bluuebunny/crossref_metadata_2025 huggingface dataset:
Cysteinyl leukotriene actions on the microcirculation of the normal and split hydronephrotic rat kidney
Authors: GULBINS E. , PAREKH N. , RAUTERBERG E. W. , SCHLOTTMANN K. , STEINHAUSEN M.
Published: March 2008

Abstract. The effects of leukotriene D4 (LTD4) and leukotriene E4 (LTE4) on renal microcirculation were determined on normal and hydronephrotic female Wistar rats. In normal kidneys, the effects of LTD4 on total renal blood flow and glomerular filtration rate were measured by a flow meter and by inulin clearance. In the split hydronephrotic kidney, the LTD4‐ and LTE4‐mediated vascular effects were localized by intravital microscopy. Intravenous infusion of low‐dose LTD4 (1×10‐9mol min‐1kg‐1) over 15 min induced a strong decrease in renal blood flow (‐43% and ‐70%) in the normal and the hydronephrotic kidney. After the infusion the glomerular filtration rate of the normal kidney was significantly reduced by 65% and the filtration fraction by 32%. The fall in filtration fraction is in accordance with the significant decrease in luminal diameters of the arcuate artery (–28%) and the proximal interlobular artery (–12%) in the hydronephrotic kidney under LTD4. The decrease in renal blood flow, glomerular filtration rate, filtration fraction and luminal diameters persisted in the normal as well as in the hydronephrotic kidney for more than 60 min beyond cessation of infusion. Local application of LTD4(1×10‐10mol 1‐1upto 1×10‐7mol 1‐1)and LTE4 (1×10‐10mol 1‐1up to 1×10‐8mol 1‐1) induced a dose‐dependent constriction of the arcuate artery and the proximal interlobular artery. The distal interlobular artery, the afferent and the efferent arteriole were not significantly affected by LTD4 or LTE4. The glomerular blood flow was dose‐dependently reduced up to 48% under local LTD4 and 43% under LTE4. The LTD4/LTE4 antagonist FPL 55712 (1×10‐8mol min‐1kg‐1, iv) significantly attenuated the effects of LTD4 infusion and local LTE4 application in the hydronephrotic kidney. This is indicative of the presence of receptors for LTD4 and LTE4 in the larger preglomerular vessels of the rat kidney. The LTD4 effects on the normal kidney were attenuated by simultaneous infusion of dopamine (5 μg min‐1kg‐1) or plasma expansion, two principal methods in the treatment of acute renal failure. The results in the normal and hydronephrotic kidney demonstrate a preferential preglomerular vasoconstriction under LTD4 and LTE4 causing a marked decrease in renal and glomerular blood flow, glomerular filtration rate and filtration fraction.
Modulation of neutrophil and monocyte function by recombinant human granulocyte macrophage colony‐stimulating factor in patients with lymphoma
Authors: KHARAZMI A. , NIELSEN H. , HOVGAARD D. , BORREGAARD N. , NISSEN N. I.
Published: March 2008

Abstract. Granulocyte macrophage colony‐stimulating factor (GM‐CSF) has been shown to inhibit the chemotaxis and enhance the oxidative burst response of human neutrophils in vitro. The present study describes the effect of recombinant GM‐CSF on the neutrophil and monocyte function in patients with lymphoma undergoing GM‐CSF treatment. Patients with either Hodgkin's or non‐Hodgkin's lymphoma were treated with various dosages (2–16 μg kg‐1body weight per day for 5 days) of rhGM‐CSF by intravenous or subcutaneous route. Prior to and on day 5 of rhGM‐CSF treatment, neutrophil and monocyte chemotaxis and chemiluminescence responses to f‐Met‐Leu‐Phe, zymosan activated serum (ZAS) and opsonized zymosan (OZ) were determined. It was observed that chemotactic response of neutrophils to f‐Met‐Leu‐Phe and ZAS was reduced, whereas the chemiluminescence response of both cell types to f‐Met‐Leu‐Phe and zymosan was enhanced by up to 43‐fold. rhGM‐CSF treatment did not affect degranulation of the neutrophils as measured by release of vitamin B12binding protein. Degree of modulation of neutrophil and monocyte function by rhGM‐CSF was independent of rhGM‐CSF dosages administered. These data suggest that phagocytic defence system may be enhanced by GM‐CSF treatment and that this cytokine may be a useful therapeutic adjunct in compromised patients.
Plasma noradrenaline in cirrhosis: a study of kinetics and temporal relationship to ascites formation
Authors: MACGILCHRIST A. J. , HOWES L. G. , HAWKSBY C. , REID J. L.
Published: March 2008

Abstract. The kinetics of plasma noradrenaline (NA) were studied in 14 patients with cirrhosis and ascites and 13 normal subjects. [3H]noradrenaline ([3H] NA) was infused intravenously to steady state and the spillover of NA into plasma and its clearance from plasma calculated. The increase in plasma NA in the cirrhotic patients was due to an increase in NA spillover (14.5 vs 3.9 nmol min‐1m‐2; P < 0.001). NA plasma clearance was also increased in the cirrhotic patients (3.5 vs 2.11 min‐1m‐2; P < 0.01). Plasma NA and dihydroxyphenylglycol (DHPG), a metabolite of NA of which a portion is formed after re‐uptake of NA into sympathetic nerve endings, were then measured in 23 patients with cirrhosis and ascites, 17 patients with cirrhosis who had never had ascites, and 34 normal subjects. Both plasma NA and DHPG were significantly increased in the patients with ascites (NA 4.7, DHPG 14.7 nmol 1‐1) and in the patients with cirrhosis but no ascites (NA 3.8, DHPG 12.0 nmol l‐1) compared with normal subjects (NA 1.9, DHPG 8.8 nmol l‐1). Therefore, the increase in plasma NA in cirrhosis is due to increased activity of the sympathetic nervous system rather than interference with the metabolism of NA or impaired neuronal uptake of NA. This increase appears to precede the development of ascites.
Haemodynamic and renal effects of urodilatin bolus injections in patients with congestive heart failure
Authors: KENTSCH M. , LUDWIG D. , DRUMMER C. , GERZER R. , MÜLLER‐ESCH G.
Published: March 2008

Abstract. Urodilatin (ANF(95–126)) is an analogue of the atrial natriuretic factor (ANF(99–126)), which has been isolated from human urine. Recently we have shown in healthy volunteers, that intravenous bolus injections of synthetic urodilatin produce more pronounced reductions of pulmonary arterial pressure than ANF(99–126). To compare haemodynamic and renal effects of synthetic urodilatin with those of ANF(99–126) in congestive heart failure (CHF), 12 patients (66.3 ± 1.4 years) received either two high dose intravenous bolus injections of 4 μg kg‐1 bw Urodilatin (URO) at a 30 min interval (n= 6) or the same doses of ANF(99–126)(n = 6).

