Epsilon-amino caproic acid additive decreases fibrin bandage performance in a swine arterial bleeding model

-Amino caproic acid (EACA), a lysine analog that inhibits the activity of plasmin, was added to Nycomed (TC-S) fibrin bandages, and the bandages were tested for hemostatic efficacy in a swine femoral artery bleeding model. The blood loss using the bandage with EACA (TC-S+EACA; 728.8±132 g, n=5) was much greater as compared to the TC-S bandage alone (TC-S; 237.8±47.9 g, n=6, p=.02). The time to “cessation of bleeding” (T_b) was also increased for animals treated with TC-S+EACA bandages compared to the TC-S controls (33.6±10.8 min vs. 9.2±2.2 min; p=.05). Although plasma fibrinogen concentration decreased in animals treated with the TC-S+EACA bandage, activated partial thromboplastin times (aPTT) and thrombin times (TT) were decreased. Animals treated with the TC-S control bandage exhibited no changes in fibrinogen, aPTT or TT. Prothrombin times (PT) were unchanged in either group. In conclusion, addition of EACA to the Nycomed product decreased fibrin bandage efficiency.     

Zonisamide as a neuroprotective agent in an adult gerbil model of global forebrain ischemia: a histological, in vivo microdialysis and behavioral study

Brief periods of global cerebral ischemia are known to produce characteristic patterns of neuronal injury both in human studies and in experimental animal models. Ischemic damage to vulnerable areas such as the CA1 sector of the hippocampus is thought to result from excitotoxic amino acid neurotransmission. The objective of this study was to determine the ability of a novel sodium channel blocking compound, zonisamide, to reduce neuronal damage by preventing the ischemia-associated accumulation of extracellular glutamate. Using a gerbil model, animals were subjected to 5 min ischemic insults. Both pre- and post-ischemic drug administration (zonisamide 150 mg/kg) were studied. Histological brain sections were prepared using a silver stain at 7 and 28 days post ischemia. The animals sacrificed at 28 days also underwent behavioral testing using a modified Morris water maze. In vivo microdialysis was performed on a separate group of animals in order to determine the patterns of ischemia-induced glutamate accumulation in the CA1 sector of the hippocampus. Pyramidal cell damage scores in the CA1 region of the hippocampus were significantly reduced in animals pre-treated with zonisamide compared to saline-treated controls, both at 7 days (drug pre-treated: 0.812±0.28, n=8; controls: 1.625±0.24, n=8; ^*P<0.05) and 28 (drug pre-treated: 0.833±0.22, n=12; controls: 1.955±0.26, n=11; ^**P<0.01) days post ischemia. However, animals receiving zonisamide post-treatment did not display significant differences from controls. Behavioral studies also showed significant preservation of function in drug-treated animals. Microdialysis studies confirmed a reduction in glutamate release in drug-treated animals compared to saline-treated controls. Our data suggest that zonisamide is effective in reducing neuronal damage by a mechanism involving decreased ischemia-induced extracellular glutamate accumulation and interruption of excitotoxic pathways.     

Sumatriptan modifies cortical free radical release during cortical spreading depression. A novel antimigraine action for sumatriptan?

Increases in concentration of brain NO are proposed to initiate and mediate migraine headache. Triggered by focal depolarisation, spreading depression (SD) represents a suitable mechanism for eliciting widespread release of nitric oxide. The current study examines the effect of sumatriptan, a 5-HT_1B/1D agonist and effective antimigraine therapy, on free radical release (nitric oxide and superoxide) in SD in the simple and complex cortices of the rat and cat. Following initiation of SD, sumatriptan pretreatment (300 μg kg⁻¹ i.v., 15 min prior to SD) modulated all phases of nitric oxide release associated with each SD in both cats and rats. As a result, superoxide levels were observed to significantly (ANOVA, post hoc LSD) increase versus vehicle treated animals (saline 1 ml kg⁻¹ i.v. 15 min prior to SD) during specific phases of each SD depolarisation. Averaged over all SD depolarisations, mean peak SD nitric oxide levels per depolarisation were 0.73±0.23 μM (n=29) in cats, and 0.42±0.09 μM (n=34) in rats. Sumatriptan significantly (Students t-test, P<0.05, two tailed hypothesis, P<0.05) modulated this increase in cortical nitric oxide concentrations to 0.32±0.06 μM (n=25) and 0.22±0.07 μM (n=37) in cats and rats. Sumatriptan appears to decrease the amplitude of nitric oxide release but enhances extracellular superoxide concentrations in both lissencephalic and gyrencephalic cortices during SD.     

