[One case of bromadiolone poisoning leading to intestinal necrosis and severe coagulopathy].

Bromadiolone is still often used in life as a poisonous rodent agent. Bromadiolone poisoning is often manifested as coagulation dysfunction, resulting in organ bleeding, including cerebral hemorrhage, intestinal bleeding, abdominal hemorrhage, etc. At present, no case of intestinal necrosis caused by bromadiolone poisoning have been reported. This article reviewed one case of intestinal necrosis and severe coagulation dysfunction, and finally confirmed bromadiolone poisoning by poison detection. The patient recovered and was discharged after surgery, vitamin K injection, plasma transfusion and other treatment methods.

[The clinical characteristics of functional hypothalamic amenorrhea with hyperandrogenism].

Objective: To explore the clinical and biochemical discriminants of hyperandrogenism in functional hypothalamic amenorrhea (FHA). Methods: From January to September 2022, a total of 56 patients with FHA group in the Obstetrics and Gynecology Hospital of Fudan University outpatient clinic were included in this retrospective cross-sectional analysis. According to the clinical or biochemical features of hyperandrogenism, FHA patients can be divided into two subgroups, namely hyperandrogenic FHA and non-hyperandrogenic FHA. Explore the differences and its significances between hyperandrogenic FHA and non-hyperandrogenic FHA by comparing anthropometry, reproductive hormones, AMH, ultrasonic manifestation, the scores of eating attitude test, depression questionnaire and anxiety scale respectively and analyzing their correlations. Results: The age of 56 FHA patients was 15-32(23.36±4.90) years, and body mass index(BMI) was (18.91±2.49) kg/m2. The age of hyperandrogenic FHA and non-hyperandrogenic FHA was (21.76±4.40) and (24.05±5.00) (P=0.109) years old respectively, and BMI was (19.14±3.15 )and (18.81±2.18) kg/m2 (P=0.702). Compared to the non-hyperandrogenic FHA, the AMH (6.46 and 3.63 ng/ml, P=0.025) and PRL (278.78 and 149.46 mU/ml, P=0.002) levels were higher in hyperandrogenic FHA group. There was no significant difference between the hyperandrogenic and non-hyperandrogenic FHA group in body composition.GAD-7 (r=0.455, P=0.005) and PHQ-9 (r=0.664, P<0.001) were correlated with EAT-26 scores in non-hyperandrogenic FHA group, but no significant correlation was shown between PHQ-9 (r=0.091, P=0.766)、GAD-7 (r=0.304, P=0.313) and EAT-26 in hyperandrogenic FHA group. Conclusions: Some patients with FHA had clinical manifestations of hyperandrogenism and mildly elevated AMH and PRL, with underlying PCOS endocrine characteristics.

[Correlation analysis between Dx-pH monitoring and proton pump inhibitor test in the diagnosis of laryngopharyngeal reflux disease].

