bluuebunny/crossref_metadata_2025 huggingface dataset:
Myofibrillar protease activity in muscle tissue from patients in catabolic conditions
Authors: LERNAU O. Z. , NISSAN S. , NEUFELD B. , MAYER M.
Published: March 2008

Abstract. Myofibrillar alkaline protease activity was shown to be present in human skeletal muscle. Endogenous myofibrillar proteins and 14C‐labelled, exogenous haemoglobin were both active as substrates, and the enzymic activity appeared to be similar to the myofibrillar protease previously described in rodent muscles. The activity of this enzyme was determined in patients undergoing surgery for a variety of diseases. Significant elevations in proteolytic activity were found in the abdominal wall muscle of patients in wasting conditions as compared with non‐catabolic diseases. In cachectic patients on total parenteral nutrition the protease activity was similar to reference values. The results imply that increased activity of the myofibrillar alkaline protease plays a role in the development of cachexia in human wasting diseases by prompting degradation of muscle proteins.
Plasma vitamin D metabolites in a patient with sporadic hypophosphataemic osteomalacia (adult‐onset type)
Authors: ULMANN ANDRE , BOUCHARD PHILIPPE , GARABEDIAN MICHELE , BOURDEAU AGNES , WITMER‐COURNOT GIULIA , LACOUR BERNARD , BALSAN SONIA , FUNCK‐BRENTANO JEAN‐LOUIS
Published: March 2008

Abstract. Sporadic hypophosphataemic osteomalacia (adult‐onset type) was demonstrated in a 40‐year‐old man on the basis of severe osteomalacia, hypophos‐phataemia, hyperphosphaturia and glycinuria. Plasma immunoreactive parathyroid hormone (iPTH) concentration was 9‐3 ng prot./ml (normal range: 4–8 ng prot./ml). Plasma 25‐hydroxy‐vitamin D and 24, 25‐dihydroxy‐vitamin D concentrations were 11 and 2–4 ng/ml respectively. Basal lα, 25‐dihydroxy‐vitamin D concentrations were slightly elevated (116 and 96 pg/ml) and increased to 240 pg/ml after 3 days on a low‐phosphorus diet. The patient was put on oral treatment with 25‐hydroxycholecalciferol (100 μ per day) and phosphorus (1500 mg per day). On the 4th month on treatment, a clinical improvement was apparent. Plasma 25(OH) D was 44 ng/ml, plasma l,25 (OH)2D was 256 pg/ml. However, plasma phosphorus remained low (0.77 mmol/l). On the 9th month of treatment a radiological improvement was evident despite a persistent hypophosphataemia (0.68 mmol/I). These facts suggest in our patient the existence of a vitamin D‐independent renal phosphorus leak.
Is there a renal phosphorus leak in recurrent renal stone formers with absorptive hypercalciuria?
Authors: TSCHOPE W. , RITZ E. , SCHMIDT‐GAYK H.
Published: March 2008

Abstract. In ten male hypophosphataemic hypercal‐ciuric recurrent renal stone formers with absorptive hypercalciuria and ten male normophosphataemic normocalciuric control persons, fasting plasma and urine chemistry was studied throughout the day under basal conditions and following an oral phosphorus load. After overnight fasting, plasma phosphorus and TMP/GFR were lower and urinary calcium higher in patients than in controls. Both in patients and controls, plasma phosphorus rose throughout the morning hours. In the afternoon, plasma phosphorus was almost equal in patients and controls. The circadian rise of plasma phosphorus despite no increase of urinary phosphorus argues against the presence of a fixed renal tubular phosphorus leak in absorptive hypercalciuria, at least in the fasting state.

Patients differed from controls not only with respect to urinary calcium, but also with respect to fasting absolute and fractional urinary excretion of sodium and chloride. Increased fractional urinary sodium was found both in normotensive and hypertensive patients. Since tubular reabsorption of phosphorus and the setting of fasting plasma phosphorus depend, among other factors, on tubular handling of sodium, the finding may be relevant for the genesis of transient fasting hypophosphataemia in absorptive hypercalciuria.
Structural and functional correlations in the atrophic mucosa of self‐emptying blind loops of rat jejunum
Authors: ROBINSON J. W. L. , MENGE H. , SCHROEDER P. , RIECKEN E. O. , MELLE G. VAN
Published: March 2008

Abstract. Marked atrophy of the mucosa develops in self‐emptying blind loops of rat jejunum. The application of microdissection techniques revealed a 74% reduction in the mucosal surface area of the blind loops, 3 weeks after their creation.

Kinetic studies of the influx of L‐phenylalanine and β‐methyI‐D‐glucoside into rings of blind loops showed that the Km for both mechanisms was unchanged, but that there was a small reduction in the Kmax, for both substrates, when expressed in terms of unit weight of incubated tissue; this attained 31% for phenylalanine and 12% for β‐methyl‐glucoside.

When the kinetic data were combined with the mor‐phometric results, it could be shown that the Vmax for both substrates, when expressed per unit area of mucosal surface, was more than twice as large in the blind loop epithelium as in normal tissue. Such findings indicate either that the individual cells of the blind loop epithelium possess more transport sites than normal. or that there is a greater proportion of absorptive cells within the blind loop mucosa.
Renin uptake by the right kidney in the rat following partial clamping of the left renal artery
Authors: MEIGNAN M. , MENARD J. , BONVALET J. P. , ROUFFIGNAC C. DE
Published: March 2008

Abstract. Renin secretion from both kidneys was studied in eleven Wistar rats for 40 min after partial clamping of the left renal artery. 14C Inulin and 3H para aminohippuric acid clearance and the arterial and venous plasma renin concentrations were measured in each kidney during control and experimental procedures.

