Borna disease virus-induced hippocampal dentate gyrus damage is associated with spatial learning and memory deficits

In neonatally inoculated rats, Borna disease virus (BDV) leads to a persistent infection of the brain in the absence of an inflammatory response and is associated with neuroanatomic, developmental, physiologic, and behavioral abnormalities. One of the most dramatic sites of BDV-associated damage in the neonatal rat brain is the dentate gyrus, a neuroanatomic region believed to play a major role in spatial learning and memory. The absence of a generalized inflammatory response to neonatal BDV infection permits direct effects of viral damage to the dentate gyrus to be examined. In this report, neonatally BDV-infected rats at various stages of dentate gyrus degeneration were evaluated in the Morris water maze, a swimming test that assesses the rats' capacity to navigate by visual cues. Our data demonstrate progressive spatial learning and memory deficits in BDV-infected rats that coincided with a gradual decline in the estimated hippocampal dentate gyrus neuron density.     

妇科癌症病人化疗期间呕吐的心理疗法

目的呕吐是癌症患化疗期间常见的症状之一,频繁的呕吐不仅给患带来痛苦,而且影响生活质量,甚至迫使患中止化疗;方法对100例妇科癌症病人采取有效的。理疗法或。理疗法加药物疗法;结果呕吐的发生率与单纯应用止吐药物患相比P<0．05,差异有显性;结论妇科癌症病人化疗期间呕吐的B理疗法或B理疗法结合药物疗法明显强于单纯药物疗法。     

A multiscale spatial filtering account of the White effect, simultaneous brightness contrast and grating induction

Blakeslee and McCourt ((1997) Vision Research, 37, 2849-2869) demonstrated that a multiscale array of two-dimensional difference-of-Gaussian (DOG) filters provided a simple but powerful model for explaining a number of seemingly complex features of grating induction (GI), while simultaneously encompassing salient features of brightness induction in simultaneous brightness contrast (SBC), brightness assimilation and Hermann Grid stimuli. The DOG model (and isotropic contrast models in general) cannot, however, account for another important group of brightness effects which includes the White effect (White (1979) Perception, 8, 413-416) and the demonstrations of Todorovic ((1997) Perception, 26, 379-395). This paper introduces an oriented DOG (ODOG) model which differs from the DOG model in that the filters are anisotropic and their outputs are pooled nonlinearly. The ODOG model qualitatively predicts the appearance of the test patches in the White effect, the Todorovic demonstration, GI and SBC, while quantitatively predicting the relative magnitudes of these brightness effects as measured psychophysically using brightness matching. The model also accounts for both the smooth transition in test patch brightness seen in the White effect (White & White (1985) Vision Research, 25, 1331-1335) when the relative phase of the test patch is varied relative to the inducing grating, and for the spatial variation of brightness across the test patch as measured using point-by-point brightness matching. Finally, the model predicts intensive aspects of brightness induction measured in a series of Todorovic stimuli as the arms of the test crosses are lengthened (Pessoa, Baratoff, Neumann & Todorokov (1998) Investigative Ophthalmology and Visual Science, Supplement, 39, S159), but fails in one condition. Although it is concluded that higher-level perceptual grouping factors may play a role in determining brightness in this instance, in general the psychophysical results and ODOG modeling argue strongly that the induced brightness phenomena of SBC, GI, the White effect and the Todorovic demonstration, primarily reflect early-stage cortical filtering operations in the visual system.     