Objective: The consistency of 24-hour oropharyngeal Dx-pH monitoring and proton pump inhibitor(PPI) test in the diagnosis of laryngopharyngeal reflux disease (LPRD) was investigated. Methods: Sixty patients with laryngopharyngeal reflux (LPR) related symptoms who had never received PPI treatment were assessed by reflux symptom index (RSI) and reflux finding score (RFS) between October 2017 and October 2018, including 28 males and 38 females, aged from 16 to 72 years, with a medium age of 38 years. Prior to treatment, all patients were evaluated with 24 hours oropharyngeal Dx-pH monitoring(Restech). After empiric therapy with PPI twice-daily for 8 weeks, the efficacy was evaluated according to posttreatment RSI score.The data was analysed with Kruskal-Wallis test, Student Newman Keuls test and consistency check. Results: (1)Among all 60 patients,13 patients (21.7%) had pathologic Ryan score and all resulted responsive to PPI;27 patients (45.0%) with a negative Ryan score were unresponsive to PPI; 20 patients (33.3%) despite a negative Ryan score resulted responsive to PPI therapy. Considering responsiveness to PPI therapy as the gold standard for the diagnosis of LPRD, the sensitivity, specificity, positive predictive value and negative predictive value of Ryan score were 39.4%, 100%, 100% and 57.4% respectively. The Kappa value was 0.369 (P<0.01). (2)Among 34 patients (56.7%) with positive Dx-pH results (24-hour oropharyngeal acid reflux events≥ 3 times), 29 patients were positive and 5 patients were negative in PPI test. Among 26 patients with negative Dx-pH results (24-hour oropharyngeal acid reflux events<3 times), 4 patients were positive and 22 patients were negative in PPI test. Considering responsiveness to PPI therapy as the gold standard for the diagnosis of LPRD, the sensitivity, specificity, positive predictive value and negative predictive value of 24-hour oropharyngeal acid reflux events were 87.9%, 81.5%, 85.3% and 84.6% respectively. The Kappa value was 0.696(P<0.01). Conclusions: There is a positive correlation between 24-hour oropharyngeal Dx-pH monitoring positive results (24-hour oropharyngeal acid reflux events≥3 times) and PPI test in the diagnosis of LPRD. The 24-hour oropharyngeal Dx-pH monitoring can be a promising tool for the diagnosis of suspected LPRD patients, and more sensitive and accurate Dx-pH diagnostic index will be required in the clinic.

The Function of Wnt Ligands on Osteocyte and Bone Remodeling.

Bone homeostasis is continually maintained by the process of bone remodeling throughout life. Recent studies have demonstrated that Wnt signaling pathways play a fundamental role in the process of bone homeostasis and remodeling. Intracellular Wnt signaling cascades are initially triggered by a Wnt ligand-receptor complex formation. In previous studies, the blocking of Wnt ligands from different osteoblastic differentiation stages could cause defective bone development at an early stage. Osteocytes, the most abundant and long-lived type of bone cell, are a crucial orchestrator of bone remodeling. However, the role of Wnt ligands on osteocyte and bone remodeling remains unclear. In our present study, we found that, besides osteoblasts, osteocytes also express multiple Wnt ligands in the bone environment. Then, we used a Dmp1-Cre mouse line, in which there is expression in a subset of osteoblasts but mainly osteocytes, to study the function of Wnt ligands on osteocyte and bone remodeling in vivo. Furthermore, we explored the role of Wnt ligands on osteocytic mineralization ability, as well as the regulatory function of osteocytes on the process of osteoblastic differentiation and osteoclastic migration and maturity in vitro. We concluded that Wnt proteins play an important regulatory role in 1) the process of perilacunar/canalicular remodeling, as mediated by osteocytes, and 2) the balance of osteogenesis and bone resorption at the bone surface, as mediated by osteoblasts and osteoclasts, at least partly through the canonical Wnt/ß-catenin signaling pathway and the OPG/RANKL signaling pathway.

[Association between serum Nε-carboxymethyl-lysine level and anterior tibial arterial plaque calcification in patients with diabetic foot post foot amputation].

Objective: To observe the correlation between Nε-carboxymethyl-Lysine (CML), the main component of advanced glycation end products and the calcification of the anterior tibial artery plaque in patients with diabetic foot post foot amputation. Methods: Sixty patients hospitalized for foot amputation operation due to diabetic foot from June 2012 to June 2016 in the Department of Orthopedics, Affiliated Hospital of Jiangsu University were prospectively recruited.The patients were categorized into mild stenosis (0

Trends in drug-resistant tuberculosis in China: data from a clinical tuberculosis centre.

