孕酮：一种极具潜力的神经保护药物

孕酮长期以来被认为是生殖和母性行为中的一种重要激素，其在脊髓损伤、脑损伤和衰老相关疾病中发挥显著的神经保护和神经再生作用。孕酮主要通过其保护血脑屏障、抗水肿、抗炎症、抗细胞凋亡及神经营养作用，同时能够改善衰老脑的功能而发挥神经保护作用。对孕酮的多效性作用的认识将促使其成为极具潜力的神经保护新药，为临床上神经系统的疑难杂症提供新的治疗方案。     

Automated prostate recognition: a key process for clinically effective robotic prostatectomy

Clinical trials of PROBOT, a robotic system for prostate surgery, have shown that robotic surgery of soft tissue can be successful. Monitoring of the progress of the resection has shown to be a necessary feature of an effective robotic system for prostate surgery. It should provide the surgeon with a reliable method of assessing the cavity during resection. An automatic system for intraoperative monitoring of the progress of the resection during robotic prostatectomy consists of two subsystems: real-time intraoperative imaging of the prostate and automatic identification of the contour of the gland on each image. The development of a fully automatic scheme for prostate recognition on transurethral ultrasound scans is reported. A genetic algorithm has been developed to automatically adjust a model of the prostate boundary until an optimum fit to the prostate in a given image is obtained. An analysis of its performance on 22 different ultrasound images showed an average error of 6.21 mm. Use of a genetic algorithm and a constrained prostate model have shown to be a robust way to automatically identify the prostate in ultrasound images. The scheme is able to produce approximate prostate boundaries, without any human intervention, on ultrasound scans of varying quality. In addition to soft tissue robotic surgery, the genetic algorithm technique is also applicable to a wide range of computer assisted surgical techniques.     

Automated prostate recognition: a key process for clinically effective robotic prostatectomy

Clinical trials of PROBOT, a robotic system for prostate surgery, have shown that robotic surgery of soft tissue can be successful. Monitoring of the progress of the resection has shown to be a necessary feature of an effective robotic system for prostate surgery. It should provide the surgeon with a reliable method of assessing the cavity during resection. An automatic system for intraoperative monitoring of the progress of the resection during robotic prostatectomy consists of two subsystems: real-time intraoperative imaging of the prostate and automatic identification of the contour of the gland on each image. The development of a fully automatic scheme for prostate recognition on transurethral ultrasound scans is reported. A genetic algorithm has been developed to automatically adjust a model of the prostate boundary until an optimum fit to the prostate in a given image is obtained. An analysis of its performance on 22 different ultrasound images showed an average error of 6.21 mm. Use of a genetic algorithm and a constrained prostate model have shown to be a robust way to automatically identify the prostate in ultrasound images. The scheme is able to produce approximate prostate boundaries, without any human intervention, on ultrasound scans of varying quality. In addition to soft tissue robotic surgery, the genetic algorithm technique is also applicable to a wide range of computer assisted surgical techniques.     

RANTES upregulation in the Alzheimer's disease brain: a possible neuroprotective role

Numerous studies demonstrate inflammatory proteins in the brain and microcirculation in Alzheimer's disease (AD) and implicate inflammation in disease pathogenesis. However, emerging literature suggests that neuroinflammation can also be neuroprotective. The chemokine RANTES has been implicated in neurodegenerative diseases including AD. The objectives of this study are to determine the expression of RANTES in AD microvessels, its regulation in endothelial cells and its effects on neuronal survival. Our data show elevated expression of RANTES in the cerebral microcirculation of AD patients. Treatment of neurons in vitro with RANTES results in an increase in cell survival and a neuroprotective effect against the toxicity of thrombin and sodium nitroprusside. Oxidative stress upregulates RANTES expression in rat brain endothelial cells. Developing strategies to augment neuroprotection and diminish inflammatory activation of multifunctional mediators such as RANTES holds promise for the development of novel neuroprotective therapeutics in AD.     

Peptide p3 may play a neuroprotective role in the brain

Alzheimer's disease (AD) is an age-related neurodegenerative disease. The amyloid-β (Aβ) peptide is considered a major etiological factor in the development of AD. BACE1-deficient mice and forebrain-specific conditional presenilin1 and presenilin2 double knockout mice (presenilins cDKO mice) both lack Aβ, but exhibit completely different phenotypes. The peptide p3 may play a neuroprotective role. A lack of peptide p3 could trigger an inflammatory response in the brain of presenilins cDKO mice.     

First effective drug for dry mouth

The Food and Drug Administration (FDA) approved oral pilocarpine (Salagen) for the treatment of dry mouth in patients receiving radiation therapy for head and neck cancer. There are possible drug interactions with the beta blockers that are often used by cardiac patients. Other side effects are sweating, nausea, and inflammation of the mucous membranes.     

