Region-Specific Sex-Dependent Pattern of Age-Related Changes of Proximal Femoral Cancellous Bone and Its Implications on Differential Bone Fragility

Despite evident interest in age-related bone changes, data on regional differences within the proximal femur are scarce. To date, there has been no comprehensive study on site-specific age-related changes in the trabecular architecture of three biomechanically important femoral subregions (medial neck, lateral neck, and intertrochanteric region) for both genders. In this study we investigated age-related deterioration in the trabecular architecture of those three subregions of the femoral neck for both genders. The research sample included 52 proximal femora (26 males, 26 females; age range, 26–96 years) from Forensic Department at University of Belgrade. Bone sections from the three regions of interest were scanned by micro-CT at University of Hamburg. The study revealed that proximal femoral microarchitecture cannot be perceived as homogeneous and, more importantly, that the aging process is not uniform. Besides the initial intersite differences, microarchitecture changed differently with increasing age, maintaining significant differences between the regions. In addition, we observed a different aging pattern between genders: deterioration was most significant in the intertrochanteric region in women, while the lateral neck was most affected in men. This finding supports epidemiological data about the differential occurrence of cervical vs. trochanteric fractures in aging males and females. In conclusion, the aging process in the proximal femur cannot be regarded as a simple function of quantitative bone loss but, rather, as an alteration of specific architecture that may degrade bone strength.     

Abnormal fatty acid distribution of the serum phospholipids of patients with non-Hodgkin lymphoma

The data about the fatty acid (FA) status of non-Hodgkin lymphoma (NHL) patients are poor. Therefore, the aim of this study was to investigate the FA profile of serum phospholipids in NHL patients related to the aggressiveness and clinical stage of NHL. We analyzed the FA profile of serum phospholipids in 47 newly diagnosed, untreated NHL patients and in 29 healthy subjects. Significantly higher (p?<?0.001) levels of palmitic (16:0), oleic (18:1 n-9) and arachidonic acids (20:4 n-6), saturated and monounsaturated FA were found in NHL patients, while linoleic acid (18:2 n-6) and the levels of total polyunsaturated FA (PUFA), n-3 PUFA, eicosapentaenoic (20:5 n-3) and docosahexaenoic (DHA, 22:6 n-3) were significantly reduced (p?<?0.01). The level of oleic acid in patients with indolent NHL was significantly lower (p?<?0.05) than in more aggressive types of disease. Contents of palmitoleic acid, docosatetraenoic (22:4 n-6), and PUFA was lower in very aggressive NHL. According to clinical stage (CS), patients with CS I had significantly higher SFA and lower n-6 FA than other three groups, and group with CS IV showed significantly decreased DHA and n-3 PUFA. Our results showed an abnormal FA profile in serum phospholipids in NHL patients.     

Route-dependent effects of cadmium/cadmium and magnesium acute treatment on parameters of oxidative stress in rat liver

The study was designed to evaluate and compare the effects of single oral (or) and intraperitoneal (i.p.) cadmium (Cd) administration on parameters of oxidative stress in liver of rats. Furthermore, investigation on protective effects of magnesium (Mg) or and i.p. pretreatment on the same parameters was performed. Wistar rats were administrated oral dose of Cd (30 mg Cd/kg b.w.)/Cd+Mg (30 mg Cd/kg b.w., 50 mg Mg/kg b.w.) or i.p. dose of Cd (1.5 mg Cd/kg b.w.)/Cd+Mg (1.5 mg Cd/kg b.w., 3 mg Mg/kg b.w.) and sacrificed after 24 h. In liver homogenates superoxide anion, malondialdehyde, non-protein sulfhydryl groups, total sulfhydryl groups content, and superoxide dismutase activity were determined. Cadmium intoxication caused the increase of superoxide anion and malondialdehyde levels and had negative effect on investigated parameters of antioxidant defense system, except on total sulfhydryl groups. The negative effect was more emphasized after i.p. Cd administration. Oral Mg pretreatment induced more pronounced positive effect than Mg given intraperitoneally that can be attributed, at least partly, to Cd and Mg interactions on the level of GIT. On the basis of the obtained results it can be concluded that both Cd and Cd+Mg effects on parameters of oxidative stress in rats liver are route-dependent.     

Spatial working memory and problem solving in schizophrenia: the effect of symptom stabilization with atypical antipsychotic medication

Reasoning and problem solving in the spatial domain are important aspects of executive function that are reliably impaired in schizophrenia, and the Groton Maze Learning Test(c) (GMLT) provides a valid measure of spatial working memory. In the current study, 34 patients with first-episode schizophrenia and 20 matched controls were assessed for baseline spatial working memory abilities using this hidden maze learning test. Approximately one month after baseline assessment, allowing for symptoms to stabilize in response to treatment with therapeutic doses of atypical antipsychotic medications for individuals with schizophrenia, all participants were again assessed with the GMLT. Prior to pharmacologic intervention, patients with schizophrenia showed significant impairments in performance of all aspects of the GMLT, including measures of learning efficiency and error monitoring. One month of treatment was associated with a reliable improvement in these domains, although impairments in accuracy and error monitoring on this spatial working memory test persisted despite symptomatic improvement. These results indicate that impairments in spatial working memory are present at the earliest stages of the illness, and that such deficits in performance remain present, albeit ameliorated, after treatment with atypical antipsychotic medication.     

Anticancer properties of the novel nitric oxide-donating compound (S,R)-3-phenyl-4,5-dihydro-5-isoxazole acetic acid-nitric oxide in vitro and in vivo

Preclinical studies have shown that nitric oxide (NO)-donating nonsteroidal anti-inflammatory drugs possess anticancer activities. Here, we report in vitro and in vivo studies showing the antitumor effect of the NO-donating isoxazole derivative (S,R)-3-phenyl-4,5-dihydro-5-isoxazole acetic acid (GIT-27NO). GIT-27NO, but not the NO-deprived parental compound VGX-1027, significantly affected viability of both rodent (L929, B16, and C6) and human (U251, BT20, HeLa, and LS174) tumor cell lines. GIT-27NO triggered either apoptotic cell death (e.g., L929 cells) or autophagic cell death (C6 and B16 cells). Moreover, GIT-27NO hampered the viability of cisplatin-resistant B16 cells. NO scavenger hemoglobin completely prevented GIT-27NO-induced death, indicating that NO release mediated the tumoricidal effect of the compound. Increase in intracellular NO upon on the treatment was associated with intensified production of reactive oxygen species, whereas their neutralization by antioxidant N-acetylcysteine resulted in partial recovery of cell viability. The antitumor activity of the drug was mediated by the selective activation of mitogen-activated protein kinases in a cell-specific manner and was neutralized by their specific inhibitors. In vivo treatment with GIT-27NO significantly reduced the B16 melanoma growth in syngeneic C57BL/6 mice. The therapeutic effect occurred at dose (0.5 mg/mouse) up to 160 times lower than those needed to induce acute lethality (80 mg/mouse). In addition, a dose of GIT-27NO five times higher than that found effective in the melanoma model was well tolerated by the mice when administered for 4 consecutive weeks. These data warrant additional studies to evaluate the possible translation of these findings to the clinical setting.     

Bilateral juxtapapillary choroidal neovascularization secondary to Birdshot chorioretinopathy—case report

Central vision loss, photopsia, floaters, and macular edema in a highly myopic patient can easily be misinterpreted as high myopia complications. In atypical cases, detailed examination and a thorough diagnostic workup are required to establish the proper diagnosis, which is often beyond the scope of diagnoses initially considered.