) (P<0.05, by ANOVA). (3) The relative content of TG in CM changes with age: F, 90–93%; S, 80–84%; W, 33–40%. (4) A low percentage of TG content is found in CM at the weaning period while high levels are detectable in VLDL (40–42%). (5) A most significant difference is noted between the jejunum and the ileum in TG synthesis at the suckling period. The ileum synthesizes 53% more TG than the jejunum (P<0.025). (6) HDL particles contain substantial amounts of FFA. Nevertheless, they were also found to be able to transport TG mainly in the suckling rat. Thus, this study demonstrates that with growth the rat is able to synthesize CM, VLDL and HDL. Our findings indicate changes in the synthesis of intestinal lipids and lipoproteins, depending on both the development and the site, which suggests an ontogeny. These modifications can be attributed to dietary and hormonal influences present during the period of development.
Biotransformation of orally administered ursodeoxycholic acid in man as observed in gallbladder bile, serum and urine
Authors: FISCHER S. , NEUBRAND M. , PAUMGARTNER G.
Published: March 2008

Abstract. The aim of this study was to evaluate the biotransformation of orally administered ursodeoxycholic acid in man. The distribution of ursodeoxycholic acid and its metabolites in gallbladder bile, in serum and in urine with emphasis on separation of their unconjugated, amidated and sulfated species in particular, was investigated. Seven gallstone patients were given 750 mg of ursodeoxycholic acid daily for 2–3 weeks. Six gallstone patients who did not receive ursodeoxycholic acid served as controls. Ursodeoxycholic acid became the major bile acid in gallbladder bile contributing 43% to total bile acids. 2% of biliary ursodeoxycholic acids were in the unconjugated form, 87% in the amidated form and 11% in the sulfated form. Iso‐ursodeoxycholic acid was found in bile in small amounts and was present only as the sulfated species and not as the amidated one. Other metabolites of ursodeoxycholic acid tentatively identified in bile were 1β, 12β, 6α‐ and 21,22‐hydroxylated derivatives of ursodeoxycholic acid. Lithocholic acid in bile tended to increase under ursodeoxycholic acid treatment and was positively correlated to ursodeoxycholic acid. The concentration of cholic acid in bile decreased significantly whereas the levels of deoxycholic acid and chenodeoxycholic acid did not change. Total bile acid concentration in serum and excretion of bile acids in urine increased from 5.4 ± 1.1 to 18.4 ± 9.5 μmol l‐1 (mean ± SD, P < 0.005) and from 5.6 ± 1.3 to 13.1 ± 7.9 μmol g‐1creatinine (mean ± SD, P < 0.05) after ursodeoxycholic acid ingestion mainly due to spillover and excretion of ursodeoxycholic acid. Ursodeoxycholic acid became the major bile acid in serum and urine contributing 46% and 50% to total bile acids. 14% ursodeoxycholic acid in serum were in the unconjugated form, 42% in the amidated form and 45% in the sulfated form; the percentages in urine were 11%, 23% and 66%. Iso‐ursodeoxycholic acid was higher in serum and urine than in bile and contributed 16% and 8% to total bile acids. Iso‐ursodeoxycholic acid was present in serum and urine only as the unconjugated and sulfated species. Other iso‐bile acids and 3β‐hydroxy‐5‐cholenoic acid were found in bile only in traces, but contributed 8% to total bile acids in serum and 10% in urine. In serum and urine the sulfated form of lithocholic acid prevailed and was significantly enhanced after ursodeoxycholic acid ingestion. Further metabolites of ursodeoxycholic acid in urine were tentatively identified to be hydroxylated at postitions 1β, 5α, 6α and 22 and contributed about 10–15% of urinary UDCA.
Liposomal dexamethasone effectiveness in the treatment of hypersensitivity pneumonitis in mice
Authors: TREMBLAY G. M. , THÉRIEN H.‐M. , ROCHELEAU H. , CORMIER Y.
Published: March 2008

Abstract. The effects of daily intranasal instillation of liposomal dexamethasone and free dexamethasone phosphate were compared in a murine model of hypersensitivity pneumonitis induced by Saccharopolyspora rectivirgula (formally known as Micropolyspora faeni). After 3 weeks of antigen and liposome instillations, lung response was evaluated by bronchoalveolar lavage cell counts, lung index and histopathology. Systemic absorption was evaluated by measuring plasma adrenocorticotropic hormone (ACTH) level. Free dexamethasone phosphate induced a dose‐dependent response with the maximal effect reached at 1 mgkg‐1. At 0.1 mgkg‐1, liposomal dexamethasone had a greater effect than free dexamethasone phosphate on bronchoalveolar cells ml‐1: 3.01 × 105± 0.35× 105 compared to 4.70×105± 0.34 × 105, and lung index: 1.22 ±0.10 compared to 1.86 ± 0.07. Effect on histopathology was similar. Plasma ACTH levels (pg ml‐1) were: 75.1 ± 14.0 for animals receiving antigen and free dexamethasone phosphate (0.2 mg kg‐1), and 149.7 ± 12.0 for animals receiving antigen and liposomal dexamethasone (0.2 mg kg‐1). In conclusion, liposome‐incorporated dexamethasone is efficient in the treatment of experimental hypersensitivity pneumonitis and, contrarily to free dexamethasone phosphate, does not inhibit ACTH secretion.
Accumulation of iron in erythroblasts of patients with erythropoietic protoporphyria
Authors: RADEMAKERS L. H. P. M. , KONINGSBERGER J. C. , SORBER C. W. J. , FAILLE H. BAART DE LA , HATTUM J. VAN , MARX J. J. M.
Published: March 2008

Abstract. We have studied the iron metabolism in nine patients with erythropoietic protoporphyria (EPP) and three patients with sideroblastic anaemia (SA). All, except one EPP patient were iron deficient. The SA patients had a secondary haemochromatosis.

