Biomedical subjects

T Almdal

Publications and source records attributed to T Almdal.

14 recordsLinked to original sources

PubMed1992

Repetitive in vivo treatment with human recombinant interleukin-1 beta modifies beta-cell function in normal rats.

It is unknown whether interleukin-1 exerts a bimodal effect on Beta-cell function in vivo, and whether interleukin-1 has a diabetogenic action in normal animals. We therefore studied: (a) acute effects 2 h after an intraperitoneal bolus injection of 4 micrograms of recombinant human interleukin-1 beta per kg body weight on blood glucose, plasma levels of insulin, glucagon and corticosterone in Wistar Kyoto rats, either untreated or pre-treated with 4 micrograms/kg of interleukin-1 daily for 3 or 5 days; (b) the cumulative effects of repetitive intraperitoneal injections of 4 micrograms/kg interleukin-1 on blood glucose, glucose tolerance, plasma levels of insulin, glucagon and corticosterone, pancreatic insulin content and pancreatic ultrastructure; and (c) blood glucose and plasma concentrations of insulin, glucagon and corticosterone 10 h after the last of five intraperitoneal injections of interleukin-1, at which time point the inhibitory effect of short-term interleukin-1 exposure on insulin secretion reaches its nadir in vitro. A single injection of 4 micrograms/kg of interleukin-1 caused a slight, but significant lowering of blood glucose 2 h after interleukin-1 injection with no significant changes in plasma insulin and in spite of increases in plasma glucagon and corticosterone. A lowering of blood glucose 2 h after interleukin-1 administration was reproduced with 40, but not 0.4 micrograms/kg of interleukin-1, and was also seen in interleukin-1 pre-treated rats. Two hours after the fifth injection of interleukin-1, intraperitoneal glucose tolerance was impaired with elevated plasma insulin and corticosterone levels and increased pancreatic insulin content, indicating a state of insulin resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Effects of epinephrine on urea synthesis in vivo in rats.

Three hours after hysterectomy the rate of urea synthesis doubles in rats. At the same time the increase in catecholamines is at a maximum, suggesting that catecholamines might be of regulatory importance. The effect of exogenous epinephrine on the rate of urea synthesis was studied in rats receiving epinephrine at rates of 2 and 20 micrograms/kg/h. The low dose increased plasma concentration of catecholamines two-fold over control values (p less than 0.01), comparable with the increase seen after surgery, and the high dose of epinephrine increased the concentration five-fold. The high dose increased the rate of urea synthesis by 30% (p less than 0.05), whereas the low dose had no effect. Following a high dose of epinephrine, alanine decreased from 358 +/- 29 to 254 +/- 17 mmol/l (p less than 0.05), indicating that the increase in urea synthesis was due to an effect on the liver rather than on extra-hepatic tissues, in that more aminonitrogen was eliminated from plasma than released into it. In conclusion, epinephrine in physiological concentrations cannot by itself account for the increase of urea synthesis seen in vivo after surgery.

Amino Acids↗

PubMed1992

Stimulatory effect of epidermal growth factor on liver regeneration after partial hepatectomy in rats.

The effect of epidermal growth factor (EGF) on liver regeneration was investigated in rats subjected to partial hepatectomy. In a dose-response study EGF in doses of 6 and 24 nmol/kg x day increased liver regeneration after treatment for 48 h compared with controls, whereas a dose of 48 nmol/kg x day had no effect. In a subsequent study EGF, 6 nmol/kg x day, accelerated liver regeneration significantly after 36, 48, and 72 h of treatment. A possible influence of EGF on other hepatotrophic factors was investigated. No changes in the concentration of gastrin, insulin, or glucagon was found in portal venous blood. This study has shown that EGF in small doses can stimulate liver regeneration, whereas higher doses are ineffective. The study suggests that EGF should be regarded as a hepatotrophic factor.

Animals↗

PubMed1992

Hormonal and neural blockade prevents the postoperative increase in amino acid clearance and urea synthesis.

