Measurement of Isfahan heavy water zero-power reactor kinetic parameters using advanced pulsed neutron source method in a near critical state.

The pulsed neutron source (PNS) technique was used to determine the prompt neutron decay constant for two different lattice pitches in the HWZPR heavy water zero power reactor. The results were compared to the variance-to-mean ratio (VTM) method. The neutron mean generation time was also calculated for both pitches, and the results were compared to previous Monte Carlo calculations. The findings of this research can be used as a benchmark nuclear codes to validate kinetic parameters.

Experimental insights into the stability of graphene oxide nanosheet and polymer hybrid coupled by ANOVA statistical analysis.

The synergistic potential of using graphene oxide (GO) nanosheets and hydrolyzed polyacrylamide (HPAM) as GO enhanced polymer hybrid (GOeP) for enhancing oil recovery (EOR) purposes has drawn attention. However, the hybridization method and stability of GOeP have not been comprehensively studied. To cover this gap, the current study evaluates the stability of GOeP under different conditions, including temperatures such as 60 and 80 °C, high and low salinities, and the presence of Mg2+ ions (6430 and 643 ppm). Hence, GO nanosheets were synthesized and characterized through XRD, Raman, FTIR, and DLS techniques. The performance of five preparation methods was assessed to determine their ability to produce stable hybrids. Zeta potential and sedimentation methods, coupled with the ANOVA statistical technique, were used for measuring and interpreting stability for 21 days. Results revealed that the stability of GOeP in the presence of brine is influenced by hydrolyzation duration, the composition of the water used in polymer hydrolyzation, the form of additives (being powdery or in aqueous solution), and the dispersion quality, including whether the GO solution was prediluted. The results revealed that the positive impact of higher temperatures on the long-term stability of GOeP is approximately seven times less significant than the reduction in stability caused by salinity. Under elevated salinity conditions, a higher Mg2+ concentration led to an 80% decrease in long-term stability, whereas the temperature impact was negligible. These findings highlight the potential of GOeP for EOR applications, offering insights into optimizing stability under challenging reservoir conditions.

Evaluation of nutritional status in patients undergoing hematopoietic SCT.

The aims of this study were to establish the nutritional status of patients during hematopoietic SCT (HSCT) and to determine if body mass index (BMI) is a valid indicator of nutritional status in this population when compared with nitrogen balance (NB). In total, 50 patients were enrolled (mean age: 25.7+/-9.0 years). Patients (14%) were underweight (BMI<18.5 kg/m(2)), 58% in a normal BMI (between 18.5 and 24.9 kg/m(2)) and 28% were overweight or obese (BMI >or= 25 kg/m(2)). NB dropped after transplantation and increased from days +5 to +20 after transplantation (P=0.006). There was a significant negative relationship between patients' BMI and time to engraftment (r=-0.45, P=0.001). Engraftment of underweight patients was 3.0 days (P=0.002) and 4.0 days (P<0.001) later than in normal and overweight or obese patients, respectively. There was no significant correlation between NB before transplantation and time to engraftment (r=-0.22, P=0.16). The results of this study demonstrate that patients undergoing HSCT may have suboptimal nutritional status and that pre-HSCT-BMI rather than NB may have a greater correlation in HSCT patients with the time of engraftment. Therefore, it may be useful to consider patient's BMI before transplantation for earlier engraftment time.

Fludarabine and busulfan as a myeloablative conditioning regimen for allogeneic stem cell transplantation in high- and standard-risk leukemic patients.

