Expression of transforming growth factor-beta receptor type 1 and type 2 in human sporadic vestibular Schwannoma

Expression of the transforming growth factor-beta (TGF-beta) protein family in the peripheral nervous system is well established, but the role of their cognate receptors TGF-beta receptor type 1 (R1) and type 2 (R2) has been less well studied. TGF-beta plays an essential role in Schwann cell proliferation and differentiation, and is involved in neurotrophic effects of several neurotrophic substances. TGF-beta is also expressed in benign peripheral nervous system tumors such as vestibular schwannomas. In the present study, we aimed to detect TGF-beta R1 and R2 in a total of 40 sporadic vestibular schwannomas using immunohistochemistry, and correlated the findings to essential clinicopathologic data. TGF-beta, TGF-beta R1, and TGF-beta R2 mRNA was further analyzed by RT-PCR in six vestibular schwannomas. TGF-beta R1 immunoexpression was found in about 95% of the tumors. TGF-beta R1 was equally present in Antoni A and Antoni B areas of the tumors. TGF-beta R2 was found immunohistochemically in 77%. In addition, all tumors showed strong expression of TGF-beta. No correlation between TGF-beta R1 or R2 expression and clinicopathologic parameters such as age, sex, clinical symptoms, growth pattern, and proliferation acitivity as measured by Ki-67 (MIB-1) staining was found. Moreover, all schwannomas studied contained TGF-beta, TGF-beta R1, and TGF-beta R2 mRNA. Therefore, the TGF-beta/TGF-beta R1 and -R2 system is present in human schwannomas, but its biologic role for tumor development and growth remains unclear.     

Flexions- und Extensionsosteotomien der proximalen Tibia

Background

Isolated deviations in flexion and extension of the leg axis are rare. These deviations can be corrected if necessary by osteotomy and the range of motion (ROM) of the knee joint can be optimized. In addition to correction in the frontal plane, the tibial slope (i.e. inclination of the surface of the tibial joint) can also be influenced by osteotomy and therefore osteotomy can also be utilized to optimize the biomechanical stability of the knee joint.

Method

Careful planning taking all three spatial planes and torsion into consideration is the foundation of a successful operation. A controlled surgical technique based on careful planning and some basic principles allows the alteration of the three dimensional alignment of the tibia.     

Psychotropic medication in geriatric psychiatric patients: use and unreported use in relation to serum concentrations

Purpose

The aim of this observational study was to describe the type, number, and serum concentration levels of psychotropic drugs in elderly patients, on admission to a geriatric psychiatric inpatient unit. We further wanted to investigate the use and unreported use of psychotropic drugs by analyzing for a broad spectrum of drugs in the serum samples.

Methods

A total of 236 patients were included. Drug use, patient characteristics, and diagnoses were recorded, and serum analysis was performed for a total of 56 psychotropic drugs in 233 of the patients.

Results

Nine out of ten patients (88 %) used one or more psychotropic drugs on admission to hospital; the mean use was 2.8 (95 % confidence interval (CI) 2.6–2.9) drugs. In 25 patients (11 %), drugs reported used were not detected in serum. Unreported use of drugs (serum analysis revealing one or more drugs not reported) was found in 100 patients (43 %). This was more common in younger patients. Psychotropic polypharmacy (use of three or more psychotropic drugs) was found in 109 patients (47 %). Patients with a main diagnosis of affective disorder used the most psychotropic drugs.

Conclusions

Psychotropic drugs are commonly used among geriatric psychiatric patients on admission to hospital. Psychotropic polypharmacy is a major concern among these patients. There was considerable unreported use of drugs within this population, and a low threshold for a broader serum analysis for psychotropic drugs appears indicated.     

Heart transplantation for end-stage heart failure caused by iron overload

Few reports exist concerning heart transplantation in recipients with end-stage myocardiopathy-associated heart failure caused by iron overload occurring with β-thalassaemia, Diamond-Blackfan syndrome or haemochromatosis. Seven potential transplant candidates (six male, one female, mean age 26 years) with such heart failure, following desferrioxamine application subcutaneously over a number of years, and intravenously during their hospitalization before transplantation, were retrospectively analysed. Five were New York Heart Association (NYHA) class IV, three experienced one or more resuscitations immediately before transplantation could be performed. Continuous, high-volume, veno-venous haemofiltration was necessary in two patients. One of these two candidates additionally had to be bridged, first with a right ventricular, then with a biventricular assist device. Five of the seven patients survived, two with haemochromatosis, one with β-thalassaemia major and one with Diamond-Blackfan syndrome following transplantation. One non-transplanted candidate with β-thalassaemia major has been recompensated for 5 years. Survival was 14–74 months. Our results demonstrate the feasibility and indication of transplantation in patients with such heart failure and the satisfying outcome of immunosuppression is described.     