The combined effect of continuous blockade of glucagon and cortisol by somatostatin and etomidate and thoracic epidural analgesia on hepatic conversion of amino nitrogen was studied in eight patients who underwent elective cholecystectomy on day 1 after operation and was compared with 16 patients who underwent operation without blockade. Surgery increased the plasma clearance of total alpha-amino nitrogen from 5.2 +/- 0.3 to 6.6 +/- 0.3 ml/sec (mean +/- sem; p less than 0.05). This increase was due to increased elimination by the liver, because the hepatic effectiveness for amino nitrogen conversion measured by the functional hepatic nitrogen clearance increased from 9 +/- 2 to 16 +/- 4 ml/sec (p less than 0.05). In contrast, during the combined neural and hormonal blockade, surgery decreased the plasma clearance of amino nitrogen from 5.3 +/- 0.3 to 3.9 +/- 0.3 ml/sec (p less than 0.05), and the blockade prevented the postoperative increase in functional hepatic nitrogen clearance. The results suggest that glucagon, cortisol, and afferent neural reflexes are mediators of the hepatic contribution to catabolism after operation.

3-Hydroxybutyric Acid↗

PubMed1992

High volume plasma exchange in fulminant hepatic failure.

We investigated the effect of repeated high volume plasma exchange with fresh donor plasma in 11 patients with fulminant hepatic failure, all initially in stage 3 or 4 encephalopathy. A daily exchange of a volume equal to the extracellular volume (20% of body weight) on three consecutive days was intended. We obtained an average of 2.6 exchanges each with a mean volume equal to 16% of the body weight. Five patients (46%, 95% confidence limits 17%-77%) survived, all with acetaminophen induced liver failure. Four of the 6 non-survivors showed a temporary improvement in cerebral function. Two of the patients woke up completely. The 6 non-survivors maintained a stable condition with a systolic blood pressure > 110 mm Hg for a mean of 6.9 days after initiating plasma exchange. Plasma exchange may be considered in acute liver failure in patients with residual liver function before transplantation is finally decided. In addition, plasmapheresis may be used to keep patients with definite liver failure clinically stable until a transplant can be performed.

Acetaminophen↗

PubMed1991

Sex hormones in postmenopausal women with primary biliary cirrhosis.

To evaluate serum sex hormone profiles in nonalcoholic postmenopausal women with liver disease, 25 women with primary biliary cirrhosis (11 in cirrhotic stage) and 46 healthy controls were studied. The patients had significantly (p less than 0.05) elevated serum concentrations of estrone and androstenedione and significantly (p less than 0.05) lower concentrations of estrone sulfate, dehydroepiandrosterone sulfate and 5 alpha-dihydrotestosterone compared with the 46 controls. Serum concentrations of sex hormone binding globulin, testosterone, non-sex hormone binding globulin-bound testosterone and non-protein-bound testosterone did not differ significantly (p greater than 0.05) between primary biliary cirrhosis patients and controls. Patients in the cirrhotic stage had significantly (p less than 0.05) higher concentrations of sex hormone binding globulin than did controls. Patients in the cirrhotic stage had significantly (p less than 0.05) higher sex hormone binding globulin and estrone sulfate levels compared with noncirrhotic patients with primary biliary cirrhosis. Otherwise, no significant differences were observed between cirrhotic and noncirrhotic patients. The observed changes in steroid concentrations may be a consequence of hepatic dysfunction.

Aged↗

PubMed1990

Contradictory effects of uncomplicated versus complicated abdominal surgery on the hepatic capacity for urea synthesis in rats.

Female Wistar rats weighing 217 g were subjected to two types of surgical stress: uncomplicated (hysterectomy) and complicated (spleen and uterus ligated, crushed, and left in situ). Liver function as assessed by amino-N conversion was measured as the capacity for urea-N synthesis preoperatively (control animals) and on Days 1, 3, and 6 postoperatively. Uncomplicated surgery transiently increased the capacity for urea-N synthesis by 30% the first postoperative day (P less than 0.001). Complicated surgery decreased the capacity for urea-N synthesis to 55% throughout the investigation period (P less than 0.001). This was not due to a general change in liver mass since galactose elimination capacity remained constant. The increase in the capacity for urea-N synthesis after uncomplicated surgery is probably due to glucagon since plasma glucagon increased whereas plasma insulin and blood glucose remained unchanged after amino acid loading. The persistent decrease in the capacity for urea-N synthesis in complicated surgery is not due to changes in these regulators: glucagon increased, insulin decreased, and the rats were hypoglycemic. All changes are expected to increase the capacity for urea-N synthesis. The mechanism for the emergence of these two distinct metabolic patterns is not known. The phenomenon is probably important for interpretation of metabolic data on clinical stress.

