Biomedical subjects

J Hirvonen

Publications and source records attributed to J Hirvonen.

At least 19 recordsLinked to original sources

PubMed1999

Scopolamine enhances middle-latency auditory evoked magnetic fields.

To study the influence of central cholinergic muscarinic transmission on human cortical middle-latency auditory evoked magnetic fields (MAEF), centrally acting antagonist scopolamine hydrobromide (0.3 mg, i.v.), and peripheral muscarinic receptor antagonist glycopyrrolate (0.2 mg, i.v.), were administered to 13 healthy subjects in a double-blind randomized cross-over design. MAEF, measured with whole-head magnetoencephalography (MEG), were elicited with clicks applied at 10-Hz rate to the left ear. The amplitudes of N(b)m and P(a)m responses were augmented by scopolamine (P < 0.01 and P < 0.08). These effects were about equally strong for responses from ipsi- and contralateral auditory cortices. Thus, the present MEG findings revealed specific modulation of cortical generators of middle-latency auditory evoked responses by muscarinic transmission. These findings might be associated with auditory processing deficits observed in dementias with cholinergic disturbances.

Acetylcholine↗

PubMed1999

Catecholamines in pericardial fluid of normotensive, spontaneously hypertensive and reserpine-treated rats.

In this study our aims were to investigate the presence and source of catecholamines in pericardial fluid of normotensive, reserpine-treated and spontaneously hypertensive rats. We found that noradrenaline is the only detectable catecholamine present in rat pericardial fluid. The effect of reserpine 6, 12, and 214 h after pre-treatment with 5 mg kg(-1) (8.2 micromol kg(-1)) i.p. shows that the concentration of noradrenaline in pericardial fluid reflects the amount of noradrenaline released within the heart rather than the amount of noradrenaline in plasma. Using spontaneously hypertensive rats (SHR) as a model for primary hypertension we could show that the level of pericardial noradrenaline is approximately threefold in the pericardial fluid of the SHRs when compared to respective values of age-matched normotensive Wistar-Kyoto rats (WKY), suggesting that there was an increased noradrenaline overflow in the hearts of the SHRs. In conclusion, determination of the noradrenaline concentration in the pericardial fluid might provide a new method for estimating the release of noradrenaline in the heart.

Animals↗

PubMed1998

Effect of diffusion potential, osmosis and ion-exchange on transdermal drug delivery: theory and experiments.

Equations expressing the effect of the diffusion potential on the trace ion transfer across a porous charged membrane have been derived. These equations have been tested with experiments with human cadaver skin. The transfer of sotalol and salicylate was measured varying the salt (NaCl) concentration in the donor and receiver compartments. It appears that osmotic pressure and ion-exchange make a significant contribution to the flux enhancement by the diffusion potential.

Administration, Cutaneous↗

PubMed1998

Experimental verification of the mechanistic model for transdermal transport including iontophoresis.

An experimental verification of the previously introduced model for transdermal transport (Kontturi and Murtomäki, J. Control. Release, 41 (1996) 177) is presented. The model comprises two penetration routes: an aqueous and a lipoidal pathway. Lipophilicity of the drug determines which route the drug uses. Constant potential iontophoresis can be used to evaluate the relative proportions of the two competing pathways. beta-blockers sotalol, timolol and propranolol, whose water-octanol partition coefficients span three orders of magnitude, are used as model compounds. Experiments reinforce the predictions of the model in that iontophoresis enhances the flux of the most hydrophilic drug, sotalol, the most whereas the flux of the least hydrophilic drug, propranolol, is enhanced the least. The effect of electroosmosis has now been included in the model.

Administration, Cutaneous↗

PubMed1998

Transdermal iontophoresis: modulation of electroosmosis by polypeptide.

