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Biomedical subjects

G Ahlborg

Publications and source records attributed to G Ahlborg.

At least 37 records · Page 2Linked to original sources
PubMed1996

Importance of a novel oxidative mechanism for elimination of intracellular cholesterol in humans.

We have recently demonstrated that cultured human alveolar macrophages efficiently convert cholesterol into excretable 27-oxygenated products. We show here that increasing the intracellular concentration of cholesterol by a factor of 10 leads to about a twofold increase in the excretion of 27-oxygenated products from cultured macrophages. Inhibition of the sterol 27-hydroxylase caused a significant intracellular accumulation of cholesterol. A direct comparison was made between flux of cholesterol and 27-oxygenated products from macrophages preloaded with [4-14C]cholesterol. Under the specific conditions employed with fetal calf serum in the culture medium, the flux of 27-oxygenated products was about 10% of that of cholesterol. Since the sterol 27-hydroxylase, which converts cholesterol to 27-oxygenated products, is present in many cell types, we suggest that 27-oxygenation is a general mechanism for removal of intracellular cholesterol. To evaluate this hypothesis, we measured the net uptake by the human liver of circulating 27-oxygenated products, which was found to be about 20 mg/24 h. This uptake corresponds to approximately 4% of the bile acid production, assuming quantitative conversion into bile acids. It is concluded that the 27-hydroxylase pathway is of significance for elimination of extrahepatic cholesterol.

Cells, Cultured↗
PubMed1996

Assessment of Reproductive Risk at Work.

The risk-assessment process involves hazard identification, dose&endash;response assessment, exposure assessment, and characterization of risk. Special competence and careful consideration are needed to assess effects on human reproduction. There is often a lack of scientific information concerning, e.g., toxic influences of chemical substances on human fertility, pregnancy, and offspring. Legislation and guidelines concerning workplace exposures need further development in many countries. It is important that occupational health and safety personnel, as well as experts in this field, assist employers and employees in the development of good workplace policies for the protection of the reproductive functioning of male and female workers. A protocol for effective risk assessment is described.

Journal Article↗
PubMed1996

Communication Concerning the Risks of Occupational Exposures in Pregnancy.

The health professional who is involved in communicating information about reproductive risks from occupational hazards needs to consider several important aspects. Uncertainties in risk assessment, timing of exposure in relation to pregnancy, and the consequences of different preventive measures for the woman (family), as well as for the employer and other persons at the workplace are examples of such aspects. The basis for the pregnant woman's perception of risk must be recognized. The risk-communication goal is that the persons concerned fully understand the risk and its possible consequences, so that they will be able to make informed decisions about how to act. More attention should be given to risk communication in the training of health professionals.

Journal Article↗
PubMed1995

Metabolism of Big endothelin-1 (1-38) and (22-38) in the human circulation in relation to production of endothelin-1 (1-21).

Healthy male volunteers received intravenous infusions of Big endothelin (ET)-1 (1-38) or Big ET-1 (22-38). Blood samples were drawn from catheters in the brachial and pulmonary arteries and the hepatic, renal, jugular and deep forearm veins. The in vivo half-lives of circulating plasma Big ET-1 (1-38) were 6.6 +/- 0.3 min for the initial phase and 23 +/- 1.4 min for the late phase. The corresponding half-lives of Big ET-1 (22-38) were considerably shorter, being 0.9 +/- 0.03 min (P < 0.01) and 3.1 +/- 0.4 min (P < 0.01), respectively. This was concordant with the efficient regional clearance of Big ET-1 (22-38), which was most prominent in the forearm muscle (51 +/- 3%), liver (44 +/- 5%) and kidney (43 +/- 3%) and less pronounced in the lungs (14 +/- 2%) and brain (22 +/- 5%). Significant fractional extraction of Big ET-1 (1-38) was only found for the liver (30 +/- 2%) and kidney (44 +/- 3%). During the infusion of Big ET-1 (1-38) a positive veno-arterial gradient of ET-1-LI was noted only for the kidney, indicating production of ET-1. In conclusion, whereas Big ET-1 (22-38) is eliminated in skeletal muscle, splanchnic, renal, pulmonary and cerebral vascular beds, Big ET-1 (1-38) is extracted mainly in the renal and splanchnic vasculature. Furthermore, plasma half-life of Big ET-1 (1-38) is much longer than that of both ET-1 and Big ET-1 (22-38) in man. Thus, for investigation of the secretory activity of the ET-1-system measurements of Big ET-1 (1-38) levels may be a better approach.

Adult↗
PubMed1995

Physical work load and pregnancy outcome.

