Sex- and smoke-related differences in gastrointestinal transit of cyclosporin A microemulsion capsules

Belgium Herbarium image of Meise Botanic Garden

Monitoreo de vancomicina administrada intraventricularmente en lactantes durante el tratamiento de ventriculitis

The objective of this study was to establish guidelines for the monitoring of intraventricularly administeredVancomycin in infants.Eleven patients with ventriculo-peritoneal shunts who developed ventriculitis were included in the study.All patients were given an intraventricular (IVT) dose of Vancomycin. Cerebrospinal fluid (CSF)samples were analysed and pharmacokinetic parameters: elimination rate constant (ke) and distributionvolume (Vd) were calculated in order to adjust the dose. Mean values of Vd and elimination half-lifefor these patients were 244 (± 162) mL and 37.1 (±23.3) hours respectively.A great variability in the Vd was observed in some patients. This change in Vd correlates with problemsin the ventricle size or with septated ventricles. In all cases a new dose was suggested according to thecalculated parameters.Due to variations in the system throughout therapy, a protocol for CSF samples collection was proposedin order to individualise Vancomycin dosage according to pharmacokinetic parameters.El objetivo de este estudio fue establecer pautas para el monitoreo de Vancomicina cuando la misma esadministrada intraventricularmente en lactantes.En este estudio se incluyeron once pacientes con derivaciones ventrículo-peritoneal. Todos los pacientesrecibieron una dosis de Vancomicina intraventricular (IVT). Las muestras de líquido cefalorraquídeo(LCR) fueron analizadas y se calcularon los parámetros farmacocinéticos: constante de velocidad deeliminación (ke) y volumen de distribución (Vd) para poder llevar a cabo un ajuste posológico. Lasmedias referidas al Vd y a la semivida de eliminación para estos pacientes fueron de 244(±162) mL y37.1(±23.3) horas respectivamente.En algunos pacientes se observó una gran variabilidad en el Vd. Este cambio en Vd se correlacionó conproblemas en el tamaño ventricular o con ventrículos septados. En todos los casos, se propuso una nuevadosis de acuerdo a los parámetros calculados.Debido a variaciones en el sistema a lo largo de la terapia, se propuso un protocolo para la recolecciónde muestras de LCR de forma tal de individualizar la dosis de Vancomicina con los parámetros farmacocinéticosobtenidos

Re-HEDP : pharmacokinetic characterization, clinical and dosimetric evaluation in osseous metastatic patients with two levels of radiopharmaceutical dose

BACKGROUND: A study for pain relief therapy with (188)Re-HEDP was done in patients with bone metastases secondary to breast and prostate cancer. MATERIALS AND METHODS: Patients received 1.3 or 2.2 GBq, in single or multiple doses. Platelets, white and red cells were evaluated during 11 weeks. Pharmacokinetic characterization was done from blood and urine samples for 5 patients along 24 hours. Urinary excretion was evaluated in other 16 patients during 6 hours. Bone uptake was estimated as remaining activity in whole body. Scintigraphic images were acquired at 2 and 24 hs post-administration. Absorbed dose in bone marrow was estimated with Mirdose3. Analgesics intake and pain score were daily recorded. Tumour markers (PSA, and Tn-structure) were monitored in 9 patients during 4 to 6 months. Single doses of low activity (1.3 GBq) were given to twelve patients. Nine patients received multiple doses. RESULTS: All except one patient had normal levels of platelets, white and red cells. Remaining dose in blood at 2 hours was 9%. Urinary elimination was 58%. Bone uptake at 24 hours was 43% (mean value; n = 5). No changes of the haematological parameters were detected along follow-up period. Pain relief was evidenced by decrease or supression of opioid analgesic and by subjective index. PSA showed a decrease in prostate cancer patients (n = 4). Tn-structure showed a significant increase after 4 to 8 months. CONCLUSION: Single or multiple dose scheme could be safely used, with administered activity of (188)Re-HEDP up to 60 mCi, with low bone marrow absorbed doses

