Extended CSF cytarabine exposure following intrathecal administration of DTC 101.

1993 ◽  
Vol 11 (11) ◽  
pp. 2186-2193 ◽  
Author(s):  
S Kim ◽  
E Chatelut ◽  
J C Kim ◽  
S B Howell ◽  
C Cates ◽  
...  
Keyword(s):  
Lateral Ventricle ◽  
High Performance ◽  
Maximum Tolerated Dose ◽  
Intrathecal Administration ◽  
Neoplastic Meningitis ◽  
Intraventricular Injection ◽  
Intraventricular Administration ◽  
Csf Pharmacokinetics ◽  
La Jolla ◽  
The Right

PURPOSE The aims of the present study were to determine ventricular and lumbar CSF pharmacokinetics and the maximum-tolerated dose (MTD) of DTC 101 (DepoFoam; DepoTech Corp, La Jolla, CA) following intraventricular administration. PATIENTS AND METHODS Twelve patients with neoplastic meningitis were treated with escalating doses of DTC 101. CSF samples were obtained from the right lateral ventricle or from the lumbar subarachnoid space and cytarabine concentrations were determined by high-performance liquid chromatography. RESULTS Therapeutic ventricular CSF concentrations were maintained for 9 +/- 2 days following administration of a single dose of DTC 101 into the lateral ventricle. Lumbar cytarabine concentrations became equal to those in the ventricle within the first 6 hours after intraventricular injection, and the subsequent decay in concentrations of free and total cytarabine were the same at both sites. Following intralumbar administration, the peak ventricular concentration of free cytarabine was reached within 1 day, and therapeutic ventricular CSF levels were maintained for several days. Therapeutic intralumbar concentration of free cytarabine was maintained for up to 14 days. The MTD was 75 mg of DTC 101, and seven of nine patients manifested cytologic responses. CONCLUSION Extended CSF exposure to therapeutic cytarabine concentrations was achieved after a single intraventricular or intralumbar dose of DTC 101, permitting drug administration once every 2 weeks.

scholarly journals Hydrocephalus after Intraventricular Hemorrhage: The Role of Thrombin

2013 ◽  
Vol 34 (3) ◽  
pp. 489-494 ◽  
Author(s):  
Feng Gao ◽  
Fuyi Liu ◽  
Zhi Chen ◽  
Ya Hua ◽  
Richard F Keep ◽  
...  
Keyword(s):  
Lateral Ventricle ◽  
Intraventricular Hemorrhage ◽  
Autologous Blood ◽  
Intraventricular Injection ◽  
Sprague Dawley ◽  
Blood Brain Barrier Disruption ◽  
Sprague Dawley Rats ◽  
Blood Injection ◽  
Brain Barrier Disruption ◽  
The Right

Previous studies demonstrated that thrombin is an important factor in brain injury after intracerebral hemorrhage. This study investigated the effect of thrombin on hydrocephalus development in a rat intraventricular hemorrhage (IVH) model. There were three parts in this study. First, male Sprague–Dawley rats had an injection of 200  μL saline, autologous blood or heparinized blood, into the right lateral ventricle. Second, rats had an injection of 50  μL saline or 3U thrombin into the right lateral ventricle. Third, rats had an injection of thrombin (3U) with a protease-activated receptor-1 (PAR-1) antagonist, SCH79797 (0.15 nmol), or vehicle into the right lateral ventricle. Lateral ventricle volumes were measured by magnetic resonance imaging and the brains were used for immunohistochemistry and western blot analyses. Intraventricular injection of autologous blood induced hydrocephalus from day 1 to 28. Heparinized blood injection resulted in less hydrocephalus at all time points compared with blood injection alone ( P<0.05). Intraventricular injection of thrombin caused significant hydrocephalus, ventricular wall damage, and periventricular blood–brain barrier disruption. Thrombin-induced hydrocephalus was reduced by co-injection of the PAR-1 antagonist SCH79797 ( P<0.05). In conclusion, thrombin contributes to hydrocephalus development after IVH and thrombin-induced hydrocephalus is through PAR-1.

scholarly journals Pharmacokinetics of Colistin in Cerebrospinal Fluid after Intraventricular Administration of Colistin Methanesulfonate