Prior to i.v. URO, no URO immunoreactivity was found in human plasma (specific RIA, no crossreactivity to ANF). Similar to ANF, the increase in diuresis (1.4 ± 0.7 to 3.7+1.6 ml min‐1) and natriuresis (169 ±114 to 430 ± 197 μmol min‐1) was moderate after URO in CHF. During the 90 min study period, mean plasma cyclic GMP levels increased much more after URO (by 53.4 ±15.1 nM) than after ANF (by 13.1 ± 30 nM; P= 0.04). In contrast to ANF, i.v. bolus injections of URO produced sustained haemodynamic effects in CHF lasting up to 90 min: The average (0–90 min) reduction of systemic vascular resistance was more pronounced after URO (‐ 578 ± 148) than after ANF (‐ 204 ± 65 dyn*s*cm‐5, P= 0.04). Average increase of stroke volume index (URO: 9.5 ±1.9; ANF: 2.8 ±1.4 ml min‐1 m‐2; P= 0.02) and reduction of pulmonary capillary wedge pressure (URO: — 10.8 ± 2.1; ANF: ‐ 3.9 ± 1.6 mmHg; P= 0.03)were more prominent after URO.

These data indicate that urodilatin bolus injections produce sustained beneficial haemodynamic effects in patients with congestive heart failure, which are prolonged and more pronounced than after ANF. The larger increase in plasma cyclic GMP levels in CHF suggests that in the cardiovascular system of heart failure patients, URO may induce a more potent stimulation of guanylate cyclase coupled ANF receptors than ANF(99–126).
Antibody mediated enhancement of HIV‐1 infection of an EBV transformed B cell line is CD4 dependent
Authors: NOTTET H. S. L. M. , JANSE I. , VOS N. M. DE , BARKER L. J. , VISSER M. R. , VERHOEF J.
Published: March 2008

Abstract. Low levels of anti‐viral antibodies may facilitate virus infection of Fc‐receptor bearing cells. For human immunodeficiency virus (HIV) it has been reported that antibodies can enhance infection of phagocytic cells. We show that HIV‐1 can infect an Epstein‐Barr virus transformed B cell line and that low levels of anti‐HIV antibodies enhance infection. The enhanced infection was characterized by an increase in viral DNA and increased HIV p24 protein production. Detection of cell surface antigen expression of CD4, the receptor for HIV, Fc‐receptor type II for IgG, but not of type I and III could be demonstrated by immunofluorescence cytometry. The enhancement was abrogated when infection was performed in presence of a monoclonal antibody directed against CD4. Based on these results we conclude that antibody mediated enhancement of HIV‐1 infection can also occur in non‐phagocytic cells in a CD4 dependent manner and that IgG Fc‐receptors other than types I or III are involved in this process.
The effects of dietary supplementation with n‐3 polyunsaturated fatty acids in patients with rheumatoid arthritis: a randomized, double blind trial
Authors: NIELSEN G. L. , FAARVANG K. L. , THOMSEN B. S. , TEGLBJÆRG K. L. , JENSEN L. T. , HANSEN T. M. , LERVANG H. H. , SCHMIDT E. B. , DYERBERG J. , ERNST E.
Published: March 2008

Abstract. Study objective: To determine the effect of dietary supplementation with n‐3 polyunsaturated fatty acids (n‐3 PUFA) on disease variables in patients with rheumatoid arthritis. Design: Multicenter, randomized, placebo controlled, double blind. Setting: Three Danish hospital Departments of Rheumatology. Patients: Fifty‐one patients with active rheumatoid arthritis. Intervention: Random allocation to 12 weeks of treatment with either six n‐3 PUFA capsules (3–6 g) or six capsules with fat composition as the average Danish diet. Main results: Significant improvement of morning stiffness and joint tenderness. No significant effect on the four other assessed clinical parameters. No serious side effects. Conclusions: Dietary supplementation with n‐3 PUFA in patients with rheumatoid arthritis improved two out of six patient reported disease parameters. Further studies are needed to clarify the more precise role of n‐3 PUFA in the treatment of rheumatoid arthritis.
Leukotriene B4 level in stimulated blood neutrophils and alveolar macrophages from healthy and asthmatic subjects. Effect of beta‐2 agonist therapy
Authors: PACHECO Y. , HOSNI R. , CHABANNES B. , GORMAND F. , MOLIERE P. , GROSCLAUDE M. , PIPERNO D. , LAGARDE M. , PERRIN‐FAYOLLE M.
Published: March 2008

Abstract. Leukotriene B4 levels were measured after stimulation by calcium ionophore A23187: (i) in peripheral neutrophils (PMN) from allergic asthmatics, rhinitis and healthy subjects; (ii) in macrophages collected by bronchoalveolar lavage. LTB4 levels in PMNs were significantly higher in non‐treated allergic asthmatics and non‐treated subjects with rhinitis compared to controls. Beta‐2 agonist‐treated asthmatics showed a significantly decreased LTB4 production which was not different from those of controls. In vitro, LTB4 production decreased significantly after PMN incubation with Salbutamol (10‐6 mo11‐1). LTB4 produced by AM collected by BAL was measured in non‐treated (n = 5) and treated (n= 11) asthmatics with inhaled beta‐2 agonist. AM collected from all controls and non‐treated asthmatics produced LTB4. By contrast, no production of LTB4 was observed in the treated group. LTB4 production decreased when normal AM were incubated in vitro with Salbutamol (10‐8 mol 1‐1). These results suggest that biochemical differences occur in PMN and macrophages from subjects treated with beta‐2 agonist, presumably in changing the 5‐lipoxygenase pathway.
Compositional analysis of the collagenous bone matrix. A study on adult normal and osteopenic bone tissue
Authors: BÄTGE B. , DIEBOLD J. , STEIN H. , BODO M. , MÜJLLER P. K.
Published: March 2008

