bluuebunny/crossref_metadata_2025_split huggingface dataset:
Actions of LY341495 on metabotropic glutamate receptor‐mediated responses in the neonatal rat spinal cord
Authors: Howson Patrick A , Jane David E 
Published: May 2003

The group II metabotropic glutamate (mGlu) receptor antagonist (2S,1′S,2′S)‐2‐(2‐carboxycyclopropyl)‐2‐(9H‐xanthen‐9‐yl)glycine (LY341495) also has activity at group I and III mGlu receptors at higher concentrations and can be used to discriminate between mGlu receptor subtypes. We report the antagonist action of LY341495 on glutamate receptors expressed in the neonatal rat spinal cord preparation and the use of this antagonist to investigate the group III mGlu receptor subtypes responsible for mediating the depression of synaptic transmission in the spinal cord mediated by the group III mGlu receptor agonists (S)‐2‐amino‐4‐phosphonobutanoic acid ((S)‐AP4) and (1S,3R,4S)‐1‐aminocyclopentane‐1,2,4‐tricarboxylic acid (ACPT‐I).
LY341495 antagonised mGlu receptor agonist‐induced responses in the spinal cord with a rank order of potency of group II > group III > group I, which is the same as that observed in human cloned mGlu receptor cell lines. Antagonism of group II and III mGlu receptor‐mediated effects were time dependent when low‐nanomolar concentrations of LY341495 were used. Although the rank order of potency of LY341495 was the same on native rat and cloned human mGlu receptors, there was a compression in the selectivity between group II and III mGlu receptors, expressed in the spinal cord.
In agreement with a previous study on cloned ionotropic glutamate receptors 100 μM LY341495 had little or no effect on N‐methyl‐D‐aspartate, (S)‐2‐amino‐3‐(3‐hydroxy‐5‐methylisoxazol‐4‐yl) propionic acid or kainate receptor‐mediated responses on motoneurones.
LY341495 exhibited low‐nanomolar potency antagonist activity against (S)‐AP4 and ACPT‐I suggesting that these agonists are activating predominantly mGlu8 and that mGlu4 receptors do not play a role in modulating synaptic transmission in the pathways stimulated in the experiments described here.

British Journal of Pharmacology (2003) 139, 147–155. doi:10.1038/sj.bjp.0705230
Inhibition of lipopolysaccharide‐inducible nitric oxide synthase, TNF‐α and COX‐2 expression by sauchinone effects on I‐κBα phosphorylation, C/EBP and AP‐1 activation
Authors: Lee Ae Kyung , Sung Sang Hyun , Kim Young Choong , Kim Sang Geon 
Published: May 2003

Sauchinone, a lignan isolated from Saururus chinensis (Saururaceae), is a diastereomeric lignan with cytoprotective and antioxidant activities in cultured hepatocytes. The effects of sauchinone on the inducible nitric oxide synthase (iNOS), tumor necrosis factor‐α (TNF‐α) and cyclooxygenase 2 (COX‐2) gene expression and on the activation of transcription factors, nuclear factor‐κB (NF‐κB), CCAAT/enhancer‐binding protein (C/EBP), activator protein‐1 (AP‐1) and cAMP‐response element‐binding protein (CREB) were determined in Raw264.7 cells as part of the studies on its anti‐inflammatory effects.
Expression of the iNOS, TNF‐α and COX‐2 genes was assessed by Northern and Western blot analyses. NO production was monitored by chemiluminescence detection using a NO analyzer. To identify the transcriptional factors affected by sauchinone, the extents of NF‐κB, C/EBP, AP‐1 and CREB activation were measured. Activation of the transcription factors was monitored by gel mobility shift assay, whereas p65 and I‐κBα were analyzed by immunocytochemical and immunoblot analyses.
Sauchinone inhibited the induction of iNOS, TNF‐α and COX‐2 by lipopolysaccharide (LPS) (IC5010 μM) with suppression of the mRNAs.
Sauchinone (1–30 μM) inhibited LPS‐inducible nuclear NF‐κB activation and nuclear translocation of p65, which was accompanied by inhibition of I‐κBα phosphorylation.
LPS‐inducible increase in the intensity of C/EBP binding to its consensus sequence was also inhibited by sauchinone. The AP‐1, but not CREB, DNA binding activity was weakly inhibited by sauchinone.
These results demonstrate that sauchinone inhibits LPS‐inducible iNOS, TNF‐α and COX‐2 expression in macrophages through suppression of I‐κBα phosphorylation and p65 nuclear translocation and of C/EBP and/or AP‐1 activation, which may constitute anti‐inflammatory effects of the lignan.

