Rivaroxaban or Enoxaparin in Nonmajor Orthopedic Surgery.

Background: Nonmajor orthopedic surgery of the lower limbs that results in transient reduced mobility places patients at risk for venous thromboembolism. Rivaroxaban may be noninferior to enoxaparin with regard to the prevention of major venous thromboembolism in these patients.

Methods: In this international, parallel-group, randomized, double-blind, noninferiority trial, we randomly assigned adult patients undergoing lower-limb nonmajor orthopedic surgery who were considered to be at risk for venous thromboembolism on the basis of the investigator's judgment to receive either rivaroxaban or enoxaparin.

Sequence identification and characterization of human carnosinase and a closely related non-specific dipeptidase.

Carnosine (beta-alanyl-L-histidine) and homocarnosine (gamma-aminobutyric acid-L-histidine) are two naturally occurring dipeptides with potential neuroprotective and neurotransmitter functions in the brain. Peptidase activities degrading both carnosine and homocarnosine have been described previously, but the genes linked to these activities were unknown. Here we present the identification of two novel cDNAs named CN1 and CN2 coding for two proteins of 56.

In vivo neutralization of endogenous brain fractalkine increases hippocampal TNFalpha and 8-isoprostane production induced by intracerebroventricular injection of LPS.

Fractalkine is a chemokine widely and constitutively expressed in the brain and, as suggested by in vitro studies, it is involved in brain inflammatory responses. In this study, we have investigated the in vivo anti-inflammatory potential of fractalkine in a model of neuroinflammation induced by intracerebroventricular injection of lipopolysaccharide (LPS) in rats. LPS induces a rapid and acute production of the pro-inflammatory cytokine, TNFalpha, in hippocampus and cerebrospinal fluid (CSF), and an increase of 8-isoprostane levels, a marker of oxidative stress, in hippocampus.

Effects of repeated treatments with an extract of Ginkgo biloba (EGb 761) on cerebral glucose utilization in the rat: an autoradiographic study.

1. The autoradiographic method based on 2-deoxy-D[1-14C]glucose ([14C]DG) was used to determine glucose utilization in 49 discrete structures of rat brain under control conditions and after the animals had received repeated treatment with an extract of Ginkgo biloba (EGb 761). 2.

Effect of eliprodil, an NMDA receptor antagonist acting at the polyamine modulatory site, on local cerebral glucose use in the rat in the rat brain.

The present investigation examined the effect of eliprodil, an atypical NMDA receptor antagonist that acts at the polyamine modulatory site, on local cerebral glucose utilization using the quantitative autoradiographic 2-[14C]deoxyglucose method in the conscious rat. Eliprodil, at doses of 3, 10 and 30 mg/kg i.p.

Effects of dorsal raphe nucleus stimulation on cerebral blood flow and flow-metabolism coupling in the conscious rat.

In the present study, we have investigated the effects of an activation of the ascending serotonergic pathway on the cerebral blood supply to a number (63) of well-defined neuroanatomical structures. To this end, we have measured the local cerebral blood flow during electrical stimulation of the dorsal raphe nucleus. Measurement of regional blood flow was performed in the conscious rat through the use of the [14C]iodoantipyrine autoradiographic technique.

[Postoperative acute adrenal insufficiency].

Acute adrenal insufficiency is an uncommon complication of lung cancer and adrenal metastasis resection. Diagnosis is difficult to establish but an early recognition and treatment may be life-saving. A 55-year-old man underwent right upper lobectomy and adrenalectomy for lung carcinoma with right adrenal metastasis.

Elevated tissue endothelin content during focal cerebral ischemia in the rat.

To study the involvement of endogenous endothelin (ET) in the development of cerebral ischemia, we measured by radioimmunoassay brain tissue content of immunoreactive (ir)-ET-1 in a model of focal cerebral ischemia in the rat. Permanent occlusion of the middle cerebral artery (OMCA) was accompanied after 24 h by a progressive but marked elevation of ir-ET-1 in the ipsilateral compared with the contralateral hemisphere (119% after 24 h; 184% after 48 h and 459% after 72 h). The pial vessels and the arteries of the circle of Willis did not respond with ir-ET-1 production.