The influence of cardiac cholinergic activation on the induction and maintenace of ventricular fibrillation

Summary The influence of cardiac cholinergic activation was studied in rats and cats on the induction and maintenance of ventricular fibrillation (VF). Acetylcholine (ACH 2–25 g/kg), in doses which did not cause bradycardia or hypotension, induced appearance of spontaneous VF (duration 2–60 sec.) in 9/20 rats which have a high sympathetic autoregulation and in 3/6 cats only, 20–40 secs after the latter had been given adrenaline. ACh (10–45 g/kg) and methacholine (10–40g/kg) also significantly prolonged the fibrillatory period induced electrically in cats and rats with and without atrial or ventricular pacing. The induction or prolongation of VF did not occur when higher doses of ACh (50–100 g/kg) were given to rats. The influence of moderate amounts of cholinergic agents on the heart may be due to localised effects resulting in asynchronous activity. Alternatively, they may produce a discharge of multiple ectopic pacemakers or a disturbance in impulse conduction. Higher doses of ACh depress the S-A and ventricular ectopic activity node thereby decreasing the probability of inducing VF.It is concluded that under conditions of raised cardiac adrenergic activity, a moderate increase in cholinergic influence can both induce and prolong VF. The relevance of these findings to the sudden infant death syndrome is discussed.     

Urinary excretion ofD-glucaric acid,an indicator of drug metabolizing enzyme activity,in patients with impaired renal function

Summary The urinary excretion rate ofD-glucaric acid, an in vivo parameter of the activity of drug metabolizing enzymes, has been determined in patients with chronic renal insufficiency (glomerular filtration rate 4.5–80 ml/min/1.73 m²). The mean value of 22.3 µmoles/d (SD 7.2; n 28) was almost identical to that of healthy controls (22.1 µmoles/d, SD 7.3; n 22). Thus, no inhibitory or enhancing effect of renal insufficiency could be detected. The ability of this parameter to indicate alterations in the activity of hepatic drug metabolism, even in patients with renal insufficiency, was demonstrated by the increased excretion rate of glucaric acid (107 µmoles/d, SD 43.5; n 8; p<0.001) after treatment for 7 days with the enzyme inducer phenobarbital. No significant correlation was found between glucaric acid excretion and sex, age, body weight or body surface in 50 patients. Glucaric acid excretion, therefore, should not be related to the creatinine content of urine samples, since creatinine excretion decreases with severity of renal insufficiency and varies with sex, age, body weight and many other conditions. A single dose of dipyrone (Novalgin^®), a further in vivo indicator of drug metabolism, increased glucaric acid excretion on the same day, but no interference was found after a single dose of cortisol.     

Arsenic: opportunity for risk assessment

Arsenic is a human carcinogen that in small amounts is widely distributed in food and water. It has been regulated for almost 100 years worldwide and in the United States, on the judgment of the Royal Commission on Arsenic that a classical threshold of toxicity exists and that a daily intake of 400 (g/day is safe. Modern regulatory thinking in the United States has not accepted safe levels for carcinogens and is thus in conflict with the arsenic standard. Recent epidemics of arsenicism have quantitatively confirmed that threshold not only for the non-cancerous arsenical skin lesions but also for arsenical skin and internal cancers. Research shows that arsenic is a general gene inducer. Genes induced are involved in proliferation, recombination, amplification and the activation of viruses. This characterizes arsenic as anindirect carcinogen and provides a molecular basis for risk assessment and the observed threshold dose response. In the United States at present, about 300 cases of occupational arsenical cancer, declining in numbers, are known. Background arsenic below the drinking water standard is not known to have produced disease. The conspicuous nature of arsenical skin disease presents an unusual opportunity for a simplified survey of arsenical skin disease to support regulatory standards for arsenic.     

Effects of valproate on xenobiotic biotransformation in rat liver

Male Wistar rats werein vivo exposed for 2 weeks to 100 g/ml sodium valproate by subcutaneous implantation of osmotic pumps and hepatocytes were isolated. As anin vitro model co-cultures of rat hepatocytes with epithelial cells were daily treated with valproate (25, 50, 100, 200g/ml) for 2 weeks. In both models the cytochrome P-450 content and the enzymatic activities of 7-ethoxycoumarinO-deethylase, aldrin epoxidase and glutathioneS-transferase were determined in valproate-treated hepatocytes, in controls and in phenobarbital-induced cells. It appeared that in both systems the cytochrome P-450 content and the 7-ethoxycoumarinO-deethylase activity increased significantly after valproate treatment. On the other hand, the activities of aldrin epoxidase and glutathioneS-transferase decreased. A cDNA probe, encoding rat P450IIB2 was used to determine whether mRNAs encoding the P450IIB subfamily were induced by valproate. It became clear that the inducing effect of valproate was even more pronouncedin vitro thanin vivo.     

