Recombinant collagen and gelatin for drug delivery

The tools of recombinant protein expression are now being used to provide recombinant sources of both collagen and gelatin. The primary focus of this review is to discuss alternatives to bovine collagen for biomedical applications. Several recombinant systems have been developed for production of human sequence collagens. Mammalian and insect cells were initially used, but were thought to be too costly for commercial production. Yeast have been engineered to express high levels of type I homotrimer and heterotrimer and type II and type III collagen. Co-expression of collagen genes and cDNAs encoding the subunits of prolyl hydroxylase has lead to the synthesis of completely hydroxylated, thermostable collagens. Human types I and III collagen homotrimers have been expressed in transgenic tobacco plants, while transgenic mice have been engineered to produce full-length type I procollagen homotrimer as well as a alpha2 (I) homotrimeric mini-collagen. Most recently, a transgenic silkworm system was used to produce a fusion protein containing a collagenous sequence. Each of these transgenic systems holds great promise for the cost-effective large-scale production of recombinant human collagens. As seen in other recombinant expression systems, transgenic silkworms, tobacco, and mice lack sufficient endogenous prolyl hydroxylase activity to produce fully hydroxylated collagen. In mice and tobacco, this was overcome by over-expression of prolyl hydroxylase, analogous to what has been done in yeast and insect cell culture. In addition to recombinant alternatives to bovine collagen, other sources such as fish and sponge collagen are discussed briefly. Recombinant gelatin has been expressed in Pichia pastoris and Hansenula polymorpha in both non-hydroxylated and hydroxylated forms. Pichia was shown to be a highly productive system for gelatin production. The recombinant gelatins produced in yeast are of defined molecular weight and physio-chemical properties and represent a new biomaterial not previously available from animal sources. Genetic engineering has made great progress in the areas of recombinant collagen and gelatin expression, and there are now several alternatives to bovine material that offer an enhanced safety profile, greater reproducibility and quality, and the ability of these materials to be tailored to enhance product performance.     

Social networks and risk of neural tube defects

The contribution of social support and social networks to risk of neural tube defects (NTDs) has not been explored, despite evidence that various aspects of the social environment contribute to their etiology. Using data from a population-based case–control study of deliveries occurring in California from 1989 to 1991, this study investigates whether social networks, as measured by the presence and frequency of various types of social contacts, are associated with NTD risk. In-person interviews were conducted with 538 (88% of eligible) mothers of NTD cases and with mothers of 539 non-malformed controls (88%) on average 5 months from the term delivery date. Unadjusted results indicate that women who reported having close friends, close relatives, or monthly contacts with close friends or relatives had 30–70% lower risks of having NTD-affected pregnancies, relative to women reporting none to any of these measures. Only the presence of close friends was associated with reduced NTD risk after adjustment for other aspects of the social network and several potential covariates. This study is the first to investigate the association between social networks and risk of NTDs. Stronger inferences await replication and extension of these results.     

Neural tube defects associated with maternal periconceptional dietary intake of simple sugars and glycemic index

BACKGROUND: Maternal diabetes, prepregnancy obesity, hyperinsulinemia, and intakes of sweets have been associated with increased risks of neural tube defects (NTDs). The interdependence of these factors suggests a common pathogenesis via altered glycemic control and insulin demand. OBJECTIVE: We investigated whether maternal periconceptional dietary intakes of sucrose, glucose, fructose, and foods with higher glycemic index values influence the risk of having NTD-affected pregnancies. DESIGN: In a population-based case-control study, all hospitals in 55 of the 58 counties in California participated. In-person interviews were conducted with the mothers of 454 NTD cases (including fetuses and infants who were electively terminated, stillborn, or born alive) and with the mothers of 462 nonmalformed controls within an average of 5 mo from the term delivery date. The risk of having an NTD-affected pregnancy was the main outcome measure. RESULTS: Risks of having an NTD-affected pregnancy were not substantially elevated in relation to periconceptional intakes of glucose or fructose. Elevated risks of approximately 2-fold were observed for higher intakes of sucrose and foods with higher glycemic index values. Elevated risks were observed for high sucrose intake irrespective of whether adjustment was made for other covariates such as maternal folic acid intake. For higher glycemic index values, adjusted elevated risks of > or = 4-fold were observed in women whose body mass index (in kg/m(2)) was > 29. CONCLUSION: Our observed associations support observations that potential problems in glucose control are associated with NTD risk even among nondiabetic women.     

Estimation of microcystins in the freshwater fish Oreochromis niloticus in an Egyptian fish farm containing a Microcystis bloom

Microcystins (MCYSTs) that accumulated in different organs of the freshwater fish Oreochromis niloticus, collected from a fish farm in Egypt containing heavy blooms of Microcystis aeruginosa, were investigated using an enzyme-linked immunosorbent assay (ELISA). The distribution of MCYSTs in the organs varied significantly. The highest MCYST level was recorded in the guts (821 ng/g fresh weight), followed by the livers (531.8 ng/g) and kidneys (400 ng/g). Smaller amounts of MCYST were detected in muscles (102 ng/g). The present study suggests that fish farms should be monitored for the presence of toxic cyanobacterial blooms to minimize the exposure of fish to potent hepatotoxins.     