OBJECTIVE: To describe the trends in prevalence of drug-resistant tuberculosis (TB) among in-patients in Beijing Chest Hospital, Beijing, China, using a 10-year retrospective study. DESIGN: From 2005 to 2014, 18 310 in-patients with TB were recruited for the study, most of whom were referrals; no distinction was made between new and previously treated cases. Drug susceptibility testing (DST) was performed in culture-positive cases using the proportion method to determine multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB). Risk factors associated with drug resistance were identified. RESULTS: A total of 5141 (28.0%) samples were culture-positive. DST results showed that 860 (16.7%) cases were MDR-TB and 176 (3.4%) were XDR-TB. MDR-TB and XDR-TB were detected in respectively 21.2% and 12.5% of new cases. The rate of MDR-TB and XDR-TB gradually increased from 2005, with MDR-TB reaching a peak in 2008 and XDR-TB in 2009. These data closely mirror national survey data on this region, patient age and occupation. CONCLUSION: Trends in MDR-TB and XDR-TB prevalence during the past decade and their inflection points were determined, which complemented reports from previous national surveys. This information is useful for fighting TB in China.

The motility of esophageal sphincters during liquid and solid bolus swallows: a multicenter normative value study of high-resolution manometry in China.

BACKGROUND: It is gradually accepted that solid bolus swallow needs to be added to the procedure of manometry. The motility differences in the upper esophageal sphincter (UES) and lower esophageal sphincter (LES) were not well described. Sierra Scientific Instruments solid-state high-resolution manometry (HRM) system, the most popular HRM system in China, lacks the Chinese normative values for both liquid and solid bolus swallow parameters. METHODS: The esophageal HRM data of 88 healthy volunteers were analyzed. The parameters of both sphincters in resting stage were summarized and those during solid and liquid swallows were compared. KEY RESULTS: Normative HRM values of sphincter parameters in solid and liquid bolus swallows in China were established. The UES residual pressure of solid bolus swallows was lower than that of liquid bolus (0.3±5.5 mm Hg vs 4.8±5.9 mm Hg, P=.000). The time parameters of UES relaxation between two types of bolus swallows were similar. In solid bolus swallows, the intrabolus pressure (IBP) (13.8±5.1 mm Hg vs 10.9±5.7 mm Hg, P=.000) and LES relaxation time (11.0±2.1 seconds vs 8.7±1.3 seconds, P=.000) were higher. The 4-second integrated relaxation pressure between both bolus swallows was similar. CONCLUSIONS & INFERENCES: The function of the UES and LES between solid and liquid bolus swallows is different. Chinese HRM parameters are different from the Chicago Classification (http://www.chictr.org.cn, Number ChiCTR-EOC-15007147).

[Classification and corrective methods of obviously asymmetric palpebral fissure of single-fold eyelid].