Busulfan and cyclophosphamide (BuCy) are currently the most widely used myeloablative regimen to treat malignancies with allogeneic stem cell transplantation. Fludarabine has considerable efficacy in both immunosuppression and tumor cells killing with a minimal extramedullary toxicity. We evaluated the efficacy of 40 mg/m(2) fludarabine i.v. for 5 days and busulfan 4 mg/kg/day p.o. for 4 days as myeloablative conditioning regimen in 70 patients (median age 24 years) with acute leukemia or chronic phase of myelogenous leukemia. They all had human leukocyte antigen-matched sibling donors. The patients received 10 mug/kg granulocyte colony stimulating factor (GCSF), 24 h after stem cell infusion until engraftment occurred. Graft-versus-host disease (GVHD) prophylaxis included 3 mg/kg cyclosporine-A i.v. from day -2 to +6 followed by 12 mg/kg p.o. until day +60. The median time of neutrophil recovery (>0.5 x 109/l) and platelet recovery (>20 x 109/l) were 10 and 12 days, respectively. Mucositis (93%) and hepatic toxicity (16%) resolved with conservative therapy. The incidence of acute GVHD grade I-II and III-IV were 38.6 and 15.7% respectively. Overall survival and disease-free survival were 71 and 64% respectively with 17 months median follow-up for surviving patients. We conclude that FluBu may be used as a substitute for BuCy with almost the same efficacy and with a lower transplant adverse effect but to increase anti-leukemic effects, especially in acute lymphoblastic leukemia patients, it needs some modifications.

3-Nitrotyrosine-dependent dopaminergic neurotoxicity following direct nigral administration of a peroxynitrite but not a nitric oxide donor.

The presence of 3-nitrotyrosine (3-NT) adducts in Lewy bodies in Parkinson's disease suggests a role for nitrative stress in dopaminergic cell death. Whether this is a direct effect of increased nitric oxide (NO) formation or requires its reaction with superoxide to form peroxynitrite is not clear. In the present study, we show that direct nigral administration of a NO donor, SNOG, in the rat produced only local toxicity to dopaminergic neurones pre-labeled with fluorogold with no 3-NT formation. However, administration of a peroxynitrite donor, SIN-1, caused widespread damage to dopaminergic neurones and marked expression of 3-NT immunoreactivity. Importantly, dopaminergic cell loss and the expression of 3-NT were completely prevented when SIN-1 was co-administered with the NO/peroxynitrite scavenger, carboxy-PTIO. The results suggest that increased NO formation is not inherently toxic to dopaminergic neurons, but when both oxidative and nitrative stress combine to cause peroxynitrite formation, neurotoxicity occurs.

Methylation of the multi tumor suppressor gene-2 (MTS2, CDKN1, p15INK4B) in childhood acute lymphoblastic leukemia.

The multi tumor suppressor genes MTS1 (CDKN2 p16INK4A) and MTS2 (CDKN1, p15INK4B) located at 9p21-22 are inactivated in some human cancers via several mechanisms including deletion and hypermethylation. We have investigated the deletion and methylation status of MTS1 and MTS2 in childhood acute lymphoblastic leukemia (ALL) of both T-cell (17 cases) and B-cell phenotypes (29 cases), and p16INK4A and p15INK4B mRNA expression in 36 of these cases. Biallelic or monoallelic loss of both MTS1 and MTS2 was observed in 12 cases of B-ALL and nine cases of T-ALL. Two cases of T-ALL showed deletion of MTS1 but not MTS2. The 5' CpG region of MTS2 was hypermethylated in 12 cases of precursor B-ALL and eight cases of T-ALL but no hypermethylation was found in the 5' CpG region of MTS1. All cases with homozygous deletion of MTS1 or MTS2 had no or low levels of mRNA expression and similar low levels of expression were found in cases in which MTS2 was present but fully methylated. Thus hypermethylation of MTS2, in contrast to MTS1, is frequent in childhood ALL. Furthermore our data show that although inactivation of MTS1 by deletion is common, inactivation of MTS2 by a combination of deletion and hypermethylation is more frequent in both B-ALL (20/29, 69%) and T-ALL (17/17, 100%). This suggests that both MTS1 and MTS2 are important targets of the 9p21-22 deletion.

Cyclosporin A and mini short-term methotrexate vs cyclosporin A as graft-versus-host disease prophylaxis in patients with beta thalassemia major undergoing allogeneic blood and marrow transplantation.

