Eyes open to stem cells: safety trial may pave the way for cell therapy to treat retinal disease in patients

A clinical trial using human embryonic stem cell (hESC) therapy for an inherited retinal degenerative disease is about to commence. The Advanced Cell Technology (ACT) trial will treat patients with Stargardt's macular dystrophy using transplanted retinal pigment epithelium derived from hESCs. Currently, no effective treatment is available for Stargardt's disease so a stem cell-based therapy that can slow progression of this blinding condition could represent a significant breakthrough. While there are some hurdles to clear, the ACT trial is a fine example of translational research that could eventually pave the way for a range of stem cell therapies for the retina and other tissues.

Nanodosimetric effects of gold nanoparticles in megavoltage radiation therapy

Background and purpose: The addition of gold nanoparticles (GNPs) to tumours leads to an increase in dose due to their high density and energy absorption coefficient, making it a potential radiosensitiser. However, experiments have observed radiosensitisations significantly larger than the increase in dose alone, including at megavoltage energies where gold's relative energy absorption is lowest. This work investigates whether GNPs create dose inhomogeneities on a sub-cellular scale which combine with non-linear dose dependence of cell survival to be the source of radiosensitisation at megavoltage energies.

An evaluation of the effect of altering nutrition and nutritional strategies in early lactation on reproductive performance and estrous behavior of high-yielding Holstein-Friesian dairy cows

Reproductive performance in the high-yielding dairy cow has severely decreased in the last 40 yr. The aim of this study was to compare the effectiveness of 4 nutritional strategies in improving the reproductive performance of high-yielding dairy cows. It was hypothesized that offering cows a high-starch ration in early lactation would enhance the onset of luteal activity, and that decreasing the severity of negative energy balance in the early postcalving period would improve reproductive parameters. Nutritional regimens aimed at improving fertility were applied to 96 Holstein-Friesian dairy animals. Upon calving, animals were allocated in a balanced manner to one of 4 dietary treatments. Primiparous animals were balanced according to live weight, body condition score and calving date. Multiparous animals were balanced according to parity, previous lactation milk yield, liveweight, body condition score and calving date. Treatment 1 was based on an industry best practice diet (control) to contain 170 g of crude protein/kg of dry matter. Treatment 2 was an individual cow feeding strategy, whereby the energy balance (EB) of individual animals was managed so as to achieve a predetermined target daily EB profile (+/- 10 MJ/d). Treatment 3 was a high-starch/high-fat combination treatment, whereby an insulinogenic (high-starch) diet was offered in early lactation to encourage cyclicity and followed by a lipogenic (low-starch, high-fat) diet to promote embryo development. Treatment 4 was a low-protein diet, containing 140 g of crude protein/kg of dry matter, supplemented with protected methionine at an inclusion level of 40 g per animal per day. The nutritional strategies implemented in this study had no statistically significant effects on cow fertility measures, which included the onset of luteal activity, conception rate, in-calf rate, and the incidence of atypical cycles. The individual cow feeding strategy improved EB in early lactation but had no benefit on conception rate to first insemination. However, conception rate to second insemination, 100-d pregnancy rate (from the commencement of breeding), and overall pregnancy rate tended to be higher in this group. The high-starch/high-fat treatment tended to decrease the proportion of delayed ovulations and increase the proportion of animals cycling by d 50 postcalving. Animals that failed to conceive to first insemination had a significantly longer luteal phase in the first cycle postpartum and a longer inter-ovulatory interval in the second cycle postpartum. With regards to estrous behavior, results indicate that as the size of the sexually active group increased, the intensity of estrus and the expression of mounting or attempting to mount another cow also increased. Furthermore, cows that became pregnant displayed more intense estrous behavior than cows that failed to become pregnant.