Sleep deprivation has a neuroprotective role in a traumatic brain injury of the rat

During the process of a brain injury, responses to produce damage and cell death are activated, but self-protective responses that attempt to maintain the integrity and functionality of the brain are also activated. We have previously reported that the recovery from a traumatic brain injury (TBI) is better in rats if it occurs during the dark phase of the diurnal cycle when rats are in the waking period. This suggests that wakefulness causes a neuroprotective role in this type of injury. Here we report that 24 h of total sleep deprivation after a TBI reduces the morphological damage and enhances the recovery of the rats, as seen on a neurobiological scale.     

Lycopene: an effective neuroprotective option against neurodeterioration induced by formaldehyde inhalation

To address the mechanisms underlying the pathophysiology of formaldehyde (FA)-induced neurotoxicological impact and to examine the neuroprotective potency of lycopene (Lyco) against neuronal damage produced by formaldehyde inhalation in rats. Fifty adult female rats were divided into five groups: G1 negative control, G2 formaldehyde-challenged group (FA 10 ppm), G3 formaldehyde-challenged group (FA 20 ppm), G4 formaldehyde-challenged group pre-treated with Lyco (Lyco + FA 10 ppm), and G5 formaldehyde-challenged group pre-treated with Lyco (Lyco + FA 20 ppm). Brain nitric oxide (NO), malonaldehyde (MDA) Bcl-2 levels, and catalase (CAT) activity were increased significantly, while, brain superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activity were decreased significantly in FA-challenged rats. Also, FA inhalation elicited significant depletion in brain brain-derived neurotrophic factor (BDNF), dopamine (DA), noradrenaline (NA), and adrenaline (AD) levels. Moreover, FA inhalation induced significant upregulation in brain X-linked inhibitor of apoptosis protein (XIAP) gene expression levels. Survivin immunopositive cells in the brain were increased in FA-challenged rats when compared to the negative control counterparts. On the other side, pre-treatment with Lyco along with FA inhalation could attenuate the adverse impacts of FA on the brain. Histopathological examination of the brain tissue revealed that the treatment with Lyco prior FA inhalation could preserve the structural organization of the brain. The present data offered a mechanistic explanation to formaldehyde neurotoxicity. Also, our findings clearly identified that the neuroprotection of Lyco is contributed to the preservation of oxidant/antioxidant homeostasis and maintenance of neuronal survival, functions, and integrity.     

Aromatase: a neuroprotective enzyme

Estradiol, in addition to its participation in neuroendocrine regulation and sexual behavior, has neuroprotective properties. Different types of brain injury induce the expression of the enzyme aromatase in reactive astroglia. This enzyme catalyzes the conversion of testosterone and other C19 steroids to estradiol. Genetic or pharmacological inhibition of brain aromatase results in marked neurodegeneration after different forms of mild neurodegenerative stimuli that do not compromise neuronal survival under control conditions. Furthermore, aromatase mediates neuroprotective effects of precursors of estradiol such as pregnenolone, dehydroepiandrosterone (DHEA) and testosterone. These findings strongly suggest that local formation of estradiol in the brain is neuroprotective and that the induction of aromatase and the consecutive increase in the local production of estradiol are part of the program triggered by the neural tissue to cope with neurodegenerative insults. Aromatase may thus represent an important pharmacological target for therapies conducted to prevent aging-associated neurodegenerative disorders.     

Pharmacokinetic and pharmacodynamic study of a clinically effective anti-CD2 monoclonal antibody

The humanized IgG1κ monoclonal antibody siplizumab and its rat parent monoclonal IgG2b antibody BTI-322 are directed against the CD2 antigen. Siplizumab is species-specific, reacting with human and chimpanzee cells but not with cells from any other species, including other non-human primates. Because siplizumab treatment has recently shown great potential in clinical transplantation, we now present the results of our previous pharmacokinetic, pharmacodynamic and safety studies of both antibodies. Fourteen chimpanzees received 1-3 doses of 0.143 to 5.0 mg/kg iv The effects were followed with flow cytometry on peripheral lymphocytes and staining of lymph nodes. Side effects were recorded. Serum antibody concentrations were followed. Across the doses, a rapid, transient depletion of CD2, CD3, CD4 and CD8 lymphocytes and NK cells was observed for both antibodies. Immune reconstitution was more rapid for BTI-322 compared to siplizumab. Paracortical lymph node T cell depletion was moderate, estimated at 45% with doses of >0.6 mg/kg. Restoration of lymph node architecture was seen after two weeks to two months for all animals. All four subjects receiving BTI-322 experienced AEs on the first dosing day, while the eight subjects dosed with siplizumab experienced few mild, transient AEs. Infusion with siplizumab and BTI-322 resulted in rapid depletion of CD2⁺ cells in circulation and tissue. Siplizumab had a longer t_1/2 and fewer AEs compared to BTI-322.     

