Biomedical subjects
Publications and source records attributed to Z Lacković.
A peripheral application of botulinum toxin type A (7 U/kg) has significantly reduced thermal and mechanical hypersensitivity in rats with the partial sciatic nerve transection as a classical model of surgical neuropathy.
Intracerebroventricular (icv) administration of betacytotoxics alters brain monoamine neurotransmission, without producing hyperglycemia. By means of in situ hybridization, we have investigated the expression of dopamine, noradrenaline and serotonin transporter (DAT, NAT, 5-HTT, respectively) mRNAs, in the brain of alloxan- and streptozotcin-icv treated rats. DAT1 mRNA expression is increased in 1-week alloxan-icv treated rats in arcuate nucleus (+51%) and ventral medial bundle /VMB/ (+32%), and decrease in VMB of 4-week alloxan- (-53%) and streptozotocin- (-9%) icv treated rats, respectively. NAT1 mRNA expression in locus coeruleus is decreased in 4-week alloxan-icv treated rats (-35%) and increased in A1 cell group of 1- (+19%) and 4- (+14%) week streptozotocin-icv treated rats. 5-HTT mRNA expression in dorsal raphe nucleus is increased in 1- (+13%) and 4- (+21%) week alloxan-icv treated rats. Observed changes may suggest altered response to antidepressants in streptozotocin-icv treated rats, used as an animal model of sporadic Alzheimer's disease.
The Internet is becoming an ever more important source of information in pharmacology and medicine. Little is known, however, about which Internet pharmacology resources are actually used by the pharmacologists - and to what extent - and how they estimate the Internet information quality and evaluation. This pilot study used an anonymous questionnaire, distributed among 250 mostly European (220/250) pharmacologists from 30 European countries attending The 2nd European Congress of Pharmacology, held in Budapest, Hungary, in 1999. According to study results, 93% of all participants use the Internet pharmacology resources: 56%, 35% and 9% of them on a daily, weekly and monthly basis, respectively. Among 56 pharmacological/medical free online databases offered, the general scientific databases were found to greatly prevail (Pub Med 60%, Evaluated MEDLINE 37%, Internet Grateful Med 29%, etc.), while drug monographs or toxicological databases were less used [e.g. ECDIN, RxList, National Toxicology Programme (NTP) < 10%]. Some 80% of the participants estimated the quality of the pharmacological information on the Internet as good or very good, while 20% thought the quality should be improved. Also, 35% of participants felt the need for improvement of the Internet pharmacological information evaluation, which should be the goal of pharmacology professional.
Spigelian hernia is a very rare anterior abdominal wall hernia with uncharacteristic symptoms and challenging diagnosis. The case of a 76-year-old male patient with colicky pain and vomiting lasting for 24 hours before admission to the hospital is presented. Physical examination of the patient revealed abdominal tenderness and a round-shaped tumefaction of 3 cm in size, located in the left lower abdominal quadrant. X-ray examination of the abdomen, obtained in left lateral position of the patient, showed small bowel ileus with distended jejunal loops. The abdominal ultrasound examination, followed by duplex ultrasonography, revealed a spigelian hernia with ischemic changes of strangulated bowel segment indicating incarceration of the herniated jejunal loop. Preoperative findings were confirmed by intraoperative diagnosis of spigelian hernia and incarcerated jejunal loop with ischemic changes and deserosation, followed by resection of the bowel segment involved and plastic surgical reconstruction of anterior abdominal wall. This case report highlights the role of duplex ultrasonography in the evaluation of circulatory status of potentially incarcerated bowel segment within hernial sac.
Immature female rats (21 days of age) were chronically intraperitoneally treated with guanethidine or muscarinic agents. The effects on the timing of puberty and ovarian wet weight, protein and total RNA and DNA contents were studied. While guanethidine (20.0 mg/kg/day) was ineffective, trihexyphenidyl and especially propantheline (15.0 mg/kg/day) delayed vaginal opening (by 23%) and the first vaginal oestrus (by 28%), and lowered ovarian weight (by 37%) and other ovarian growth parameters. Carbachol (0.2 mg/kg/day) reversed the effects of propantheline. Thus, in contrast to the adrenergic system, the cholinergic system appears to substantially contribute to the accurate onset of female puberty and ovarian growth in the rat.
