The pharmacokinetics of THC in fat and brain: resulting functional responses to marihuana smoking

A pleasant sensory perception (PSP), the high of THC or of marihuana consumption, is a consistent functional response to this drug only manifested by man, and which occurs concurrently with an increased heart rate. However, it has not been possible to relate consistently magnitude and duration of these functional markers to THC plasma concentration, whatever the route of administration. A re-analysis of all the available clinical and experimental data reporting the pharmacokinetics and storage of THC in tissues in function of time, have indicated that the discrepancies between functional responses and plasma molecular THC concentration may be accounted for by the pharmacokinetics of THC. The instant uptake and unlimited storage of THC by neutral fat limits the molecular concentration of the drug present in the plasma to a level which does not exceed 6 x 10(14) molecules/ml. The physicochemical nature of the membrane lipid bilayer (of the blood-brain barrier) will restrict the access of THC into the bilayer receptors and its: reactive enzymes. The PSP and increased heart rate of marihuana is correlated with the molecular concentration of THC in the bilayer (blood-brain barrier) of the order of 10(12)-10(14) molecules/ml. This number in turn would be related to the number of functional THC receptor sites in the lipid bilayer. THC would exert its functional properties on PSP and heart rate through a molecular transmission to specific receptor site and bilipid layer physicochemical interations. Rapid uptake and slow release of THC in fat associated with a rate-limited uptake into brain may be a general philogenetic mechanism which would protect brain function from prolonged exposure to xenobiotics like THC and other fat soluble drugs. Copyright 2001 John Wiley & Sons, Ltd.     

Assessment of fitness for purpose of an insect bioassay using the desert locust (Schistocerca gregaria L.) for the detection of paralytic shellfish toxins in shellfish flesh.

We have developed a bioassay using 5th instar desert locusts (Schistocerca gregaria L.) for the detection of saxitoxin-the paralytic shellfish poison in shellfish flesh. The bioassay procedure is to inject 10 locusts with a shellfish extract, and assess their conditions at time points up to 2h post injection, looking for an endpoint of paralysis. From the proportion responding, the equivalent dose of pure saxitoxin could be estimated. Performance characteristics of the bioassay were assessed using shellfish samples spiked with saxitoxin, and we found the bioassay could detect and quantify toxin levels in the range of regulatory relevance. Relative toxicities of selected saxitoxin analogues differed from those reported in mammalian systems. Variation for repeatability conditions was acceptable but variation was higher under reproducibility conditions. This was related to (a) batches of insects from different suppliers, (b) different operators, and (c) different observers assessing the endpoint. We also noted adverse reactions with some shellfish species. These problems may be resolved by further refinement of the method and operator training, before formal validation. Nevertheless, we suggest the method potentially offers a simple, ethically acceptable, broad-specificity functional bioassay, which is desirable in any toxin-monitoring programme.     

Study of paralytic shellfish poisoning toxin profile in shellfish from the Mediterranean shore of Morocco

Since 1992, a monitoring program for bivalve molluscs contaminated by algal toxins was established at different stations along the Mediterranean Moroccan shores. The monitored stations were tested every 2 weeks. The presence of toxicity was determined using the mouse bioassay method. Toxin profile was carried out by HPLC/FD in selected contaminated tissues. According to the outcomes of this surveillance from 1994 to 1999, reliable information on toxicity of shellfish was obtained. They indicate that PSP is a recurrent toxicity in molluscs along the Mediterranean shore of Morocco. It has been noted a difference of PSP accumulation among individual shellfish. The cockle (Achanthocardia tuberculatum) presents toxicity throughout the year, while other specimens from the same area such as clam (Callista chione), warty venus (Venus gallina) and marine beans (Donax trunculus) accumulate it seasonally from January to April, after which they depurate the toxin. Moreover, the study of toxin profiles among individual shellfish was undertaken. It was found that shellfish presented a complex profile pointing to contamination by Gymnodinium catenatum.     

云芝精华（PSP）防治口腔白斑癌变的临床研究

目的 探寻能阻断或逆转口腔上皮异常增生的中草药,评价PSP对白斑癌变的防治效果。方法 对有上皮异常增生的口腔白斑患者连续给PSP口服3月,观察其治疗前后的临床症状,并作病理切片分析。结果 充血糜烂症状见有明显改善,约40%患者的疼痛,牵拉、粗糙感有不同程度好转,约60%患者的上皮异常增生程度得到减轻。结论 PSP对口腔白斑有阻断癌变的临床疗效。     