Peripheral type benzodiazepine binding sites following transient forebrain ischemia in the rat: effect of neuroprotective drugs.

Recent studies have demonstrated that measurement of peripheral type benzodiazepine binding sites (PTBBS) levels may be useful as an index for quantification of neuronal damage. In the present study, we investigated the accuracy of this index as a marker of neuronal damage induced by transient forebrain ischemia in the rat (4-vessel occlusion model). Seven days after ischemia, a good correlation was found between the increase of PTBBS levels (measured using [3H]PK 11195 as a specific radioligand) in hippocampal, striatal and cortical homogenates and the duration of ischemia.

The quantification of brain lesions with an omega 3 site ligand: a critical analysis of animal models of cerebral ischaemia and neurodegeneration.

Previous investigations have indicated that the detection and quantification of omega 3 (peripheral type benzodiazepine) binding site densities that are associated with reactive astroglia and macrophages could be of widespread applicability in the localization and indirect assessment of neural tissue damage in the central nervous system. In the present study, we analyze the usefulness of this approach in a number of experimental models that are characterized by (or putatively involve) neuronal degeneration. One week after the systemic administration of the excitotoxin, kainate, a marked increase in omega 3 site densities (as assessed by [3H]PK 11195 binding) was noted, an increase that was most prominent in known regions of selective vulnerability (hippocampus and septum).

Time course of effects of unilateral lesions of the nucleus basalis of Meynert on glucose utilization by the cerebral cortex. Positron tomography in baboons.

In order to investigate the effects of a partial cholinergic deafferentation on the functional activity of the cortex, the cerebral metabolic rate of glucose (CMRGlu) was measured with positron emission tomography and 18F-2-fluoro-2-deoxy-D-glucose in 5 baboons (Papio anubis) both before and serially following stereotaxic electrocoagulation of the left nucleus basalis of Meynert (NbM). Four days postlesion, significant metabolic depression was present in the entire ipsilateral cerebral cortex, most marked in the frontotemporal region, and which slowly recovered close to normal within 6-13 weeks. Postmortem studies showed that the lesions were located largely in the NbM, and that a significant decrease in choline-acetyltransferase (ChAT) activity was present in the ipsilateral frontal, temporal and parietal cortices.

Ifenprodil and SL 82.0715 as cerebral anti-ischemic agents. I. Evidence for efficacy in models of focal cerebral ischemia.

Recent studies have strongly implicated the excitatory neurotransmitter glutamate in the cascade of pathological mechanisms that cause neuronal loss after certain types of brain ischemia. The neurotoxic effects of glutamate are mediated, at least in global ischemia, via NMDA receptors. In the present study we have examined the effects of compounds that possess NMDA receptor antagonist properties (ifenprodil, SL 82.

Temporal evolution of regional energy metabolism following focal cerebral ischemia in the rat.

Focal cerebral ischemia in the rat was induced by occlusion of the left middle cerebral artery. The temporal evolution of regional energy metabolism was studied over the 14 days consequent to the induction of ischemia in the frontal, cingulate, parietal, and occipital cortices as well as in the striatum. Regional concentrations of adenosine triphosphate (ATP), phosphocreatine, and lactate and, in addition, glucose and the cerebral/plasma glucose ratio (C/P) were measured in the hemispheres both ipsilateral and contralateral to the occlusion.

The quantification of cerebral infarction following focal ischemia in the rat: influence of strain, arterial pressure, blood glucose concentration, and age.

Focal cerebral ischemia was induced by occlusion of the middle cerebral artery in rats. The volumetric assessment of infarcted tissue, 2 days following occlusion, was calculated from the examination of eight preselected coronal sections. Five differing rat strains were examined.

Imaging of primary and remote ischaemic and excitotoxic brain lesions. An autoradiographic study of peripheral type benzodiazepine binding sites in the rat and cat.

Seven days after unilateral middle cerebral artery occlusion in rats, peripheral type benzodiazepine binding sites (PTBBS), using [3H]PK 11195 as a specific radioligand, were greatly increased in the cortical and striatal regions surrounding the focus of infarction with smaller increases in the ventrolateral and posterior thalamic complexes and in the substantia nigra, all ipsilateral to the occlusion. Similarly, PTBBS increases were observed in the caudate nucleus and entorhinal cortex of cats likewise subjected to prior unilateral occlusion of the middle cerebral artery. Intrastriatal administration of N-methyl-D-aspartate (250 nmol) in the rat resulted in a dramatic ipsilateral increase in PTBBS levels in the striatum and in the deeper laminae of the ipsilateral frontoparietal cortex.