British Journal of Pharmacology (2003) 139, 11–20. doi:10.1038/sj.bjp.0705231
PPAR‐α and ‐γ but not ‐δ agonists inhibit airway inflammation in a murine model of asthma: in vitro evidence for an NF‐κB‐independent effect
Authors: Trifilieff Alexandre , Bench Anne , Hanley Marcus , Bayley Debbie , Campbell Emma , Whittaker Paul 
Published: May 2003

Peroxisome proliferator‐activated receptors (PPARs) are ligand‐activated transcription factors that have been proposed to regulate inflammation by antagonising the nuclear factor‐κB (NF‐κB) signalling pathway. We investigated the role of PPARs using synthetic agonists in murine models of airway inflammation, and addressed the possible effect on NF‐κB signalling in vitro using a human epithelial cell line, A549.
Sensitised BALB/c mice exposed to an aerosol solution of ovalbumin had an increased number of airway eosinophils, neutrophils and lymphocytes. When given intranasally an hour before the aerosol challenge, a PPAR‐α (GW 9578) and PPAR‐γ (GI 262570) selective agonist as well as a dual PPAR‐α/γ (GW 2331) agonist selectively inhibited allergen‐induced bronchoalveolar lavage eosinophil and lymphocyte but not neutrophil influx. In contrast, a PPAR‐δ agonist (GW 501516) was inactive.
When given intranasally an hour before challenge, PPAR‐α and PPAR‐γ selective agonists as well as a dual PPAR‐α/γ agonist did not inhibit lipopolysaccharide‐induced bronchoalveolar lavage neutrophil influx or tumour necrosis factor‐α (TNF‐α) and KC production.
In A549 cells, selective agonists for PPAR‐α, ‐γ and ‐δ did not inhibit intracellular adhesion molecule‐1 expression following stimulation with proinflammatory cytokines. In addition, IL‐8 release and the activation of an NF‐κB‐responsive reporter gene construct were inhibited only at micromolar concentrations, suggesting that these effects were not PPAR‐mediated.
Our in vivo data show that agonists of PPAR‐α and ‐γ, but not ‐δ, inhibit allergen‐induced bronchoalveolar lavage eosinophil and lymphocyte influx. In vitro data suggest that this effect might not be mediated by antagonism of the NF‐κB pathway.

British Journal of Pharmacology (2003) 139, 163–171. doi:10.1038/sj.bjp.0705232
Effect of resiniferatoxin on the noxious heat threshold temperature in the rat: a novel heat allodynia model sensitive to analgesics
Authors: Almási Róbert , Pethö Gábor , Bölcskei Kata , Szolcsányi János 
Published: May 2003

