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Introduction: It is well known that women with history of gestational diabetes (GDM) are at risk of future DM. Whether they are at a higher risk of hypertension and cardiovascular risk remained to be determined., Objectives: To determine whether Chinese women who have been diagnosed GDM according to the new IADPSG criteria have a higher risk of hypertension & arterial stiffness than women with normal glucose tolerance (NGT) during pregnancy., Methods: Chinese women who had participated in the HAPO study between 2001 and 2006 in Hong Kong were followed up at a median of 6years postpartum. All underwent anthropometric & BP measurements. Central systolic and diastolic blood pressures (SBP & DBP), augmentation index (AI) and pulse wave velocity (PWV) were assessed by using SphygmoCor(®) PVx.A total of 608 women (494 NGT, 114 GDM) were followed up till early 2012., Results: Although there was no significant difference in the rate of hypertension, the central SBP (106±12 vs 102±13mmHg, p=0.03), AI (22.1±8.3 vs 18.9±8.5%, p<0.001) and PWV (6.8±1.0 vs 6.6±0.8, p=0.03) were all higher in women with history of GDM., Conclusion: The findings suggest a higher risk of subclinical atherosclerosis amongst women with GDM despite the blood pressure may appear normal at the time of follow up., (Copyright © 2012. Published by Elsevier B.V.)

Objectives: We aimed to determine the longitudinal course and outcome of chronic insomnia in a five-year prospective study in Hong Kong Chinese adults., Methods: Two thousand three hundred and sixteen middle-aged adults (53.3% females, 46.3 ± 5.1 years old at follow-up) were recruited at baseline and follow-up. Participants were divided into three groups: non-insomnia, insomnia symptoms, and insomnia syndrome (insomnia symptoms plus daytime symptoms). Upper airway inflammatory diseases, mental problems, and medical problems were additionally assessed at follow up., Results: The incidence of insomnia (symptoms and syndrome) was 5.9%. The persistence rate of insomnia syndrome was 42.7% for insomnia syndrome and 28.2% for insomnia symptoms. New incidence of insomnia was associated with younger age, unemployment, and daytime symptoms, while persistence of insomnia was associated with female sex, lower education level, and daytime symptoms at the baseline (p<0.05). Baseline insomnia syndrome was significantly associated with upper airway inflammatory diseases (including asthma and laryngopharyngitis; adjusted OR=1.97-17.9), mental problems, and medical conditions (including arthritis, psychiatric disorders, chronic pain, and gastroesophageal reflux disease; AOR=2.29-3.77), whereas baseline insomnia symptoms were associated with poor mental health (AOR=2.43), psychiatric disorders (AOR=2.39), and chronic pain (AOR=2.95)., Conclusions: Chronic insomnia is a common problem with considerable persistence and incidence rates among middle-aged Chinese adults. Insomnia syndrome has a higher persistence rate with more mental and medical comorbidities when compared with insomnia symptoms without daytime consequences., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background and Study Aims: Delayed gastric emptying (DGE) is the commonest gastrointestinal (GI) complication in type 2 diabetes. We aimed to evaluate the association between DGE and cardiovascular autonomic neuropathy (CAN) in type 2 diabetes., Patients and Methods: A total of 71 Chinese patients (39 men and 32 women, aged 60-90 years) and 30 controls (12 men and 18 women, aged 50-79 years) were studied in Nanjing, China. The gastric emptying was assessed by 13C-octanoic acid breath test (OBT) and gastric emptying ultrasonography (GEU). Cardiovascular autonomic neuropathy (CAN) was assessed by a scoring system being validated before., Results: The diabetic patients, except for a higher plasma glucose level, had similar characteristics compared to the non-diabetic controls. Diabetic patients had higher incidence of DGE and CAN than controls (48.5% vs. 10.7%, p = 0.001). Among diabetic patients with DGE (n = 27), 18 (66.7%) had CAN and 9 (33.3%) did not. Corresponding figures for those without DGE (n = 39) were 14 (35.9%) and 25 (64.1%), respectively (p = 0.014). Diabetes was independently associated with the risk of DGE with odd ratio (95% CI) of 15.6 (1.92, 127.06) (p = 0.010). The presence of diabetes or CAN was independently associated with the half gastric emptying time after adjusting for age, gender, plasma glucose and blood pressure., Conclusions: We found a much prolonged gastric emptying time in Chinese patients with type 2 diabetes as compared to non-diabetic controls. There was a high rate of CAN in diabetic patients, and it was associated with gastric emptying.