Pronounced physical exertion may influence intraabdominal pressure and uterine blood flow, hormonal balance, and nutritional status, all of which are important determinants of embryonic and fetal development and survival. Most of the epidemiologic evidence of reproductive effects from occupational physical activity concerns gestational age/premature birth, birth weight/intrauterine growth retardation, and spontaneous abortion. Strenuous work, especially when involving long hours of standing and walking, seems to increase the risk of preterm delivery. The effect on intrauterine growth and spontaneous abortion risk is less clear. As a single factor, heavy lifting has in most circumstances not been associated with a significantly increased risk of these outcomes. In general, heavy work duties should be avoided, and enough rest periods assured, especially in late pregnancy.

Abortion, Spontaneous↗
PubMed1995

Reproductive effects of chemical exposures in health professions.

Numerous chemical substances are handled by persons working in the health care sector. At exposure levels that may occur in the occupational setting, some of these substances are potentially harmful to the reproductive processes. Among the potentially harmful substances are anesthetic gases, antineoplastic agents, and sterilants. The epidemiological evidence of increased risks for adverse reproductive effects (eg, subfertility, spontaneous abortions, congenital defects) from such exposure is not unequivocal. However, due to the toxic potential, exposures should be kept at a minimum, and this may be especially important for workers who are pregnant or are planning to achieve pregnancy.

Abortion, Spontaneous↗
PubMed1995

Metabolic and vascular effects of circulating endothelin-1 during moderately heavy prolonged exercise.

The aims were to investigate 1) the effects of endothelin-1 (ET-1) during exercise and 2) the influence of exercise on arterial ET-1 levels. Six healthy subjects performed two exercises of 2 h duration at 50% of peak oxygen uptake preceded by intravenous infusion of physiological saline or ET-1 (4 pmol.kg-1.min-1). Blood specimens were taken from arterial and hepatic vein catheters. Arterial ET-1 rose 15-fold during the infusion. Splanchnic blood flow fell after ET-1 and remained lower than in control subjects during exercise (P < 0.001). Splanchnic glucose production was approximately 25% lower compared with control values during the whole exercise period (P < 0.01). Neither heart rate, arterial glucagon, insulin, catecholamines, renin, glucose, lactate, nor glycerol levels differed from control exercise values. The calculated gluconeogenesis from glycerol and lactate did not differ from the control values. ET-1 levels rose approximately twofold in the control exercise (P < 0.01) and in another group of seven subjects performing 1 h of exercise at 70% of peak oxygen uptake (P < 0.001). In conclusion, ET-1 levels increased during exercise without ET-1 administration. In addition, circulating ET-1 has a (direct or indirect) regulatory action on splanchnic blood flow and glucose metabolism during exercise (and possibly under pathophysiological conditions) in humans.

Adult↗
PubMed1995

Circulating endothelin-1 reduces splanchnic and renal blood flow and splanchnic glucose production in humans.

The effect of minimal changes in circulating plasma endothelin-1 (ET-1) was studied in 12 healthy subjects receiving either 60 min of ET-1 (0.2 pmol.kg-1.min-1) or physiological saline intravenously. Blood was drawn from arterial, renal, and central hepatic vein catheters. Arterial ET-1-like immunoreactivity (ET-1-LI) increased from 4.7 +/- 0.4 (SE) to 8.6 +/- 1.0 pmol/l during ET-1 infusion. After 10 min, plasma ET-1-LI had increased to 6.12 +/- 0.29 pmol/l. For comparison the plasma ET-1-LI level was 12.9 +/- 4.2 pmol/in five patients with sepsis syndrome. Mean arterial blood pressure rose from 92 +/- 3 to 99 +/- 4 mmHg. Estimated splanchnic and renal blood flows fell by 18 +/- 5 and 10 +/- 3%, respectively, and splanchnic glucose production fell by 42 +/- 6% within 10 min of the ET-1 infusion and differed compared with corresponding control values. Only estimated splanchnic blood flow had increased 60 min after the ET-1 infusion. No change in splanchnic uptake of lactate or glycerol was seen. In conclusion, we suggest that circulating ET-1 with small or no demonstrable change in plasma concentration interferes with vasoactivity and splanchnic glycogenolyses in health and possibly pathophysiological conditions.

Adult↗
PubMed1995

ET-3 is extracted by and induces potent vasoconstriction in human splanchnic and renal vasculatures.