Transcapillary fluid balance in immature rats. Interstitial fluid pressure,serum and interstitial protein concentration,and colloid osmotic pressure

Several of the factors governing transcapillary fluid balance were studied in anesthetized rats from the age of 1 to 60 days. Serum albumin and total protein concentrations rose from 1.7 and 2.4 g/100 ml at birth to 4.1 and 6.2 g/100 ml in adult rats, while colloid osmotic pressure rose from 5.3 to about 20 mm Hg. Interstitial fluid collected from subcutis by the wick technique showed protein concentrations of approximately 60% of serum values in all age groups, and its colloid osmotic pressure rose from about 3 to 10 mm Hg during maturation. Arterial pressure rose from about 50 mm Hg in newborn rats to 120 mm Hg in adult animals. Iliac venous pressure was only 0.5–1 mm Hg in 10-day-old rats compared to 3 mm Hg in adult animals. Interstitial fluid pressures of 0 to ?1 mm Hg were obtained in all age groups with the “wick-in-needle” technique. The data suggest an average capillary pressure of less than 5 mm Hg in newborn animals and a pre- to postcapillary resistance ratio similar to that of adult animals. The safety factors against edema formation seem to be small in immature rats.     

GCK-MODY diabetes as a protein misfolding disease: The mutation R275C promotes protein misfolding,self-association and cellular degradation

GCK-MODY, dominantly inherited mild hyperglycemia, is associated with more than 600 mutations in the glucokinase gene. Different molecular mechanisms have been shown to explain GCK-MODY. Here, we report a Pakistani family harboring the glucokinase mutation c.823C > T (p.R275C). The recombinant and in cellulo expressed mutant pancreatic enzyme revealed slightly increased enzyme activity (k_cat) and normal affinity for α-D-glucose, and resistance to limited proteolysis by trypsin comparable with wild-type. When stably expressed in HEK293 cells and MIN6 β-cells (at different levels), the mutant protein appeared misfolded and unstable with a propensity to form dimers and aggregates. Its degradation rate was increased, involving the lysosomal and proteasomal quality control systems. On mutation, a hydrogen bond between the R275 side-chain and the carbonyl oxygen of D267 is broken, destabilizing the F260-L271 loop structure and the protein. This promotes the formation of dimers/aggregates and suggests that an increased cellular degradation is the molecular mechanism by which R275C causes GCK-MODY.     

Increasing use of anticoagulants in Germany and its impact on hospitalization rates for genitourinary bleeding

Journal of Thrombosis and Thrombolysis - The aim of the study was to compare nationwide time trends of prescribed oral anticoagulants (OAC) with the time trend of genitourinary bleedings (GUB) in...     

What is microglia neurotoxicity (Not)?

Microglia most likely appeared early in evolution as they are not only present in vertebrates, but are also found in nervous systems of various nonvertebrate organisms. Mammalian microglia are derived from a specific embryonic, self‐renewable myeloid cell population that is throughout lifetime not replaced by peripheral myeloid cells. These phylogenic and ontogenic features suggest that microglia serve vital functions. Yet, microglia often are described as neurotoxic cells, that actively kill (healthy) neurons. Since it is from an evolutionary point of view difficult to understand why an important and vulnerable organ like the brain should host numerous potential killers, we here review the concept of microglia neurotoxicity. On one hand it is discussed that most of our understanding about how microglia kill neurons is based on in vitro experiments or correlative staining studies that suffer from the difficulty to discriminate microglia and peripheral myeloid cells in the diseased brain. On the other hand it is described that a more functional approach by mutating, inactivating or deleting microglia is seldom associated with a beneficial outcome in an acute injury situation, suggesting that microglia are normally important protective elements in the brain. This might change in chronic disease or the aged brain, where; however, it remains to be established whether microglia simply lose their protective capacities or whether microglia become truly neurotoxic cells. GLIA 2014;62:841–854