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Biomedical subjects

J Mattila

Publications and source records attributed to J Mattila.

At least 91 records · Page 5Linked to original sources

The cold-induced TSH secretion is resistant to alterations in the physicochemical properties of the intracerebral infusions.

The purpose of the present study was to see how different methodological factors affect TSH secretion in male rats. The cold-induced TSH secretion was rather resistant to variations in the volume, pH and osmolality of solutions infused bilaterally into the anterior hypothalamus or into the 3rd ventricle of the rat brain. Only rather high pH (11.30) and osmolality (870 mosmol/kg) significantly inhibited the TSH cold-response. A short term immobilization (sham-infusion) or ether anaesthesia did not cause any significant alterations in TSH secretion. It is concluded that the cold-induced TSH secretion is not easily affected by nonspecific methodological factors.

Animals↗

Comparative pharmacokinetics of metronidazole and tinidazole as influenced by administration route.

Serum kinetics of metronidazole and tinidazole were compared in four separate randomized crossover studies. Single doses of each drug were given to healthy volunteers through intravenous infusion (500 mg over 20 min, six persons), by mouth (500 mg, nine persons), by rectum (1,000 mg, six persons), or intravaginally (500 mg, six persons). Concentrations of the unchanged drugs in serum, measured by high-pressure liquid chromatography, were similar after oral and intravenous administration, with mean peaks of 9.0 and 9.4 micrograms/ml for metronidazole and 7.5 and 10.1 micrograms/ml for tinidazole. Concentrations of tinidazole were significantly higher than those of metronidazole from 4 h onwards after intravenous infusion, and from 3 h onwards after administration by mouth. After rectal administrations, a significant difference was seen only at 48 h. After vaginal dosing, however, concentrations of metronidazole were significantly higher than those of tinidazole between 1.5 and 12 h. Bioavailability of either drug, calculated according to the formula (area under the curve for oral administration)/(area under the curve for infusion), was practically complete after oral administration and was poorer after rectal and especially vaginal administration. Whenever the parameters were calculable, the elimination half-life of tinidazole (range of means, 14.0 to 14.7 h) was significantly longer and total clearance (40.3 to 47.6 ml/min) was lower than the corresponding values of metronidazole (7.9 to 8.8 h and 71.8 to 80.1 ml/min, respectively).

Administration, Oral↗

Effects of some putative amino acid neurotransmitters on the stimulated TSH secretion in male rats.

The importance of several amino acids (glycine, L-glutamic acid, L-serine, taurine and beta-alanine) in the regulation of the stimulated secretion of TSH was studied in male rats using both peripheral and central administration of the amino acids. Glycine (10-200 mg/kg i.p.), L-glutamic acid (10-500 mg/kg i.p.) and L-serine (500 mg/kg i.p.) decreased significantly the cold-induced TSH secretion whereas beta-alanine (1-500 mg/kg i.p.) and taurine (10-100 mg/kg i.p.) were not effective. The effect of L-glutamic acid (100 mg i.p.) was partially antagonized by bicuculline (1 mg/kg i.p.) but not by picrotoxin (1 or 2 mg/kg i.p.). Only glycine (50 and 100 mg/kg i.p.) inhibited the TRH-stimulated TSH secretion. When the intracerebroventricular route was used, L-serine (50 micrograms/rat) decreased the TSH could response whereas glycine and L-glutamic acid (1-50 micrograms/rat) had no clear effect. We conclude that glycine, glutamate and serine inhibit the cold-induced TSH secretion in the male rat. The action of serine and glycine is possibly mediated through the periventricular hypothalamus and the anterior pituitary, respectively. The inhibition caused by glutamate seems to be partially mediated through the bicuculline-sensitive GABA receptors in the hypothalamus. Taurine and beta-alanine play no role in the control of rat TSH secretion.

Amino Acids↗

Penetration of metronidazole and tinidazole into the aqueous humor in man.