After clamping, the arterial plasma renin concentration increased and correlated positively with the plasma renin concentration in both renal veins. However, the plasma renin concentration of the right renal vein was lower than the arterial concentration (P<0–01). The slope correlating the two variables is significantly lower than unity (P < 0–05, n ‐ 19). As the left kidney secreted a large amount of renin, calculation of secretion by the right kidney decreased to negative values, implying renin uptake by this kidney.

These data suggest the existence of a balance between the two kidneys. Renin secretion appears to maintain an equilibrium between release by the juxtaglomerular apparatus and removal from the blood into interstitial space. Release seems to predominate in the hypo perfused kidney, and removal in the contralateral kidney. This may result from the increase of the circulating angiotensin II, since we observed a direct correlation between renin uptake and the arterial plasma renin concentration.
Insulin and glucose uptake and insulin sensitivity in patients with peripheral arterial insufficiency
Authors: HAMMARSTEN JAN , HOLM GÖRAN , HOLM JAN , SCHERSTéN TORE
Published: March 2008

Abstract. There have been previous reports of evidence for increased insulin sensitivity in patients with intermittent claudication as the only symptom of arterial insufficiency. This study was designed to evaluate the role of peripheral tissue with respect to insulin sensitivity in such patients. Intravenous glucose tolerance tests (IVGTT) and intravenous insulin tolerance tests (IVITT) were performed in patients with peripheral arterial insufficiency and in controls. During IVGTT the plasma insulin values were significantly lower in patients with arterial insufficiency. During IVITT the venous concentration of glucose decreased more and the area over the glucose curve was significantly larger, suggesting a higher insulin sensitivity in this group. The low insulin values could not be referred to a larger distribution volume or an increased degradation rate, suggesting decreased pancreatic insulin release in this group. At the time of surgery for arterial insufficiency and for varicose veins in controls, the uptake of insulin and glucose and the release of lactate were measured over the leg before and after a glucose load. The uptake of insulin over the leg correlated positively with the arterial insulin concentration and the uptake of glucose in both groups. The insulin uptake had a tendency to be increased in legs with arterial insufficiency during the glucose challenge. The glucose uptake in the leg did not differ in the basal state, but was 3 times higher in the legs of patients with arterial insufficiency during glucose challenge. The increased glucose uptake in this group could be ascribed to a high insulin sensitivity in the leg, as defined by glucose uptake per unit of insulin taken up.
Effects of parathroid hormone and calcitonin on plasma and nephrogenous cclic adenosine‐3.,5 ‐monophosphate in normal subjects and in pathological conditions
Authors: CANIGGIA ANGELO , GENNARI CARLO , LORE FAUSTO , NUTI RANUCCIO , GALLI MARCO
Published: March 2008

Abstract. To evaluate the response of bone cells and kidne to parathroid hormone (PTH) and calcitonin (CT), the acute effects of these hormones given intravenousl on plasma cclic adenosine 3′,5′‐monophos‐phate (cAMP), nephrogenous cAMP and clearance ratio (cAMPxreatinine), have been studied in normal subjects and in patients with Paget's disease, hpoparathroidism and osteopetrosis.

Twent‐five subjects were given bovine snthetic PTH, thirt‐eight calcitonin (sixteen salmon, eighteen human and four porcine CT).

A different relative potenc of calcitonins in increasing plasma cAMP has been observed in normal subjects, according to previous results on the plasma calcium lowering effect. Paget's disease patients showed a greater increase in plasma cAMP following infusion than normal subjects.

The measurement of nephrogenous cAMP and the clearance ratio (cAMP: creatinine) demonstrated a minor involvement of the kidne in the production of cAMP after CT infusion; the late increase observed in nephrogenous cAMP was probabl due to a parathroid rebound following the hpocalcaemic effect of CT.
Hormonal and metabolic characteristics of geneticall obese Zucker and dietar obese Sprague‐Dawle rats
Authors: NOSADINI ROMANO , URSINI FULVIO , TESSARI PAOLO , GAROTTI MARIA CHIARA , BIASI FLORA DE , TIENGO ANTONIO
Published: March 2008

Abstract. The endocrine‐metabolic plasma pattern and the capacit of isolated perfused livers to produce triglcerides and ketone bodies have been studied in geneticall and diet‐acquired obese rats (Zucker and Sprague‐Dawle obese rats), and in control groups of the same strains.

An increased plasma insulin/glucagon molar ratio with hperinsulinaemia and hpoglucagonaemia was associated with hpertriglceridaemia, normal ketonaemia, elevated free fatt acids and normal or slight hperglcaemia in obese rats.

During oleate perfusion, the livers of Zucker and Sprague‐Dawle obese rats showed an increase in triglceride output and liver triglceride content. The ketone bod output as well as the mitochondrial carnitine palmitol transferase activit were normal or slightl decreased.

In our rat population, a positive correlation between the insulin/glucagon molar ratio and triglceride output has been found.
Lipoprotein snthesis and secretion b cultured human intestinal mucosa
Authors: RACHMILEWITZ D. , SHARON P. , EISENBERG S.
Published: March 2008

Abstract. We tested whether cultured human jejunal mucosa incorporates fatt acid into esterified lipids and whether organ culture can serve as a model ss'em to stud lipoprotein secretion b the human gut. Jejunal biopsies obtained from seven subjects were cultured for 24 h in medium containing 2 μCi of [3H]palmitic acid. More than 95% of the radioactivit incorporated b the tissue was found to be associated with esterified lipids: triglcerides, cholesterol esters and phospholipids, 7–8±1–2, 0–5±01 and 14‐0±1–5 nmol/10 mg weight respectivel. During the culture labelled triglcerides, phospholipids and cholesterol esters were secreted to the medium. Most of the newl snthesized esterified lipids in the medium were found in the d < 1 019 g/ml and d= 1019–1063 g/ml fractions. The majorit of the newl snthesized triglcerides were found in the d < 1 019 g/ml fraction. Labelled cholesterol esters were enriched in the d= 1 ‐063‐1‐21 g/ml fraction.