The bone marrow aspirates of patients with SA and also three patients with EPP had a high incidence of ring sideroblasts. Ultrastructural examination of the bone marrow consistently showed finely dispersed electron‐dense deposits localized in mitochondria of erythroblasts in all patients with EPP and SA. Mito‐chondrial electron energy‐loss spectroscopy (EELS) indicated identical iron compounds in erythroblasts of all EPP and SA patients.

These findings indicate that the mitochondrial iron utilization is disturbed in EPP and SA. The observation of mitochondrial iron deposition in erythroblasts in EPP and SA suggests that this feature is not of pathognomonic value for diagnosis of SA, but is apparently the result of an inefficient haem synthesis, in EPP due to a defective ferrochelatase. The mitochondrial iron deposition does not depend on the iron status (iron overload or iron deficiency) of the EPP patient.
Coxsackie B3 myocarditis induces a decrease in energy charge and accumulation of hyaluronan in the mouse heart
Authors: WALDENSTRÖM A. , FOHLMAN J. , ILBÄCKY N. G. , RONQUIST G. , HÄLLGREN R. , GERDIN B.
Published: March 2008

Abstract. Interstitial oedema in chronic inflammation and ischaemia is related to an accumulation of hyaluronan (hyaluronic acid; HA) in the interstitium. As interstitial oedema will affect the oxygen transport in the interstitium we have evaluated whether accumulation of HA is related to signs of myocardial energy depletion in virus induced myocarditis. Myocarditis was induced in Balb/c mice by inoculation of Coxsackie B3 virus. The extractable HA content of the myocardium increased progressively from a baseline value of 153 ± 26 μg g‐1 dry weight to a maximum of 286 ± 78 μg g‐1 dry weight at day 7, whereafter there was a slight decline. Affinity histochemistry visualized HA in the endo‐perimysium in healthy myocardium. At day 5 after Coxsackie B3 inoculation there was a general widening of the endomysium, which exhibited a positive staining for HA. In conjunction with focal inflammatory infiltrates the staining for HA was even more pronounced.

The energy rich adenylates were reversibly affected by the Coxsackie B3 infection. There was a slight, but significant decline in EC from 0.74 ± 0.05 in the control group to a minimum value of 0.64 ± 0.10 at day 5, whereafter a restitution was observed at days 7 and 10. The total adenine nucleotide pool was similarly decreased from 27.8 ± 2.9 μmol g‐1 dry weight in controls to 24.6 ± 2.1 μg g‐′ dry weight at day 5, and normalized at days 7 and 10.

The data suggest that virus induced myocarditis is associated with a local accumulation of HA in the myocardium. Accumulation of HA is reasonably not a major pathophysiological component in the disturbed energy metabolism seen, but may be of interest for genesis of arrhythmias and possibly sudden death.
Long‐term treatment with octreotide in patients with the Zollinger‐ElIison syndrome
Authors: RUSZNIEWSKI P. , RAMDANI A. , CADIOT G. , LEHY T. , MIGNON M. , BONFILS S.
Published: March 2008

Abstract. This study reports the effects of 4 and 5‐year treatment with octreotide (200 μg sc bid) in the Zollinger‐Ellison syndrome (ZES). No symptoms related to acid hypersecretion were observed in the four patients throughout the study, and upper GI endoscopy was normal. Basal acid output (BAO) measured 12 h after injection, was below 10 mmol h‐1 in three to four patients and previous ranitidine treatment was discontinued. In the fourth case (pre‐treatment BAO value: 115 mmol h‐1), BAO progressively decreased to 42 mmol h‐1 after 5 years of octreotide treatment. At the end of the study, serum gastrin levels were 58.5% (30–68) of the pretreatment values and two patients had normal gastrin levels. Peak acid output (PAO) decreased markedly after 2, 4 and 5 years, by 68% (35–89) suggesting that octreotide had exerted an antitrophic effect on parietal cell mass. Diffuse hyperplasia of fundic argyrophil cells present in two patients before octreotide, decreased during the treatment. Mean argyrophil cell density for all patients was not significantly modified. Antral gastrin‐cell density was in the normal range. No long‐term side effect of octreotide treatment was observed. Although octreotide may not be considered as a substitute for benzimidazoles in the treatment of ZES, its specific properties may be of therapeutic benefit in some ZES patients.
Sodium‐lithium countertransport: does it matter how it is calculated?
Authors: ADEBAYO G. I. , HEMERYCK L. , HALL M. , FEELY J.
Published: March 2008

Abstract. On the basis of a preliminary observation that sodium‐lithium countertransport showed different intra‐individual variations when calculated by two standard methods despite using the same sets of lithium efflux data, we decided to compare values by the two methods in a much larger number (50) of volunteers. Although there was significant correlation between the two sets of values (r =0.936), mean value by M‐l was significantly higher than that by M‐2 (P<0.007). Using appropriate statistical methodology, the limits of agreement between M‐l and M‐2 values (‐0.066 to 0.096 mmol L cell‐1 h‐1) were considerable; and the 95% confidence limits of the bias (i.e. mean difference) did not include zero. Furthermore, neither the 95% confidence interval for the correlation coefficient nor that for the slope of regression line included 10. These suggest lack of agreement between the two sets of values. The probable cause of this difference is discussed.
Chronic lead exposure in rats: effects on blood pressure
Authors: NOWACK R. , WIECEK A. , EXNER B. , GRETZ N. , RITZ E.
Published: March 2008

