Reinnervation of dopamine-denervated striatum by substantia nigra transplants: immunohistochemical and electrophysiological correlates

This study evaluated whether or not fetal substantia nigra tissue, grafted to striatum previously lesioned with 6-hydroxydopamine, provides functional dopaminergic reinnervation of striatum. Falck-Hillarp histochemistry and immunofluorescent staining for tyrosine hydroxylase demonstrated extensive networks of nerve fibers which extended 1-1.5 mm from the nigral grafts into striatal tissue. Multibarrel micropipettes were used to record neurons electrophysiologically and test neuronal responses to phencyclidine which was applied locally by pressure microejection. "Distal" neurons, defined as those striatal neurons more than 2.0 mm from the nigral graft, fired at an average spontaneous rate of 13.4 spikes/s and were relatively insensitive to the effects of locally applied phencyclidine. However, "proximal" neurons, defined as those neurons less than 1.0 mm from nigral grafts, fired at a significantly lower average rate of 4.9 spikes/s, and were significantly more sensitive than distal neurons to the effects of phencyclidine. These results suggest that fetal substantia nigra grafts can provide functionally significant reinnervation of striatum previously lesioned with 6-hydroxydopamine.     

Effect of inhibitors of electron transport and oxidative phosphorylation on trypanosoma cruzi respiration and growth

Antimycin A and 2-heptyl-4-hydroxyquinoline N-oxide, two specific inhibitors of the b-c₁ segment of the respiratory chain, affected the respiration of Trypanosoma cruzi epimastigote forms. The half-maximum inhibitory concentration were about 0.05 and 0.04 μg/mg cells (dry wt.), respectively. The maximum effect of antimycin (about 80% inhibition of respiration) was at about 0.1 μg antimycin/mg cells. Differential spectrophotometry of T. cruzi epimastigotes in the presence of antimycin, cyanide (or sulfide) and uncouplers, revealed the presence of functional cytochromes aa₃, b and c₅₅₈. In the stationary growth phase respiration by T. cruzi was completely inhibited by cyanide and effectively ihibited by sulfide, but in the expontential growth phase respiration was about 20% insensitive to 5 mM cynaide. Cyanide- and antimycin-insensitive respiration was completely inhibited by salicylhydroxamic acid (2 mM).Antimycin inhibited the operation of the tricarboxylic acids cycle in T. cruzi, as shown by the lesser production of ¹⁴CO₂ and by the modification of ¹⁴C distribution in epimastigotes incubated with [1-¹⁴C]glucose, [2-¹⁴C]acetate or NaH¹⁴CO₃. The inhibition of electron transport by antimycin increased the rate of the fumarate reductase reaction, an alternative electron pathway for the oxidation of reduced pyridine nucleotides.Addition of carbonyl cyanide 3-chlorophenylhydrazone to epimastigotes increased the rate of respiration and promoted the oxidation of reduced cytochrome b components, thus showing that these components are subjects to respiratory (acceptor) control. Pentachlorhenol similarly affected the cytochrome b redox level but did not modify the rate of respiration. The uncouplers released N,N′-dicyclohexycarbodiimide inhibition of respiration, and uncouplers and cyanide significantly decreased the ATP level in epimastigotes. The combined effects of the assayed inhibitors on respiration, cytochrome b redox level, ATP content and energy charge confirmed the operation of oxidative phosphorylation in T. cruzi epimastigotes. Antimycin, uncouplers and N,N′-dicyclohexylcarbodiimide inhibited growth of T. cruzi, thus proving the essential role of oxidative phosphorylation for the parasite.     

