ACE inhibition reduces activity of the plasminogen/plasmin and MMP systems in the brain of spontaneous hypertensive stroke-prone rats

The spontaneously hypertensive stroke-prone rat (SHR-SP) is an experimental model of malignant hypertension which lead to secondary alterations of the extracellular matrix. Our aim was to determine ACE-inhibitor related changes of proteases involved in the reconstruction of the extracellular matrix in the brain. Twelve SHR-SP rats were randomized into two groups. Each group was treated with either an antihypertensive dose of ramipril or placebo for 6 months. Brain tissue plasminogen activator (t-PA) and urokinase (u-PA) were quantified by using casein-dependent plasminogen zymography, matrix metalloproteinase (MMP)-2 and MMP-9, by MMP-zymography, and tissue inhibitor of MMP (TIMP)-1 and -2, by reverse zymography. The amounts of u-PA, t-PA, and MMPs were significantly reduced in animals treated with ACE inhibitor. Plasminogen zymography showed a 39% reduction of u-PA in the basal ganglia (p < 0.0001); t-PA expression was reduced by 26% in the cortex and by 33% in the basal ganglia (p < 0.0001). MMP-2 expression was reduced by 15% in the cortex (p < 0.05) and by 10% in the basal ganglia (p < 0.05); MMP-9 expression significantly decreased by 37% in the cortex and by 25% in the basal ganglia (p < 0.0001 each). No differences were observed in the amount of TIMP-1 or TIMP-2. These findings provide new insights into the biochemical mechanisms underlying extracellular matrix proliferation and its modulation by ACE inhibitors. Therapeutic alterations that influence the proteolytic systems might prove important in the prevention of extracellular matrix accumulation and secondary microvascular vessel wall changes.     

An association of pleuropulmonary blastoma and cystic nephroma: possible genetic association.

The association of pleuropulmonary blastoma and cystic nephroma is an uncommon entity, with only 4 cases of such an association in the same patient described in English literature. We report a 5th histologically documented case in a 32-month-old boy. The boy underwent a pulmonary biopsy that showed a pleuropulmonary blastoma and a nephrectomy that showed a cystic nephroma. The pleuropulmonary mass showed an important regression with postbiopsy chemotherapy, allowing subsequent tumorectomy. To date very little is known about this rare entity, and a genetic link between these 2 tumors is hypothesized.     

Heparan sulfate on endothelial cells mediates the binding of Plasmodium falciparum-infected erythrocytes via the DBL1alpha domain of PfEMP1

Plasmodium falciparum may cause severe forms of malaria when excessive sequestration of infected and uninfected erythrocytes occurs in vital organs. The capacity of wild-type isolates of P falciparum-infected erythrocytes (parasitized red blood cells [pRBCs]) to bind glycosaminoglycans (GAGs) such as heparin has been identified as a marker for severe disease. Here we report that pRBCs of the parasite FCR3S1.2 and wild-type clinical isolates from Uganda adhere to heparan sulfate (HS) on endothelial cells. Binding to human umbilical vein endothelial cells (HUVECs) and to human lung endothelial cells (HLECs) was found to be inhibited by HS/heparin or enzymes that remove HS from cell surfaces. (35)S-labeled HS extracted from HUVECs bound directly to the pRBCs' membrane. Using recombinant proteins corresponding to the different domains of P falciparum erythrocyte membrane protein 1 (PfEMP1), we identified Duffy-binding-like domain-1alpha (DBL1alpha) as the ligand for HS. DBL1alpha bound in an HS-dependent way to endothelial cells and blocked the adherence of pRBCs in a dose-dependent manner. (35)S-labeled HS bound to DBL1alpha-columns and eluted as a distinct peak at 0.4 mM NaCl. (35)S-labeled chondroitin sulfate (CS) of HUVECs did not bind to PfEMP1 or to the pRBCs' membrane. Adhesion of pRBCs of FCR3S1.2 to platelet endothelial cell adhesion molecule-1 (PECAM-1)/CD31, mediated by the cysteine-rich interdomain region 1alpha (CIDR1alpha), was found be operative with, but independent of, the binding to HS. HS and the previously identified HS-like GAG on uninfected erythrocytes may act as coreceptors in endothelial and erythrocyte binding of rosetting parasites, causing excessive sequestration of both pRBCs and RBCs.     