Objective: Visceral fat is believed to be important in the pathogenesis of metabolic syndrome and fatty liver. In this study, we examined the relationship between mesenteric fat thickness and other sonographic indices of adiposity and the presence of fatty liver among subjects with polycystic ovary syndrome (PCOS)., Subjects and Methods: A total of 117 Chinese subjects with PCOS were evaluated (mean age, 28.6 ± 6.5 yr; mean body mass index, 24.3 ± 5.3 kg/m(2)). Anthropometric measurements and metabolic risk profile, including a standard oral glucose tolerance test, were assessed in all subjects. All subjects underwent an ultrasound examination for measurement of thickness of mesenteric, preperitoneal, and sc fat as well as evaluation for fatty liver., Results: Forty-six (39.3%) of the subjects had fatty liver. PCOS subjects with fatty liver had higher body mass index, waist circumference, waist-hip ratio, and systolic blood pressure; a more unfavorable lipid profile with higher triglyceride; lower high-density lipoprotein cholesterol; higher fasting glucose and insulin; higher 2-h glucose during oral glucose tolerance test; lower SHBG; and higher alanine aminotransferase. Subjects with fatty liver had increased thickness of preperitoneal, mesenteric, and sc fat, as well as increased carotid intima-media thickness. Abdominal fat thickness showed moderate correlation to alanine aminotransferase as well as fasting insulin. On multivariate logistic regression, fasting insulin and mesenteric fat thickness were identified as independent predictors of fatty liver among subjects with PCOS., Conclusion: Fatty liver is present in a significant proportion of Chinese patients with PCOS. Sonographic measurement of mesenteric fat is an independent determinant of fatty liver among subjects with PCOS and identifies subjects at increased cardiovascular risk.

Aim: This study aimed to confirm the hypothesis that adiponectin levels can enhance the discriminative value of waist circumference (WC) in predicting impaired glycaemic status and clustering of risk factors., Methods: We used receiver operating characteristic (ROC) curve analysis to define the optimal cut-off value of adiponectin to predict diabetes in Chinese men with no relevant past medical history. This value was combined with WC to increase its discriminative power in ascertaining impaired glycaemic status and various cardiovascular risk factors., Results: In 360 men (mean+/-S.D.; age: 41.3+/-9.2 years), the mean+/-S.D. adiponectin level was 5.2+/-2.7 microg/mL. Based on oral glucose tolerance tests (OGTTs), 84 men (23.3%) had undiagnosed diabetes, 52 (14.4%) had impaired glucose tolerance (IGT) and 224 (62.3%) had normal glucose tolerance. On ROC analysis, 5.7 microg/mL was the optimal cut-off value of adiponectin in this population to predict diabetes. Compared with subjects who had normal WC (defined as less than 90 cm) and high adiponectin levels (> or =5.7 microg/mL), the likelihood ratio of diabetes was 2.54 in those with central obesity and hypoadiponectinaemia., Conclusion: The combined use of low adiponectin levels and large WC measures has greater discriminative power than using either index alone to identify subjects at particular risk of glucose intolerance and clustering of risk factors., (Copyright 2010 Elsevier Masson SAS. All rights reserved.)

Aims: To examine the independent and joint effects of multiple genetic variants on a cardiac end-point in an 8-year prospective study of a Chinese diabetic cohort., Methods: Seventy-seven single nucleotide polymorphisms (SNPs) of 53 candidate genes for inflammation, thrombosis, vascular tone regulation and lipid metabolism were genotyped in 1297 Chinese patients with no prior history of coronary heart disease (CHD) or heart failure at baseline. Cardiac end-point was defined by the occurrence of CHD and/or heart failure., Results: In Cox regression model, after adjustment for baseline confounding variables including age, sex, smoking status, duration of diabetes, glycaemic control, lipid levels, waist circumference, blood pressure, albuminuria and estimated glomerular filtration rate, genetic variants, including Ala/Ala of SCYA11 (eotaxin) Ala23Thr, Cys/Cys or Cys/Ser of PON2 (paraoxonase 2) Ser311Cys and Arg/Arg of ADRB3 (beta3-adrenergic receptor) Trp64Arg, were independently associated with incident cardiac end-point, with respective hazard ratios (95% confidence interval) of 1.70 (1.10-2.61, P=0.037), 1.42 (1.08-1.88, P=0.013) and 3.84 (1.18-12.50, P=0.025). Analysis of the joint effect of the risk alleles showed significant increased risk of the cardiac end-point with increasing number of risk alleles (P<0.001). The adjusted risk for the cardiac end-point was 4.11 (P=0.002) for patients carrying four risk alleles compared with those carrying one or no risk allele., Conclusions: The independent risk conferred by genetic variants encoding pathways such as inflammation and lipid metabolism, not adequately reflected by conventional biomarkers, may identify high-risk individuals for intensified control of modifiable risk factors.

Background: Women with polycystic ovary syndrome (PCOS) frequently exhibit central obesity, glucose intolerance, atherogenic dyslipidaemia and hypertension which are characteristic features of the metabolic syndrome (MetS)., Methods: A total of 295 premenopausal Chinese women with PCOS diagnosed by the Rotterdam criteria (mean age: 30.2 +/- 6.4 years) and 98 control subjects without PCOS were evaluated for prevalence of MetS and cardiovascular risk factors, including dyslipidaemia and dysglycaemia., Results: Using the 2005 modified Adult Treatment Panel III criteria, MetS (presence of three or more risk factors) was found in 24.9% of PCOS women compared to 3.1% of controls. The prevalence of MetS in PCOS women increased from 16.7% at under 30 years of age to 53.3% at over 40 years. MetS was also more prevalent in overweight and obese (41.3%) than normal-weight PCOS women (0.9%). However, multivariate regression analysis showed that women with PCOS had a 5-fold increase in risk of MetS (odds ratio 4.90; 95% confidence interval: 1.35-17.84) compared with women without PCOS even after controlling for age and BMI, suggesting PCOS alone is an independent risk factor for MetS., Conclusions: There is high prevalence of MetS in Hong Kong Chinese women with PCOS despite their relatively young age. Recognition of these cardiometabolic risk factors requires a high level of awareness in conjunction with early and regular screening.