Abstract. The collagenous constituents of mature bone of 30 individuals 22–93 years of age were studied by post‐mortem morphological and biochemical analysis. Morphometric evaluation of the second lumbar vertebral body revealed striking interindividual differences in bone mass, mean trabecular density and mean trabecular thickness. Collagen extracted from vertebral trabecular bone by limited pepsin digestion consisted mainly of collagen I (92%) and collagen V (8%). Immunohistochemistry revealed a distinct distribution of these two collagen types within the bone matrix. The degree of lysyl hydroxylation of the α2(I) collagen chain correlated inversely with the trabecular bone volume (TBV) and with the mean trabecular plate density. This correlation was statistically significant for the entire study group as well as for the female and male subgroups. Within the female subgroup, the lysyl hydroxylation/TBV ratio was higher in postme‐nopausal than in premenopausal women and was highest in women with established osteoporosis. No significant correlation was found between the level of lysyl hydroxylation and the age of the patients. The α 1(1) collagen chain showed a nearly constant degree of lysyl hydroxylation in all 30 samples. The results provide convincing evidence that morphometric changes associated with osteopenia in adult bone are accompanied by an altered level of lysyl hydroxylation of the α2(I)‐chain of collagen I. The biochemical alterations observed may be responsible for the deposition of a deficient bone matrix in osteopenic conditions.
Defect of epidermal 12(S)‐hydroxyeicosatetraenoic acid receptors in psoriasis
Authors: ARENBERGER P. , KEMÉNY L. , RUZICKA T.
Published: March 2008

Abstract. 12‐hydroxyeicosatetraenoic acid (12‐HETE) is assumed to play a central role in the pathophysiology of psoriasis. Since its effects in skin are mediated by specific high‐affinity receptors, we studied the receptor characteristics in cultured epidermal cells from involved and apparently healthy skin of psoriasis patients by radioligand binding assay. Involved and uninvolved psoriatic epidermal cells showed a fourfold decrease in the number of 12‐HETE binding sites as compared with normal healthy individuals and patients with atopic dermatitis, while receptor affinity remained unchanged. The decrease in receptor number was evident in psoriatic cells even in long‐term culture and was not due to receptor down‐regulation, defective response to interferon gamma or to protease degradation of receptor protein. The decrease in the number of 12‐HETE receptors detectable even in clinically normal psoriatic skin functionally leads to diminished 12‐HETE uptake and may thus represent a primary central molecular defect in the pathophysiology of the disease.
Erythrocyte Li+/Na+ and Na+/H+ exchange, cardiac anatomy and function in insulin‐dependent diabetics
Authors: SEMPLICINI A. , LUSIANI L. , MARZOLA M. , CEOLOTTO G. , MOZZATO M. G. , ZANETTE G. , DONADON V. , STEFANINI M. G. , ZANUTTINI D. , PESSINA A. C.
Published: March 2008

Abstract. It has been proposed that an increased activity of cell membrane Na+/H+ exchange, mirrored by increased erythrocyte Li +/Na+ exchange, may facilitate cell hypertrophy and hyperplasia.

Patients with insulin‐dependent diabetes mellitus may develop a specific cardiomyopathy with systolic and diastolic abnormalities and increased thickness of the left ventricle.

Therefore, we have investigated the relationships between erythrocyte Li+/Na+ and Na+/H+ exchange and echocardiographic parameters in 31 male insulin‐dependent diabetics (aged 17–68), in good metabolic control. Three had untreated mild hypertension. In all patients the urinary albumin excretion rate was less than 200 μg min‐1.

Ten patients had a Li+/Na+ countertransport higher than 0.37 mmol 1‐1 cell h‐1 the upper normal limit for our laboratory (0.49 ± 0.10, mean ± SD). In comparison with the patients with normal counter‐transport, they had increased interventricular septum thickness and relative wall thickness (h/r). End diastolic volume and cardiac index were reduced while blood pressure and urinary albumin excretion rate were similar.

In the whole study group, interventricular septum thickness was significantly correlated to Li+/Na+ exchange (r= 0.61, P< 0.001) and Na +/H+ exchange (r= 0.35, P<0.05), independently of the effect of age and blood pressure.

Posterior wall thickness was correlated to Li+/Na+ exchange (r= 0.38, P<0.05) and h/r to Li+/Na + exchange (r= 0.41, P < 0.05) and to Na +/H + exchange (r= 0.44, P<0.05). Li +/Na+ exchange was negatively correlated to cardiac index (r=—0.37, P<0.05). Urinary albumin excretion rate was negatively correlated to posterior wall thickness (r=— 0.40, P < 0.05) and h/ r (r=—0.44,P<0.05), and positively to cardiac index (r= 0.40, P<0.05) and it did not influence the correlations between erythrocyte Na+ transport and echocardiographic parameters.

An increased activity of the erythrocyte Li+/Na+ and Na+/H+ exchange may, therefore, indicate high risk of developing cardiac hypertrophy in male insulindependent diabetics. A widespread abnormality of cell Na+/H+ exchange is likely to contribute to the development of cardiac hypertrophy and diabetic cardiomyopathy in these patients.
Central obesity and hyperinsulinaemia in women are associated with polymorphism in the 5‘ flanking region of the human insulin gene
Authors: WEAVER J. U. , KOPELMAN P. G. , HITMAN G. A.
Published: March 2008

Abstract. presented to the European Association for the Study of Diabetes, September 1990 and the 6th International Congress on Obesity, October 1990

Abstract. Obesity is a multifactorial disease with a marked genetic component. The situation is further complicated by the heterogeneity of obesity demonstrated by the topographical distribution of body fat, e.g. upper body (central) and lower body (gluteal) obesity. Furthermore, the distribution of fat shows a stronger heritable tendency compared with total body fat. Central obesity is characterized by hyperinsulinaemia and insulin resistance, a feature in common with non‐insulin dependent diabetes mellitus, hypertension and atherosclerosis. In order to study the molecular genetics of central obesity we have examined 56 severely obese (mean body mass index 40), unrelated British Caucasoid young non‐diabetic women for associations of restriction fragment length polymorphism of candidate genes with anthropometric measurements and indices of insulin secretion and resistance. The candidate genes examined were insulin receptor, insulin sensitive glucose transporter and insulin.

