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Biomedical subjects

A Berglund

Publications and source records attributed to A Berglund.

At least 19 recordsLinked to original sources

Human fibroblasts lacking trans-stilbene oxide active glutathione transferase exhibit increased cell death when exposed to polycyclic aromatic hydrocarbons.

Glutathione transferases (GST) are detoxifying enzymes who act with many endogenous and exogenous substances such as polycyclic aromatic hydrocarbons (PAH). The GST activity towards trans-stilbene oxide (GST-tSBO) is inherited in an autosomal dominant fashion and can be separated in high (GST-positive) and low (GST-negative) phenotypes when measured in blood. Human fibroblast cultures were established from males matched for age, smoking habits and clinical manifestations of atherosclerosis. Matched pairs of GST-negative and GST-positive fibroblasts were studied. There was a very strong correlation between the levels of GST-tSBO in peripheral blood and in cultured fibroblasts within the same individual. When fibroblasts were exposed to benzo(a)pyrene (BP) or dimethylbenzanthracene (DMBA) GST-negative cells produced relatively more collagen than GST-positive cells. GST-negative fibroblasts showed a greater cell death than GST-positive fibroblasts as well among controls as after exposure to PAH. It is concluded that lack of GST-tSBO is easily discriminated in cultured skin fibroblasts. GST-negative and GST-positive fibroblasts showed different susceptibility towards some toxic stimuli that might be of importance in atherogenesis.

Aged

Weight reduction versus antihypertensive drug therapy in obese men with high blood pressure: effects upon plasma insulin levels and association with changes in blood pressure and serum lipids.

OBJECTIVES: First, to compare dietary and antihypertensive drug treatment in obese men with mild hypertension with respect to effects upon insulin, glucose, lipid metabolism and blood pressure. Second, to test the hypothesis that in the diet group changes in blood pressure and serum lipid concentration were associated with changes in plasma insulin concentration. DESIGN: A 6-week run-in period followed by random assignment to either diet or drug treatment, lasting for 1 year. Blood pressure measurements were performed blind after 5 and 45 min rest, and during isometric exercise. Plasma insulin and blood glucose concentrations were measured before and after an oral glucose load. SETTING: Outpatient clinic in a city hospital. PATIENTS: Sixty-four men aged 40-69 years with a body mass index > or = 26 kg/m2 and with a diastolic blood pressure of 90-104 mmHg when untreated were recruited (screening after an advertisement in a newspaper). Exclusion criteria were diabetes mellitus, organ damage secondary to hypertension and diseases that may have interfered with compliance and the interpretation of results. Sixty-one patients completed the study. INTERVENTIONS: Dietary treatment was based upon weight reduction and sodium restriction. Drug treatment used a stepped-care approach with atenolol as first choice drug. MAIN OUTCOME MEASURES: Absolute reductions in blood pressure, plasma insulin, blood glucose, serum lipid concentration and the waist:hip circumference ratio. RESULTS: Mean body weight decreased in the diet group and increased in the drug-treatment group. Plasma insulin concentrations, the waist:hip circumference ratio and serum lipid profile improved in the diet group compared with the drug group. Blood pressure control was significantly better in the drug group. In the diet group the changes in mean arterial pressure after 5 min rest and serum triglyceride levels correlated with changes in plasma insulin concentrations independent of changes in body mass index or body weight. CONCLUSIONS: Diet treatment was inferior to drug treatment in controlling hypertension, but superior in lowering plasma insulin concentrations and improving the serum lipid profile. The hypothesis of a relation between changes in blood pressure, serum triglycerides and plasma insulin was supported.

Adult

Release of mercury vapor from dental amalgam.