An increasing‐temperature hot plate (ITHP) was introduced to measure the noxious heat threshold (45.3±0.3°C) of unrestrained rats, which was reproducible upon repeated determinations at intervals of 5 or 30 min or 1 day.
Morphine, diclofenac and paracetamol caused an elevation of the noxious heat threshold following i.p. pretreatment, the minimum effective doses being 3, 10 and 200 mg kg−1, respectively.
Unilateral intraplantar injection of the VR1 receptor agonist resiniferatoxin (RTX, 0.048 nmol) induced a profound drop of heat threshold to the innocuous range with a maximal effect (8–10°C drop) 5 min after RTX administration. This heat allodynia was inhibited by pretreatment with morphine, diclofenac and paracetamol, the minimum effective doses being 1, 1 and 100 mg kg−1 i.p., respectively.
The long‐term sensory desensitizing effect of RTX was examined by bilateral intraplantar injection (0.048 nmol per paw) which produced, after an initial threshold drop, an elevation (up to 2.9±0.5°C) of heat threshold lasting for 5 days.
The VR1 receptor antagonist iodo‐resiniferatoxin (I‐RTX, 0.05 nmol intraplantarly) inhibited by 51% the heat threshold‐lowering effect of intraplantar RTX but not α,β‐methylene‐ATP (0.3 μmol per paw). I‐RTX (0.1 or 1 nmol per paw) failed to alter the heat threshold either acutely (5–60 min) or on the long‐term (5 days). The heat threshold of VR1 receptor knockout mice was not different from that of wild‐type animals (45.6±0.5 vs 45.2±0.4°C).
In conclusion, the RTX‐induced drop of heat threshold measured by the ITHP is a novel heat allodynia model exhibiting a high sensitivity to analgesics.

British Journal of Pharmacology (2003) 139, 49–58. doi:10.1038/sj.bjp.0705234
Amniotic fluid index in normal pregnancy: An assessment of gestation specific reference values among Indian women
Authors: Khadilkar Suvarna S. , Desai Sabita S. , Tayade Sadhana M. , Purandare Chittaranjan N. 
Published: May 2003

AbstractAim:  To obtain a gestational reference range for the amniotic fluid index (AFI) among Indian women.Methods:  An analysis of AFI estimations was undertaken in 517 Indian women with normal pregnancy between 16 and 42 weeks of gestation. It was a prospective, cross‐sectional study conducted in a university teaching hospital. Women with fetal anomalies, pregnancy‐induced hypertension, diabetes mellitus, and other maternal complications were excluded from the study. The median, the 5th and the 95th percentile values were calculated for each gestational week and these values were compared with other studies.Results:  The median reached its peak at the 27th week of gestation. We observed ∼ 6 cm as the lower limit of normal (5th percentile) and ∼ 18 cm (95th percentile) as upper limit of normal AFI at term for our population, whereas in the Caucasian population, the values were ∼ 7 cm and ∼ 20 cm, respectively. All gestation specific AFI values were lower in the studied population of Indian women compared with other studies on Caucasian population (P < 0.01 for 5th percentile & P < 3.26 × 10−7 for 95th percentile), but slightly higher than the Chinese population.Conclusion:  Amniotic fluid index values differ in different populations. We standardized the reference values for normal AFI in Indian women. We found that they are lower in the population studied compared with reported values in the Caucasian population, but slightly higher than the Chinese population.
The clinical efficacy and efficiency of a 100‐IU starting dose of recombinant follicle stimulating hormone (Puregon®) in Korean women undergoing in vitro fertilization and embryo transfer
Authors: Moon Shin Yong , Kim Seok Hyun , Ku Seung Yup , Jee Byoung Chul , Choi Young Min , Lee Jin Yong 
Published: May 2003