Abstract. The influence of Pb exposure on blood pressure was investigated in Wistar Kyoto, Sprague Dawley and stroke prone spontaneously hypertensive rats. In short‐term experiments, a dose‐dependent decrease of blood pressure was found with administration of Pb acetate in drinking fluid. This effect was more pronounced in young, male as compared to old, female animals. Pressor responses to noradrenalin and ANG II were decreased. In contrast, long‐term Pb exposure of more than 1 year duration consistently caused hypertension. In SHR‐sp a high proportion of animals died from cerebrovascular haemorrhage even before developing hypertension. Chronically Pb exposed hypertensive rats had increased plasma volume and total body sodium despite normal renal function. Plasma concentrations of catecholamines and PRA were normal. The results show a biphasic effect of Pb on blood pressure. An important role of renal sodium retention in chronic Pb‐induced experimental hypertension is suggested.
Effect of IgM‐enriched intravenous immunoglobulin (Pentaglobin) on endotoxaemia and anti‐endotoxin antibodies in bone marrow transplantation
Authors: JACKSON S. K. , PARTON J. , BARNES R. A. , POYNTON C. H. , FEGAN C.
Published: March 2008

Abstract. Endotoxin was measured in over 1000 plasma samples from bone marrow transplant patients in a randomized trial of the IgM‐enriched intravenous immunoglobulin (IVIG) Pentaglobin. Peak endotox aemia was significantly reduced (P = 0.02) in patients receiving Pentaglobin and 70% of all pyrexias of unknown origin were associated with endotoxaemia. Gut mucosal damage, assessed by lactulose/mannitol ratios, was significantly associated (P= 0.02) with endotoxaemia. Specific IgM antibody to endotoxin core‐glycolipid was significantly raised (P<0.01) in patients receiving the IVIG, and the IgM fraction of Pentaglobin was found to contain most of the antiendotoxin antibody activity of the IVIG. These results suggest a role for IgM‐enriched WIG as a prophylactic agent for the reduction of endotoxaemia and its consequences in bone marrow transplant patients.
Plasma aluminium in a reference population: the effects of antacid consumption and its influence on biochemical indices of bone formation
Authors: SHARP C. A. , PERKS J. , WORSFOLD M. , DAY J. P. , DAVIE M. W. J.
Published: March 2008

Abstract. Aluminium is involved in the etiology of several complications of chronic renal failure and has been firmly established as having toxic effects on bone tissue. We have measured plasma aluminium together with serum osteocalcin, procollagen I C‐terminal peptide and total alkaline phosphatase activity in healthy subjects and in a group of subjects who consumed aluminium‐containing and non‐aluminium containing antacid preparations, with normal renal function. Age‐related healthy reference ranges for plasma aluminium are presented and the effects of chronic antacid consumption on plasma aluminium and biochemical markers of bone formation investi gated.

In 172 healthy subjects the mean plasma aluminium concentration was 4.4 ± 2.9 μg L‐1, men having a significantly greater circulating aluminium load than women (5–4 ± 2.8 μg L‐1 vs. 4.0 ± 2.8 μg L‐1 respect ively (P = 0.0039)). Older men were found to have significantly higher plasma aluminium levels than younger men. Increased plasma aluminium was seen in subjects taking antacids although this was not asso ciated with significant changes in most indices of bone formation.
Lipoprotein(a) levels in relation to diabetic complications in patients with non‐insuIin‐dependent diabetes
Authors: HEESEN B. J. , WOLFFENBUTTEL B. H. R. , LEURS P. B. , SELS J. P. J. E. , MENHEERE P. P. C. A. , JÄCKLE‐BECKERS S. E. C. , KRUSEMAN A. C. NIEUWENHUIJZEN
Published: March 2008

Abstract. The relationship between serum levels of lipoprotein(a) (Lp(a)) and the presence of chronic diabetic complications was studied in 194 patients with non‐insulin‐dependent diabetes mellitus (NIDDM; 75 males, 119 females; age 66±11 years; duration of diabetes, 11 (range 1–35) years). They were taking various treatments (diet alone, oral hypoglycaemic agents and/or insulin). Metabolic status and prevalence of diabetic complications were assessed by detailed history, physical examination, laboratory analysis and ECG. Average metabolic control was moderate (HbAle, 8.2±1.7%). Median serum Lp(a) level was 183 U 1‐‐1 (range 8–2600 U I‐1), which was significantly higher than in control subjects of comparable age (median 101; range 8–1747 U I‐1; P<0.05), while HDL‐cholesterol levels were lower (1.14 ± 0.38 vs. 1.35 ± 0.35 mmol l‐1; P=0.001), and total cholesterol levels were comparable. No significant relation ships between diabetes treatment or metabolic control and Lp(a) levels were observed. In the quartile of patients with the highest Lp(a) levels. total cholesterol and triglycerides were slightly higher (P < 0.05), where as HDL‐cholesterol was not different. With increasing Lp(a) levels, higher prevalences of preproliferative retinopathy and of coronary artery disease (CAD) were observed, but not of the other complications. No relationship was found between the degree of albuminuria and Lp(a) levels. We conclude that in NIDDM patients, Lp(a) levels are elevated compared with non‐diabetic subjects, and that higher Lp(a) levels are associated with higher prevalences of CAD and of retinopathy.
Forearm muscle metabolism in primary hypothyroidism
Authors: HARRIS P. E. , WALKER M. , CLARK F. , HOME P. D. , ALBERT K. G. M. M.
Published: March 2008

