Neuronal activity evoked by chronically implanted intracortical microelectrodes

The averaged evoked compound action potentials (AECAPs) were recorded from the ipsilateral pyramidal tract of awake, unrestrained cats before, during, and after continuous electrical stimulation of the cerebral cortex via chronically implanted activated iridium or platinum-30% iridium (Pt30%Ir) microelectrodes. After stimulating 24 h at 20 pulses per second (pps), using charge-balanced, 200-microseconds pulse pairs of 40 to 80 microA (400 to 800 microC/cm2, 8 to 16 nC/phase (ph), 2 to 4 A/cm2), there was a transient elevation of the threshold of the early (direct) and of the alte (transynaptic) components of the AECAP. After cessation of continuous stimulation at 80 microA, the threshold of the early component of the AECAP remained elevated for as long as 24 h and the late component as long as 4 days, indicating significant but reversible depression of the electrical excitability of cortical neurons close to the microelectrodes. In three cats stimulated 23 h/day for 1 week, the AECAP also recovered to their prestimulus threshold. In contrast, pulsing for 24 h at 320 microA (3200 microC/cm2, 64 nC/ph, 16 A/cm2) produced marked elevation of the threshold of the AECAPs which was not reversed by 7 to 12 days after termination of intracortical stimulation. The electrical excitability of neurons adjacent to (unpulsed) microelectrodes 2 mm from the pulsed electrode was not affected. The observations reported here, in conjunction with the histologic results reported in the companion paper, indicate that both the Pt30%Ir and the iridium microelectrodes can be operated safely at currents to at least 80 microA, charge/ph of 16 A/cm2, and a charge density of 800 microC/cm2 X ph. However, on the basis of the electrophysiologic criteria, both types appear to be unsafe when pulsed at 320 microA (64 nC/ph, 3200 microC/cm2 X ph, 16 A/cm2).     

Effect of goldenseal (Hydrastis canadensis) and kava kava (Piper methysticum) supplementation on digoxin pharmacokinetics in humans.

Phytochemical-mediated modulation of P-glycoprotein (P-gp) and other drug transporters may give rise to many herb-drug interactions. Serial plasma concentration-time profiles of the P-gp substrate, digoxin, were used to determine whether supplementation with goldenseal or kava kava modified P-gp activity in vivo. Twenty healthy volunteers were randomly assigned to receive a standardized goldenseal (3210 mg daily) or kava kava (1227 mg daily) supplement for 14 days, followed by a 30-day washout period. Subjects were also randomized to receive rifampin (600 mg daily, 7 days) and clarithromycin (1000 mg daily, 7 days) as positive controls for P-gp induction and inhibition, respectively. Digoxin (Lanoxin, 0.5 mg) was administered p.o. before and at the end of each supplementation and control period. Serial digoxin plasma concentrations were obtained over 24 h and analyzed by chemiluminescent immunoassay. Comparisons of area under the curve (AUC)((0-3)), AUC((0-24)), C(max,) CL/F, and elimination half-life were used to assess the effects of goldenseal, kava kava, rifampin, and clarithromycin on digoxin pharmacokinetics. Rifampin produced significant reductions (p < 0.01) in AUC((0-3)), AUC((0-24)), CL/F, t(1/2), and C(max), whereas clarithromycin increased these parameters significantly (p < 0.01). With the exception of goldenseal's effect on C(max) (14% increase), no statistically significant effects on digoxin pharmacokinetics were observed following supplementation with either goldenseal or kava kava. When compared with rifampin and clarithromycin, supplementation with these specific formulations of goldenseal or kava kava did not appear to affect digoxin pharmacokinetics, suggesting that these supplements are not potent modulators of P-gp in vivo.     

Activity measurements of the high-energy pure beta-emitters 89Sr and 90Y by the TDCR efficiency calculation technique.

The absolute activities of the pure beta-emitters 89Sr and 90Y have been determined by a direct method, namely the triple-to-double coincidence ratio (TDCR) efficiency calculation technique. This undertaking has extended further the number of radionuclides that have been standardized by this non-extrapolation liquid scintillation (LS) method. Both measurements were carried out within the framework of international key comparisons under the auspices of the International Bureau of Weights and Measures (BIPM). The TDCR results agreed well with those of other participating national laboratories, most using alternative (tracer) methods.     

Adequacies of skin puncture for evaluating biochemical and hematological blood parameters in athletes.