Because of its long-term clinical use there is more information and research data available about dental amalgam than about any other dental restorative material. However, on and off the safety of dental amalgam has been called in question and during the 80's the mercury controversy came to the fore, not only within the profession but also among the general public. Sources of mercury vapor contamination within dentistry were identified and attempts made to evaluate the contributions to the daily mercury uptake which can be attributed to dental amalgam. Mercury can be released from dental amalgam by evaporation and electrochemical corrosion as well as from amalgam particles which have been swallowed. A major route for mercury uptake from amalgam restorations is through inhalation of mercury vapor. The present study focused on experimental and analytical difficulties associated with the measurement of mercury vapor released in the oral cavity. A careful methodological study of the kind of source of mercury vapor that is prevalent and on the methods for measuring the intra-oral release of mercury vapor was carried out. With this as a basis quantitative determinations of the release rate of mercury vapor from amalgam restorations were made on healthy human subjects not occupationally exposed to mercury. The daily uptake of mercury from inhaled mercury vapor was calculated and salivary and urinary mercury levels were determined. In addition the release rate of mercury vapor from different types of amalgam was studied in vitro and in vivo. The findings may be summarized as follows: The only relevant measurable quantity when determining the mercury vapor released from amalgam restorations is the amount released per time unit, i.e. the amount of mercury vapor collected during intra-oral sampling is proportional to the sampling time. The diffusion of mercury atoms inside an amalgam restoration results in the formation of a concentration gradient in the surface of the amalgam. This mercury diffusion is the rate-determining step for mercury vapor release in the long run. In the short run the mercury concentration gradient prevalent on the amalgam surface on the measuring occasion is the apparent rate-determining step. The daily uptake of mercury from inhaled mercury vapor released from dental amalgam seems to make a very small contribution to the total body burden of mercury, in comparison with what can be tolerated in the work environment. The in vitro results revealed obvious differences regarding the release rate of mercury vapor from dissimilar amalgam types.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult

Time trends in incidence rates of acute, non-traumatic extremity ischaemia: a population-based study during a 19-year period.

Time trends in the occurrence of acute limb ischaemia were studied from 1965 to 1983 in a defined geographical area in Sweden. Data were obtained from a computerized register which covers all instances of inpatient care for a population of 1.3 million. Analysis based on 5394 first admissions for acute arterial occlusion revealed that the annual number increased by 2.7 per cent yearly in women and 3.9 per cent in men whereas the age-adjusted incidence remained stable for women and increased by 2.6 per cent yearly for men. A study of 1189 patients who underwent surgical procedures showed that the annual number of embolectomy procedures increased 7.6 per cent for females and 8.6 per cent for males. The corresponding age-adjusted incidence rose annually by 3.0 per cent for women and by 7.5 per cent for men. The introduction of the Fogarty catheter and an increasing interest in vascular surgery may have contributed to the increasing rates of operations during the period of study.

Adult

Cardiovascular effects of weight reduction versus antihypertensive drug treatment: a comparative, randomized, 1-year study of obese men with mild hypertension.

The aim of the study was to compare cardiovascular effects of weight reduction and sodium restriction with antihypertensive drug treatment in obese middle-aged men with mild hypertension in an open randomized trial lasting for 1 year, preceded by a 6-week run-in period. In the diet group (n = 31), weight decreased by 7.8 kg and salt intake by 2 g/day. In the other group (n = 30), treatment was structured with atenolol as the first line drug. The differences in antihypertensive response were highly significant when measured as casual blood pressure, with drug treatment being favoured. Echocardiographic estimations of left ventricular morphology and function showed no difference in effects between the two treatment modalities. Further analyses showed that the presence of previous antihypertensive treatment was modulating the effect of intervention on left ventricular mass. The response to treatment in plethysmographic estimations of resistance at maximal dilatation in the forearm did not differ between the groups. We conclude that drug treatment was superior to the diet regimen in controlling hypertension, that no differences were observed in effects on cardiovascular structure and that previous antihypertensive treatments seems to be a potent confounding factor that should be taken into consideration in future studies.

Adult

Hypoglycaemic episodes during intensified insulin treatment: increased frequency but no effect on cognitive function.

