Peripheral blood leucocyte zinc depletion in babies with intrauterine growth retardation.

The zinc content of peripheral blood leucocytes from the cord blood of 63 normal and 20 preterm babies, and of 27 babies with evidence of idiopathic intrauterine growth retardation (IUGR) was measured. Leucocyte zinc depletion was present in babies with acute IUGR (IUGR babies compared with controls, mean 47.8 v 51.5 ng zinc/mg dry weight), but was especially severe in those with prolonged IUGR (mean 43.2 ng zinc/mg dry weight), while preterm babies were normal (mean 51.9 ng zinc/mg dry weight). We suggest that this fetal tissue zinc depletion is caused by maternal zinc depletion, and may reflect a reduction of whole body zinc status.     

Fertility of long-term male survivors of acute lymphoblastic leukemia diagnosed during childhood

Fertility impairments among men treated during childhood for cancer are known to occur after some, but not all, types of anti-cancer therapy. This is the first study to evaluate proven fertility among adult male survivors of childhood acute lymphoblastic leukemia (ALL). In a retrospective cohort study, proven fertility (ever fathered a pregnancy) was evaluated by self-report among 213 men treated for ALL before age 18 on protocols of the Children's Cancer Group (CCG). Controls (N = 145) were drawn from among male siblings. Overall, with a proportional hazards analysis, proven fertility of male survivors was not different from that of controls (relative fertility (RF) = 0.95, 95% CI 0.63-1.43). However, married men treated before age 10 with high dose (24 cGy) cranial radiotherapy (RT), without spinal RT, had only 9% of the fertility of controls (Relative risk, RR = 0.09, 95% CI 0.01-0.82). High dose cranial RT at older ages was not associated with a statistically significant fertility deficit (RR = 0.56, 95% CI 0.25-1.28). In this first study of proven fertility among men treated for childhood leukemia, the majority of survivors showed no evidence of fertility impairment compared to controls. However, men treated at a young age with high dose cranial RT may have impaired fertility. These results suggest that further investigation of men with these treatments is needed to confirm and extend these findings.     

Differential localization of prostaglandin E synthase isoforms in human placental cell types

Increased prostaglandin E(2)(PGE(2)) synthesis involves multiple enzymes and two isoforms of the terminal enzyme of this biosynthetic pathway, PGE synthase (PGES), were recently identified. Cytosolic PGES (cPGES) is identical to the Hsp90 chaperone, p23, and is reportedly functionally coupled to constitutive PG endoperoxide H synthase-1 (PGHS-1). Microsomal PGES (mPGES), on the other hand, is inducible by proinflammatory cytokines such as IL-1beta. We have studied the cellular localization of both enzyme isoforms in human placenta at term and early gestation (10 weeks). Cytosolic PGES was immunolocalized to the fibroblasts and macrophages in villous stroma, whereas mPGES was localized in the extravillous trophoblasts (EVTs) as well as macrophages in both term and early gestation tissues. Microsomal PGES was also observed in cytotrophoblasts (CTs), but not in syncytiotrophoblasts (STs), in early gestation. Apoptotic early gestational STs were heavily stained with cPGES. We also investigated the cellular localization of cPLA(2)and PGHS-2 in early gestation and at term. Cytosolic PLA(2)was immunolocalized to the stroma and STs at term, but was only observed in CTs in early gestation. PGHS-2, on the other hand, was immunolocalized to both extravillous and STs in early gestation and at term. Our results suggest that mPGES could play a role in trophoblast invasion via its association with EVTs in the basal plate, whereas cPGES could be involved in apoptosis or repair mechanisms.     