MK-801 increases locomotor activity without elevating extracellular dopamine levels in the nucleus accumbens

In vivo microdialysis was used in freely moving rats to determine whether the locomotor stimulant effects of dizocilpine maleate (MK-801) were related to increased dopamine (DA) release within the nucleus accumbens (N. Acc.). Each experiment began with a baseline period of at least 2 h (starting 15–20 h after insertion of concentric, removable dialysis probes), during which activity records and dialysate samples were collected every 20 min. Rats in the first experiment then were injected with MK-801 (0.125, 0.25, or 0.50 mg/kg, i.p.) or saline, and activity and extracellular levels of DA, dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) were measured for a further 160 min post-injection. In a second experiment, rats were given 1.5 mg/kg d-amphetamine sulphate 40 min after receiving the same doses of MK-801, and testing was continued for 120 min. Rats in a third experiment were given low, autoreceptor-preferring doses of apomorphine hydrochloride (25 or 50 μg/kg, s.c.) or its vehicle 40 min after injection of 0.25 mg/kg MK-801 and then monitored for 120 min. MK-801 produced strong and consistent increases in locomotor activity that were augmented by amphetamine and greatly reduced by the low doses of apomorphine. MK-801 did not increase extracellular DA levels within the N. Acc. when given alone, and it failed to influence the changes in extracellular DA produced by d-amphetamine and apomorphine. MK-801 did produce consistent, dose-related increases in DOPAC and HVA that were probably not related to transmitter release. These results indicate that the increases in locomotor activity seen following MK-801 do not arise from a drug-induced increase in DA levels within the N. Acc. © 1996 Wiley-Liss, Inc.     

大鼠卡氏肺孢菌肺炎肺泡灌洗液中炎性细胞及TNFα水平变化

为探讨使用糖皮质激素 (GC )患者诱发大鼠卡氏肺孢菌肺炎 (PCP )的炎症反应强度及TNF α对PCP的防御作用 ,采用清洁级SD大鼠 ,皮下注射醋酸可的松配合低蛋白饮食建立免疫抑制诱导的PCP模型。分PCP组、细菌性肺炎组、阴性组、健康对照组 ,支气管肺泡灌洗液 (BALF )沉淀行细胞计数及分类 ,ELISA法测定BALF中TNF α值。结果显示 ,免疫抑制后 ,并发PCP鼠BALF中细胞计数、中性粒细胞比例比未并发PCP鼠高 ,但增高幅度低于并发细菌感染鼠 ;并发PCP鼠的BALF中TNF α明显低于未并发PCP鼠 ,而并发细菌感染后TNF α升高。GC致免疫抑制状态下 ,TNF α分泌减少 ,可能为PC感染创造条件 ,PCP与细菌性肺炎在炎症免疫反应上存在差异。     

Phencyclidine blocks two potassium currents in spinal neurons in cell culture

We studied the effects of phencyclidine (PCP) on the transient and delayed outward K+ currents recorded from spinal cord neurons grown (10-20 days) in cell culture. Sodium channels were blocked with tetrodotoxin (1 microM) and solutions containing low calcium concentrations in the presence of Mg2+ or Co2+ (5 mM) were used to reduce Ca2+ currents. PCP decreased the amplitude and prolonged the decay phase of the action potentials recorded at a holding potential of -70 mV. PCP (0.1-0.5 mM) was more effective than tetraethylammonium (TEA) or 4-aminopyridine (4-AP) in reducing both transient and delayed currents. The amplitude of the transient current during control experiments was always larger than that of the delayed current. It appeared that 4-AP (5 mM) was more potent in blocking the transient current, while TEA (10 mM) modified the delayed current more effectively. Both currents were also reduced by about 10% when the cell soma was perfused with Co2+. This suggested that a small fraction of the total outward current is a Ca2+-activated K+ current. The PCP-induced blockade of K+ currents in central neurons coupled with the profound synaptic effects of the drug may provide the basis for explaining the psychopathology of this hallucinogenic agent.     