We compared the effects of cyclosporin A (CsA) alone as graft-versus-host disease (GVHD) prophylaxis vs cyclosporine with short-course methotrexate (MTX) in patients with thalassemia. In all, 140 patients were enrolled in this study. The first group, of 50 patients, received CsA alone at 3 mg/kg i.v. from day -2 to +5 followed by 12.5 mg/kg p.o., which was tapered according to the patient's condition. The other group, of 90 patients, received the combination of CsA+MTX in which CsA was used with the above-mentioned dose and MTX was on 10 mg/m(2) day +1 and 6 mg/m(2) on days +3 and +6. Incidence of acute GVHD grade II-IV in the CsA group was 78% and in the CsA+MTX group was 52.2%, which was statistically significant (P=<0.001). There were no significant differences in the incidence of chronic GVHD between the two groups. The mean neutrophil engraftment to 0.5 x 10(9)/l was 14 and 23 days for CsA group and CsA+MTX group, respectively (P=<0.001). There were no significant differences for platelet recovery between the two groups. Graft failure in the CsA and CsA+MTX groups was seven (14%) and nine (10%) patients, respectively (P=0.58). Overall survival in the CsA and CsA+MTX groups was 77 and 85%, respectively. Disease-free survival in the CsA and CsA+MTX groups were 58 and 80%, respectively.

Genome-wide screening for genetic changes in a matched pair of benign and prostate cancer cell lines using array CGH.

Copy number alterations in a matched pair of benign epithelial and prostate cancer cell lines derived from the same patient were assessed using array-based comparative genomic hybridisation (aCGH). The cancer cell line showed a gain of chromosome 7, deletion of chromosome 8, gains (including high level) and losses on chromosome 11, loss of 18p and gain of 20q. Deletions on chromosome 8 were confirmed with microsatellite markers. The aCGH results were compared to gene expression data obtained using DNA microarrays and suggested the involvement of caspases and ICEBERG on 11q and E2F1 on chromosome 20q.

Diagnostic procedures for catheter malfunction in programmable implantable intraperitoneal insulin infusion devices.

OBJECTIVE: To evaluate the roles of 1) abdominal radiography, 2) a pressure diagnostic procedure (PDP) using a standardized diluent infusion into the catheter sideport, and 3) radiocontrast imaging of the catheter lumen as procedures for diagnosing catheter malfunction in diabetic patients implanted with a programmable intraperitoneal infusion device. RESEARCH DESIGN AND METHODS: Sixteen type I diabetic patients implanted with Infusaid programmable intraperitoneal insulin pumps were studied. The ability of the above three procedures to assist diagnosis of catheter malfunction and distinguish between occlusion and catheter breakage was retrospectively analyzed. Glycated hemoglobin was measured to determine the clinical importance of catheter malfunctions and decreases in pump flow due to insulin aggregation in the pump chamber. RESULTS: Mean glycated hemoglobin levels increased significantly from 8.0 +/- 0.3 to 9.0 +/- 0.4% (P < 0.05) before and after catheter malfunction, but not during pump flow slowdowns. Mean peak pressure during PDP was 1.96 +/- 0.14 psi (P < 0.01 vs. normal) in reversibly occluded catheters and 1.86 +/- 0.35 psi (P < 0.05 vs. normal) in broken catheters, compared with 1.32 +/- 0.23 psi in normal catheters. Decay times during PDP were > 50 s for both reversibly occluded and broken catheters (P < 0.001 vs. normal of 3.6 +/- 0.82 s). Abdominal radiographs and sideport injections of contrast material were used to distinguish the types of broken catheters. CONCLUSIONS: Catheter breakage and occlusion are complications in implantable insulin infusion systems and result in metabolic deterioration. The presence of a sideport allows pressure data and radiographic procedures to assist in determining the cause of catheter malfunction. A diagnostic algorithm was generated to improve efficiency in investigating catheter problems.

Insulin antibody responses after long-term intraperitoneal insulin administration via implantable programmable insulin delivery systems.