2012 ◽  
Vol 56 (8) ◽  
pp. 4416-4421 ◽  
Author(s):  
Roberto Imberti ◽  
Maria Cusato ◽  
Giovanni Accetta ◽  
Valeria Marinò ◽  
Francesco Procaccio ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
High Performance ◽  
Compartment Model ◽  
Intraventricular Administration ◽  
Central Nervous System Infections ◽  
Daily Dose ◽  
Csf Pharmacokinetics ◽  
Colistin Methanesulfonate ◽  
The One ◽  
Microbiological Cure

ABSTRACTIntraventricular colistin, administered as colistin methanesulfonate (CMS), is the last resource for the treatment of central nervous system infections caused by panresistant Gram-negative bacteria. The doses and daily regimens vary considerably and are empirically chosen; the cerebrospinal fluid (CSF) pharmacokinetics of colistin after intraventricular administration of CMS has never been characterized. Nine patients (aged 18 to 73 years) were treated with intraventricular CMS (daily doses of 2.61 to 10.44 mg). Colistin concentrations were measured using a selective high-performance liquid chromatography (HPLC) assay. The population pharmacokinetics analysis was performed with the P-Pharm program. The pharmacokinetics of colistin could be best described by the one-compartment model. The estimated values (means ± standard deviations) of apparent CSF total clearance (CL/Fm, where Fm is the unknown fraction of CMS converted to colistin) and terminal half-life (t1/2λ) were 0.033 ± 0.014 liter/h and 7.8 ± 3.2 h, respectively, and the average time to the peak concentration was 3.7 ± 0.9 h. A positive correlation between CL/Fm and the amount of CSF drained (range 40 to 300 ml) was observed. When CMS was administered at doses of ≥5.22 mg/day, measured CSF concentrations of colistin were continuously above the MIC of 2 μg/ml, and measured values of trough concentration (Ctrough) ranged between 2.0 and 9.7 μg/ml. Microbiological cure was observed in 8/9 patients. Intraventricular administration of CMS at doses of ≥5.22 mg per day was appropriate in our patients, but since external CSF efflux is variable and can influence the clearance of colistin and its concentrations in CSF, the daily dose of 10 mg suggested by the Infectious Diseases Society of America may be more prudent.

scholarly journals Development and Validation of an HPLC Method for Analysis of Topotecan in Human Cerebrospinal Fluid and Its Application in Elimination Evaluation of Topotecan after Intraventricular Injection

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4643
Author(s):  
Naoki Yoshikawa ◽  
Ai Yamada ◽  
Tsubasa Yokota ◽  
Yusei Yamada ◽  
Mariko Kinoshita ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Anticancer Drugs ◽  
High Performance ◽  
Intrathecal Injection ◽  
Elimination Rate ◽  
Intrathecal Administration ◽  
Hplc Method ◽  
Effective Dosage ◽  
Intraventricular Injection ◽  
Limit Of Quantitation

Intrathecal administration of anticancer drugs is an effective dosage strategy, but the elimination of intraventricular drugs is not uniform in all patients. For safety, a system to evaluate local pharmacokinetics in the ventricles after administration is desired. In this study, we developed a simple and reproducible method to measure topotecan concentration in the cerebrospinal fluid (CSF) and confirmed its clinical applicability. High-performance liquid chromatography (HPLC) analysis was performed using a C18 column to measure the total topotecan concentration in the CSF. Clinical CSF samples were obtained from a 1-year old child with poor CSF absorption and stagnation. The patient received topotecan via an intraventricular subcutaneous reservoir. The HPLC method complied with the validation criteria. The lower limit of quantitation of this method was 0.04 µM. Using the developed method, we could determine the difference in topotecan CSF concentrations at 24 and 48 h after administration. The patient’s topotecan elimination rate was extremely low, and signs of adverse effects were observed at high CSF concentration of topotecan. The developed method could detect the delay in topotecan elimination after intrathecal injection. The findings of this study are valuable for the development of personalized treatments for the intrathecal administration of anticancer drugs.