A role for monomeric G-proteins in synaptic plasticity in the rat dentate gyrus in vitro

Recent studies have implicated Ras signalling in synaptic plasticity. In this study we have investigated a role for the low molecular weight G proteins Ras, Rap, Ra1 and Rac in long-term potentiation and depression using Clostridium Sordelli Lethal Toxin-82 (LT-82), which inactivates Ras, Rap, Ra1 and Rac, and manumycin A, a Ras inhibitor. Perfusion of hippocampal slices with LT-82 (200 ng/ml) attenuated LTP (83±10%, n=5, P<0.01, compared with controls of 160±11% at 60 min post HFS, n=5). LT-82 had no effect on LTD (63±1% at 100 ng/ml, n=5 and 66±1% at 200 ng/ml, n=4, compared to controls of 56±6%, n=6). Manumycin A (2μM) had no effect on LTP (162±2%, n=5, compared to controls of 167±13%, n=5), but significantly attenuated LTD (88±6%, n=5, P<0.01, compared to controls of 63±9%, n=7). LT-82 (200 ng/ml) significantly increased the amplitude of the isolated NMDA-EPSP at 60 min post-drug application (240±40%, n=5, P<0.01, compared with controls of 100±4%, n=5). However, manumycin A, had no significant effect on NMDAR-EPSP amplitude (92±2%, n=5, compared with controls). These results demonstrate an important role for Ras in LTD and a role for Rap, Ra1 and Rac in LTP.     

Plasma homovanillic acid and treatment response in a large group of schizophrenic patients

Plasma levels of homovanillic acid (pHVA), a metabolite of dopamine, were measured in ninety-five Chinese schizophrenic patients free of neuroleptics for at least four weeks. These patients were treated with classical antipsychotics for six weeks. Pretreatment pHVA was positively correlated with the subsequent clinical response (r=0.408, p<0.0001). Good responders (BPRS improvement 50%, n=47) had higher pretreatment pHVA levels than poor responders (BPRS improvement < 50%, n=48) (15.7±8.4 ng/ml versus 9.9±3.7 ng/ml, p<0.0001). A higher than 15 ng/ml pretreatment pHVA level was associated with a more consistent clinical response to the subsequent treatment. Using a pHVA level of 12 ng/ml as a demarcation point, 72% of patients (34 of 47) who had pHVA 12 responded whereas 65% (31 of 48) who had <12 did not respond (chi-square=13.02, p<0.0001). These results suggest that higher pretreatment pHVA levels may predict a better clinical response to antipsychotics. Based upon the pHVA findings, two hypothetical subtypes of schizophrenia are proposed.     

Response to cyanide of two types of glomoid cells in mature rat carotid body

Cells belonging to glomoids of mature rat carotid bodies were studied using the whole-cell patch clamp technique following acute dissociation. The recorded population encompassed two subtypes: one type (n=202), termed G(out), was characterized by a small voltage-dependent inward current (43±9pA, mean ±S.E.M.), large outward current (671±31 pA@⁺40 mV), high membrane resistance (1910 ± 110M Ω) and low capacitance (5.1 ± 0.1pF). A second subtype (n=56), termed G(in), had significantly lower membrane resistance (177 ± 35 MΩ), membrane capacitance (15.0 ± 1.0 pF) and little voltage-dependent current. Neither subtype supported generation of multiple action potentials during depolarization in the current clamp mode. Intracellular staining of the recorded cells by Lucifer yellow showed co-localization of both subtypes to clusters of cells which stained positively for catecholamines. Somal diameter was slightly, but significantly, larger for G(in) cells 8.7 ± 0.4 μM, n=7) compared to G(out) cells (7.8±0.2 μM, n=31) and all cells had fine cytoplasmic process s extending around neighboring cells. During recordings using the perforated patch technique, histotoxic hypoxia significantly decreased a voltage-dependent outward current in G(out) cells by 113±60pA (n=13), and decreased the holding current by 10±4pA (n=13) from a control value of −32±6pA. In G(in) cells, cyanide significant decreased membrane resistance and decreased holding current by 55±28pA from a control value of +120±42pA (n=7), but caused no significant change in outward current. These results show that glomoids of mature rat carotid bodies contain at least two types of cells which differ in their morphologic and electrophysiologic characteristics. The subtypes rapidly respond to histotoxic hypoxia and thus may mediate separate roles in the organ response to chemostimuli.     

