[A retrospective study of postoperative adjuvant therapy following immunotherapy combined with targeted therapy and sequential curative surgical procedures for initially unresectable hepatocellular carcinoma].

Objective: To report the clinical efficacy of adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical procedures in patients with initially unresectable hepatocellular carcinoma. Methods: This is a retrospective case series study. Data from 100 patients who underwent adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical procedures with long-term survival were collected from December 2018 to December 2022 at the Faculty of Hepato-Pancreato-Biliary Surgery, First Medical Center, Chinese People's Liberation Army General Hospital. According to inclusion and exclusion criteria, 47 cases were included, among which patients who met the discontinuation criteria and maintained a drug-free tumor-free status. Thirty-nine male and eight female patients were included, with an age of (54.2±18.8)years(range:38 to 73 years) at initial diagnosis. At the time of initial diagnosis, 43 cases (91.5%) were classified as Barcelona Clinic Liver Cancer stage C. Survival curves were made using Kaplan Meier method. Results: Forty-seven patients underwent R0 resection, all achieved a drug-free tumor-free state through postoperative adjuvant therapy based on pathological examination results. Thirty-six patients(76.6%) maintained a drug-free tumor-free survival status for more than 6 months,28 patients(59.6%) for more than 12 months,and 8 patients(17.0%) for more than 24 months. The longest drug-free tumor-free survival in this cohort reached 48 months. The median follow-up time in this study was 32 months. After diagnosis, the overall survival rates at 1- and 3- years were 97.7%(95%CI:93.4% to 100%) and 90.7%(95%CI:82.5% to 99.8%). The postoperative recurrence-free survival rates at 1- and 3- years were 91.0%(95%CI:83.0% to 99.8%) and 71.3%(95%CI:58.7% to 86.5%). Conclusions: The adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical approach provides long-term survival benefits for patients with initially unresectable hepatocellular carcinoma. Standardized adjuvant therapy maybe sustain long-term tumor-free status,and achieve drug-free tumor-free survival.

Characteristics of flight delays during solar flares.

Solar flares are one of the severest solar activities that have important effects on near-Earth space. Previous studies have shown that flight arrival delays increase as a result of solar flares, but the intrinsic mechanism behind this relationship is still unknown. In this study, we conducted a comprehensive analysis of flight departure delays during 57 solar X-ray events by using a huge amount of flight data (~ 5 × 106 records) gathered over a 5-year period. It is found that the average flight departure delay time during solar X-ray events increased by 20.68% (7.67 min) compared to quiet periods. Our analysis also revealed apparent time and latitude dependencies, with flight delays being more serious on the dayside than on the nightside and longer (shorter) delays tending to occur in lower (higher) latitude airports during solar X-ray events. Furthermore, our results suggest that the intensity of solar flares (soft X-ray flux) and the Solar Zenith Angle directly modulate flight departure delay time and delay rate. These results indicate that communication interferences caused by solar flares directly affect flight departure delays. This work expands our conventional understanding of the impacts of solar flares on human society and provides new insights for preventing or coping with flight delays.

Additional flight delays and magnetospheric-ionospheric disturbances during solar storms.

Although the sun is really far away from us, some solar activities could still influence the performance and reliability of space-borne and ground-based technological systems on Earth. Those time-varying conditions in space caused by the sun are also called solar storm or space weather. It is known that aviation activities can be affected during solar storms, but the exact effects of space weather on aviation are still unclear. Especially how the flight delays, the top topic concerned by most people, will be affected by space weather has never been thoroughly researched. By analyzing huge amount of flight data (~ 4 × 106 records), for the first time, we quantitatively investigate the flight delays during space weather events. It is found that compared to the quiet periods, the average arrival delay time and 30-min delay rate during space weather events are significantly increased by 81.34% and 21.45% respectively. The evident negative correlation between the yearly flight regularity rate and the yearly mean total sunspot number during 22 years also confirms such correlation. Further studies show that the flight delay time and delay rate will monotonically increase with the geomagnetic field fluctuations and ionospheric disturbances. These results indicate that the interferences in communication and navigation during space weather events may be the most probable reason accounting for the increased flight delays. The above analyses expand the traditional field of space weather research and could also provide us with brand new views for improving the flight delay predications.

[Effects of p16/pRb and JNK signaling pathways in hydroquinone-induced malignant transformation of TK6 cells].