The effect of quinapril on functional status of elderly patients with diastolic heart failure

This double-blind, placebo-controlled study evaluated the effects of the ACE inhibitor, quinapril, on the functional status of elderly frail heart failure patients with preserved systolic function. Seventy-four elderly patients, mean (SD) age 78 (7) years, with symptomatic heart failure (NYHA II–III) and normal or only mildly impaired left ventricular systolic function (ejection fraction 40%) were randomly assigned to receive either quinapril or matched placebo (titrated to 40 mg/day) for 6 months. There were no significant differences at baseline in terms of age, cardiac function, aetiology, concomitant treatment, and echocardiographic values between active and placebo groups. Mean 6-minute walk distance increased at six months in the quinapril group [241.2 (132.0) v 267.3 (124.0) metres, p = 0.04] and in the placebo group [214.6 (114.5) v 267.6 (117.0) metres, p = 0.003]. The mean increases between the two groups were not significantly different. There were no significant changes in quality of life scores. The number of adverse drug events was similar in the two groups. Patients in the quinapril group were less likely to have worsening heart failure or to be admitted to hospital but these changes were not statistically significant. Conclusions. The present study confirmed the feasibility of single-centre drug trials in very elderly heart failure patients although recruitment and retention remain problematic. It did not show a beneficial effect of quinapril on exercise tolerance and quality of life in elderly heart failure patients with preserved systolic function.     

Transforming sheltered workshops into affirmative businesses: an outcome evaluation

This paper examines the outcomes associated with Voices, Opportunities and Choices Employment Club (VOCEC), which used the resources of a sheltered workshop to evolve affirmative businesses for people receiving mental health services. Quantitative and qualitative methodologies were used to understand the impact of VOCEC on employment and well-being outcomes compared to the former sheltered workshops and to competitive work. The results suggest that VOCEC has been successful in creating paid employment opportunities at levels approximating minimum wage and establishing a structure to incubate new businesses. The evaluation revealed the process by which Associates experience their participation as rewarding. It also indicated constraints on participation within the VOCEC model.     

A 59-year-old woman with tuberculous meningitis masked by hepatic encephalopathy

Tuberculous meningitis is a difficult diagnosis to make. The presenting symptoms, signs, and laboratory values are often nonspecific and can be attributed to other underlying conditions. Imaging and cerebrospinal fluid analysis can be more helpful. Extra pulmonary tuberculosis is not uncommon, and tuberculous meningitis represents 5% of extrapulmonary cases in the United States with the risk for tuberculosis increased six times for foreign-born persons. We report the case of a foreign-born cirrhotic patient with tuberculous meningitis whose diagnosis was likely delayed because of signs and symptoms of her underlying hepatic disease.     

The opportunity costs of informal care: does gender matter?

In this paper, we investigate the costs borne by both male and female carers in terms of their forgone formal employment opportunities. Traditionally, informal care was supplied by women but nowadays women are not only more likely to work, but also likely to be significant contributors to family finances. For women, this implies that the size of any forgone earnings cost of informal care is increasing. At the same time, population ageing is making for increasing numbers requiring care. From a policy perspective it is therefore helpful to consider a less traditional but nevertheless important source of informal care, men. We find that both male and female carers bear indirect costs in that they are less likely to be in paid work than otherwise similar non-carers and when they are in paid work they earn significantly less. However, we find that the motivation for lower employment participation is not the same for men as it is for women.     

Breast cancer risk among the survivors of atomic bomb and patients exposed to therapeutic ionising radiation.

Radiation induced breast cancer is a highly complex phenomenon, which most likely involves the accumulation of several genetic and epigenetic events. Studies of atomic bomb survivors, patients who underwent multiple fluoroscopic examinations during treatment for pulmonary tuberculosis, those who received therapeutic radiation for benign breast disease, such as acute post-partum mastitis, or those with an enlarged thymus or skin haemangioma and patients with Hodgkin's disease treated by mantle radiotherapy established that the risk of breast cancer increases with exposure to ionising radiation. The carcinogenic effect of therapeutic or accidental radiation is highest when exposure occurs during childhood and exposure after age 40 imparts low or minimal risk. The risk of bilateral breast cancer is not significantly increased in the survivors of atomic bomb and therapeutic radiations. Fractionated exposures for therapeutic radiation are similar to a single exposure of the same total dose in their ability to induce breast cancer; this risk remains high for many years after exposure. Younger age at first full term pregnancy confers a protective effect against the risk of breast cancer in the survivors of atomic bomb but long-term data on this beneficial effect after therapeutic radiation is not available.