AbstractAim:  A prospective, non‐comparative study was conducted to evaluate the efficacy and efficiency of a starting dose of 100 IU recombinant follicle stimulating hormone (rhFSH, Puregon®) in women undergoing ovarian stimulation prior to in vitro fertilization (IVF).Methods:  A total of 40 women were down‐regulated with gonadotropin releasing hormone agonist (long protocol), then treated with a fixed dose of 100 IU rhFSH for the first 4 days, and the dose of gonadotropin administration was adjusted according to patient's response thereafter. A maximum number of 3 embryos were transferred in 32 patients.Results:  Nine patients were treated with intracytoplasmic sperm injection, and 24 with conventional IVF. The duration of stimulation was 10.8 ± 1.8 days, serum estradiol concentration on human chorionic gonadotropin day was 1693.0 ± 1651.2 pg/mL, and 1480 ± 450 IU rhFSH was used. A mean number of 8.4 ± 5.7 oocytes were retrieved, 4.9 ± 4.3 embryos obtained, 2.4 ± 0.9 embryos transferred, and 3.5 ± 3.2 embryos cryopreserved. The proportion of mature oocytes was 71.6%, and the fertilization rate was 86.4%. Clinical pregnancy was achieved in 8 patients (25.0%), and all of these pregnancies are ongoing or delivered. There were 3 cases of twin gestations (37.5%). The implantation rate was 13.1% (11/84). There was one case of moderate ovarian hyperstimulation syndrome, however, the patient recovered within 7 days without any complications.Conclusion:  The starting dose of 100 IU rhFSH has a good safety profile, and is adequate in controlled ovarian hyperstimulation for IVF with a small amount of gonadotropin administered.
Effects of methylergometrine and oxytocin on thoracic epidural pressure during cesarean section
Authors: Kikutani Takehiko , Shimada Yoichi 
Published: May 2003

AbstractAim:  The effects of oxytocics on thoracic epidural pressure during cesarean section were studied in 60 parturients, (American Society of Anesthesiologist physical status, class I or II) after obtaining informed consent.Methods:  The subjects were randomized to either a ergometrine (n = 30) or oxytocin treatment group (n = 30). The subjects were anesthetized with 11–12 mg of intrathecal isobaric bupivacaine (0.5%), and an epidural catheter was placed at Th 11/12, and was connected to a pressure transducer to continuously monitor thoracic epidural pressure. We analyzed epidural pressure, blood pressure, and heart rate 5 min after administering intrathecal bupivacaine (SAB5m), immediately before skin incision (pre‐incision), immediately after delivery of the placenta (placenta‐del), and 5 min after delivery of the fetus (CS5m).Results:  In both groups, epidural pressures were found to be elevated after delivery compared with their levels before the skin incisions were made, (P < 0.0001). Epidural pressures at placenta‐del (P = 0.0055) and CS5m (P < 0.0001) were higher than at SAB5m in the ergometrine group. Epidural pressures at placenta‐del were also higher than at SAB5m in the oxytocin group (P < 0.0001). Epidural pressures at placenta‐del were lower in the ergometrine group compared with the oxytocin group (P = 0.0122), but epidural pressures at CS5m were higher in the ergometrine group compared with the oxytocin group (P < 0.0001).Conclusions:  We conclude that there is an increase in thoracic epidural pressure after fetal delivery, which appears to be associated with uterine contraction.
Muscle pH regulation: role of training
Authors: JUEL C. 
Published: May 2003

In most cell types, including resting skeletal muscle fibers, internal pH (pHi) is kept constant at a relatively alkaline level. The high pHi is obtained in spite of a chronic acid load resulting from cellular metabolism and passive influx of protons driven by electrochemical forces. Regulation of pHi depends on continuous activity of membrane transport systems that mediate an outflux of H+ (or bicarbonate influx), whereby the acid load is counterbalanced. The transporters involved in muscle pH regulation at rest are the Na+/H+ exchange system as well as the Na+‐dependent and Na+‐independent Cl–bicarbonate transport systems. The Na+/H+ exchanger seems to be active at resting pHi levels in skeletal muscle. Therefore, pH homeostasis in skeletal muscle most likely involves an equilibrium between counter‐directed H+ fluxes.A minor fraction of H+ release during intense exercise is mediated by the Na+/H+ exchanger. The capacity of this system is increased with training and hypoxia in rat skeletal muscle. The dominant acid extruding system associated with intense exercise is the lactate/H+ co‐transporter. It has been demonstrated that the capacity of the lactate/H+ co‐transporter of rat skeletal muscle is upregulated with training and chronic electrical stimulation, and that it is reduced upon denervation and hindlimb unweighting. Moreover, athletes can have an elevated lactate/H+ co‐transport capacity, whereas the thigh muscle of spinal cord‐injured individuals has a lower transport capacity than the one of healthy untrained subjects. Thus, it appears that the capacity of the lactate/H+ transporter is affected by the level of muscle activity in both rats and humans. In addition, the rate of H+ release from muscle may also be influenced by capillarization and local blood flow. Finally the resulting pH displacement during acid accumulation is determined by the cellular buffer capacity, which may also undergo adaptive changes.
Relationship of physical exercise and ageing to growth hormone production
Authors: Hurel S. J. , Koppiker N. , Newkirk J. , Close P. R. , Miller M. , Mardell R. , Wood P. J. , Kendall‐Taylor P. 
Published: May 2003