Intracerebroventricular application of low, nondiabetogenic doses (500 micrograms kg-1) of alloxan and streptozocin is followed by alterations of the dopaminergic system in rat striatum. In this brain region the dopamine content significantly increased, while the density of dopaminergic D1 receptors significantly decreased seven days after the intracerebroventricular application of betacytotoxics, as compared with the control group. The density of dopaminergic D2 receptors in striatum remained unchanged. Dopaminergic D1 and D2 receptors operate through signalling mechanism of G proteins, but no changes of Gs and Gi proteins content have been found in rat striatum after the intracerebroventricular application of betacytotoxics. As intracerebroventricular, nondiabetogenic administration of betacytotoxics produces changes of the striatal dopamine content and D1 receptor density similar to that produced by peripheral, diabetogenic administration of these drugs, the effect might be related not solely to pancreatic beta cells damage, but to alterations of the brain insulin system, as well.
Specific binding of [3H]SCH 23390 to dopamine D1 receptors in the striatum and olfactory tubercle in 14-day alloxan-induced diabetic rats was investigated. The Scatchard analysis revealed decreased D1 receptor density in the striatum (Bmax values were 548 +/- 23 fmol/mg protein for the control and 466 +/- 33 fmol/mg for the diabetic rats). No change was observed in the olfactory tubercle (Bmax; 299 +/- 27 fmol/mg for the control and 317 +/- 32 fmol/mg for the diabetic rats). Thus, specific binding of [3H]SCH 23390 to striatal and olfactory tubercle membranes showed region-specific changes of brain dopamine D1 receptors in alloxan diabetic rats.
In recent years the effect of experimental diabetes mellitus on brain neurochemistry has been under an intensive investigation. In most of these studies diabetes was produced by a peripheral administration of streptozotocin or alloxan. In line with previous reports, a week after such an application of alloxan (200 mg/kg s.c.) we found the concentration of serotonin, dopamine and norepinephrine to be increased in the brain of a diabetic rat. Accumulation of these monoamines, produced by inhibition of monoamine oxydase with pargyline (100 mg/kg i.p.) decreased in animals made diabetic by alloxan or streptozotocin (100 mg/kg i.p.) suggesting a decrease in deamination rate. Surprisingly, however, one week after an intracerebroventricular administration of non-diabetogenic doses of streptozotocin (5-20 mg/kg) or alloxan (20 mg/kg), changes in brain monoamines were similar to those observed in diabetic animals. This observation apparently suggests that the CNS effect of streptozotocin or alloxan is not necessarily related to a diabetogenic, beta-cytotoxic action of these substances.
Experimental alloxan- or streptozotocin-produced diabetes in rats was accompanied by an increase in the levels of norepinephrine, dopamine, and serotonin, whereas the contents of metabolites, i.e., 5-hydroxyindoleacetic acid and homovanillic acid, in the whole brain gradually decreased with the duration of diabetes. Among the striatum, thalamus, and hypothalamus of alloxan diabetic rats, monoamine alterations were observed only in the hypothalamus; after 1 week an increase of norepinephrine content and after 13 weeks an increase of norepinephrine and dopamine contents were found. Tissues of 11 brain regions of 10 diabetic and 12 control patients post mortem were investigated for monoamine concentrations. Patients were all male, of similar age and interval between death and autopsy. Diabetic patients had an increase in the content of serotonin in the medial and lateral hypothalamus. The content of dopamine increased in the medial hypothalamus, putamen, and medial and lateral pallidus. In diabetic patients, the content of norepinephrine increased in the lateral pallidus and decreased in the nucleus accumbens and claustrum. Thus, it seems that diabetes mellitus in rats, as well as in humans is associated with regionally specific changes in brain monoamines.
The binding of [3H]SCH 23390, a selective dopamine D-1 receptor radioligand, to rat kidney cortical membranes was studied. Scatchard analysis revealed a single class of binding sites. Of dopamine, noradrenaline and serotonin, dopamine was the most potent of these to displace [3H]SCH 23390 binding. The selective D-1 ligands SCH 23390 and SK & F 38393 were more potent to displace [3H]SCH 23390 than the selective D-2 ligands S-sulpiride and LY 171555, thus indicating that [3H]SCH 23390 binds predominantly to dopamine D-1 receptor sites.
