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Biomedical subjects

K Savolainen

Publications and source records attributed to K Savolainen.

At least 73 records · Page 4Linked to original sources
PubMed1986

Validity of toxicity documents of pesticides and good laboratory practice.

Attention has been centered on the validity of the original toxicity reports supporting the registration of pesticides. In Finland, the present standard of the toxicity reports on pesticides was studied. Of the 299 pesticide formulations on the Finnish market only 96 were supported by original toxicity reports. Altogether 16 US formulations and 121 reports, as well as 11 control formulations with 170 reports were selected for the study. Reports from the questionable laboratories proved to be invalid according to the OECD guide-lines more frequently (61%) than those from control laboratories (20%). The frequency of invalid reports among long-term studies was higher (38%) than among acute studies (26.4%). The percentage of valid toxicity studies for the registration of pesticides in Finland was increased from about 50% in the fifties and sixties to 93% in 1980. The lack of reports on old pesticide formulations rather than the validity of the toxicity reports creates a problem in pesticide registration in Finland.

Animals↗
PubMed1986

Ethylenethiourea and nabam induced alterations of function and morphology of thyroid gland in rats.

Male Wistar rats were given 0-200 mg/l of nabam and 0-300 mg/l of ethylenethiourea (ETU) in drinking water ad libitum for 28 d to study their effect on thyroid gland function and morphology. Blood samples for RIA hormone assays (T3, T4, TSH) were taken and thyroids of each rat were dissected out for routine light and electron microscopic analysis after sacrifice performed under CO2 anesthesia. Nabam (8.4-30.5 mg/kg bw/d) inhibited dose-dependently T4-secretion and increased T3-secretion, but had no effect on basal TSH-secretion. ETU (10.6-23.4 mg/kg bw/d) inhibited dose-dependently T4- and T3-secretion. ETU also increased basal TSH-secretion tenfold, obviously due to the lack of negative feedback by T4 and T3. Light microscopic analysis revealed neither nabam nor ETU induced morphological alterations in thyroids. Both but especially ETU induced, ultrastructural changes, namely increased number of myelin bodies, dilatation of the rough endoplasmic reticulum, and increased vacuolization in the epithelial cells of thyroid follicles. The functional alterations are obviously connected with, and preceed slight ultrastructural degenerative changes in thyroid follicle epithelial cells even at low doses of nabam, and ETU, after a short-term oral administration.

Animals↗
PubMed1985

The effect of maneb, zineb, and ethylenethiourea on the humoral activity of the pituitary-thyroid axis in rat.

Ethylenebisdithiocarbamates (EBDCs) maneb and zineb are widely used fungicides the final metabolite of which is ethylenethiourea (ETU). EBDCs distort the humoral activity of the thyroid gland, and ETU is especially active in this respect. Male Wistar rats were exposed either to exogenous (100 ng i.p.) or endogenous (+4 degrees C) TRH stimulation. ETU (100-500 mg/kg i.p.) caused no changes in serum TSH levels whereas zineb (70-500 mg/kg i.p.) significantly decreased the bursts induced by cold or exogenous TRH. Maneb (20-200 mg/kg i.p.) significantly decreased the cold-induced TSH response while it had no effect on the TRH-stimulated TSH secretion. None of the agents caused significant changes in serum T3 or T4 levels. It seems that maneb, and zineb, but not ETU, inhibit rat TSH secretion through an action on the endogenous TRH at the hypothalamic or pituitary level. The mechanism behind this action may be the inhibition of dopamine-beta-hydroxylase.

Animals↗
PubMed1985

Dithiocarbamate fungicides decrease histochemical reactivity of cholinesterases in the gut wall of the rat.

The toxicity of dithiocarbamate fungicides is poorly known, especially in the autonomic nervous system. Male Wistar rats were given tetraethylthiuramdisulfide (DSF), maneb, and zineb as a suspension in saline i.p. 200 mg/kg daily for 4 d. Rats received a similar dose of ethylenethiourea (ETU) as a solution in saline i.p., and the control rats received a corresponding volume of saline i.p. After decapitation, pieces of ileum were taken, and the enzyme histochemical reactivity for the acetylcholinesterase (AChE) and for the nonspecific cholinesterase (nsChE) in the ilea of the treated and control animals was studied. The reaction intensities in the samples were estimated by eye using a scale from 0 (no reaction product) to 3+ (maximal reaction). DSF was used as an internal standard. Controls showed the maximal reaction for the AChE and for the nsChE. Maneb, ETU and zineb showed consistent decrease in the reactivity for the AChE (+ +) and for the nsChE (+ +). The decrease by DSF of the reactions for both the AChE (+) as well as for the nsChE(+) was even more pronounced indicating a possible nerve damage to the cholinergic innervation of rat intestine. Kinetic differences may explain the divergent effects between the agents studied.

