Expression of rat insulin-like growth factor binding protein-6 in the brain, spinal cord, and sensory ganglia

Insulin-like growth factors (IGFs) are important trophic factors during development as well as in the adult or damaged nervous system. Their trophic actions are modulated by interactions with six distinct IGF binding proteins. The mRNA expression profiles of binding proteins 2, 4 and 5 in the normal developing and adult CNS are well characterized and are shown to have distinctive, non-overlapping distributions. The IGF binding protein-6 (BP6) is also expressed in the CNS, however, details regarding its mRNA expression distribution in the developing and adult nervous system is limited. BP6 has the unique property of preferentially binding the IGF-II ligand. Coupled with the fact that this ligand is the most abundantly expressed IGF in the adult CNS, this suggests that the IGF-II/BP6 complex has a unique role in modulating IGF-II function in the adult brain. In this report the anatomical distribution of BP6 messenger RNA in the developing and adult rat nervous system is presented. In the embryonic animal the CNS expression is tightly restricted to trigeminal ganglia and, relative to the rest of the embryo, this structure has the highest expression. The expression in the forebrain and cerebellum does not occur until after postnatal day 21 and then is primarily associated with GABAergic interneurons. The highest levels of expression in the adult animal are in the hindbrain, spinal cord, cranial ganglia, and dorsal root ganglia. These nuclei in the hindbrain and periphery that express BP6 are all associated with the coordination of sensorimotor function in the cerebellum, which indicates an important role for the BP6/IGF-II complex in the function and maintenance of these systems.     

The future of criminal violence: juveniles tried as adults

Juveniles tried as adults (JTA) represent a select and small subsample of juvenile offenders. This study seeks to provide a profile of habitually violent JTAs transferred to the adult penal system and to compare them with their adult counterparts. Twenty-nine incarcerated violent male juveniles tried as adults were compared with a sample of 27 incarcerated violent male offenders across demographic, neuropsychological, criminal history, psychopathy, and substance abuse variables. The JTAs were characterized by a high rate of gang membership (96%), substance abuse (alcohol, marijuana, and phenylcyclidene), and use of guns. In the juvenile sample, 65 percent used guns in violence not leading to arrest, and 93 percent used guns in a violent crime leading to arrest. Juvenile offenders were similar to their adult counterparts in patterns of criminality, although adult offenders had higher psychopathy scores. Both groups revealed generally intact neuropsychological functioning with the exception of a higher rate of perseverative responses in the adult sample. The results are discussed in terms of the implication of the degree of violence in a young offender population.     

Target-dependent axonal sprouting following vagal-hypoglossal nerve anastomosis in cats

Purpose: To investigate the relationships between the axonal sprouting and target neurotization by central neurons after nerve heterocon-nection. Methods: Unilateral (right) vagal-hypoglossal nerve anastomosis (VHA) was performed in adult cats. Following 3-315 days postoperation (dpo), quantitative analyses and ultrastructural changes in the proximal portion of the vagal-hypoglossal heteroconnected nerve as well as the time course of neuronal regeneration were studied. Along with this, horseradish peroxidase (HRP) retrograde tracing technique was used to label the neurons of dorsal motor vagal nucleus (DMV) and nucleus ambiguus (NA) to ascertain if target neurotization was established. Results: The contralateral (left) intact vagus nerve proximal to the level of ansa cervicalis showed an average of 33 +/- 1 myelinated and 74 +/- 4 unmyelinated axons in 727 &mgr;m(2) sectional area of the nerve. In the heteroconnected nerve at the corresponding level just proximal to the anastomosis site, there was a marked increase in the number of small axons sprouting from the unmyelinated nerve fibers between 18 and 25 dpo. The number of these axonal sprouts appeared to decline at 32 dpo but its increase of 131 % was sustained until the late regeneration stage at 315 dpo when compared with the contralateral nerve serving as a control. The mean number of myelinated axons per area unit (727 &mgr;m(2)) was reduced to 18 at 3 dpo but was immediately restored to the normal range at 7 dpo. The retrograde labelling of neurons in both the DMV and NA was first detected at 22 dpo and was progressively increased peaking by about 67 dpo. Conclusions: We conclude that compared with the unmyelinated axons, the myelinated axons may acquire a superior interaction with the new target. Furthermore, the postoperative neurotization of tongue muscles may initiate and facilitate the retraction of the redundant axonal sprouts.     

Expression of cytochrome p450 and other biotransformation genes in fetal and adult human nasal mucosa.

Despite recent progress in the identification and characterization of numerous nasal biotransformation enzymes in laboratory animals, the expression of biotransformation genes in human nasal mucosa remains difficult to study. Given the potential role of nasal biotransformation enzymes in the metabolism of airborne chemicals, including fragrance compounds and therapeutic agents, as well as the potential interspecies differences between laboratory animals and humans, it would be highly desirable to identify those biotransformation genes that are expressed in human nasal mucosa. In this study, a global gene expression analysis was performed to compare biotransformation enzymes expressed in human fetal and adult nasal mucosa to those expressed in liver. The identities of a list of biotransformation genes with apparently nasal mucosa-selective expression were subsequently confirmed by RNA-polymerase chain reaction (PCR) and DNA sequencing of the PCR products. Further quantitative RNA-PCR experiments indicated that, in the fetus, aldehyde dehydrogenase 6 (ALDH6), CYP1B1, CYP2F1, CYP4B1, and UDP glucuronosyltransferase 2A1 are expressed preferentially in the nasal mucosa and that ALDH7, flavin-containing monooxygenase 1, and glutathione S-transferase P1 are at least as abundant in the nasal mucosa as in the liver. The nasal mucosal expression of CYP2E1 was also detected. These findings provide a basis for further explorations of the metabolic capacity of the human nasal mucosa for xenobiotic compounds.     