OBJECTIVE: To determine whether insulin antibodies are generated in diabetic patients after short- and long-term intraperitoneal insulin use and, if so, whether they are of potential clinical interest. Insulin antibodies commonly develop in diabetic patients who use subcutaneous human insulin, although their clinical significance remains controversial. Few data are available regarding insulin antibody responses to intraperitoneal insulin. RESEARCH DESIGN AND METHODS: We studied insulin antibody levels and clinical diabetes control in 25 type 1 diabetic patients treated for 3-6 years with intraperitoneal surfactant-stabilized porcine modified human insulin delivered by implantable programmable insulin delivery systems. RESULTS: All patients had preimplantation insulin antibody levels < 20 microU/ml, with a mean value of 2 +/- 2 microU/ml (1 SD). Mean antibody levels increased throughout the study period to a mean maximum of 197 +/- 326 microU/ml (P < 0.02) with 11 of 25 (44%) patients' levels exceeding 20 microU/ml (insulin responders). The mean time to significant antibody development was 21.8 +/- 4.4 months. Of the 11 responder patients, 4 had clinical syndromes that consisted of increasing daily insulin requirements and/or nocturnal hypoglycemia despite minimal nighttime basal insulin infusion rates associated with peak antibody levels > 200 microU/ml. None of the nonresponder patients (antibody levels < 20 microU/ml) had these clinical findings. CONCLUSIONS: Our results indicate that insulin antibody levels observed during intraperitoneal administration of human insulin are 1) similar to those reported during subcutaneous administration; although the rise in antibody level may be delayed compared with subcutaneous human insulin, 2) associated with a patient subset who are insulin antibody responders after switching from subcutaneous to intraperitoneal human insulin, 3) associated with a decrease in levels among responder patients regardless of whether they discontinue or continue pump use, and 4) associated with increased insulin needs and/or nocturnal hypoglycemia despite minimal basal rate insulin infusion at nighttime when antibody levels exceed 200 microU/ml.

Esophageal cancer in Iran.

Esophageal cancer is among the 10 most frequent cancers in the world. Iran is one of the known areas with a high incidence of esophageal cancer. Most of the patients in Iran have been reported from the north and northeast regions of the country. In one survey by the Iran Cancer Institute, 9% of all cancers and 27% of gastrointestinal cancers were esophageal carcinoma. The male to female ratio was 1.7/1. The distal portion of the esophagus is involved more often than other parts. Consumption of wheat flour, exposure to residues from opium pipes, drinking hot tea, and chewing nass (a mixture of tobacco, lime, ash, and other ingredients) are the suspect etiologic agents for esophageal cancer in Iran. Dysphagia, weight loss, anorexia, abdominal pain, and odynophagia are the common symptoms and signs of Iranian patients with esophageal cancer. For clinical staging, chest computed tomographic scanning is performed. Adenocarcinoma of the esophagus is not as common in Iran as in western countries. Public education, nutritional support, and eradication of opium addiction may decrease the morbidity and mortality that result from esophageal cancer. Surgery has traditionally been the mainstay of esophageal cancer treatment in Iran. Radiotherapy is mainly used postoperatively. The usual combination chemotherapy regimen is cisplatin plus flurouracil (5-Fu). Semin Oncol 28:153-157.

Comparison of somatodendritic and axon terminal dopamine release in the ventral tegmental area and the nucleus accumbens.

Fast cyclic voltammetry at a carbon fibre microelectrode was used to measure dopamine release following electrical or chemical stimulation in rat brain slices incorporating either the ventral tegmental area or the core region of the nucleus accumbens. Electrical or chemical stimulation gave clear voltammetric signals which corresponded to dopamine; less dopamine was released in the ventral tegmental area than in the nucleus accumbens. In contrast to the nucleus accumbens, electrically stimulated dopamine release in the ventral tegmental area was not sensitive to tetrodotoxin, was not modified by the presence of dopamine uptake inhibitors, or agonist or blockers acting at dopamine D2 autoreceptors.

The role of ventral tegmental dopamine neurons in locomotor sensitization following quinpirole or (+)-amphetamine: ex vivo voltammetric evidence.

