Decreased signal transduction in rat parotid cell aggregates during aging is not due to loss of alpha 1-adrenergic receptors

Specific binding of the agonist, 3H-epinephrine, and antagonist, 3H-prazosin, to alpha 1-adrenergic receptors in both intact and broken rat parotid cell preparations was measured as a function of age in Wistar rats. Agonist binding exhibited approximately tenfold weaker affinity (Kd approximately 10 nM) for both intact and broken cells than did the antagonist (Kd approximately 1 nM). In addition, Bmax for the agonist was only 25 to 50% of that of the antagonist (7-10 fmol/mg protein vs. 15-30 fmol/mg protein) in both preparations. Binding affinity decreased significantly between ages 3 and 24 months for the antagonist but not the agonist in both intact and broken cells. The number of binding sites did not change with age in intact cells when measured with either agonist or antagonist, or when measured with agonist in broken cells, but increased markedly (approximately two fold) with age in broken cells for the antagonist. The latter results support the hypothesis that the aged rat parotid cell exhibits a naturally occurring, post-alpha 1-adrenoreceptor defect in signal transduction.     

Reengineered salivary glands are stable endogenous bioreactors for systemic gene therapeutics

The use of critical-for-life organs (e.g., liver or lung) for systemic gene therapeutics can lead to serious safety concerns. To circumvent such issues, we have considered salivary glands (SGs) as an alternative gene therapeutics target tissue. Given the high secretory abilities of SGs, we hypothesized that administration of low doses of recombinant adeno-associated virus (AAV) vectors would allow for therapeutic levels of transgene-encoded secretory proteins in the bloodstream. We administered 10(9) particles of an AAV vector encoding human erythropoietin (hEPO) directly to individual mouse submandibular SGs. Serum hEPO reached maximum levels 8-12 weeks after gene delivery and remained relatively stable for 54 weeks (longest time studied). Hematocrit levels were similarly increased. Moreover, these effects proved to be vector dose-dependent, and even a dosage as low as 10(8) particles per animal led to significant increases in hEPO and hematocrit levels. Vector DNA was detected only within the targeted SGs, and levels of AAV copies within SGs were highly correlated with serum hEPO levels (r = 0.98). These results show that SGs appear to be promising targets with potential clinical applicability for systemic gene therapeutics.     

Incidence of exertional right ventricular wall motion abnormalities in patients with coronary artery disease

To evaluate the role of analysis of right ventricular function with exercise in patients with presumed coronary artery disease referred for radionuclide ventriculography, the records of 55 patients referred to our laboratory over a 19-month period were reviewed. All underwent rest and exercise first-pass radionuclide stress testing and cardiac catheterization within a period of four months. Three groups were identified: (1) patients with normal exercise right ventricular function (n = 24); (2) patients with exercise-induced right ventricular regional wall motion abnormalities (n = 15); and, (3) patients with abnormal resting right ventricular function without new exercise abnormalities (n = 16). Patients in each group were similar in age, sex, baseline left ventricular function, medication usage, and indication for study. The incidence of right coronary artery disease was identical in the three groups, as was the incidence of left ventricular functional abnormalities with exercise. Patients with proximal right coronary artery disease were more likely to have reduced left ventricular ejection fraction and more extensive coronary artery disease than those without disease at this site. We conclude that: (1) analysis of rest and exercise right ventricular function does not allow prediction of coronary anatomy in an unselected group of patients; (2) normal right ventricular function with exercise is compatible with extensive coronary artery disease, including proximal right coronary artery disease; and (3) abnormal exercise right ventricular function may be due to exertional left ventricular dysfunction in the absence of proximal right coronary artery disease.     

Wirksamkeit periduraler Steroidinjektionen in der Therapie von nichtradikulären chronischen Rückenschmerzen

Background

Chronic lumbar pain syndromes without neurological deficits are generated by a multitude of causes. Functional, morphological and psychosocial factors are discussed. In many cases a diseased intervertebral disc is found on radiological examination but the clinical relevance of these findings is not clear. For this study it was postulated that a diseased disc results in a local inflammatory reaction therefore causing pain and impairing treatability of patients. An epidural injection of steroids can reduce inflammation and therefore improve treatability and ultimately treatment outcome.

Methods

A double blind randomized prospective trial was carried out. Patients treated in hospital for a chronic lumbar pain syndrome without neurological deficits within a multimodal treatment program were screened for indications for an epidural steroid injection (e.g. diseased lumbar disc and intention to treat). Patients eligible for the study were randomized into two groups. The treatment group received an epidural injection of 80 mg triamcinolone and 8 ml bupivacaine 0.25?%. The control group received only an epidural injection of 8 ml bupivacaine 0.25?%.

Results

In both groups pain intensity and treatability showed a statistically significant improvement after the epidural injection. The differences between the control and treatment groups were small and not clinically relevant. A small subgroup might profit from the steroid injection. In addition the treatability was dependent on psychometric values and the long-term outcome from a reduction of muscular skeletal dysfunctions.

Discussion

After the epidural injection the decrease in pain and increase in treatability was statistically significant. The mechanism of the improvement is not clear and should be examined further. The epidural injection of a steroid in this subgroup of patients did not lead to a clinical improvement in the outcome.