Boiled biopsies adsorbed negligible amounts of radioactive palmitic acid and did not snthesize esterified lipids. The addition of puromcin to the culture medium and preincubation with colchicine resulted in decreased uptake of the labelled fatt acid and decreased secretion of esterified lipids to the medium. These experiments indicate that cultured human intestinal mucosa is a suitable model to stud lipid snthesis and lipoprotein secretion b the human intestine.
Irradiation and gastro‐intestinal fibrinolsis: an experimental stud in the rat
Authors: STENBERG BJÖRN , RISBERG BO , PETERSON HANS‐INGE
Published: March 2008

Abstract Tissue fibrinolsis in the rat stomach and transverse colon was studied after X‐ra irradiation of the abdomen. Tissue biopsies were examined on un‐heated fibrin plates and with a histochemical technique modified from Todd.

A significantl increased fibrinoltic activit was found in the mucosa of the stomach and colon 3 das after irradiation, while fibrinolsis localized to submucosal vessels was unchanged.

Mucosal fibrinolsis in the stomach was significantl inhibited b intragastric administration of tranexamic acid.
Microanalsis and X‐ra fluorescence spectrometr of platelets in diseases with elevated muscle calcium
Authors: YAROM R. , BLATT J. , GORODETSK R. , ROBIN G. C.
Published: March 2008

Abstract. Electron microscopic X‐ra microanalsis and X‐ra fluorescence spectrometr were done on platelets from patients with Duchenne muscular dstroph and idiopathic scoliosis (both these conditions are known to be associated with increased intramo‐fibre calcium)

A significant increase in calcium and phosphorus concentrations was found in the dense granules and whole cells of both conditions.

The findings suggest that idiopathic scoliosis like Duchenne muscular dstroph is a multisstem disease with detectable changes in platelets.
Increased frequency of late pre‐β lipoproteins (LP β) in isolated serum very low density lipoproteins in uraemia
Authors: NORBECK HANS ERIK , CARLSON LARS A.
Published: March 2008

Abstract. Hypertriglyceridaemia, which is caused by raised levels of the triglyceride rich serum very low density lipoproteins (VLDL), is common in uraemia. Here we report qualitative studies on VLDL in this condition. VLDL were isolated from serum of 137 uraemic patients by ultracentrifugation, subjected to agarose electrophoresis and stained for lipids. An increased frequency of presence of electrophoretically slow migrating, discrete VLDL band, the so‐called late pre‐β lipoproteins, LPβ, was found, 76% in uraemia versus 30% in controls. Patients on haemodialysis had a higher frequency of LPβ than those not on dialysis, 94% versus 69%. Furthermore the cholesterol/trigly‐ceride ratio of VLDL was raised by about 30% in uraemia. Since the cholesterol enriched LPβ is believed to represent an end stage of the catabolism of VLDL these data suggest that there is a delayed clearance of VLDL remnants in uraemia. In haemodialysis patients heparin might have contributed to the higher frequency of LPβ.
Haemodynamic and metabolic effects of combined adrenergic α‐ and β‐receptor blockade with labetalol in the exercising human forearm
Authors: HARTLING O. J. , SVENDSEN T. L. , TRAP‐JENSNE J.
Published: March 2008

Abstract. At rest supine acute intravenous administration of the combined adrenergic α‐ and β‐receptor blocking compound labetalol (1 mg/kg body weight) to young, healthy, male subjects, produced a clear‐cut fall in arterial blood pressure. During dynamic forearm exercise, forearm blood flow decreased by 17‐2%, and calculated vascular resistance increased by 11‐3% after labetalol. Forearm oxygen uptake decreased (14‐6%), suggesting an increased mechanical efficiency. Lactate release from the exercising forearm decreased (17‐6%), probably because of the β‐receptor blockade. Forearm uptake of glucose and free fatty acids remained unchanged. Arterial blood glucose concentration attained a higher level after labetalol. Arterial plasma concentration of FFA was reduced during exercise and post‐exercise probably because β‐receptor mediated lipolysis was antagonized.
Release of platelet‐activating factor (PAF‐acether) from alveolar macrophages by the calcium ionophore A 23187 and phagocytosis
Authors: ARNOUX BERNARD , DUVAL DANIELE , BENVENISTE JACQUES
Published: March 2008

Abstract. Platelet‐activating factor (PAF‐acether) was recovered from rabbit, rat and human alveolar macrophages stimulated with the Ca++ ionophore A23187. PAF‐acether release was also obtained from rat and rabbit macrophages in the presence of zymosan, but not from human alveolar preparations in spite of the phagocytic activity exhibited by the latter cells. Observed releases were active, Ca++ dependent, and plateaued at 45 min. No PAF‐acether was released from lungs washed out of their macrophages, another argument against the mastocyte origin of this mediator. Given the potent bronchoconstrictive activity of PAF‐acether, its release from alveolar macrophages may provide an alternative explanation for non IgE‐dependent asthmas and the implication of platelets in pulmonary diseases.
Influence of renal denervation on urine concentration in awake and anaesthetized dogs
Authors: KURKUS J. , SADOWSKI J. , GELLERT R. , KRUŚ S. , ZWOLIŃSKA J.
Published: March 2008