An association of the class 3 allele of the hypervari‐able region in the 5′ flanking region of the insulin gene was found with upper segment obesity (P=0.005). Furthermore, the class 3 allele was also associated with fasting hyperinsulinaemia (P=0.01), stimulated insulin secretion (P= 0.01) and insulin resistance as calculated from the homeostatic model of assessment (HOMA; P= 0.008). No such associations were found with the other candidate genes studied.

This data suggests that polymorphisms in the 5′ flanking region of the insulin gene may affect expression of the gene and thereby modulate insulin production in severely obese female subjects.
Human recombinant C5a enhances lipopolysaccharide‐induced synthesis of interleukin‐6 by human monocytes
Authors: GROSS V. , ANDUS T.
Published: March 2008

Abstract. The effect of human recombinant C5a (hrC5a) on the synthesis of interleukin‐6 (IL‐6) was studied in human monocytes. Monocytes incubated in the absence of hrC5a and of bacterial lipopolysacchar‐ide (LPS) produced only low amounts (< 100 U/ 2×106 cell/16 h) of IL‐6 activity. LPS in concentrations from 10 pg ml‐1 to 10 ng ml‐1 greatly stimulated the synthesis of IL‐6 to about 50.000 U/106 cells/16 h. When hrC5a was added to the monocyte media maximal IL‐6 synthesis was reached at lower LPS concentrations, i.e. at 0.1 ng ml‐1 LPS in the presence of 100 ng ml‐1 hrC5a. Maximal IL‐6 production was not significantly enhanced by hrC5a. Metabolic labelling with [35S]‐methionine followed by immunoprecipi‐tation of IL‐6 showed that the increased IL‐6 activity in the medium of hrC5a treated monocytes was due to a stimulation of the de novo synthesis of IL‐6. Increased amounts of IL‐6 mRNA were found in monocytes treated with LPS and hrC5a compared with monocytes stimulated only with LPS. HrC5a prolonged the elevation of IL‐6 mRNA levels after stimulation of monocytes with LPS. HrC5a thus enhanced the LPS‐induced synthesis of IL‐6 by human monocytes.
Regional effects and clearance of endothelin‐1 across pulmonary and splanchnic circulation
Authors: WAGNER O. F. , VIERHAPPER H. , GASIC S. , NOWOTNY P. , WALDHÄUSL W.
Published: March 2008

Abstract. To determine the impact of i.v. endothelin‐1 on systemic, pulmonary and splanchnic circulation, as well as the peptide's regional clearance, hepatic venous and right heart catheterization was performed in healthy volunteers. During the peptide's continuous i.v. administration (0.4 pmol x kg‐1 x min‐1, 60 min) its plasma concentration rose from 21±0.5 to 9.5 ± 5.3 pmol/1 (pulmonary artery), from 2.1±0.9 to 5.0±1.6 pmol/1 (femoral artery), and from 1.5 ± 0.6 to 2.9±1.2 pmol/1 (hepatic vein). This was accompanied by an increase in mean systolic arterial pressure from 127±14 to 131 ± 12mmHg(P<0.05). Concomitantly, cardiac output and heart rate decreased from 7.0 ±1.1 to 5.8 ±1.01/min and from 63 ± 6 to 56 ± 5 beats/min, respectively, while total vascular resistance increased from 964 ± 273 to 1204 ±338 dyn x cm x s‐5 (P<0.01). No major changes in pulmonary circulation were observed, while splanchnic vascular resistance increased from 4472±1056 to 5361 ± 1420 dyn x cm x s‐5 (P<0.01) and estimated hepatic blood flow decreased from 1403 ± 218 to 1218 ± 219 ml min‐1 (P<0.01).

During endothelin‐1 infusion the pulmonary vascular bed accounted for approximately 53% of the peptide's overall disposal. Since the splanchnic area receives blood previously cleared during passage across the pulmonary vascular bed and the splanchnic plasma flow represented only 25 to 30% of the pulmonary plasma flow, the absolute amount of endothelin‐1 disposed in the splanchnic region represented only about 3%. However, the regional fractional extraction rates were comparable (mean splanchnic fractional extraction: 35.5 ± 2.1 %; mean pulmonary fractional extraction: 49.2 ± 14.9%), and thereby indicate a potentially similar efficacy of the pulmonary and splanchnic vascular bed to extract endothelin‐1.

In conclusion we showed pulmonary clearance to be a main cause of the short half‐life of endothelin‐1 in man. Furthermore, the hemodynamic changes induced by the slight increases in regional concentrations of endothelin‐1 provide evidence for a role of endothelin‐1 in the regulation of circulation under (patho‐) physiological conditions.
Eicosanoid levels in bronchoalveolar lavage fluid of young female smokers and non‐smokers
Authors: ZIJLSTRA F. J. , VINCENT J. E. , MOL W. M. , HOOGSTEDEN H. C. , HAL P. Th. W. VAN , JONGEJA R. C.
Published: March 2008