A comparison of hypotensive and non-hypotensive hemorrhage on Fos expression in spinally projecting neurons of the paraventricular nucleus and rostral ventrolateral medulla

The protein, Fos, detected immunohistochemically, was used to identify neurons in the brain that were activated after hemorrhage in the conscious rat. Spinally projecting neurons in the paraventricular nucleus (PVN) and rostral ventrolateral medulla (RVLM) were identified by the presence of rhodamine-labeled latex beads which had been previously injected into the upper thoracic spinal cord. On the experimental day, conscious rats underwent either (1) withdrawal of 4 ml of blood from a carotid cannula (n = 8) which reduced mean arterial pressure from 96.6 ± 2.7 to 42.7 ± 7.1mmHg, (2) withdrayl of 2 ml of blood (n = 4) which did not affect mean arterial pressure. Animals that were not hemorrhaged were used as controls (n = 6). After the 4 ml hemorrhage, dense concentrations of Fos-positive cells nuclei were found in the lamina terminalis, supraoptic nuclei (SON), PVN and in the medulla. In contrast, the density of Fos-positive cells in 2 ml-hemorrhaged rats was not different from controls except in the SON and in the medial PVN in 2 of 4 rats. After the 4 ml hemorrhage 14.4 ± 1.2% of the spinally projecting neurons in the PVN and 22.7 ± 6.1% in the RVLM expressed Fos (P < 0.001 compared to control). After the 2 ml hemorrhage the proportion was 12.2 ± 3.1% in the PVN (P < 0.001 compared control) but only 5.4 ± 2.2% in the RVLM (P > 0.05 compared to control) . The results suggest that spinally projecting neurons in the PVN and RVLM participate in the reflex responses to hemorrhage. PVN-spinal neurons may respond to changes in blood volume even when arterial pressure does not alter.     

Antithrombotic efficacy of single subcutaneous administration of a recombinant nematode anticoagulant peptide (rNAP5) in a canine model of coronary artery thrombolysis

We examined the adjunctive benefit of recombinant nematode anticoagulant peptide (rNAP5), a factor Xa inhibitor, in a canine model of recombinant (rt)-PA-induced thrombolysis. In anesthetized dogs, a stable occlusive thrombus was formed by electrolytic injury of the vessel wall, after which the animals were administered rt-PA (1.44 mg/kg, i.v.) and rNAP5 (0.1 mg/kg, s.c.; n=13), or rt-PA plus vehicle (1–2 ml, s.c.; n=13). Hemodynamic and coagulation parameters were monitored for 360 minutes. Single subcutaneous administration of rNAP5 resulted in a prolonged and sustained increase in the activated partial thromboplastin time (>10-fold), whereas prothrombin time was unchanged. The template bleeding time was not altered significantly throughout the protocol (maximum 1.4-fold). The incidence of reperfusion was similar in the two groups with a trend toward faster reperfusion in the rNAP5 group (34±4 minutes) compared to the vehicle group (63±15 minutes; p=0.07). After reperfusion, 80% of the vessels in the vehicle group reoccluded, whereas only 14% of vessels reoccluded in the rNAP5-treated group. Times to reocclusion were 65±21 minutes and 221±28 minutes, respectively (p<0.05). Single subcutaneous administration of rNAP5 sustained the coronary artery blood flow after reperfusion, such that at the end of protocol the flow was 47% of the preocclusion value as compared to the vehicle group in which the flow was 11% (p<0.05). Cyclic flow reductions were most prominent during rt-PA-induced reperfusion and were similar in both groups. The results indicate that a single subcutaneous administration of rNAP5 provides a sustained antithrombotic effect in maintaining the coronary artery patency during rt-PA-induced thrombolysis.     