Adult Children and the Transition of Aging Parents

Abstract

This study explores the experiences of adult children as they transition their functionally and/or cognitively declining aging parents from independent living to supervised housing. A qualitative grounded theory approach was used to chronicle the experiences of adult children as their caregiving responsibilities intensified and their parents' health declined. Purposive, snowball sampling was used to enlist adult children (n = 16) who were in the process of transitioning an aging parent from an independent living situation to one providing assistance with everyday care and tasks. Semi-structured telephone interviews were conducted and designed to follow a pattern of increased frailty of the parent(s) and escalating involvement of the adult child. Two major themes emerged from the data: Changing places and everlasting love. Adult children began to intervene when cognitive or physical declines compromised the safety and well-being of the older adult and began to assume responsibility for day-to-day needs. As disabilities intensified, adult children relied on siblings, friends, social services, and health care providers to assist in planning and implementing caregiving responsibilities. Deep respect and abiding love of the aging parent(s) sustained the adult child throughout the caregiving experience.     

Prediction of left ventricular mass from the electrocardiogram.

Multiple stepwise regression methods were used to derive electrocardiographic (ECG) models for prediction of the echocardiographic left ventricular (LV) mass index from standard 12-lead ECG measurements using data files of 203 men and 252 women. The correlation between echocardiographic and ECG estimates of LV mass index was R2 = 0.58 for men and R2 = 0.42 for women. A separate logistic regression model was derived for classification of LV hypertrophy as a dichotomized dependent variable. This classifier chose R (aVL), T (V6), and S (V1) for men and R (aVL), T (V6), and S (I) for women and produced a moderate sensitivity (53.7% for men and 63.4% for women) and specificity (94.9% for men and 92.9% for women). We conclude that the initial performance of these and other recently developed multivariate estimators of LV mass and LV hypertrophy classifiers is promising enough to subject them to further studies to evaluate their utility as risk predictors.     

A Mirror in the Mind: A Case of Visual Allaesthesia in Homonymous Hemianopia

We report the case of a 61-year-old female patient with intracranial bleeding in left parietal and parieto-temporal regions and a history of epilepsy and migraine. MR images showed lesions of the optic radiation, but primary visual cortical areas were intact. Perimetric testing revealed an incomplete right hemianopia. The patient claimed that visual percepts from her intact field were projected as “mirror images” into the hemianopic field. The illusory images were weak and sometimes difficult to detect, but focusing spatial attention on the “mirror” image increased its saliency. Drawings the patient made of her pseudo-hallucinations revealed that the illusions were lateral transpositions instead of mirror images of real objects. The illusions were tilted in clockwise direction and were never colored, although color discrimination was unimpaired in the patient's left hemifield. We quantified the characteristics of the pseudohallucinations in several experiments: The patient was asked to adjust the position, rotation angle, and size of a white test card in her blind field so that it corresponded with the illusory projection of a card of standard size and position that was presented in the intact field. The test card was compressed in horizontal size by 20% and positioned 17° visual angle to the right of the standard, shifted 1.5° upward or downward, and rotated in clockwise direction by 22.6° on average. Large objects in the intact field were projected incompletely into the blind area. Our patient's symptoms are similar to those reported in earlier case studies of visual allaesthesia. We hypothesize that the “mirror image” is induced by sparse input from contralesional V1 via the corpus callosum upstream of the lesion site and a lack of inhibition or hyperexcitability of ipsilesional early visual areas after deafferentation. The rotation of the illusions may be induced by the parietal lesions causing faulty co-ordinate computations, e.g., an inability to integrate visual and otholitic input.     