Abstract. To evaluate indicators of inflammatory changes in the airways of young smokers we have measured the levels of several eicosanoids in bronchoalveolar lavage (BAL) fluid of 18 female smokers (age 33 ±2 years) and 9 female non‐smokers (age 29 ± 2 years) who were hospitalized for treatment not related to any pulmonary disease. In each BAL specimen the following eicosanoids were determined by radioimmunoassay: prostaglandin (PG) E2; PGF2x; 9α, 1 lβ‐PGF2, a metabolite of PGD2; 6‐keto PGF1x, a metabolite of prostacyclin; thromboxane (Tx) B2, a metabolite of TxA2; the 5‐lipoxygenase products 5‐hydroxy‐eicosa‐tetraenoic acid (HETE), leukotriene (LT) B4 and LTC4; the 12‐lipoxygenase product 12‐HETE; and the 15‐lipoxygenase product 15‐HETE. The concentrations of the cyclooxygenase products (pg ml‐1) in the BAL fluid of the non‐smokers were: PGE2 15.4±1.9, PGF2x, 7.6±1.0, 9α,11β‐PGF2 8.7±1.8, TxB2 8.8 ± 1.3, and 6‐keto PGF1α only 1.5±0.8. The concentration of the lipoxygenase products were: 15‐HETE 781 ± 200,12‐HETE 193 ± 33,5‐HETE 14.0 ± 3.1, LTC49.5±3.1, LTB46.2± 1.4. BAL fluid from smokers contained two‐ to three‐fold higher levels of TxB2 and PGF2α (P < 0.05). The levels of TxB2 and PGF2α were positively correlated to the number of package years (rs= 0.55 and rs= 0.65, P<0.02). The concentrations of 5‐, 12‐ and 15‐HETE tended to be higher in BAL fluid from smokers, but this was not significant. We conclude that in BAL fluid from females who denied pulmonary symptoms, the concentration of 12‐ and 15‐lipoxygenase products is 15 — 100‐fold higher than that of 5‐lipoxygenase or cyclooxygenase products. In these subjects smoking is associated with higher concentrations of bronchoconstrictive cyclooxygenase products and a tendency towards higher levels of 5‐, 12‐ and 15‐HETE, probably reflecting inflammatory changes in the airways. Therefore, these results indicate that smoking induces formation of the metabolites that may play a role in the development of chronic airways obstruction especially when inflammatory changes become more pronounced after greater exposure to tobacco smoke.
Affinity of anti‐HBs antibody after hepatitis B vaccination
Authors: RADKOWSKI M. , LASKUS T. , GOCH A. , ŚLUSARCZYK J.
Published: March 2008

Abstract. A novel method based on mathematical analysis of the dose‐response curve obtained by radioimmunoassay was used to determine anti‐HBs affinity and concentration in 29 healthy subjects vaccinated with plasma‐derived hepatitis B vaccine. Anti‐HBs affinity as well as its serum concentration increased with time in most vaccine recipients; however, the pattern of affinity maturation varied widely between individual subjects. In 20 subjects the highest increase in antibody affinity was observed after the third dose of vaccine, whereas in nine cases values of affinity remained low and relatively constant throughout the time of the study.
Haemodynamic and renal effects of urodilatin in healthy volunteers
Authors: KENTSCH M. , LUDWIG D. , DRUMMER C. , GERZER R. , MÜLLER‐ESCH G.
Published: March 2008

Abstract. Urodilatin (ANF(95–126)), an analogue of the atrial natriuretic factor (ANF(99–126)), has recently been isolated from human urine. To study haemodynamic and renal effects of synthetic urodilatin, 18 healthy male volunteers (age 26.1±0.8 years; X ± SEM) received i.v. bolus injections of urodilatin at doses of 1, 2 or 4 μg kg‐1 body weight (bw) (n= 6 per dosage group). Urodilatin dose‐dependently increased heart rate and cardiac index. A dose‐dependent increase in plasma cyclic GMP levels was also observed. Urinary cyclic GMP excretion, urine flow and natriur‐esis increased 7‐fold, 5‐fold and 4‐fold, respectively. Renal effects were not different between dosage groups.

Compared with ANF(99–126), after urodilatin the reduction in mean pulmonary arterial pressure (PAP) was more pronounced (2 μg kg‐1, n= 6; ANF ‐1.8 ± 0.5, URO: ‐5.5±1.1 mmHg, P<0.05). Furthermore, after urodilatin the reduction of PAP lasted continuously from 2 up to 90 min after injection, while ANF(99–126) produced only a transient decrease of PAP. Similarily the reduction of pulmonary capillary wedge pressure (PCWP) by urodilatin from 9.3±1.2 to 3.8±0.9 mmHg (P<0.05) was also sustained up to 90 min post administration. These data in healthy volunteers suggest that, due to prolonged reduction of PAP and PCWP with increases of cardiac index and reduction of systemic vascular resistance, urodilatin might exhibit beneficial effects in cardiovascular disease.
The response of hepatic lipase and serum lipoproteins to acute hyperinsulinaemia in type 2 diabetes
Authors: BAYNES C. , HENDERSON A. D. , RICHMOND W. , JOHNSTON D. G. , ELKELES R. S.
Published: March 2008

Abstract. Hepatic lipase has a putative role in the catabolism of HDL particles and, while its activity is dependent upon insulin in the rat, no such insulin responsiveness has been demonstrated in man. We studied 21 patients with type 2 diabetes to examine whether hepatic lipase activity was influenced by hyperinsulinaemia during a 2–4 h isoglycaemic clamp study. Acute changes in lipids, lipoproteins and apoli‐poproteins were also documented in pre‐ and post‐clamp serum. Hepatic lipase activity during hyperinsulinaemia was compared with activity measured after an equivalent period without insulin. For comparison, nine non‐diabetic subjects (matched for age and body mass index) underwent similar clamp studies. In the control experiment without insulin, hepatic lipase activity did not change significantly (mean 9.7 {range 2.3–22.3} in the morning and 9.9 {3.0–22.5} mmol h‐1 l‐1 in the afternoon, NS). In contrast, after the hyperinsulinaemic clamp, hepatic lipase activity fell significantly in diabetic subjects from 12.8 {4.4–30.6} to 10.4 {3.3–31.3} mmol h‐1 l‐1, P<0.0002 along with serum triglycerides and total and LDL cholesterol. The change in hepatic lipase activity was positively related to the fasting apoprotein B concentration (Spearman r = 0.54, P= 0.016). In the normal subjects, a similar decline in hepatic lipase activity was observed during hyperinsulinaemia (from 15.1 {9.8–32.7} to 12.6 {6.3–28.3} mmol h‐1 l‐1, P<0.01) along with decreases in total, HDL and LDL cholesterol, triglycerides and apoproteins A1 and B. The change in hepatic lipase activity was positively related to fasting apoprotein B and total cholesterol concentration (both r= 0.72, P= 0.042) and both the fasting LDL cholesterol (r = 0.82, P=0.021) and the change in LDL cholesterol during the clamp study (r = 0.81, P= 0.022). Thus, acute physiological hyperinsulinaemia in normal and type 2 diabetic man causes a decrease in hepatic lipase activity. This may reflect a direct effect of insulin or, alternatively, it may be secondary to insulin‐mediated alterations in lipopro‐tein metabolism.
Classification of dynamical diseases by new mathematical tools: Application of multi‐dimensional phase space analyses to the pulsatile secretion of parathyroid hormone
Authors: HARMS H.‐M. , PRANK K. , BROSA U. , SCHLINKE E. , NEUBAUER O. , BRABANT G. , HESCH R. D.
Published: March 2008