500 mg of metronidazole or tinidazole were given as a 20-min infusion each to 10 patients who were hospitalized for elective cataract extraction. Metronidazole and tinidazole concentrations in aqueous humor were 5.2 +/- (SE) 0.5 and 5.3 +/- 0.7 micrograms/ml, respectively, 20-70 min after the end of the infusion. Aqueous humor/serum concentration ratios were 0.38 and 0.47 on the average for metronidazole and tinidazole, respectively.

Aged↗

Serum immunoglobulin and complement alterations in interstitial cystitis.

Sera from 41 patients with interstitial cystitis were tested for immunoglobulins (IgA, G, M), complement components (C1q, C3, C4) and for C1-esterase inhibitor. There was a statistically highly significant depletion of the serum levels of complement component C4 (p less than 0.001) and immunoglobulin G was markedly elevated (p less than 0.001). Our results suggest the classical pathway activation of the complement system and support the possibility that a chronic local immunological process is involved in the pathogenesis of the disease.

Complement Activating Enzymes↗

Inhibition of the TSH secretion by histamine in male rats.

The effect of histamine (HA) on the cold-stimulated and the TRH-induced TSH secretion was studied in male rats utilizing HA and specific HA antagonists and histaminergic drugs as tools. L-histidine (1000 and 1500 mg/kg ip) inhibited the cold-stimulated but not the TRH-induced TSH secretion. Mepyramine (5-50 mg/kg ip) and cimetidine (50-250 mg/kg ip) had no effect on the TSH-cold-response, but the TRH-induced TSH secretion was enhanced by them. HA (1 mg/kg sc), 2-pyridylethylamine (2PEA; 10 mg/kg ip) and impromidine (1 mg/kg sc) decreased the TRH-induced TSH secretion but did not affect the TSH cold-response. When infused into the third ventricle HA (1-50 micrograms/rat), impromidine (0.1 and 1.0 microgram/rat) and 2PEA (50 micrograms/rat) decreased the cold-stimulated TSH-secretion. The locus of the inhibitory action of HA seems to be both at the anterior pituitary, where it is mediated through H1- and H2-receptors and in the hypothalamus, where the effect appears to be mediated through H2-receptors. At least a part of this particular action might be explained by other mechanisms since neither H1- nor H2-receptor antagonists were able to counteract the effect of HA.

Animals↗

Possible involvement of nigrostriatal dopamine system in the inhibition of thyrotropin secretion in the rat.

The dopaminergic inhibition of cold-stimulated thyrotropin (TSH) secretion was studied in male rats. Serum TSH levels were decreased by apomorphine (1 mg/kg i.p.) but not by dopamine (DA, 0.2--5 mg/kg s.c.). This effect of apomorphine was abolished by haloperidol (1 mg/kg i.p.), metoclopramide and sulpiride (10 mg/kg i.p.) but not by domperidone (0.1--5 mg/kg i.p.). Domperidone does not cross the blood-brain barrier while the other DA receptor antagonists do so. High doses of domperidone itself inhibited the cold-induced TSH secretion whereas the other DA antagonists did not. DA (1--10 micrograms/rat) into the medial basal hypothalamus (MBH) had no effect but 10--50 micrograms/rat into the 3rd ventricle inhibited the cold-stimulated TSH secretion. 6-Hydroxydopamine infusion after desipramine pretreatment (25 mg/kg i.p.) did not affect TSH secretion when given into the MBH (2 micrograms/rat), the 3rd ventricle (100 micrograms/rat) or unilaterally into the substantia nigra (SN, 6 micrograms/nucleus), but bilateral nigral infusions abolished the TSH cold response. The inhibitory effect of apomorphine (0.1 and 0.5 mg/kg i.p.) was amplified only in the rats whose SN was unilaterally destroyed. These results show that tuberoinfundibular DA neurons do not affect TSH secretion. Instead, the inhibition is mediated through the hypothalamic projections of the nigrostriatal DA system.