Animals↗
PubMed1985

Effect of dithiocarbamate fungicides and thiurams on 3H-haloperidol binding in rat brain.

Dithiocarbamates and disulfiram have been shown to be neurotoxic. As one biochemical indicator of the toxicity, dopamine-beta-hydroxylase is inhibited in the brain. Consequently, noradrenaline synthesis is decreased and dopamine tends to accumulate in the brain. It was decided to examine whether cerebral dopaminergic D2-receptor binding is affected by these agents after their short-term administration to rats. It appeared that ferbam, maneb, nabam, zineb, disulfiram, thiram and ethylene thiourea did not change significantly D2-receptor binding at doses which were already overtly toxic.

Animals↗
PubMed1985

Status of the toxicity reports of pesticides for their registration in Finland.

Recently, attention has centered on the validity of toxicity reports for the registration of pesticides. In Finland, a study was conducted to evaluate the validity of the toxicity reports of pesticides done in U. S. laboratories. Twenty-seven pesticide formulations of the 230 on the market in Finland were selected for the study. The material contained 61 toxicity reports of 16 pesticide formulations done in U. S. laboratories considered questionable, 64 reports from U. S. laboratories considered reliable, and 142 reports originating from European laboratories, totally 267 reports. These reports were divided into valid according to the Organization for Economic Cooperation and Development (OECD) guidelines, and included those with minor discrepancies but in compliance with the good laboratory practice at the time of the study (group I), and and invalid according to the OECD guidelines (group II). After a closer evaluation of the 125 U. S. reports, 85 reports were considered valid and 40 invalid. As a function of time, the proportion of valid studies of all studies on pesticides for the registration purposes in Finland increased during 1961-1981 from 47 to 93%, being 100% at the present time. The lack of information of pesticide formulations registered earlier creates a problem to be solved in the future in Finland, rather than the lack of the validity of toxicity reports.

Animals↗
PubMed1985

Conversely exposure-related effects between atmospheric m-xylene concentrations and human body sense of balance.

Effects of fixed and fluctuating concentrations of m-xylene in air were studied on human psychophysiological functions. Nine healthy male volunteers were exposed to m-xylene 4 hrs a day, 3 hrs in the morning and 1 hr in the afternoon, with a 40 min. break in between. The subjects were sedentary or exercised at 100 W for 10 min at the beginning of each session in the chamber. The m-xylene concentrations in the air were fixed (8.2 mumol/l; 870 mg/m3) or fluctuated with peaks (5.2-16.4 mumol/l; 550-1740 mg/m3) but the TWA (8 hrs) concentration of m-xylene was always 4.1 mumol/l (435 mg/m3). The two control days, with and without exercise, were similar to the exposure days, but without exposure. Reaction times were measured with a device in which subjects responded to visual and auditory stimuli. Body sway was measured with the subjects' eyes open and closed with a strain gauge transducer platform. Changes in reaction times did not correlate with m-xylene concentrations in the air. Changes of average and maximal body sway were, however, consistently negatively correlated with the intensity of the atmospheric exposure to m-xylene at the beginning of each session in the chamber. Physical exercise combined with exposure to m-xylene improved rather than impaired body sway.

Adult↗
PubMed1985

Changes in the sense of balance correlate with concentrations of m-xylene in venous blood.

Nine healthy male volunteers were exposed to m-xylene for four hours a day, three hours in the morning and one hour in the afternoon, with a 40 minute break in between, at six day intervals during six succeeding weeks to explore the effects of m-xylene on the sense of balance. The atmospheric m-xylene concentrations were either fixed at 8.2 mumol/l (200 ppm) or they fluctuated (5.2-16.4 mumol/l; 135-400 ppm) with peaks of 16.4 mumol/l and duration of 10 minutes at the beginning of each exposure session. The subjects were sedentary or exercised at 100 W for 10 minutes at the time of the peaks. The two control days, with and without exercise, were similar to the exposure days but without exposure. Body sway was measured with the subjects' eyes open and closed before they entered the chamber and in the chamber immediately after the cessation of the peak exposure when blood samples for gas chromatographic analysis were also drawn. Changes in the eyes closed/open ratio of the average and maximal body sway along the sagittal and lateral axes were calculated using the morning value as a reference. Changes in the eyes closed/open ratios of both average and maximal body sway correlated positively with blood m-xylene concentrations during fixed (8.2 mumol/l) exposure at rest and during fluctuating exposure combined with exercise as analysed with linear regression analysis. The results suggest that m-xylene has a dose related effect on the sense of balance at moderate atmospheric levels.