Tuning the Mammalian Circadian Clock: Robust Synergy of Two Loops

The circadian clock is accountable for the regulation of internal rhythms in most living organisms. It allows the anticipation of environmental changes during the day and a better adaptation of physiological processes. In mammals the main clock is located in the suprachiasmatic nucleus (SCN) and synchronizes secondary clocks throughout the body. Its molecular constituents form an intracellular network which dictates circadian time and regulates clock-controlled genes. These clock-controlled genes are involved in crucial biological processes including metabolism and cell cycle regulation. Its malfunction can lead to disruption of biological rhythms and cause severe damage to the organism. The detailed mechanisms that govern the circadian system are not yet completely understood. Mathematical models can be of great help to exploit the mechanism of the circadian circuitry. We built a mathematical model for the core clock system using available data on phases and amplitudes of clock components obtained from an extensive literature search. This model was used to answer complex questions for example: how does the degradation rate of Per affect the period of the system and what is the role of the ROR/Bmal/REV-ERB (RBR) loop? Our findings indicate that an increase in the RNA degradation rate of the clock gene Period (Per) can contribute to increase or decrease of the period - a consequence of a non-monotonic effect of Per transcript stability on the circadian period identified by our model. Furthermore, we provide theoretical evidence for a potential role of the RBR loop as an independent oscillator. We carried out overexpression experiments on members of the RBR loop which lead to loss of oscillations consistent with our predictions. These findings challenge the role of the RBR loop as a merely auxiliary loop and might change our view of the clock molecular circuitry and of the function of the nuclear receptors (REV-ERB and ROR) as a putative driving force of molecular oscillations

Monitoreo de vancomicina administrada intraventricularmente en lactantes durante el tratamiento de ventriculitis

El objetivo de este estudio fue establecer pautas para el monitoreo de Vancomicina cuando la misma es administrada intraventricularmente en lactantes. En este estudio se incluyeron once pacientes con derivaciones ventrículo-peritoneal. Todos los pacientes recibieron una dosis de Vancomicina intraventricular (IVT). Las muestras de líquido cefalorraquídeo (LCR) fueron analizadas y se calcularon los parámetros farmacocinéticos: constante de velocidad de eliminación (ke) y volumen de distribución (Vd) para poder llevar a cabo un ajuste posológico. Las medias referidas al Vd y a la semivida de eliminación para estos pacientes fueron de 244(±162) mL y 37.1(±23.3) horas respectivamente. En algunos pacientes se observó una gran variabilidad en el Vd. Este cambio en Vd se correlacionó con problemas en el tamaño ventricular o con ventrículos septados. En todos los casos, se propuso una nueva dosis de acuerdo a los parámetros calculados. Debido a variaciones en el sistema a lo largo de la terapia, se propuso un protocolo para la recolección de muestras de LCR de forma tal de individualizar la dosis de Vancomicina con los parámetros farmacocinéticos obtenidos

Monitoring of intraventricularly administered vancomycin in infants in the treatment of ventriculitis

El objetivo de este estudio fue establecer pautas para el monitoreo de Vancomicina cuando la misma es administrada intraventricularmente en lactantes. En este estudio se incluyeron once pacientes con derivaciones ventrículo-peritoneal. Todos los pacientes recibieron una dosis de Vancomicina intraventricular (IVT). Las muestras de líquido cefalorraquídeo (LCR) fueron analizadas y se calcularon los parámetros farmacocinéticos: constante de velocidad de eliminación (ke) y volumen de distribución (Vd) para poder llevar a cabo un ajuste posológico. Las medias referidas al Vd y a la semivida de eliminación para estos pacientes fueron de 244(±162) mL y 37.1(±23.3) horas respectivamente. En algunos pacientes se observó una gran variabilidad en el Vd. Este cambio en Vd se correlacionó con problemas en el tamaño ventricular o con ventrículos septados. En todos los casos, se propuso una nueva dosis de acuerdo a los parámetros calculados. Debido a variaciones en el sistema a lo largo de la terapia, se propuso un protocolo para la recolección de muestras de LCR de forma tal de individualizar la dosis de Vancomicina con los parámetros farmacocinéticos obtenidos.The objective of this study was to establish guidelines for the monitoring of intraventricularly administered Vancomycin in infants. Eleven patients with ventriculo-peritoneal shunts who developed ventriculitis were included in the study. All patients were given an intraventricular (IVT) dose of Vancomycin. Cerebrospinal fluid (CSF) samples were analysed and pharmacokinetic parameters: elimination rate constant (ke) and distribution volume (Vd) were calculated in order to adjust the dose. Mean values of Vd and elimination half-life for these patients were 244 (± 162) mL and 37.1 (±23.3) hours respectively. A great variability in the Vd was observed in some patients. This change in Vd correlates with problems in the ventricle size or with septated ventricles. In all cases a new dose was suggested according to the calculated parameters. Due to variations in the system throughout therapy, a protocol for CSF samples collection was proposed in order to individualise Vancomycin dosage according to pharmacokinetic parameters