Objective: To investigate the cell cycle and apoptosis in hydroquinone (HQ) -induced malignant transformation of TK6 cells and its related regulatory mechanisms. Methods: TK6 cells were exposed to 20 µmol/L HQ, 24 h/time, once a week, for 19 weeks as experimental group and TK6 cells treated with phosphate buffer (PBS) for 19 weeks was used as control group from March 2014. In regulatory mechanism research, the cells were divided into four groups: control group, experimental group, control inhibitor group and experimental inhibitor group (inhibitor groups were added 10 µmol/L P600125) . Cell cycle and apoptosis were detected by flow cytometry. The protein expression of cell cycle-related proteins and JNK signaling pathway proteins were detected by Western blot. Results: Flow cytometry showed that compared with control group, the ratio of cells in the G0/G1 phase of the experimental group was significantly decreased (P=0.001) , and the ratio of cells in the S phase was significantly increased (P=0.002) . Western blotting demonstrated that the protein expressions of p-Rb (Ser780) , E2F1, Cyclin D1, p-p16 (Ser152) , JNK1, p-JNK1 (Thr183/Tyr185) , c-jun, p-c-jun (Ser63) (P=0.015, 0.021, 0.001, 0.001, 0.005, 0.001, 0.039, 0.003) were up-regulated, while the protein expressions of Rb (P=0.048) and p16 (P=0.002) were significantly down-regulated. After exposed to SP600125, compared with experimental group, there were no significant changes in cell cycle distribution (P=0.946) and apoptosis rate (P=0.923) in experimental inhibitor group. The expression of c-jun (P=0.040) protein was down-regulated, while the expression of Rb (P=0.027) protein was up-regulated in experimental inhibitor group. Conclusion: In HQ-induced TK6 cells malignant transformation, the cell cycle is arrested in the S phase, and the p16/pRb signaling pathway is inhibited, while the JNK signaling pathway is activated. However, the activated JNK signaling pathway may not be involved in the regulation of cell cycle.

[Management of the nondisplaced type Herbert D1 scaphoid fracture with robot navigation combined with wrist arthroscopy].

To investigate the feasibility and the clinical efficiency of robot navigation combined with wrist arthroscopy in minimally invasive treatment of nondisplaced type Herbert D1 scaphoid fracture. A retrospective analysis was performed on 9 patients who underwent nondisplaced type Herbert D1 scaphoid fracture in Xuzhou Renci Hospital from December 2019 to January 2021. Before the operation and at the last follow-up, grip strength, pinching force, modified wrist Mayo score and visual analogue scale (VAS) of wrist pain were recorded and compared. The average follow-up time was 14.1 months (7.5-24.0 months). All the fractures achieved primary healing after an average of 13.3 weeks (10-18 weeks). The average flexion and dorsal extension activity of the injured wrist was 51.2°±9.4°, 68.0°±7.3°, and the radial and ulnar deviation was 19.3°±6.2°, 45.7°±7.8°, respectively. At the final follow-up, there were statistically significant differences in grip strength, pinch strength, wrist Mayo score and VAS when compared with those before the operation (all P<0.05). The results demonstrated that robot navigation combined with wrist arthroscopy for nondisplaced type Herbert D1 scaphoid fracture is effective and minimally invasive with a short recovery time and satisfactory healing rate.

Cross-clade immunogenicity and safety of an AS03A-adjuvanted prepandemic H5N1 influenza vaccine in Hong Kong.