Abstract. The role of renal nerves in urine concentration was studied in clearance experiments with unilaterally renal‐denervated dogs prepared by surgical bladder division. Urine concentration was assessed under conditions of: (1) stimulation of ADH release by dehydration or barbiturate anaesthesia; (2) mannitol diuresis, and (3) isotonic saline diuresis. Differences in TH‐.O/GF'R between the intact and denervated kidney were not significant in any of the experimental groups. However, in dehydrated conscious dogs Uosm of the intact kidney (939 ± 58 mmol/kg H2O) was significantly higher (P < 0.05) than that of the denervated organ (806 ± 51 mmol/kg H2O). In the intact kidney the medullary content of total solutes and sodium per kg wet tissue was 684 ± 26 mmol and 208 ± 12 mmol, respectively. This was significantly higher (P < 0.005) than corresponding values of 581 ± 23 mmol and 171 ± 14 mmol per kg wet tissue measured in the denervated organ. We suggest that a slight impairment of urine concentration (lower Uosm) in the denervated kidney of conscious dogs may depend on decreased medullary hypertonicity.
Subcellular localization and properties of adenosine triphosphatase in human polymorphonuclear leucocytes
Authors: SMITH G. P. , PETERS T. J.
Published: March 2008

Abstract. Magnesium‐dependent adenosine triphosphatase (Mg2+‐ATPase) activities were studied in human neutrophilic polymorphonuclear leucocytes. Kinetic studies on whole leucocyte homogenates produced curvilinear kinetics suggesting the presence of at least two forms of Mg2+‐ATPase.

Neutrophils were homogenized in isotonic sucrose and, after low‐speed centrifugation, the supernatant was subjected to analytical subcellular fractionation. Gradient fractions were assayed for Mg2+‐ATPase and for principal organelle marker enzymes. Mg2+‐ATPase was distributed between the plasma membrane, mitochondrial and cytosol fractions. Kinetic and inhibitor studies on Mg2+‐ATPase from each localization indicated the presence of three forms of the enzyme. The plasma membrane and mitochondrial activities had a Km value of 0.2 mmol/1 for ATP, whilst the Km for the cytosolic enzyme was 1 ‐8 mmol/I. Inhibitor studies showed further differences between the three enzymes.

Neutrophils were isolated from control subjects, patients with chronic granulocytic leukaemia and patients in the third trimester of pregnancy. The specific activities (mUnits/mg protein) of Mg2+‐ATPase, in contrast to those of alkaline phosphatase, were similar in all three patient groups. This result, together with the fractionation experiments and inhibitor studies, strongly suggest that the ATPase is not attributable to neutrophil alkaline phosphatase.
Human gastric mucosal adenylate cyclase activity: effects of various cytoprotective prostaglandins
Authors: SIMON BERND , KATHER HORST
Published: March 2008

Abstract. Several prostaglandins prevent ulcer formation (called cytoprotection) by a mechanism other than inhibition of gastric acid secretion. One suggestion is that they increase cyclic AMP in non‐parietal cells.

A variety of prostaglandins with potent cytoprotective properties were tested for their capacity to modulate adenylate cyclase activity in homogenates of human gastric mucosa. Prostaglandin E2, prostacyclin (PGI2) and 15(S)‐methyl‐PGE2 stimulated the cyclase in human gastric mucosal biopsy specimens in a dose‐dependent manner. Cytoprotective prostaglandins without antisecretory properties such as PGF2 β were also able to activate the enzyme system dose‐depen‐dently. In contrast, cytoprotective prostaglandins such as PGD2, the PGE1‐analogue, SC‐29333, and the pro‐staglandin‐like compound C83 did not stimulate human gastric adenylate cyclase. Whereas PGD2 did not modulate enzyme activity at all, SC‐29333 and C83, at concentrations greater than 10 µmol/l, inhibited basal and PGE2‐stimulated enzyme activities. These studies suggest that cyclic AMP is not directly related to the cytoprotective effect of prostaglandins, at least in human gastric mucosa.
Effects of hypothyroidism and cholesterol feeding on the clearance of chylomicron remnants in vivo and by rat hepatocyte monolayers
Authors: FLORÉN CLAES HENRIK , NILSSON ÅKE
Published: March 2008

Abstract. The hepatic catabolism of chylomicron remnants in normal rats and in hypothyroid rats which were either normocholesterolaemic or made hypercholesterolaemic by feeding cholesterol and cholic acid was studied in vivo and in hepatocyte monolayers.

In vivo, the clearance of injected chylomicron remnants labelled with either cholesteryl‐ or retinyl ester was delayed in the hypercholesterolaemic hypothyroid rats, but not in normocholesterolaemic hypothyroid rats.

Cholesteryl‐ester‐rich hepatocytes from hypercholesterolaemic hypothyroid rats took up remnants less efficiently than did normal hepatocytes. Hepatocytes from normocholesterolaemic hypothyroid rats had a lower cholesteryl ester content and took up remant particles to a greater degree than did normal hepatocytes. When normal hepatocytes were incubated with hypercholesterolaemic serum or with mevalonolactone, which increased cell cholesteryl ester content, there was a slight suppression of remnant uptake. Also, addition of triiodothyronine to hepatocyte monolayers suppressed rather than increased uptake of chylomicron remants in hepatocytes.

Thus, the study suggests that chylomicron remnant uptake by the liver is not inhibited by hypothyroidism per se but by the cholesterol accumulation in hepatocytes that is the consequence of cholesterol and bile acid feeding of the rats. Although the cholesteryl ester content in hepatocytes seems to determine remnant uptake, the regulation of uptake does not seem to be as effective as that of the LDL receptor in extrahepatic cells.
Influence of previous diuretic intake on the humoral and hormonal profile of idiopathic oedema
Authors: THIBONNIER M. J. , MARCHETTI J. P. , CORVOL P. L. , MENARD J. E. , SIRE O. G. , MILLIEZ P. L.
Published: March 2008

Abstract. Three groups of women underwent water loading tests: normal subjects, idiopathic oedema patients who had taken no medication for at least 3 months, and a second oedema group with recent diuretic intake.