Abstract. The biological importance of dynamic hormonal secretion has been demonstrated [1]. There is good evidence from recent studies that parathyroid hormone (PTH) which plays an important role in bone physiology is secreted in a pulsatile manner [2–5]. In this study we performed a classification of two ‘dynamical diseases’ namely osteoporosis and hyperpara‐thyroidism by the visualization of dynamic PTH‐secretion in multidimensional phase spaces [6].
Verapamil increases serum ionized calcium and serum phosphate in patients with post‐surgical hypoparathyroidism
Authors: SJÖDÉN G. , ROSENQVIST M. , NORDENSTRÖM J. , BJÖRKHEM I. , ERIKSSON S. A. V. , KRIEGHOLM E.
Published: March 2008

Abstract. The calcium homeostasis in eight patients with postoperative hypoparathyroidism was examined before and after 2 weeks of administration of verapamil in an oral dose of 80 mg three times daily. Serum ionized calcium increased during verapamil treatment (from mean ± SD of 110 ± 006 to 1.24 ± 0.38 mmol 1‐1; P <0.05), as well as total serum calcium corrected for protein (from 2.11±0.13 to 2.18 ± 0.13 mmol l‐1; P < 0.05). During treatment with verapamil there was an increase in serum phosphate (from 1.08 ±0.15 to 1.19±0.20 mmol l‐1P≤ 0.05) and in the urinary excretion of phosphate (P/creatinine ratio from 1.22±0.69 to 1.83 ± 0.97; P≤0.05). The serum 1,25‐dihydroxyvitamin‐Dj and serum parathyroid hormone were below the detection limits both before and after verapamil treatment. There were no significant changes either of the intestinal absorption of calcium or of the urinary calcium excretion. Serum osteocalcin was insignificantly reduced after treatment (1.60 ± 0.70 before treatment and 1.25 ± 0.71 μg l‐1 after treatment).

Thus in patients with post‐surgical hypoparathyroidism verapamil has effects on calcium and phosphorous homeostasis. Since calcium absorption was not influenced by verapamil, it is suggested that verapamil affects bone mineral metabolism.
Functional and structural determinants of glomerulosclerosis in the fawn‐hooded rat
Authors: WESTENEND P. J. , NOOYEN Y. A. , KROGT J. A. VAN DER , BRUMMELEN P. VAN , WEENING J. J.
Published: March 2008

Abstract. The effect of uninephrectomy (UN) at 4 months of age was studied on several parameters involved in the development of glomerulosclerosis (GS) in male spontaneously hypertensive Fawn‐Hooded rats. Protein excretion per animal was significantly more increased in UN rats at 2 months after operation compared to sham operated controls (202±104 vs. 88±37 mg 24 h‐1, P=0.005) and remained significantly higher throughout the rest of the observation period. At 11 months of age UN rats had a marked increase in the incidence of GS, 37± 16% compared to 5 ± 3% (P < 0.001) in controls. No differences were observed in mean arterial blood pressure.

Functional studies in separate groups of rats at 5 months of age showed an increase in single kidney glomerular filtration rate in UN rats (0.40±0.07 vs. 0.28±0.09 ml min‐1 100 g, P= 0.006). Single kidney renal plasma flow and filtration fraction were not altered. Mean glomerular volume was increased 1 month after UN (1.86 ± 0.25 vs. 1.39 ± 0.25 times 106μm3, P=0.003). Urinary noradrenaline excretion per animal (24‐h) showed a high sympathic nervous tone in both sham and UN rats. Total urinary dopamine and kallikrein excretion per animal were not influenced by UN.

These data indicate that after UN the development of GS in this rat strain is accelerated in association with compensatory hyperfiltration and glomerular volume expansion, which may play a role in the pathogenesis of GS.
Identification of the defective NADPH‐oxidase component in Chronic Granulomatous Disease: a study of 57 European families
Authors: CASIMIR C. , CHETTY M. , BOHLER M.‐C. , GARCIA R. , FISCHER A. , GRISCELLI C. , JOHNSON B. , SEGAL A. W.
Published: March 2008

Abstract. Chronic Granulomatous Disease (CGD) manifests as a predisposition to infection as a result of defective function of the NADPH oxidase of phago‐cytic cells. Proteins identified as part of this system include two subunits of a cytochrome b (cytochrome b‐245) and two cytosolic factors. The affected oxidase component was determined in 63 CGD patients from 57 families, by Western blotting of extracts of their neutrophils with antibodies to those proteins. 38 (67%) of the families were X‐linked with a defect of the β subunit of the cytochrome. 13 (23%) lacked p47‐phox, 3 (5%) p67‐phox, and 3 (5%) the α subunit of the cytochrome.
Sustained high plasma 5‐aminolaevulinic acid concentration in a volunteer: no porphyric symptoms
Authors: MUSTAJOKI P. , TIMONEN K. , GORCHEIN A. , SEPPÄLÄINEN A. M. , MATIKAINEN E. , TENHUNEN R.
Published: March 2008

Abstract. The pathogenesis of the acute porphyric attack is not known. One hypothesis is that porphyrin precursors, especially 5‐aminolaevulinic acid (ALA), are toxic for neuronal tissue. This was tested by infusing ALA in a male volunteer after a loading dose at a rate of 50–80 mg h‐1 for 92.5 h. During the experiment plasma ALA concentration was 9.11 μmol 1‐1 and porphobilinogen concentration 3–6 μmol 1‐1 which are the levels seen during acute attacks. Urinary excretion of these porphyrin precursors was also markedly increased. ALA infusion caused no subjective symptoms and no change in pulse rate, blood pressure, or autonomic nerve function or conduction velocity of peripheral nerves. Photosensitivity was not demonstrable. It is concluded that sustained high plasma ALA concentration does not cause porphyria‐like symptoms.
Importance of beta‐adrenoceptor function in fat cells for lipid mobilization
Authors: WAHRENBERG H. , LÖNNQVIST F. , HELLMÉR J. , ARNER P.
Published: March 2008

