Neonatal rigid-akinetic syndrome and dentato-olivary dysplasia

This report describes a male infant who presented since birth with rigidity and hypokinesia. Severe developmental delay, episodic central hypoventilation, and drug-resistant epilepsy progressively added to the extrapyramidal signs in the following months and led to the patient's death at 10 months of age. Neuroradiologic and neurometabolic evaluations were negative. Normal cerebrospinal metabolites excluded a defect in dopamine metabolism, and treatment with levodopa failed to improve his motor symptoms. Neuropathologic findings demonstrated dentato-olivary dysplasia. While isolated dentato-olivary dysplasia has been described in a few cases of Ohtahara syndrome, to our knowledge, the association with infantile parkinsonism has not been previously reported.     

Tolbutamide reduces glioma cell proliferation by increasing connexin43, which promotes the up-regulation of p21 and p27 and subsequent changes in retinoblastoma phosphorylation

Our previous work has shown that tolbutamide increases gap junctional permeability in poorly coupled C6 glioma cells and that this effect is similar and additive to that found with dbcAMP, a well-known activator of gap junctional communication. Furthermore, the increase in gap junctional communication promoted by tolbutamide or dbcAMP is concurrent with the inhibition of proliferation of C6 glioma cells. In the present work, we show that tolbutamide and dbcAMP increase the synthesis of the tumor suppressor protein Cx43 and that they decrease the level of Ki-67, a protein expressed when cells are proliferating. These effects were accompanied by a reduction in the phosphorylation of pRb, mainly on Ser-795, a residue critical for the control of cell proliferation. The decrease in the phosphorylation of pRb is not likely to be mediated by a reduction in the levels of D-type cyclins, since instead of decreasing the expression of cyclins, D1 and D3 increased slightly after treatment with tolbutamide or dbcAMP. However, the Cdk inhibitors p21 and p27 were up-regulated after treatment with tolbutamide and dbcAMP, suggesting that they would be involved in the decrease in pRb phosphorylation. When Cx43 was silenced by siRNA, neither tolbutamide nor dbcAMP were able to up-regulate p21 and consequently to reduce glioma cell proliferation, as judged by Ki-67 expression. In conclusion, tolbutamide and dbcAMP inhibit C6-glioma cell proliferation by increasing Cx43, which correlates with a reduction in pRb phosphorylation due to the up-regulation of the Cdk inhibitors p21 and p27.     

Tumor necrosis factor alpha drugs in rheumatoid arthritis: systematic review and metaanalysis of efficacy and safety

Background  

To analyse available evidence on the efficacy and safety of anti-TNFα drugs (infliximab, etanercept and adalimumab) for treating rheumatoid arthritis (RA).     

Carotid angioplasty with cerebral protection and stenting: report of 164 patients (194 carotid percutaneous transluminal angioplasties)

BACKGROUND: The introduction of cerebral protection devices with systematic stent placement has changed the nature of carotid artery stenosis treatment, reducing the immediate periprocedural complications and delayed restenosis. METHODS: We treated 164 patients with 194 carotid artery stenosis procedures; 92% of them were symptomatic patients. RESULTS: The morbidity rate of our series was 1.03% and the mortality was 1.9%. CONCLUSIONS: In the future, carotid stenosis treatment should perhaps be performed as a preventative measure and not used as a cure for full-blown symptoms. This could be effective in reducing the morbidity and mortality rates of this pathology.     

Reduced fitness of HIV-1 resistant to CXCR4 antagonists

HIV-1 strains with a syncytium-inducing phenotype that use CXCR4 (X4 strains) have been associated with faster disease progression and AIDS. Antiviral agents designed to block CXCR4 may prevent the emergence of X4 HIV strains but resistant strains that maintain the X4 phenotype can be raised by sequential passage in cell cultures. We have demonstrated that a laboratory adapted strain (NL4-3) and a cloned clinical isolate (CI-1) of HIV-1 cultured in the presence of the CXCR4 antagonist, AMD3100, became resistant to the compound without a change in co-receptor use. These strains became resistant through divergence with respect to the wild-type virus. Conversely, a clinical isolate made resistant to AMD3100 switched co-receptor use from X4 to R5 through a change in diversity from the original virus population. When dual infection competition/heteroduplex tracking assays were performed, all AMD3100-resistant strains, regardless of co-receptor use showed a significantly diminished fitness compared with the wild-type virus. Single virus infections, at a similar multiplicity of infection, also indicated that the wild-type strains possess better replicative ability than their corresponding resistant strains. Thus, viral resistance development to a CXCR4 antagonist such as AMD3100 is associated with reduced viral fitness.     

Involvement of cardiomyocyte survival-apoptosis balance in hypertensive cardiac remodeling

The balance between cell death and cell survival is a tightly controlled process, especially in terminally differentiated cells, such as the cardiomyocyte. Accumulating data support a role for cardiomyocyte apoptosis in the development of several cardiac diseases, including the transition from hypertensive compensatory hypertrophy to heart failure. This review briefly summarizes the status of the knowledge regarding the death-survival balance of cardiomyocytes in the context of hypertensive heart disease. Several molecular and cellular aspects as well as the most relevant pathophysiological implications are presented. Moreover, diagnosis tools under development and the possibilities for pharmacological intervention are also examined.     

Cell-surface-expressed HIV-1 envelope induces the death of CD4 T cells during GP41-mediated hemifusion-like events

Cells expressing the HIV-1 envelope glycoprotein complex (gp120/gp41, Env) induce the death of target cells either after cell-to-cell fusion or after cell-to-cell contact in a fusion-independent fashion. Here, we demonstrate that Env-induced death of single cells (including primary CD4 T cells) required gp120 and gp41 function. The gp41 peptide C34, which blocked syncytium formation, completely inhibited the death of single target cells by specifically acting on gp41 function. Moreover, Env-induced single cell death was exclusively observed in CD4 cells and was associated with specific gp41-mediated transfer of lipids from the membrane of Env-expressing cells to the target cell but not with detectable cytoplasm mixing (complete fusion). We conclude that after gp120 function, gp41 mediates close cell-to-cell contacts, thereby triggering cell death in single uninfected cells in the absence of detectable cell-to-cell fusion.