Ninety-seven patients with insulin dependent diabetes mellitus (IDDM) were randomized to intensified conventional treatment (ICT, n = 44) or regular treatment (RT, n = 53). The mean HbA1c level (+/- SEM) was reduced from 9.5 +/- 0.2% to 7.4 +/- 0.1% in the ICT group (P less than 0.001), and from 9.4 +/- 0.2% to 9.0 +/- 0.2% (P less than 0.01) in the RT group. The difference between the groups was significant (P less than 0.001). During a period of 3 years, 57% of the ICT patients (95% confidence interval 44-73%) and 23% of the RT patients (95% CI, 11-34%) (P less than 0.001) had at least one episode of serious hypoglycaemia, with the need for third-party assistance or resulting in coma. Eighteen of the 32 ICT patients who initially had adrenergic symptoms during hypoglycaemia changed to predominantly neuroglycopenic symptoms. This was the case with only 8 of 38 RT patients (P less than 0.01). The change in symptoms was related to the increased frequency of serious hypoglycaemia, but neither symptoms nor frequency of hypoglycaemia bor any relationship to insulin dose, body mass index, duration of diabetes or autonomic nerve function. The results of several neuropsychological tests did not differ between the groups at baseline, and did not change during the study. There were no signs of deteriorating cognitive function in the patients with serious hypoglycaemic episodes.

Adult

Increased smooth muscle cell proliferation by dimethylbenzanthracene is correlated to variations in activity of ornithine decarboxylase but not arylhydrocarbonhydroxylase.

Polycyclic aromatic hydrocarbons of cigarette smoke have been suggested to be involved in atherogenesis. After being converted to epoxides by monooxidases in the arterial wall the hydrocarbons may exert toxic or mutagenic effects on the smooth muscle cells (SMC). In a previous study we found that dimethylbenzanthracene (DMBA), an inducer of arylhydrocarbonhydroxylase (AHH), increased SMC proliferation and viability. In the present work we intended to study whether these effects were mediated by AHH. Alpha-naphtoflavone (ANF), a non specific AHH inhibitor, decreased SMC proliferation. The effects of ANF were totally counteracted by serum, partially by albumin and not at all by platelet derived growth factor. AHH activity was not detectable nor basally nor after induction in SMC, and this made us conclude that the effects of DMBA and ANF on SMC proliferation were not mediated by AHH. On the other hand the activity of ornithine decarboxylase was influenced by DMBA and ANF in parallel to proliferation, suggesting the involvement of this enzyme in the described DMBA effects on SMC proliferation. This mechanism might be of relevance for the pathogenesis of atherosclerosis especially in relation to cigarette smoking.

9,10-Dimethyl-1,2-benzanthracene

An immunoassay for histamine based on monoclonal antibodies.

Monoclonal antibodies with high specificity for histamine as well as for 1-methylhistamine were obtained after immunization of mice with a conjugate where the histamine was coupled via its ring 1-nitrogen to dog serum albumin. An immunoassay was developed for the quantitation of histamine release from basophils and 1-methylhistamine release from mast cells after provocation. The test method is based on competitive inhibition between histamine and a labelled histamine conjugate for the antigen binding sites of the antibodies. The separation step is performed by the addition of solid phase bound anti-mouse subclass specific antibodies. The sensitivity of the assay is 2 micrograms/l for histamine and 0.1 micrograms/l for 1-methylhistamine. No cross-reactivity was obtained with other metabolites of histamine or with histidine. Serotonin and dopamine were detectable, but only in doses (mg/l) well above the normal concentration found in the circulation. The immunoassay has been evaluated for its capacity to measure histamine release in vitro. A good correlation with the conventional fluorometric assay was obtained when histamine released from allergen stimulated leucocytes from allergic patients was tested. Urinary samples from patients undergoing hyposensitization showed a mean excretion of 1-methylhistamine at a level of 131 mumol MeHi/mol creatinine. The release of histamine and 1-methylhistamine in vivo was examined in plasma samples taken during a bronchial provocation test. A significant elevation above the basal analyte level occurred ten minutes after provocation.

Animals

Hip fractures in women with breast cancer.