Objectives: To identify the characteristics of Hong Kong Chinese women with polycystic ovarian syndrome and to compare different diagnostic criteria., Design: Retrospective study., Setting: Gynae-endocrinology Clinics in the Prince of Wales Hospital, Hong Kong., Patients: Ninety Hong Kong Chinese women with polycystic ovarian syndrome who were diagnosed according to the hospital's criteria., Main Outcome Measures: Prevalence of typical features of polycystic ovarian syndrome, including anovulation and hyperandrogenism (with other endocrine causes excluded), polycystic ovarian features on ultrasonography, luteinising hormone predominance, obesity, and insulin resistance., Results: Almost all (98.9%) patients with polycystic ovarian syndrome presented with anovulation, only 48.9% of them had clinical or biochemical evidence of hyperandrogenism. Typical ultrasound appearances of polycystic ovaries were observed in 86.7% of patients. Luteinising hormone predominance and insulin resistance were demonstrated in 67.8% and 40.7% of the cohort, respectively. Eight-six (95.6%) patients should have also been diagnosed with polycystic ovarian syndrome based on the 2003 Rotterdam new criteria. About 60% of patients who screened positive for insulin resistance had normal fasting serum glucose levels. The same proportion who had full screening for insulin resistance by oral glucose tolerance tests and fasting serum glucose to insulin ratios had discordant results of these two tests., Conclusions: The 2003 Rotterdam new diagnostic criteria for polycystic ovarian syndrome are generally applicable to the Hong Kong Chinese population. Early detection of insulin resistance in patients with polycystic ovarian syndrome can be ensured by performing an oral glucose tolerance test combined with measurement of fasting serum glucose to insulin ratio.

We report on two patients with systemic lupus erythematosus, both of whom developed suppurative thyroiditis. One suffered from Staphylococcus aureus-induced thyroiditis and the other had tuberculous thyroiditis. The occurrence of tuberculous thyroiditis in systemic lupus erythematosus has not previously been reported. The diagnoses were made by fine-needle aspiration biopsy and subsequent bacteriological confirmation. Transient alteration of thyroid function was observed in both patients. In patients with systemic lupus erythematosus who present with fever and anterior neck pain, infection of the thyroid gland should be considered, and appropriate investigations undertaken.

Unlabelled: Leptin plays an important role in the regulation of body weight and energy balance. Women have higher circulating leptin level than men. In this study, we examined serum leptin concentrations in Type 2 diabetic men and women with or without nephropathy. Fasting plasma glucose (FPG), lipid profile, and serum leptin concentrations were measured in 34 Type 2 diabetic patients with nephropathy (DMN), 12 normoalbuminuric Type 2 diabetic subjects (DM) and 34 non-diabetic control subjects, all matched for age and body mass index (BMI)., Result: Patients with diabetic nephropathy had lower high-density lipoprotein cholesterol and higher triglyceride, FPG, urinary albumin/creatinine ratio (ACR) and serum creatinine than the other two groups. There was a significant trend in serum leptin concentrations (P<0.001, analysis of variance ANOVA) across the three groups with the main difference being detected between DMN and control subjects (DMN: 17.5 +/- 16.8 ng/ml, DM: 14.6 +/- 10.5 ng/ml and control: 9.1 +/- 7.1 ng/ml). Women had higher serum leptin concentration than men in the control group (12.5 +/- 7.3 ng/ml versus 4.2 +/- 2.0 ng/ml, P=0.001) and in the DM group (18.9 +/- 11 ng/ml versus 8.6 +/- 5.9 ng/ml, P=0.07) whereas this gender difference was not observed in the DMN group (18.6 +/- 17.0 ng/ml versus 16.8 +/- 17.0 ng/ml, P=0.754). On multivariate analysis, ACR (=0.411, P<0.001) and BMI (=0.240, P=0.002) were independently associated with serum leptin concentrations (R2=0.194, F=22.1, P<0.001) in the whole group. In the DMN group, ACR (=0.370, P=0.016) was the only independent determinant of serum leptin concentrations (R2=0.159, F=11.4, P=0.016). Serum leptin concentrations were higher in Type 2 diabetic patients with nephropathy than normoalbuminuric diabetic patients and controls. Diabetic men with nephropathy had proportionally higher serum leptin such that the gender difference in leptin observed in non-nephropathic individuals was abolished.

Diabetes is associated with an increased risk of cardiovascular disease (CVD). We studied risk factors for CVD in a cohort of Chinese type 2 diabetic patients recruited between July 1994 and August 1998. Ischemic heart disease (IHD) was defined as a history of: (i) confirmed coronary artery disease (with typical electrocardiographic changes or a positive exercise tolerance test) in patients under care of a cardiologist; (ii) documented myocardial infarction; or (iii) coronary interventions such as angioplasty or coronary artery bypass graft. Cerebrovascular accident (CVA) was defined as any definite cerebral vascular event with or without residual neurological deficit. CVD was defined as a history of IHD or CVA. The study enrolled 3333 patients, including 1370 men (41.1%) and 1963 women (58.9%) of mean age 55.9+/-13.3 years (range, 16-91 years; median, 57 years). A total of 279 patients (8.4%) had CVD (including 4.1% with CVA, 4.9% with IHD, and 0.6% with both CVA and IHD). Men had an overall higher rate of CVD than women (10.1% vs. 7.1%, p=0.002). All cardiovascular diseases showed a progressive increase in prevalence with increasing age with the peak among those aged