Evidence that L-type calcium channels do not contribute to static vestibular function in the guinea pig vestibular nucleus

Labyrinthine-intact guinea pigs received unilateral, brainstem cannula injections of (1) 2.5 μg of the selective dihydropyridine L-type Ca²⁺ channel agonist, Bay K 8644 (n = 4 animals; (2) 10 μg Bay K 8644 (n = 4); 12.5 μg of the selective dihydropyridine L-type Ca²⁺ channel antagonist, nifedipine (n = 4); or 40 μg nifedipine (n = 4). In 11/16 cases, the lesion associated with the cannula tip was located within or near the border of the right vestibular nucleus (VN) complex. All cannula injections were delivered in a 1 μl volume of artificial cerebrospinal fluid (ACSF) and dimethylsulphoxide (DMSO) (70% DMSO, 30% ACSF for Bay K 8644; 80% DMSO, 20% ACSF for nifedipine), adjusted to a pH of approx. 7.0. The effects of these injections were compared with control injections of ACSF/DMSO in our previous studies. Animals were observed for signs of a labyrinthine syndrome (i.e. spontaneous ocular nystagmus, yaw and roll head tilt) directed to the contralateral or ipsilateral side. In no case did Bay K 8644 or nifedipine cause ocular motor or postural symptoms similar to those produced by a unilateral labyrinthectomy. These results suggest that L-type Ca²⁺ channels do not contribute significantly to the resting activity of VN neurons and therefore do not contribute to static vestibular function at the level of the VN.     

Prolonged exposure to alcohol: effect on CRF mRNA levels, and CRF- and stress-induced ACTH secretion in the rat

We have conducted studies in intact adult male rats, designed to examine the effect of a 3- or 7-day exposure to alcohol (EtOH) on the pituitary's response to corticotropin-releasing hormone (CRF) or stress, and on CRF expression in the hypothalamus. In a first series of experiments, rats exposed to EtOH vapors for 7 days had mean blood alcohol levels (BAL) of 127 ± 12mg%. At the end of the 7-day period, basal plasma ACTH levels were 69 ± 10pg/ml in control rats and 121 ± 23pg/ml in EtOH animals (P 0.01). Resting corticosterone levels were 39 ± 11ng/ml in control animals, and 101 ± 24ng/ml in EtOH rats (P 0.01). In all experiments described here, there was no statistical difference (P > 0.05) between the body weights of controls (animals kept in chambers with normal atmosphere) and EtOH-exposed animals. In control animals, the injection of 0.3–10 μg ovine CRF per rat caused dose-related increases in plasma ACTH levels measured 10 min later. All doses of CRF also significantly (P 0.01) stimulated ACTH secretion by EtOH rats, but there was no clear dose-response curve. Though EtOH-treated animals responded to the lower dose of CRF (0.3 μg) with larger increases in plasma ACTH levels than control rats, the only statistical difference (P 0.01) between control and EtOH rats was observed following administration of 10 μg CRF, which caused a blunted response in EtOH animals. These results suggested that alcohol caused an increased sensitivity and decreased maximum responsiveness of the pituitary to CRF. In a second series of experiments, we examined the effect of a 7-day exposure to EtOH on the hypothalamic-pituitary-adrenal response to mild electroshocks (1.0 mA, 0.5 s duration, 2 shocks/min, 10 min total duration). At the end of the 7-day period, BAL were 158 ± 20mg%, and basal ACTH values were 58 ± 9pg/ml for control rats and 175 ± 52pg/ml for EtOH animals (P 0.01). Resting corticosterone levels for control and EtOH rats were 32 ± 10and115 ± 26ng/ml, respectively (P 0.01). Though stress-induced ACTH levels were statistically equivalent (P > 0.05) in control and EtOH rats (978 ± 220vs768 ± 153pg ACTH/ml), the increase over basal values were significantly (P 0.01) smaller in rats exposed to alcohol. A third series of experiments investigated the effect of a 3- or 7-day exposure to EtOH on CRF expression in the hypothalamus. Both periods of EtOH exposure caused an approximate 2-fold increase (P 0.01) in CRF mRNA levels in the hypothalamus. These results indicate that exposure of male rats to alcohol vapors for 7 days significantly alters the activity of the hypothalamic-pituitary-adrenal axis.     