Amino Acids↗

PubMed1990

Effect of gastrin on liver regeneration after partial hepatectomy in rats.

Gastrin has been shown to be an important trophic hormone for the mucosa of the stomach and the proximal intestine. In the present study the effect of gastrin on liver regeneration after partial hepatectomy in rats was investigated. After partial hepatectomy a significant rise in the concentration of gastrin in portal venous blood was found six, 12, and 18 hours after 70% hepatectomy. The effect of changes in the endogenous gastrin concentration on the liver regeneration was investigated in rats subjected to antrectomy or to fundectomy. Partial hepatectomy was done three weeks after the primary surgery. We found antrectomy to decrease liver regeneration, whereas fundectomy had no effect. Administration of pentagastrin 300 micrograms/kg sc three times daily for two and four days after partial hepatectomy significantly increased the rate of liver regeneration compared with controls. This study suggests that gastrin has a hepatotrophic effect. Whether this effect is caused by a direct action of gastrin on the hepatocytes or it is an indirect effect mediated by for instance insulin, glucagon or epidermal growth factor has to be further investigated.

Animals↗

PubMed1989

Vitamin D, parathyroid hormone, and bone mineral content of lumbar spine and femur in primary biliary cirrhosis.

In order to elucidate the pathogenesis and degree of osteopoenia in primary biliary cirrhosis (PBC) we conducted a cross-sectional study of 47 non-selected female patients with biopsy-proven PBC. Bone mineral content (BMC) of the lumbar spine, femoral neck and femoral shaft was determined using dual photon absorptiometry. Compared to healthy females of corresponding decades the PBC patients exhibited significantly decreased mean BMC-values in lumbar spine (88%, P less than 0.05) and femoral neck (92%, P less than 0.05) but not in femoral shaft (96%, NS). Bone mineral content was not significantly associated with duration of liver disease, impairment of liver function (serum concentrations of albumin, clotting factors II + VII + X, bilirubin, alkaline phosphatase galactose elimination capacity or histology), variables reflecting calcium homeostasis (serum concentrations of ionized calcium, parathyroid hormone, vitamin D binding protein, 25-hydroxy vitamin D3 and 1,25-dihydroxy vitamin D3) or previous treatment with glucocorticosteroids. In view of our negative findings we suggest that future studies in this field should focus on physical activity and female sex hormones as determinants for the prevention of osteopoenia in females with primary biliary cirrhosis.

Adult↗

PubMed1989

Decrease in ureagenesis by partial hepatectomy does not influence acid-base balance.

It has been suggested that urea synthesis participates directly in body pH homeostasis by removal of bicarbonate. To elucidate this hypothesis sodium bicarbonate or sodium chloride was infused (11.5 mumol/min) for 90 min into control rats and into rats that had undergone an 85% hepatectomy immediately before starting the infusion. Urea synthesis rate was 2.6 +/- 0.3 mumol/min (mean +/- SE) in controls, and was significantly (P less than 0.01) reduced to 1.0 +/- 0.2 mumol/min in partially hepatectomized rats. At the start of bicarbonate infusion, pH was 7.38 and 7.34 in control and partially hepatectomized rats, respectively, and at the end of infusion, pH was 7.56 and 7.51. Standard bicarbonate at start of bicarbonate infusion was 21.9 and 21.3 mM in controls and partially hepatectomized, respectively, and it increased to 32.7 and 29.9 mM at end of infusion. In saline-infused rats a slight decrease of approximately 0.05 pH units was observed during the experiment, but again no difference emerged between control and partially hepatectomized rats. It is concluded that a major role of the liver in the regulation of acid-base balance is unlikely.

Acid-Base Equilibrium↗

PubMed1989

Cerebral blood flow and liver function in patients with encephalopathy due to acute and chronic liver diseases.