Behavioural sensitization to the locomotor stimulating effects of (+)-amphetamine or quinpirole was induced in rats by intermittent drug administration. Following expression of sensitization, locomotor activity scores on day 9 were: vehicle 87 +/- 9, (+)-amphetamine 1441 +/- 227 and quinpirole 2078 +/- 214. Electrically stimulated dopamine release was measured on day 12 in ventral tegmental slices using fast cyclic voltammetry. Dopamine release was significantly elevated in the (+)-amphetamine- and quinpirole-treated groups when compared to vehicle-treated controls over a wide range of stimulation frequencies (5-200 Hz) and pulses (1-200). Quinpirole (1 microM) in the perfusion fluid attenuated dopamine release following 40-pulse, 200-Hz electrical stimulation, by 31.6 +/- 2.8% in the ventral tegmental area of the vehicle-treated group, by 14.8 +/- 5.6% in the (+)-amphetamine-treated group and 8 +/- 7.3% in the quinpirole-treated group. This study shows that dopamine release is increased in the ventral tegmental area following sensitization with either a direct or indirectly acting dopamine agonist. The findings that dopamine release was elevated at all stimulation frequencies in sensitized animals, and that quinpirole only attenuated this release at the highest stimulation frequency, would suggest that in addition to D2 autoreceptor subsensitivity, other mechanisms contribute to the enhanced release of dopamine in these animals.

Involvement of inducible nitric oxide synthase in inflammation-induced dopaminergic neurodegeneration.

The loss of dopaminergic neurones in the substantia nigra with Parkinson's disease may result from inflammation-induced proliferation of microglia and reactive macrophages expressing inducible nitric oxide synthase (iNOS). We have investigated the effects of the supranigral administration of lipopolysaccharide on iNOS-immunoreactivity, 3-nitrotyrosine formation and tyrosine hydroxylase-immunoreactive neuronal number, and retrogradely labelled fluorogold-positive neurones in the ventral mesencephalon in male Wistar rats. Following supranigral lipopolysaccharide injection, 16-18 h previously, there was intense expression of NADPH-diaphorase and iNOS-immunoreactivity in non-neuronal, macrophage-like cells. This was accompanied by intense expression of glial fibrillary acidic protein-immunoreactive astrocytosis in the substantia nigra. There were also significant reductions in the number of tyrosine hydroxylase(50-60%)- and fluorogold (65-75%)-positive neurones in the substantia nigra. In contrast, tyrosine hydroxylase-immunoreactivity in the ventral tegmental area was not altered. Pre-treatment of animals with the iNOS inhibitor, S-methylisothiourea (10 mg kg(-1), i.p.), led to a significant reduction of lipopolysaccharide-induced cell death. Similar reduction of tyrosine hydroxylase-immunoreactivity and fluorogold-labelled neurones in the substantia nigra following lipopolysaccharide administration suggests dopaminergic cell death rather than down-regulation of tyrosine hydroxylase. We conclude that the expression of iNOS- and 3-nitrotyrosine-immunoreactivity and reduction of cell death by S-methylisothiourea suggest the effects of lipopolysaccharide may be nitric oxide-mediated, although other actions of lipopolysaccharide (independent of iNOS induction) cannot be ruled out.

Behavioural and immunohistochemical changes following supranigral administration of sonic hedgehog in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated common marmosets.

Sonic hedgehog (SHH) has trophic actions on dopaminergic cell cultures and protects them from MPP(+) toxicity but its in vivo actions have not been explored. We now investigate the effects of unilateral supranigral administration of SHH on nigro-striatal function in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated common marmosets. SHH (0.1 or 1.0 microg) or vehicle was stereotaxically injected into the region of the right substantia nigra twice with an interval of 5 weeks between administrations. The first or second administration of low dose SHH (0.1 microg) did not significantly improve motor disability or locomotor activity compared to time-matched vehicle-treated animals. There was, however, an approximately 30% improvement in both motor disability and locomotor activity following the first administration of high dose SHH (1.0 microg). No further improvements occurred following the second high dose SHH treatment. Acute oral administration of L-3,4-dihydroxyphenylalanine (L-DOPA) produced a smaller increase in locomotor activity and greater reversal of motor disability in animals treated with SHH than occurred in vehicle-treated common marmosets. In the substantia nigra pars compacta, ipsilateral to SHH administration, the number of tyrosine hydroxylase-positive neurones was increased by 21% (P > 0.05) and 57% (P < 0.05) in low and high dose SHH groups respectively compared to the untreated contralateral hemisphere. There was no difference in the number of glial fibrillary acidic protein-positive cells. SHH may improve nigro-striatal function by restoring tyrosine hydroxylase positivity. This is reflected by an improvement in basal disability and a reduction in the lesion-induced response to L-DOPA.