OBJECTIVE: To discuss the classification of obviously asymmetric palpebral fissure of single-fold eyelid and their corrective methods performed with double-fold eyelid blepharoplasty simultaneously. METHODS: Forty patients with obviously asymmetric palpebral fissure of single-fold eyelid of two eyes were admitted to Linyi People's Hospital in Shandong province from January 2010 to September 2014, asking for double-fold eyelid blepharoplasty. The preoperative difference of palpebral fissure width between two eyes reached 1.0-2.0 (1.44±0.23) mm. Obviously asymmetric palpebral fissures of single-fold eyelid were divided into three types according to the characteristics of eyelids of two eyes and were corrected by following methods performed with double-fold eyelid blepharoplasty with total incision simultaneously. (1) Twenty-four patients only with different sagging skin of upper eyelids were corrected by resecting sagging skin of eyelids' margins, and the width of the widest position of resected eyelids' skin was twice as wide as that of the sagging skin of eyelids' margins (the same below). (2) Among 6 patients only with different palpebral fissure width, 4 patients whose difference of palpebral fissure width was not bigger than 1.4 mm were corrected by the method of resecting surplus skin, and the width of the widest position of resected eyelids' skin with narrower palpebral fissure was 1 mm wider than the difference of palpebral fissure width between two eyes (the same below). The other 2 patients whose difference of palpebral fissure width between two eyes was bigger than 1.4 mm were corrected by the method of resecting surplus skin and shortening aponeurosis of levator muscle of upper eyelid. The width of shortened aponeurosis of levator muscle of eyelids with narrower palpebral fissure was 1 mm wider than difference of palpebral fissure width between two eyes (the same below). (3) Among 10 patients with mixing symptoms of sagging upper eyelids skin and difference of palpebral fissure width bigger than 1.0 mm after smoothing sagging upper eyelids' skin, 7 patients whose difference of palpebral fissure width was not bigger than 1.4 mm were corrected by resecting sagging skin and the method of resecting surplus skin. The other 3 patients whose difference of palpebral fissure width was bigger than 1.4 mm were corrected by resecting sagging skin, shortening aponeurosis of levator muscle of upper eyelids and resecting surplus skin. Palpebral fissure widths of patients were measured during follow-up. Difference of palpebral fissure width between two eyes was calculated and the last difference was recorded. Data were processed with paired sample t test. RESULTS: Nine patients who showed incomplete closure of palpebral fissure on the sides of resected eyelids skin or shortened aponeurosis of levator muscle of upper eyelids after operations were treated with erythromycin eye ointment drop in eyes and recovered one week to one month after operations, with no complication of conjunctivitis or keratitis. Double-fold eyelids of all patients who were followed up for 8 to 12 months showed natural shape, smooth lines. No patient showed obvious asymmetry of palpebral fissure between two eyes, and no recurrence of asymmetric palpebral fissure was observed. Difference of palpebral fissure width was 0.1-0.5 (0.19±0.09) mm in the last follow-up, which was obviously smaller than that before operation (t=39.202, P<0.001). CONCLUSIONS: Obviously asymmetric palpebral fissure of single-fold eyelid can be corrected during the operation of double-fold eyelid blepharoplasty. Patients only with different sagging skin of upper eyelids can be corrected by resecting sagging skin of eyelids' margins. Patients only with different palpebral fissure width between two eyes can be corrected by the method of resecting surplus skin or combining the method of shortening aponeurosis of levator muscle of upper eyelids. Patients with different sagging skin of upper eyelids and different palpebral fissure width can be corrected by resecting sagging skin of eyelids' margins and the method of resecting surplus skin or combining the method of shortening aponeurosis of levator muscle of upper eyelids.

Mortality and cost of radiation therapy for oesophageal cancer according to hospital accreditation level: a nationwide population-based study.

This study examined and analysed the relationship between the cost-effectiveness and outcome of radiotherapy for oesophageal cancer among hospitals with varying accreditation levels. We selected 428 oesophageal cancer patients from medical and non-medical centres using the National Health Insurance Research Database, which is maintained by the Taiwanese National Health Research Institutes, and compared their medical expenditure and the outcome of their radiotherapy treatment. In this study cohort of patients with oesophageal cancer, 278 patients were treated in medical centres (mean age: 60.1 years) and 150 patients were treated in non-medical centres (mean age: 62.0 years, P = 0.16). The medical centre group exhibited significantly lower medical expenses, mortality and risk of death compared with the non-medical centre group (adjusted hazard ratio = 1.38, 95% confidence interval = 1.11-1.71). Our study determined that radiotherapy for oesophageal cancer costs significantly less, and medical centres had lower mortality rates than non-medical centres. These findings could provide professional organisations and healthcare policy makers with essential information for allocation of resources.

Impact of the free-vaccine policy on timely initiation and completion of hepatitis B vaccination in Fujian, China.