Uptake of leucine and alanine by cultured cerebral capillary endothelial cells

Pure cultures of rat cerebral capillary endothelium have been used to study the A- and L-systems of amino acid transport. Leucine is taken up by a non-concentrative mechanism that can be saturated, and competivively inhibited by phenylalanine. Uptake is rapid, with equilibiration apparent 3–min (al experiments performed at 37 °C). The K_M for transport was 83 μM ± 26(mean ±S.E.M.., n = 3 which is in good agreement with recent vi vivo report using unanesthtissed rats. Alanine was transported by a saturable, concentrative mechanism. Dependence on Na⁺ -ions was demonstrated by lack of specific uptake in Na⁺ -ffree buffer and reduced uptake after preincubation in ouabain — Na⁺, K⁺ -ATPase inhibitor. The K_M was 325 μM ±88 (mean ± S.E.M., n = 3). The finding ac an active A-system transporter in vitro suggests that the cells may have lost the polarity they demonstrate in vivo. The relevance of these findings to transport of nutrients nd drugs across the blood-brain barrier is discussed.     

Serotonergic mechanisms of the lateral parabrachial nucleus on DOCA-induced sodium intake

It has been shown that the serotonergic mechanisms of the lateral parabrachial nucleus (LPBN) inhibit NaCl intake in different models of angiotensin II (ANG II)-dependent NaCl intake in rats. However, there is no information about the involvement of LPBN serotonergic mechanisms on NaCl intake in a model of NaCl intake not dependent on ANG II like deoxycorticosterone (DOCA)-induced NaCl intake. Therefore, in this study we investigated the effects of bilateral injections of serotonergic agonist and antagonist into the LPBN on DOCA-induced 1.8% NaCl intake in rats. Male Holtzman rats were treated with s.c. DOCA (10 mg/rat each every 3 days). After a period of training, in which the rats had access to 1.8% NaCl during 2 h for several days, the rats were implanted with stainless steel cannulas bilaterally into the LPBN. Bilateral injections of the serotonergic receptor antagonist methysergide (4 μg/0.2 μl each site) in the LPBN increased 1.8% NaCl intake (32.2±3.9 versus vehicle: 15.0±1.6 ml/2 h, n=10) and water intake (12.5±3.5 versus vehicle: 3.2±1.0 ml/2 h). Injections of the serotonergic 5HT_2A/2C receptor agonist DOI (5 μg/0,2 μl each site) in the LPBN reduced 1.8% NaCl intake (6.8±1.7 versus saline: 12.4±1.9 ml/2 h, n=10) and water intake (2.2±0.8 versus saline: 4.4±1.0 ml/2 h). Besides the previously demonstrated importance for the control of ANG II-dependent water and NaCl intake, the data show that the serotonergic inhibitory mechanisms of the LPBN are also involved in the control of DOCA-induced NaCl intake.     

Microinjection of orexin into the rat nucleus tractus solitarius causes increases in blood pressure

Orexin A (OX-A) and orexin B (OX-B), also known as hypocretin-1 and hypocretin-2, have been suggested to play a role cardiovascular control. The nucleus tractus solitarius (NTS), located in the dorsal medulla plays an essential role in neural control of the cardiovascular system. Orexin-immunoreactive axons have been demonstrated within this nucleus suggesting that NTS may be a site through which OX acts to influence cardiovascular control. We report here that microinjection of OX-A into the NTS of urethane anesthetized rats causes increases in blood pressure (10⁻⁹ M, mean AUC=607.1±65.65 mmHg s, n=5) and heart rate (10⁻⁹ M, mean AUC=16.15±3.3 beats, n=5) which returns to baseline within 90 s. We show that these effects are dose related and site specific. Microinjection of OX-B into NTS elicited similar increases in BP (mean AUC=680.8±128.5 mmHg s, n=4) to that of OX-A suggesting specific actions at the OX₂R receptor. These observations support the conclusion that orexins act as chemical messengers in the NTS likely influencing the excitability of cardiovascular neurons in this region and thus regulating global cardiovascular function.     