Abstract.Thyrotoxicosis is associated with increased skeletal muscle glucose metabolism and lipid oxidation in the fasted state. Conversely, in hypothyroidism, glucose metabolism is reduced. The present study has assessed in patients the effects of chronic thyroid hormone deficiency, on insulin‐stimulated skeletal muscle metabolism, using a combination of the fore arm and hyperinsulinaemic euglycaemic clamp techniques. Seven female patients presenting with primary auto‐immune hypothyroidism were studied at presentation and 4–9 months after being rendered bio chemically euthyroid. No significant differences were demonstrated between the hypothroid and euthyroid states in forearm muscle blood flow, or in glucose or lipid metabolism.
Chemotaxis of polymorphonuclear neutrophils (PMN) in patients suffering from recurrent infection
Authors: BRENNEIS H. , SCHMIDT A. , BLAAS‐MAUTNER P. , WÖRNER I. , LUDWIG R. , HANSCH G. M.
Published: March 2008

Abstract. PMN function was tested in patients suffering from recurrent infections. In 65 out of 240 patients lack of oxygen radical production or reduced chemo‐tactic activity was found. In most cases the reduction was transient and associated with clinical impairments of the patients. Only a few patients had primary cellular defects. In one of those patients the expression of β2 integrins was reduced, while PMN of the other patients expressed β2 integrins normally. Thus, cellular defects other than the reduced expression of β2 integrins might also result in impaired chemotactic activity.
Influence of intravenous n‐3 lipid supplementation on fatty acid profiles and lipid mediator generation in a patient with severe ulcerative colitis
Authors: GRIMMINGER F. , FÜHRER D. , PAPAVASSILIS C. , SCHLOTZER E. , MAYER K. , HEUER K.‐U. , KISS L. , WALMRATH D. , PIBERHOFER S. , LÜBBECKE F. , KRÄMER H.‐J. , STEVENS J. , SCHÜTTERLE G. , SEEGER W.
Published: March 2008

Abstract. N‐3 fatty acids were supplied to a 36‐year‐old female patient suffering from ulcerative colitis and severe steroid side‐effects, in a sequence of parenteral and enteral administration. During a moderately active period of disease, 200 ml d‐1 fish oil‐derived lipid emulsion (eicosapentaenoic acid [EPA], 4–2 g; docosahexaenoic acid [DHA], 4.2 g) was infused for 9 days, in parallel with rapid tapering of the steroid dose. Disease activity declined rapidly, and the patient was subsequently provided with 16 fish oil capsules per day (EPA, 2.9 g; DHA, 1.9 g) for 2 months. At the end of this period of therapy, severe colitis recurred with intestinal and extraintestinal manifestations. The n‐3 lipid emulsion was then used for intravenous alimentation (29 days, maximum dose 300 ml per day); during this time, marked improvement of the inflammatory bowel disease was noted. During both periods of parenteral n‐3 lipid administration, total plasma EPA and DHA contents increased several‐fold, surpassing that of arachidonic acid; this plasma n‐3 fatty acid enrichment was only maintained to a minor extent during the intermediate period of dietary fish oil supplementation. The intravenously administered EPA‐containing triglycerides were rapidly hydrolyzed, as evidenced by the appearance of substantial quantities of EPA in the plasma free fatty acid fraction. Platelet and neutrophil total membrane content of EPA and DHA as well as n‐3 fatty acid/AA membrane ratios similarly increased during the periods of intravenous n‐3 lipid administration and declined during oral fish oil uptake. In contrast, erythrocyte membrane enrichment in EPA and DHA occurred only after the prolonged (2 month) period of dietary n‐3 lipid supplementation. Ex vivo stimulation of neutrophils with A23187 showed progressive increase in 5‐series leukotriene‐ and 5‐HEPE‐generation during both periods of n‐3 lipid infusion, in parallel with the rise of plasma EPA contents. Maximum 5‐series/4‐series leukotriene ratios surpassed 0.25. Similarly, ratios of thromboxane B3/B2 liberated from ex vivo stimulated platelets surpassed 0.4 during ongoing n‐3 lipid infusion. The profound changes in fatty acid profiles and lipid mediator generation may be related to the reduction in colitis activity observed during the periods of intravenous n‐3 lipid supplementation.
Abdominal and femoral adipose tissue lipolysis and cardiovascular disease risk factors in men
Authors: MAURIÈGE P. , DESPRÉS J.‐P. , MOORJANI S. , PRUD'HOMME D. , LAMARCHE B. , BOUCHARD C. , NADEAU A. , TREMBLAY A. , LUPIEN P. J.
Published: March 2008

Abstract. The relationships between subcutaneous abdominal and femoral fat cell lipolyses, plasma free‐fatty acid (FFA) levels and metabolic variables considered as risk factors for cardiovascular disease (CVD) (plasma glucose, insulin and lipoprotein levels) were investigated in 54 men, aged 36 ± 3 (SD) years, covering a wide range of body fatness values (body mass indices from 19 to 34 kg m‐2). Although there were no consistent relationships between femoral fat cell weight and the metabolic profile, positive and significant associations were found between abdominal fat cell weight and most of the metabolic indices. However, abdominal fat cell lipolysis measured with an α2:‐(clonidine) or a β‐agonist (isoproterenol) was unrelated to metabolic variables. In contrast, femoral fat cell lipolysis measured in the presence of clonidine was positively associated with fasting plasma insulin, cholesterol (CHOL) and apolipoprotein (apo) B levels, as well as with LDL‐CHOL and LDL‐apo B concentrations. No association was found between isoprotere‐nol‐stimulated lipolysis of femoral adipocytes and the metabolic profile. Comparison of two subgroups of men with either low or high femoral residual lipolysis with clonidine revealed that subjects with the lowest femoral α2‐adrenergic component (i.e. the highest residual lipolysis) displayed significant alterations in both plasma lipid‐lipoprotein and glucose‐insulin levels which could be predictive of an increased risk of CVD. Free fatty acid (FFA) levels measured in the fasting state and during an oral glucose tolerance test (OGTT) were positively associated with fasting plasma insulin and triglyceride levels as well as with both glucose and insulin areas measured during the OGTT. However, regional adipose tissue lipolysis measured in riiro was unrelated to plasma FFA levels. These results support the view that both femoral adipose tissue lipolysis and plasma FFA levels are significant correlates of plasma glucose‐insulin homeostasis and lipoprotein‐lipid levels, in men. However, as adipose tissue lipolysis and plasma FFA are unrelated to each other, they may be associated with risk variables through independent mechanisms.
Anaerobes and their fermentation products in faeces of patients with familial adenomatous polyposis before and after subtotal colectomy and ileorectal anastomosis
Authors: MEIJER‐SEVERS G. J. , CATS A. , VERSCHUEREN R. C. J. , SANTEN E. VAN. , KLEIBEUKER J. H.
Published: March 2008