The purpose of the present investigation was to study changes in cerebral blood flow (CBF) in hepatic encephalopathy, to ascertain whether this was related to the changes in liver function and whether these changes gave any prognostic information. CBF, determined by the intravenous xenon-133 method, and liver functions, assessed by the prothrombin index, bilirubin concentration, and the galactose elimination capacity, were studied in patients with acute fulminant liver failure and in patients with encephalopathy due to chronic liver diseases--that is, cirrhosis of various etiologies. The CBF range in healthy young subjects (age, 23-42 years) was 44-61 ml/100 g/min; in patients with grade I + II encephalopathy (mean +/- SEM) it was 32.8 +/- 3.6 ml/100 g/min in acute (n = 4; age, 28 +/- 8 years) and 37.0 +/- 3.3 ml/100 g/min in chronic liver patients (n = 10; age, 51 +/- 2 years). In grade III + IV encephalopathy it was 28.7 +/- 3.8 ml/100 g/min in acute (n = 8; age, 28 +/- 3 years) and 32.9 +/- 3.7 ml/100 g/min in chronic patients (n = 12; age, 49 +/- 3 years). CBF did not correlate with the liver function and was of no prognostic value. The liver function was markedly reduced in all the patients, without any differences between patients with acute or chronic liver diseases or the different degrees of hepatic encephalopathy. In conclusion, a marked reduction of the CBF was seen in hepatic encephalopathy, irrespective of the etiology of the disease.

Adult↗

PubMed1988

Dexamethasone increases the capacity of urea synthesis time dependently and reduces the body weight of rats.

Rats of 230 g were treated with 0.1 mg of dexamethasone twice daily for 2 days (n = 5) and 14 days (n = 9). Controls received isotonic saline. During the first week of dexamethasone treatment the rats lost weight rapidly (up to 9 g/day). The weight loss diminished during the second week of treatment. The fasting blood insulin concentration increased sevenfold in the dexamethasone-treated rats. Fasting blood glucagon and glucose concentrations were not different from controls. In the dexamethasone-treated rats the fasting alpha-amino-N concentrations were lower: 4.0 +/- 0.3 mmol/l (mean +/- SEM) versus 6.8 +/- 0.3 mmol/l in controls. The capacity of Urea-N Synthesis, determined during alanine loading was: after 2 days of treatment 14.7 +/- 1.7 mumol/(min 100 g), after 14 days of treatment 7.9 +/- 0.8 mumol/(min 100 g), and in controls 7.5 +/- 1.0 mumol/(min 100 g) (mean +/- SEM). In conclusion, glucocorticoid treatment leads to a transient change in the liver function as to hepatic amino-N conversion, implying that more amino-N than normal is eliminated as urea-N after 2 days of treatment. This may contribute to the early, but not the late body weight loss.

Animals↗

PubMedDate not supplied

Influence of epidermal growth factor on liver regeneration after partial hepatectomy in rats.

The role of epidermal growth factor on liver regeneration after partial hepatectomy in rats was investigated. After a 70% hepatectomy in rats, the concentration of epidermal growth factor in portal venous blood was unchanged compared with unoperated controls. However, small amounts of epidermal growth factor could be identified in portal venous blood after intestinal instillation of epidermal growth factor. Brunner's glands and the submandibular glands secrete epidermal growth factor. Extirpation of Brunner's glands decreased liver regeneration, whereas removal of the submandibular glands had no effect on liver regeneration. Epidermal growth factor antiserum reduced liver regeneration significantly. Oral or s.c. administration of epidermal growth factor had no effect on liver regeneration, whereas epidermal growth factor enhanced the effect of insulin and glucagon on liver regeneration. The results suggest that endogenous epidermal growth factor participates in stimulation of liver regeneration after partial hepatectomy in rats. Epidermal growth factor given together with insulin and glucagon had a synergistic effect on liver regeneration which suggests that liver regeneration in the rat is controlled by multiple regulatory peptides.

Animals↗

PubMedDate not supplied

Bacteremia in patients suffering from cirrhosis.

In a five-year retrospective study, there were 57 episodes of bacteremia among 1623 admissions (3.5%) of patients suffering from cirrhosis. Gram-positive bacteria were found in 70% of the episodes, gram-negative bacteria in 30%. All of the gram-positive bacteria found were fully sensitive to methicillin and to gentamicin. The gram-negative bacteria found were all sensitive to gentamicin, but only 50% were sensitive to ampicillin. The distribution between gram-positive and gram-negative bacteria was the same, irrespective of whether the patients acquired the infection inside or outside the hospital. More than 50% of the patients suffered from one or more of the following complications of cirrhosis: ascites, encephalopathy and haematemesis. Twenty-one patients died within seven days after the bacteremia was diagnosed. Bacteremia is a serious complication of advanced cirrhosis, and it is recommended that adequate antibiotic treatment is started when septicemia is suspected.

Adolescent↗