Survival of spermatogonial stem cells in the rat after split dose irradiation during LH-RH analogue treatment

A rat model has been created in which a single injection of an LH-RH analogue depot preparation (Zoladex, ICI 118630) produced a temporary interruption of the pituitary-gonadal axis. This effect applied during irradiation was investigated as a possible mechanism to protect the testis from radiation damage. A local testicular irradiation dose of 6.0 Gy was given either as a single dose or as a fractionated (2 X 3.0 Gy) dose at different time intervals ranging from 8 to 72 h. Stem cell survival was measured 11 weeks after irradiation by means of the repopulation index and the number of haploid cells (spermatids) measured by flow cytometry. Serum gonadotrophins and testosterone concentrations were measured to evaluate hormonal recovery. No significant differences were observed between serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone and the duration of the fractionation interval. Stem cell survival was higher following fractionated irradiation in comparison with the single dose. For the 8 h interval an increase in recovery ratio was found, amounting to a factor of 5 of the single dose value. The fluctuating pattern of the recovery curves indicated changes in radiosensitivity of stem cells. The combination of hormonal inhibition of spermatogenesis and fractionated irradiation led to a decrease in the absolute numbers of stem cells. However, the stem cell recovery curves were identical to those seen without hormonal inhibition. It was concluded that hormonal pretreatment with Zoladex during split dose irradiation had no protective effect on stem cell survival.     

The role of new vessels and macrophages in the development and resolution of edema following a cortical freeze lesion in the mouse

The role of an influx of macrophages and neovascularity in the resolution of vasogenic edema is not well defined. The inhibition of these processes with x-irradiation or parenteral corticosteroid administration was used to evaluate their contribution to the resolution of edema around a cortical freeze lesion in mice. The resorption of Evans blue, a marker of protein extravasation, was delayed in x-irradiated mice on the second day following a freeze lesion (p = 0.0075), which correlates with a delay in macrophage infiltration around the lesion. The specific gravity of the lesion and its border regions was significantly less in x-irradiated animals on day 7 than in controls (p = 0.00062), which correlates with a delay in new vessel formation around the lesion. Administration of corticosteroids from the time of production of the freeze lesion resulted in a specific gravity significantly less than control when measured eight days after the lesion (p = 0.01). Macrophages may participate by inhibiting the development of the macromolecular portion of vasogenic edema. The development of neovascularity correlates with the resorption of the aqueous portion of vasogenic edema. As with x-irradiation, corticosteroids administered from the time of freeze lesion inhibited the resorption of the aqueous portion of vasogenic edema, but they may suppress the spread of edema in this experimental model.     

Huntington's disease phenocopies are clinically and genetically heterogeneous

Huntington's disease (HD) classically presents with movement disorder, cognitive dysfunction and behavioral problems but is phenotypically variable. One percent of patients with HD‐like symptoms lack the causative mutation and are considered HD phenocopies. Genetic diseases known to cause HD phenocopies include HD‐like syndromes HDL1, HDL2, and HDL4 (SCA17). HD has phenotypic overlap with dentatorubral‐pallidoluysian atrophy, the spinocerebellar ataxias and neuroferritinopathy. Identifying the genetic basis of HD phenocopies is important for diagnosis and may inform the search for HD genetic modifiers. We sought to identify neurogenetic diagnoses in the largest reported cohort of HD phenocopy patients. Two hundred eighty‐five patients with syndromes consistent with HD, who were HD expansion‐negative, were screened for mutations in PRNP, JPH3, TBP, DRPLA, SCA1, SCA2, SCA3, FTL and FRDA. Genetic diagnoses were made in 8 subjects: we identified 5 cases of HDL4, 1 of HDL1 and 1 of HDL2. One patient had Friedreich's ataxia. There were no cases of DRPLA, SCA1, SCA2, SCA3, or neuroferritinopathy. HD phenocopies are clinically and genetically diverse and a definitive genetic diagnosis is currently possible in only a minority of cases. When undertaken, it should be clinically directed and patients and clinicians should be prepared for the low probability of reaching a genetic diagnosis in this group of patients. © 2008 Movement Disorder Society     

Posttraumatische Rekonstruktionen am Rückfuß

Trauma und Berufskrankheit - Die posttraumatische Arthrose des Rückfußes geht typischerweise mit Fehlstellungen des Rückfußes und/oder der benachbarten Gelenke einher. Ziel der...