The submarine volcano eruption at the island of El Hierro: physical-chemical perturbation and biological response.

On October 10 2011 an underwater eruption gave rise to a novel shallow submarine volcano south of the island of El Hierro, Canary Islands, Spain. During the eruption large quantities of mantle-derived gases, solutes and heat were released into the surrounding waters. In order to monitor the impact of the eruption on the marine ecosystem, periodic multidisciplinary cruises were carried out. Here, we present an initial report of the extreme physical-chemical perturbations caused by this event, comprising thermal changes, water acidification, deoxygenation and metal-enrichment, which resulted in significant alterations to the activity and composition of local plankton communities. Our findings highlight the potential role of this eruptive process as a natural ecosystem-scale experiment for the study of extreme effects of global change stressors on marine environments.

Metronomic chemotherapy with daily, oral etoposide plus bevacizumab for recurrent malignant glioma: a phase II study.

BACKGROUND: We evaluated bevacizumab with metronomic etoposide among recurrent malignant glioma patients in a phase 2, open-label trial. METHODS: A total of 59 patients, including 27 with glioblastoma (GBM) and 32 with grade 3 malignant glioma, received 10 mg kg(-1) bevacizumab biweekly and 50 mg m(-2) etoposide daily for 21 consecutive days each month. The primary end point was a 6-month progression-free survival, and secondary end points included safety and overall survival. Vascular endothelial growth factor (VEGF), VEGFR-2, carbonic anhydrase 9 (CA9) and hypoxia-inducible factor-2alpha (HIF-2alpha) were assessed semiquantitatively in archival tumours using immunohistochemistry and were correlated with outcome. RESULTS: Among grade 3 and GBM patients, the 6-month progression-free survivals were 40.6% and 44.4%, the radiographic response rates were 22% and 37% and the median survivals were 63.1 and 44.4 weeks, respectively. Hypertension predicted better outcome among both grade 3 and GBM patients, whereas high CA9 and low VEGF were associated with poorer progression-free survival (PFS) among those with GBM. The most common grade > or = 3 adverse events included neutropaenia (24%), thrombosis (12%), infection (8%) and hypertension (3%). Two patients had asymptomatic, grade 1 intracranial haemorrhage and one on-study death occurred because of pulmonary embolism. CONCLUSION: Bevacizumab with metronomic etoposide has increased toxicity compared with previous reports of bevacizumab monotherapy. Its anti-tumour activity is similar to that of bevacizumab monotherapy or bevacizumab plus irinotecan. (ClinicalTrials.gov: NCT00612430).

Induction of latent human cytomegalovirus by conventional gamma irradiation and prevention by treatment with INACTINE PEN110.

BACKGROUND AND OBJECTIVES: Two different leucocyte-inactivation technologies--gamma irradiation and INACTINE PEN110--were evaluated for their effects on cell-associated human cytomegalovirus (CMV). MATERIALS AND METHODS: In vitro CMV-infected cells were spiked into leucoreduced red blood cell concentrates (RCC) or medium at a final concentration of 0.5 - 1 x 10(7) cells/ml to mimic non-leucoreduced levels of leucocytes. The spiked RCC/medium was divided into three equal units and treated with gamma irradiation at the US Food and Drug Administration (FDA)-approved dose of 25 Gy, with 0.1% v/v PEN110 at 22 degrees C for 24 h, or stored at 4 degrees C as a control. The treated and control cells were recovered and tested using infectivity, viability and polymerase chain reaction (PCR) assays. RESULTS: Gamma-irradiated CMV-infected cells produced active virus, as shown by both infectivity assays and PCR quantification of viral DNA. PCR analysis demonstrated higher CMV DNA levels in gamma-irradiated, latently infected monocytic THP-1 cells than untreated control cells. The increased virus production in gamma-irradiated cells was paralleled by an increased metabolic rate and the development of enlarged multinuclear cells. In contrast, PEN110 treatment terminated virus replication and completely inactivated the infected cell. CONCLUSIONS: These results demonstrate that gamma irradiation, at levels currently used to treat RCC, has the capacity to induce expression of CMV, whereas PEN110 inhibits CMV replication and efficiently inactivates the infected cells.

Formulation and intestinal absorption enhancement evaluation of water-in-oil microemulsions incorporating medium-chain glycerides.

We developed self-emulsifying water-in-oil (w/o) microemulsions incorporating medium-chain glycerides and measured their conductance, viscosity, refractive index and particle size. Formulation of Calcein (a water-soluble marker molecule, MW = 623), or SK&F 106760 (a water-soluble RGD peptide, MW = 634) in a w/o microemulsion having a composition of Captex 355/Capmul MCM/Tween 80/Aqueous (65/22/10/3, % w/w), resulted in significant bioavailability enhancement in rats relative to their aqueous formulations. Upon intraduodenal administration the bioavailability was enhanced from 2% for Calcein in isotonic Tris, pH 7.4 to 45% in the microemulsion and from 0.5% for SK&F 106760 in physiological saline to 27% in the microemulsion formulation. The microemulsion did not induce gross changes in GI mucosa at a dosing volume of 3.3 ml/kg. These results suggest that water-in-oil microemulsion systems may be utilized for enhancement of intestinal drug absorption.

A chronic Access Port model for direct delivery of drugs into the intestine of conscious dogs.

Gastric physiologic properties and emptying can significantly affect the stability and absorption of drugs given orally. A method to deliver drugs directly into the intestines and peritoneal cavity in conscious dogs by using a modified Vascular-Access Port (VAP) was developed and validated. Modified silastic VAP catheters size 7 or 9 French were placed in the duodenum, jejunum, colon, and/or peritoneal cavity in nine adult male dogs. Catheter placement was validated in six dogs by using contrast radiography and by monitoring the fecal excretion of blood after injection of blood via the VAP directly into the intestines. Three dogs were successfully used to evaluate the absorption of a peptide that inhibits platelet aggregation. Results showed this to be a feasible, easily validated model for delivering drugs directly into the intestines of conscious dogs.