Idiopathic oedema in drug‐free patients was characterized by an abnormal capillary permeability, lower basal protein values, a dramatic drop in urinary output in the upright position due to reduced glomerular filtration, enhanced reabsorption of sodium and water and stimulation of aldosterone and antidiuretic hormone (AVP) secretions. In these idiopathic oedema cases, osmolar AVP regulation was disrupted but AVP control by plasma volume was maintained.

In the basal state, patients with recent diuretic intake were characterized by a gain in body weight and by depletion of plasma volume and plasma potassium. In these subjects, urinary output in the upright posture was as insufficient as in drug‐free patients but was due to higher sodium reabsorption. Renal insensitivity to AVP action was also observed. Osmolar regulation and volume regulation of AVP were both disrupted in these cases with recent diuretic intake.
Dose‐dependent, and long‐lasting, effects of repeated intravenous injections of calcium on the canine secretin‐stimulated pancreatic juice secretion
Authors: NOEL‐JORAND M. C. , VERINE H. J. , SARLES H.
Published: March 2008

Abstract. The effects of repeated intravenous calcium administration on pancreatic juice secretion were investigated in four Thomas fistula dogs. During stimulation by 1.0 U kg‐1 h‐1 GIH secretin, three Ca doses were administered: 2, 4 and 8 μmol kg‐1 min‐1 during 1 h, saline being used in control tests; one dose only was tested per day. It was found that Ca administration induced both acute and long‐lasting effects. Acute effects were characterized by an increased response to secretin stimulation. Fluid, HCO3‐, protein and Ca outputs increased significantly in a dose‐dependent manner, the increase of protein output being the most dramatic. Long‐lasting effects, until now unrecognized, were characterized by a progressive increase of protein secretion during the first hour of secretin stimulation. This increase kept going during the 3 months of repeated calcium injections. Although protein plugs were observed in the juice, sometimes stopping the flow of juice, no pancreatic lesion was found. A second protocol showed that, after discontinuing calcium injections, the long‐lasting effects decreased progressively, but protein hypersecretion was still significant 3.5 months later. The importance of these findings regarding chronic pancreatitis due to hyperparathyroidism is discussed.
Serum lipoprotein lipid and apolipoprotein concentrations in grossly obese patients before and after jejuno‐ileal shunt operation
Authors: VESSBY B. , BOBERG M. , LINDAHL B. , LITHELL H. , THORÉN L. , WERNER I.
Published: March 2008

Abstract. Fourteen grossly obese patients were studied before and 2, 6, 12 and 24 months after jejuno‐ileal bypass. The major weight loss occurred during the first 6 months while there was no significant change of the mean body weight during the last 12 months of the study. During the initial period of pronounced weight loss there were significant reductions of all lipoprotein classes, e.g. at 2 months the very low density lipoprotein triglycerides had decreased by 41% (P < 0.01), the low density lipoprotein cholesterol by 42% (P < 0.001), the high density lipoprotein cholesterol by 27% (P < 0.001) and the serum apolipoprotein B, A‐I and A‐II concentrations by 30% (P < 0.001), 17% (P < 0.001) and 27% (P < 0.01) respectively. The fractional removal rate (K2) at the intravenous fat tolerance test had increased by 38% (P < 0.01), indicating an increased removal capacity of triglyceride‐rich lipoproteins. At 24 months the very low density lipoprotein triglycerides, the low density lipoprotein cholesterol and the apolipoprotein B concentration remained reduced by 28% (P < 0.05), 48% (P < 0.001) and 35% (P < 0.001) respectively. The intravenous fat tolerance test K2 remained significantly increased by 44% (P < 0.05). However, the high density lipoprotein cholesterol and the apolipoprotein A‐I and A‐II concentrations had successively increased again to pre‐operative levels. The low density lipoprotein cholesterol/high density lipoprotein cholesterol ratio was decreased by 44% (P < 0.001) and the apolipoprotein A‐I/apolipoprotein B ratio had increased by 74% (P < 0.001), both changes presumably beneficial in regard of atherogenicity. The apolipoprotein A‐I/high density lipoprotein cholesterol and apolipoprotein B/low density lipoprotein cholesterol ratios had increased by 23% (P < 0.001) and 28% (P < 0.001) respectively. The data indicate that the reduction of high density lipoprotein may be a transient phenomenon during the initial period of weight loss but that definite changes occur in the high density lipoprotein and low density lipoprotein composition which are apparent also 2 years after surgery.
Development of bone mineral loss in insulin‐treated diabetes: a 1 1/2 years follow‐up study in sixty patients
Authors: McNAIR P. , CHRISTIANSEN C. , CHRISTENSEN M. S. , MADSBAD S. , FABER O. K. , BINDER C. , TRANSBØL I.
Published: March 2008

Abstract. The change in bone mass during 1 1/2 years was determined in a longitudinal study of sixty adult insulin‐treated diabetic out‐patients. During the study period the mean bone mass decreased by 1.30 ± 0.28 (SEM) % (P < 0.001), to a mean value of 91.0 ± 1.7% of normal (P < 0.001). The rate of bone loss was significantly higher in patients with 1–6 years of diabetes (n= 29, bone loss: 1.96 ± 0.32%/1 1/2 years) than in patients with longer duration of the disease (n= 31, bone loss: 0.61 ± 0.44%/l 1/2 years, P < 0.02). The endogenous insulin secretion estimated with the glucagonstimulated serum C‐peptide concentration decreased during the observation period in 58.6% of the patients with 1–6 years of diabetes compared to 16.1% among patients with 7–11 years of diabetes (P < 0.002). The rate of bone mineral loss was almost 3 times higher in the twenty‐two patients in whom endogenous insulin secretion had deteriorated (2.12 ± 0.30%/l 1/2 years) than in the thirty‐eight patients without as well as with unchanged or increased insulin secretion (0.78 ± 0.39%/l 1/2 years, P < 0.01). In twenty patients with an increased insulin dose during the study period the mean bone mineral loss was 2.05 ± 0.36%/l 1/2 years compared to a mean bone mineral loss of 0.91 ± 0.38%/l 1/2 years in the forty patients with unchanged or decreased insulin dosage (P < 0.05).

