Caffeic acid phenethyl ester modulates methotrexate-induced oxidative stress in testes of rat.

The aim of this study was to investigate the possible protective role of caffeic acid phenethyl ester on testicular toxicity of methotrexate in rats. Nineteen male rats were divided into three groups as follows: group I, control; group II, methotrexate-treated; group III, methotrexate + caffeic acid phenethyl ester-treated. In the second day of experiment, a single dose of methotrexate was intraperitoneally administered to groups II and III, although a daily single dose of caffeic acid phenethyl ester was intraperitoneally administered to group III for 7 days. At the end of the experiment, the testes of the animals were removed and weighed. In the tissue, the level of lipid peroxidation as malondialdehyde and activities of superoxide dismutase were higher in the methotrexate group than in the control group. Lipid peroxidation levels and superoxide dismutase activities were decreased in caffeic acid phenethyl ester + methotrexate group compared with methotrexate group. The activities of catalase in the methotrexate group decreased insignificantly although its activities were significantly increased by caffeic acid phenethyl ester administration. The activity of glutathione peroxidase did not change in the groups. There was significant difference in body weight between control and methotrexate-induced groups. In conclusion, the administration of methotrexate causes elevation of oxidative stress although treatment with caffeic acid phenethyl ester has protective effects on the oxidative stress in testes.

The role of ultrasonographic measurements of the median nerve in the diagnosis of carpal tunnel syndrome.

AIM: The aim of study was to assess the usefulness of ultrasonographic measurements of the median nerve in the diagnosis of carpal tunnel syndrome. MATERIALS AND METHODS: Eighty-six patients with carpal tunnel syndrome confirmed by electromyography and 45 asymptomatic controls were included in the study and underwent high-resolution ultrasonography of the wrists. The cross-sectional area and flattening ratio at the level of the pisiform bone of the proximal carpal tunnel were measured. Data from the patient group and control group were compared to determine the statistical significance. The accuracy of the ultrasonographic diagnostic criteria for carpal tunnel syndrome was evaluated using receiver-operating characteristic (ROC) analysis. RESULTS: One hundred and forty-eight wrists of 86 patients with carpal tunnel syndrome and 76 wrists of 45 control patients were examined. All measurements showed significant differences between patients and controls. Increased cross-sectional area of the median nerve was the most predictive measurement of carpal tunnel syndrome. Using the ROC curve, a cut-off value of >10.5 mm2 at the level of pisiform bone provided a diagnostic sensitivity of 89% and specificity of 94.7% CONCLUSION: The ultrasonographic measurement of the median nerve cross-sectional area is a sensitive, specific and useful non-invasive method for the diagnosis of carpal tunnel syndrome.

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.

Comparison of open carpal tunnel release and local steroid treatment outcomes in idiopathic carpal tunnel syndrome.

To compare the efficacy of local steroid injection and open carpal tunnel release, a symptom and functional status questionnaire (Boston Questionnaire) and sensory and motor nerve conduction studies were performed in 90 patients with electrophysiologically proven idiopathic carpal tunnel syndrome, of whom 44 were treated surgically and 46 by two-dose steroid injection. Electrophysiologic studies and the Boston Questionnaire were applied before and at the 3rd and 6th months after treatment. Both groups showed significant improvement at first follow-up. The surgically treated group showed a significant and further improvement of symptoms and conduction values between the 3rd- and 6th-month evaluations, whereas no significant change was observed in the patient group treated by steroid injection. By the end of follow-up, 5% of the hands in the open carpal tunnel release (OCTR) group and 13% of the hands in the local steroid injection (LSIG) group showed electrophysiological worsening, and 5% of the hands in the OCTR group and 22% of the hands in the LSIG group showed symptomatic worsening. Our results show that steroid injection provides an improvement comparable with that from surgical release of the median nerve at a 3-month interval. However, this improvement is not long-lasting.

Carpal tunnel syndrome in carpet workers.

OBJECTIVE: Repetitive and forceful use of wrist and finger flexors is purported to be an occupational risk factor for carpal tunnel syndrome (CTS). While weaving carpet, wrist and finger flexors and extensors are used repetitively, with pinching movements and forced grasping. We aimed to investigate CTS frequency in hand-made carpet workers. METHODS: Seventy women from carpet workshops in the city center and 30 healthy unemployed women were evaluated by clinical examination and electrophysiology. The relationship between CTS development and employment duration, and work produced per year were also investigated. Our study is cross-sectional. RESULTS: CTS was present in 31 hands (22.1%) of workers and in four hands (6.7%) of the control group. The estimated relative risk of developing CTS was 3.3 times greater in carpet-workers than it was in controls. Considering all hands, we could not find any correlation between CTS development and employment duration (P = 0.977), or with work produced per year (P = 0.505); but these two were the prominent factors contributing to delayed median sensory latency (P = 0.013, P = 0.009, respectively). CONCLUSIONS: We could not find any correlation between CTS development and employment duration, or with work produced per year; but these two were the prominent factors contributing to delayed median sensory latency The results indicates that women working in the hand-made carpet industry have a higher risk of CTS development.