Abstract. The role of peripheral catecholamine sensitivity in lipid mobilization was investigated in 78 healthy non‐obese subjects by comparing beta‐adre‐nergic regulation of lipolysis in isolated adipocytes with circulating catecholamines and glycerol (lipolysis index). Small intra‐individual variations (5–7%) in adipocyte lipolytic beta‐adrenoceptor sensitivity (ED50) for isoprenaline were found. However, large inter‐individual variations (almost 105‐fold) in isoprenaline ED50 were observed in abdominal or gluteal adipocytes, which correlated (r = ‐0.52) negatively with the resting plasma noradrenaline levels. A correlation was also observed between circulating noradrenaline and adipocyte ED50 for noradrenaline (r= ‐0.38). In subjects with high (ED50 < 10‐1 mol 1‐1) as compared to low isoprenaline sensitivity (ED50 > 10‐10 mol 1‐1) physical exercise induced a two times greater increase in plasma glycerol (P < 0.01), in spite of a 50% less marked increase of plasma noradrenaline (P < 0.01). Findings with beta‐adrenoceptor mRNA and with total beta‐adrenoceptor number or affinity for agonist did not show any strong correlation with the resting plasma noradrenaline level (r<0.25). In conclusion, inter‐individual variations in beta‐adrenoceptor sensitivity and its relation to circulating noradrenaline can be ascribed to specific modulations of either BAR‐subtypes or in the postreceptor activation of lipolysis. These variations in adipocyte beta‐adrenoceptor sensitivity may participate in the regulation of peripheral nervous activity and play a putative role in lipolysis during exercise when subjects with high beta‐adrenoceptor sensitivity increased their ability to mobilize lipids despite a reduced noradrenaline response.
Attempts to accelerate glucagon absorption: effects of adding a vasodilator and of injection using a ‘sprinkler’ needle
Authors: SIMMONS K. L. , WILLIAMS G.
Published: March 2008

Abstract. Glucagon injected subcutaneously or intramuscularly may take up to 30 min to reverse hypogly‐caemia. We investigated whether glucagon absorption could be accelerated by two manoeuvres known to enhance insulin absorption: addition of a powerful local hyperaemic agent (10 nmole α‐calcitonin gene‐related peptide; CGRP), and injection using a multi‐hole ‘sprinkler’ needle. Glucagon (1 mg) given by conventional injection to six normal subjects produced peak plasma glucagon concentrations of 1–48 ± 0.23 (SEM) ng ml‐1 after 20 min and a peak glycaemic response of 7.8 ± 0.8 mmol 1‐1 at 25 min. Glucagon injected with CGRP or using the sprinkler needle did not produce any significant differences in plasma glucagon or glycaemia profiles, compared with conventional injection. Further studies demonstrated that glucagon is itself a powerful vasodilator, causing a 300–500% increase in local blood flow, comparable to that induced by CGRP. Because of its intense local hyperaemic action, the absorption of subcutaneously‐injected glucagon may be optimal and seems unlikely to be accelerated by pharmacological or other means.
Evidence that human kidney produces a protein similar to lithostathine, the pancreatic inhibitor of CaCO3 crystal growth
Authors: VERDIER J. M. , DUSSOL B. , CASANOVA P. , DAUDON M. , DUPUY P. , BERTHEZENE P. , BOISTELLE R. , BERLAND Y. , DAGORN J. C.
Published: March 2008

Abstract. Pancreatic juice is supersaturated in calcium carbonate. CaCO3 crystal growth is controlled by lithostathine, a secretory protein synthesized by pancreatic acinar cells, first described as a constituent of pancreatic stones. It was recently reported that, in the thin descending limb of the Henle's loop, urine was supersaturated in CaCO3 (Coe FL, Parks JH: Defenses of an unstable compromise: crystallization inhibitors and the kidney's role in mineral regulation. Kidney Int. 1990: 38, 625–631. This observation suggested the presence in kidney of a similar inhibitor. In this study, we show that a protein immunologically related to lithostathine is actually present in urine of healthy subjects and in renal stones. Immunocytochemistry of kidney sections localized the protein to cells of the proximal tubules and thick ascending limbs of the Henle's loops. Protein extracts of renal stones inhibited CaCO3crystal growth in vitro and this inhibition was significantly lifted by incubating the extracts with antibodies to lithostathine. The protein is not immunologically related to nephrocalcin. Because of its structural and functional similarities with pancreatic lithostathine, it was called renal lithostathine.
Effect of a somatostatin analogue, octreotide, on renal haemodynamics and albuminuria in acromegalic patients
Authors: DULLAART R. P. F. , MEIJER S. , MARBACH P. , SLUITER W. J.
Published: March 2008

Abstract. Although insulin‐like growth factor I increases renal function, the renal haemodynamic abnormality underlying the glomerular hyperfiltration in acromegaly is unknown. In normal subjects, amino acids and low doses of dopamine increase the glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), presumably by a predominant vasodila‐tion of the afferent and efferent glomerular arterioles, respectively.

We studied baseline GFR and ERPF (determined with 125I‐iothalamate and131I‐hippuran, respectively), the renal stimulatory effects of amino acid and dopamine infusion, and albuminuria before and after 3 months octreotide treatment in seven acromegalic patients with metabolically active disease. Octreotide reduced growth hormone concentrations from 14.7 ± 3.0 to 5.5 ±1.0 μg I‐1 (mean±SEM,n= 7; P< 0.001) and insulin‐like growth factor I levels from 412± 1.31 to 2.44±0.68 kU I‐1 (J><0.02). Glucagon concentrations did not change. Baseline GFR and ERPF declined from 132 ± 5 to 117 ±6 and from 547±32 to 478 ± 31 ml min‐1 1.73 m‐2, respectively (P<0.05 for both). Initially the response to amino acids was impaired (increment in GFR: 4.8±6.0%, NS; ERPF: ‐1.5 ±6.8%, NS), whereas the response to dopamine was normal (GFR: 10.6± 1.1%, P < 005: ERPF: 33.2 ± 3.1%, P<0.01). After octreotide, amino acid infusion increased GFR by 15.0 ± 6.8% (P < 0.02) and ERPF by 11.3 ± 5.6% (P < 0.02), while the dopamine response was unchanged. Initially, six patients were normo‐albuminuric and one had intermittent micro‐albuminuria. Octreotide reduced albuminuria by 22% overnight (median; P<005), and by 65% during the clearance studies (P<0.05).

