Biomedical subjects

A Nurten

Publications and source records attributed to A Nurten.

7 recordsLinked to original sources

PubMed2004

TGF-beta1 neutralizing antibodies decrease the fibrotic effects of ischemic priapism.

The objective of this study was to evaluate the possible role of transforming growth factor beta 1 (TGF-beta1) antibodies (ab) for the prevention of fibrotic effects of priapism in a rat model. In total, 30 adult Sprague-Dawley rats were divided into five groups. Priapism with 6 h (group 1), priapism with 6 h+ab (group 2), priapism with 24 h (group 3), priapism with 24 h+ab (group 4) and control (group 5). Priapism was induced with a vacuum erection device and a rubber band was placed at the base of the erect penis. At 1 h after the initiation of priapism, TGF-beta1 antibodies were given intracavernosaly. All rats underwent electrical stimulation of the cavernous nerve after 8 weeks. Intracavernous and systemic blood pressures were measured during the procedure. Rats in group 1 showed significantly higher (intracavernosal pressure (ICP) pressures to cavernous nerve stimulation and had higher ICP/BP ratios when compared to other groups. Similarly, histopathologic examination revealed less fibrosis in group 2, compared with the other groups. Consequently, TGF-beta1 antibodies antagonise the fibrotic effects of TGF-beta1, especially in cases with duration of priapism less than 6 h.

Animals↗

PubMed2003

Scopolamine-induced convulsions in fasted mice after food intake: determination of blood glucose levels, [3H]glutamate binding kinetics and antidopaminergic drug effects.

The present study was performed to evaluate the role(s) of hypoglycemia, changes in [(3)H]glutamate binding kinetics and dopaminergic activity in the occurrence of scopolamine-induced convulsions in fasted mice after food intake. Plasma glucose levels and density (B(max)) and affinity (K(d)) of [(3)H]glutamate binding sites in whole brain synaptic membranes were determined in animals fed ad lib or fasted for 48 h and treated intraperitoneally (i.p.) with 3 mg/kg scopolamine or saline and allowed to eat for 5 min. Fasting for 48 h decreased plasma glucose levels. After refeeding, plasma glucose concentrations increased in saline treated animals, but remained unchanged in scopolamine treated animals which consumed less food. Fasting for 48 h also produced significant changes in the kinetics of [(3)H]glutamate binding. The B(max) and K(d) of the binding sites decreased in fasted animals. These changes were partially antagonized by scopolamine treatment and food intake. For the evaluation of the contribution of dopaminergic activity, another group of mice fasted for 48 h and pretreated (i.p.) with saline or dopamine antagonists, 2 mg/kg chlorpromazine or 2 or 4 mg/kg haloperidol, were treated 10 min later with either saline or 3 mg/kg scopolamine. Then 20 min later, they were allowed to eat ad lib and were observed for 30 min for the incidence and onset of clonic convulsions. Pretreatment of both 2 mg/kg chlorpromazine and 4 mg/kg haloperidol markedly suppressed the convulsions. These results indicate that the decrease in the [(3)H]glutamate binding induced by fasting, its antagonism by scopolamine treatment and food intake, and the dopaminergic hyperactivity may be possible factors contributing to the occurrence of convulsions.

Animals↗

PubMed2001

The effects of different 4-aminopyridine and morphine combinations on the intensity of morphine abstinence.