Discovery of potent inhibitors of dihydroneopterin aldolase using CrystaLEAD high-throughput X-ray crystallographic screening and structure-directed lead optimization

Potent inhibitors of 7,8-dihydroneopterin aldolase (DHNA; EC 4.1.2.25) have been discovered using CrystaLEAD X-ray crystallographic high-throughput screening followed by structure-directed optimization. Screening of a 10 000 compound random library provided several low affinity leads and their corresponding X-ray crystal structures bound to the enzyme. The presence of a common structural feature in each of the leads suggested a strategy for the construction of a directed library of approximately 1000 compounds that were screened for inhibitory activity in a traditional enzyme assay. Several lead compounds with IC(50) values of about 1 microM against DHNA were identified, and crystal structures of their enzyme-bound complexes were obtained by cocrystallization. Structure-directed optimization of one of the leads thus identified afforded potent inhibitors with submicromolar IC(50) values.     

After the fall: women's views of fractures in relation to bone health at midlife

Past research has established the link between low energy fractures and the risk for future fractures. These fractures are potential markers for investigation of bone health, and may be precursors for osteoporosis. In spite of its significant public health burden, including burden of illness and economic costs, many individuals are not aware of the risk factors for and consequences of osteoporosis. This is a study of women aged 40 and older who experienced low energy fractures (e.g., from non-trauma sources and falls from no higher than standing height). We gathered data, using focus group interviews, about their experiences and understanding of the fractures in relation to bone health. Women often attributed the fractures to particular situations and external events (e.g., slipping on ice, tripping on uneven ground), and viewed the fractures as accidents. Women often felt that others are at risk for poor bone health, but believed that they themselves are different from those really at risk. Although the fractures are potential triggers for preventive efforts, few women connected their fracture to future risk. What is perceived by women (and others) as random and an accident is often a predictable event if underlying risk factors are identified. Only when there is more awareness of poor bone health as a disease process and fractures as markers for bone fragility will women, men and health care providers take action to prevent future fractures and established bone disease.     

Keeping up appearances: using qualitative research to enhance knowledge of dental practice

Current issues in dentistry including a focus on patients' wishes for outcomes and dentists' role in that process raise important questions that cannot be addressed by quantitative, statistical study alone. The intriguing complexities and ambiguities that are emerging with ever-improving techniques and materials in dentistry, as well as competing demands for attention in dental health, require a range of research methodologies to address important existing and future research questions. Qualitative research, much like what a dentist does in an office visit, can seem intuitive and almost common sense in nature. Yet behind that research, when it is done well, lie years of training and practice, rules of evidence, guidelines for rigor, and various subspecializations in its pursuit. Qualitative research begins with a clearly defined problem; identifies the appropriate strategy to gather data from people, existing documents, and other sources of information that will help address the problem; uses a multifaceted tool kit of analytic methods to work with those data; and proceeds to investigate the data for their insight into the research problem and interpretation of the findings. This article provides an overview of common approaches to qualitative methods and resources to explore their potential for dental research.     

The relation between tissue kallikrein excretion rate, aldosterone and glomerular filtration rate in human pregnancy

The changes in renal kallikrein synthesis through normal pregnancy and its relation to aldosterone excretion and the glomerular filtration rate was investigated. Overnight urinary kallikrein and aldosterone excretion rates and glomerular filtration rate were measured at 18 weeks, 34 weeks, term and postpartum in normal human pregnancy. Kallikrein excretion was raised at 18 weeks compared with the nonpregnant state (   P < 0.001  ) but was significantly reduced at term. The reduction in renal kallikrein was not due to falling aldosterone concentration, which increased in the third trimester, compared with 18 weeks (   P = 0.002  ) and remained elevated at term compared with the nonpregnant state (   P < 0.001  ). Glomerular filtration rate remained elevated at term despite the reduced kallikrein excretion rate. These data are consistent with the hypothesis that increased aldosterone production is one factor responsible for increased kallikrein synthesis which contributes to elevated glomerular filtration rate in early pregnancy. Other factors clearly inhibit renal kallikrein production at term. In the face of plasma volume expansion associated with increased mineralo-corticoid production, the effects of reduced kallikrein synthesis at term on glomerular perfusion and reabsorption of sodium by the distal tubule may predispose to blood pressure elevation in late pregnancy.