OBJECTIVE: The authors tested the effect of blood sampling (skin versus venous puncture) on some biochemical and hematological blood parameters in athletes to answer whether skin puncture could be used as a substitute for venous puncture. DESIGN: Comparative study of 2 methods of blood samples collection. SETTING: The blood was collected in the same athletes at 3 different moments of the preparatory training phase. PARTICIPANTS: Fourteen male indoor soccer players (22 +/- 1 years old) and 7 female handball players (18 +/- 1 years old) participated. MAIN OUTCOME MEASUREMENT: Blood was collected in heparin and K3EDTA by Vacutainer BD or Microvette Sarstedt system for biochemical and hematological analyses, respectively. RESULTS: There were no significant statistical differences between the 2 methods for the values of creatine kinase, urea, creatinine, lymphocytes, and platelets. The other hematological analyzes and uric acid exhibited significant higher values in skin blood, although they were all within the normal expected range. A high degree of correlation was observed between the 2 techniques for all parameters. CONCLUSIONS: Skin puncture is a reliable, easy, accurate, and less invasive sampling method for assessing hematological and some biochemical parameters in athletes, respecting that blood samples should always be obtained from the same site, especially in follow-up studies.     

Expression of measles virus nucleocapsid protein in osteoclasts induces Paget's disease-like bone lesions in mice.

We targeted the MVNP gene to the OCL lineage in transgenic mice. These mice developed abnormal OCLs and bone lesions similar to those found in Paget's patients. These results show that persistent expression of MVNP in OCLs can induce pagetic-like bone lesions in vivo. INTRODUCTION: Paget's disease (PD) of bone is the second most common bone disease. Both genetic and viral factors have been implicated in its pathogenesis, but their exact roles in vivo are unclear. We previously reported that transfection of normal human osteoclast (OCL) precursors with the measles virus nucleocapsid (MVNP) or measles virus (MV) infection of bone marrow cells from transgenic mice expressing a MV receptor results in formation of pagetic-like OCLs. MATERIALS AND METHODS: Based on these in vitro studies, we determined if the MVNP gene from either an Edmonston-related strain of MV or a MVNP gene sequence derived from a patient with PD (P-MVNP), when targeted to cells in the OCL lineage of transgenic mice with the TRACP promoter (TRACP/MVNP mice), induced changes in bone similar to those found in PD. RESULTS: Bone marrow culture studies and histomorphometric analysis of bones from these mice showed that their OCLs displayed many of the features of pagetic OCLs and that they developed bone lesions that were similar to those in patients with PD. Furthermore, IL-6 seemed to be required for the development of the pagetic phenotype in OCLs from TRACP/MVNP mice. CONCLUSIONS: These results show that persistent expression of the MVNP gene in cells of the OCL lineage can induce pagetic-like bone lesions in vivo.     

Systematic review of effectiveness of bisphosphonates in treatment of low bone mineral density and fragility fractures in juvenile idiopathic arthritis.

AIMS: To evaluate the currently available evidence for the effectiveness of bisphosphonates in children with low bone mineral density (BMD) and fragility fractures associated with juvenile idiopathic arthritis (JIA), and the safety of bisphosphonates in JIA and other conditions. METHODS: Literature databases were searched using a structured search strategy. The effectiveness review included any studies of children with JIA treated with bisphosphonates. The safety review also included studies of osteogenesis imperfecta. Quantitative data analysis was not undertaken because of the heterogeneity of the studies; findings were summarised using tables and narrative synthesis. RESULTS: Ninety four studies were identified. Sixteen studies (78 JIA children) were included in the effectiveness review: one randomised controlled trial, three controlled cohort studies, 11 case series, and one case report. At baseline, children had low BMD below the expected values for age and sex matched children. In all studies, treatment with bisphosphonates increased BMD compared with baseline: the mean percentage increase in spine BMD ranged from 4.5% to 19.1%. Overall, studies were heterogeneous and of variable quality. A total of 59 papers were included in the safety review; treatment durations were up to three years. The most common side effect was a flu-like reaction with intravenous treatment. This occurred during the first infusion and was transient; the symptoms were managed with paracetamol and did not occur during subsequent cycles. CONCLUSIONS: Bisphosphonates are a promising treatment for low BMD and fragility fractures in children with JIA. However, the quality of the current evidence is variable and better studies are needed to more clearly assess their role.