CSF: diagnosis of neurosyphilis in a patient hospitalized for an acute brain stroke

We report the case of a sixty-eight years old patient, who was admitted to the emergency for paresthesis associated with dysarthra and speech complaints. Neuroimaging revealed the presence of stenosis caused by arteritis. The notion of history of syphilis infection led to diagnosis of neurosyphilis. Diagnosis is difficult due to its clinical polymorphism and requires using several tests in the cerebrospinal fluid (CSF) because infection involving the central nervous system. Neurosyphilis is diagnosed by finding elevated cell count (80 leukocytes/mm3), high protein level (1.07 g/L) and positive IgG oligoclonal bands. In addition CSF and blood should be titrated with the VDRL and TPHA tests which are difficult to interpret. The diagnosis of active neuro-syphilis requires positive, non specific and specific inflammatory tests.     

Changes at the focus of experimental ischemic stroke treated with neuroprotective agents

The aim of the present work was to compare the morphological changes occurring at the focus of experimental ischemic stroke treated with agents of the neurotrophic group (alpha-GPC, cerebrolysin), an agent with nootropic properties (piracetam), and a mixed-action agent (vinpocetin). Experiments were performed on 18 rats. Transient cerebral circulatory lesions (acute ischemia) were produced in the right hemisphere by clipping the stem of the innominate artery for 40 min. Light microscopic and electron microscopic studies were performed on fragments of cerebral cortex, brainstem, and cerebellum. Use of alpha-GPC and cerebrolysin increased the tolerance of neurons to ischemic damage and slowed the execution of the cell death program. Intracellular changes were seen and were interpreted as adaptive and reparative: these included folding of the nuclear membrane, abundance of polyribosomes, and endoplasmic reticulum and Golgi complex hypertrophy. These agents preserved the structures of the nuclear membranes and major cellular organelles. When piracetam and vinpocetin were used, all morphological measures indicated inadequate energy provision for repair processes in the acute stage of ischemic stroke. Morphological signs of functional tension of cerebral cortex neurons were seen, with gliocytes in different stages of apoptosis, along with the phenomenon of incomplete separation of gliocytes during proliferation, pathological changes to myelin and non-myelinated fibers, and abnormalities in synapse structure. __________ Translated from Morfologiya, Vol. 130, No. 6, pp. 40–46, November–December, 2006.     

Developing optimal search strategies for detecting clinically sound prognostic studies in MEDLINE: an analytic survey

Background

Clinical end users of MEDLINE have a difficult time retrieving articles that are both scientifically sound and directly relevant to clinical practice. Search filters have been developed to assist end users in increasing the success of their searches. Many filters have been developed for the literature on therapy and reviews but little has been done in the area of prognosis. The objective of this study is to determine how well various methodologic textwords, Medical Subject Headings, and their Boolean combinations retrieve methodologically sound literature on the prognosis of health disorders in MEDLINE.

Methods

An analytic survey was conducted, comparing hand searches of journals with retrievals from MEDLINE for candidate search terms and combinations. Six research assistants read all issues of 161 journals for the publishing year 2000. All articles were rated using purpose and quality indicators and categorized into clinically relevant original studies, review articles, general papers, or case reports. The original and review articles were then categorized as 'pass' or 'fail' for methodologic rigor in the areas of prognosis and other clinical topics. Candidate search strategies were developed for prognosis and run in MEDLINE – the retrievals being compared with the hand search data. The sensitivity, specificity, precision, and accuracy of the search strategies were calculated.

Results

12% of studies classified as prognosis met basic criteria for scientific merit for testing clinical applications. Combinations of terms reached peak sensitivities of 90%. Compared with the best single term, multiple terms increased sensitivity for sound studies by 25.2% (absolute increase), and increased specificity, but by a much smaller amount (1.1%) when sensitivity was maximized. Combining terms to optimize both sensitivity and specificity achieved sensitivities and specificities of approximately 83% for each.

Conclusion

Empirically derived search strategies combining indexing terms and textwords can achieve high sensitivity and specificity for retrieving sound prognostic studies from MEDLINE.

     

Event-related brain potentials in a varied-set memory search task: A reconsideration

Event-related potentials (ERPs) were recorded in 19 healthy subjects as they completed two Sternberg (1969, American Scientist, 57, 421–457) memory tests. In separate sessions, either single digits (i.e., 0–9) or 10 abstract figures were used as stimuli. In both sessions, memory set sizes were 1 (M1), 2 (M2), or 4 (M4). The amplitude and latency of the parietal P400 and the frontocentral negativity preceding P400 varied significantly with set size, but only between M1 and M2, whereas reaction time increased dramatically from M1 to M2 and from M2 to M4. These findings challenge previous assertions that the ERPs reflect aspects of the exhaustive serial search proposed by Sternberg. A late parietal positivity (P620), which failed to vary with set size, was larger in response to figures than to digits and may represent the search for, or utilization of, semantic traces of the stimuli.