The extent to which the free-vaccine policy impacts the initiation and completion of a hepatitis B vaccine series is poorly understood. The aim of this study was to evaluate the impact of the free-vaccine policy on hepatitis B vaccination. A provincial survey was conducted in 2006 in Fujian Province, south-east of China, where the free-vaccine policy for hepatitis B was announced in 2002 and implemented in 2003. A total of 1628 children were investigated, and 1443 (88.6%) were included in this analysis. Among the children studied, 55.2% were vaccinated within 24 h of birth, and 76.1% completed the hepatitis B vaccine series on time. The rate of hepatitis B surface antibody positivity increased from 29.9% among children born in 1992 to 90.5% among children born in 2005, while the corresponding HBV infection rate decreased from 30.4% to 1.72%. Logistic regression indicated that, compared to children born between 1996 and 2001, the odds ratios (ORs) for timely initiation were 2.57 (95% confidence interval [CI], 1.71-3.84), 5.24 (95% CI, 3.26-8.43) and 9.06 (95% CI, 4.48-18.34) among children born in 2003, 2004 and 2005, respectively; the corresponding ORs for completing the vaccine series were 4.23 (95% CI, 1.97-9.10), 3.76 (95% CI, 1.81-7.82) and 4.94 (95% CI, 1.74-14.00) among children born in 2003, 2004 and 2005, respectively. Children with delayed vaccine initiation (>24 h after birth) were less likely to complete the vaccine series than those who received a timely first dose (OR = 0.02, 95% CI, 0.005-0.09). The impact of the free-vaccine policy on vaccine initiation and vaccine series completion did not differ by children's residence area (rural vs urban). As hypothesized, the odds of completing the vaccine series increased after the free-vaccine policy was announced in 2002 among children with delayed initiation (>24 h after birth) but not among those with timely initiation (≤ 24 h after birth). In conclusion, the free-vaccine policy significantly improved the timely initiation and completion of the vaccine series. The impact of this policy on completion of the vaccine series was larger among children with delayed vaccine initiation.

Five-year follow-up of a prospective study comparing laparoscopic Nissen fundoplication with Stretta radiofrequency for gastroesophageal reflux disease.

AIM: Laparoscopic Nissen fundoplication (LNF) and Stretta radiofrequency (RF) are used as main alternative strategies to manage medication-refractory GERD. This study was therefore prospectively evaluated outcomes of patients with refractory GERD 5 years after LNF or Stretta RF. METHODS: A total of 215 consecutive patients with refractory GERD underwent LNF (N.=102) and Stretta RF (N.=113) in our department between 2007 and 2008. They were followed-up for 5 years, during which the outcome measures including symptom scores of regurgitation, heartburn, chest pain, belching, hiccup, cough and asthma as well as the proton pump inhibitor (PPI) use and complications. RESULTS: Of the 215 patients, 179 patients following LNF (N.=87) or Stretta RF (N.=92) completed the designated 5-year follow-up and were included in the final analysis. At the end of 5-year follow-up, the post-treatment scores were statistically lower as compared with the pre-treatment scores in both groups, while the symptom improvements after Stretta were significantly lower than that after LNF (p < 0.05). Besides, 81 (91%) patients achieved complete PPI therapy independence after LNF, comparing with 47 (51.1%) after Stretta RF (P<0.05). No significant differences in post-treatment complications were observed except for the abdominal distention. CONCLUSION: Even though laparoscopic Nissen fundoplication and Stretta RF are capable of controlling GERD symptoms effectively and safely in selected patients, LNF could improve more in symptoms and PPI elimination.

The changes of vitreous pH values in an acute glaucoma rabbit model.

The changes of vitreous pH values under acute glaucoma status have never been reported. In this study, we measured the changes of vitreous pH values in an acute glaucoma rabbit model. Under ketamine and xylazine anesthesia, the anterior chamber of the right eye of New Zealand white rabbits was cannulated and connected to a polygraph for continuous intraocular pressure (IOP) monitoring and a mini-pump for persistent injection of viscoelastic substance, Healon GV. The measurement of vitreous pH was done by inserting a pH probe via a third opening through the sclera into the vitreous. Different IOP levels were maintained by varied amounts of Healon GV injections into the anterior chamber. The changes of vitreous pH values following the intracameral injections were recorded and evaluated. The changes of vitreous pH values were minimal when IOPs were maintained at lower than 35 mmHg. Vitreous pH values decreased significantly from 7.32 to less than 7.03, when the IOPs were kept at 70 mmHg or higher. However, the decrease of pH values was reversible if IOP was held at 70 mmHg for less than 10 minutes and then reduced to normal level at once. In addition, with MTT viability assay, it was noted that the decrease in vitreous pH was associated with a higher percentage of retinal cell death.