Predictors of early hospital readmission in HIV-infected patients with pneumonia

OBJECTIVE: Although hospitalization patterns have been studied, little is known about hospital readmission among HIV-infected patients in the era of highly active antiretroviral therapy. We explored the risk factors for early readmission to a tertiary care inner-city hospital among HIV-infected patients with pneumonia in Vancouver, Canada. DESIGN: Case-control study. SETTING: Tertiary care, university-affiliated, inner-city hospital. PARTICIPANTS: All HIV-infected patients who were hospitalized with Pneumocystis carinii pneumonia (PCP) or bacterial pneumonia (BP) between January 1997 and December 2000. Case patients included those who had early readmissions, defined as being readmitted within 2 weeks of discharge (N = 131). Control patients were randomly selected HIV-infected patients admitted during the study period who were not readmitted within 2 weeks of discharge (N = 131), matched to the cases by proportion of PCP to BP. MEASUREMENTS: Sociodemographic, HIV risk category, and clinical data were compared using chi2 test for categorical variables, and the Wilcoxon rank-sum test was used for continuous variables. Multivariable logistic regression was performed to determine the factors independently associated with early readmission. We also reviewed the medical records of 132 patients admitted to the HIV/AIDS ward during the study period and collected more detailed clinical data for a subanalysis. MAIN RESULTS: Patients were at significantly increased odds of early readmission if they left the hospital against medical advice (AMA) (adjusted odds ratio [OR], 4.26; 95% confidence interval [95% CI], 2.13 to 8.55), lived in the poorest urban neighborhood (OR, 2.03; 95% CI, 1.09 to 3.77), were hospitalized in summer season (May though October, OR, 2.36; 95% CI, 1.36 to 4.10), or had been admitted in the preceding 6 months (OR, 2.55; 95% CI, 1.46 to 4.47). Gender, age, history of AIDS-defining illness, and injection drug use status were not significantly associated with early readmission. CONCLUSIONS: Predictors of early readmission of HIV-infected patients with pneumonia included: leaving hospital AMA, living in the poorest urban neighborhood, being hospitalized in the preceding 6 months and during the summer months. Interventions involving social work may address some of the underlying reasons why these patients leave hospital AMA and should be further studied.     

Caffeine-induced taste aversion and mimetic responses

Novel tastes preceded a range of caffeine doses (10-80 mg/kg) in a taste aversion training trial. One week later rats which had doses of 30 mg or higher showed strong aversions as measured by a single bottle consumption test. The 10 and 20 mg dose produced the most hyperactivity and apparently enhanced intake of the taste paired with caffeine. During the training trial, rats receiving the 80 mg dose exhibited copious gapes and chin-rubs, mimetic responses to noxious tastes. Gapes also occurred in these subjects during the aversion test. Consumption was more sensitive than mimetic responding as a measure of the aversive effects of caffeine. Only the 80 mg dose produced neophobia. Tests with isotonic injections indicated that tonicity was not the source of the aversions.     

超高效液相色谱/串联质谱分析生活饮用水中2,4-滴、2,4,6-三氯酚和五氯酚的方法研究

目的:建立检测生活饮用水中2,4-滴、2,4,6-三氯酚和五氯酚的超高效液相色谱/串联质谱法(UPLC-MS/MS)。方法:水样经高速离心,Waters ACQUITY UPLC BEHC181.0×50 mm柱分离,以纯水和乙腈为流动相,采用UPLC-ESI-MS/MS法,以负离子检测方式,多离子反应监测(MRM)定量法检测生活饮用水中2,4-滴、2,4,6-三氯酚和五氯酚。结果:经方法学验证,该方法对2,4-滴、2,4,6-三氯酚和五氯酚的最低检测限分别为0.5、3.0、1.0μg/L(进样量10μl)。在线性范围中,相关系数r均大于0.99,平均回收率分别在85%~115%之间。结论:方法快速、灵敏度高、操作简单、定量准确、测定浓度范围宽阔,是生活饮用水样品中2,4-滴、2,4,6-三氯酚和五氯酚含量快速检测的理想方法。对东莞市生活饮用水样品检测表明:此水体中2,4-滴、2,4,6-三氯酚和五氯酚的含量都低于检测限。