There is evidence that the development of retinopathy in type 2 diabetes is associated with a microsatellite polymorphism at 5' of the aldose reductase gene. The study examined whether cataract was associated with clinical/metabolic factors and/or the microsatellite polymorphism using a cohort of consecutively recruited Hong Kong Chinese patients with type 2 diabetes (n=567). Amongst these patients, 157 (28%) had cataract. The patients with cataract were older in age and age at diagnosis and had longer diabetes duration than those without cataract (all at p<0.01). They also had higher systolic blood pressure (p<0.01), HbA1c (p<0.05) and fasting plasma glucose levels (p<0.01; all with adjustment for the significance). Moreover, we found that the patients with cataract over-presented the microsatellite allele Z (23 vs. 30%, p<0.01) and its genotypes (Z,Z+Z,non-Z; 38 vs. 50%, p<0.01), but under-presented the allele Z-4 (8.3 vs 4.8%, p<0.05) and its genotypes (Z-4, Z-4+Z-4,non-Z-4; 16 vs. 10%, p<0.05). Using multiple logistic regression analysis (R2=0.25, p<0.01), we found that the presence of cataract was correlated positively with age, but inversely with the presence of allele Z-4. In conclusion, our data indicate that the occurrence of cataract is common in the Chinese type 2 diabetes population, with age and the aldose reductase gene as important determinants.

Weber-Christian disease is an inflammatory disorder of fatty tissue which usually presents with raised red tender nodules in the skin. Although there may be additional systemic upset, there are very few reports of neurological features associated with this condition. We report a patient with biopsy-confirmed systemic Weber-Christian disease in whom a transient partial myelopathy, of probable inflammatory origin, was the most prominent feature. Based on recent reports of the effects of immune mediators on neuronal function, a possible pathogenetic explanation for this syndrome is suggested.

We examined the determinants of glycaemic control in a consecutive cohort of 562 newly-referred Chinese type 2 diabetic patients (57% women) during a 12-month period. All patients underwent a structured assessment with documentation of clinical and biochemical characteristics. Pancreatic beta-cell function was assessed by fasting plasma C-peptide concentration. Insulin deficiency was defined as fasting plasma C-peptide <0.2 pmol/ml. Insulin resistance (IR) was calculated using the homeostasis model assessment (HOMA) based on a product of fasting plasma glucose and insulin concentrations. Treatment was considered appropriate when insulin-deficient patients were treated with insulin and non-insulin-deficient patients were treated with oral agents or diet. Mean (+/-SD) age was 54.3+/-13.8 years (range 17-87 years) and disease duration was 5.0+/-5.9 years. At the time of referral, 70.5% (n=396) were on drug therapy (9% on insulin and 62.8% on oral agents), 20.6% (n=116) were on diet and 9% (n=50) had not received any form of treatment. The mean HbA(lc) was 8.4+/-2.3%. The geometric mean (x// antilog SD) of IR was 4.62x//2.51 (range 0. 63-162.7) and correlated only with waist : hip ratio (WHR, p=0.008). The geometric mean of plasma C peptide was 0.47x//2.89 nmol/l and correlated with BMI (p<0.001). Glycated haemoglobin was correlated positively with age (p=0.013), disease duration (p<0.001), IR (p<0. 001) and negatively with BMI (p<0.001). Glycated haemoglobin was lower in patients who had seen a dietitian (7.9% vs. 8.7%, p<0.001) or diabetes nurse (7.8% vs. 8.7%, p<0.001) or who performed self blood glucose monitoring (7.9% vs. 8.6%, p=0.001) and higher among smokers (8.9% vs. 8.2%, p=0.003). Compared to insulin-deficient patients (n=118), non-insulin-deficient patients (n=413) had features resembling that of the Metabolic Syndrome with increased WHR (p=0.005), blood pressure (p<0.001), BMI (p=0.001) and were older (p=0.04). Amongst the insulin-deficient patients, 27% were treated with oral agents or diet. Patients receiving appropriate therapy (n=362) had a lower HbA(lc) than those treated inappropriately (n=173) (8.2% vs. 8.7%, p=0.02). On multivariate analysis, short disease duration (p<0.001), low IR (p<0.001), high BMI (p=0.001), diabetes education (p<0.001), lack of smoking (p=0. 014) and choice of appropriate treatment (p=0.009) were the independent determinants of good glycaemic control.

By means of intracellular recordings from sympathetic ganglion in vitro, the present study was to investigate whether the receptors of substance P (SP) and 5-hydroxytryptamine (5-HT) exist in the same neuron or separately in different neurons of guinea pig celiac ganglion (CG) and inferior mesenteric ganglion (IMG) and whether there are some interactions between the two transmitters. Of the 133 neurons of CG, 66 (49.6%) responded to both SP and 5-HT, 40 (30.1%) only to SP or 5-HT, 27 (20.3%) insensitive to both. The corresponding numbers of the corresponding groups of neurons of the 129 IMG neurons are 47 (36.4%), 65 (50.4%) and 17 (13.2%). Continuous superfusion of IMG with 5-HT did not affect SP depolarization, while continuous superfusion of IMG with SP did not affect 5-HT depolarization. The results indicate that SP receptor and 5-HT receptor may exist in the same neuron, and neither affects each other.