OBJECTIVEThe normal decline in physiological function with ageing is associated with a decrease in bioavailable growth hormone. Growth hormone has been shown to alter body composition and increase fat‐free mass in older men. Increased physical fitness is accompanied by an increase in 24‐h growth hormone release. The purpose of this study was to examine the effect of exercise on declining growth hormone concentrations with increasing age.DESIGN AND PATIENTSThe growth hormone production of 10 male subjects running over 40 miles per week was compared to 10 healthy age‐matched sedentary males (controls 57.7 ± 2.8 vs. runners 60.5 ± 3.4 years). All subjects underwent a basal assessment including a two‐hour serum growth hormone profile followed by estimation of maximal exercise capacity on a cycle ergometer with growth hormone estimations at peak exercise activity and every five minutes whilst cycling at 40% of maximal exercise capacity.RESULTSMaximal exercise capacity confirmed the lifestyles of the two groups (VO2 max controls 22.36 ±6.05 vs. runners 34.91 ± 13.13 l/min/kg, P = 0.01). The runners had lower body‐mass indices than controls (BMI 22.3 ± 1.5 vs. 25.5 ± 2.0 kg/m2, P = 0.002). Peak growth hormone level during a two‐hour resting profile was higher in the runners (median (range) controls 2.10 (0.20–12.20) vs. runners 5.25 (0.80–21.00) mU/l, P = 0.03) as was the average growth hormone level during the two hour profile (mean growth hormone per 2 h median (range): controls 0.54 (0.03–4.88) vs. runners 2.17 (0.25–7.45) mU/l, P = 0.04). Growth hormone production at maximal exercise capacity was similar. Sex hormone binding globulin and testosterone were significantly higher in the runners.CONCLUSIONSThe results suggest that regular intensive exercise in older male subjects is associated with higher growth hormone and testosterone levels and that exercise may have a role in counteracting the normal decline in growth hormone with ageing.
Repeated intramuscular injections of testosterone undecanoate for substitution therapy in hypogonadal men
Authors: Nieschlag Eberhard , Büchter Dorothee , Von Eckardstein Sigrid , Abshagen Katrin , Simoni Manuela , Behre Hermann M. 
Published: May 2003

OBJECTIVETo investigate the suitability of intramuscular testosterone undecanoate (TU) injections for substitution therapy in hypogonadal men.STUDY DESIGNClinical, open‐label, non‐randomized trial of 13 hypogonadal men receiving 4 intramuscular injections of 1000 mg TU in 4‐ml castor oil at 6‐week intervals. General wellbeing, sexual parameters, clinical chemistry, hormone levels, prostate size and prostate‐specific antigen (PSA) were evaluated over 24 weeks and compared with baseline values.RESULTSTestosterone serum levels were never found below the lower limit of normal and only briefly after the 3rd and 4th injection above the upper limit of normal, while peak and trough values increased over the 24‐week observation period. Oestradiol and dihydrotestosterone followed this pattern, not exceeding the normal limits. No serious side‐effects were noted. Slight increases in body weight, haemoglobin, haematocrit, prostate volume and PSA, suppression of gonadotrophins as well as increased ejaculation frequency occurred as signs of adequate testosterone substitution.CONCLUSIONTestosterone undecanoate is well tolerated by the patients. The injection intervals can be extended even beyond the 6‐week periods chosen in the present study. Altogether, intramuscular testosterone undecanoate appears to be well suited for long‐term substitution therapy in hypogonadism and hormonal male contraception.
Oestrogens prevent the increase of human serum soluble interleukin‐6 receptor induced by ovariectomy in vivo and decrease its release in human osteoblastic cells in vitro
Authors: Girasole Giuseppe , Giuliani Nicola , Modena Alberto Bacchi , Passeri Giovanni , Pedrazzoni Mario 
Published: May 2003