Adult↗
PubMed1984

Immediate effects of m-xylene on the human central nervous system.

Male volunteers were exposed to m-xylene vapour for 4 h a day either sedentary or with a period of 10 min exercise twice a day with stable (8.2 mumol/l) m-xylene concentrations or fluctuating concentrations with peaks (16.4 mumol/l). The TWA concentration was always the same (8.2 mumol/l). The body balance of the subjects was clearly impaired in the anteroposterior (a-p) direction, especially with their eyes closed during the peaks at rest, whereas it was improved when exercise was included in spite of the higher blood m-xylene concentrations. When on the contrary, the situation was reversed in the lateral direction. Complex audiomotor reactions were impaired after the peaks combined with exercise, whereas changes in simple reaction times were similar in pattern to those found for body balance in the a-p direction. The results suggest a complex interaction between physiological factors and m-xylene and development of adaptation or tolerance during the exposure.

Air Pollutants, Occupational↗
PubMed1984

Neurotoxic effects of disulfiram on autonomic nervous system in rat.

Two groups of male Wistar rats weighing about 140 (WI) and 200 g (WII) and a group of Sprague-Dawley (S.D.) rats (140 g) received oral disulfiram 220-580 mg/kg (DSF) daily for one or three weeks. Isolated ilea of both control and treated rats showed similar responses to acetylcholine, but the responses to 5-hydroxytryptamine (5-HT) were decreased after one and three weeks' treatment in the WI and SD rats. Pretreatment with reserpine intensified this effect in treated WI rats. A distinct decrease in the histochemical reactivity for the acetylcholinesterase and the non-specific cholinesterase was observed in the nerve plexuses of the gut wall indicating a DSF-induced nerve damage. Autonomic (cholinergic) nerves seemed thus to be affected by DSF. The two rats strains studied did not differ in their responses to 5-HT.

Acetylcholine↗
PubMed1984

Long-term follow-up after Billroth I and II partial gastrectomy. Gastrointestinal tract function and changes in bone metabolism.

Late results of Billroth I (BI) partial gastrectomy for peptic ulcer in 19 patients were compared with those in 19 patients who had undergone Billroth II (B II) operation. The groups were matched for age and sex and were re-examined 21 to 27 years postoperatively. The study included notation of abdominal symptoms and haematologic status and tests of calcium metabolism with serum D-vitamin concentrations [S-25(OH)D2 and S-25(OH)D3], A-vitamin absorption, lactose and d-xylose tolerance and barium meal transit time to assess intestinal function, gastroscopy with biopsies, and measurement of bone mineral density, using the 241Am gamma ray attenuation method. In the paired comparisons of B I and B II patients, no significant difference was found in haematologic status or results of intestinal function tests. The serum alkaline phosphatase activity was significantly higher after B II than after B I, whereas S-25(OH)D2 and S-25(OH)D3 were significantly higher in the B I group. Other data for calcium metabolism showed no significant intergroup difference. Bone mineral density likewise was not significantly different in the two groups, but in both of them the values were significantly lower than in healthy control subjects. Most patients in both Billroth groups had atrophic mucosal gastritis.

Aged↗
PubMed1982

Short-term exposure of human subjects to m-xylene and 1,1,1-trichloroethane.

Inhalation exposure of male volunteers to m-xylene (8.2 mumol/l, 200 ppm) and 1,1,1-trichloroethane (TCE) (8.2 and 16.4 mumol/l, 200 and 400 ppm), as well as to a combination of TCE (16.4 mumol/l) and xylene (8.2 mumol/l), induced only slight changes in psychophysiological functions such as body sway and reaction time. Exposure to the 8.2 mumol/l concentration of xylene or TCE tended to improve the performances, whereas TCE exposure at 16.4 mumol/l alone or in combination with xylene tended to have an opposite effect. The results thus suggest a biphasic acute effect of TCE on the central nervous system (CNS) and reveal that xylene and TCE together exhibit neither kinetic interaction nor synergistic nor antagonistic acute effects on the CNS functions studied.

Adult↗
PubMed1982

Metabolic interaction between m-xylene and ethanol.