Aim: To study the effects of several 5-hydroxytryptamine (5-HT) receptor subtype antagonists on 5-HT-induced depolarization and the effects of 5-HT1P receptor agonist on the membrane potential in the neurons of guinea pig inferior mesenteric ganglion (IMG)., Methods: Intracellular recordings were made from neurons of the isolated guinea pig IMG., Results: Cyproheptadine (5-HT1/2 antagonist 10 mumol.L-1, n = 7) and BRL 24924 (5-HT1P antagonist 10 mumol.L-1, n = 19) reversibly suppressed 5-HT slow response; pressure ejection of MCPP (5-HT1P agonist 10 mmol.L-1) induced a slow depolarization in most of 5-HT sensitive neurons (10/14)., Conclusion: 5-HT-induced slow depolarization is mediated by 5-HT1P receptor.

By means of intracellular recordings from spinal cord slices of neonatal rats in vitro, the effects of 5-hydroxytryptamine (5-HT), nor-adrenaline (NA) and adrenaline (AD) on membrane potential in sympathetic preganglionic neurons (SPN) were observed, in order to clarify whether these neuron contain a single type of the monoamine receptor or in combination with more than one type of receptors. The results showed that: (1) 5-HT, NA and AD induced membrane depolarization respectively in 57.1% (16/28), 60% (15/25) and 52.4% (11/21) of SPN. (2) According to the reactions of SPN to the three monoamines, several subtypes of SPN could be divided: those sensitive to all the three monoamines (3/19), those sensitive to two of them (9/19), those only sensitive to one type of monoamines (4/19) and those insensitive at all (3/19). The significance of coexistence of more than one type of the three monoamines in a single neuron remains to be elucidated.

The work was carried out to investigate the relationship of non-cholinergic late slow excitatory potential (LS-EPSP) with 5-hydroxytryptamine (5-HT) and substance P (SP) in the neurons of the guinea pig celiac ganglion (CG) using intracellular electrodes in vitro. During repetitive stimulation of the splanchnic nerve (SN), LS-EPSP following a series of action potentials could be recorded in 161 out of 206 neurons (78.2%); Application of 5-HT and SP by superfusion or pressure ejection induced 5-HT depolarization in 102 out of 149 neurons (68.5%) and SP depolarization in 98 out of 188 neurons (52.1%), respectively; Most neurons, from which LS-EPSP could be recorded during stimulation of SN, were sensitive to 5-HT (73/88, 83.0%) and SP (68/114, 59.7%). However, only a small number of neurons not showing LS-EPSP during stimulation of SN were sensitive to 5-HT (10/26, 38.5%, P < 0.0001) and SP (11/36, 30.6%, P < 0.01). The results support the viewpoint that both 5-HT and SP are involved in the formation of LS-EPSP as transmitters; In addition, both effects of 5-HT and SP were examined in 133 neurons. There were 66 of these neurons (49.6%) to be sensitive to both 5-HT and SP, suggesting that there may be some functional relations between 5-HT and SP in the neurons of guinea pig CG.

Pancreatic ganglia contain 5-hydroxytryptamine (5-HT)-immunoreactive axons, some of which are extensions of myenteric neurons located in the pyloric antrum and proximal duodenum. The present study investigated the effect of 5-HT on the membrane potential of cat pancreatic ganglion neurons by means of intracellular recordings in vitro. Pressure application of 5-HT evoked a fast depolarization in 29 of 147 neurons and a slow depolarization in 89 of 147 neurons. A biphasic response was observed in 10 of 108 neurons. The 5-HT-induced slow depolarizing response was not altered in a low Ca2+ (0.1 mM), high Mg2+ (15 mM) solution nor by hexamethonium (10(-4) M) or atropine (10(-6) M). The fast depolarizing response was associated with a decrease of membrane input resistance (-17.2%). The slow depolarizing response was associated with either a decrease (-19.6%) in 24, an increase (+25.0%) in 20, or without a detectable change of membrane input resistance in 10 out of 54 neurons tested. Conditioning hyperpolarization increased the amplitude of both fast and slow depolarizing responses. A low Na+ (68.5 mM) solution and a high K+ (23.5 mM) solution significantly reduced the amplitude of the slow depolarizing response. A low Cl- (9.6 mM) solution had no significant effect on the slow depolarization. The 5-HT3 receptor antagonist MDL 72222 (Bemesetron) blocked the 5-HT-evoked fast depolarizing response. BRL 24924 (Renzapride) and 5 HT-DP, antagonists for the putative 5-HT1P receptor, blocked the slow depolarizing response. The 5-HT3 receptor agonist 2-methyl-5-HT evoked a fast depolarizing response and MCPP, an agonist for the putative 5-HT1P receptor, evoked a slow depolarizing response. Spiperone (a 5-HT1A receptor antagonist) and mianserin (a 5-HT2 receptor antagonist) had no effect on either depolarizing response to 5-HT. The results show that pancreatic ganglion neurons responded to 5-HT with fast and slow depolarizing responses. The data suggest that these responses were mediated by the 5-HT3 receptor and the putative 5-HT1P receptor, respectively.