Presence of neuropeptide Y in the rat seminal vesicle and its effects on noradrenaline- and nerve-induced contractions.

1. Immunohistochemical and functional studies have been performed to localize and determine the effects of neuropeptide Y (NPY) in the rat seminal vesicle. 2. An abundant presence of NPY-immunoreactive nerves, mainly concentrated in the smooth muscle layer of the seminal vesicle was found. Chronic 6-hydroxydopamine treatment (four doses of 50 mg kg-1 i.p. on days 1, 2, 4 and 6; rats killed one week after the last injection) led to a large reduction but not abolition of the NPY-immunoreactivity. 3. NPY (1-250 nM) did not affect the resting tone of the seminal vesicle. 4. The seminal vesicle was contracted by electrical field stimulation (EFS) and by exposure to 5 microM noradrenaline (NA). These contractions were abolished by phentolamine (1 microM). Tetrodotoxin (0.5 microM) abolished EFS-evoked contractions but did not affect NA-evoked contractions. 5. Seminal vesicles, from animals chronically-treated with reserpine (5 mg kg-1 i.p. on days 1 and 2; rats killed on day 3), were contracted by NA but not by EFS. 6. NPY (0.25-250 nM), concentration-dependently, inhibited EFS-evoked contractions by up to 70% maximum inhibition. Contractions evoked by EFS with short trains of pulses were inhibited by NPY to a greater degree than those with longer trains. 7. NPY had no significant effect on NA-evoked contractions. 8. These data provide strong evidence that the motor transmission in rat seminal vesicle is predominantly if not exclusively, adrenergic. It is further concluded that a rich NPY-containing innervation is present in the smooth muscle layer of rat seminal vesicle. The primary effect of NPY is modulation of adrenergic motor transmission by a prejunctional inhibition of NA release.

Neuropeptide Y in rat detrusor and its effect on nerve-mediated and acetylcholine-evoked contractions.

1. Immunohistochemical and isolated organ bath techniques were used to detect the presence of neuropeptide Y (NPY) in the rat urinary bladder and to determine its effect on tone, spontaneous activity and contractile responses of the detrusor muscle to electrical field stimulation, acetylcholine and alpha,beta-methylene ATP (alpha,beta-MeATP). 2. A very rich presence of NPY-immunoreactive nerve fibres was found mainly within the bundles of detrusor muscle cells. Chronic treatment with 6-hydroxydopamine did not affect the density of NPY-positive nerve fibres. 3. NPY (> 1 nM) enhanced the force and frequency of spontaneous contractions and generated a rise in the resting tone of the detrusor. These effects of NPY on the tone and the spontaneous activity remained unaffected by atropine (3 microM), indomethacin (10 microM) and aspirin (100 microM) but were abolished by Ca(2+)-withdrawal from the bathing medium. 4. The enhancing effects of NPY on the spontaneous contractions and the resting tone were not prevented by the induction of purinoceptor desensitization. 5. NPY (1-250 nM) potentiated electrical field stimulation (EFS, 1-64 Hz, 0.1 ms pulses duration, 10s train duration)-evoked, tetrodotoxin (0.5 microM)-sensitive contractions. The atropine (3 microM)-resistant component of EFS-evoked contractions was also potentiated by NPY. By contrast, the nifedipine (1 microM)-resistant but atropine-sensitive component of EFS-evoked contraction was inhibited by NPY. 6. NPY (250 nM) did not affect acetylcholine-evoked contractions, but potentiated alpha,beta-MeATP-evoked contractions. 7. It is concluded that NPY-innervation of rat urinary bladder is largely confined to the detrusor muscle and is abundant and mainly non-adrenergic. It is further concluded that the enhancing effect of NPY on detrusor spontaneous activity and tone is caused by Ca2+ influx through nifedipine-sensitive Ca2+ channels and is not mediated through acetylcholine or cyclo-oxygenase-sensitive eicosanoids or ATP.8. The results are consistent with the hypothesis that intrinsic NPY in the rat detrusor innervation contributes to the motor transmission in two ways: by promoting non-cholinergic motor transmission and by inhibiting prejunctionally the cholinergic transmission.