Abstract. In view of the importance of short‐chain fatty acids (SCFA) for the colonic epithelial function and their possible relation with the reported spontaneous regression of rectal polyps after subtotal colectomy with ileorectal anastomosis, we compared the SCFA concentrations in faeces of five familial adenomatous polyposis (FAP) patients before, and in 10 FAP patients after operation to each other and to those of 10 healthy controls. Anaerobe cultural counts and concentrations of organic acids were also investigated in the same faecal samples from FAP patients and controls.

The preoperative cultural counts were not significantly different from those of the controls. After colectomy, the Bacteroides (P<0.002; P<0.02), and bifidobacteria counts (P<0.02; P<0.005) were decreased compared to controls and untreated FAP patients. The ratio of acetic acid to total SCFA significantly increased, which coincided with a proportional decrease of the other SCFA.

The frequently observed regression of rectal polyps after colectomy cannot be explained from these results. One would rather expect a possible stimulation of polyp growth and dedifferentiation of colonic epithelial cells.
T‐cell receptor gene rearrangements in lymphoid and non‐lymphoid leukaemias
Authors: CASARES S. , RODRIGUEZ J. M. , MARTIN A. , PARRADO A.
Published: March 2008

Abstract. Rearrangements of δ‐, Γ‐, and β‐ T‐cell receptor (TcR) chain genes were analysed in 64 haematologic malignancies comprising T‐ and B‐lineage acute lymphoblastic leukaemias (ALL), B‐chronic lymphocytic leukaemias (CLL), acute myeloid leukaemias (AML) and acute undifferentiated leukaemias (AUL). The TcR genes were rearranged in 5/6 T‐ALL. In non‐T‐leukaemias the frequency of TcR gene rearrangements was higher in B‐lineage ALL (8/11), although they were all detected in B‐CLL (5/29), AML (1/16) and AUL (2/4). Immunoglobulin (Ig) gene rearrangements were observed in 1/6 T‐ALL and 2/14 AML. The analysis of these gene configurations has a diagnostic application since it allows the definition of the clonality of malignant proliferation and although they are not lineage specific such configurations represent a further parameter to evaluate, together with the immunophenotype and morphology, in the assignment or exclusion of the differentiation lineage of the haematologic malignancies.
The association between rifamycin‐SV (R‐SV) related hyperbilirubinaemia and antipyrine clearance as a new test of liver function in cirrhosis
Authors: PERSICO M. , ROMANO M. , VILLANO N. , MONTELLA F. , GENTILE S.
Published: March 2008

Abstract. Several clearance tests have been used to assess the residual hepatic efficiency in liver cirrhosis. However, the altered clearance values found in cirrhotic patients may reflect not only the impairment in liver function but also a derangement in the hepatic blood‐flow. Therefore, this study was designed to explore the possibility that the competition between Rifamicyn‐SV and bilirubin at the hepatic uptake site might be used as an index for quantitative assessment of residual hepatic efficiency in 48 patients with chronic liver disease. In this test, the interference of hepatic blood flow would be negligible. Antipiryne clearance was also evaluated in the same subjects in order to explore the cytoplasmic microsomial efficiency. Rifamicyn‐SV intravenous load was followed by a sustained increase in bilirubinaemia which significantly related with the degree of liver function as assessed by the Chil‐Pugh criteria. Also, antipiryne clearance was significantly altered in cirrhotic patients compared to controls. Moreover, a positive correlation was found between the Rifamicyn‐SV test and Antipiryne clearance. We suggest that a combination of these tests might be of use in the quantitative assessment of liver function.
Increase in plasma 3,4‐dihydroxyphenylalanine (DOPA) appearance rate after inhibition of DOPA decarboxylase in humans
Authors: ELDRUP E. , HETLAND M. LUND , CHRISTENSEN N. JUEL
Published: March 2008

Abstract. Concentrations of DOPA in plasma are relatively high as compared to norepinephrine. The significance of plasma DOPA has not been elucidated. One would expect that substantial amounts of DOPA are derived from sympathetic nerves. There appears, however, neither to be a depot of DOPA in nerves nor is there a close correlation between plasma DOPA and sympathetic activity. The aim of the present study was to obtain further information about plasma DOPA by studying DOPA kinetics in healthy humans both with and without inhibition of DOPA decarboxylase by benserazide. Plasma DOPA and other catecholamines were measured by reverse‐phase HPLC with electrochemical detection and DOPA clearance and appearance rate were studied using infusion of 3H‐DOPA.