The objective of this research was to further evaluate the relative importance of electrorepulsion and electroosmosis to the mechanism of enhanced transport across the skin during iontophoresis. Specifically, the impact of iontophoresing into the skin positively and negatively charged polypeptides (poly-L-lysines and poly-L-glutamic acids, respectively) on the membrane's permselectivity and hence on the quantity and direction of electroosmotic flow, was examined. Experiments were performed in vitro at pH 7.4 using conventional methodology; electroosmosis during the iontophoresis of the polypeptides into and across the skin was tracked in the usual way via the movement of the polar, uncharged, non-metabolizable marker, D-mannitol. Electrotransport of the cationic polypeptides attenuated electroosmotic flow in the normal anode-to-cathode direction; the degree of inhibition was correlated both with the initial concentration of poly-L-lysine in the anodal chamber and with the molecular weight of the polypeptide employed (from 1 to 25 kilodaltons). Iontophoresis of the anionic poly-L-glutamic acids from the cathode provoked a slight increase in electroosmotic flow in the 'reverse' direction (i.e. from the receptor phase beneath the skin towards the cathode chamber located on the epidermal side of the membrane); this effect, however, was much less dramatic than that produced in the opposite sense by the cationic polypeptides. The results suggest that driving large positively-charged polypeptide molecules into the skin leads to neutralization of the membrane's negativity, a subsequent loss of permselectivity and a concomitant attenuation of electroosmosis in the conventional anode-to-cathode direction. Presumably, the relatively poor iontophoretic permeability of these species (which becomes more and more evident with increasing molecular weight) results in a sufficiently important association of the polypeptide with the skin during the period of current passage. Much less significant effects are realized by the cathodal iontophoresis of poly-anions due to the difficulty of 'pushing' negative ions into an already negatively-charged membrane.

Administration, Cutaneous↗

PubMed1998

Effects of naltrexone and ethanol on auditory event-related brain potentials.

Acute effects of ethanol (0.55 g/kg) and the opioid antagonist naltrexone (50 mg) on auditory event-related brain potentials (ERP) (i.e., electrical brain activity time-locked to sensory stimuli) were investigated in 13 healthy social drinkers, using a double-blind, placebo-controlled, design. The subjects' task was to attend to tones presented to a designated ear while ignoring tones to the other, and to detect deviant tones among the attended tones. When administered alone, naltrexone significantly reduced the amplitude of the later part of negative difference (Nd[l]), suggesting impaired selective attention. However, this effect might have been caused by naltrexone-induced nausea. Ethanol, when ingested alone, attenuated the amplitude of the N1, and increased the peak latencies of the mismatch negativity (MMN) and N2b that have been suggested to reflect automatic change detection in audition and allocation of attentional resources to processing of stimulus deviance, respectively. In contrast, the P1 amplitude was augmented by alcohol, but only when the tones were attended. When ethanol and naltrexone were simultaneously ingested, however, the alcohol-induced P1 amplitude augmentation was canceled, thus tentatively suggesting opioidergic mediation of this alcohol effect. In contrast, the MMN peak latency was increased significantly more in the interaction condition than in the ethanol condition, thus suggesting that the detrimental effects of alcohol on involuntary attention switching were augmented by naltrexone. Furthermore, the N2b amplitude was significantly suppressed in the interaction condition, suggesting attentional impairment.

Adult↗

PubMed1998

Acute-phase response in dairy cows with surgically-treated abdominal disorders.

Ninety-seven dairy cows suffering from traumatic reticuloperitonitis, abomasal displacement, and other gastrointestinal disorders or dystocia were referred for abdominal surgery. Plasma protein concentrations, including plasma fibrinogen and haptoglobin, and conventional haematological variables were determined both pre- and postoperatively. The examined variables were not of value in predicting the outcome of the abdominal disorders in general, but fibrinogen concentrations may be helpful in postoperative monitoring of infectious complications, such as peritonitis. Fifty-five per cent of the cows had increased haptoglobin concentrations preoperatively and abdominal surgery led to an additional haptoglobin increase for a further 2-3 days. It is recommended that pre- and postoperative haptoglobin values should be compared when monitoring infectious complications. Non-parametric receiver operating characteristics (ROC) analysis suggested that plasma haptoglobin concentration was the most accurate parameter for differentiating traumatic reticuloperitonitis from other gastrointestinal disorders, but plasma fibrinogen and globulin concentrations were also of value in this respect.

Abdomen↗

PubMed1997

Pulmonary and serum surfactant phospholipids and serum catecholamines in strangulation. An experimental study on rats.