Time-dependent kinetics. V: Time course of drug levels during enzyme induction (one-compartment model)

Equations were derived to describe the time course of drug levels during auto- and heteroinduction under a variety of input conditions. These equations were based on a pharmacokinetic theory of induction which assumes that metabolic clearance increases exponentially to a maximum value and that the rate of this increase is governed by the degradation rate constant of the induced enzyme (k). Closed form solutions could be obtained only for intravenous single-dose (case I) and multiple-dose (case IV) administration. For each of the other cases, constant-rate intravenous infusion (case III), oral single-dose administration (case II), and multiple-dose administration (case V), an exact solution (not closed form) and an approximation (closed form) were derived. Two sets of equations were derived for each of the five cases to take into consideration the possibility of a latency term ().Plots of drug amount X(or concentration C) vs. time (t) were constructed. In case I, a log Xvs. tplot was convex, the slope increasing with time. In case II, Xincreased,reached a peak, and decayed as in case I. In case III ( > 5In 2V/Q) Creached a preinduction steady state before decreasing to a lower (induced) steady state. When =0, Creached a maximum before decreasing to the same induced steady state. The behavior of Cvs. tfor cases IV and V was similar to that for case III. Determination of parameters was attempted in case III. Nonlinear least-square fitting of generated data with 3–9% error yielded reasonable estimates of k.This work was supported by NIH Research Contracts N0l-NS-1-2282 and N01-NS-6-2341.Parts I, II, III, IV, and VI of this series can be found in theJournal of Pharmaceutical Sciences.     

Lack of correlation between changes in cyclic nucleotides and subsequent induction of tyrosine hydroxylase in rat adrenal medulla

Summary Pretreatment of rats with dexamethasone (2.5 mol/kg, a dose which blocks the release of ACTH from the pituitary gland) abolished the reserpine-mediated increase in cAMP and the increase in the cAMP/cGMP ratio in the adrenal medulla. In contrast, the reserpine-mediated induction of tyrosine hydroxylase (TH) remained unchanged. Hypophysectomy had a similar effect to dexamethasone treatment. Since changes in cAMP and changes in the cAMP/cGMP ratio are not indispensible prerequisites for the subsequent induction of TH, a causal relationship between the two phenomena seems to be excluded.     

输卵管切除术对超排卵的影响

目的:探讨单侧输卵管切除,切除侧卵巢对超排卵的反应性。方法:以因输卵管妊娠行单侧输卵管切除后不孕接受IVF-ET治疗的患者45例共52个周期为研究组,并以同期因输卵管阻塞(无输卵管积水)不孕行IVF-ET治疗的患者875例共913个周期为对照,分析输卵管切除侧卵巢与对侧卵巢对超排卵的反应性。结果:①两组的促性腺激素(Gn)用量、用药天数、hCG日E_2水平、卵裂率、平均移植胚胎数、种植率、临床妊娠率、流产率、异位妊娠率差异无统计学意义(P>0.05)。但单侧输卵管切除组的获卵数减少,差异有统计学意义(P<0.05)。②研究组卵泡晚期(注射hCG日)两侧卵巢大小(分别为35.1±6.5mm、38.2±5.9 mm)有差异,P<0.05。取卵日两组卵泡数(个)分别为6.7±4.5、8.6±3.3(P<0.05),回收卵子数(个)分别为4.9±3.7、6.4±3.6,P<0.05。结论:单侧输卵管切除者切除侧卵巢在行超排卵时,其卵泡晚期(注射hCG日)卵巢较小,取卵日的卵泡数和回收卵子数明显减少,手术可能影响卵巢的血液供应和超排卵效果。