The binding of D2-dopamine receptor ligand [3H]spiperone and selective D1-ligand [3H]SCH 23390 to the rat adrenal gland and striatum has been compared. [3H]Spiperone showed specific binding in both tissues revealing a Bmax of 887 fmol mg-1 protein and KD of 0.38 nM, and B of 34 fmol mg-1 protein and KD of 0.66 nM in the striatum and adrenal gland, respectively. On the other hand, [3H]SCH 23390 showed a specific binding to the striatal tissue with Bmax of 747 fmol mg-1 protein and KD of 0.70 nM, while in the adrenal tissue no specific binding was observed. These results apparently indicated only D2-dopamine receptor binding sites being present in the rat adrenal gland.
The content of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and norepinephrine (NE) was analysed in 71 human spinal cords obtained post-mortem. The highest content of 5-HT, 5-HIAA and NE was found in the lumbar enlargement of the spinal cord. 5-HT and 5-HIAA content increased from fetal to adult spinal cord whereas the content of NE decreased. Characteristic segmental distribution of measured monoamines was present in adult spinal cord only. In two patients spinal cord lesion led to the reduction in spinal cord content of 5-HT, 5-HIAA and NE and loss of characteristic segmental distribution of these substances. These results are in general agreement with observations on spinal cord of different animal species.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The hypothesis presented in this paper is that dopamine (DA) is a widely distributed neurotransmitter and/or cotransmitter in the autonomic nervous system. This hypothesis is based on the following evidence. Morphologically, DA-containing neurons have been demonstrated in autonomic ganglia, and dopaminergic axons have been identified in kidney and canine paw pad. On the basis of pharmacological experiments, the existence of dopaminergic nerves was suggested in vas deferens, stomach, and mesenteric artery. Biochemically, we found intensive catabolism of DA in different peripheral tissues of the rat and human. Furthermore, dopaminergic receptors have a widespread distribution in the body, and a high concentration of DA occurs in plasma with only some originating from the adrenal gland. The concentration of plasma DA closely reflects the activity of the autonomic nervous system. These observations together with our finding of relatively high concentrations of DA and its metabolites in several peripheral nerves suggest the possibility of a widely distributed peripheral dopaminergic system.
Specific dopaminergic recognition sites were identified in membranes prepared from rat vas deferens with the ligand (3H)-haloperidol. Specific binding, defined as the difference of (3H)-haloperidol binding in the presence or absence of an excess of unlabelled haloperidol (100 microM), was saturable and a Scatchard analysis of the data revealed a Kd = 21 nM and a Bmax = 74 fmol/mg prot. (+)-Butaclamol was several times more active in displacing (3H)-haloperidol from binding sites than its pharmacologically inactive enantiomer, (-)-butaclamol, demonstrating stereospecificity of binding. Dopamine displaced 50% of (3H)-haloperidol binding at a concentration of approximately 10 microM, while norepinephrine, epinephrine and serotonin were practically ineffective at this concentration. Our results support the notion that there are dopaminergic receptors in the rat vas deferens. We speculate that some of the known effects of dopamine and dopaminergic drugs on sexual behavior may be mediated peripherally and not solely via the CNS as is usually assumed.
Dopamine (DA) and its metabolites, homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC), have been measured in peripheral tissues of the rat and human by gas chromatography-mass spectrometry. The content of HVA and DOPAC in peripheral tissue is higher than in blood and is usually higher than the content of DA. In the rat, chemical denervation with 6-hydroxydopamine decreased the tissue content of DOPAC. Inhibition of monoamine oxidase increased tissue DA. Apparently, in vivo, a large quantity of peripheral DA is catabolized rather than converted to norepinephrine (NE). These observations suggest that either NE synthesis is inefficient, with a large quantity of DA wasted and not converted to NE, or that DA is physiologically utilized as a neurotransmitter and/or cotransmitter in many peripheral nerves. A survey of the reported actions of DA on peripheral tissues suggests that the latter proposal is more likely.