Design of an intermediate high voltage EM for 3-D studies of biological material and its integration with a system for remote access

1995 ◽  
Vol 53 ◽  
pp. 66-67 ◽  
Author(s):  
Mark H. Ellisman
Keyword(s):  
High Voltage ◽  
High Performance ◽  
Remote Access ◽  
3 Dimensional ◽  
Voltage Electron ◽  
Remote Operation ◽  
High Voltage Electron Microscope ◽  
La Jolla ◽  
Performance Computing ◽  
Advanced Version

The increased availability of High Performance Computing and Communications (HPCC) offers scientists and students the potential for effective remote interactive use of centralized, specialized, and expensive instrumentation and computers. Examples of instruments capable of remote operation that may be usefully controlled from a distance are increasing. Some in current use include telescopes, networks of remote geophysical sensing devices and more recently, the intermediate high voltage electron microscope developed at the San Diego Microscopy and Imaging Resource (SDMIR) in La Jolla. In this presentation the imaging capabilities of a specially designed JEOL 4000EX IVEM will be described. This instrument was developed mainly to facilitate the extraction of 3-dimensional information from thick sections. In addition, progress will be described on a project now underway to develop a more advanced version of the Telemicroscopy software we previously demonstrated as a tool to for providing remote access to this IVEM (Mercurio et al., 1992; Fan et al., 1992).

Prediction of persistent ventricular dilation by initial ventriculomegaly and clot volume in a porcine model

2021 ◽  
pp. 1-8
Author(s):  
Grace Y. Lai ◽  
William Chu Kwan ◽  
Karolina Piorkowska ◽  
Matthias W. Wagner ◽  
Pouya Jamshidi ◽  
...  
Keyword(s):  
Porcine Model ◽  
Autologous Blood ◽  
Ventricular Volume ◽  
Intraventricular Injection ◽  
Clot Lysis ◽  
Ventricular Dilation ◽  
Ventricular Volumes ◽  
Clot Burden ◽  
The Right ◽  
The Relationship

OBJECTIVE While intraventricular hemorrhage (IVH) is associated with posthemorrhagic ventricular dilation (PHVD), not all infants affected by high-grade IVH develop PHVD. The authors aimed to determine clot-associated predictors of PHVD in a porcine model by varying the amount and rate of direct intraventricular injection of whole autologous blood. METHODS Seven 1-week-old piglets underwent craniectomy and injection of autologous blood into the right lateral ventricle. They survived for a maximum of 28 days. MRI was performed prior to injection, immediately postoperatively, and every 7 days thereafter. T1-weighted, T2-weighted, and susceptibility-weighted imaging (SWI) sequences were used to segment ventricular and clot volumes. Spearman correlations were used to determine the relationship between blood and clot volumes and ventricular volumes over time. RESULTS The maximum ventricular volume was up to 12 times that of baseline. One animal developed acute hydrocephalus on day 4. All other animals survived until planned endpoints. The interaction between volume of blood injected and duration of injection was significantly associated with clot volume on the postoperative scan (p = 0.003) but not the amount of blood injected alone (p = 0.38). Initial postoperative and day 7 clot volumes, but not volume of blood injected, were correlated with maximum (p = 0.007 and 0.014) and terminal (p = 0.014 and 0.036) ventricular volumes. Initial postoperative ventricular volume was correlated with maximum and terminal ventricular volume (p = 0.007 and p = 0.014). CONCLUSIONS Initial postoperative, maximum, and terminal ventricular dilations were associated with the amount of clot formed, rather than the amount of blood injected. This supports the hypothesis that PHVD is determined by clot burden rather than the presence of blood products and allows further testing of early clot lysis to minimize PHVD risk.

Custom templates based heterogeneous resource allocation for data-intensive applications

2020 ◽  
Author(s):  
◽  
Ronny Bazan Antequera
Keyword(s):  
High Performance ◽  
Real Data ◽  
University Of Missouri ◽  
Application Performance ◽  
Data Intensive ◽  
Edge Based ◽  
The Right ◽  
Heterogeneous Cloud ◽  
Data Intensive Applications ◽  
Cloud Resources