Blunted renal responses to angiotensin II infusion in lifetime captopril-treated spontaneously hypertensive rats.

Previously, we had found that inhibition of the renin-angiotensin system in the early lifespan of spontaneously hypertensive rat could prevent the development of hypertension in this animal model. In the present study we evaluated the responses of blood pressure and renal function to intracerebroventricular administration of angiotensin II in long-term captopril-treated spontaneously hypertensive rats. Spontaneously hypertensive rats had been mated and their pups were treated with captopril through drinking water after birth. Age-matched Wistar-Kyoto and spontaneously hypertensive rats drinking tap water were used as control groups. At 4 months of age, the basal mean arterial blood pressure of captopril-treated hypertensive rats was the lowest among those of controlled hypertensive and normotensive rats (98+/-5 vs. 160+/-4 and 126+/-4 mmHg, respectively). Intravenous administration of angiotensin II caused similar increments of blood pressure in all rat groups. However, intracerebroventricular administration of angiotensin II to captopril-treated hypertensive rats induced a significantly less increase of arterial blood pressure in comparison with other groups. The sensitivity of baroreflex in captopril-treated hypertensive rats was also the lowest among all rat groups. The basal urine flow, sodium and potassium excretion rates, and osmolar clearance of captopril-treated hypertensive rats were significantly higher than those of controlled hypertensive rats. Intracerebroventricular infusion of angiotensin II caused significant increases in urine flow, electrolytes excretion, osmolar clearance, and free water reabsorption rate of both normotensive and controlled hypertensive rats. However, the same angiotensin II treatment did not change any of the renal excretion indices in captopril-treated hypertensive rats. Our results suggest that lifetime captopril treatment can decrease the activity of the renin-angiotensin system in the brain of hypertensive animals, which caused increases in basal urine flow and excretion of electrolytes and enhanced the sensitivity of baroreflex. It is likely that changes in the renal and baroreflex functions underlie the prevention of hypertension elicited by long-term captopril treatment.

Coupling of the TCR to integrin activation by Slap-130/Fyb.

SLAP-130/Fyb (SLP-76-associated phosphoprotein or Fyn-binding protein; also known as Fyb/Slap) is a hematopoietic-specific adapter, which associates with and modulates function of SH2-containing leukocyte phosphoprotein of 76 kilodaltons (SLP-76). T cells from mice lacking SLAP-130/Fyb show markedly impaired proliferation following CD3 engagement. In addition, the T cell receptor (TCR) in SLAP-130/Fyb mutant cells fails to enhance integrin-dependent adhesion. Although TCR-induced actin polymerization is normal, TCR-stimulated clustering of the integrin LFA-1 is defective in SLAP-130/Fyb-deficient cells. These data indicate that SLAP-130/Fyb is important for coupling TCR-mediated actin cytoskeletal rearrangement with activation of integrin function, and for T cells to respond fully to activating signals.

Vitamin D(3) attenuates 6-hydroxydopamine-induced neurotoxicity in rats.