Sequential antimicrobial therapy: treatment of severe lower respiratory tract infections in children

Although there have been a number of studies in adults, to date there has been little research into sequential antimicrobial therapy (SAT) in paediatric populations. The present study evaluates the impact of a SAT protocol for the treatment of severe lower respiratory tract infection in paediatric patients. The study involved 89 paediatric patients (44 control and 45 SAT). The SAT patients had a shorter length of hospital stay (4.0 versus 8.3 days), shorter duration of inpatient antimicrobial therapy (4.0 versus 7.9 days) with the period of iv therapy being reduced from a mean of 5.6 to 1.7 days. The total healthcare costs were reduced by 52%. The resolution of severe lower respiratory tract infection with a short course of iv antimicrobials, followed by conversion to oral therapy yielded clinical outcomes comparable to those achieved using longer term iv therapy. SAT proved to be an important cost-minimizing tool for realizing substantial healthcare costs savings.

Group art therapy as an adjunctive treatment for people with schizophrenia: multicentre pragmatic randomised trial

Objectives To evaluate the clinical effectiveness of group art therapy for people with schizophrenia and to test whether any benefits exceed those of an active control treatment.

Rescue of glandular dysmorphogenesis in PTEN-deficient colorectal cancer epithelium by PPARγ-targeted therapy

Disruption of glandular architecture associates with poor clinical outcome in high-grade colorectal cancer (CRC). Phosphatase and tensin homolog deleted on chromosome ten (PTEN) regulates morphogenic growth of benign MDCK (Madin Darby Canine Kidney) cells through effects on the Rho-like GTPase cdc42 (cell division cycle 42). This study investigates PTEN-dependent morphogenesis in a CRC model. Stable short hairpin RNA knockdown of PTEN in Caco-2 cells influenced expression or localization of cdc42 guanine nucleotide exchange factors and inhibited cdc42 activation. Parental Caco-2 cells formed regular hollow gland-like structures (glands) with a single central lumen, in three-dimensional (3D) cultures. Conversely, PTEN-deficient Caco-2 ShPTEN cells formed irregular glands with multiple abnormal lumens as well as intra- and/or intercellular vacuoles evocative of the high-grade CRC phenotype. Effects of targeted treatment were investigated. Phosphatidinylinositol 3-kinase (PI3K) modulating treatment did not affect gland morphogenesis but did influence gland number, gland size and/or cell size within glands. As PTEN may be regulated by the nuclear receptor peroxisome proliferator-activated receptor-? (PPAR?), cultures were treated with the PPAR? ligand rosiglitazone. This treatment enhanced PTEN expression, cdc42 activation and rescued dysmorphogenesis by restoring single lumen formation in Caco-2 ShPTEN glands. Rosiglitazone effects on cdc42 activation and Caco-2 ShPTEN gland development were attenuated by cotreatment with GW9662, a PPAR? antagonist. Taken together, these studies show PTEN-cdc42 regulation of lumen formation in a 3D model of human CRC glandular morphogenesis. Treatment by the PPAR? ligand rosiglitazone, but not PI3K modulators, rescued colorectal glandular dysmorphogenesis of PTEN deficiency.

Serum erythropoietin levels in paroxysmal nocturnal haemoglobinuria: Implications for therapy

In order to assess the rationale and possible indications for the use of recombinant erythropoietin in paroxysmal nocturnal haemoglobinuria (PNH), we have measured endogenous erythropoietin (Epo) levels in 18 patients with PNH and in 44 patients with iron deficiency anaemia (IDA), In both groups of patients we found a significant inverse correlation between Epo and haemoglobin (Hb). However, the mean Epo level was significantly higher in the PNH group (385 mU/ml) than in the IDA group (136 mU/ml), The range of Epo levels at any given Hb was greater in the PNH group than in the IDA group. There was a significant positive correlation between Epo and absolute reticulocyte count, Since Epo administration is unlikely to benefit patients with high levels of endogenous Epo, we conclude that in the majority of patients with PNH there is no indication for treatment with Epo.