Morphometric and immunohistochemical characterization of the intimal layer throughout the arterial system of elderly humans

The purpose of the present study was to obtain insight into the natural development of adaptive intimal thickening and atherosclerosis in the arterial tree of human species. The morphometry and composition of the intimal layer were studied in the arterial system of elderly individuals. Post mortem, a total of 703 arterial segments were dissected from 24 subjects (age 81.9 ± 9.9 years). From each subject, segments were dissected from 31 different arteries. Area stenosis [(plaque area/vessel area) × 100%] was determined in each segment. By (immuno)histochemistry, lipid content and the presence of inflammatory cells (macrophages) were assessed in the coronary, common carotid, brachial, radial and internal iliac arteries. Adaptive intimal thickening or advanced atherosclerosis was observed in all studied artery types. Area stenosis was highest in the coronary arteries (median, 30%) and lowest in the arteries supplying the brain (median, ≤ 7%). Plaques hiding a lipid‐rich core and plaques with macrophage infiltration were observed in all five selected artery types. In summary, the present observation demonstrates that intimal thickening is a systemic process involving most artery types. Within elderly humans, features of advanced atherosclerotic disease, a lipid‐rich core and macrophages, can be observed in the intimal layer of artery types that are recognised for their relation with clinical syndroms as well as artery types that remain clinically silent.     

Towards practical soft X-ray spectromicroscopy of biomaterials

Scanning transmission X-ray microscopy (STXM) is being developed as a new tool to study the surface chemical morphology and biointeractions of candidate biomaterials with emphasis on blood compatible polymers. STXM is a synchrotron based technique which provides quantitative chemical mapping at a spatial resolution of 50 nm. Chemical speciation is provided by the near edge X-ray absorption spectral (NEXAFS) signal. We show that STXM can detect proteins on soft X-ray transparent polymer thin films with monolayer sensitivity. Of great significance is the fact that measurements can be made in situ, i.e. in the presence of an overlayer of the protein solution. The strengths, limitations and future potential of STXM for studies of biomaterials are discussed.     

Association analysis of a polymorphism in the G‐protein stimulatory α subunit in patients with major depression*

Growing evidence suggests that G‐proteins may be involved in pathogenesis and treatment of affective disorders. Several studies have reported altered levels and/or activities of stimulatory G‐proteins in depression. The aim of this study was to investigate whether a polymorphism in the stimulatory α subunit of G‐proteins (T/C point mutation in exon 5; ATT → ATC at codon 131) is associated with major depression or response to antidepressant treatment. Therefore, we performed a case‐control association study with 212 depressive patients and 137 healthy, unrelated controls. There was no evidence for an association between the investigated polymorphism in the Gα_s gene and major depression, as well as to treatment response. The results of our study are in concordance with recently published findings which do not support the hypothesis that the gene for the stimulatory α subunit of G‐proteins is a major susceptibility factor in the pathophysiology of major depression. © 2002 Wiley‐Liss, Inc.     

Effect of hydroxyapatite/tricalcium-phosphate coating on osseointegration of plasma-sprayed titanium alloy implants

This study determined the effects of a plasma-sprayed hydroxyapatite/tricalcium phosphate (HA/TCP) coating on osseointegration of plasma-sprayed titanium alloy implants in a lapine, distal femoral intramedullary model. The effects of the HA/TCP coating were assessed at 1, 3, and 6 months after implant placement. The HA/TCP coating significantly increased new bone apposition onto the implant surfaces at all time points. The ceramic coating also stimulated intramedullary bone formation at the middle and distal levels of the implants. Fluorescent bone labeling indicated that new bone formation occurred primarily during the first 3 months after implantation, with comparatively little activity detected in the latter stages of the study. There was no associated increase in pullout strength at either 3 or 6 months; however, post-pullout evaluation of the implants indicated that the HA/TCP coating itself was not the primary site of construct failure. Rather, failure was most commonly observed through the periprosthetic osseous struts that bridged the medullary cavity. The demonstrated osteoconductive activity of HA/TCP coating on plasma-sprayed titanium alloy implant surfaces may have considerable clinical relevance to early host-implant interactions, by accelerating the establishment of a stable prosthesis-bone interface.     

Autocrine and paracrine growth regulation of human breast cancer

Summary We consider the hypothesis that estrogen control of hormone dependent breast cancer is mediated by autocrine and paracrine growth factors secreted by the breast cancer cells themselves. Though we show direct, unmediated effects of estrogen on specific cell functions, we also provide evidence that human breast cancer cells secrete a collection of growth factors (IGF-I, TGF, TGF, a PDGF-like competency factor, and at least one new epithelial colony stimulating factor). Some of these are estrogen-regulated in hormone dependent cells, and are constitutively increased in cells which acquire independence either spontaneously or byras transfection. Collectively, the secreted growth factors are capable of promoting tumor formation by MCF-7 cells in nude mice, though not to the same extent as estrogens. There would seem to be potential for clinical intervention in the autocrine and paracrine control of breast cancer cells, including some cells which are no longer dependent on estrogens.     

Epidemiological link between obesity,type 2 diabetes mellitus and cancer

There exists a complex interaction between obesity, type 2 diabetes mellitus (T2DM) and cancer, and an increase in the incidence of cancer is expected with the growing obesity-diabetes pandemic. The association of cancer with diabetes mellitus and obesity appears to be site-specific, the highest risk being for post-menopausal breast cancer, endometrial cancer, and colorectal cancer. Moreover, there is worsening of hyperglycaemia with the onset of cancer, evidencing a bi-directional link between cancer and diabetes mellitus and the need for monitoring for diabetes in cancer survivors. In this review, we look at the epidemiological evidence from observational studies and Mendelian randomization studies linking obesity, diabetes, and cancer, as well as the complex pathophysiological mechanisms involved, including insulin resistance with associated hyperinsulinaemia, the effect of chronic low-grade inflammation, and the effect of various adipokines that are associated with obesity and T2DM. Additionally, we describe the novel therapeutic strategies, based on their role on the discrete pathophysiological mechanisms involved in the tumourigenesis.     

Recovery of motor and language abilities after stroke: the contribution of functional imaging

In recent years, functional imaging techniques, like functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and transcranial magnetic stimulation (TMS), have shown that the improvement of motor and language function after ischemic stroke is accompanied by extensive reorganizational changes in the human cortex. To better understand these changes and to judge to what extent they could be responsible for clinical improvement, some basic principles of the organization of the motor and language system are discussed.Non-invasive functional imaging can have only a limited contribution in determining which of the possible underlying neural mechanisms, as they are known from animal experiments, play a role in functional recovery. However, they make it possible to define the functional consequences of anatomical lesions in individual patients and to correlate these functional consequences in the motor and language system with the clinical deficit. They can be used to assess the influence on the cortical reorganization of established and newer physiotherapies, logopedics and medical intervention, and they could be a useful tool in determining prognosis.