OBJECTIVEInterleukin‐6 (IL‐6) seems to be a key mediator of the increased bone loss that follows loss of ovarian function. Based on this and on evidence that oestrogen deficiency may also increase cell sensitivity to IL‐6, we studied the effects of ovariectomy and of oestrogen replacement therapy on the serum levels of IL‐6 and of soluble IL‐6 receptor (sIL‐6R) in vivo.DESIGN AND PATIENTSThirty‐seven fertile women undergoing surgery for benign uterine diseases were divided into 3 groups and monitored for 12 months: hysterectomized women (n = 9), ovariectomized untreated women (n = 12) and ovariectomized women starting treatment with transdermal estradiol (E2, 50 μg/d) 1 month after surgery (n = 16).RESULTSHysterectomy alone caused no significant changes of sIL6R whereas serum levels of sIL‐6R rose progressively after ovariectomy (mean ± SEM: 31 ± 9% and 38 ± 7% over baseline, at 6 and 12 months, respectively; P < 0.01). Oestrogen replacement therapy prevented the increase of sIL6R over a 1‐year period. A similar pattern was also found for serum IL‐6 but the changes did not reach statistical significance. In ovariectomized (OVX) women there were significant correlations between serum sIL‐6R levels and FSH (r = 0.59; P < 0.01), oestradiol (r = − 0.43; P < 0.01), testosterone (r = − 0.41; P < 0.05), osteocalcin (r = 0.42; P < 0.05) and bone alkaline phosphatase (r = 0.44; P < 0.05). To examine whether oestrogen directly regulates sIL‐6R secretion by bone cells, we studied in vitro the basal and phorbol ester (PMA) stimulated release of sIL‐6R in a human osteoblastic cell‐line (MG‐63) and in a tumour‐derived osteoclastic cell line (GCT‐51). Osteoblastic (but not osteoclastic) cells spontaneously produced considerable amounts of sIL‐6R and the protein kinase‐C activator PMA (10−8 M) increased the release of sIL‐6R by osteoblasts more than 3‐fold. More strikingly, 17β E2 (but not 17α) significantly inhibited both the spontaneous‐ and PMA‐induced release of sIL‐6R by osteoblastic cells (P < 0.05).CONCLUSIONSThese results indicate that oestrogen loss causes alterations of the IL‐6 system, and that sIL‐6R is under the direct inhibitory control of oestrogens both in vivo and in vitro.
Effect of Whole Blood Storage on Factor VIII Recovery in Fresh Frozen Plasma and Cryoprecipitate
Authors: Allersma D.P. , Imambaks R.M.R. , Meerhof L.J. 
Published: May 2003

AbstractDepending on logistics, whole blood has to be stored for several hours after collection. If storage time exceeds 8 h, storage has to be at 1–6 °C to comply with FDA regulations. In the Netherlands, however, whole blood is also stored for 12–15 h at 20–24 °C using butane‐1,4‐diol cooling devices. We compared these two storage methods for factor VIII recovery in plasma and cryoprecipitate. At laboratory scale a significantly higher factor VIII recovery was found in plasma prepared from whole blood stored at ambient temperature; in cryoprecipitate this was confirmed but differences were not significant. However, as a result of inefficient cooling in routine procedure, no significantly different factor VIII recoveries were found in plasma prepared from whole blood stored at either of the two temperatures. From our study we conclude that overnight storage of whole blood at ambient temperature using butane‐1,4‐diol cooling devices has to be favoured.