Responses of single lingual nerve fibers to thermal and chemical stimulation

The goals of this study were to characterize the responses of: (1) thermally-sensitive fibers of the lingual branch of the trigeminal nerve to cooling from 35° to 10°C at a rate of 1°C/s; and (2) these neurons to a mid-range concentration of NaCl (150 mM), glucose (150 mM), citric acid (0.3 mM), and quinine-HCl (3 mM) at 35° and 25°C. A cluster analysis of 47 neurons' responses to cooling revealed two major groups and one minor group. Group 1 neurons (n=19) had a shorter latency, exhibited faster time-to-peak activity, and responded over a smaller range of temperature compared to Group 2 neurons (n=22). Group 3 neurons (n=6) exhibited the longest response latency and responded over a wider cooler range of temperature. Twenty-five out of thirty-one thermally-sensitive, non-tactile lingual neurons responded weakly to at least one chemical stimulus, with some neurons responding to 2, 3, or all 4 chemical stimuli. Group 1 neurons responded to more chemical stimuli at 35°C, while Group 2 neurons responded more at 25°C. Under their optimal temperature conditions, Group 1 and Group 2 neurons responded most often to citric acid and least often to glucose, with NaCl and Q-HCl eliciting an intermediate number of responses. As a whole, the responses of thermally-sensitive fibers to chemical stimulation were modest at best with an absence of chemical specificity. There was no evidence of a ‘best' stimulus, although there was a suggestion of temporal coding.     

Acetylcholine release from frontal cortex in the waking rat measured by microdialysis without acetylcholinesterase inhibitors: effects of diisopropylfluorophosphate

Acetylcholine (ACh) release was measured in frontal cortex of awake quietly resting rats by microdialysis without using cholinesterase blockers in the perfusate. Resting release was 16.61 ± 2.05 fmol/h (±.S.E.M., n = 18). Injection of sublethal doses of the acetylcholinesterase blocker, diisopropylfluorophosphate produced dose-dependent increases in ACh release, reaching 79.9 fmol/h with a dose of 0.7-times the LD₅₀ Although this irreversible inactivation of acetylcholinesterase increased ACh recovery to more than 700% of control values, levels of ACh in the perfusate never reached those seen in physostigmine-treated animals. The relationship between the amount of acetylcholinesterase inactivation and the quantity of ACh in the perfusate suggests that the extracellular ACh concentrations are controlled by simple enzyme kinetics. Within 2 h after enzyme inactivation, extracellular choline levels fell significantly, suggesting that ACh degradation by acetylcholinesterase plays an important role in regulating the amount of choline in the extracellular space.     

Cerebral O2 consumption in young Eker rats, effects of GABA blockade: implications for autism

Since there is a strong correlation between tuberous sclerosis and autism, we used a tuberous sclerosis model (Eker rat) to test the hypothesis that the increased regional cerebral O₂ consumption in the Eker rat might be associated with autism. We also examined whether this increased cerebral O₂ consumption was related to changes in the activity of the gamma-aminobutyric acid (GABA) inhibitory system. Young (4 weeks) male control Long Evans (n = 14) and Eker (n = 14) rats (70–100 g) were divided into control and bicuculline (1 mg/kg/min for 2 min then 0.1 mg/kg/min for 13 min, GABA_A receptor antagonist) treated animals. Cerebral regional blood flow (¹⁴C-iodoantipyrine) and O₂ consumption (cryomicrospectrophotometry) were determined in isoflurane anesthetized rats. We found significantly increased basal O₂ consumption in the cortex (6.3 ± 0.7 ml O₂/min/100 g Eker vs. 5.1 ± 0.2 ml O₂/min/100 g control), hippocampus and cerebellum, but not the pons. Regional cerebral blood flow was also elevated in the cortex and hippocampus in Eker rats at baseline, but cerebral O₂ extractions were similar. Bicuculline significantly increased O₂ consumption in the cortex (6.5 ± 0.3) and all other regions of the control rats, but had no effect on cortex (5.9 ± 1.5) or other regions of the Eker rats. Cerebral blood flow followed a similar pattern. In conclusion, Eker rats had significantly elevated cerebral O₂ consumption and blood flow, but this was not affected by GABA receptor blockade. This suggested a reduced activity of the GABA_A receptor in the brains of Eker rats. This may have important implications in the treatment of autism.     