The glutamatergic system is deeply involved in the development of opiate dependence and in the manifestation of opiate abstinence syndrome. In this study the effect of the increase in the endogenous glutamate (GLU) release due to 4-aminopyridine (4-AP), a potassium channel blocker, during the development of morphine (M) physical dependence and during the naloxone (NL)-precipitated abstinence syndrome was investigated. For the development of physical dependence M was intraperitoneally (i.p.) injected for 9 days 105 min following i.p. saline administration to a group of rats. In the first 3 days the dose of M was 10 mg x kg(-1). In the second 3 days the initial dose was doubled (20 mg x kg(-1)) and in the last 3 days the dose of M was raised to 40 mg x kg(-1). On day 10, the rats were divided into three groups at random and these three groups were i.p. given saline 105 min before 80 mg x kg(-1)M, 2 mg x kg(-1) 4-AP 105 min after 80 mg x kg(-1) M, and 80 mg x kg(-1) M 105 min before 2 mg x kg(-1) 4-AP, respectively. In a second group of rats, the rats were i.p. given 2 mg x kg(-1) 4-AP 105 min prior to M administration, which was increased every 3 days (10 mg x kg(-1), 20 mg x kg(-1), 40 mg x kg(-1)). On day 10, the rats were divided into two groups whose first injection was saline and 2 mg x kg(-1) 4-AP, respectively. The second injections of both groups after an interval of 105 min following the first one contained 80 mg x kg(-1) M. In contrast, one group of rats received only i.p. saline at every other injection time (the control group). Furthermore, another group of rats was i.p. administered 2 mg x kg(-1) 4-AP once a day, as the first injection. At the second injection time they were i.p. given saline. After a period of 15 min following the last administration on day 10, the rats belonging to all groups were i.p. injected with 2 mg x kg(-1) NL and immediately placed in a metal cage. Body weight loss (g), teeth chattering, rearing, wet-dog shaking, grooming, and jumping were determined or counted for 15 min. Penile erection, defecation, and diarrhoea were separately scored with one point for every individual occurrence, and the total score was named 'total number of others'. The administration of 4-AP before M appeared to intensify the development of dependence, and was most probably due to the Ca2+-induced inactivation of NMDA receptors as a result of excess release of GLU when the 4-AP took effect. The inactivation of NMDA receptors should have acted as a transient blockade of the receptors during the chronic administration period, and as well as after a single administration on day 10 before M injection and before abstinence. The intensification of the abstinence syndrome may be dependent on the excessive GLU released by 4-AP.

4-Aminopyridine↗

PubMed1999

The importance of the number of NMDA receptors in the development of supersensitivity or tolerance to and dependence on morphine.

Opiate or NMDA receptor antagonists given during and/or after the development of tolerance and dependence have been reported to prevent these developments. In the present study, MK801 (dizolcipine) and naltrexone (NX), two antagonists of NMDA and opiate receptors, respectively were used in rats to find any correlations between changes in NMDA receptor kinetics, and the intensity of tolerance and dependence. Thus, six different groups of rats were formed. The rats in the groups were given saline (S)+S, S+morphine (M), NX+S, NX+M, MK801+S and MK801+M, respectively, once per day for 8 days. On day 9, the rats from each group were divided into four subgroups. The rats of the first subgroup were subjected to the determination of tail-flick latency. The rats of the second subgroup were administered 1 mg kg-1 naloxone (NL) 2 h after administration of 3 mg kg-1M. The rats of the third subgroup were implanted with two M pellets and after 72 h they were challenged with NL. The remaining rats received drugs also on day 9 according to the previous administration paradigm. Two hours after the administrations, their brains were utilised for the determination of NMDA receptor kinetics, employing [3H]glutamate. The measurement of tail-flick latency showed the prevention by NX or MK801 of the development of tolerance to M. The rats, which were administered 3 mg kg-1M 2 h before 1 mg kg-1 NL injection, on day 9 showed that only NX given previously along with M attenuated the intensity of the development of M dependence. NX administered alone intensified the development of dependence on a single dose of M. The development of M dependence upon the M pellet implantation was intensified by the previous administration of NX or MK801 concomitantly with M. The administration of M or MK801 alone, or NX together with M, caused significant upregulation of NMDA receptors. NX alone, and MK801 given concurrently with M led to a significant downregulation. So, in light of the previous findings and the present experimental data it can be said that: (1) supersensitivity to opioids may be a downregulation of NMDA as well as an upregulation of the opioid receptor; (2) either upregulation or downregulation of NMDA receptors may facilitate subsequent development of opioid dependence; (3) tolerance to opioid may necessitate both upregulation of NMDA receptors and downregulation of opioid receptors; and (4) beneficial effects of opioid antagonists in the treatment of opiate dependence and CNS injuries may be strongly related to the down regulation of NMDA receptors.

Analgesics, Opioid↗

PubMed1999

Scopolamine-induced convulsions in food given fasted mice: effects of clonidine and tizanidine.