OBJECTIVE: To present Hong Kong'Äìspecific data from a large Asian population (also involving Thailand, Singapore, and Taiwan) on safety and manufacturing consistency across four AS03(A)-adjuvanted H5N1 vaccine formulations in terms of immune response against the A/Vietnam/1194/2004 strain. Immunogenicity against the heterologous A/Indonesia/05/2005 strain was also assessed. NCT Number: 00449670. DESIGN: Prospective, observer-blind study. SETTING: Out-patient clinic of a tertiary hospital in Hong Kong. PARTICIPANTS: A total of 360 subjects aged 18 to 60 years were randomised into six groups to receive two doses (21 days apart) of the study vaccine. INTERVENTIONS: One of the four adjuvanted formulations (3.75 microgram H5N1 haemagglutinin [HA]+AS03(A)) of the vaccine (H5N1-AS03(A)) or one of the two non-adjuvanted (3.75 microgram H5N1 [HA]) formulations of the vaccine (H5N1-DIL). MAIN OUTCOME MEASURES: Blood samples collected before vaccination and 21 days after each vaccine dose were analysed using haemagglutination-inhibition and neutralisation assays. Solicited, unsolicited, and serious adverse events were recorded. RESULTS: Manufacturing consistency across all four vaccine formulations was demonstrated. After two doses, the AS03(A)-adjuvanted prepandemic influenza vaccine demonstrated high seroprotection rates against the A/Vietnam/1194/2004 strain (95.8%) and good immunogenicity against the heterologous A/Indonesia/05/2005 strain (45.7%), as compared to the non-adjuvanted vaccine (4.6% and 1.5%, respectively). The seroconversion rates induced by the adjuvanted formulations in terms of viral neutralising antibodies against the two strains were much higher than those induced by the non-adjuvanted formulations. There were no safety concerns for any of the adjuvanted vaccine formulations. CONCLUSIONS: The AS03(A)-adjuvanted H5N1 prepandemic influenza vaccine demonstrated good immunogenicity and an acceptable safety profile in Hong Kong.

Human papillomavirus-16/18 AS04-adjuvanted cervical cancer vaccine: immunogenicity and safety in healthy Chinese women from Hong Kong.

OBJECTIVE: To assess the immunogenicity and safety of human papillomavirus-16/18 AS04-adjuvanted cervical cancer vaccine in Chinese women aged 18 to 35 years enrolled from Hong Kong. DESIGN: Double-blind, randomised controlled trial with vaccine and placebo groups. SETTING: Single-centre study in Hong Kong. PARTICIPANTS: Three hundred women enrolled (150 per group) between March 2006 and June 2007. INTERVENTIONS: Subjects received three doses of human papillomavirus-16/18 vaccine or placebo (aluminium hydroxide), administered intramuscularly at 0, 1, and 6 months. MAIN OUTCOME MEASURES: Human papillomavirus-16/18 seroconversion rates and geometric mean titres at month 7 (in human papillomavirus-16/18 recipients); reactogenicity and safety (in all subjects). RESULTS: A total of 294 women completed the study (148 in the vaccine group, 146 in placebo group). All initially seronegative subjects in the vaccine group had seroconverted for human papillomavirus-16/18 antibodies by month 7. Anti-human papillomavirus-16 and anti-human papillomavirus-18 antibody geometric mean titres were 10 422 (95% confidence interval, 8730-12 442) EL.U/mL and 4649 (3975-5437) EL.U/mL, respectively. High compliance (99% in both groups) was observed for the three-vaccination course. The frequencies of local injection site reactions were higher in the vaccine than placebo group; pain being the most common symptom in both groups. Regarding solicited symptoms, fatigue and myalgia were the most frequent in both groups. Five serious adverse events (four in vaccine group, one in placebo group) were reported, but all were considered unrelated to the vaccinations. CONCLUSION: The human papillomavirus-16/18 AS04-adjuvanted vaccine was highly immunogenic, safe, and generally well tolerated in Chinese women from Hong Kong.

Implementation of an intuitive writing interface and a laparoscopic robot for gynaecological laser assisted surgery.

The research reported in this paper aims at applying the human handwriting skill to improve and facilitate the control of laser-assisted laparoscopic surgery operations performed by gynaecological surgeons. For the purpose, a laparoscopic robot was interfaced with a digitizing tablet. This interface, further called the intuitive writing interface (IWI), directly converts the hand trajectory, handwritten on the tablet, into an input signal to the robot. It replaces the traditional complex manipulations performed by the surgeon during manual laparoscopic surgery by natural handwriting. It provides the surgeon with an intuitive 'what-you-draw-is-what-you-cut' control facility by employing his/her familiar handwriting skills to control the laser ablation process accurately. The system was successfully built and tested in vitro. Performance tests on the robot resulted in tracking errors in the order of 1 mm in the target plane at an ablation speed of 20 mm/s. The high accuracy of the system was successfully demonstrated by cutting characters 4 mm high on an apple. These results indicate that laser ablation performance is upgraded by the IWI to the accuracy levels of human handwriting, which is much higher than can be obtained with manual laser laparoscopy. Safety features include the use of pen contact with the tablet as a safety switch, and back drivability in the robot joints for easy manual positioning and evacuation in case of emergency.