不同类型的急性脑梗死患者辅助性T细胞及甲基CpG结合蛋白2表达水平变化及其临床意义

目的 探讨不同类型的急性脑梗死患者辅助性T细胞(CD4+T cells,CD4+T细胞)及甲基CpG结合蛋白2(Methyl-CpG-binding protein 2,MECP2)表达水平变化及其临床意义.方法 选取本院2017年2月-2019年2月收治的急性脑梗死患者156例作为病例组,按照请奥加兰(Orgaran...     

Response of rat superior salivatory units to chorda tympani stimulation

Unit responses to chorda tympani stimulation in urethane anesthetized rats were characterized by response latency and frequency following ability. One hundred and fifty one units responded with constant latencies, mean: 16.9 msec, S.D.: 7.8 msec. Responses recorded from within the superior salivatory nucleus (SSN) had significantly longer latencies (18.8 ± 6.8, n = 94) than those from surrounding areas (13.5 ± 8.3, n = 50) (p < 0.001). This difference was due to the higher incidence of responses with latencies between 2.7 and 10 msec outside of the SSN (44%) compared to SSN responses (8%). Ability to follow high frequency stimulation ranged from 2–550 Hz, and was the same for SSN neurons and those outside the nucleus. The population of responses localized to the SSN, with latencies greater than 10 msec and with high (> 100 Hz) frequency following, had a mean latency of 20.5 msec. The estimated conduction velocity for these presumed preganglionic, parasympathetic neurons is 0.85 M/sec ± 0.25, significantly slower than that reported for similar responses in cats. The antidromic nature of these responses requires confirmation.     

Interaction between local and global visual orientation signals in subjects with unilateral brain lesions

Two groups of right handed, male stroke patients with lesions confined to the left (LH, n=10) or right (RH, n=10) cerebral hemisphere were tested on visual vertical judgements with isolated line stimuli and lines presented in the context of a tilted frame. The psychometric functions indicate no reduction in the precision of orientation judgements among the brain injured subjects when compared with age-matched controls (n=6) with cardiovascular disease, but the systematic shift in perceived vertical induced by a tilted visual frame was significantly larger for RH-subjects than for LH-subjects or controls (mean illusion 6 and 3° respectively). The results are interpreted within the “two visual systems”-theory of the rod-and-frame effect and it is suggested that the right hemisphere is dominantly involved in the integration of visual and vestibular input.     

High dose weekly oral prednisone improves strength in boys with Duchenne muscular dystrophy

Daily prednisone improves strength in boys with Duchenne muscular dystrophy, but side effects are almost universal. We used a different dosing regimen of prednisone to determine if benefit to boys with Duchenne muscular dystrophy might be maintained with fewer side effects. Twice weekly oral prednisone was given each Friday and Saturday (5 mg/kg/dose). This total dose is twice as high as the daily low dosage prednisone regimen (0.75 mg/kg/day). Twenty boys (8.0±1.2 years) were treated. Historical control groups included 18 untreated boys (6.1±1.6 years) and four boys (7.3±0.6 years) treated with daily prednisone. Strength (using a hand-held manometer and grip meter) and timed functional testing were measured. There was an improvement in upper extremity strength for 95% of boys (n=20) at 6 months using quantitative strength testing. Improvement in lower extremity strength occurred in all boys with antigravity quadriceps strength (17/17). The improvement (P=0.001 for proximal upper extremities; P=0.002 for grip; and P<0.0001 for proximal lower extremities) was significant compared to untreated boys. Sixteen boys were treated continuously for more than 12 months (22±1.5 months). Of these, 15 remained significantly stronger than prior to treatment and 8/16 showed additional gains in strength after six months of treatment. Six boys were on the weekly prednisolone 2 years or longer without interruption. All six had upper and lower extremity strength at follow-up that was as good or better than at baseline. Functional testing improved in boys less than 8 years without contractures. Three boys without antigravity quadriceps strength at the start of treatment lost the ability to walk unassisted within 6 months. Eight other boys lost the ability to ambulate unassisted between 12 and 24 months of treatment. In each, progressive contractures developed. Linear growth was maintained in all boys on weekly treatment. Obesity rates did not differ from untreated boys. Twice weekly prednisone improved strength over 6–12 months in the majority of boys, but did not slow contracture development. Sustained benefit beyond 12 months is possible with fewer side effects compared to daily prednisone.