The plasma clearance of DOPA was 1·02 1 min‐1. Approximately 20% of this value could be explained by DOPA being decarboxylated in the kidneys and excreted as dopamine. The DOPA appearance rate was 1·13 μg min‐1 and the extremities accounted for approximately 1/5 of this value. After inhibition of DOPA decarboxylase by benserazide the DOPA appearance rate increased 7‐fold, whereas the DOPA clearance only decreased slightly and insignificantly. These findings are probably explained by two factors: (1) There is normally a large production of DOPA in some tissues from which DOPA spillover into plasma only occurs to a minor extent and tracer DOPA only mixes with this compartment to a small degree; (2) These compartments are permeable to benserazide, which blocks the decarboxylation of DOPA, which then leaves the tissues and spillover to plasma. Our results are compatible with the view that substantial amounts of DOPA are normally decarboxylated in sympathetic nerves, and spillover to plasma only if DOPA cannot be decarboxylated to dopamine. We conclude that plasma DOPA concentration neither reflects sympathetic nerve activity nor tyrosine hydroxylase activity. Provided plasma DOPA to a major extent is derived from sympathetic nerves it probably reflects the minimal fraction of DOPA synthesized but not decarboxylated to dopamine in nerves.
Platelet transmembrane signalling responses to collagen in familial hypercholesterolaemia
Authors: COOPER M. B. , TAN K. C. B. , BETTERIDGE D. J.
Published: March 2008

Abstract Washed platelets from patients with familial hypercholesterolaemia (FH) were found to be more reactive towards collagen than those from control subjects. The dose required to achieve half maximum aggregation was found to be 0·6 ml‐1 for FH patients whilst that for control subjects was 1·25 μg ml‐1. In both types of platelet, intracellular Ca2+ levels, as monitored by the Ca2+‐dependent photoprotein, aequorin, rose on stimulation with collagen and then fell to basal levels, probably due to resequestration by the reticular system. This effect was not due to exhaustion of the supply of aequorin since sustained Ca2+ influx induced by the ionophore, A23187, gave a stable signal that did not return to baseline. Similarly, inositol 1,4,5, trisphosphate levels increased in the cytosol after stimulation and then fell to unstimulated values. When stimulated with collagen, platelets from FH patients showed a greater extent of cytoplasmic calcium mobilization (P < 0·05) when compared to controls, coupled with a greater extent of inositol phospholipid hydrolysis (P < 0·05). At doses of collagen sufficient to give either 100% or 50% aggregation, platelets from patients or control subjects showed the same amplitude of ATP release at either dose suggesting that the trigger for vesicle release is more sensitive in FH.
Effects of bile salt and phospholipid hydrophobicity on lithogenicity of human gallbladder bile
Authors: ERPECUM K. J. VAN , PORTINCASA P. , STOLK M. F. J. , HEIJNING B. J. M. VAN DE , ZAAG E. S. VAN DER , BROEK A. M. W. C. VAN DEN , HENEGOUWEN G. P. VAN BERGE , RENOOIJ W.
Published: March 2008

Abstract Increased biliary bile salt and phospholipid hydrophobicity may promote nucleation of cholesterol crystals and gallstone formation. We therefore compared bile salt composition (determined by gas‐liquid chromatography) in patients with cholesterol (n= 35) and pigment (n= 16) gallstones (group A). Bile salt composition and cumulative bile salt hydrophobicity index were not different between both stone types. Hydrophobicity index or % of individual bile salts did not correlate with cholesterol saturation index or nucleation time. In an additional 21 cholesterol stone patients (group B) biliary bile salt and phospholipid hydrophobicity as determined by high‐pressure liquid chromatography did not correlate with cholesterol saturation index or nucleation time. In both group A and group B, cholesterol stone patients with cholesterol crystals in their fresh biles had a higher % deoxycholic acid, a lower % cholic acid and a higher bile salt hydrophobicity index than crystal‐negative patients. This study indicates the need for further research on the role of bile salt hydrophobicity in the pathogenesis of gallstones.
Effects of systemic complement activation on renal circulation of rats
Authors: SCHLOTTMANN K. , GULBINS E. , RAUTERBERG E. W. , STEINHAUSEN M.
Published: March 2008

Abstract In a variety of immunopathological diseases activation of the complement cascade occurs either systemically or localized in the kidney. To elucidate the functional impact of complement activation upon the renal microcirculation, we administered cobra venom factor of Naja naja kaouthia (CVF) i.v. into thiobarbital anaesthetized female rats. CVF is a potent activator of the alternative pathway of complement by forming the C3‐convertase CVF, Bb which cannot be downregulated by the natural inhibitor factors H and I and thereby leads to generation of the anaphylatoxins C3a and C5a and formation of the membrane attack complex (MAC). We utilized creatinine clearance and flowmeter measurements in the normal kidney and intravital microscopy of the split hydronephrotic rat kidney model to observe the microvascular changes. Bolus injection of CVF (100 U kg‐1) resulted in an immediate reduction of RBF (– 68% after 10 min), which remained decreased during the entire experiment (90 min). Systemic blood pressure was significantly reduced only in the early period (– 23% of control: 126 mmHg after 10 min). After an initial anuric phase of 30 min duration, the glomerular filtration rate was significantly diminished by 47%. White cell count was decreased by about 50% after the experiments. Application of the competitive thromboxane A2‐antagonist, BM 13505, reversed all renal and systemic CVF‐effects. Continuous infusion of the competitive leukotriene D4‐antagonist, ICI 198615, attenuated the late renal CVF‐effects (i.e. 30 min after injection of CVF). Depletion of polymorphonuclear cells (PMN) attenuated the CVF‐effects similar to BM 13505. Intravenous administration of CVF in the hydronephrotic kidney model resulted in a massive constriction of the interlobar and arcuate artery, with a fall in glomerular blood flow comparable to the reduction of RBF in the normal kidney. Diameters of the afferent arterioles—most sensitive to many vaso‐constricting agents—were not significantly altered. Our results suggest that injection of CVF and the liberation of high amounts of the anaphylatoxins, C3a and C5a, induces the release of TXA2, which contributes to the early renal effects and the formation of cysteinyl‐leukotrienes which play an important role in the late phase of systemic complement activation. Utilizing the split hydronephrotic kidney model we demonstrated the predominant action of complement activation on the large preglomerular vessels for the first time. PMN are seemingly involved in the liberation of secondary mediators which appear to reduce renal blood flow and glomerular filtration.
Circulating human megakaryocytes in cardiac diseases
Authors: VAN PAMPUS E. C. M. , HUIJGENS P. C. , ZEVENBERGEN A. , VERHEUGT F. W. A. , LANGENHUIJSEN M. M. A. C.
Published: March 2008