Ingestion of a moderate dose of ethanol (0.8 g/kg) by volunteers prior to 4-h inhalation exposure to m-xylene (6.0 or 11.5 mmol/m3) caused marked alterations in xylene kinetics. After ethanol intake the blood xylene level rose about 1.5-2.0-fold and urinary methylhippuric acid excretion declined by about 50% suggesting that ethanol decreased the metabolic clearance of xylene by about one half during xylene inhalation. This effect was noticeable up until a few hours after completed xylene exposure. Urinary excretion of 2,4-xylenol, the minor m-xylene metabolite, was generally not decreased by ethanol and sometimes the reverse seemed to be the case. The disturbance of xylene kinetics can be hypothesized to be caused mainly by ethanol-mediated inhibition of microsomal metabolism. When four volunteers who ingested ethanol prior to m-xylene inhalation at the higher concentration were monitored for blood acetaldehyde, transiently raised levels were found without notable effects on ethanol elimination. This observation may explain why some individuals experienced dizziness and nausea during the combined ethanol-xylene exposure.

Acetaldehyde↗
PubMed1982

Biphasic effects of inhaled solvents on human equilibrium.

Nine healthy male students were exposed for 4 hours at 6-day intervals to atmospheric concentrations of m-xylene (8.2 mumol/l; 200 p.m.) and 1,1,1-trichloroethane (TCE) (8.2 and 16.4 mumol/l; 200 and 400 p.m.) and also to a combination of 8.2 mumol/l of xylene and of 16.4 mumol/l of TCE. The exposures took place during 6 consecutive weeks. Body sway was recorded with the subjects' eyes closed and open on each day with a strain gauge transducer platform prior to and during the exposures. For the average and for the maximal body sway, the ratio of the sway with the eyes closed to the sway with the eyes open was calculated for each recording. Xylene and TCE at 8.2 mumol/l in air tended to decrease the ratio, whereas the higher TCE concentration alone or in combination with xylene tended to have an opposite effect of the same magnitude. The results support the idea that TCE might exhibit a biphasic pattern of acute effects on the central vestibular system. Pharmacokinetic interactions between xylene and TCE were not observed.

Adult↗
PubMed1982

The effect of partial gastrectomy on bone mineral metabolism.

The occurrence of postgastrectomy bone disease was studied in 42 patients who had been subjected to gastric surgery for duodenal or gastric ulceration 5-7 years earlier. Hypocalcemia, hypophosphatemia, and an increase in serum alkaline phosphatase were infrequent. No difference was observed in S-25OHD between the patients and controls, but S-24,25(OH)2D was higher in the patients. The bone mineral density (BMD) values showed no statistically significant difference between the patients and controls before or after the operation. There was a slight fall in BMD values during the follow-up period, but the decrease was similar in the patients and controls and was not statistically significant. The histomorphometric analysis revealed a greater amount of trabecular bone and osteoid in the patients. The means of the osteoid variables were well within normal limits, but a very slight increase in osteoid volume was observed in 4 of the 35 patients. It is concluded that a partial gastrectomy and vagotomy had not caused significant disturbances in bone mineral metabolism. The vitamin D status of the patients was good owing to the adequate dietary regimens that had been given to the patients.

Adult↗
PubMed1982

Osteomalacia in fractures of the proximal femur.

The occurrence of osteomalacia was studied in 58 hip fracture patients who were admitted to the University Central Hospital of Kuopio for operative treatment. Findings indicating osteomalacia were frequent in the series. Hypocalcaemia was found in 70 per cent and an increase in serum alkaline phosphatase in 22 per cent of the patients. Urinary calcium excretion was decreased in 45 per cent and urinary hydroxyproline excretion was increased in 70 per cent of the cases. The serum levels of 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D were significantly decreased in the patients compared with the controls. Histomorphometric analysis revealed no difference in the amount of trabecular bone in the patients compared with the controls, but the amount of osteoid and resorption surfaces was increased in the patients. Histological osteomalacia was found in 12 out of 50 patients (24 per cent). In 10 of these 12 cases the diagnosis of osteomalacia was supported by biochemical changes. There was only one patient, a 29-year-old man with glutein enteropathy who had an evident reason for osteomalacia. The most obvious cause of osteomalacia was the lack of vitamin D due to a deficient diet and lack of exposure to sunlight. The conclusion drawn was that osteoporosis was the main cause and osteomalacia was an important aggravating factor in the bone fragility in these hip fracture patients.

Aged↗