Neurodevelopmental evaluation of 9-month-old infants exposed to low levels of lead in utero: involvement of monoamine neurotransmitters.

The objective of this work is to investigate the neurotoxicty of low-level lead exposure in utero on infants and the possible involvement of dopaminergic and serotonergic neurotransmitters. The correlation analysis for cord blood lead level, the concentrations of dopamine metabolite homovanillic acid (HVA) and serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in cord plasma and the neurodevelopmental scales of infants were conducted on 244 9-month-old children. Both score of sociability subscale and 5-HIAA concentration were correlated with cord blood lead level. The sociability score was negatively correlated with the concentration of HVA, whereas both the coordination score and the global score were negatively correlated with the concentration of 5-HIAA. With partial correlation analysis, after taking HVA into account, the significant negative correlation between the sociability score and the cord blood lead level that existed in the linear correlation analysis disappeared, and the score of global scale correlated negatively with lead level in cord blood. When taking 5-HIAA into account, the scores of all the neurodevelopmental subscales except the language subscale were significantly negatively correlated with lead level in cord blood. The results indicated that low-level lead exposure in utero could produce a neurotoxic effect on the developing serotonergic system in infants. The neurotoxicity of low-level lead exposure in utero may affect the sociability of infants. Serotonergic activity was shown to have a potential effect on neurodevelopmental assessment. It may interfere with the association between low-level lead exposure in utero and other neurodevelopmental performances of 9-month-old children.

Effect of soman on N-methyl-D-aspartate-stimulated [3H]norepinephrine release from rat cortical slices.

Effects of soman on N-methyl-D-aspartate (NMDA) evoked [3H]norepinephrine (NE) release were examined in rat brain cortical slices. NMDA increased [3H]NE release in a concentration-dependent manner. Soman could inhibit the increase evoked by NMDA, but carbachol, an agonist of cholinergic receptor, could potentiate the increase evoked by NMDA. Atropine (a selective muscarinic antagonist) attenuated the release of [3H]NE induced by NMDA in the presence of carbachol or acetylcholine (ACh), but had no effect on the release of [3H]NE induced by NMDA alone. Both d-tubocurarine (an antagonist of nicotinic receptor) and atropine had no effect on the release of [3H]NE induced by NMDA in the presence of soman. These results suggested that soman has a direct action at non-cholinergic sites, probably at NMDA receptors.

Inhibition by soman of NMDA-stimulated [3H]norepinephrine release from rat cortical slices, studies of non-cholinergic effect.

Effects of soman, an irreversible cholinesterase (ChE) inhibitor, on [3H]norepinephrine (NE) release evoked by N-methyl-d-aspartate (NMDA) were studied in rat brain cortical slices. Soman inhibited NMDA-stimulated [3H]NE release in a concentration-dependent manner. This effect was neither reversed by atropine, an antagonist of the muscarinic receptor, nor by d-tubocurarine, an antagonist of the nicotinic receptor. Incubation of the slices with NMDA antagonists, AP5, MK-801, ketamine or magnesium, resulted in inhibitory effects on NMDA-stimulated [3H]NE release. Soman significantly shifted the inhibition curves downward and significant interactions between these chemicals and soman were observed. Glycine potentiated the release of [3H]NE stimulated by NMDA, and soman did not alter this effect of glycine. Soman also inhibited the release of [3H]NE evoked by K+ in a concentration-dependent manner. NMDA-stimulated [3H]NE release was inhibited by tetrodotoxin (TTX), an antagonist of voltage-dependent sodium channels, and a significant interaction between soman and TTX was observed. The [3H]NE release induced by NMDA was dependent on extracellular calcium concentrations and was inhibited by nifedipine, a selective blocker of the L-type voltage-dependent calcium channels (VDCC), or cadmium, a non-specific blocker of VDCC. However, no significant interaction between the effects of soman and calcium, nifedipine, or cadmium was observed. Taken together, the results suggested that: (1) soman has a direct action at non-cholinergic sites; (2) soman may interfere with some of the regulatory sites of the NMDA receptor-ion channel complex; and (3) the voltage-dependent sodium channel, but not VDCC, may be a site of action for soman.

Mechanisms Underlying the Inhibition of Soman on NMDA-stimulated [(3)H]Norepinephrine Release from Rat Cortical Slices, Role of Phospholipase C and Protein Kinase C.

