Hypotensive effect of the active fragment derived from factor XII is mediated by an activation of the plasma kallikrein-kinin system

Plasma protein fraction (PPF) contaminated by factor XII active fragment (XIIf) may cause hypotensive reactions when infused to patients. This study was planned to assess in conscious normotensive rats whether the blood pressure response to the factor XIIf is mediated by an activation of the plasma kallikrein-kinin system or by stimulation of prostaglandin synthesis. To test whether the factor XIIf-induced blood pressure fall is due partially to an enhanced generation of vasodilating prostaglandins, the blood pressure effect of XIIf (1 microgram i.v.) was investigated 15 min after treatment with indomethacin (5 mg i.v.), an inhibitor of cyclo-oxygenase. Factor XIIf reduced mean blood pressure similarly in indomethacin- and vehicle-treated rats (-23 +/- 4 mmHg, n = 5, and -23 +/- 5 mmHg, n = 4, respectively). Other rats received factor XIIf 15 min after depletion of circulating prekallikrein by the administration of dextran sulfate. Thirty minutes after a 0.25 mg i.v. dose of this agent, plasma prekallikrein activity averaged 0.12 +/- 0.015 mumol/min/ml (n = 6) as compared to 2.48 +/- 0.31 mumol/min/ml in control rats (n = 4, P less than .001). Factor XIIf decreased mean blood pressure by only 4 +/- 2 mm Hg in rats pretreated with dextran sulfate. Thus, it was possible to blunt the acute hypotensive effect of factor XIIf by depleting circulating prekallikrein, but not by inhibiting prostaglandin production. This strongly suggests that the blood pressure effects of factor XIIf is mediated by a stimulation of the plasma kallikrein-kinin system.     

Immunoreactivity of an antibody to a beta/A4 sequence with Alzheimer paired helical filaments and tau protein.

beta/A4, a peptide that forms the extracellular amyloid fibrils of Alzheimer senile plaques, has also been proposed to be a component of Alzheimer paired helical filaments (PHFs). We compared BR88, an antiserum to amino acids 1-12 of beta/A4, with BR126, an antiserum to the sequence SEKLDFKDRVQS in tau protein, since tau protein is the only confirmed component of PHFs. In enzyme-linked immunosorbent assays (ELISAs), both antibodies reacted with pronase-treated PHFs better after PHFs were treated with guanidine. tau protein shares no sequence homology with beta/A4. Nevertheless, BR88 cross-reacted with human recombinant tau isoforms by ELISA and Western blot analysis with potencies comparable to those for anti-tau antibodies. BR88 reacted with a beta/A4 peptide as well on a molar basis as with tau protein and showed some reactivity to the tubulin-binding region of tau protein. In conclusion, the beta/A4 antiserum BR88 cross-reacts with tau protein, possibly explaining its reactivity with PHFs.     

Periocular involvement in cutaneous leishmaniasis

OBJECTIVE: Although cutaneous leishmaniasis (CL) occurs mostly in the facial area, periocular involvement accounts for 2-5% of the facial lesions. CL lesions localized in the periocular region can easily be confused with various other diseases. The aim of this study was to examine the frequency of periocular involvement in CL in the Cukurova region of Turkey, as well as the clinical characteristics, diagnosis and methods of treatment of this disease. METHODS: Between December 1998 and December 2004, patients who were diagnosed with CL were evaluated prospectively with respect to periocular involvement. RESULTS: From the 2066 patients evaluated with CL, 2622 lesions were identified. In 59 (2.9%) of these patients, a total of 66 (2.5%) lesions were located in the periocular area. Thirty-two (48.5%) of these lesions were of the papular type, 15 (22.7%) the nodulo-ulcerative type, 10 (15.2%) the plaque type, and nine (13.6%) the nodular type. Dacryocystitis was identified in four patients with periocular involvement. Over the follow-up period, no ocular or periocular deformities or complications developed in these patients. CONCLUSION: Patients suspected of CL should be evaluated and treated early in the course of their disease to prevent any permanent ocular or periocular deformities.     

Effects of the antimigraine compound zolmitriptan ('Zomig') on psychomotor performance alone and in combination with diazepam in healthy volunteers

