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Biomedical subjects

H Savolainen

Publications and source records attributed to H Savolainen.

At least 37 records · Page 2Linked to original sources
PubMed1999

Differentiation between vasculoprotective and uterotrophic effects of ligands with different binding affinities to estrogen receptors alpha and beta.

Estrogen-based drug therapy in cardiovascular diseases has been difficult because it has not been possible to separate the wanted vasculoprotective effect from the unwanted effects of the hormone to the reproductive system. Here, we demonstrate that, after endothelial denudation of rat carotid artery, the mRNA of the classical estrogen receptor (ERalpha) is constitutively expressed at a low level whereas the expression of the novel ERbeta mRNA increases >40-fold. Under in situ hybridization and immunohistochemistry, ERbeta mRNA and protein colocalize with the smooth muscle cells in the media and neointima. Treatment of ovariectomized female rats with the isoflavone phytoestrogen genistein, which shows 20-fold higher binding affinity to ERbeta than to ERalpha, or with 17beta-estradiol, which does not differentiate between the two receptors, provides similar dose-dependent vasculoprotective effect in rat carotid injury model. In addition in concentrations <10 microM, both ligands are equally inhibitory to the replication and migration of smooth muscle cells in vitro. However, only treatment with 17beta-estradiol, but not with genistein, is accompanied with a dose-dependent uterotrophic effect. The results suggest that preferential targeting to ERbeta will provide vasculoprotective estrogen analogs devoid of effects to the reproductive system.

Animals↗
PubMed1999

New mechanistic model for organic diisocyanate-induced respiratory disease.

The pathophysiological mechanisms of organic diisocyanate-induced respiratory disease remain largely unknown. Some 20% of patients have specific antibodies towards diisocyanate monomers whereas even in this circumstance their presence does not correlate very well with results in clinical provocation tests. The formation of diisocyanate haptens is the trigger for the immunological reactions. However, it is known that the reactions with protein and other macromolecules may be slow and hydrolysis of the isocyanate moities to corresponding amines as catalyzed by bicarbonate is more rapid. The liberated amines, or their intermediates, probably have an important role in the activation of tissue thromboplastin activator, loss of serum antitrypsin activity, and, finally, in neurogenic inflammation. Hypothetically, susceptible individuals probably include those which are slow acetylators of exogenous amines and carries of heterozygous antitrypsin phenotypes.

Humans↗
PubMed1999

Isolation and separation of proteoglycans.

Proteoglycans contain a polypeptide core and an oligosaccharide chain composed of aminohexoses and uronic acid. The glycan chain is attached to the polypeptide in a bond to serine hydroxyl. The glycan chains may contain up to 200 disaccharide units and the proteoglycan molecular mass ranges from a few thousands to millions. Their physiological functions are related to barriers limiting diffusion across the membranes, articular lubrification, blood coagulation and cellular adhesion. The tissue proteoglycans can be extracted with 4 M guanidine hydrochloride and purified with chromatographic techniques. The soluble proteoglycans can be precipitated with cetylpyridinium chloride, purified by chromatography or by dialysis. All proteoglycan species are amenable to electrophoresis on polyacrylamide gels, and after blotting on polyvinylidene fluoride membranes, they can be stained for glycans. Proteoglycan analyses have shown their value in clinical mucopolysaccharidosis diagnostics, in occupational toxicology and in coagulation studies. Experimental applications include cell adhesion studies in tumor biology, regeneration in neurosciences or maturation of skin and kidneys.

Animals↗
PubMed1999

Distal pulse palpation: is it reliable?

The aim of this study was to evaluate the reliability of distal pulse palpation. The dorsalis pedis and the tibialis posterior arteries of 25 patients with suspected lower limb arterial disease were independently palpated by three vascular surgeons and three medical students in the outpatient clinic and by two vascular nurses and one physician in the vascular laboratory. The palpation findings were compared to the ankle/brachial index (ABI). Palpable and unpalpable pulses were best separated with ABI 0.76 as the cutoff point. The degree of misdiagnosis was unacceptably high, with an underdiagnosis of more than 30%. The agreement was highest (kappa 0. 68, good) among the vascular laboratory personnel in the peaceful vascular laboratory and lowest (kappa 0.38, fair) among the vascular surgeons in the busy outpatient clinic. The poor agreement and the high proportion of misdiagnosis obtained in the outpatient clinic argue against the use of pulse palpation as a single diagnostic method. Palpable pulses with low ABIs clearly state the need for more objective measurements whenever ischemia is suspected. Yet, by carefully palpating both pedal arteries under good, nonhurried conditions the reproducibility and accuracy of pulse palpation can be tolerable.