Previous reports have demonstrated that exogeneous administration of glial cell line-derived neurotrophic factor (GDNF) reduces ventral mesencephalic (VM) dopaminergic (DA) neuron damage induced by 6-hydroxydopamine (6-OHDA) lesioning in rats. Recent studies have shown that 1,25-dihydroxyvitamin D(3) (D3) enhances endogenous GDNF expression in vitro and in vivo. The purpose of present study was to investigate if administration of D3 in vivo and in vitro would protect against 6-OHDA-induced DA neuron injury. Adult male Sprague-Dawley rats were injected daily with D3 or with saline for 8 days and then lesioned unilaterally with 6-OHDA into the medial forebrain bundle. Locomotor activity was measured using automated activity chambers. We found that unilateral 6-OHDA lesioning reduced locomotor activity in saline-pretreated animals. Pretreatment with D3 for 8 days significantly restored locomotor activity in the lesioned animals. All animals were sacrificed for neurochemical analysis 6 weeks after lesioning. We found that 6-OHDA administration significantly reduced dopamine (DA), 3,4-dihydroxy-phenylacetic acid (DOPAC) and homovanilic acid (HVA) levels in the substantia nigra (SN) on the lesioned side in the saline-treated rats. D3 pretreatment protected against 6-OHDA-mediated depletion of DA and its metabolites in SN. Using primary cultures obtained from the VM of rat embryos, we found that 6-OHDA or H(2)O(2) alone caused significant cell death. Pretreatment with D3 (10(-10) M) protected VM neurons against 6-OHDA- or H(2)O(2)-induced cell death in vitro. Taken together, our data indicate that D3 pretreatment attenuates the hypokinesia and DA neuronal toxicity induced by 6-OHDA. Since both H(2)O(2) and 6-OHDA may injure cells via free radical and reactive oxygen species, the neuroprotection seen here may operate via a reversal of such a toxic mechanism.

Blockade of alpha1-adrenoceptors and cardiac depressant effect by a newly synthetic antihypertensive drug, DL-017 of quinazoline derivative.

The electromechanical effects of 3-[[4-(2-methoxy phenyl)piperazin-1-yl]methyl]-5-(methylthio)-2,3-dihydroimidazo[1,2-c]quinazoline (DL-017), a newly synthesized quinazoline-derived antihypertensive agent, on mammalian cardiac tissues were evaluated. In driven canine Purkinje fibers, DL-017 decreased twitch tension, the maximal rate of upstroke of the action potential (Vmax), and intracellular Na+ activity (a(i)Na) in a concentration-dependent manner. The action potential duration was decreased in canine Purkinje fibers but increased in guinea pig papillary muscles. In guinea pig ventricular papillary muscles, phenylephrine in the presence of 1 microM propranolol increased the twitch tension in a concentration-dependent manner. At 10 microM, phenylephrine significantly decreased a(i)Na and shortened the action potential duration. DL-017 at 0.01 microM inhibited these phenylephrine-induced effects and shifted the concentration-dependent curve to the right. In sinoatrial nodes, DL-017 inhibited pacemaker activity, involving decreases in the slope of diastolic depolarization and Vmax and an increase in a delay of repolarization. These results suggest that, in addition to blockade of alpha1-adrenoceptors and Na+ channels, DL-017 reduces cardiac excitability and contractility in association with inhibition of slow inward Ca2+ and outward K+ channels. Since two order higher concentrations are required, the contribution of DL-017 to cardiac depressant from blockade of ionic channels seems to be less important when this compound is clinically used as an antihypertensive drug.

Prolonged exposure to hyperbaric oxygen induces neuronal damage in primary rat cortical cultures.

While seizure attack is one of the serious complications during the hyperbaric oxygen (HBO) therapy, there is still no direct evidence showing that HBO can induce neuronal damage in the brain. The objective of this study was first to investigate whether HBO would lead to neurotoxicity in the primary rat cortical culture. Second, since alterations in neurotransmitters have been suggested in the pathophysiology of central nervous system (CNS) oxygen toxicity, the protective effects of the N-methyl-D-aspartate (NMDA) receptor antagonism and nitric oxide (NO) synthase inhibition on the HBO-induced neuronal damage were examined. The results showed that HBO exposure to 6 atmosphere absolute pressure (ATA) for 30, 60, and 90 min increased the lactate dehydrogenase (LDH) activity in the culture medium in a time-dependent manner. Accordingly, the cell survival, measured by the 3,(4,5-dimethyl-2-thiazolyl)2, 5-diphenyl-tetrazolium bromide (MTT) assay, was decreased after HBO exposure. Pretreatment with the NMDA antagonist MK-801 protected the cells against the HBO-induced damage. The protective effect was also noted in the cells pretreated with L-N(G)-nitro-arginine methyl ester, an NO synthase inhibitor. Thus, our results suggest that activation of NMDA receptors and production of NO play a role in the neurotoxicity produced by hyperbaric oxygen exposure.

