Ganoderma lucidum inhibits proliferation and induces apoptosis in human prostate cancer cells PC-3

Ganoderma lucidum (Reishi), an oriental medical mushroom, has been widely used in Asian countries for centuries to prevent or treat different diseases, including cancer. However, the mechanism(s) responsible for the effects of Ganoderma lucidum on cancer cells remain to be elucidated. We have previously demonstrated that Ganoderma lucidum down-regulated the expression of NF-kappaB-regulated urokinase plasminogen activator (uPA) and uPA receptor (uPAR), which resulted in suppression of cell migration of highly invasive human breast and prostate cancer cells. In this study, we investigated the effects of Ganoderma lucidum on cell proliferation, cell cycle, and apoptosis in human prostate cancer cells PC-3. Our data demonstrate that Ganoderma lucidum inhibits cell proliferation in a dose- and time-dependent manner by the down-regulation of expression of cyclin B and Cdc2 and by the up-regulation of p21 expression. The inhibition of cell growth was also demonstrated by cell cycle arrest at G2/M phase. Furthermore, Ganoderma lucidum induced apoptosis of PC-3 cells with a slight decrease in the expression of NF-kappaB-regulated Bcl-2 and Bcl-xl. However, the expression of proapoptotic Bax protein was markedly up-regulated, resulting in the enhancement of the ratio of Bax/Bcl-2 and Bax/Bcl-xl. Thus, Ganoderma lucidum exerts its effect on cancer cells by multiple mechanisms and may have potential therapeutic use for the prevention and treatment of cancer.     

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.     

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.     

Glucose analog inhibitors of glycogen phosphorylases as potential antidiabetic agents: recent developments

Diabetes is among the largest contributors to global mortality through its long term complications. The worldwide epidemic of type 2 diabetes has been stimulating the quest for new concepts and targets for the treatment of this incurable disease. A new target is glycogen phosphorylase (GP), the main regulatory enzyme in the liver responsible for the control of blood glucose levels. One of several approaches to influence the action of GP is the use of glucose derivatives as active site inhibitors. This field of research commenced 10-15 years ago and, due to joint efforts in computer aided molecular design, organic synthesis, protein crystallography, and biological assays, resulted in glucopyranosylidene-spiro-hydantoin 16 (K(i) = 3-4 micro M) as the most efficient glucose analog inhibitor of GP of that time. The present paper surveys the recent developments of this field achieved mainly in the last five years: the synthesis and evaluation of glucopyranosylidene-spiro-thiohydantoin 18 (K(i) = 5 micro M) which has proven equipotent with 16, and is available in gram amounts; furanosylidene- and xylopyranosylidene-spiro-(thio)hydantoins whose ineffectiveness (K(i) > 10 mM) confirmed the high specificity of the catalytic site of GP towards the D-glucopyranosyl unit; "open" hydantoins like methyl N-(1-carboxamido-D-glucopyranosyl)carbamate 37 (K(i) = 16 micro M) and N-acyl-N'-(beta-D-glucopyranosyl)ureas among them the to date best glucose analog inhibitor N-(2-naphthoyl)-N'-(beta-D-glucopyranosyl)urea (35, K(i) = 0.4 micro M) which can also bind to the so-called new allosteric site of GP; C-(beta-D-glucopyranosyl)heterocycles (tetrazole, 1,3,4-oxadiazoles, benzimidazole (K(i) = 11 micro M), and benzothiazole). Iminosugars like isofagomine (45, IC(50) = 0.7 micro M), noeuromycin (53, IC(50) = 4 micro M), and azafagomine (54, IC(50) = 13.5 micro M) also bind strongly to the active site of GP, however, substitution on the nitrogens makes the binding weaker. The natural product five-membered iminosugar DAB (56) exhibited IC(50) approximately 0.4-0.5 micro M. Azoloperhydropyridines which can be regarded iminosugar-annelated heterocycles show moderate inhibition of GP: nojiritetrazole 12 (K(i) = 53 micro M) is the best inhibitor and fewer nitrogens in the five-membered ring weakens the binding. Physiological investigations have been carried out with N-acetyl-beta-D-glucopyranosylamine 6, spiro-thiohydantoin 18, isofagomine 45, and DAB 56 to underline the potential use of these compounds in the treatment of type 2 diabetes. Computational methods suggest to synthesize further anomerically bifunctional glucose derivatives which may be good inhibitors of GP.     

Optokinetic stimulation in microgravity: torsional eye movements and subjective visual vertical

INTRODUCTION: Microgravity provides unique sensory inputs to the vestibular and oculomotor systems. We sought to determine the effects of long-term spaceflight on sensing of spatial orientation. METHODS: Two cosmonauts participated in experiments on human vestibulo-visual interactions during a long-term mission (178 d) in the MIR station in 1995. During circular optokinetic stimulation (OKS) the tonic torsional eye position (torsional beating field, TBF) and the subjective visual vertical (SVV) were recorded on several days of the space mission as well as pre- and post-flight. A reference data set was obtained from healthy subjects on Earth, in whom the TBF was measured in upright and in prone positions. RESULTS: Neither cosmonaut showed changes in the SVV or the TBF values during the first days in microgravity. On flight day 149, cosmonaut A showed an increase of both values, which continued to rise by 4- and 10-fold until the end of the flight (TBF: 8.1 degrees; SVV: 216.8 degrees). This cosmonaut reported that the increase was accompanied by a loss of spatial orientation. In contrast, cosmonaut B's values remained at pre-flight levels (TBF: 1.6 degrees; SVV: 4.4 degrees). Post-flight values of the TBF did not significantly differ from pre-flight values for either cosmonaut. Subjects showed an increase of the TBF by more than a factor of 2 in prone position (range -7.7 degrees to +10.2 degrees) compared with upright position (range -3.7 degrees to +3.4 degrees). CONCLUSIONS: Pre-flight, post-flight and during the first part of the flight, both cosmonauts exhibited values similar to those of normal subjects in an upright position. The increased TBF values of cosmonaut A from flight day 110 on were within the range of the normal subjects in prone (face-down) position, when the gravity vector cannot be used to stabilize the TBF against the rotating stimulus (the axis of rotation is parallel to the gravity vector). The increasing deviations of cosmonaut A's SVV values in-flight suggest the presence of an internal body reference system, which weakened throughout the flight and thus lost its stabilizing effect.