Severe instability despite a constrained knee prosthesis with central stabilizer:A case report

We report on the clinical failure of a constrained total condylar knee with a central stabilizer in a revision case. The knee was very unstable, with a valgus deviation of more than 45°. At surgery, the instability was normalized, but the valgus deviation recurred during the first year.     

The hemodynamic effects of triglycyl-lysine-vasopressin (Glypressin) in patients with parkinsonism and orthostatic hypotension

The hemodynamic effects of triglycyl-lysine-vasopressin (TGLVP) were investigated in a single-blind study in seven patients with chronic orthostatic hypotension and parkinsonism. Blood pressure, heart rate, and stroke volume were measured in the supine position before and after bolus injection of either placebo or TGLVP (5.0, 7.5, or 10.0 micrograms/kg of body weight). After 40 min in the supine position, the patients were head-up tilted to 45 degrees for 20 min. All patients underwent four tilt studies with different medication. The TGLVP increased supine blood pressure by approximately 25% and total peripheral resistance by approximately 46%, and reduced heart rate by approximately 13%. No changes in supine stroke volume or cardiac output were seen. The TGLVP slightly reduced the relative fall in blood pressure and increased heart rate during the tilt. After TGLVP, blood pressure levels during tilt were similar to supine levels prior to medication. The TGLVP did not change the effects of tilt on stroke volume or cardiac output. Only few and mild side effects were experienced and no cardiotoxic effects were observed. In conclusion, TGLVP showed marked blood pressure effects of very small doses in this category of patients. The clinical effects of TGLVP and other vasopressor-specific analogs of vasopressin should be tested in these patients.     

Diversity of Francisella tularensis Schu4 antigens recognized by T lymphocytes after natural infections in humans: identification of candidate epitopes for inclusion in a rationally designed tularemia vaccine

The T lymphocyte antigens, which may have a role in protection against tularemia, were predicted by immunoinformatics analysis of Francisella tularensis Schu4. Twenty-seven class II putative promiscuous epitopes and 125 putative class I supertype epitopes were chosen for synthesis; peptides were tested in vitro for their ability to bind HLA and to induce immune responses from PBMCs of 23 previously infected subjects. While the immune responses of individual subjects showed heterogeneity, 95% of the subjects responded strongly to a pool of 27 promiscuous peptides; 25%, 33%, and 44% of subjects responded to pools of 25 A2, A24, and B7 peptides, respectively. These data can aid in the development of novel epitope-based and subunit tularemia vaccines.     

Antioxidants modulate mitochondrial PKA and increase CREB binding to D-loop DNA of the mitochondrial genome in neurons

The protein kinase A (PKA) and the cAMP response element (CRE) binding protein (CREB) signaling pathways mediate plasticity and prosurvival responses in neurons through their ability to regulate gene expression. The PKA-CREB signaling mechanism has been well characterized in terms of nuclear gene expression. We show that the PKA catalytic and regulatory subunits and CREB are localized to the mitochondrial matrix of neurons. Mitochondrial CRE sites were identified by using both serial analyses of chromatin occupancy and chromatin immunoprecipitation. Deferoxamine (DFO), an antioxidant and iron chelator known to inhibit oxidative stress-induced death, activated mitochondrial PKA and increased mitochondrial CREB phosphorylation (Ser-133). DFO increased CREB binding to CRE in the mitochondrial D-loop DNA and D-loop CRE-driven luciferase activity. In contrast, KT5720, a specific inhibitor of PKA, reduced DFO-mediated neuronal survival against oxidative stress induced by glutathione depletion. Neuronal survival by DFO may be, in part, mediated by the mitochondrial PKA-dependent pathway. These results suggest that the regulation of mitochondrial function via the mitochondrial PKA and CREB pathways may underlie some of the salutary effects of DFO in neurons.