In conclusion, afferent glomerular vasodilation appears to be an important characteristic of the glomerular hyperfiltration in acromegaly. Octreotide reverses this abnormality and reduces albuminuria.
Bone mass and biochemical parameters of bone metabolism in men with spinal osteoporosis
Authors: RESCH H. , PIETSCHMANN P. , WOLOSZCZUK W. , KREXNER E. , BERNECKER P. , WILLVONSEDER R.
Published: March 2008

Abstract. With advancing age both sexes have an increased incidence of osteoporotic fractures, although fractures are more common in women than in men. Whereas in women several potential risk factors have been identified, less is known about osteoporosis in men. A total of 27 Austrian men (mean age: 65 ± 2 years) with atraumatic spine fractures were studied. In all patients, medical history gave no evidence of disease or medications causing osteoporosis. Peripheral bone mass was determined by single‐photonabsorptiometry on the distal non‐dominant forearm; lumbal bone density was measured by quantitative computed tomography. Serum levels of calcium, phosphate, alkaline phosphatase, osteocalcin, testosterone, estrogen, parathyroid hormone and 25‐hy‐droxy‐vitamin D as well as 2‐h‐urinary‐OH proline and calcium excretion were measured. All data were compared with those of an age and sex matched control group consisting of 19 healthy males. A significant difference in mean peripheral and axial bone mass (SPA: P<0.004; QCT: (P<0.001) was observed between osteoporotic men and controls. When compared to controls, serum levels of alkaline phosphatase (P<0.012), urinary OH proline (P<0.05) and urinary calcium excretion (P<0.003) were significantly higher in the osteoporotic males. Additionally, there was a significant positive correlation between serum alkaline phosphatase and urinary OH proline excretion (r=0.32; P<0.04) in the osteo‐porotics. All other biochemical parameters showed no significant differences. Our results may lead to the assumption that osteopenia in men is related to increased bone turnover.
Nutritional behaviour and quality of life during oncological polychemotherapy: Results of a prospective study on the efficacy of oral nutrition therapy in patients with acute leukaemia
Authors: OLLENSCHLÄGER G. , THOMAS W. , KONKOL K. , DIEHL V. , ROTH E.
Published: March 2008

Abstract. A total of 29 patients with acute leukaemia were prospectively randomized before starting cytos‐tatic treatment to be nourished either with intensified oral nutrition (intervention group) or ad libitum nutritional intake during the whole tumour therapy (median 22 weeks). All menus of free choice (daily offer of 1.0–2.0 g protein, 30–50 kcal kg‐1 body weight (BW)). Beyond this, intervention patients nutrition education, daily visits by the dietician and record of food intake, as well as a weekly assessment of subjective well‐being (linear analogue self assessment ‘LASA’). From the LASA items, the factors: ‘malaise’, ‘psychological distress’, ‘therapy side‐effects’ were extracted by principal component analysis, and correlated to nutrient intake and nutritional status. At the end of antineoplastic induction therapy, after continuous hospitalization of 10 weeks (median), 31.3% of the controls had regained their initial nutritional status, and 68.8% of the intervention group. Mean daily energy intake was 23.2 kcal kg‐1 BW during weeks with weight loss (constant weight: 30.9, weight gain: 39.3 kcal kg‐1 BW). Nutritional. behaviour correlated with subjective well‐being, low intake with complaints of tumour treatment side effects and weight loss with malaise.
Insulin sensitivity and secretion in healthy elderly human subjects with ‘abnormal’ glucose tolerance
Authors: BROUGHTON D. L. , WEBSTER J. , TAYLOR R.
Published: March 2008

Abstract. Glucose tolerance deteriorates dramatically with advancing age. It is not known whether the underlying pathophysiology is different in older subjects. We employed a two step hyperinsulinaemic euglycaemic glucose clamp with [614C] glucose infusion to compare peripheral and hepatic insulin sensitivity in eight elderly (EAGT) with eight young (YAGT) subjects with abnormal (matched) glucose tolerance and nine elderly subjects with normal glucose tolerance (ENGT). There was no difference in basal HGO (EAGT 14.5 ±0.9, YAGT 15.3 ±1.1 μmol kg‐1 min‐1). Glucose turnover was similar in both groups at step 1 (EAGT 13.2 ± 0.8, YAGT 13.4±0.8 μmol kg‐1‐min‐1) and step 2 (EAGT 25.1±3.1, YAGT 27.2 ± 2.7 μmol kg‐1 min‐1). HGO was lower in the EAGT subjects at step 1 (2.3 ±0.4 vs. 4.3±0.6 μmol kg‐1 min‐1P=0.01). Incremental serum insulin response to oral glucose was comparable (EAGT 66.8 ±11.6 YAGT 57.8±12.2 mU 1‐1, h). Compared to the ENGT group the EAGT group was insulin resistant with a lower MCR of glucose at step 1 (2.03 ±0.28 vs. 3.23±0.44 ml kg‐1 minv‐1P=0.04) and at step 2 (6.18±0.83 vs. 9.64±0.38 ml kg‐1 min‐1P=0.004) and had a lower early insulin response (AUC 0–30 min 5.9±1.1 vs. 9.8±± 1.4 mU 1‐1. hP=0.04). We conclude that elderly and young subjects with abnormal glucose tolerance have similar pathophysiology but in such older subjects insulin suppression of HGO is similar to that seen in normal older subjects. Compared to normal elderly subjects the EAGT subjects are insulin resistant and have reduced early insulin secretion and both of these factors are importnat determinants of the glycaemic change.