Regional distribution of proteinase K-resistant alpha-synuclein correlates with Lewy body disease stage

Lewy bodies (LBs) containing alpha-synuclein (alphaSYN) fibrils are the hallmark lesions of Parkinson disease, dementia with LBs, and related neurodegenerative diseases. Here we have investigated the susceptibility to proteolysis of alphaSYN from brain samples of patients with different subtypes of LB diseases. While soluble alphaSYN was completely degradable in all samples, the affected brain regions additionally contained insoluble, proteinase K (PK)-resistant alphaSYN. In brainstem-predominant subtype LB disease cases, PK-resistant alphaSYN was found in the medulla and substantia nigra, but not in cerebral cortex. In limbic subtype LB disease cases, PK resistance of alphaSYN spread to the cingulate and parahippocampal cortex, and further to the frontal cortex in neocortical subtype LB disease cases. Variable amounts of neuritic PK-resistant alphaSYN were found in the striatum of all cases. Thus, PK resistance of alphaSYN may be useful for the development of biomarkers of LB diseases.     

Structurally related mycotoxins ochratoxin A, ochratoxin B, and citrinin differ in their genotoxic activities and in their mode of action in human-derived liver (HepG2) cells: implications for risk assessment

To elucidate the effects of three structurally related mycotoxins, namely, ochratoxin A (OTA), ochratoxin B (OTB), and citrinin (CIT), on human health, we investigated their acute toxic, mitogenic, and genotoxic effects in the human-derived liver cell line (HepG2). These compounds are found in moldy foods in endemic areas of nephropathy, which is associated with urinary tract cancers. In agreement with previous experiments, we found that OTA causes a dose-dependent induction of micronuclei (MN) and DNA migration in the single-cell gel electrophoresis (SCGE) assay, which was statistically significant at concentrations of > or =5 microg/ml. In contrast, OTB was devoid of genotoxic activity under identical conditions, but the compound caused pronounced inhibition of cell division even at doses lower than OTA (10 microg/ml). CIT caused an effect similar to that of OTA in MN assays (significant at dose levels of > or =2.5 microg/ml) but was negative in the SCGE test. All compounds failed to induce mutations in Salmonella/microsome assays in strains TA 98 and TA 100 after addition of HepG2-derived enzyme homogenate (S9-mix). By use of DNA-centromeric probes we found that induction of MN by OTA involves chromosome breaking effects (55-60% of the MN were centromere negative), whereas CIT-induced MN were predominantly centromere positive (78-82%). Our findings indicate that OTB is devoid of genotoxic activity in human-derived cells and therefore probably not a genotoxic carcinogen in humans. In contrast, CIT was an equally potent inducer of MN in HepG2 cells as OTA, but this effect is caused by a different mechanism, namely, aneuploidy. Furthermore, our data suggest that combined exposure to structurally related mycotoxins that cause DNA damage via completely different mechanisms may significantly increase the cancer risk of humans consuming moldy foods.     

Hypothesis of regulation of hip joint cartilage activity by mechanical loading

Hypothesis of regulation of proteosynthetic activity of chondrocytes is suggested. A deformation of the cartilage caused by contact hip joint stress and consequent deformation of the chondrocytes are considered as main factors that could influence the metabolism of the cartilage.     

Cimicifuga extract BNO 1055: reduction of hot flushes and hints on antidepressant activity

Ethanolic- and isopropanolic-aqueous extracts of Cimicifuga racemosa are used for the treatment of climacteric complaints. As hot flushes and psychic complaints seem to be special targets for Cimicifuga extracts in clinical studies, these parameters were studied in experimental animals. Hot flush equivalents were measured in castrated rats as a quick increase in peripheral temperature with the aid of a transmitter implanted subcutaneously on the ventral side. The hot flush equivalents proved to respond to estrogen and the antidopaminergic drug veralipride but they were also reduced very effectively by Cimicifuga extract BNO 1055 (which is contained in Klimadynon/Menofem). In addition, an ethanolic-aqueous extract of C. racemosa was studied in the tail suspension test (TST), a behavioural test indicative for antidepressant activity. A significant decrease of the period of immobility was observed after treatment with 30 mg/kg body weight (bw) imipramine or with 50 or 100 mg/kg bw Cimicifuga extract. These findings in pharmacological tests-a reduction of the frequency of hot flush equivalents and hints on antidepressant activity of Cimicifuga extracts-are in good agreement with the therapeutical responses in climacteric women.     