Our previous studies indicated that soman inhibits N-methyl-d-aspartate (NMDA)-stimulated [(3)H]norepinephrine (NE) release from rat cortical slices by acting at a non-cholinergic site. In order to characterize the mechanisms, neomycin, a phospholipase C (PLC) inhibitor, and polymyxin B (PMB), a rather selective protein kinase C (PKC) inhibitor, were used to examine a possible involvement of PLC and PKC in the inhibitory effect of soman on NMDA-stimulated [(3)H]NE release. The role of pertussis toxin (PTX)-sensitive G-protein was also investigated by application of PTX. Neomycin (0.03-1.0mm) inhibited the release in a concentration-dependent manner, which was inhibited by 1.0mm soman. However, no significant interaction between soman and neomycin was observed. In addition, PMB (1.0mug/ml) significantly inhibited release by 15.8%. With the presence of 1.0mm soman, inhibition of release decreased from 29% (without PMB) to 5% (1.0mug/ml PMB). Furthermore, both in the presence and absence of 1.0mm soman, no significant differences for [(3)H]NE release were found between PTX (1.0mug/ml)-treated and non-treated slices. These results suggest that the mechanism of the inhibitory effect of soman on NMDA-stimulated [(3)H]NE release in cortical slices appear to involve the effect on PKC, but not PLC and PTX-sensitive G-protein.

The development of neurobehavioral toxicology in China: the 1994 Hänninen Lecture.

With the rapid growth of industrialization in China, occupational and environmental exposure to chemicals has increased in frequency and in types of chemical exposures. A growing number of Chinese researchers are showing a special interest in exploring the effects of chemicals on the central nervous system. This paper presents a comprehensive review of neurobehavioral toxicology in China. It describes research into the "reference values" of the Neurobehavioral Core Test Battery (NCTB) tests, the development and improvement of the computer-administered Chinese version of the Neurobehavioral Evaluation System (NES-C), and exploration of related biomarkers. On the basis of this research, baseline data for the reference values for six subtests of the NCTB were preliminarily recommended. The upgraded NES-C2 has proven to possess higher stability and validity compared with the previous version, NES-C. Biomarkers derived from the changes in levels of neurotransmitter metabolites might be used as supplementary biomarkers of Pb-induced neurotoxicity.

Effect of melatonin, piperonyl butoxide, or cobalt chloride on L-cysteine-induced lipid peroxidation in homogenate from whole brain of mice.

Brain homogenates exposed to a low concentration of L-cysteine (0.05, 0.1, 0.5, 1.0, and 2.0 mM) were significantly increased in their concentration of malondialdehyde (MDA) + 4-hydroxyalkenals (4-HDA) as compared to control samples, in a concentration-dependent manner. The increased lipid peroxidation by L-cysteine was attenuated or completely abolished by co-incubation with melatonin (2 mM), a potent free radical scavenger, piperonyl butoxide (1 mM), an inhibitor of mixed function oxidase, or cobalt chloride (0.01, 0.02 or 0.05 mM), another inhibitor of mixed function oxidase, but not allopurinol (0.1 mM), an inhibitor of xanthine oxidase. In addition, when a brain homogenate heated at 85 degrees C for 1 min was incubated with or without L-cysteine at 37 degrees C for 20 min, MDA + 4-HDA levels in the homogenate was not changed between L-cysteine and control. These results suggest that L-cysteine-induced lipid peroxidation may be involved in the enzymatic mixed function oxidation systems in brain.

Antagonistic effect of melatonin against cyanide-induced seizures and acute lethality in mice.

The effect of melatonin on potassium cyanide-induced neurotoxicity was investigated in vivo. The ED50 value of potassium cyanide, as measured by induction of tonic and clonic seizures, was significantly increased by 1.5- or 1.8-fold by s.c. preinjection of melatonin (20, 100 or 345 mg/kg) in mice. The preventive effect of melatonin against potassium cyanide-induced seizures was dose dependent. The LD50 value of potassium cyanide, based on 24-h mortality, was also significantly increased by 1.3-fold by preinjection of melatonin. Potassium cyanide (8 mg/kg, s.c.) increased lipid peroxidation in whole brain of mice, and the increased lipid peroxidation was completely abolished when cyanide-induced seizures were stopped by preadministration of melatonin. These results suggest that melatonin, a pineal hormone, may protect against cyanide-induced neurotoxicity with its free radical scavenging effects in mice.