The effect of nifedipine on electrophysiological membrane properties and nicotinic neurotransmission of guinea pig celiac ganglion neurons was studied using intracellular recordings in vitro. Nifedipine in concentrations of 0.1-10 microM did not affect membrane potential, membrane input resistance or the amplitude and duration of action potentials induced by intracellular current injection. Higher doses of nifedipine (0.1-1 mM) significantly reduced the amplitude and extended the duration of action potentials induced by intracellular current injection. Superfusion of the ganglia with nifedipine in concentrations of 0.1-10 microM significantly inhibited nicotinic fast excitatory postsynaptic potentials (f-EPSPs) and orthodromic action potentials evoked by nerve stimulation. This depressant effect of nifedipine on synaptic transmission was eliminated with high Ca2+ (12.5 mM). Nifedipine (10 microM) did not affect the postsynaptic effect of exogenous acetylcholine (ACh), but significantly reduced the quantal content but not the quantal size of evoked f-EPSPs in a low Ca2+ (0.5 mM), high Mg2+ (5.5 mM) Krebs solution. Nifedipine in concentration of 10 microM did not affect afterspike hyperpolarization (AH) and post-tetanic hyperpolarization (PTH), which have been recognized to be generated mainly by an increase of calcium-dependent potassium conductance. Higher doses of nifedipine (0.1-1 mM) significantly depressed AH and PTH. These experimental results suggest that nifedipine in concentrations of 0.1-10 microM exerts an inhibitory effect on nicotinic neurotransmission without affecting the membrane properties of the guinea pig celiac ganglion neurons. This inhibitory effect of nifedipine on synaptic transmission may result from blocking L-type calcium channels and reducing the quantal release of ACh from the presynaptic nerve terminals.

Reversible effects of nifedipine, a calcium channel blocker, on 3 types of calcium-dependent potentials in the celiac ganglion cells of the guinea pigs in vitro were investigated by means of intracellular recordings. Nifedipine (0.1-1 mmol/L) inhibited the spike afterhyperpolarization, the post-tetanic membrane potential in dose-dependent manner. Nifedipine (0.1 mumol/L) also depressed the Ca2+ spike potential in a Na(+)-free/high Ca2+ solution plus TEA. Thus the results indicate that nifedipine in clinical therapeutic dosage may directly reduce Ca2+ conductance and then in higher concentration may also depress secondarily Ca(2+)-dependent potassium conductance. These actions of nifedipine may underlie the mechanism of blockade of quantal release of ACh from presynaptic membrane as well as the modulation of excitability of sympathetic postganglionic neuron.

By means of intracellular recording technique, it was observed that: (1) Application of serotonin (5-HT) caused in a portion of the neurons of the guinea pig inferior mesenteric ganglia (IMG) a slow depolarization similar to non-cholinergic late slow excitatory postsynaptic potential (ls-EPSP). (2) Prolonged superfusion of 5-HT markedly suppressed the ls-EPSP in 5-HT sensitive neurons. (3) The ls-EPSP elicited in 5-HT sensitive neurons as well as the 5-HT depolarization could be enhanced by fluoxetine 5-HT reuptake inhibitor; In contrast, the ls-EPSP of 5-HT insensitive neurons was not appreciably changed by this drug. (4) Pretreating the guinea pigs with para-chlorophenylalanine (PCPA), a 5-HT biosynthesis inhibitor, markedly reduced the occurrence rate and amplitude of ls-EPSP. These results indicate that ls-EPSP of the guinea pig IMG is possibly mediated by several transmitters including 5-HT.

The non-cholinergic late slow excitatory postsynaptic potential (ls-EPSP) of the guinea pig inferior mesenteric ganglion (IMG) was previously believed to be mediated by substance P (SP) or several other neuropeptides. Yet, the pharmacological evidence presented here indicates that serotonin (5-HT) may be another transmitter for the ls-EPSP in the guinea pig IMG. Repetitive stimulation of the presynaptic nerves elicited ls-EPSP in about half of the IMG neurons. Application of 5-HT or SP caused, in a portion of the IMG neurons, a slow depolarization similar to ls-EPSP. Fifty-six out of 88 (63.6%) neurons with ls-EPSP and 13 out of 35 (37.1%) neurons with ls-EPSP were sensitive to 5-HT and SP, respectively. Superfusion of the ganglia with 5-HT markedly suppressed the ls-EPSP evoked in 5-HT sensitive neurons. Similarly, exogenously applied SP attenuated the ls-EPSP of SP-sensitive neurons. However, prolonged superfusion of 5-HT or SP had no effect on the ls-EPSP elicited in 5-HT or SP-insensitive neurons, respectively. Furthermore, the ls-EPSPs elicited in 5-HT-sensitive neurons as well as the 5-HT-induced depolarization were reversibly suppressed by cyproheptadine, a 5-HT antagonist, and enhanced by fluoxetine, a 5-HT reuptake inhibitor. In contrast, the ls-EPSP of 5-HT insensitive neurons and SP-induced depolarization were not appreciably changed by those two drugs. Pretreatment with p-chlorophenylalanine, a 5-HT biosynthesis inhibitor, did not change the general electrophysiological characteristics of the neurons and did not suppress nicotinic neurotransmission, but markedly reduced the occurrence rate of ls-EPSP from 53.8% to 15.1% (P less than 0.005). Collectively, our results indicate that, besides SP, 5-HT may be involved in mediating the ls-EPSP in a subpopulation of neurons in the guinea pig IMG. The type of transmitter mediating ls-EPSP is apparently not limited to 5-HT and SP, as about 30% of the neurons with ls-EPSP were found to be insensitive to both 5-HT and SP and prolonged superfusion with both did not affect appreciably the ls-EPSP elicited in these neurons.