Abstract Both bone marrow and circulating megakaryocytes may produce platelets. Changes in number and properties of the circulating megakaryocytes in cardiac diseases may provide information about thrombopoiesis in these disease states. Circulating megakaryocytes were obtained by retrograde aspiration through wedged pulmonary artery catheters from patients without cardiac abnormalities, patients with cardiac diseases and patients with disorders known to affect the megakaryocyte‐platelet axis or marrowblood barrier. Their number, ploidy distribution and expression of the β1‐integrin adhesion antigens were estimated. We found evidence for an increased number of circulating megakaryocytes during acute myocardial infarction and in patients with triple vessel disease. A significantly higher proportion of circulating megakaryocytes obtained within 60 h after acute myocardial infarction, expressed CDw49b (α‐chain of VLA2), CDw49e (α‐chain of VLA5), and CDw49f (α‐chain of VLA6) compared to megakaryocytes of patients without cardiac diseases. In myocardial infarction the increase in number of circulating megakaryocytes together with the higher proportion that expressed the β1‐integrin adhesion antigens favour the hypothesis that these megakaryocytes are acutely released from the bone marrow. This could reflect either a selective response to an increased demand for circulating platelets or be the result of an aselective mechanism resulting from damage to the marrow‐blood barrier following the acute infarction or thrombolytic therapy administered.
Low levels of essential fatty acids are related to impaired delayed skin hypersensitivity in malnourished chronically ill elderly people
Authors: CEDERHOLM T. E. , BERG A. B. , JOHANSSON E. K. , HELLSTRÖM K. H. , PALMBLAD J. E. W.
Published: March 2008

Abstract Essential fatty acid (FA) deficiency, which may accompany protein‐energy malnutrition (PEM), has been associated with impaired inflammatory reactions. We evaluated this relationship by analysing FA profiles and delayed cutaneous hypersensitivity in 20 malnourished elderly non‐cancer patients and in 20 age‐matched control patients. As indicated by serum cholesterol and serum triglycerides, the lipid levels were decreased by about one‐third in the subjects with PEM. In comparison with the controls, there was a reduction in the ω3 FA (e.g. eicosapentanoate) in total serum lipids (mgl‐1) and serum phospholipids (%) of 40% and 47%, respectively. Reductions in serum ω6 FA (e.g. linoleate and arachidonate) levels corresponded to the drop in total FA concentrations (30%). The cutaneous hypersensitivity was impaired in 14 of the malnourished patients. The magnitude of the skin reaction was positively correlated (P < 0·05) to the concentrations of eicosapentanoate in serum lipids and serum phospholipids, as well as to the linoleate concentration in total serum lipids. Six of the malnourished patients took part in a nutritional intervention programme for 3 months. In parallel with an improvement in the nutritional status there was a 35% increase (P < 0·05) in the total ω3 FA serum concentration. Negative skin tests became positive and the median skin induration enlarged threefold (P < 0·05). Thus, deficiency of ω3 FA might be one factor contributing to cutaneous anergy in elderly malnourished patients.
Serum ionized calcium, intact PTH and novel markers of bone turnover in bedridden elderly patients
Authors: SORVA A. , VÄLIMÄKI M. , RISTELI J. , RISTELI L. , ELFVING S. , TAKKUNEN H. , TILVIS R.
Published: March 2008

Abstract. Chronic immobilization could markedly affect calcium and bone metabolism in elderly people. To investigate this, and to test the theory of ‘type II’ osteoporosis in bedridden elderly patients with low vitamin D status, 55 such subjects were examined. Serum concentrations of ionized calcium (Ca++), intact parathyrin (PTH) and two novel markers of bone collagen formation (carboxyterminal propeptide of type I procollagen; PICP) and resorption (carboxyterminal crosslinked telopeptide of type I collagen; ICTP) were measured. The effects on these parameters after 40 weeks of supplementation with vitamin D (1000 IU d‐1) and/or calcium (1g d‐1) were subsequently prospectively evaluated. Despite low (mean 11·6 nmol l‐1) serum 25‐hydroxyvitamin D levels (25‐OHD), those of 1,25‐dihydroxy‐vitamin D (1,25‐(OH)2D) were mostly normal. Neither correlated with Ca++ or PTH. PTH correlated negatively not only with Ca++ (r=–0·328, P < 0·05) but also with ICTP (r=–0·306, P < 0·05). Mean PICP was normal but ICTP was elevated and tended to correlate positively with Ca++ (r=–0·268, P= 0·06). Vitamin D supplementation did not change PICP or ICTP considerably, despite slightly increased 1,25‐(OH)2D and slightly decreased PTH. Ca++ values were normal and remained stable. In conclusion, Ca++ and PTH are poor indicators of vitamin D status in chronically immobilized elderly subjects. Furthermore, the results suggest that the increased bone resorption is not due to ‘type II’ secondary hyperparathyroidism; rather the resorption is primarily increased. Correction of vitamin D deficiency does not seem to benefit ageing bones unless adequate mechanical loading is provided.
Effect of degenerative spinal and aortic calcification on bone density measurements in post‐menopausal women: links between osteoporosis and cardiovascular disease?
Authors: BANKS L. M. , LEES B. , MACSWEENEY J. E. , STEVENSON J. C.
Published: March 2008