Lead cytotoxicity in primary cultured rat astrocytes and Schwann cells.

The cytotoxic effects of lead acetate on primary cultured astrocytes and Schwann cells (SCs) were studied for comparing the sensitivity of the two kinds of cells and exploring the possible mechanism of lead cytotoxicity. The results indicated that the number of astrocytes detached from the culture surfaces were dependent on the concentration and time of lead exposure. Under phase contrast microscopy, increases in the number of vacuoles were observed at doses of 50 and 100 micrograms ml-1 lead after 96 h of lead exposure for astrocytes and 1, 5 and 10 micrograms ml-1 lead after 24 h of lead exposure for SCs. By scanning electron microscopy, the surface changes in astrocytes began to appear at the dose of 10 micrograms ml-1 lead, whereas in SCs it began in 1 microgram ml-1 lead. By transmission electron microscopy, astrocytes exposed to 10, 50 and 100 micrograms ml-1 lead had increased lysosomal densities, the presence of nuclear inclusions and enlargement of rough endoplasmic reticulum, whereas SCs exposed to 1 microgram ml-1 lead began to show swelling of mitochondria and endoplasmic reticulum, cytoplasmic vacuolizations and numerous myelinoid bodies. Increases in the content of lactic dehydrogenase (LDH) leakage from the astrocytes exposed to 100 micrograms ml-1 lead and SCs exposed to 1, 5 and 10 micrograms ml-1 lead were observed, respectively. Decreases in sulphydryl group (SH) levels in astrocytes exposed to 50 and 100 micrograms ml-1 lead and SCs exposed to 1, 5 and 10 micrograms ml-1 lead were also observed. A dose of 1.0 mmol l-1 reduced glutathione (GSH) and 2.0 mmol l-1 dithiothreitol (DTT) could protect astrocytes from lead-induced SH decrease and LDH leakage. Doses of 10-100 mumol l-1 cAMP were shown to have a protective effect on lead-induced SH decrease in SCs. No significant changes of GSH or lipid peroxidation (LPO) were observed in astrocytes. The results indicated that SH was involved in lead-induced cytotoxicity of astrocytes and SCs, and SCs were more sensitive to lead-induced cytotoxicity than astrocytes.

Preventive effect of melatonin against cyanide-induced seizures and lipid peroxidation in mice.

Subcutaneous injection of potassium cyanide (6, 8, and 9 mg/kg) caused a severe tonic seizure in a dose-dependent manner. However, the incidence of seizures induced by potassium cyanide was significantly inhibited by preadministration of melatonin (20 mg/kg, s.c.) Lipid peroxidation in homogenates from whole brain of mice was significantly increased (39%, 106% and 132%, respectively) by the exposure to potassium cyanide (0.01, 0.05, and 0.1 mM). The potassium cyanide (0.1 mM)-induced lipid peroxidation was prevented by melatonin (0.1, 0.5, 1.0, or 2 mM) in a concentration-dependent manner. These results suggest that free radicals formation and subsequent lipid peroxidation may contribute in part to the development of seizures induced by cyanide in mice.

Alterations of striatal monoamine metabolites in young rats following pre- and postnatal lead exposure.