Adult↗
PubMed1998

Urinary NAG and GAG as biomarkers of renal effects in exposure to 2-alkoxyalcohols and their acetates.

Many sensitive biomarkers are available for the surveillance of the early health effects of chemicals on humans. This study was conducted to evaluate the usefulness of glycosaminoglycans (GAG) as biomarkers of early kidney effects in exposure to 2-alkoxyethanols and their acetates. GAG were compared with effects on the urinary beta-N-acetylglycosaminidase activity (NAG). According to the results of the present study, the excretion rate of GAG was higher among women than men. On the other hand, the excretion rate of GAG was lower among exposed subjects than among the controls, and the level was decreased at the tested levels of exposure. The NAG activity was higher in most of the exposed groups than in the controls. The data indicated that an appropriate urinary limit value for ethoxyacetic acid was 30 mmol/mol creatinine in postshift samples and that this value corresponded to an 8-hour exposure level of 2 cm3/m3 2-ethoxyethylacetate. Urinary butoxyacetic acid excretion of 60 mmol/mol creatinine corresponded to the inhalation exposure level of 5 cm3/m3 2-butoxyethanol and its acetate in postshift samples.

Acetates↗
PubMed1998

Hand-arm vibration syndrome with proximal ulnar artery occlusion.

The case of a man exposed during 25 years to vibration while maneuvering a heavy earth moving tractor is reported. The first clinical manifestation of hand-arm vibration syndrome was a bilateral Raynaud's phenomenon followed five years later by digital necrosis. The arteriography revealed a proximal and bilateral ulnar artery occlusion. Bilateral median nerve conduction abnormalities were also present. Vibration exposure level was much higher than the threshold level proposed by the European Commission. Laboratory examinations for vasculitis and other vascular diseases were all negative. The purpose of this report is to show that vibration can be responsible for proximal occlusion of a medium sized artery and severe neurovascular abnormalities which must be distinguished from the usual vasospastic Raynaud's phenomenon and the classical hypothenar hammer syndrome. An early and correct diagnosis is crucial because continued repetitive trauma can result in irreversible ischemic injury and loss of digits.

Angiography↗
PubMed1997

[Do the isocyanate monomer standards still protect against attacks of occupational asthma? Should a standard including polyisocyanates be evolved?].

Field surveys of diisocyanates at the workplaces in Switzerland and particularly in car repair shops, where HDI was the most used, showed that the monomer levels comply with the Swiss permissible exposure limit (PEL) in the great number of situations. Cases of medical surveillance associated with industrial hygiene measurements demonstrate that occupational asthma was also observed in situations where the monomer concentrations are low although high peaks of prepolymers are often recorded. From the statistical data on compensations, the annual incidence of occupational asthma over the period 1988 to 1992 remains around 54 cases with a mean cost of 21,000 sFr. per case per year. It is suggested that a PEL on the prepolymers should be introduced in the Swiss PEL list to enhance the efficiency of prevention policy.

Asthma↗
PubMed1997

Biological monitoring of occupational exposure to 1-methoxy-2-propanol.

At the end of a workweek 23 silkscreen printers gave a urine sample for capillary gas chromatographic analysis for 1,2-propanediol. The mean concentration was 2.52 (S.D. 2.01) mmol mol creatinine(-1) (median=1.76, n=23). The urinary excretion of 1,2-propanediol was linearly dependent on the preceding 1-methoxy-2-propanol exposure measured in the worker's breathing zone [y=0.99+0.28x, n=23, r=0.67, where y is the urinary 1,2-propanediol concentration, in mmol mol creatinine(-1) and x is the concentration, in cm3 m(-3), of 1-methoxy-2-propanol (90.2%), 1-ethoxy-2-propyl acetate (5.8%), 1-methoxy-2-propyl acetate (2.1%) and 1-ethoxy-2-propanol (1.9%) in the air].

Chromatography, Gas↗
PubMed1997

[Voluntary mercury poisoning: biological consequences and psychiatric significance].

A young patient suffering from schizophrenia had intense headaches and photophobia which were induced by intra-ocular injections of mercury. The clinical diagnosis was established once foreign bodies were visualized on regular X-rays of the patients skull. The mercury intoxication in combination with the secondary irreversible lesions to the eyes necessitated a bilateral enucleation and the use of a chelating treatment with sodium-dimercapto-1-propane sulfate (DMP). Automutilation is a very rare and dramatic complication of schizophrenia. The psychiatric handling and meaning of such dramatic automutilation is discussed in this case report together with a recent review of the toxicologic treatment of mercury intoxication in humans.

Adult↗
PubMed1997

Flour protein antigens in occupational flour hypersensitivity.