The authors investigated whether the incidence of first hip fracture, an indicator of osteoporosis, is lower in breast cancer patients, who are assumed to have higher levels of endogenous estrogens, than in other women. A population-based Swedish cohort comprising 9,673 women with invasive breast cancer diagnosed from 1958 through 1983 was followed up with respect to the occurrence of a first hip fracture during the period 1965-1983. Overall, the number of observed acute fractures (n = 387) was slightly higher than expected (n = 348.6) (standardized incidence ratio (SIR) = 1.1, 95% confidence interval (CI) 1.0-1.2). Risk for trochanteric fractures was slightly higher than expected (SIR = 1.2, 95% CI 1.0-1.4), but risk for cervical fractures was not (SIR = 1.0, 95% CI 0.9-1.1). Risk for trochanteric fracture decreased with increasing age at breast cancer diagnosis, reaching standardized incidence ratios close to unity after the age of 70 years. Duration of follow-up appeared to be unrelated to the risk of either type of fracture. The authors conclude that the incidence of first hip fracture is not lower in breast cancer patients than in other women.

Adult

Metabolic effects of controlled-release metoprolol in hypertensive men with impaired or diabetic glucose tolerance: a comparison with atenolol.

In a double-blind, randomized, cross-over study with a single-blind placebo run-in period a new controlled-release (CR) formulation of metoprolol 200 mg once daily was compared with atenolol tablets 100 mg once daily in 22 patients (age 60.9 +/- 0.93 (SE) years) with primary hypertension and impaired or diabetic glucose tolerance. Each period lasted for three weeks. The two agents produced similar blood pressure 3 h as well as 24 h after drug intake. Three hours after drug intake, heart rate was lower on atenolol than metoprolol CR treatment, indicating a higher degree of beta-receptor blockade for atenolol at this point in time, when the plasma concentration of atenolol was most likely to be close to its peak. Concentrations of blood glucose, serum insulin, and serum C-peptide in the fasting state or after an oral glucose load did not differ between the active agents. HbA1c was marginally, but significantly, lower on atenolol than metoprolol CR treatment. No differences were found in serum levels of total, low density lipoprotein (LDL), and high density lipoprotein (HDL) cholesterol or apoA-I, and apoB lipoproteins or triglycerides. In comparison to the placebo run-in period, both agents showed an unexpected improvement in glucose tolerance, a decrease in HDL cholesterol and for metoprolol CR a small, but significant decrease in LDL cholesterol. Thus, treatment with metoprolol CR tablets producing even plasma levels without high peak concentrations and conventional atenolol treatment had similar effects on metabolic control in hypertensive men and abnormal glucose tolerance.

Aged

Estimation by a 24-hour study of the daily dose of intra-oral mercury vapor inhaled after release from dental amalgam.

The difficulties associated with estimations of daily doses of inhaled mercury vapor released from dental amalgam are considerable. Existing data are often unreliable, especially if they are based on a single or a small series of samples of intra-oral concentrations of mercury vapor before, during, and after chewing stimulation. In the present paper, the aim was to obtain a more representative estimation of the daily dose of mercury vapor inhaled from amalgam fillings by measurement of amounts of mercury vapor released in the oral cavity during 24 h, under conditions that were as normal as possible. A series of measurements was carried out on each of 15 subjects, with at least nine occlusal surfaces restored with dental amalgam, and on five subjects without any amalgam restorations. The subjects had to follow a standardized schedule for 24 h, whereby they ate, drank, and brushed their teeth at pre-determined time periods. The amount of mercury vapor released per time unit was measured at intervals of 30-45 min by means of a measuring system based on atomic absorption spectrophotometry. None of the subjects was professionally exposed to mercury, and all of their amalgam fillings were more than one year old. Study casts were made for each subject, and the area of the amalgam surfaces was measured. Samples of urine and saliva were analyzed so that values for the mercury concentrations and the rate of release of mercury into saliva could be obtained. The average frequency of fish meals per month was noted.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Antihypertensive effect of diet compared with drug treatment in obese men with mild hypertension.