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.

Acupuncture therapy in the management of persistent primary nocturnal enuresis--preliminary results.

OBJECTIVE: This study aimed to assess the comparative therapeutic efficacy of traditional Chinese acupuncture. MATERIAL AND METHODS: During the period from January 1997 to April 1999, 50 children (23 boys, 17 girls) suffering from primary persistent nocturnal enuresis, aged 9-18 years, were included in the study. The response rate was monitored at 2 and 4 weeks, and then every 3 months by recording dry nights on a calendar. RESULTS: The efficacy of treatment, which was expressed as a percentage of dry nights, was high. Within 6 months, 43 (86%) patients were completely dry and 2 (10%) patients were dry on at least 80% of nights. CONCLUSIONS: Treatment using acupuncture in patients with persistent enuresis nocturna appeared to be most efficacious both in terms of the percentage of dry nights at the end of treatment and in relation to the stability of results, even after the end of the study.

Is there any change of stroke incidence during Ramadan?

Ramadan is a special month for Muslims, as fasting during Ramadan is a religious duty. In this study we investigated whether stroke incidence differs during Ramadan compared to other months. All patients with stroke admitted to any hospital in the Isparta Province between 1991-1995 were included in this study. Patients were divided into 2 groups according to the month of onset of stroke. The first group included patients with strokes that occurred in Ramadan and the second group strokes with onset in other months. The stroke incidence of Isparta has been found to be 137 per 100,000 for people older than 25 years. There were no statistically significant differences between the age and sex distribution of patients and the incidences of strokes in both groups. We concluded that fasting during Ramadan has no affect on stroke occurrence in the Isparta Province.

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.

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.

Gamma-vinyl-GABA potentiates the severity of naloxone-precipitated abstinence signs in morphine-dependent rats.

Effects of gamma-vinyl-GABA (GVG), an antiepileptic drug that inhibits GABA transaminase and increases extracellular GABA concentrations in the brain, were investigated on the morphine abstinence syndrome (AS) in male Wistar rats. Two morphine pellets (75 mg morphine base in each) were implanted subcutaneously on the back of the rats. Seventy-two hours after the morphine implantation, naloxone (NL, 2 mg kg-1) was injected intraperitoneally (i.p.) to induce precipitated morphine AS. GVG was administered at the doses of 250 mg kg-1 (n = 11) and 500 mg kg-1 (n = 11) i.p. 24 h prior to AS and at the dose of 500 mg kg-1 (n = 13) i.p. 6 h prior to AS. Immediately after NL injections, rats were observed for 5 min and AS signs (jumping, teeth chattering, wet dog shake, diarrhoea, ptosis and defecation) were assessed. The behavioural signs of GVG-treated rats were compared with the control groups (n = 10) during the AS. Jumping, wet dog shake, teeth chattering were found to be significantly increased in all of the GVG-treated groups. Ptosis was found to have increased in only 500 mg kg-1 GVG groups. GVG potentiated the severity of morphine AS signs. GVG does not seem to have any therapeutic potential for treatment of morphine abstinence unlike some other drugs that enhance GABAergic transmission.

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.

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.

Epidemiology of enuresis in Turkish children.

To establish the prevalence of enuresis in Turkish children and to identify common methods of managing enuresis, a self-administered questionnaire was distributed to parents of 5754 children aged 7-12 years. From a response rate of 96% the overall prevalence of any reported nocturnal enuresis was 11.5% and diurnal enuresis was 0.5%. The prevalence of enuresis was higher in boys than in girls. Turkish parents primarily administered behavioural techniques for the management of enuresis. These results suggest that prevalence rates for nocturnal enuresis in Turkish children are similar to those in previous studies reported from Western Europe, the USA and Australia.

The combination of tizanidine markedly improves the treatment with dextromethorphan of heroin addicted outpatients.