Elevations of phospholipid and catecholamine concentrations in the blood are regarded as the vital reactions in asphyxial deaths, which leave few or no morphological signs in the body. These vital reactions were tested here, under strict experimental conditions, employing rapid asphyxia. Rats anaesthetized with barbiturate were strangled with a rope 2 mm thick tightened with a force of 29.4 N (3 kp). The main surfactant components, phosphatidyl choline and phosphatidyl ethanol amine, were measured in serum and lung samples, and catecholamines in the serum. The lungs were also investigated histologically. The serum phospholipid concentration in the strangulated rats was 1.36 +/- 0.32 g/l, versus 1.04 +/- 0.17 g/l in the controls (barbiturate intoxication), P < 0.001, but no change in their content was observed in the lungs (26.21 +/- 4.04 mg/g vs. 25.15 +/- 3.64 mg/g dry weight). Histologically, focal emphysema and tiny haemorrhages were seen in the lungs of both groups with similar frequency. Mean serum noradrenaline (NA) and adrenaline (A) concentrations were significantly higher in the strangulation group (NA = 5.4 +/- 2.6 ng/ml vs. 2.8 +/- 0.1 ng/ml, P < 0.001 and A = 6.0 +/- 3.4 ng/ml vs. 3.8 +/- 3.0 ng/ml, P < 0.05). The results support the notion that phospholipid and catecholamine concentrations are increased in the blood upon suffocation and could thus be taken as indicators of hypoxia. Further investigations into postmortem phospholipid change or stability are needed. There are reports that phospholipid concentration remain quite stable for two days post mortem, whereas catecholamine concentrations tend to rise quite soon after death.

Animals↗

PubMed1997

Fatal occlusion of the left coronary main stem by a fragment from the femoral artery: a previously unreported complication of cardiac catheterization.

A 59-year-old man with grade III angina pectoris and 80% stenosis of the left anterior descending coronary artery developed an acute total occlusion of the artery during percutaneous transluminal coronary angioplasty (PTCA). Attempts at recanalisation and resuscitation were ineffective, and the patient died. The medico-legal autopsy revealed obstruction of left main coronary artery by a ringshaped piece of arterial wall that had been torn out of the femoral artery at the punction site and driven around the tip of the catheter into the orifice of the left coronary artery, filling it. This kind of complication of PTCA has not been described previously.

Angina Pectoris↗

PubMed1997

Suicide mortality among medical doctors in Finland: are females more prone to suicide than their male colleagues?

BACKGROUND: Suicide mortality among medical practitioners is in many countries significantly higher compared with other professionals and the general population. Differences between male and female physicians are difficult to estimate reliably because previous comparisons are mainly based on crude mortality rates. METHODS: Age-specific mortality rates were calculated for physicians, other professionals and the general population, males and females separately, as well as standardized mortality ratios (SMR) comparing physicians with the other groups. Crude mortality rates were calculated for the specialist groups. RESULTS: The SMR for male (female) physicians was 0.9 (2.4) compared with the general male (female) population and 2.4 (3.7) compared with other male (female) professionals. The SMR between male and female physicians was 1.2 (95% CI 0.9-1.7). CONCLUSIONS: Our results do not support the claim that female physicians have a greater risk of suicide than their male colleagues, but are concordant with previous observations of a higher suicide rate in female physicians compared with the general population and other female professionals.

Adult↗

PubMed1997

Iontophoretic delivery across the skin: electroosmosis and its modulation by drug substances.

PURPOSE: The long-term objective of this research is to understand how the efficiency of iontophoresis depends upon the structural and physicochemical properties of the administered drug. Specifically, the ability of certain drug species to alter the permselective properties of the skin was examined. METHODS: Using conventional in vitro methodology, the inhibition of electroosmotic flow induced by the iontophoresis of five different beta-blockers (of varying lipophilicity) was examined. The concomitant electrotransport of the most lipophilic species (propranolol) and the convective movement of solvent in the anode-to-cathode direction were measured. In addition, the possibility that electroosmosis might be augmented by the delivery of anionic drugs was also considered. RESULTS: Iontophoresis of lipophilic, cationic beta-blockers caused a concentration-dependent inhibition of conventional electroosmosis. The most hydrophilic analogs elicited no effect. As a result of this charge neutralization phenomenon, the optimal concentration for propranolol iontophoresis was significantly less than the maximum achievable in aqueous solution. Only a very modest improvement in convective solvent flow was induced by the cathodal iontophoresis of anionic compounds. CONCLUSIONS: The permselectivity of the skin can be altered by drugs which are positively charged and which possess a significant, adjacent hydrophobic surface. The latter seems able to "anchor" the molecule in the skin and the counter charge to the membrane's negative character ensures a tight association. Both lipophilicity and a positive charge are essential-without either, the phenomenon is not observed. The conformational flexibility of the drugs studied to-date, however, prevents unambiguous conclusions about the three-dimensional nature of the putative "binding site".