The effect of nifedipine, a calcium channel blocker, on nicotinic transmission, was studied in the isolated celiac ganglia of the guinea pig by means of intracellular recordings. Nifedipine in concentration of 0.1-10 mumol/L did not affect resting membrane potential, input membrane resistance and action potential induced by intracellular stimulation in all cells tested, but obviously inhibited nicotinic transmission. The depressant effect of nifedipine on synaptic transmission could be limited by low Ca2+ and antagonized by high Ca2+. Nifedipine did not affect acetylcholine (ACh) sensitivity of postsynaptic membrane, but decreased frequency of miniature excitatory postsynaptic potentials (mEPSPs) in high K+ Kreb's solution and reduced quantal content without effect on quantal size of evoked EPSPs in low Ca2+ /high Mg2+ kreb's solution. The results indicate that nifedipine in therapeutic dose exerts depressant effect on synaptic transmission through blocking Ca2+ entry into presynaptic membrane and reducing quantal release of ACh from presynaptic nerve terminals.

The effects of 5-hydroxytryptamine (5-HT) on lateral horn cells contained in thin in vitro slices of neonatal rat spinal cord were investigated by means of intracellular recording techniques. Superfusion of 5-HT (1-100 microM) to lateral horn cells caused a concentration-dependent membrane depolarization leading to, in some instances, repetitive cell discharges. A number of lateral horn cells could be activated antidromically by stimulating the ventral rootlets. The conduction velocity of the antidromic spikes was estimated to be 0.3-2 m/s which corresponds to that of the axons of rat sympathetic preganglionic neurons reported by others. The 5-HT depolarization evoked in neurons that could be activated antidromically was similar to that elicited from unidentified lateral horn cells. The depolarization induced by 5-HT could be partially eliminated by low Ca/high Mg solution or tetrodotoxin in a portion of lateral horn cells and was accompanied by an increase in membrane resistance. The response was nullified near the membrane potential at which the spike after hyperpolarization was abolished; a clear reversal of polarity was not observed at a more negative potential level. The 5-HT depolarization was reversibly blocked by methysergide and cyproheptadine and enhanced by fluoxetine, a 5-HT-uptake inhibitor. The results indicate that the indoleamine primarily exerted an excitatory action on lateral horn cells, including those tentatively identified as sympathetic preganglionic neurons, by a direct depolarization which appears to be mediated by decrease of a voltage-sensitive K conductance and partly by an indirect effect via the release of an excitatory substance(s).

A short train of nerve stimulation evoked in a portion of neurons of the guinea pig inferior mesenteric ganglia a slow hyperpolarization (slow IPSP) which persisted when the preceding orthodromic spikes were reduced to subthreshold EPSPs by curare, was reversibly abolished in a low Ca solution, and was not blocked by atropine; furthermore, the post-tetanic hyperpolarization induced by direct intracellular stimulation was generally smaller than the slow IPSP evoked by nerve stimulation. The slow IPSP was often associated with a fall in membrane resistance and its amplitude decreased with membrane hyperpolarization. The results indicate that the slow hyperpolarization is a synaptic potential, and differs from the slow IPSP observed in mammalian and amphibian paravertebral ganglionic neurons in that it is atropine insensitive.

Neuropharmacological and histochemical evidence presented here indicates that serotonin (5-HT) is the transmitter mediating one of the postsynaptic potentials in the guinea pig celiac ganglion. Repetitive nerve stimulation elicited in celiac neurons, in addition to the nicotinic fast excitatory postsynaptic potential (EPSP), a slow EPSP that was resistant to cholinergic antagonists. Application of 5-HT caused a depolarization with membrane characteristics similar to those of the slow EPSP; furthermore, the latter was reversibly suppressed by 5-HT. The slow depolarization evoked by either nerve stimulation or 5-HT was augmented by fluoxetine, a 5-HT reuptake blocker, and depressed by cyproheptadine, a 5-HT receptor blocker; in addition, tryptophan, a precursor of 5-HT, enhanced differentially the slow EPSP. Lastly, histochemical study revealed dense networks of 5-HT immunoreactive nerve fibers encircling many ganglionic neurons.

Superfusion of norepinephrine (NE) (1-50 microM) onto lateral horn cells, including antidromically identified sympathetic preganglionic neurons (SPNs), situated in thin transverse neonatal rat thoracolumbar spinal cord slices caused a membrane depolarization and repetitive cell discharges. The NE depolarization was associated with an increase in membrane resistance, and the response became smaller upon conditioning hyperpolarization; a clear reversal of polarity, however, was not observed. Pretreating the slices with phentolamine and prazosin but not yohimbine or propranolol prevented the depolarizing effect of NE. This finding, in conjunction with the evidence of the presence of noradrenergic fibers in the spinal cord, suggests that NE may serve as an excitatory neurotransmitter to neurons of the lateral horn.