Influence of ascending serotonergic pathways on glucose use in the conscious rat brain. II. Effects of electrical stimulation of the rostral raphé nuclei.

Although lesions of the rostral raphé nuclei have minimal effects on integrated functional activity, as studied by the 2-deoxyglucose technique, the repercussions of activating the ascending serotonergic pathways have yet to be reported in the literature. To examine this question, we studied the consequences of the electrical stimulation of the rostral (median or dorsal) raphé nuclei on local cerebral glucose use in the conscious rat. Glucose use was determined by quantitative autoradiography in 105 defined brain structures.

Influence of ascending serotonergic pathways on glucose use in the conscious rat brain. I. Effects of electrolytic or neurotoxic lesions of the dorsal and/or median raphé nucleus.

The regional cerebral metabolic effects of manipulations of the central serotonergic pathways are largely unknown. To address this topic, we have examined the consequences of electrolytic lesions of the rostral (median and/or dorsal) raphé nuclei on local cerebral glucose utilization (CMRglu) in the unanaesthetized rat brain. These studies were complemented by comparing control rats to rats that received prior intraventricular administration of the serotonergic neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT).

Cortical hypometabolism and its recovery following nucleus basalis lesions in baboons: a PET study.

The cerebral metabolic rate for glucose was measured serially with positron emission tomography and [18F]fluorodeoxyglucose in five baboons with stereotactic electrocoagulation of the left nucleus basalis of Meynert (NbM). Four days after lesion, a significant metabolic depression was present in the ipsilateral cerebral cortex, most marked in the frontotemporal region, and which recovered progressively within 6-13 weeks. These data demonstrate that adaptive mechanisms efficiently compensate for the cortical metabolic effects of NbM-lesion-induced cholinergic deafferentation.

Effects of the GABA receptor agonist, progabide, upon local cerebral glucose utilization.

The effects of a specific GABA receptor agonist, progabide, have been examined on local cerebral glucose utilization through the use of the autoradiographic [14C]2-deoxyglucose technique in conscious rats. The intraperitoneal administration of progabide (80-320 mg.kg-1) resulted in a heterogeneous pattern of significantly reduced glucose utilization throughout the 50 discrete regions of the brain that were studied.

Serotonergic neuron stimulation modulates thalamocortical glucose use in the conscious rat.

We have studied the effects, in the conscious rat, of electrical stimulation of the dorsal or median raphe nuclei on integrated functional activity, as assessed by the quantitative 2-deoxyglucose autoradiographic technique. Stimulation of serotonergic neurons elicits metabolic changes in cortical and thalamic regions that are not limited to those structures known to receive the densest serotonergic innervation. The thalamic nuclei that are activated by raphe stimulation include those that subserve the processing of somesthetic, accessory visual, and limbic information.

Concentrations of putative neurovascular transmitters in major cerebral arteries and small pial vessels of various species.

The levels of noradrenaline, neuropeptide Y, 5-hydroxytryptamine, and substance P were measured and compared between the large arteries of the circle of Willis and the small cerebral vessels of the pia mater in the rat, rabbit, cat, and monkey. In all species, noradrenaline and neuropeptide Y concentrations were greater in the larger arteries than in small pial vessels. Noradrenaline concentrations were dramatically reduced following cervical sympathectomy, with the extent of diminution differing greatly in the various species; the effects of cervical ganglionectomy on neuropeptide Y concentrations were less pronounced.

Neurochemical studies on the existence, origin and characteristics of the serotonergic innervation of small pial vessels.

Substantial concentrations of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA), comparable to those found in brain tissue, were measured in the small pial vessels of the rat, rabbit and cat. Both rat and rabbit pial vessels exhibited a high affinity uptake process with kinetic parameters similar to those identified for the cerebral cortex. Labelled 5-HT, taken up by isolated rabbit pial vessels was released, in a calcium-dependent manner, by potassium-induced depolarization.