OBJECTIVE: To determine whether dietary treatment has a similar antihypertensive effect to conventional drug treatment while being superior to drugs in improving serum lipid concentrations in obese men with mild hypertension. DESIGN: Six week run in period followed by randomisation to either diet or drug treatment groups for one year. SETTING: Outpatient clinic in city hospital. PATIENTS: 61 Men aged 40-69 years, body mass index greater than or equal to 26, diastolic blood pressure 90-104 mm Hg when untreated. Exclusion criteria were signs of organ damage secondary to hypertension and diseases that might have interfered with compliance or with interpretation of results. INTERVENTIONS: Dietary treatment was based on weight reduction, restriction of sodium, and decrease of excess alcohol intake (defined as greater than or equal to 250 g alcohol per week). Drug treatment used a stepped care approach with atenolol as drug of first choice. MAIN OUTCOME MEASURES: Diastolic blood pressure less than 90 mm Hg; absolute reductions in blood pressure and serum lipid concentrations. RESULTS: Mean body weight decreased 7.6 kg in the diet group and increased 0.9 kg in the drug treatment group (p less than 0.0001), and mean sodium excretion decreased 42 and 10 mmol/24 h respectively (p = 0.019). There was no difference in reported alcohol intake. Mean systolic blood pressure decreased 4 mm Hg in the diet group and 16 mm Hg in the drug group (p = 0.003) and diastolic blood pressure 3 and 11 mm Hg respectively (p = 0.002). Diastolic blood pressure of 90 mm Hg was attained by 29% of the diet group (nine men) and 73% (22) of those receiving drug treatment (mean difference 44%, 95% confidence interval 21 to 67%, p = 0.001). Dietary treatment produced decreases in mean serum concentrations of total and low density lipoprotein cholesterol as well as triglycerides and an increase in high density lipoprotein cholesterol concentration. In the drug treatment group the changes were in the opposite direction, and the groups differed significantly in all but total cholesterol. CONCLUSIONS: Dietary treatment was inferior to conventional drug treatment in controlling mild hypertension but superior in lowering serum concentrations of lipids.

Adult

Model of mercury vapor transport from amalgam restorations in the oral cavity.

A model of the oral cavity was used as the basis for a discussion of the conditions prevalent during the transport of mercury vapor from amalgam restorations via the saliva to the gas phase of the oral cavity during respiration or during pumping of air through the mouth. It was found that the mercury diffusion rate through the saliva layer is independent of the air flow rate through the oral cavity. Mercury appears to be transported as atoms both in the aqueous phase of saliva and in the gas phase. The majority of the mercury atoms reaching the gas phase appears to originate directly from the surface of the amalgam restorations, passing through the saliva layer, while only a minority originates from mercury dissolved in the aqueous phase. The amount of mercury released per unit of time to the gas phase was shown to be independent of the air flow rate during respiration and pumping. Furthermore, the released mercury atoms are distributed partly to the gas phase, from which they are respired to the lungs and the environment, and partly to the saliva and the gastro-intestinal tract, by swallowing.

Dental Amalgam

Influence of calmodulin on the human red cell membrane skeleton.

The calcium receptor calmodulin interacts with components of the human red cell membrane skeleton as well as with the membrane. Under physiological salt conditions, calmodulin has a calcium-dependent affinity for spectrin, one of the major components of the membrane skeleton. It is apparent from our results that calmodulin inhibits the ability of erythrocyte spectrin (when preincubated with filamentous actin) to create nucleation centers and thereby to seed actin polymerization. The gelation of filamentous actin induced by spectrin tetramers is also inhibited by calmodulin. The inhibition is calcium dependent and decreases with increasing pH, similar to the binding of calmodulin to spectrin. Direct binding studies using aqueous two-phase partition indicate that calmodulin interferes with the binding of actin to spectrin. Even in the presence of protein 4.1, which is believed to stabilize the ternary complex, calmodulin has an inhibitory effect. Since calmodulin also inhibits the corresponding activities of brain spectrin (fodrin), it appears likely that calmodulin may modulate the organization of cytoskeletons containing actin and spectrin or spectrin analogues.

Actins