According to the hypothesis implying that the main mechanism underlying opiate addiction is the blockade by opiates of NMDA receptor functions and subsequent upregulation and supersensitivity of the receptors, noncompetitive NMDA receptor blocker dextromethorphan (DM) has been successfully used in the heroin addict treatment. As the stimulation of NMDA receptors modulates the release of neurotransmitters and hormones such as NE, D, ACh, GH, LH, LSH, ACTH etc., all of which have been found responsible for the manifestation of abstinence syndrome signs including craving and neuronal death by excessive stimulation of NMDA receptors, the incomplete blockade of the NMDA receptors minimizes the intensity of the abstinence syndrome and provides the downregulation of the receptors. In the present study, tizanidine (TIZ), which inhibits the release of endogenous excitatory aminoacids by the agonistic activity on alpha 2-adrenoreceptors, was combined with DM to obtain further benefits. Forty-four male and three female heroin addicts were the subjects of the study. Their daily mean heroin intake was about 2.28 g street heroin. The main duration of heroin use was approximately 3.4 years. Two to three hours after abrupt withdrawal, the outpatients were given 15 mg DM every hour, 25 or 50 mg chlorpromazine (CPZ) + 4 mg TIZ every six hours and 10 mg diazepam + 10 mg hyoscine N-butyl Br + 250 mg dipyrone every six hours three hours following CPZ. The addicts were controlled twice a day. Yawning, rhinorrhea, perspiration, piloerection, restlessness, insomnia, emesis, diarrhea, craving, rejection of smoking and pupils were observed and/or questioned. Two of the 47 outpatients took heroin on the first days.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnostic value of electrical stimulation of lumbosacral roots in radiculopathies.

Needle electrical stimulation of the lumbosacral roots at the laminar level of the Th12-L1 or L1-2 intervertebral spaces were performed in 24 normal subjects and 58 patients with various kinds of lumbar radiculopathy (unilateral L4, L5 and S1 herniated nucleus pulposus and lumber stenosis). The root stimulation method was compared with conventional needle EMG. Lumber electrical stimulation showed root abnormalities objectively in 80% of patients while the diagnostic value of needle EMG was 65%. Therefore, electrical root stimulation is superior to routine EMG for localizing lumbar root involvement. However, the only needle EMG demonstrated the root pathology in 7 cases (12%) and single electrophysiological abnormality was found by the root stimulation in 16 cases (27%). Thus, both electrophysiological methods should be complementary to each other in evaluation of the lumbar radioculopathy.

Morphine physical dependence intensification by hypoglycemia: NMDA receptor involvement.

The destruction of N-methyl-D-aspartate (NMDA) receptor-bearing neurons by insulin-induced hypoglycemia has long been known to be due to excessively released aspartate and glutamate. In this study, the effects of NMDA-bearing neuron destruction by insulin-induced hypoglycemia on the development of morphine (M) physical dependence, which was found related to functional states of NMDA receptors, were investigated. NMDA receptor antagonists CGP 39551 and MK-801 were used to see whether they could change intensity of precipitated abstinence syndrome by preventing destruction. Therefore, two groups of fasting rats injected IP with physiological saline, and another two groups given IP 10 mg/kg CGP 39551 and 0.5 mg/kg MK-801 received 15 IU/kg crystalline zinc insulin IP. After 2 h, the rats were orally given 2 x 4 ml of 5% glucose solution. On the third day, two pellets containing 75 mg base M were SC implanted to all rats. On the sixth day, they were IP given 2 mg/kg naloxone (NL). Then jumps, wet-dog shakes, and defecation were counted while diarrhea and ptosis were rated for 15 min. The rats given insulin manifested significantly more intense NL-precipitated abstinence syndrome than controls. The rats administered CGP 39551 showed a less intense physical dependence than those injected with only insulin. But, the intensity was still significantly higher than controls. In the rats that received MK-801, the abstinence syndrome was more or less equal to that in controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Prenatal exposure to morphine or naloxone intensifies morphine dependence at maturity.

Pregnant rats were SC injected with physiological saline (control) or 10 mg/kg morphine (morphine group) or 2 mg/kg naloxone (naloxone group) three times daily during the last 5 days of gestation. Three weeks after birth, male young rats of each group were taken and placed in separate cages. When their body weight reached 130-150 g, 10 rats from control, morphine, and naloxone groups were SC implanted with two pellets containing 75 mg morphine base (total 150 mg). Three days following implantation, rats were IP given 2 mg/kg naloxone for precipitated abstinence syndrome. Immediately after naloxone injection, rats were strictly observed for 15 min and jumping, wet-dog shakes, teeth-chattering, diarrhoea, defecation, and ptosis counted or rated. All abstinence syndrome signs were significantly higher in the morphine or naloxone group than in control. On the basis of the previous experimental findings supporting the idea that opiate physical dependence is related to the binding of opiate, possibly other than their own, to NMDA receptors and the upregulation and/or supersensitivity associated with the binding, the intensification of morphine dependence has been attributed to the long-lasting NMDA receptor upregulation and/or supersensitivity.