Differential effects of nifedipine on nerve-mediated and noradrenaline-evoked contractions of rat anococcygeus muscle.

In rat anococcygeus muscle the inhibitory effect of nifedipine (0.01, 0.1, 1.0 and 10 microM) was determined on adrenergic twitches in response to electrical field stimulation (trains of 4 pulses, 0.1 ms pulse duration, 10 Hz) and on twitch-matching contractions evoked by noradrenaline. Nifedipine concentration-dependently reduced the neurogenic twitch with an IC50 of 0.083 microM. Nifedipine reduced the noradrenaline-evoked contraction to a markedly lesser degree (IC50 > 10 microM). The difference in the magnitude of inhibition of electrically evoked twitch and twitch-matching noradrenaline-evoked contraction was statistically significant at every concentration of nifedipine. It is concluded that inhibition of the twitch by nifedipine involves some other mechanism(s) in addition to its Ca2+ channel blocking property in smooth muscle.

The presence and the effects of neuropeptide Y in rat anococcygeus muscle.

Isolated anococcygeus muscle from male rats was examined for the presence of neuropeptide Y-immunoreactive nerves and for the effects of neuropeptide Y on its tone and its contractile/relaxant responses to electrical field stimulation, acetylcholine, guanethidine and noradrenaline. Using peroxidase anti-peroxidase immunohistochemistry in stretch preparation of the anococcygeus, neuropeptide Y-immunoreactive nerve fibres were observed, in abundance, running along both vascular as well as non-vascular smooth muscle cells. Neuropeptide Y (> 250 nM) evoked phentolamine and tetrodotoxin-resistant contractile response. Neuropeptide Y, even in subspasmogenic concentrations, potentiated contractions evoked by acetylcholine, guanethidine and noradrenaline. Electrical field stimulation (trains of 3-4 pulses, 0.1 ms, 10 Hz) of the isolated anococcygeus preparation produced robust, phentolamine and tetrodotoxin sensitive contractions. Neuropeptide Y (< 10 nM) exerted a biphasic effect on the electrical field stimulation-evoked contractions; an early potentiation was followed by a delayed and progressive inhibition. Neuropeptide Y (> 10 nM) caused a concentration-dependent potentiation of electrical field stimulation-evoked contraction alone, matching its potentiation of noradrenaline-evoked contraction. Electrical field stimulation (5 pulses, 0.1 ms, 10 Hz) of guanethidine (50 microM)-contracted anococcygeus induced a relaxant response and neuropeptide Y (1-100 nM) exerted a concentration-related slight and variable effect on the electrical field stimulation-evoked relaxant response (1 nM, augmentation; 10 nM, no effect; 100 nM, reduction). It is concluded that rat anococcygeus muscle has a rich neuropeptide Y-containing innervation and neuropeptide Y is mostly stored within adrenergic nerves. The main functional roles of neuropeptide Y in the anococcygeus muscle are likely to be post-junctionally mediated facilitation and prejunctionally mediated inhibition of adrenergic motor transmission.

Glial cell line-derived neurotrophic factor concentration dependently improves disability and motor activity in MPTP-treated common marmosets.

Glial cell line-derived neurotrophic factor (GDNF) has previously reduced motor deficits and preserved nigral dopamine neurones in rhesus monkeys with a unilateral MPTP-induced lesion of substantia nigra. We now report on the ability of GDNF to reverse motor deficits induced by parenteral administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to common marmosets resulting in bilateral degeneration of the nigrostriatal pathway. Prior to GDNF administration, all MPTP-treated animals showed akinesia or bradykinesia, rigidity, postural instability and tremor. Intraventricular injection of GDNF (10, 100 or 500 microg) at 9 and 13 weeks post MPTP treatment resulted in a concentration dependent improvement in locomotor activity and motor disability which became significant after administration of 100 and 500 microg of GDNF. The most prominent improvements were in alertness, checking movements, and posture. It is concluded that intraventricular GDNF administration improves bilateral Parkinsonian motor disability following MPTP treatment and this may reflect an action of GDNF on remaining nigral dopaminergic neurones.