We recently reported that scopolamine pretreated mice fasted for 48 h developed clonic convulsions soon after they were allowed to eat ad libidum. Pretreatment with MK-801, the non-competitive NMDA antagonist, decreased the incidence of these convulsions. We suggested that a possible scopolamine-induced glutamatergic hyperactivity could account for these convulsions. Using alpha2-agonists, clonidine, which has been shown to inhibit glutamate release, and tizanidine, the present study was performed to find some additional data for the role of glutamate in the underlying mechanism of scopolamine-induced convulsions in food given fasted mice. Animals fasted for 48 h and pretreated (i.p.) with saline, clonidine (0.05, 0.10, 1 mg/kg) or tizanidine (0.10, 0.15, 0.30, 0.45 mg/kg) were treated (i.p.) with either saline or scopolamine (3 mg/kg). Then 20 min later, they were allowed to eat ad libidum and were observed for 30 min for the incidence and onset of clonic convulsions. All doses of clonidine pretreatment completely suppressed (0%) scopolamine-induced clonic convulsions (75%). On the other hand, only 0.15 mg/kg tizanidine pretreatment significantly decreased (15%) the incidence of convulsions; however as well as 0.15 mg/kg, both 0.30 and 0.45 mg/kg tizanidine pretreatments significantly increased latency to the onset of convulsions.

Animals↗

PubMed1998

N-methyl-D-aspartate antagonists, glutamate release inhibitors, 4-aminopyridine at neuromuscular transmission.

It is thought that glutamate (GLU) and acetylcholine (ACh) are co-released in the neuromuscular junction (NMJ). Consequently, GLU is also a mediator or modulator of neuromuscular transmission (n-m) together with ACh. Therefore we decided to investigate the role of GLU in n-m by using isolated rat phrenic nerve-hemidiaphragm preparations. Since the GLU receptors present at NMJ have been reported to be predominantly N-methyl-D-aspartate (NMDA) subtype, some non-competitive and competitive NMDA receptor blockers, MK801, ketamine, dextromethorphan and CGP 37849, and GLU release inhibitors, clonidine, guanfacine, tizanidine were used at their optimum concentrations in medium after having found them from dose-response curves. The preparations were first stimulated indirectly in the presence of the optimum concentrations of the drugs used and tensions developed were recorded isometrically through a force displacement transducer on a polygraph linked to a computer + Math coprocessor by an analog converter. All drugs at their optimum concentrations suppressed contractions significantly. Prolyl-glycinamide (PLG) or phenyl-succinate, both of which are the inhibitors of GLU production also suppressed the contraction significantly, following depletion of GLU stores by tetanic contraction in nerve endings. 4-Aminopyridine, which has been shown to release GLU augmented the contractions which were also completely abolished by the NMDA receptor antagonists or GLU release inhibitors at their higher concentrations than their optimum ones. The direct stimulation of the muscles elicited statistically insignificant but higher contractions than controls at the optimum concentrations of the antagonists or inhibitors in medium. The results were discussed and it was concluded that blockade of NMDA receptors, the inhibition of GLU released or the suppression of GLU production inhibit the contractions of the rat-isolated hemidiaphragms elicited by indirect electrical stimulation, without altering acetylcholinergic part of the contraction cascade.

2-Amino-5-phosphonovalerate↗

PubMed1997

Scopolamine-induced convulsions in food given fasted mice: effects of physostigmine and MK-801.

We recently reported that scopolamine pretreated mice fasted for 48 h developed clonic convulsions soon after they were allowed to eat a small amount of food for 30 s. The present experiments were performed to determine whether animals also develop convulsions when they were allowed to eat ad libitum and to find some evidence for the contribution of the cholinergic and/or glutamatergic systems in the underlying mechanism(s) of convulsions. Animals fasted for 48 h were treated with 3 mg/kg scopolamine or saline. Twenty minutes later, they were allowed to eat either ad libitum or a small portion of food for 30 s. Scopolamine pretreated animals after starting to eat ad libitum or a small amount in a restricted time developed convulsions in a few minutes, the incidence being 76 and 54%, respectively. Pretreatment of 0.17 mg/kg MK-801, the noncompetitive NMDA antagonist, decreased the incidence of scopolamine-induced convulsions (22%) without affecting latency to the onset of seizures. Pretreatment of 0.1 mg/kg physostigmine, the cholinesterase inhibitor, changed neither the incidence (90%) nor latency to the onset of scopolamine-induced convulsions.

Animals↗