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Biomedical subjects

H Sjöberg

Publications and source records attributed to H Sjöberg.

13 recordsLinked to original sources

Positive effects of anabolic steroids, vitamin D and calcium on muscle mass, bone mineral density and clinical function after a hip fracture. A randomised study of 63 women.

A total of 63 women who had an operation for a fracture of the hip was randomly allocated to one year of treatment either with anabolic steroids, vitamin D and calcium (anabolic group) or with calcium only (control group). The thigh muscle volume was measured by quantitative CT. The bone mineral density of the hip, femur and tibia was assessed by quantitative CT and dual-energy x-ray absorptiometry and of the heel by quantitative ultrasound. Quantitative CT showed that the anabolic group did not lose muscle volume during the first 12 months whereas the control group did (p<0.01). There was less bone loss in the proximal tibia in the anabolic group than in the control group. The speed of gait and the Harris hip score were significantly better in the anabolic group after six and 12 months. Anabolic steroids, even in this moderate dose, given in combination with vitamin D and calcium had a beneficial effect on muscle volume, bone mineral density and clinical function in this group of elderly women.

Aged↗

An assessment of human liver-derived in vitro systems to predict the in vivo metabolism and clearance of almokalant.

The ability of various human derived in vitro systems to predict various aspects of the in vivo metabolism and kinetics of almokalant have been investigated in a multicenter collaborative study. Although almokalant has been withdrawn from further clinical development, its metabolic and pharmacokinetic properties have been well characterized. Studies with precision-cut liver slices, primary hepatocyte cultures, and hepatic microsomal fractions fortified with UDP-glucuronic acid all suggested that almokalant is mainly glucuronidated to the stereoisomers M18a and M18b, which is in good agreement with the results in vivo. Both in vivo and in vitro studies indicate that the formation of M18b dominates over that of M18a, although the difference is more pronounced with the in vitro systems. Molecular modeling, cDNA-expressed enzyme analysis, correlation analysis, and inhibition studies did not clearly indicate which P450 enzymes catalyze the oxidative pathways, which may indicate a problem in identifying responsible enzymes for minor metabolic routes by in vitro methods. All of the in vitro systems underpredicted the metabolic clearance of almokalant, which has previously been reported to be a general problem for drugs that are cleared by P450-dependent metabolism. Although few studies on in vivo prediction of primarily glucuronidated drugs have appeared, in vitro models may consistently underpredict in vivo metabolic clearance. We conclude that in vitro systems, which monitor phase II metabolism, would be beneficial for prediction of the in vivo metabolism, although all of the candidate liver-derived systems studied here, within their intrinsic limitations, provided useful information for predicting metabolic routes and rates.

Anti-Arrhythmia Agents↗

Optimal processors for images with an arbitrary number of gray levels.

We present a new group of processors, optimal in a maximum-likelihood sense, for target location in images with a discrete number of gray levels. The discrete gray-level distribution can be of any arbitrary form. We compare the performance of the processor derived for five discrete levels with the performance of a processor derived for a continuous Gaussian distribution and show that there are cases when only the processor derived for discrete levels will exhibit satisfactory performance. We give an explanation of this difference based on moment analysis and show how the correlation orders are related to statistical moments of the input scene.

Journal Article↗

How interactions between drugs and agarose-carrageenan hydrogels influence the simultaneous transport of drugs.

The diffusional transport of a series of small drug molecules (<400 Da) in agarose gel with and without kappa-carrageenan (a negatively charged polysaccharide) is studied. The drug molecules have amphiphile character, the hydrophilic part being a tertiary amine which is the same in all six drugs. The difference in structure resides in the hydrophobic part which give these molecules different properties such as a difference in CMC-values (critical micelle concentration). The transport studies show that the apparent diffusion coefficients (Dapp) of all the drugs in 1% (w/w) agarose gel are almost identical and with a value similar to that in water. These results were anticipated because of the small size of the drugs, the low concentration of agarose, and the lack of interaction between the diffusant and the polymer. In agarose gels also containing 0.02% (w/w) kappa-carrageenan, however, the Dapp-values are significantly decreased for all drugs, except for lidocaine. This lowering of the Dapp is ascribed to the interaction between the drug molecules and kappa-carrageenan. The Dapp-values of the drugs in the gel system containing kappa-carrageenan correlate well with the adsorption isotherms of the same drugs in the drug/kappa-carrageenan/water system obtained previously [1] and the Dapp-values follow the order: chlorpromazine<clomipramine<amitriptyline<imipramine<doxepin. Chlorpromazine has the lowest Dapp, with the highest degree of adsorption, and doxepin with the lowest degree of adsorption has the highest Dapp. Furthermore, results from the simultaneous transport of two drugs, chlorpromazine and amitriptyline, in the agarose gel containing kappa-carrageenan are also presented and clearly indicate a transport competition with good correlation to the adsorption isotherms.

Adsorption↗

A new method for diffusion measurement in polymeric films based on a stacked sheet concept.

PURPOSE: To develop and evaluate a simple, yet well defined, method to measure diffusion in semi-solids, i.e. polymeric materials. METHODS: The method was based on a concept where equivalent discs of polymeric films were cut and stacked on top of each other. The diffusion process was allowed to proceed unidimensionally through the stack of films perpendicular to the film surface. After an appropriate time, the stack was analysed disc by disc with respect to solute content and from the concentration profile so obtained the diffusion coefficient was calculated. RESULTS: An all-in-one device was developed, manufactured in stainless-steel, that cuts circular discs and stores each one successively in a "stack" in the cell compartment. CONCLUSIONS: Data from a silicone based system shows that the method, although simple, is accurate and reproducible.