Animals↗

Studies on the mechanism of the GABAergic inhibition of TSH secretion in male rats.

The mechanism of the GABAergic inhibition of the TSH cold-response was studied in male rats. Picrotoxin, a putative GABA receptor antagonist (4 mg/kg but not 0.5 or 2 mg/kg intraperitoneally) significantly decreased the cold-stimulated TSH secretion but did not modify the TRH-induced (100 ng intraperitoneally) TSH-response. The inhibitory effects of two GABAergic drugs muscimol (1 mg/kg subcutaneously) and aminooxyacetic acid (10 mg/kg intraperitoneally) were not antagonized by picrotoxin (1-4 mg/kg intraperitoneally), by phenoxybenzamine (2.5 or 5 mg/kg intraperitoneally), by two 5-HT antagonists cyproheptadine (5 mg/kg intraperitoneally and R 41468 (2.5 mg/kg intraperitoneally) or by pimozide (0.5, 1.5 or 2.5 mg/kg subcutaneously). The results suggest that neither picrotoxin-sensitive GABA receptors nor noradrenaline, 5-HT or dopamine pathways seem to be involved in the inhibitory action of GABAergic drugs on the TSH cold-response in male rats.

Animals↗

Studies on the role of the pineal gland in the regulation of TSH secretion in postpuberal male rats.

The role of the pineal gland in the regulation of thyroid-stimulating hormone (TSH) secretion was studied in postpuberal male rats using 12:12 h light:dark cycles. Pinealectomy, performed 3--4 days before decapitation, had no effect on the basal or thyrotropin-releasing hormone stimulated TSH secretion, but significantly decreased the cold-induced TSH response both at noon and at midnight. Neither hypothalamic thyrotropin-releasing hormone concentrations nor serum thyroid hormone levels were affected by pinealectomy. Melatonin injected intravenously (1 and 10 mg/kg) or intracerebroventricularly (5 and 50 microgram/rat) had no effect on the basal or cold-stimulated TSH levels, neither was the thyrotropin-releasing hormone induced (50 and 125 ng/rat i.p.) TSH response modified by melatonin (1 mg/kg i.v.). Arginine vasotocin (1 and 100 ng/rat) given intracerebroventricularly had no effect on the basal or cold-stimulated TSH secretion. These results suggest that the pineal has no influence on the basal activity of the hypothalamus-pituitary-thyroid system, but it seems that the cold-induced TSH response depends to a considerable degree on the intact pineal gland.

Animals↗

Complex role of 5-HT in the regulation of TSH secretion in the male rat.

The role of 5-hydroxytryptamine (5-HT) in the regulations of TSH secretion was studied in male rats using both peripheral and central administration of the drugs. Basal TSH levels were not modified by moderate doses of 5-HT (subcutaneously) or its precursors or antagonists (intraperitoneally) given 1 h before decapitation. The cold-stimulated TSH secretion was decreased by L-tryptophan (L-TRP, 400 mg/kg i.p.), quipazine (10 mg/kg i.p.) and 5-HT (1 or 5 mg/kg s.c. or i.v.) as well as by p-chlorophenylalanine (pCPA, 20 or more mg/kg i.p.) when the drugs were given 1 h before sampling. pCPA (100-400 mg/kg i.p.) was active 24-48 h after the injection but repetitive administration did not affect TSH levels. 5-HT (5 mg/kg s.c.) was effective also in pinealectomized animals. L-TRP and 5-hydroxytryptophan potentiated the TRH-stimulated TSH secretion when given 1 h before killing. 5-HT (10 microgram/rat) infused into the third ventricle enhanced the cold-stimulated TSH secretion when given 30-45 min before sampling. When injected into the medial basal hypothalamus, 50-HT (1-10 microgram/rat) had no effect on basal or stimulated TSH levels. The results suggest: (1) 5-HT does not play any role in the regulation of basal TSH secretion; (2) in the cold-stimulated TSH secretion 5-HT has a stimulatory action evidently inside the blood-brain barrier and also an inhibitory effect obviously outside this barrier.