Dam rats were given lead (0, 0.58, 1.76, and 5.27 mmol/l) containing water ad lib from day 16 of gestation to weaning of the offspring on day 21 postpartum. The pups continued drinking the same lead containing water until the postnatal day 30. At the 30th day postpartum, the pups in each lead treated group were divided into four groups. The first group contains six male pups (PN30M). The second, third, and fourth groups contain six female pups (PN30F, PN60a, PN60b), respectively. The six female pups from control group formed the fifth group (PN60c). PN60a continued drinking the same lead-containing water until the postnatal day 60. PN60b were dosed with distilled water instead of lead-containing water from the 30th day to the 60th day postpartum. PN60c began to expose to 5.27 mmol Pb/l from the 30th day to the 60th day postpartum. The rats in PN30M and PN30F were decapitated on the 30th day postartum, whereas PN60a, PN60b, and PN60c were decapitated on the 60th day postpartum. The contents of metabolites of monoamine neurotransmitters: homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC), 3-methoxy-4-hydroxyphenylglycol (MHPG), and 5-hydroxyin-doleacetic acid (5-HIAA) in striatum were determined using high performance liquid chromatography with electrochemical detection (HPLC-ECD). There were significant increases in the concentrations of HVA (1.58 ± 0.30 vs. 1.17 ± 0.12 ng/mg wet tissue in the 5.27 mmol Pb/l group of PN30M, p < 0.01; and 1.44 ± 0.08 vs. 1.17 ± 0.10 ng/mg wet tissue in the 5.27 mmol Pb/l group of PN60a, p < 0.05) and DOPAC (2.39 ± 0.25, 2.47 ± 0.28, 2.39 ± 0.44 vs. 1.82 ± 0.24 ng/mg wet tissue in three lead treated groups of PN60a, p < 0.05). The significant decreases in the concentration of MHPG (37.33 ± 5.53, 32.02 ± 6.87, 33.31 ± 2.41 vs. 43.85 ± 4.93 ng/mg wet tissue in the 0.58 mmol Pb/l group of PN60a, p < 0.05; in the 1.76 and the 5.27 mmol Pb/l group of PN60a, p < 0.01) and 5-HIAA (0.23 ± 0.04 vs. 0.38 ± 0.05 ng/mg wet tissue in the 5.27 mmol Pb/l group of PN30M, p < 0.05; 0.26 ± 0.09 vs. 0.45 ± 0.09 ng/mg wet tissue in the 5.27 mmol Pb/l group of PN30F, p < 0.05; 0.31 ± 0.08 vs. 0.44 ± 0.08 ng/mg wet tissue in the 5.27 mmol Pb/l group of PN60a, p < 0.05) were observed. No significant changes in the concentration of monoamine metabolites were observed either in rats of PN60b or PN60c. The results demonstrated the disturbances of monoamine metabolism in the striatum of developmental lead exposed rats.

Alterations of monoamine metabolites and neurobehavioral function in lead-exposed workers.

Neurobehavioral and neurochemical effects of occupational lead exposure were investigated by WHO Neurobehavioral Core Test Battery (NCTB) testing and a series of monoamine neurotransmitters and their metabolites analyzing in workers from lead smeltery and storage-battery manufacturing factory and matched controls. Indicators of lead exposure, the blood lead (PbB) and zinc protophorphyrin (ZPP) levels were found significantly higher in the exposed group compared with that of the controls (70.55 micrograms/dL vs 3.67 micrograms/dL; and 294.92 micrograms/dL vs 38.32 micrograms/dL, respectively). Furthermore, elevated urinary homovanillic acid (HVA) and impairment of certain neurobehavioral performances were also found in the lead exposed workers; the latter included attention/response speed, manual dexterity, perceptual-motor speed, visual perception/memory, and motor speed/steadiness. Positive or negative correlations were observed between certain parameters. Thus, homovanillic acid (HVA) is positively correlated with PbB and ZPP; dopamine (DA) negatively correlated with Benton visual retention (BVR); and HVA negatively correlated with digit symbol (DSy), BVR, and pursuit aiming (PA). It is suggested that the alterations of dopamine and its metabolites HVA in urine associated with impairment of neurobehavioral function might be served as biomarkers of lead-induced neurotoxicity.

Central mechanism of indomethacin analgesia.

The analgesic effect of indomethacin was investigated by using the visceral pain model in rabbits. After intravenous administration of indomethacin (2 mg/kg), the maximum increase of the visceral pain threshold was 0.42 +/- 0.31 mA (P < 0.05). The analgesic effect lasted 40 min. After intraventricular microinjection of indomethacin (50 micrograms), the maximum increase of the visceral pain threshold was 0.37 +/- 0.43 mA. After intravenous administration of indomethacin, the content of norepinephrine in perfusates of rabbit fourth ventricle was significantly increased from 18.10 +/- 8.05 to 32.16 +/- 6.15 mg/40 microliters (P < 0.05), compared with data for the control group. The content of beta-endorphin in the perfusate after indomethacin administration was decreased from 5-25 min and slightly increased from 25-35 min, compared with the data for the control group, but there was no significant difference (P > 0.05). Furthermore, intraventricular microinjection of phentolamine (50 micrograms) could block the analgesic effect of an intravenous injection of indomethacin, while naloxone could not. The results imply that prostaglandins of the central nervous system could induce hyperalgesia. Indomethacin injected centrally and peripherally has an analgesic effect on visceral pain. This analgesic effect is mediated by alpha-adrenoceptors. beta-Endorphin does not participate in the analgesic action of indomethacin.