Prenatal exposure to morphine alters kinetic properties of NMDA receptor-mediated synaptic currents in the hippocampus of rat offspring.

Whole-cell patch-clamp recordings of pharmacologically isolated N-methyl-D-asparate (NMDA) receptor-mediated evoked excitatory postsynaptic currents (EPSCs) were made, to study whether prenatal exposure to morphine affected functional properties of synaptic NMDA receptors in hippocampal slices of 2-week-old rat offspring from morphine-addicted mothers. The saturated amplitude of synaptic NMDA receptor-mediated EPSCs from morphine-treated offspring was about twofold larger than that from vehicle-control offspring. The apparent dissociation constant (Kd) values of NMDA receptors for Mg2+ at 0 mV were 7.5 +/- 1.4 and 7.9 +/- 1.3 mM in slices from vehicle-control and morphine-treated offspring, respectively. In addition, no distinguishable changes in the voltage-dependent nature and the reversal potential of NMDA receptors occurred in morphine-treated offspring, suggesting no alterations of Mg2+ blockade and ion selectivity to NMDA receptors. The 10-90% rise times of NMDA receptor-mediated EPSCs in morphine-treated offspring became longer than those in vehicle-control offspring. The decay of NMDA receptor-mediated EPSCs in both morphine-treated and vehicle-control offspring could be described by the sum of a fast and a slow exponential function. The slow, but not fast, decay times of synaptic NMDA receptor-mediated currents in morphine-treated offspring became slower than those in vehicle-control offspring. Collectively, these results suggest that prenatal exposure to morphine altered kinetic properties of synaptic NMDA receptors in hippocampal CA1 pyramidal neurons of rat offspring during early life. The extended duration of synaptic NMDA receptor-mediated currents presumably provided more Ca2+ entry through NMDA receptors in morphine-treated offspring, and its further prolongation by depolarization in such young offspring strengthened NMDA receptor-dependent functions. Thus, in light of pathophysiological implications within the central nervous system of morphine-treated offspring during early life, the present study may provide important insights and serve as a basis for therapeutic intervention in conditions under which NMDA receptors become abnormal.

Activation of gonadotropin-releasing hormone receptors produces neuronal excitation in the rat hippocampus.

Whole-cell patch-clamp recordings of evoked action potentials were made in CA1 and CA3 pyramidal neurons of rat hippocampal slices. Previously we have demonstrated that activation of gonadotropin-releasing hormone (GnRH) receptors induces a long-lasting enhancement of synaptic transmission mediated by ionotropic glutamate receptors in CA1 pyramidal neurons of rat hippocampal slices. Here, we further studied whether activation of GnRH receptors could modulate intrinsic neuronal excitability in CA1 and CA3 pyramidal neurons of rat hippocampal slices. The use of a specific GnRH analog, leuprolide (10(-8) M), elicited a relatively long-term increase in evoked action potentials in CA1 and CA3 pyramidal neurons, respectively. The GnRH receptor-induced increase in evoked action potentials in both CA1 and CA3 pyramidal neurons could be abolished by a potent GnRH receptor antagonist, [acetyl-3,4-dehydro-Pro1,D-p-F-Phe2,D-Trp(3,6)]-LHRH (10(-8) M). The present study suggests that activation of GnRH receptors can lead to an increase of intrinsic neuronal excitability of both CA1 and CA3 pyramidal neurons in the rat hippocampus, an important integrative region for reproductive process, both endocrinologically and behaviorally.