Abstract. The effect of spinal degenerative changes and aortic calcification on bone mineral density measurements was studied in 115 healthy early postmenopausal women. Lateral lumbar spine radiographs and quantitative computer tomography images were used to determine the presence and severity of aortic calcification and degenerative changes in the lumbar spine. Women with spinal degenerative calcification had higher spine bone density when measured by dual photon absorptiometry compared to those without calcification (P < 0·01), but this was not reflected by the quantitative computer tomography or the proximal femur bone densities, suggesting that spinal calcification artefactually increases spinal bone density when measured by dual photon techniques. Women with aortic calcification had significantly lower quantitative computer tomography and proximal femur bone density compared to those without calcification (both P < 0·05). These women may be at increased risk for both osteoporosis and cardiovascular disease, suggesting a common aetiological factor such as oestrogen deficiency.
Kinetics of 13CO2 elimination after ingestion of 13C bicarbonate: the effects of exercise and acid base balance
Authors: LEESE G. P. , NICOLL A. E. , VARNIER M. , THOMPSON J. , SCRIMGEOUR C. M. , RENNIE M. J.
Published: March 2008

Abstract. In order to investigate the effects of muscular work and preceding exercise on the retention of exogenous labelled bicarbonate, we studied the effects of oral administration of [13C]bicarbonate (0·1 mg kg‐1) in five subjects at rest before exercise and during and after 1 h of treadmill walking at 73% VO2max on three separate occasions. Elimination of CO2 from labelled bicarbonate was 62·6±8·1% at rest, 103·6±11·3% during exercise (P<0·01) and 43·0±4·7% during recovery from exercise (P= 0·01). During exercise mean residence time (MRT) was shorter than at rest (35±7 min vs. 54±9min, P < 0·02) and CO2 pool size was larger (998±160 ml CO2kg‐1, vs. 194±28ml CO2kg‐1, P < 0·001). Compared to values obtained at rest, during recovery from exercise, MRT and CO2 pool size were reduced (34±5min, P < 0·05; 116±19 ml CO2kg‐1, P < 0·02, respectively). In an additional five subjects acidosis and alkalosis were induced prior to administration of oral [13C]bicarbonate at rest. Elimination of bicarbonate was lower during acidosis (46·1±5·6%, P < 0·01) but was unaltered (50·9±5·6%, NS) during alkalosis, compared to the values obtained at resting pH. During acidosis MRT and CO2 pool size decreased (37±3min, P<0·01 and 123±10ml CO2kg‐1, P < 0·01, respectively) whereas in alkalosis MRT was unchanged (65±8 min NS) but CO2 pool size was increased (230±23ml CO2kg‐1, P < 0·05). The kinetics of elimination of 13CO2 from administered bicarbonate after exercise are different to those at rest and resemble acidosis. The appropriate correction factor for sequestered 13C should be used in metabolic studies of the post‐exercise state when using 13C tracers.
Influence of lung volume on collateral resistance during methacholine‐induced bronchospasm
Authors: COTÉ M.‐C. , SÉRIÈS F. , LAVIOLETTE M. , LABERGE F. , ATTON L. , CORMIER Y.
Published: March 2008

Abstract. We tested the hypothesis that lung inflation in response to a bronchospasm could be beneficial by maintaining the lung collateral channels open. Six mild asthmatics were studied on 2 separate days. The first day we determined the methacholine dose response and measured collateral resistance (Rcoll) before and during the metacholine‐induced bronchospasm and the effects of decreasing lung volumes on Rcoll. The lung volume changes were induced by applying progressively increasing positive extrathoracic pressures (PEP). The second day we measured the changes in end‐expiratory lung volume (EELV) resulting from the inhaled methacholine and from the applied positive extrathoracic pressure. With the inhalation of methacholine, the FEV1 decrease ranged from 26–43% of the baseline values while Rcoll increased significantly in only three of the six subjects. EELV remained unchanged in one subject and increased by 1408, 990, 260, and 44ml in four others. It was not measured in one subject. Decreasing EELV by PEP increased Rcoll in all subjects. By extrapolation of the lung volume‐Rcoll relationship, we calculated that Rcoll would have increased by 18227%, 6843%, 994%, 140%, and 128% if EELV had not increased in the five subjects in whom ΔEELV was measured. We conclude that an increase in EELV in response to an induced bronchospasm helps maintain open and functional collateral pathways despite the bronchoconstriction.
Brittleness of gallstones to lithotripsy: effect of physicochemical and ultrastructural characteristics
Authors: CHOUDHURI G. , AGARWAL D.K. , PHADKE R.V. , RAMESH V. , HAUSER W. , KUMAR J. , NEGI T.S. , KULSHRESHTHA A.
Published: March 2008

Abstract. Why some gallstones do not fragment easily to lithotripsy is unclear. The aim of the present study was to determine gallstone factors associated with resistance to fragmentation. Seventy‐six cholesterol rich gallstones were subjected to physical evaluation, in vitro computed tomography, chemical analysis by infra red spectroscopy, and ultrastructural studies (of 26 matched stones) by scanning electron microscopy and energy dispersive X‐ray microanalysis. In vitro lithotripsy was performed with the Siemens Lithostar Plus machine at a constant energy level. Of 76 stones, 33 required > 1000 shocks for effective fragmentation (largest diameter ≤ 5 mm); they had significantly higher maximum diameter (P<0·001), volume (P<0·001), weight (P<0·001) and lower stone density distribution (SDD) index (P<0·05) and lower calcium bilirubinate content (P<0·001) than those requiring ≤1000 shocks. Large (> 15 mm; P<0·05), round stones (P<0·02) and gallstones with SDD index of <50 HU (P<0·05) were more difficult to fragment. Clinical application of these parameters may help in better selection of patients for this non‐surgical mode of therapy for gallstones.