The hemopexin domain of MMP-9 inhibits angiogenesis and retards the growth of intracranial glioblastoma xenograft in nude mice

Matrix Metalloproteinase-9 (MMP-9) consists of a prodomain, catalytic domain with 3 fibronectin-like type II modules and C-terminal hemopexin-like (PEX) domain. These domains play distinct roles in terms of proteolytic activity, substrate binding and interaction with inhibitors and receptors. To assess the potential of the MMP-9-PEX domain to interfere with tumor progression, we stably transfected human glioblastoma cells with an expression vector containing a cDNA sequence of the MMP-9-PEX. The selected clones exhibited decreased MMP-9 activity and reduced invasive capacity. We assessed how secretion of MMP-9-PEX by glioblastoma cells affects angiogenic capabilities of human microvascular endothelial cells (HMECs) in vitro. MMP-9-PEX conditioned medium treatment caused a reduction in migration of HMECs and inhibited capillary-like structure formation in association with suppression of vascular endothelial growth factor (VEGF) secretion and VEGF receptor-2 protein level. The suppression of HMECs survival by conditioned medium from MMP-9-PEX stable transfectants was associated with apoptosis induction characterized by an increase in cells with a sub-G0/G1 content, fragmentation of DNA, caspase-3, -8 and -9 activation and poly (ADP-ribose) polymerase (PARP) cleavage. A significant tumor growth inhibition was observed in intracranial implants of MMP-9-PEX stable transfectants in nude mice with attenuation of CD31 and MMP-9 protein expression. These results demonstrate that MMP-9-PEX inhibits angiogenic features of endothelial cells and retards intracranial glioblastoma growth.     

Cardiac frequency, phase and errors in one-dimensional sensorimotor tracking.

One dimensional manual tracking was investigated in relation to actual heart rate and phase of cardiac cycle. Higher heart rate was combined with increased tracking error incidence and decreased successful tracking time (light spot inside target). Error incidence was time-locked with respect to the phase of cardiac cycle.     

Reducing maternal mortality: can we derive policy guidance from developing country experiences?

Developing countries are floundering in their efforts to meet the Millennium Development Goal of reducing maternal mortality by 75% by 2015. Two issues are being debated. Is it doable within this time frame? And is it affordable? Malaysia and Sri Lanka have in the past 50 years repeatedly halved their maternal mortality ratio (MMR) every 7-10 years to reduce MMR from over 500 to below 50. Experience from four other developing countries--Bolivia, Yunan in China, Egypt, and Jamaica-confirms that each was able to halve MMR in less than 10 years beginning from levels of 200-300. Malaysia and Sri Lanka, invested modestly (but wisely)--less than 0.4% of GDP--on maternal health throughout the period of decline, although the large majority of women depended on publicly funded maternal health care. Analysis of their experience suggests that provision of access to and removal of barriers for the use of skilled birth attendance has been the key. This included professionalization of midwifery and phasing out of traditional birth attendants; monitoring births and maternal deaths and use of such information for high profile advocacy on the importance of reducing maternal death; and addressing critical gaps in the health system; and reducing disparities between different groups through special attention to the poor and disadvantaged populations.     

SARS-associated coronavirus transmission, United States

To better assess the risk for transmission of the severe acute respiratory syndrome-associated coronavirus (SARS-CoV), we obtained serial specimens and clinical and exposure data from seven confirmed U.S. SARS patients and their 10 household contacts. SARS-CoV was detected in a day-14 sputum specimen from one case-patient and in five stool specimens from two case-patients. In one case-patient, SARS-CoV persisted in stool for at least 26 days after symptom onset. The highest amounts of virus were in the day-14 sputum sample and a day-14 stool sample. Residual respiratory symptoms were still present in recovered SARS case-patients 2 months after illness onset. Possible transmission of SARS-CoV occurred in one household contact, but this person had also traveled to a SARS-affected area. The data suggest that SARS-CoV is not always transmitted efficiently. Routine collection and testing of stool and sputum specimens of probable SARS case-patients may help the early detection of SARS-CoV infection.     

Reproductive Health Knowledge About Miscarriage: A Cross-Sectional Study of University Students

Maternal and Child Health Journal - To assess university students’ knowledge of reproductive health information about miscarriage. A single-centre, cross-sectional study was carried out using...