This longitudinal study further supports the hypothesis that the bone mineral loss in insulin‐treated diabetic patients begins with the onset of clinical diabetes and that its development is associated with the deterioration of the beta‐cell function and with the increment in insulin dosage. The rate of bone mineral loss is high during the first few years of clinical diabetes, but levels off with increasing duration of the disease.
Role of the liver in the degradation of very low density lipoproteins: a study of lipolysis by heparin releasable liver lipase and uptake during isolated rat liver perfusion
Authors: BERRY E. M. , ALDINI R. , BARON H. , EISENBERG S.
Published: March 2008

Abstract. The role of the liver and of a heparin‐releas‐able liver lipase in the metabolism of very low density lipoprotein (VLDL) was investigated in vitro and during recycling rat liver perfusion. Rat plasma VLDL and nascent hepatic VLDL were labelled biosyntheti‐cally in their lipid moieties. Incubation in vitro of VLDL with the lipase caused hydrolysis of VLDL‐tri‐glycerides (>80%) and VLDL‐phosphatidylcholine (> 30%). Nascent VLDL was a better substrate for the enzyme. The hydrolytic activities were inhibited by 70–90% when rat plasma (10–30 vol%) was added to the incubation mixture.

VLDL‐triglycerides and cholesterol esters were taken up by the liver during 180 min recycling perfusion. The rate of disappearance of nascent VLDL was faster than that of plasma VLDL (half‐life times of 56.2 ±13.9 and 125.0±24.8 min respectively). Injection of heparin into the perfusion medium caused accelerated uptake of the hydrolysed VLDL‐triglycer‐ide by the liver. Addition of plasma (d> 1.006 g/ml) to the perfusion at a concentration of 10 vol% delayed the rate of disappearance of VLDL from the perfusate by about 50–75%.

These studies have established the capacity of the hepatic lipase to hydrolyse VLDL‐lipids and the ability of the liver to degrade nascent and plasma VLDL particles. These two activities, however, are depressed by plasma and therefore previous studies of VLDL metabolism may have to be re‐examined when based on incubations or perfusions in the absence of plasma.
Quantitative liver function and morphology after paracetamol administration to rats
Authors: POULSEN H. E. , PETERSEN P. , VILSTRUP H.
Published: March 2008

Abstract. The functional status of the liver after paracetamol administration to rats was dissociated with regard to cytosolic and microsomal functions. The cytosolic function, measured as galactose elimination capacity, was unchanged even after high doses of paracetamol. The microsomal function, measured as the prothrombin time, was reversibly decreased to a minimum 12 h after paracetamol administration and showed dose dependence. The structural changes of the liver cells were centrilobular necroses and dilatation of the endoplasmic reticulum. They were most marked 36 h after paracetamol and were not correlated to the functional impairment. We conclude that during acute paracetamol induced liver damage to rats different functions of the liver are unequally influenced and that the structural changes occur later than the functional ones. The paracetamol intoxicated rat is a promising model for further investigation of dissociation of subcellular functions during acute liver damage.
Responses to salmon calcitonin in chronic renal failure: relation to histological and biochemical indices of bone turnover
Authors: CUNDY T. , HEYNEN G. , GASPAR S. , EARNSHAW M. , BARTLETT M. , PATN S. , KANIS J. A.
Published: March 2008

Abstract. Twenty‐one patients with chronic renal failure and bone disease or hypercalcaemia were studied before and following single (twenty patients) or repeated (fourteen patients) intravenous injection of synthetic salmon calcitonin. Significant correlations were noted before treatment between bone surfaces occupied by osteoblasts or osteoclasts and plasma levels of immunoreactive parathyroid hormone, alkaline phosphatase and hydroxyproline. Following a single injection of 2–200 i.u. salmon calcitonin, plasma levels of calcium and phosphate fell for 6–8 h, but rose subsequently to pre‐injection levels at 24 h. The magnitude and duration of the hypocalcaemic response was not clearly dose dependent, but correlated with measured indices of bone cell activity. Repeated administration of calcitonin (10–200 i.u. thrice weekly for up to 2 months) lowered plasma calcium in the majority of patients and restored plasma calcium to normal in four previously hypercalcaemic patients. Mean levels of alkaline phosphatase increased but no significant changes in plasma phosphate, immunoreactive parathyroid hormone and calcitonin, or hydroxyproline occurred. Calcium absorption (six studies) did not change during treatment. We conclude that synthetic salmon calcitonin is an effective short‐term inhibitor of bone resorption in patients with chronic renal failure. Its use as a possible treatment for hypercalcaemia and hyperparathyroid bone disease in chronic renal failure is discussed.
Clofibrate treatment and bile cholesterol saturation: short‐term and long‐term effects and influence of combination with chenodeoxycholic acid
Authors: ANGELIN BO , EINARSSON KURT , LEIJD BARBRO
Published: March 2008

Abstract. In order to determine whether the clofibrate‐induced increase in bile cholesterol saturation is transitory, duodenal bile samples were analysed from sixteen hyperlipoproteinaemic patients before and after 6 months to 2 years treatment with clofibrate, 2 g daily. Standardized dietary and weight conditions were obtained. In all but two subjects cholesterol saturation remained elevated (150 ± 7%, mean ± SEM) compared to pretreatment values (112 ± 6%, P < 0.01).