Lymphangioma of the ovary after radiation due to Wilms' tumor in the childhood

OBJECTIVE: To report a case of lymphangioma of the ovary after radiation due to Wilms' tumor in the childhood. PATIENT: A 19-year-old nulliparous female. INTERVENTIONS: The vaginal ultrasound showed the left ovary enlarged to 4.4 cm x 2.9 cm x 4.5 cm in size including a 3.5 cm x 2.6 cm x 3.2 cm measuring cystic solid tumor without hypervascularity. For exclusion of a malignant tumor, a laparoscopy for excision of the tumor and deep incision of the left ovary with a bipolar needle was performed to exclude deeper tumor of stromal origin. The histological examination of the tissue showed a lymphangioma beside normal ovarian tissue. CONCLUSION: To our knowledge, this is the first report of lymphangioma of the ovary after radiation due to Wilms' tumor in the childhood. The impact of this finding on the patient's fertility remains unclear. As in other organs exposed to radiation, lymphangioma can also occur in the ovary. Careful follow up should be considered to this patients, because malignant transformation can not be excluded.     

The roles of pathways in the spinal cord lateral and dorsal funiculi in signaling nociceptive somatic and visceral stimuli in rats

The spinothalamic tract (STT) is a major ascending nociceptive pathway, interruption of which by cordotomy is used for pain relief, whereas the dorsal column (DC) pathway is usually not considered to be involved in pain transmission. However, recent clinical studies showed good relief of visceral pain in cancer patients after a DC lesion. Electrophysiological recordings in animals suggest that the analgesic effect is due to interruption of axons ascending from postsynaptic dorsal column (PSDC) neurons located in the vicinity of the central canal. In this behavioral study, we used a decrease in exploratory activity in rats after a noxious stimulus as an indicator of perceived pain, independent of withdrawal reflexes. Intradermal capsaicin injection almost abolished exploratory activity in na?ve animals or in rats after a DC lesion, but did not change it in rats after ipsilateral dorsal rhizotomy or a lesion of the lateral funiculus on the side opposite to the injection. In contrast, a bilateral DC lesion counteracted the decrease in exploratory activity induced by noxious visceral stimuli for at least 180 days after the surgery. Although neurons projecting in both the STT and the PSDC path can be activated by noxious stimuli of cutaneous or visceral origin, our results suggest that the STT plays a crucial role in the perception of acute cutaneous pain and that the DC pathway is important for transmission of visceral pain.     

Primary antiphospholipid antibody syndrome masquerading as progressive supranuclear palsy

We report a case of a patient with clinical features of progressive supranuclear palsy and raised titres of anticardiolipin antibodies in blood, thrombocytopenia and livedo reticularis on skin. Magnetic resonance imaging of brain and isotope scan of brain were distinctive of vascular disorder.     

Cell-binding properties of glycoprotein B of Aujeszky's disease virus

The glycoprotein B (gB) of Aujeszky's disease virus (ADV) has a role in virus entry and cell-to-cell spread. In this report we examined the cell-binding properties of native ADV gB purified from the virus envelope by affinity chromatography. The binding of gB to the surface of susceptible cells BHK-21 and MDBK was specific, dose-dependent, and nearly saturable, which is characteristic of conventional receptor-ligand interactions. The purified gB was shown to specifically bind to immobilised heparin. The addition of soluble exogenous heparin and heparinase treatment of cells inhibited the binding of gB to the cells. Cell-associated gB could also be dissociated from the cells by soluble heparin. The results indicated that ADV gB binds specifically to cellular heparan sulphate. The binding of gB to cells inhibited the attachment of virus to cells and thus the formation of viral plaques. The results suggest that ADV gB may have a function in the initial attachment of ADV to the surface of susceptible cells.