Subjektive Qualitätskonzepte im Vergleich zu objektiven Qualitätskriterien

Background

The need for quality management in prevention and health promotion continues to grow. The role of the participants’ and course instructors’ views on quality in prevention and health promotion has been insufficiently considered. The aim of the present study was to examine the participants’ and course instructors’ views on quality in movement-related prevention and health promotion.

Methods

Four participants and four course instructors were questioned using semistructured interviews. The data were analyzed according to the structured content analysis according to Kuckartz.

Results

The views on quality of participants and course instructors were comparable. Within the participants’ and course instructors’ views on quality in movement-related prevention and health promotion the “individual relationship between therapist and patient”, “personal atmosphere”, and “class structure” were identified as important quality dimensions, while proof of effectiveness seemed to be less important. Moreover, the understanding of proof of effectiveness turned out to be inconsistent.

Conclusions

Compared to the prevention guideline of the German statutory health insurers, participants’ and course instructors’ views on quality point out the importance of process quality. In contrast, proof of effectiveness and the qualification of the course instructor play a minor role in subjective quality concepts.

     

A gelatin in situ-overlay technique localizes brain matrix metalloproteinase activity in experimental focal cerebral ischemia

To determine the activity of matrix metalloproteinases (MMP), especially MMP-2 and MMP-9, which play an important role in ischemic stroke and intracerebral hemorrhage, we adapted a simple and rapid method for localizing gelatinase activity to a gelatin film in situ-overlay technique previously used in cancer research. Ten micrometer cryosections of rat brain from controls and animals subjected to 3 h of ischemia and 48 h of reperfusion (suture model for transient cerebral ischemia) were used. After thawing, a gelatin film with a polyester base was put on the slide, incubated for 24 h at 37 degrees C, stained with Ponceau S, and then discolored in bi-distilled water. Non-staining areas on the film corresponded to lysis zones, caused by activated MMPs. This was proven by MMP incubation at various concentrations on the plain gelatin film and pretreatment with EDTA (an MMP inhibitor), which prevents lysis zones in normal and ischemic brains. As confirmatory tests, SDS-PAGE zymography was used to define MMP activity, and also MMP-2 immunohistochemistry to detect the possibly cellular origin of MMPs. Normal rat brain exhibited a low background activity, which was visible as a light halo-like lysis zone over and around the brain. Areas in normal brain with medium MMP activity were within the white matter (corpus callosum, anterior commissure, and cerebellum). Ischemic brain exhibited high activity lysis zones within the infarcted area (detected by microtubuli associated protein-2 staining). These zones consisted of microscopically small lysis holes with a diameter of about 10-20 microm. Immunohistochemistry showed that especially microvessels expressed MMP antigen. SDS-PAGE zymography differentiated between a high level of activated MMPs in the ischemic area and a low level in the non-ischemic basal ganglia. The gelatin film in situ-overlay technique is able to localize MMP activity in ischemic rat brain tissue on a microscopic level.     

Application of physical surface methods to the study of the stability and structure of bone-metal interfaces

Summary The bonding mechanism between bone and metallic implants has been studied using specific surface techniques (ESCA, RHEED) and X-ray diffraction methods.The growth process of different metals commonly used in surgical implantation has been observed on human bone. We have shown that in the case of a bone-titanium interface an intermediate compound is built which is certainly contributing to its stability. In gold-bone interfaces, such a compound has not been observed, and growth seems less regular.

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Application des méthodes de la physique des surfaces á l'étude de la stabilité et de la structure des interfaces os-métal

Résumé Le mécanisme de liaison entre os et implant métallique a été étudié en utilisant des techniques spécifiques des surfaces (spectrométrie des photo-électrons: ESCA; diffraction des électrons rapides: RHEED), et la diffraction des rayons X.Le processus de croissance de différents métaux utilisés en implantologie chirurgicale a été observé sur l'os humain. Nous avons pu montrer que dans le cas d'un interface os-titane, un composé intermédiaire est formé, composé favorisant certainement la stabilité de l'implant. Dans le cas d'un interface os-or, la croissance semble moins régulière, et un tel composé intermédiaire n'a pas pu être mis en évidence.