[11C]5-HTP and microPET are not suitable for pharmacodynamic studies in the rodent brain

The PET tracer [¹¹C]5-hydroxytryptophan ([¹¹C]5-HTP), which is converted to [¹¹C]5-hydroxytryptamine ([¹¹C]5-HT) by aromatic amino acid decarboxylase (AADC), is thought to measure 5-HT synthesis rates. But can we measure these synthesis rates by kinetic modeling of [¹¹C]5-HTP in rat? Male rats were scanned with [¹¹C]5-HTP (60 minutes) after different treatments. Scans included arterial blood sampling and metabolite analysis. 5-HT synthesis rates were calculated by a two-tissue compartment model (2TCM) with irreversible tracer trapping or Patlak analysis. Carbidopa (inhibitor peripheral AADC) dose-dependently increased [¹¹C]5-HTP brain uptake, but did not influence 2TCM parameters. Therefore, 10 mg/kg carbidopa was applied in all subsequent study groups. These groups included treatment with NSD 1015 (general AADC inhibitor) or p-chlorophenylalanine (PCPA, inhibitor of tryptophan hydroxylase, TPH). In addition, the effect of a low-tryptophan (Trp) diet was investigated. NSD 1015 or Trp depletion did not affect any model parameters, but PCPA reduced [¹¹C]5-HTP uptake, and the k₃. This was unexpected as NSD 1015 directly inhibits the enzyme converting [¹¹C]5-HTP to [¹¹C]5-HT, suggesting that trapping of radioactivity does not distinguish between parent tracer and its metabolites. As different results have been acquired in monkeys and humans, [¹¹C]5-HTP-PET may be suitable for measuring 5-HT synthesis in primates, but not in rodents.     

Lineage tracing reveals dynamic changes in oligodendrocyte precursor cells following cuprizone‐induced demyelination

The regeneration of oligodendrocytes is a crucial step in recovery from demyelination, as surviving oligodendrocytes exhibit limited structural plasticity and rarely form additional myelin sheaths. New oligodendrocytes arise through the differentiation of platelet‐derived growth factor receptor α (PDGFRα) expressing oligodendrocyte progenitor cells (OPCs) that are widely distributed throughout the CNS. Although there has been detailed investigation of the behavior of these progenitors in white matter, recent studies suggest that disease burden in multiple sclerosis (MS) is more strongly correlated with gray matter atrophy. The timing and efficiency of remyelination in gray matter is distinct from white matter, but the dynamics of OPCs that contribute to these differences have not been defined. Here, we used in vivo genetic fate tracing to determine the behavior of OPCs in gray and white matter regions in response to cuprizone‐induced demyelination. Our studies indicate that the temporal dynamics of OPC differentiation varies significantly between white and gray matter. While OPCs rapidly repopulate the corpus callosum and mature into CC1 expressing mature oligodendrocytes, OPC differentiation in the cingulate cortex and hippocampus occurs much more slowly, resulting in a delay in remyelination relative to the corpus callosum. The protracted maturation of OPCs in gray matter may contribute to greater axonal pathology and disease burden in MS.     

高效液相色谱流通池法测定紫草中假紫草素的含量

高效液相色谱法测定紫草提取物中的假紫草素时,出现20个峰,需时75min,主峰保留时间55min,常规方法制备工作曲线很费时。本文报道一种新的工作曲线法——流通池法的原理和方法,测定结果与常规方法一致,可以节省时间。     

Effects of mining-derived metals on riffle-dwelling benthic fishes in Southeast Missouri, USA

We studied the ecological effects of mining-derived metals on riffle-dwelling benthic fishes at 16 sites in the Viburnum Trend lead–zinc mining district of southeast Missouri. Fish community attributes were compared to watershed features and to physical and chemical variables including metal concentrations in sediment pore water and fish. Ozark sculpin (Cottus hypselurus), rainbow darter (Etheostoma caeruleum), Ozark madtom (Noturus albater), and banded sculpin (Cottus carolinae) were the most abundant fishes collected. Species richness and density of riffle-dwelling benthic fishes were negatively correlated with metal concentrations in pore water and in fish. Sculpin densities were also negatively correlated with metal concentrations in pore water and in fish, but positively correlated with distance from mines and upstream watershed area. These findings indicate that metals associated with active lead–zinc mining adversely affect riffle-dwelling benthic fishes downstream of mining areas in the Viburnum Trend. Sculpins may be useful as a sentinel species for assessing mining-related impacts on fish communities.     

Predictors of agitation in nursing home residents

Agitation in nursing home residents presents a serious challenge to caregivers and may place residents at risk for harm. Understanding the etiology of agitation can assist clinicians in developing nonpharmacologic interventions for preventing and treating this problem. The purpose of this study was to examine independent and common predictors of resident agitation with structural equation modeling. Agitation was measured with both a standardized staff report rating scale and direct behavioral observation. No indirect or mediating effects were found. Cognitive impairment, vision and hearing impairment, and gender were found to be independent predictors of agitation as measured by direct behavioral observation. Only cognitive impairment was found to be predictive of agitation as measured by the standardized staff report scale. An unexpected finding was that vision impairment appeared to exert a protective effect for agitation in these severely cognitively impaired residents. The clinical implications of these findings are discussed as well as the relative merits of the two methods of measuring agitation.     

Sulfuric acid and streptococci clearance from respiratory tracts of mice.

The inhalation of 15 mg/cu m (3.2mu count median diameter) of H2SO4 aerosol for four hours after exposure to radioactive aerosol resulted in a reduction in the rate of clearance of nonviable streptococci from the lungs and noses of mice. A second exposure to H2SO4 lasting 90 minutes (15 mg/cu m, 3.2mu count median diameter) for four days prior to the radioactive aerosol resulted in a reduced rate of clearance of nonviable streptococci from the noses but not the lungs. Neither of these exposure regimens caused an alteration in the rate of reduction of viable streptococci from the lungs or noses. Inhalation of 1.5 mg/cu m of H2SO4 (0.6mu coung median diameter) for four daily 90-minute exposures prior to, or for four hours after exposure to Streptococcus caused no alteration in the normal rate of clearance of viable or nonviable streptococci from the noses or lungs.