To investigate splanchnic and renal vascular effects and elimination of endothelin-3 (ET-3), ET-3 (10 pmol.kg-1.min-1 iv for 20 min) was given to six healthy male volunteers. Arterial plasma ET-3-like immunoreactivity (ET-3-Li) increased 10-fold to 111 +/- 31 pmol/l (P < 0.01). The initial half-life of plasma ET-3-Li determined in three subjects was 1.7 +/- 0.2 min. The fractional extraction of ET-3-Li was 68 +/- 7% in the splanchnic and 63 +/- 4% in the renal vascular beds. Mean arterial blood pressure fell from 86 +/- 4 to 94 +/- 4 mmHg (10%) (P < 0.05). Splanchnic and renal blood flows fell by 43 +/- 3% (P < 0.05) and 29 +/- 4% (P < 0.05), respectively, during the infusion. Splanchnic and renal vascular resistances rose by 92 +/- 22% (P < 0.05) and 58 +/- 7% (P < 0.05). In conclusion, ET-3 infusion in humans induces splanchnic and renal vasoconstriction of similar magnitude as previously shown during endothelin-1 infusion, presumably by ETB receptor activation. Plasma ET-3 is efficiently extracted in the splanchnic and renal vascular regions.

Adult↗
PubMed1995

Cancer incidence and mortality of patients with suspected solvent-related disorders.

OBJECTIVE: The aim of this study was to study the incidence of cancer and deaths from cancer and other diseases among patients referred to the 11 clinics of occupational medicine in Sweden between 1967 and 1987 for examination because of exposure to organic solvents. METHODS: The cohort comprised 5791 persons, 5283 men and 508 women. Information about cancer incidence and causes of death was collected from the Cancer Register of the National Board of Health and Welfare and the National Death Register of Statistics Sweden, respectively. The expected values were calculated from the national death rates and incidence rates of cancer. RESULTS: The overall mortality rate was close to expected, but the mortality rate was decreased for diseases of the circulatory system [standardized mortality ratio (SMR) 0.7, 95% confidence limit (95% CI) 0.5-0.9] and increased for suicide (SMR 2.0, 95% CI 1.2-3.2). The total cancer incidence was slightly elevated [standardized incidence ratio (SIR) 1.2, 95% CI 0.99-1.4], and some specific cancer sites showed an increased incidence, although the lower confidence limits surpassed one. Malignancies of the lymphohematopoietic system and cancer of the uterine cervix had an increased risk (SIR 1.9, 95% CI 1.2-3.2, and SIR 3.7, 95% CI 2.2-6.2, respectively). Patients with presumerably high solvent exposure had an SIR of 1.4 for all malignancies (95% CI 0.9-2.1) and those with presumerably low exposure had an SIR of 1.1 (95% CI 0.9-1.4). CONCLUSIONS: The study showed an increased risk for malignancies of the hematopoietic system and the uterine cervix among patients originally examined with regard to solvent-induced disorders. There was also an increased risk of suicide and a decreased risk of death from diseases of the circulatory system. There was no increased risk for deaths from mental or neurological disorders.

Adult↗
PubMed1994

Big ET-1 infusion in man causes renal ET-1 release, renal and splanchnic vasoconstriction, and increased mean arterial blood pressure.

OBJECTIVE: The aim was to study the vascular effects of big endothelin-1 (big ET-1) infusion and its possible conversion to ET-1. METHODS: Six healthy subjects were given an intravenous infusion of big ET-1 in a dose of 8 pmol.kg-1.min-1 for 20 min. Blood samples were taken before, during, and up to 3 h after the infusion from arterial, hepatic, and renal vein catheters for the determination of splanchnic and renal blood flows, as well as ET-1-like immunoreactivity (ET-1-LI) from these vascular beds. RESULTS: Intravenous infusion of big ET-1 was followed by a doubling of arterial ET-1-LI from 4.17(SEM 0.39) to 8.42(0.49) pmol.litre-1 (p < 0.001) and a significant increase in the renal release of ET-1-LI from 1.50(0.18) to 8.68(0.64) pmol.min-1 (p < 0.001) but no splanchnic release. Big ET-1 infusion also caused a decrease in heart rate from 57(4) to 45(3) beats.min-1 (p < 0.001) and an increase in mean arterial pressure from 86(1.3) to 106(3.2) mm Hg (p < 0.001), which lasted for at least 2 h. Renal blood flow fell from 1.38(0.06) to 0.83(0.04) litre.min-1 (p < 0.001) while splanchnic blood flow fell from 1.34(0.11) to 0.83(0.05) litre.min-1 (p < 0.001). CONCLUSIONS: Big ET-1 infusion causes a drop in heart rate, an increase in mean arterial pressure and decreases in splanchnic and renal blood flows. Arterial plasma ET-1 levels doubled and big ET-1 infusion also induced a significantly increased renal, but not splanchnic, release of ET-1-LI, suggesting a unique renal handling of circulating big ET-1. When the results of the infusion of big ET-1 are compared with our previous experiments using ET-1 infusion, more marked haemodynamic changes (as reflected in the increase in mean arterial pressure, the drop in heart rate, and the duration of renal vasoconstriction) are seen despite lower arterial plasma ET-1-LI levels.