Modeling trajectories of regional volume loss in progressive supranuclear palsy

Progressive supranuclear palsy is a neurodegenerative disease with progressive brain atrophy over time. It is unknown which specific brain regions decline over time, whether regional volume loss occurs in a linear fashion, and whether regional atrophy correlates with clinical decline over time in progressive supranuclear palsy. Twenty‐eight subjects meeting probable progressive supranuclear palsy criteria were prospectively recruited and completed 96 MRI scans over 2 years. Mixed‐effect models were utilized to determine which regions had significant atrophy over time and whether decline was linear or nonlinear. We assessed 13 regions across the brain, as well as whole‐brain and ventricular volume. Regional trajectories were also correlated with change in clinical measures of executive function and gait and ocular motor impairment. A linear decline was observed in all frontal and temporal regions, the superior parietal lobe, the thalamus, the caudate nuclei, and the midbrain, as well as in the whole brain. Ventricular expansion was also linear. Nonlinear decline was observed for the caudal middle frontal lobe and globus pallidus. Rates of change in the superior frontal lobe, thalamus, and midbrain were beyond those expected in normal aging. Decline in frontal lobe volume and the midbrain area correlated best to decline in clinical measures. In progressive supranuclear palsy, atrophy is occurring in multiple brain regions, particularly in those that have previously been implicated in the disease. Decline is mainly linear but can be nonlinear for some regions. The frontal lobe and midbrain seem to be playing the most significant roles in the progressive worsening of clinical signs in progressive supranuclear palsy. © 2013 Movement Disorder Society     

“Atypical” atypical parkinsonism: New genetic conditions presenting with features of progressive supranuclear palsy,corticobasal degeneration,or multiple system atrophy—A diagnostic guide

Recently, a number of genetic parkinsonian conditions have been recognized that share some features with the clinical syndromes of progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and multiple system atrophy (MSA), the classic phenotypic templates of atypical parkinsonism. For example, patients with progranulin, dynactin, or ATP13A gene mutations may have vertical supranuclear gaze palsy. This has made differential diagnosis difficult for practitioners. In this review, our goal is to make clinicians aware of these genetic disorders and provide clinical clues and syndromic associations, as well as investigative features, that may help in diagnosing these disorders. The correct identification of these patients has important clinical, therapeutic, and research implications. © 2013 Movement Disorder Society     

Differentiation of Progressive Supranuclear Palsy: clinical,imaging and laboratory tools

Progressive supranuclear palsy (PSP) is the most common atypical parkinsonian syndrome comprising two main clinical subtypes: Richardson's syndrome (RS), characterized by prominent postural instability, supranuclear vertical gaze palsy and frontal dysfunction; and PSP‐parkinsonism (PSP‐P) which is characterized by an asymmetric onset, tremor and moderate initial therapeutic response to levodopa. The early clinical features of PSP‐P are often difficult to discern from idiopathic Parkinson's disease (PD), and other atypical parkinsonian disorders, including multiple system atrophy (MSA) and corticobasal syndrome (CBS). In addition, rare PSP subtypes may be overlooked or misdiagnosed if there are atypical features present. The differentiation between atypical parkinsonian disorders and PD is important because the prognoses are different, and there are different responses to therapy. Structural and functional imaging, although currently of limited diagnostic value for individual use in early disease, may contribute valuable information in the differential diagnosis of PSP. A growing body of evidence shows the importance of CSF biomarkers in distinguishing between atypical parkinsonian disorders particularly early in their course when disease‐modifying therapies are becoming available. However, specific diagnostic CSF biomarkers have yet to be identified. In the absence of reliable disease‐specific markers, we provide an update of the recent literature on the assessment of clinical symptoms, pathology, neuroimaging and biofluid markers that might help to distinguish between these overlapping conditions early in the course of the disease.     

精神分裂症患者分级康复干预效果观察

目的探讨对精神分裂症患者进行分级康复干预的效果。方法将65例精神分裂症患者随机分为两组,均予以精神科常规治疗及护理,研究组应用个人和社会功能量表进行分级康复干预。观察8周。于干预前后采用个人和社会功能量表、阳性与阴性症状量表评定干预效果。结果干预后两组阳性与阴性症状量表评分均较干预前显著降低（P〈0．01）,同期两组间比较差异无显著性（P〉0．05）;个人和社会功能量表总分较干预前显著升高（P〈0．05或0．01）,研究组显著高于对照组（P〈0．05）。结论对精神分裂患者进行分级康复干预,有利于改善患者的社会功能,促进患者回归社会。     

人性化护理干预对住院青少年精神分裂症患者康复的影响

目的 探讨人性化护理干预对住院青少年精神分裂症患者康复的影响.方法 将114例住院青少年精神分裂症患者随机分为两组,均予以精神科常规药物治疗,观察组予以人性化护理干预,对照组予以常规护理干预,观察8周.于干预前后采用阳性与阴性症状量表、个人和社会功能量表、护士用住院病人观察量表评定临床效果.结果 干预后两组阳性与阴性症状量表评分均较干预前显著下降（P＜0.01）,观察组较对照组下降更显著（P＜0.01）;个人和社会功能量表、护士用住院病人观察量表评分均较干预前显著升高（P＜0.01）,观察组较对照组升高更显著（P＜0.01）.结论 人性化护理干预对改善青少年精神分裂症患者的临床症状,提高社会功能和生活质量具有重要作用.     

比较两种云芝糖肽对体外人癌细胞株的抗癌作用

本文应用四株人体肿瘤细胞株作为靶细胞,比较了云芝糖肽PSP与PSK在体外对它们的作用。结果表明PSP与PSK的抗癌生物活性基本相同,二者均对靶细胞增殖具有中等抑制作用。PSP在1000μg/ml的浓度时对人肺腺癌细胞株(SPC)仍能引起一系列的形态学异常变化,如细胞肿大,核染色质凝聚,锯齿状核和多核现象。