The effects of vasopressin (VP) on lateral horn cells including a number of sympathetic preganglionic neurons contained in thin in vitro slices of neonatal rat spinal cord were investigated by means of intracellular recording techniques. Superfusion of (Arg8)-vasopressin (AVP, 0.01-1 microM) caused a depolarization leading, in the majority of lateral horn cells, to repetitive discharges. The AVP depolarization which could be partially reduced by low Ca/high Mg solution or tetrodotoxin, was accompanied by an increase in membrane resistance and the response was nullified near the membrane potential at which the spike afterhyperpolarization was abolished. A clear reversal of the response was not observed upon further hyperpolarization. The AVP response was blocked by the VP1 antagonist, D-(CH2)5 Tyr (Me)-AVP, whereas, deamino (D-Arg8-vasopressin), a VP2 agonist, at high concentrations (greater than or equal to 50 microM) was either ineffective or produced a small depolarization. The results indicate that AVP, acting mainly on VP1 receptors, excited lateral horn cells by a direct depolarization and an indirect effect via the release of an excitatory transmitter(s). A reduction of a voltage-dependent K conductance may underlie the depolarizing effect of AVP.

Neurokinin A (NKA) applied either by superfusion (0.1-10 microM) or by pressure ejection evoked a slow membrane depolarization in neurons of the inferior mesenteric ganglia in vitro. The NKA-induced depolarization which was not significantly affected by reducing the Ca concentration or by tetrodotoxin was associated in most cases by a small-to-moderate increase in membrane resistance; however, conditioning hyperpolarization increased rather than decreased the response. The depolarization elicited by NKA was eliminated in the presence of substance P (SP) and the depolarization by SP in the presence of NKA. The results suggest that the actions of NKA on prevertebral neurons are similar to that of SP and that these two peptides may act on the same receptors or share similar ionic channels.

The presence of neurokinin-A-like immunoreactivity in guinea-pig inferior mesenteric ganglia was detected by radioimmunoassay procedures. Pretreating the animals with capsaicin 7 days prior to experimentations reduced the mean content of neurokinin-A-like immunoreactivity by 85% from its control value of 150 +/- 31.3 fmol per ganglion. High-performance liquid chromatography revealed that neurokinin-A-like immunoreactivity was heterogenous as in addition to neurokinin A, peaks corresponding to the amphibian tachykinin eledoisin and to neuropeptide K were detected, and they too were depleted by capsaicin. Electrophysiological studies showed that neurokinin A applied either by superfusion or by pressure ejection evoked a slow depolarization in the majority of inferior mesenteric ganglia neurons in vitro. Neurokinin-A-evoked depolarizations in the majority of cells tested were associated with a small increase in membrane input resistance. However, the responses were increased by membrane hyperpolarization: the extrapolated mean equilibrium potential of neurokinin-A-induced depolarization was -36 mV. Removal of extracellular sodium but not chloride ions suppressed the neurokinin-A-induced depolarization. The slow depolarization elicited either by exogenously applied substance P or by repetitive stimulation of hypogastric nerves was reversibly eliminated in the presence of neurokinin A. Collectively, our studies suggest that neurokinin-A-like immunoreactivity may coexist with substance-P-like immunoreactivity in capsaicin-sensitive fibers in the guinea-pig prevertebral ganglia and that the similarity of the actions of neurokinin A on the one hand and substance P on the other raises the possibility that non-cholinergic excitatory potentials elicited in the inferior mesenteric ganglia may be generated by not one but a number of closely related tachykinins.

Intracellular recordings were made from the cells in the interm ediolateral nucleus (IML) of neonatal rat spinal cord slices in vitro. Both resting and active electrophysiological properties of the cellular membrane were investigated. Resting membrane potential ranged from -46 to -70 mV. The means of input resistance, time constant and membrane capacitance were 108.3 +/- 67.9 M omega (mean +/- SD), 9.9 +/- 5.6 ms and 138.6 +/- 124.2 pF, respectively. Repetitive firing at high frequency (up to 150 Hz) could be produced in thirty five cells (85.4%) in response to intracellular injection of depolarizing current, while single spike firing produced in the remaining cells (15.6%). The amplitude and duration of action potentials evoked by intracellular stimulation were 63.4 +/- 9.0 mV and 2.4 +/- 0.6 ms, respectively. The threshold at the level of 18.7 +/- 6.2 mV was more depolarized than the resting potential. In most of cells, spikes induced by intracellular stimulation were followed by afterhyperpolarization, whose peak amplitude and duration were 5.1 +/- 2.7 mV and 90 +/- 31.8 ms, respectively. EPSP, orthodromic action potentials and, rarely, IPSP could be evoked by dorsal root stimulation, and antidromic action potentials were obtained by ventral root stimulation. Identification of sympathetic preganglionic neuron and functional significance of electrophysiological properties were discussed.

Serotonin (5-HT) in the guinea pig celiac-superior mesenteric plexus was quantitatively measured by HPLC and visualized by an immunohistochemical method. Preincubation of the ganglia in a Krebs solution containing L-tryptophan and pargyline markedly elevated the content of 5-HT and K+ solution caused a release of 5-HT into the incubation medium. 5-HT immunoreactivity was localized to dense but unevenly distributed nerve fibers throughout the plexus and to small diameter cells commonly referred to as small intensely fluorescent cells. These findings provide evidence of an extensive network of 5-HT-containing neural elements in the guinea pig prevertebral ganglia.