Adult↗
PubMed1994

Inhibitory effects of neuropeptide Y on splanchnic glycogenolysis and renin release in humans.

Neuropeptide Y (NPY) is stored in sympathetic nerves and NPY levels increase several times during exercise. NPY administration during prolonged exercise causes reduced splanchnic glucose production. To elucidate the effects of NPY on adrenaline (Adr)-stimulated splanchnic glycogenolysis these substances were infused to seven healthy subjects in the post-absorptive state. Blood samples were drawn from an arterial and a central hepatic vein catheter for determination of splanchnic blood flow, exchanges of metabolites and arterial levels of NPY, catecholamines, insulin, glucagon and renin in the basal state and during 20 min Adr infusion (0.1-0.3 nmol kg-1 min-1). After basal values were reached a 60 min NPY infusion was initiated. At 40 min of NPY infusion the Adr infusion was repeated. Adr alone increased splanchnic blood flow (41%, P < 0.01), arterial glucose concentration (29%, P < 0.001) and splanchnic glucose production (102%, P < 0.01). During the NPY infusion both splanchnic blood flow and arterial glucose fell (P < 0.05). Although the combined NPY and Adr infusion caused the same proportional increases in splanchnic blood flow, arterial glucose and splanchnic glucose production as with Adr alone the absolute values were lower (all P < 0.05). Arterial insulin as well as Adr and noradrenaline increased with the combined NPY-and Adr infusion as with Adr alone. Arterial plasma renin activity was 12% lower with the combined NPY and Adr-infusion compared to Adr infusion alone. These results indicate further an inhibitory effect of NPY on splanchnic glycogenolysis and suggest that NPY inhibits Adr-stimulated renin release.

Adult↗
PubMed1994

Effect of beta-receptor blockade on splanchnic and muscle metabolism during prolonged exercise in men.

The importance of beta-receptor stimulation for the metabolism and circulation in the liver and exercising muscle was studied in six men during 3 h of leg exercise at 50% of maximum oxygen uptake. At 160 min of exercise, 0.15 mg propranolol/kg body wt was given intravenously. The results were compared with a previously studied control group examined in the same way but without beta-receptor blockade. The data show that beta-blockade during prolonged leg exercise, compared with exercising controls, results in 1) reduced splanchnic and leg blood flows (P < 0.005-0.01); 2) higher epinephrine and norepinephrine levels (P < 0.001); 3) unchanged respiratory exchange values, indicating unchanged carbohydrate oxidation; 4) a less marked drop in leg glucose uptake, suggesting reduced muscle glycogenolysis; 5) a higher splanchnic glucose output (P < 0.05) but lower splanchnic uptakes of lactate and glycerol after propranolol (P < 0.025-0.01), i.e., diminished uptake of gluconeogenic precursors, indicating accelerated hepatic glycogenolysis; and 6) unchanged glycerol levels with a lower splanchnic glycerol uptake, indicating reduced lipolysis. The data imply that, despite lower glycogen stores during prolonged exercise, liver glycogenolysis, as opposed to exercising muscle glycogenolysis, may be accelerated during beta-receptor blockade.

Adrenergic beta-Antagonists↗
PubMed1994

Endothelin-1 infusion reduces splanchnic glucose production in humans.

Two groups of six healthy subjects received an intravenous endothelin-1 (ET-1) infusion (4 pmol.kg-1.min-1 for 20 min) in the basal state. Blood was drawn from catheters in an artery (n = 12), a hepatic vein (n = 12), and a renal vein (n = 6) for determinations of blood flows and substrate exchanges. During the ET-1 infusion, splanchnic and renal blood flows were reduced by approximately 50 (P < 0.01) and 25% (P < 0.001), respectively. Arterial glucose concentration and splanchnic glucose production fell by approximately 4 (P < 0.01) and 55% (P < 0.001), respectively. The latter was still 30% below basal level 3 h after the infusion (P < 0.001). Arterial glycerol increased by 64% (P < 0.01), whereas arterial lactate was unchanged. Splanchnic uptakes of lactate and glycerol were unchanged. Arterial insulin and glucagon showed transient falls with a maximal drop of approximately 35% (P < 0.001) during the infusion. In conclusion, ET-1 infusion causes reduced splanchnic glucose production due to reduced glycogen-derived glucose release. The latter could partly be connected with the transient fall in arterial glucagon, but the prolonged suppressive effect on splanchnic glycogenolysis seems to be linked with other ET-1-related factors. We propose that the underlying mechanism to the transient falls in both arterial glucagon and insulin might be coupled to the ET-1-arginine-NO system.