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI-COLUMBIA AT REQUEST OF AUTHOR.] The increase of data-intensive applications in science and engineering fields (i.e., bioinformatics, cybermanufacturing) demand the use of high-performance computing resources. However, data-intensive applications' local resources usually present limited capacity and availability due to sizable upfront costs. Moreover, using remote public resources presents constraints at the private edge network domain. Specifically, mis-configured network policies cause bottlenecks due to the other application cross-traffic attempting to use shared networking resources. Additionally, selecting the right remote resources can be cumbersome especially for those users who are interested in the application execution considering nonfunctional requirements such as performance, security and cost. The data-intensive applications have recurrent deployments and similar infrastructure requirements that can be addressed by creating templates. In this thesis, we handle applications requirements through intelligent resource 'abstractions' coupled with 'reusable' approaches that save time and effort in deploying new cloud architectures. Specifically, we design a novel custom template middleware that can retrieve blue prints of resource configuration, technical/policy information, and benchmarks of workflow performance to facilitate repeatable/reusable resource composition. The middleware considers hybrid-recommendation methodology (Online and offline recommendation) to leverage a catalog to rapidly check custom template solution correctness before/during resource consumption. Further, it prescribes application adaptations by fostering effective social interactions during the application's scaling stages. Based on the above approach, we organize the thesis contributions under two main thrusts: (i) Custom Templates for Cloud Networking for Data-intensive Applications: This involves scheduling transit selection, engineering at the campus-edge based upon real-time policy control. Our solution ensures prioritized application performance delivery for multi-tenant traffic profiles from a diverse set of actual data intensive applications in bioinformatics. (ii) Custom Templates for Cloud Computing for Data-intensive Applications: This involves recommending cloud resources for data-intensive applications based on a custom template catalog. We develop a novel expert system approach that is implemented as a middleware to abstracts data-intensive application requirements for custom templates composition. We uniquely consider heterogeneous cloud resources selection for the deployment of cloud architectures for real data-intensive applications in cybermanufacturing.

Intrathecal treatment trial of rituximab in progressive MS

Neurology ◽  
2018 ◽  
Vol 91 (20) ◽  
pp. e1893-e1901 ◽  
Author(s):  
Joakim Bergman ◽  
Joachim Burman ◽  
Jonathan D. Gilthorpe ◽  
Henrik Zetterberg ◽  
Elena Jiltsova ◽  
...  
Keyword(s):  
Progressive Multiple Sclerosis ◽  
Intrathecal Administration ◽  
Control Group ◽  
Csf Biomarkers ◽  
Ventricular Catheter ◽  
Frontal Horn ◽  
Severe Infections ◽  
Phase 1B ◽  
The Right

ObjectivesTo perform a phase 1b assessment of the safety and feasibility of intrathecally delivered rituximab as a treatment for progressive multiple sclerosis (PMS) and to evaluate the effect of treatment on disability and CSF biomarkers during a 1-year follow-up period.MethodsThree doses of rituximab (25 mg with a 1-week interval) were administered in 23 patients with PMS via a ventricular catheter inserted into the right frontal horn and connected to a subcutaneous Ommaya reservoir. Follow-ups were performed at 1, 3, 6, 9, and 12 months.ResultsMild to moderate vertigo and nausea were common but temporary adverse events associated with intrathecal rituximab infusion, which was otherwise well tolerated. The only severe adverse event was a case of low-virulent bacterial meningitis that was treated effectively. Of 7 clinical assessments, only 1 showed statistically significant improvement 1 year after treatment. No treatment effect was observed during the follow-up period among 6 CSF biomarkers.ConclusionsIntrathecal administration of rituximab was well tolerated. However, it may involve a risk for injection-related infections. The lack of a control group precludes conclusions being drawn regarding treatment efficacy.ClinicalTrials.gov identifierNCT01719159.Classification of evidenceThis study provides Class IV evidence that intrathecal rituximab treatment is well tolerated and feasible in PMS but involves a risk of severe infections.

scholarly journals Pharmacokinetics of danofloxacin in African catfish (Clarias gariepinus) after intravenous and intramuscular administrations

2019 ◽  
Vol 67 (4) ◽  
pp. 602-609
Author(s):  
Mohamed Aboubakr ◽  
Ahmed Soliman
Keyword(s):  
Bacterial Infections ◽  
High Performance ◽  
Clarias Gariepinus ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
African Catfish ◽  
Caudal Vein ◽  
Group 2 ◽  
Total Body ◽  
The Right