Zolmitriptan (Zomig^TM) is a 5HT_1B/1D agonist which has the ability to cross the intact blood-brain barrier to access central as well as peripheral receptors. Because of the potential for central nervous system side effects, this randomized, double-blind, placebo-controlled, 6-period crossover study evaluated the effects of 2.5 and 5 mg doses of zolmitriptan on psychomotor performance and investigated any pharmacodynamic or pharmacokinetic interaction with diazepam. Twelve healthy volunteers received the following "treatments" as single doses: zolmitriptan 2.5 mg, zolmitriptan 5 mg, diazepam 10 mg, zolmitriptan 2.5 mg+diazepam 10 mg, zolmitriptan 5 mg+diazepam 10 mg and placebo. Pre-dose and at 1, 4, 8, and 24 h post-dose, the following validated battery of psychomotor tests was performed: Bond-Lader visual analogue scales (calmness, contentedness, and alertness factors), critical flicker fusion test, choice reaction time (recognition, motor, and total reaction times), finger-tapping test, number cancellation test and digit symbol substitution test. Plasma concentrations of zolmitriptan, its active metabolite, and diazepam and its active metabolites were measured at the same timepoints. Zolmitriptan 2.5 and 5 mg had no effect on psychomotor function when given alone. In contrast, diazepam 10 mg had profound effects, consistent with its sedative properties, but there was no synergism on concomitant administration of either dose of zolmitriptan. Plasma concentrations of zolmitriptan, diazepam, and their respective active metabolites were similar when the two drugs were given alone or in combination.     

Microstructure of the non-rapid eye movement sleep electroencephalogram in patients with newly diagnosed Parkinson's disease: effects of dopaminergic treatment.

We investigated non-rapid eye movement (non-REM) sleep in patients with newly diagnosed Parkinson's disease (PD) who had never previously received dopaminergic medication. There were no significant differences in the conventional sleep parameters between de novo patients with PD and a healthy control group, but the length of stage 1 sleep and the number of awakenings increased significantly upon administration of dopaminergic drugs. Analyzing the quantitative electroencephalogram (EEG), we observed a significant reduction in the low-delta frequency range and a nonsignificant increase in the sigma frequency range in de novo patients with PD. The dopaminergic medication also nonsignificantly reduced the low-delta and sigma frequencies, the latter to the level of the controls. Possible mechanisms that may account for the observed differences are discussed. It is suggested that Parkinson's disease as well as the application of dopaminergic drugs exerts a desynchronizing effect on the sleep EEG that is reflected in a disruption of sleep continuity.     

Quadriceps tendon and patellar ligament: Cryosectional anatomy and structural properties in young adults

Structural tensile properties analyses of 10-mm-wide central sections of quadriceps tendon-bone (QT-B) and bone-patellar ligament (B-PL) complexes from young male donors (mean age 24.9 years, range 19–32 years) were complemented by a cryosectional analysis: each QT-B complex was composed of the segment of the quadriceps tendon with the proximal half of the patella attached, each B-PL complex was composed of the distal half of the patella with the patellar ligament attached. A servohydraulic materials testing machine was used to assess ultimate failure load of 16 unconditioned and 16 preconditioned QT-B and B-PL complexes at an extension rate of 1 mm/s. Ligaments/tendons were preconditioned during 200 cycles from 50 to 800 N at 0.5 Hz. On cryosections the quadriceps tendons were significantly longer and thicker and exhibited a significantly larger bony attachment area than the patellar ligaments. Cross-sectional areas of 10-mm-wide, full-thickness, central parts of unconditioned quadriceps tendons were significantly greater and measured 64.6±8.4 mm² with respect to the cross-sectional area of patellar ligament, measuring 36.8±5.7 mm² (P<0.0025). Ultimate failure loads for unconditioned complexes resulted at 2173±618 N for QT-B complexes and at 1953±325 N for B-PL complexes (P=0.43). Ultimate failure load values measured 2353±495 N for preconditioned QT-B complexes and 2376±152 N for preconditioned B-PL complexes, respectively (P=0.77). Despite the fact that initial testing length, area of unconditioned QT-B and B-PL complexes were significantly different, displacement at ultimate load, energy to failure and total energy were not. In terms of ultimate tensile strength, the 10-mm-wide central part of the QT-B complex compared favourably to the tensile properties of the human femur-anterior cruciate ligament-tibia complex from a comparable young age group. The evidence from anatomic, cryosectional and structural properties analyses suggests that the QT-B complex may be a valuable and versatile adjunct to the surgeon's armamentarium in reconstructive cruciate ligament surgery.     

Special status of lateral clavicular fracture]

Fractures of the lateral clavicle have different biomechanical conditions compared with fractures of the medial and central third; they therefore demand different therapy. Some 237 patients with fractures of the clavicle were followed, of which 75 (33%) were located in the lateral third of the clavicle. At the 5-year follow-up after exclusively conservative treatment, good results were found for Neer types I and III and 3 J?ger/Breitner type IIb fractures, while 4 out of 13 J?ger/Breitner type II a fractures ended in pseudarthroses (31%). Conservative treatment is recommended for Neer types I and III, as well as for the more stable J?ger/Breitner type II b and old II a fractures. Therefore, a new bandage is presented. It prevents the posterior and upward dislocation of the proximal fragment by vertical compression and rotation of the distal fragment by fixation of the arm. Open reduction and internal fixation by preferably extraarticular implants is recommended for unstable and dislocated J?ger/Breitner type II a fractures. For fractures of the lateral clavicle, good results can be achieved when the instability is recognized and adequately treated.