In nine of the patients, duodenal bile was obtained also after 6 weeks of treatment. Although two patients with increased saturation at 6 weeks displayed a return to basal values at 2 years, the majority showed no consistent changes between these two occasions.

Addition of chenodeoxycholic acid to clofibrate medication led to a normalization of cholesterol saturation (from 145 ± 9 to 89 ± 18%, P < 0.01) in eight out of nine patients studied. The serum levels of total cholesterol and triglycerides, very low density lipopro‐tein and high density lipoprotein cholesterol were not significantly changed. However, the low density lipoprotein (LDL) cholesterol concentration was increased by 15–20% (from 4.8 ±0.3 to 5.7 ± 0.4 mmol/l, P <0.01).

It is concluded that clofibrate induces changes in biliary lipid composition which are consistent over at least 2 years of treatment. Possible measures to avoid these effects must therefore also be taken over a prolonged time. Chenodeoxycholic acid prevents the lithogenic effect of clofibrate but it cannot presently be recommended as an adjunct to clofibrate treatment since it simultaneously causes a rise in the serum concentration of LDL‐cholesterol.
Gastro‐entero‐pancreatic hormones in normal pregnancy: response to a protein rich meal
Authors: HORNNES PETER J. , KÜHL CLAUS , LAURITSEN KELD B.
Published: March 2008

Abstract. The plasma concentrations of gastrin, gastric inhibitory polypeptide (GIP), gut glucagon‐like‐immunoreactivity (gut GLI), insulin, glucagon, and pancreatic polypeptide (PP) were studied following the ingestion of a protein rich meal in late pregnancy and postpartum in 11 normal women. In pregnancy, the fasting plasma concentrations of glucose (mean ± SEM in pregnancy: 4.1 ± 0.1 mmol1‐1, postpartum: 4.7 ± 0.1 mmol1‐1, p<0.01), gut GLI (25± 3 v. 33± 2 pmol‐eqv 1‐1, P<0.01) and PP (7.9 ± 1.0 v. 13.0± 1.2 pmol 11, P<0.01) were decreased, gastrin and GIP unaltered, and insulin (90± 9 v. 72 ± 5 pmol 11, P<005) and glucagon (17±1 v. 13 ± 1 pmol 1‐1, P<0.01) increased.

The gastrin, GIP and glucagon responses to the meal were unaffected by pregnancy, whereas the responses of gut GLI (integrated responses in pregnancy: 1217 ± 325 pmol‐eqv 1‐1 postpartum 2223± 404 pmol‐eqv 1‐1, P<005) and PP (9801 &± 1440 v. 14,078 ± 1543 pmol 1‐1, P<001) were impaired and the insulin response enhanced (27,973 ± 6814 v. 11,409 ± 3102 pmol 1‐1, P<001) in pregnancy.

The physiological implications of these findings are at present not known in detail. They may, however, be important for the altered carbohydrate metabolism in pregnancy and also for the changes occurring during gestation in gastrointestinal physiology.
Tissue fibrinolysis in experimental gastric ulcer: a study in the rat
Authors: STENBERG BJÖRN , RISBERG BO , HEDMAN LARS , PETERSON HANS‐INGE
Published: March 2008

Abstract. Gastric mucosal lesions were induced in rats by pyloric ligature and intragastric instillation of hydrochloric acid. Within 4 h all rats developed focal mucosal lesions. Early regeneration was observed 72 h after release of the pyloric ligature and replacement of the hydrochloric acid by a phosphate buffer. A significantly increased gastric mucosal fibrinolytic activity was found 4 h after pylorus ligation. The submucosal vascular fibrinolysis remained unchanged. Following release of the pyloric ligature the increased mucosal fibrinolysis returned to normal values after 72 h. Intravenous administration of tranexamic acid significantly decreased the mucosal and vascular fibrinolytic activity without influencing the formation of induced gastric lesions. Increased mucosal fibrinolysis is probably not involved in the development of mucosal lesions.
The effect of captopril on catecholamines, renin activity, angiotensin II and aldosterone in plasma during physical exercise in hypertensive patients
Authors: MANHEM P. , BRAMNERT M. , HULTHÉN U. L. , HÖKFELT B.
Published: March 2008

Abstract. The studies were designed to explore the effect of the converting enzyme inhibitor captopril on the activity of the sympathetic nervous system during basal conditions and following graded physical exercise in patients with essential hypertension. Seven males and two females, aged 36–59 years, were hospitalized under metabolic ward conditions and treated for 7 days with captopril given orally in increasing dosages, the final dose being 600 mg daily. The patients were subjected to an individual, graded submaximal work test (bicycling) for 20 min before medication and then again in an identical manner during medication with 600 mg captopril. Blood samples were drawn before exercise and then after 10 and 20 min of work for the determination of plasma angiotensin II (PA II), plasma aldosterone (PAC), plasma renin activity (PRA), plasma noradrenaline (PNA) and plasma adrenaline (PA). Before medication blood pressure (mmHg) was 195/133 immediately before exercise, 230/129 after 10 min of moderate exercise and 263/105 following 20 min of nearly maximal work. During treatment with captopril the respective blood pressure values were 154/110, 200/100 and 245/98. Captopril had no significant effect on the changes in heart rate following physical exercise. PA II and PAC were substantially reduced and PRA considerably increased by captopril. PA II, PAC and PRA increased in response to exercise both before and following captopril. The exercise stimulated increase in PNA and PA was almost identical before and during captopril. Thus, captopril had no major effect on the activity of the sympathetic nervous system in patients with essential hypertension, neither during basic conditions nor during heavy physical exercise in spite of a profound decrease in PA II.
Responsiveness of the renin‐aldosterone system during exercise in young patients with essential hypertension
Authors: PEDERSEN E. B. , KORNERUP H. J. , LARSEN J. S.
Published: March 2008

