DNA sequence variations in the prolyl isomerase Pin1 gene and Alzheimer's disease

Senile plaques and neurofibrillary tangles (NFT) are the prominent lesions in the brain of Alzheimer's disease (AD) patients. NFT are mainly composed of an abnormally phosphorylated form of tau protein, which has lost its function to bind microtubules and promote their assembly. Tau hyperphosphorylation critically decreases tau function and precedes neurodegeneration. The majority of tau phosphorylation sites are Ser/Thr-Pro motifs, which are known to exist in two distinct cis and trans conformations. The prolyl isomerase Pin1 catalyses the conversion of those conformations. Pin1 binds to tau specifically at the Thr231-Pro site and restores tau function, either by inducing conformational changes or facilitating dephosphorylation. It has been shown that Pin1 expression levels inversely correlate with the predicted vulnerability of different brain areas to neurodegeneration and soluble Pin1 is depleted in neurons from AD brains; furthermore, Pin1 knock-out mice develop signs and symptoms of tau-related pathologies late in life. It seems that Pin1 plays an important role in maintaining tau function, thereby preserving neuronal homeostasis and preventing age-dependent neurodegeneration. DNA sequence variations in Pin1 gene may affect its expression level or function and influence the individual risk for developing AD. We screened by denaturing high performance liquid chromatography the genomic DNA of 120 AD subjects and 134 age-matched controls and we found very few and rare sequence variations in the promoter region and in exons 2 and 3. We conclude that Pin1 is a very well conserved gene, whose rare nucleotide variations have no effect on the individual genetic risk for AD.     

Cognitive impairment and chronic alcohol abuse: A neuropsychological study

Twenty-eight chronic alcoholic subjects were submitted to our Mental Deterioration Battery. The scores obtained by this group, corrected for age and educational level, were compared with those achieved by a control group. Our data do not confirm a selective impairment of the functions related to the right hemisphere; they show a diffuse cerebral damage and suggest, perhaps, a major impairment of the verbal functions subserved by the left hemisphere. Therefore, according to our data the question of selective hemispheric impairment as opposed to more diffuse cerebral damage in chronic alcoholism still remains open.     

ON THE REACTION OF ACETAMIDOMETHANOL WITH NATIVE AND REDUCED BOVINE PANCREATIC TRYPSIN INHIBITOR (KUNITZ INHIBITOR)

The stability of native and reduced bovine pancreatic trypsin inhibitor (Kunitz inhibitor) in anhydrous hydrogen fluoride and their reaction with acetamidomethanol, in the same solvent, have been investigated. The bovine Kunitz inhibitor appears to be stable in liquid hydrogen fluoride but the reduced molecule loses about 50% of its ability to regain inhibitory power, upon air oxidation, by exposure to this solvent. Tyrosine residues appear to be affected by acetamidomethylation of the native protein to give a modified inhibitor which is still highly active in inhibiting trypsin. The extent of correct refolding, upon reoxidation, of the reduced tyrosine modified-inhibitor is greatly diminished. Tyrosine modification can be prevented by carrying out the acetamidomethylation reaction in the presence of excess anisole. The stability constants and the standard free energies of binding of the complexes between trypsin and the native and the tyrosine modified-inhibitor have been determined.     

Paroxysmal positional vertigo as a complication of osteotome sinus floor elevation

Paroxysmal positional vertigo (PPV) is a high prevalence, vestibular end organ disorder due to the detachment of the utricular otoconia floating in the posterior or lateral semicircular canal. Even though in the majority of cases the etiology of PPV is unknown, it may follow viral infection, vascular disorders and head trauma after different surgical procedures. The aim of this study was to investigate the correlation between PPV and the surgical trauma induced by the vibratory and percussive forces on the upper maxilla during the osteotome sinus floor elevation procedure. We performed a complete otoneurological examination on 146 patients affected by atrophic ridges before and after upper maxilla surgery. Four patients showed a PPV of the posterior semicircular canal controlateral to the implanted side 1 or 2 days after the surgical procedure, which promptly was solved with the Epley re-positioning maneuver. We hypothesize that the surgical trauma, and specifically the pressure exerted by the osteotomes, determines the detachment of the otoliths from the utricular macula while the patient head position, hyper-extended and tilted opposite to the side where the surgeon is working, favors the entry of these free-floating particles in the posterior semicircular canal of the implanted side. Although this disease is rather frequent in the normal population and it is a benign, self-limiting peripheral disorder, it should be considered by the oral surgeon as a possible complication of pre-prosthetic upper maxilla surgery, and the patient should be informed before undergoing surgery.