Adrenergic beta-Antagonists↗

PubMed1997

Influence of transient overdistension on bladder wall morphology and enzyme histochemistry.

Bladder overdistension has been found to cause transitional morphological changes in innervation which correlate with changes in micturition and bladder contractility. We investigated the influence of overdistension on bladder wall morphology using histological and enzyme histochemical methods. Overdistension was induced in female rats for 3 h by forced diuresis and balloon obstruction of the bladder neck. Oedema was seen beneath the mucosa at 12 h, with hyperemia and haemorrhages. The urothelium was mostly intact, although enzymes leaked out of the epithelial cells. The changes were increased at 24 h. The urothelium also showed some disruptions and degenerative vacuolization. The oedema reached its maximum at 48 h, and large numbers of inflammatory cells were also seen. The urothelium was disruptured in many places and vacuolated, but the subendothelial capillaries remained normal. Damage to some muscle cells was seen. After 7 days the oedema had disappeared and the urothelium was continuous. Enlarged nuclei were seen as white spots in the epithelial cells. Numbers of inflammatory cells were similar to those in the controls. Overdistension causes damage primarily to the bladder urothelium, and to a lesser extent to the muscular layer. Urothelium integrity is destroyed for several days, which makes it possible for various substances to penetrate the bladder wall and allows for bacterial adherence. The damage however is, almost completely healed within one week.

Alkaline Phosphatase↗

PubMed1996

Mismatch negativity subcomponents and ethyl alcohol.

Effects of ethanol (0.55 and 0.85 g/kg) on event-related potentials were investigated by presenting 50-ms standard and 25-ms deviant pure tones to 9 social drinkers during a reading task, in a single-blind, placebo-controlled paradigm. Whereas the lower ethanol dose had no impact on ERPs with an 0.8-s inter-stimulus interval (ISI), it attenuated the N1, P2, and mismatch negativity (MMN) amplitudes with a longer ISI of 2.4 s. The higher alcohol dose increased the N1 peak latency with both ISIs. It also suppressed the N1 and MMN amplitudes with the longer ISI. The MMN suppression did not, however, occur at scalp sites below the Sylvian fissure, thus suggesting that ethanol affected only the frontal MMN subgenerator. Moreover, the different dose responses of the N1, P2, and MMN (subcomponents) to ethanol may indicate that the neurotransmitter systems underlying their generation are, to some extent, different.

Adult↗

PubMed1996

Postmortem changes in serum noradrenaline and adrenaline concentrations in rabbit and human cadavers.

Postmortem changes in serum noradrenaline and adrenaline concentrations in adrenectomised rabbits and in human sudden death cases were measured with HPLC in order to obtain information of the usefulness of these biogenic amines as indicators of antemortem stress. It appeared that serum concentrations increased with time postmortem, except for adrenaline in the adrenectomised rabbits. The values varied considerably between individuals in both materials. It is concluded that postmortem assays of serum catecholamines cannot be used in practice to demonstrate antemortem stress, although this would theoretically be a promising approach, e.g., in cases of suffocation. So far there seems to be no reliable and conclusive method for estimating short lasting antemortem stress in individual forensic cases.

Animals↗

PubMed1996

Quantitative determination of bovine serum haptoglobin in experimentally induced Escherichia coli mastitis.

A high performance liquid chromatography (HPLC) method was developed, validated and used to analyse haptoglobin concentrations in serum samples taken from eight cows which had been challenged twice intramammarily with Escherichia coli. The results of the HPLC were compared with those from a photometric assay. The kinetics of the haptoglobin response were analysed with pharmacokinetic computer software. In contrast with the photometric assay, the HPLC was sufficiently sensitive to detect normal background levels of bovine serum haptoglobin. The serum haptoglobin concentrations of healthy cows ranged from 22 to 47 mg litre-1. As the concentration of haptoglobin increased, the results of the two methods correlated well (r = 0.96). A 52-fold increase in serum haptoglobin was detected after the first challenge with E coli. The mean pharmacokinetic parameters of the response after the first challenge were: lag phase 12 hours, t2/1increase 20 hours, tmax 72 hours, t1/2decrease 46 hours, and mean residence time 112 hours. The second challenge three weeks later resulted in a significantly lower haptoglobin response, the area under curve being 35 per cent of that after the first challenge. The clinical signs and inflammatory changes in the milk did not differ significantly between the challenges.