The plasma pharmacokinetics of danofloxacin was studied in healthy African catfish (Clarias gariepinus) following a single intravenous (IV) and intramuscular (IM) administration of 10 mg/kg at 22 °C. Catfish were divided into two groups (each group containing 78 fish), then danofloxacin mesylate (10 mg/kg) was administered IV (into the caudal vein) in Group 1 and IM (into the right epaxial muscle) in Group 2, and blood was obtained from the caudal vein before (0 h) and after (0.25, 0.5, 1, 2, 4, 8, 12, 24, 36, 48, 72 and 96 h) of drug administration. High-performance liquid chromatography was used for the determination of plasma concentration, and a non-compartmental model was used for the analysis of pharmacokinetic parameters. After IV administration, elimination half-life (t1/2λz, 24.49 h), mean residence time (MRT, 30.14 h), volume of distribution at steady state (Vdss, 1.07 L/kg) and total body clearance (CLT, 0.035 L/h/kg) were determined. After IM administration, t1/2λz, MRT, peak concentration (Cmax), time to reach Cmax and bioavailability were 47.64 h, 61.06 h, 5.22 µg/mL, 1 h and 67.12%, respectively. After IM administration, danofloxacin showed good bioavailability and long t1/2λz. The favourable pharmacokinetic characteristics after IM administration support the use of danofloxacin for the treatment of susceptible bacterial infections in catfish.

scholarly journals ShenLian Extract Enhances TGF-β Functions in the Macrophage-SMC Unit and Stabilizes Atherosclerotic Plaques

2021 ◽  
Vol 12 ◽  
Author(s):  
Li Liu ◽  
Qi Li ◽  
Jie Yin ◽  
Zheng Zhao ◽  
Lidong Sun ◽  
...  
Keyword(s):  
High Performance ◽  
Macrophage Polarization ◽  
Neutralizing Antibody ◽  
Immunofluorescent Staining ◽  
Phenotypic Switching ◽  
Atherosclerotic Plaques ◽  
M2 Macrophage ◽  
Inflammatory Microenvironment ◽  
Phenotypic Transformation ◽  
The Right

Background/Aim: Macrophage polarization and phenotypic switching of smooth muscle cells (SMCs) are multi-faceted events dominating atherosclerosis (AS) progression. TGF-β was proved to been one of the bridge on the crosstalk between macrophage and SMC. ShenLian (SL) was extracted from a potent anti-atherosclerotic formula. However, its exact mechanism rebalancing inflammatory microenvironment of AS remain largely unknown. Within the entirety of macrophage and SMC, this study investigated the pharmacological effects of SL on stabilizing atherosclerotic plaques.Methods: The main components of SL were examined by high performance liquid chromatography. Co-culture and conditioned medium models of macrophage/SMC interactions were designed to identify the relationship between macrophage polarization and switching of SMC phenotypes. Flow cytometry, immunofluorescent staining, RT-PCR, western blotting, and ELISA were used to determine the expression of molecules relating to AS progression. An atherosclerosis animal model, established by placing a perivascular collar on the right common carotid artery in ApoE−/− mice, was used to investigate whether TGF-β is the key molecular mediator of SL in crosstalk between macrophage and SMC. Plaque size was defined by nuclear magnetic resonance imaging. Key markers related to phenotypic transformation of macrophage and SMC were determined by immunohistochemical staining.Results: Results revealed that, accompanied by rebalanced M2 macrophage polarization, SL supported SMC phenotypic transformation and functionally reconstruct the ECM of plaques specifically in macrophage-SMC co-cultural model. Molecularly, such activity of SL closely related to the activation of STAT3/SOCS3 pathway. Furthermore, in co-culture system, up-regulation of α-SMA induced by SL could neutralized by 1D11, a TGF-β neutralizing antibody, indicating that SL mediated Macrophage-SMC communication by enhancing TGF-β. In the AS model constructed by ApoE−/− mice, effects of SL on phenotypic transformation of macrophage and SMC has been well verified. Specific blocking of TGF-β largely attenuated the aforementioned effects of SL.Conclusion: Our findings highlighted that TGF-β might be the responsive factor of SL within macrophage and SMC communication. This study revealed that crosstalk between macrophage and SMC forms a holistic entirety promoting atherosclerotic plaque stability.

Sign in / Sign up

Export Citation Format

Share Document