5-Hydroxytryptophan↗

Further evidence of the dual role of noradrenaline in regulation of thyrotrophin secretion in male rats.

The dual role previously suggested for noradrenergic neurons in TRH-TSH regulation was studied in male rats. Alpha-Methyl-p-tyrosine (alpha MPT) significantly decreased brain noradrenaline (NA) and dopamine (DA) levels 0.5-6 h after the injection. Maximum inhibition of TSH cold-response occurred at 4 h. One h after administration of L-dopa the brain DA (but not NA) level was considerably elevated. TSH cold-response was not significantly changed. The effects of alpha MPT and Ca-fusarate on the cold-induced TSH secretion were antagonized by neither dihydroxyphenylserine (DOPS; this drug restores NA stores) nor by L-dopa (which restores DA levels). DOPS even potentiated the depressive effect of alpha MPT and Ca-fusarate. When given into the third ventricle, NA did not modify basal TSH levels but decreased the cold-induced TSH secretion. When infused directly into the median eminence of the medial basal hypothalamus, NA reduced both basal and cold-induced TSH secretion. Pinealectomy decreased the TSH cold-response but NA seemed to retain its ability to inhibit TSH secretion. These results demonstrate that besides the possible stimulatory action on TSH secretion, noradrenergic neurons also have an inhibitory effect outside the blood-brain barrier, possibly in the median eminence.

Animals↗

Macroglobulinemia with abdominal symptoms caused by intestinal extracellular macroglobulin.

A 54-year-old woman had a marked splenomegaly, diarrhoea and abdominal cramps. Her serum contained monoclonal IgM with lambda light chains, and lambda light chains were also excreted in the urine. Bone marrow and spleen punctures failed to reveal the classic morphological changes associated with Waldenström's macroglobulinemia. A peroral jejunal biopsy disclosed homogenous extracellular material consisting of IgM, lambda and kappa light chains were demonstrable in a large number of the plasma cells and plasmacytoid cells in post-mortem specimens of bone marrow, spleen and some lymph nodes by the peroxidase-anti-peroxidase techniques. The causes of the "discrepancy" between the serum findings and tissue findings are discussed.

Biopsy↗

Modification of GABAergic activity and thyrotropin secretion in male rats.

The effect of GABA on basal and stimulated TSH secretion was studied in male rats. The effects of drugs on basal TSH levels were not consistent. Muscimol(0.5 mg/kg subcutaneously, but not 2 mg/kg) increased whereas baclofen (10 mg/kg intraperitoneally), amino-oxyacetic acid (AOAA, 20 mg/kg intraperitoneally) and bicuculline (2 mg/kg intraperitoneally, but not 1 or 4 mg/kg) decreased basal TSH concentrations. Muscimol, AOAA and baclofen dose-dependently reversed the TSH cold-response, as did a large dose of di-n-propylacetate (DPA, 400 mg/kg intraperitoneally) and 500 mg/kg (but not 50, 100 or 1500 mg/kg intraperitoneally) of GABA itself. Bicuculline was not effective alone. Neither did it modify the effects of muscimol, AOAA and GABA on the cold-stimulated TSH response. None of the drugs studied (AOAA, GABA, bicuculline) modified TRH-induced (100 ng intraperitoneally) TSH-response. GABA injected into the third ventricle (5-50 microgram/rat) or into the medial basal hypothalamus (MBH, 5 microgram/rat) had no effect on the basal TSH levels. However, the TSH cold-response was inhibited when GABA (5 microgram/rat) was infused into the MBH but not when it was infused into the third ventricle (5-50 microgram/rat). The results suggest that GABAergic pathways may have an inhibitory effect on the stimulated TSH secretion in male rats. The locus of this inhibition is not situated in the anterior pituitary, but possibly in the MBH.

Animals↗