Animals↗

PubMed1996

Acute phase response in heifers with experimentally induced mastitis.

Ten pregnant heifers were inoculated in both hind udder quarters with a mixture of Actinomyces pyogenes, Fusobacterium necrophorum and Peptostreptococcus indolicus. Development of the experimental mastitis was monitored by sequential clinical and bacteriological examinations, and by blood acute phase protein profiles. Sequential changes in plasma fibrinogen, serum haptoglobin, acid-soluble glyco-proteins and alpha 1-proteinase inhibitor activity were analysed and compared with both the clinical and bacteriological findings and the final outcome of the disease after calving. All ten heifers developed moderate to severe clinical mastitis. Four recovered completely, had a normal lactation after calving and exhibited only transient fever and moderate local signs. In six of the heifers the course of the disease was severe, and the inoculated quarters failed to produce milk after calving. The acute phase response of the four heifers that recovered was also significantly milder than that of the other six heifers. Haptoglobin and acid-soluble glycoproteins were most effective in indicating the severity of the infection and predicting the final outcome of the disease. Fibrinogen was a reliable indicator for detecting the presence of bacterial infection in all heifers. alpha 1-Proteinase inhibitor activity was of low diagnostic value in this study.

Actinomyces↗

PubMed1996

Transdermal delivery of peptides by iontophoresis.

Transdermal administration by iontophoresis (enhanced transport via the skin using the driving force of an applied electric field) has been successfully demonstrated but no formal relationship between peptide sequence/structure and efficiency of delivery has been established. There are notable examples, such as the lipophilic leutinizing hormone releasing hormone (LHRH) analogs, Nafarelin and Leuprolide, that exhibit down-regulation of their own transport across the skin under the influence of an iontophoretic current. The hypothesis that this phenomenon is due to neutralization of the skin's net negative charge by these cationic peptides was examined with LHRH oligopeptides. The impact of these compounds on the electroosmotic flow of solvent into the skin, which is induced by iontophoresis and which contributes significantly to the electrotransport of large, positively charged ions, was examined and quantified. Close juxtaposition of cationic and lipophilic residues profoundly inhibited electroosmosis and, presumably, peptide flux. The results indicate that the lipophilicity of the oligopeptides facilitates van der Waals interactions with hydrophobic patches along the transport route, thereby permitting the positively charged oligopeptide to interact with carboxylate side chains that give the skin its net negative charge at neutral pH. The lipophilic, cationic oligopeptide, therefore, becomes anchored in the transport path, neutralizing the original charge of the membrane, and completely altering the permselective properties of the skin.

Administration, Cutaneous↗

PubMed1995

Hypothermia markers: serum, urine and adrenal gland catecholamines in hypothermic rats given ethanol.

The effect of ethanol (2 g/kg) on body temperature and catecholamine (CA) secretion in the cold (-20 degrees C) was investigated in adult male and female rats. The temperature dropped more rapidly in the females, being approximately 10 degrees C after 3 h as compared with 18 degrees C in the males. Controls received the same dose of ethanol but were kept at +20 degrees C. Increased concentrations of adrenaline (A) and noradrenaline (NA) were already observed in the serum and urine of the females after 0.5 h of exposure, but at 1 h in the males. Serum values were low in the females after 2 and 3 h and urine values high in connection with the deep hypothermic state. The urine values of the males were also high at the end of exposure, when they, too, were hypothermic. Depletion of amines was observed in the adrenals during the hypothermia phase, while CA concentrations tended to rise in the serum of the rats kept in the warm. The CA index (A:NA) was generally > 1 in both the serum and urine of the cold-exposed rats. The results show that female rats are less resistant to hypothermia than males, as indicated by their more rapid drop in body temperature and exhaustion of CA secretion. It is also apparent that urine CAs are worth measuring in cases of accidental hypothermia and possibly also other types of stress. An elevated CA index (> 1) seems to be an additional marker of hypothermia, showing a proportionally greater increase in the secretion of A than NA during cold stress.

Adrenal Glands↗