Thirty serum samples from clinical cases of flour hypersensitivity were analyzed for wheat or rye flour protein antibodies. The patients included 20 bakers and 10 others who also had occupational flour exposure. Twenty-three cases had antiflour antibodies which recognized antigens other than control sera in the flour protein patterns. The immunologic response of individual cases seemed very variable in view of the numerous differences between the cases in the antigen-antibody reactions. For the practical purposes, the flour protein antigens were divided in three groups, i.e., those larger than 80 kDa, those between 80 and 50 kDa and those smaller than 50 kDa. Cases with flour-induced dermatitis (n = 8) showed sensitization towards antigens in all size classes while those with rhinitis or asthma showed more antigens with a molecular weight less than 50 kDa. The test offers a possibility to independently verify an exposure to flour while it does not substitute for the conventional immunologic diagnostic tests.

Adolescent↗
PubMed1996

Urinary hexane diamine as an indicator of occupational exposure to hexamethylene diisocyanate.

The occupational exposure of 19 men to hexamethylene diisocyanate (HDI) vapour was monitored during one 8-h shift. It ranged from 0.30 to 97.7 micrograms/m3. This was compared with the urinary output of hexane diamine (HDA) liberated by acid hydrolysis from its conjugates in post-shift samples. The excretion varied from 1.36 to 27.7 micrograms g creatinine, and there was a linear association of HDI air concentration with urinary HDA excretion. The validity of the urinary analysis was confirmed by simultaneous blind analysis in another laboratory. The results had an excellent linear concordance. Thus, it seems that while the gas chromatographic-mass spectrometric detection method requires sophisticated apparatus, the results are very useful to occupational health practices. A biological exposure index limit of 19 micrograms HDA/g creatinine in a post-shift urine specimen is proposed as an occupational limit level of HDI monomer (time-weighted average = 75 micrograms/m3). Most importantly, biological monitoring of HDA is sensitive enough to be used at and below the current allowable exposure limit levels.

Aerosols↗
PubMed1996

Urinary alkoxyacetic acids and renal effects of exposure to ethylene glycol ethers.

OBJECTIVES: Ethylene glycol ethers and their acetates are widely used in industry, because of their hydrophilic and simultaneously lipophilic properties. Ethylene glycol ethers and their acetates are mainly metabolised to alkoxyacetic acids, but there is also a minor pathway through ethylene glycol to oxalic acid. The main pathway of ethylene glycol ethers is associated with significant clinical or experimental health effects and the minor pathway is also interesting because formation of urinary stones depends principally upon the urinary concentration of oxalate and calcium. METHODS: Excretion of alkoxyacetic and oxalic acids was examined among silkscreen printers for an entire working week. The aim of the study was to evaluate alkoxyacetic acids as early indicators of exposure to glycol ethers and to evaluate their toxicity to kidneys. The load of alkoxyacetic and oxalic acids was compared with the excretion of calcium, chloride, ammonia, and glycosaminoglycans (GAG). Morning urine was chosen for the main analysis, as the overall metabolite, ethoxyacetic acid (EAA), has a long elimination time from the body. RESULTS: The excretion of calcium increased according to the urinary alkoxyacetic acid load. The excretion of ammonia and chloride was higher among the exposed workers than among the controls. The highest urinary alkoxyacetic acid load was also associated with increased excretion of GAG, which may reflect the toxicity of metabolites of ethylene glycol ether. The excretion of GAG correlated positively with that of calcium in the printers with highest exposure. The tendency to form urinary stones was 2.4-fold higher among silkscreen printers than among office workers. CONCLUSION: On the basis of renal effects our study indicates the need for establishing a new biological exposure limit before a workshift that is clearly below 100 mmol ethoxyacetic acids per mol creatinine in morning urine of people occupationally exposed to ethylene glycol ethers.

Acetic Acid↗
PubMed1995

[Protein antigens in case of asthma, rhinitis and dermatitis in patients occupationally exposed to flour].

21 patients gave sera to clarify their clinical hypersensitivity towards flour proteins. 6 had dermatitis, 3 rhinitis and the others asthma. 3 patients showed a control reactivity towards the electrophoretically separated flour protein antigens while others had antibodies to flour antigen with molecular weights less than 100 kD or 80 kD in the case of rye. Reactivity towards antigens with molecular weight higher than 50 kD was typical of dermatitis patients, while the rhinitis and asthma cases' sera reacted towards lighter flour proteins in the 20-30 kD range. The procedure is simple, a random serum sample (5 ml) suffices, and it allows demonstration of sensitization to flour protein in a way which may be helpful in the evaluation of exposure and the diagnosis of allergic conditions due to flour dust, a major etiology of occupational respiratory disease.

Adolescent↗