Pain flare following external beam radiotherapy and meaningful change in pain scores in the treatment of bone metastases.

BACKGROUND AND PURPOSE: To examine the incidence of pain flare following external beam radiotherapy and to determine what constitutes a meaningful change in pain scores in the treatment of bone metastases. PATIENTS AND METHODS: Patients with bone metastases treated with external beam radiotherapy were asked to score their pain on a scale of 0-10 before the treatment (baseline), daily during the treatment and for 10 days after completion of external beam radiation. Pain flare was defined as a two-point increase from baseline pain in the pain scale of 0-10 with no decrease in analgesic intake or a 25% increase in analgesic intake employing daily oral morphine equivalent with no decrease in pain score. To distinguish pain flare from progression of pain, we required the pain score and analgesic intake to return back to baseline levels after the increase/flare. They were also asked to indicate if their pain changed during that time compared to pre-treatment level. The change in pain score was compared with patient perception. RESULTS: Eighty-eight patients were evaluated in this study. There were 49 male and 39 female patients with the median age of 70 years. Twelve of 88 patients (14%) had pain flare on day 1. The overall incidence of pain flare during the study period ranged from 2 to 16%. A total of 797 pain scorings were obtained. Patients perceived an improvement in pain when their self-reported pain score decreased by at least two points. CONCLUSIONS: Our study confirms the occurrence of pain flare following the external beam radiotherapy in the treatment of bone metastases. Further studies are required to predict who are at risk for flare. Appropriate measures can be taken to alleviate the pain flare. The finding in the meaningful change in pain scores supports the investigator-defined partial response used in some clinical trials.     

利用LC-MS/MS法快速鉴定盐酸头孢吡肟中的同分异构体杂质

目的建立应用LC-MS/MS技术快速鉴定盐酸头孢吡肟原料药中的同分异构体杂质的方法。方法以乙腈-10 mmol·L^-1乙酸铵(5∶95)为流动相经C₁₈柱分离,通过电喷雾串联质谱在线检测，获得相关的色谱和质谱信息。结果在所建立的条件下，盐酸头孢吡肟及其同分异构体杂质获得有效分离，主成分和其同分异构体杂质的保留时间分别为15.28 min和9.18 min，同时它们的二级质谱产物离子信息及其裂解方式呈现明显的差异。结论本法能快速、准确地分离鉴定盐酸头孢吡肟原料药中的同分异构体杂质，从而可以对其原料药进行质量控制。     

角膜内皮细胞计和超声角膜测厚仪测量角膜中央厚度的比较

目的　比较角膜内皮细胞计和超声角膜测厚仪测量的角膜厚度值之间的差异性。方法　分别应用角膜内皮细胞计和超声角膜测厚仪对 5 3例 (10 6眼 )的中央角膜厚度进行测量 ,对两组测量值进行配对t检验、直线相关分析 ,并对两种仪器三次测量值行组内相关系数分析。结果　应用超声角膜测厚仪检测的角膜厚度均值为 (5 2 1 77± 32 16 ) μm ,角膜内皮细胞计数计检测的均值为 (5 15 4 8± 30 39) μm ,后者显著低于前者 (P<0 0 0 1) ,两者呈显著正相关 (r=0 938,P <0 0 0 1) ,超声法和角膜内皮细胞计法测厚的组内相关系数分别为0 95和 0 93。结论　角膜内皮细胞计测量值低于超声测厚仪测量值 ,但从临床角度来看 ,这种差异并不能否定角膜内皮计用于角膜测厚的可靠性 ,角膜内皮细胞计测量值的一致性甚至超过了超声测厚仪 ,并有非接触性检查的优点。角膜内皮细胞计和超声测厚仪均能为我们提供较为准确的角膜厚度值 ,但临床测量时应当知道两种检查方法之间的差异 ,并认识到各自的优劣 ,才能更好地选择应用不同的设备。对于随访患者应采用同一种仪器来进行检测才具有更好的可比性     

Effects of rat urotensin Ⅱ on coronary flow and myocardial eNOS protein expression in isolated rat heart

AIM: To examine the effects of urotensin Ⅱ, a recently discovered endogenous peptide, on coronary flow (CF), cardiac function, and endothelial nitric oxide synthase (eNOS) expression in isolated rat hearts. METHODS: Heart was isolated and perfused retrogradely via the aorta in Langendorff mode. Rat urotensin Ⅱ was administered in the perfusion solution. The eNOS content in myocardium was determined by Western blot. RESULTS: Rat urotensin Ⅱ had no effect on the heart rate, left ventricular systolic pressure, left ventricular end-diastolic pressure, or ±dp/dtmax. While rat urotensin Ⅱ dose-dependently increased CF. CF was increased by 11.43 %, 6.67 %, 6.62 %, 6.56 %, 6.36 %, and 5.86 % respectively in a time-dependent manner at 5, 10, 15, 20, 25, and 30 min after injection of rat urotensin II 6.66×10-2μg. The maximal effect on CF was found at 5 min following urotensin II administration. NG-nitro-L-arginine methyl ester (L-NAME) did not prevent the increased CF in response to urotensin II. Rat uroten