Adult↗
PubMed1993

Trichloroethylene exposure in vapour degreasing and the urinary excretion of N-acetyl-beta-D-glucosaminidase.

In order to elucidate the potential nephrotoxicity of low level occupational exposure to trichloroethylene (TRI), urine analysis of the tubular enzyme N-acetyl-beta-D-glucosaminidase (U-NAG) was included in a cross-sectional study of metal degreasers in central Sweden. Eighty-six percent of 8-h TRI in air measurements were well below 50 mg/m3. Normal levels of NAG were found in morning urine samples from 29 workers compared to a historical reference group. A weak positive correlation (r = 0.48; P < 0.01) was observed between U-NAG activity and the concentration of the TRI metabolite trichloroacetic acid in urine but not with other estimates of recent or long-term exposure. In conclusion, TRI does not seem to be nephrotoxic at low exposure levels.

Acetylglucosaminidase↗
PubMed1993

Differences in vascular effects and removal of endothelin-1 in human lung, brain, and skeletal muscle.

To investigate the effects and elimination of endothelin-1 in humans, an intravenous infusion of endothelin-1 (ET-1) (4 pmol kg-1 min-1 for 20 min) was given to 10 healthy volunteers. Arterial plasma endothelin-1 like immunoreactivity (ET-1-LI) increased eleven-fold. The fractional extraction of ET-1-LI was 41% and 30% across the pulmonary and skeletal muscle vascular beds, respectively. The lung eliminated almost half of the administered ET-1. No fractional extraction was found in the cerebral circulation. The pulmonary oxygen uptake (VO2) was increased slightly by endothelin-1. Across both the cerebral and skeletal muscle vascular beds the arterio-venous oxygen difference decreased (P < 0.05), suggesting vasodilation, the effect lasting up to 1 h after the end of endothelin-1 infusion in the cerebral circulation. Arterial-pulmonary artery oxygen difference increased by 20%. ET-1 infusion led to a decrease in heart rate (10%), cardiac output (14%) and stroke volume (8%) (all with P < 0.05) as well as a 7% increase in mean arterial blood pressure. Pulmonary and systemic vascular resistance increased by 67% and 25%, respectively (P < 0.05). These results demonstrate the regional differences in the removal of circulating endothelin-1, the lung being mainly responsible for the plasma elimination. Endothelin-1 seems to exert both vasoconstrictive and vasodilatory actions in humans, probably depending on differences in receptor populations and endothelium configuration in various vascular beds.

Adult↗
PubMed1993

High lactate and NH3 release during arm vs. leg exercise is not due to beta-adrenoceptor stimulation.

To investigate the differences in metabolic response between arm exercise (AE) and leg exercise (LE) and to elucidate the underlying mechanisms, seven men were studied during 20 min of AE or LE both with (beta) and without (control, C) nonselective beta-blockade (beta B) (propranolol). The work loads corresponded to 59 and 60% of peak pulmonary O2 uptake (VO2) during LE and AE, respectively. Pulmonary VO2 increased more slowly at the onset of exercise during AEC (half time = 61 +/- 9 s) than during LEC (half time = 35 +/- 3 s) and was not affected by beta B. At the onset of exercise the arteriovenous O2 difference across the exercising limb increased above that of steady state during AEC but not during LEC. This demonstrates that the adjustment of O2 delivery is slower than that of arm VO2 during AE. Despite the smaller exercising muscle mass, the release of lactate and NH3 was about twofold higher during AEC than during LEC. The difference in metabolic response between AE and LE was not altered by beta B. Lactate release was not reduced by beta B but, if anything, tended to increase during both AE and LE (beta vs. C). beta B increased NH3 release during LE (beta vs. C) but not during AE (beta vs. C). We conclude that AE compared with LE at the same relative work load is associated with a greater release of lactate and NH3, indicating a more severe metabolic stress during AE. Furthermore, the present data suggest that the increase in blood lactate at these submaximal exercise intensities is caused by factors other than beta-adrenoceptor stimulation.

Adult↗