Abstract. The effect of exercise of gradually increased intensity, i.e. 75 W for 20 min followed by 100 W for 20 min, on plasma renin concentration (PRC) and plasma aldosterone concentration (PAC) was studied in young patients with essential hypertension and normotensive control subjects. During exercise without previous sodium loading PRC and PAC increased to the same degree in both hypertensives and normotensives during light exercise; PRC increased further significantly in the normotensives (63 to 72 μIU/ml (medians), P < 001) but not in the hypertensives (46 to 51 μIU/ml) during heavy exercise. PRC and PAC were significantly correlated during both 75 W (p = 0–633, P<005) and 100 W (p = 0–635, P<005) exercise in the normotensives, but not in the hypertensives. During exercise after loading with 500 ml sodium chloride (0–85 mol/1) PRC and PAC increased in both hypertensives (28 to 42 μIU/ml, P< 0.01; 0.11 to 0.53 nmol/1, P < 001) and normotensives (22 to 33 μIU/ml, P<002; 012 to 0–34 nmol/1, P<00), although to a considerably lower degree than without previous loading. PRC and PAC were, however, significantly higher in the hypertensive than in the normotensive group after exercise. It is suggested that the responsiveness of the renin‐aldosterone system is abnormal during exercise in young patients with mild essential hypertension, both without and with previous intravenous sodium loading.
Hypotensive and renal effects of Captopril
Authors: PESSINA A. C. , GATTA A. , SEMPLICINI A. , ROSSI G. P. , CASIGLIA E. , MILANI L. , AMODIO P. , MERKEL C. , PAGNAN A. , PALÙ C. DAL
Published: March 2008

Abstract. The effects of Captopril on blood pressure and renal function were evaluated in ten patients with different degrees of hypertension. In seven, blood pressure was reduced after 7 weeks of therapy; in three it remained practically unchanged. No correlation was found between the standing plasma renin activity before treatment and the hypotensive response. Plasma renin activity increased significantly from the median value of 5.4 (range 1–16.7) to 9.5 (range 2.6–19.8)ngml1 h1 (P< 005) and urine aldosterone significantly fell from 13 (range 2–3–52–5) to 7.4 (range 1.6–14) μg 24 h‐1 (P<001) during therapy. Renal plasma flow decreased from 534 (range 300–616) to 471 (range 333–606) ml min‐1, but the difference was not significant, and glomerular filtration rate fell significantly form 122 (range 64–143) to 88 (range 71–116) ml min‐1 (P<0–05). No urinary excretion of alpha2‐macroglobulin was observed during Captopril. 24 h proteinuria, albumin and transferrin clearance, alanine‐amino transferase, gammaglutamyl transfer‐ase and alpha glucosidase excretion rate and malate‐dehydrogenase clearance remained unaltered throughout the treatment. This indicates that neither glomerular permeability nor renal tubular function were affected by the drug.
Pathogenesis of Gilbert's syndrome
Authors: FEVERY JOHAN
Published: March 2008

Chronic unconjugated hyperbilirubinaemia is a frequent finding. Overt haemolysis, dyserythropoiesis and other diseases including hepatobiliary, cardiac and thyroid disorders [1] have to be ruled out. The diagnosis of Gilbert's syndrome is then usually put forward if the history and clinical and laboratory investigations are normal. This benign disorder is found in approximately 2–5% of the population. It was said to be mainly present in young male adults, but we feel that it is as frequent in females as in males if one takes into account that the normal serum bilirubin levels in adult females are only two‐thirds of those found in males [2]. Our recent investigations in rats indicate that this might be due to inhibition of bilirubin conjugation by testosterone whereas progestogens combined with oestrogens produce a stimulation; if this holds for man, it could also explain why Gilbert's syndrome is usually not apparent before puberty.
Bile salt measurements in Gilbert's syndrome
Authors: DOUGLAS J. G. , BECKETT G. J. , NIMMO I. A. , FINLAYSON N. D. C. , PERCY‐ROBB I. W.
Published: March 2008

Abstract. Fasting and post‐prandial conjugated bile salt concentrations and intravenous glycocholate tests were normal in seven patients with Gilbert's syndrome. These findings indicate that the hepatic handling of conjugated bile salts in Gilbert's syndrome is normal.
Biochemical and histological changes in pulmonary fibrosis induced in rabbits with intratracheal bleomycin
Authors: LAURENT GEOFFREY J. , McANULTY ROBIN J. , CORRIN BRYAN , COCKERILL PETER
Published: March 2008

Abstract. Pulmonary fibrosis was induced in rabbits by an intratracheal instillation of bleomycin. Histologi‐cally, at 2 weeks there was inflammation but only limited evidence of increased collagen deposition; at 8 weeks the inflammatory response had subsided and increased collagen deposition, characteristic of early interstitial fibrosis, was observed. Biochemical analyses showed bleomycin treatment caused marked increases in the total amounts of RNA, DNA, mixed protein, collagen and elastin when compared to controls (P < 0.001 in all cases). Furthermore the increases were essentially complete by 2 weeks where the contents had increased by 110±13%, 60±%, 148±12%, 94±15% and 89±% respectively (P < 0.001 in all cases). When collagen and elastin were expressed as concentrations with respect to wet weight, total protein or DNA content, the changes were not statistically significant. No changes were observed in the relative amounts of type I and type III collagen.

It is concluded that: (1) compared to biochemical analysis, histology is relatively insensitive in detecting the early increases in connective tissue proteins; (2) measurements of lung collagen and elastin should be expressed as total lung contents wherever possible; the concentration of these proteins may remain unchanged, especially in the early stages of fibrosis, due to concomitant increases in other lung constituents; (3) changes in the relative amounts of types I and III collagens do not play a major role in the pathology of this form of pulmonary fibrosis.