Effects of Lovastatin Alone or Combined with Irradiation on Tumor Cells in Vitro and in Vivo

PURPOSE: To evaluate the effect of lovastatin alone or combined with radiation on U87MG and FaDu cells in vitro and U87MG tumors in vivo. MATERIAL AND METHODS: Cell number, p21(WAF1) expression, apoptosis, reproductive cell death, and cell-cycle distribution were investigated after incubation of U87MG and FaDu cells in vitro. The effect of lovastatin (50 mg/kg/day) on tumor growth and on tumor growth delay after single-dose irradiation with 20 Gy was investigated using U87MG tumors in nude mice. RESULTS: Lovastatin dose dependently decreased cell number and proliferation of U87MG and FaDu cells. The proportion of cells in G0/G1 phase, apoptosis and p21 protein expression increased after lovastatin alone or combined with 4-Gy irradiation in both cell lines. Effects of lovastatin on cell cycle and cell number were more pronounced in U87MG compared to FaDu. No radiosensitization of clonogenic cells by lovastatin could be demonstrated in both cells lines, but the colony-forming ability after lovastatin alone was decreased in FaDu cells. In vivo, lovastatin decreased tumor volume over time but did not increase growth delay after irradiation of U87MG tumors with 20 Gy. CONCLUSION: The data support effects of lovastatin on proliferation, apoptosis and colony-forming ability in vitro and tumor volume in vivo. At the drug concentration achievable, lovastatin did not improve the effects of radiation on U87MG tumors in vivo.     

Reduced genital sensitivity in female patients with multiple system atrophy of parkinsonian type.

According to the consensus statement on the diagnosis of multiple system atrophy (MSA), erectile dysfunction is required for male patients to fulfil the urinary incontinence criterion. However, there is no equivalent item for female patients. We questioned 19 female patients with MSA of the parkinsonian type (MSA-P), 28 female patients with Parkinson's disease (PD), and 27 healthy controls on their genital sensitivity. A total of 47% of the MSA patients but only 4% of the PD patients and 4% of the control group admitted to reduced genital sensitivity, a highly significant difference (P < 0.001). Moreover, the appearance of reduced genital sensitivity in female MSA patients showed a close temporal relation to the onset of the disease. If these preliminary results can be confirmed and further specified in a larger sample, a historical item of reduced genital sensitivity in female patients might become a diagnostic feature for MSA, comparable to erectile dysfunction in male patients.     

Effects of graft pooling of foetal rat and mouse tissue and immunosuppression in the 6-hydroxydopamine rat model of Parkinson’s disease

 We employed intracerebral co-transplantation of foetal xenogeneic striatal mouse tissue and allogeneic rat substantia nigra into the adult rat brain to elucidate the effects of xenogeneic mouse graft on the function and survival of an allogeneic rat graft in 6-hydroxydopamine lesioned Sprague-Dawley rats. Foetal mouse striatum (STR) and rat substantia nigra (VM) were transplanted as non-pooled separate deposits or a pooled cell suspension with or without cyclosporin A (Cy A). Immunosuppressed recipients of pooled rat and mouse co-grafts showed a significantly better compensation of amphetamine-induced rotational behaviour compared with non-immunosuppressed animals with pooled rat and mouse co-grafts 3 and 6 weeks post-grafting.Tyrosine hydroxylase (TH) immunohistochemistry revealed a non-significant reduction in survival in pooled (1806.3±367.5 cells) rat and mouse co-transplants without immunosuppression compared with immunosuppressed pooled (3383.3±732.7 cells) animals with allo- and xenogeneic tissue and controls (3506.4±839.3 cells). Graft volumes were significantly reduced in pooled transplants without immunosuppression (0.1±0.026 mm³; ANOVA post-hoc SchefféF-test, P<0.0001) compared with immunosuppressed recipients (0.7±0.1 mm³) and controls (0.6±0.1 mm³). In non-pooled allo- and xenogeneic grafts without immunosuppression the survival rate of the TH-immunoreactive cells and graft volumes were reduced (2359.3±479.5 cells; 0.2±0.043 mm³) compared with immunosuppressed animals (2927.3±946.6 cells; 0.6±0.2 mm³) and controls (2701.1±693.8 cells; 0.3±0.1 mm³) without reaching a level of significance. Rejection of mouse tissue was observed in all non-immunosuppressed recipients. In summary: (i) continued immunosuppression yielded significant beneficial effects on function and beneficial effects on survival of pooled grafts with an immunogenetic disparity; (ii) the rejection of a xenogeneic graft component may compromise survival and function of other, allogeneic graft components; and (iii) transplantation of non-pooled allo- and xenogeneic tissues may result in a better survival of the graft compared with pooled cell suspensions. Received: 25 March 1996 / Accepted: 1 December 1996     

Role of DAT‐SPECT in the diagnostic work up of Parkinsonism

The diagnosis of idiopathic Parkinson's disease (PD) can be achieved with high degrees of accuracy in cases with full expression of classical clinical features. However, diagnostic uncertainty remains in early disease with subtle or ambiguous signs. Functional imaging has been suggested to increase the diagnostic yield in parkinsonian syndromes with uncertain clinical classification. Loss of striatal dopamine nerve terminal function, a hallmark of neurodegenerative Parkinsonism, is strongly related to decreases of dopamine transporter (DAT) density, which can be measured by single photon emission computed tomography (SPECT). The use of DAT‐SPECT facilitates the differential diagnosis in patients with isolated tremor symptoms not fulfilling PD or essential tremor criteria, drug‐induced, psychogenic and vascular Parkinsonism as well as dementia when associated with Parkinsonism. This review addresses the value of DAT‐SPECT in early differential diagnosis, and its potential as a screening tool for subjects at risk of developing PD as well as issues around the assessment of disease progression. © 2007 Movement Disorder Society     

Coralline hydroxyapatite bone graft substitutes: preliminary report of radiographic evaluation

A new bone graft substitute made by conversion of the calcium carbonate exoskeleton of reef-building sea coral into hydroxyapatite has recently become clinically available. The normal radiographic appearance of two forms of this material is described. In the immediate postoperative period, the exoskeletal architecture of these implants is readily appreciated. With graft incorporation over the ensuing months, their intrinsic structure is gradually lost in association with poor marginal definition. Evolving radiographic findings reflect the biocompatible nature of these implants, which provides the potential for ingrowth of native bone with preservation of the coralline scaffold, resulting in enhanced biomechanical properties.