Diffusion↗

Different effects on the expression of CYP7 and CYP27 in rabbit liver by cholic acid and cholestyramine.

It was recently reported that both cholesterol 7 alpha-hydroxylase CYP7 and sterol 27-hydroxylase CYP27 are subject to negative feedback control by bile acids in isolated rat hepatocytes and rat liver (Twisk et al., (1995) Biochem. J. 305, 505-511; Vlahcevic et al. XIII International Bile Acid Meeting, September 30-October 2, 1994, Abstract 17). In the present work a series of experiments was performed to study whether there is a coordinate regulation of CYP7 and CYP27 also in rabbit liver. Treatments of rabbits with cholic acid or cholestyramine resulted in marked suppression and induction, respectively, of CYP7 mRNA. In contrast, there were no significant effects on the CYP27 mRNA expression, amount of CYP27 protein or mitochondrial 27-hydroxylase activity. Thus, there is an apparent difference between rat and rabbit with respect to regulation of CYP27 by bile acids. It is concluded that, in rabbit, there is little or no coordinate regulation of CYP7 and CYP27 at a transcriptional level, and that CYP27 is not subject to a negative feedback control by bile acids neither at a transcriptional nor at a posttranscriptional level.

Animals↗

Liver mitochondrial cytochrome P450 CYP27 and recombinant-expressed human CYP27 catalyze 1 alpha-hydroxylation of 25-hydroxyvitamin D3.

A cytochrome P450 catalyzing 1 alpha-hydroxylation of 25-hydroxyvitamin D3 was purified from pig liver mitochondria. It also catalyzed 27-hydroxylation of 25-hydroxyvitamin D3 and 25-hydroxylation of vitamin D3. The ratio between the 1 alpha-, 27-, and 25-hydroxylase activities remained essentially constant during the purification. Substrates for sterol 27-hydroxylase CYP27 inhibited and a monoclonal antibody raised against CYP27 immunoprecipitated the 1 alpha-, 27-, and 25-hydroxylase activities. Apparently homogeneous preparations of CYP27 from pig and rabbit liver mitochondria catalyzed 1 alpha-hydroxylation. Human liver mitochondrial CYP27 was expressed from its cDNA in Escherichia coli. The nucleotide sequence encoding the N terminus of CYP27 was modified in the first eight codons to achieve expression in E. coli. The purified recombinant-expressed CYP27 reconstituted with the electron-transferring system of adrenal mitochondria catalyzed 1 alpha-hydroxylation of 25-hydroxyvitamin D3. Expression of unmodified CYP27 cDNA in simian COS cells confirmed the 1 alpha-hydroxylase activity toward 25-hydroxyvitamin D3.

Animals↗

Plasma calcitonin levels in patients with cystic fibrosis.

Plasma levels of calcitonin were investigated in patients with cystic fibrosis and compared with age- and sex-matched healthy controls. About forty per cent of the cystic fibrosis patients had plasma calcitonin levels that were markedly higher than normal. Elevated levels were found predominantly in female patients. In general, patients with marked pulmonary involvement had high plasma calcitonin levels. Immunoextraction and gel chromatography, carried out on plasma of one of the patients demonstrated monomer-like forms of calcitonin similar to those found in the healthy subjects.

Adolescent↗

The variation of hand steadiness with physical stress.

The performance of 12 subjects in a hand steadiness task was compared at different work loads. Hand steadiness expressed in the form of values of hand shakiness was found not to increase linearly with work intensity. On the contrary, the relation between hand shakiness and activation level, induced by physical work, was found to be positively accelerated by an exponent of 1.6. Subjective effort measured by a ratio estimation method grew, likewise, according to a positively accelerating function with an exponent of about 1.6, while subjective effort according to the "RPE" category scale like hear rate grew linearly with work load.

Journal Article↗

Interactions between heart rate, psychomotor performance and perceived effort during physical work as influenced by beta-adrenergic blockade.

Effects of a single intravenous dose of propranolol (0,25 mg/kg body weight) were examined in 15 healthy male subjects who performed three reaction-time tasks of different complexity, while pedalling at five work loads on a cycle ergometer. Comparisons between measurements after propranolol and after injection of a placebo solution showed a pronounced reduction of heart rate and an increase in catecholamine excretion following propranolol. Comparisons of psychomotor performance showed no significan difference between the propranolol and placebo conditions. Nor did self-estimates of perceived physical and task-induced efforts reveal any significant effects of propranolol. The results support the notion that heart rate is not a prominent cue for perceived effort.

Adult↗

Interaction of task difficulty, activation, and work load.

The performance of 25 subjects in three reaction tasks of different complexity was compared at different activation levels induced by five different work loads on a bicycle ergometer. Heart rate and blood pressure were used as indexes of activation. The results were in agreement with the Yerkes-Dodson law in that the optimal physiological activation level for rapid performance varied with the degree of task difficulty, relatively lower activation being more favorable the more difficult the task.

Adult↗

Relations between heart rate, reaction speed, and subjective effort at different work loads on a bicycle ergometer.

The hypothesis concerning an inverted-U relationship between activation and performance was examined by comparing the performance of 25 subjects in a choice-reaction task at five different work loads on a bicycle ergometer. Heart rate was used as an index of activation. The results were in full agreement with the hypothesis, performance being more efficient at a medium activation level than at high and low levels.

Adult↗