Extracellular matrix-induced synthesis of a low molecular weight collagen by fetal calf ligament fibroblasts

Fetal calf ligamentum nuchae fibroblasts, cultured from animals of different gestational age, synthesize a unique, low molecular weight collagen termed FCL-1 (Sage, H., Mecham, R., Johnson, C., and Bornstein, P., 1983, J. Cell Biol. 97:1933-1938). Previous studies on the elastogenic differentiation of these cells in vitro demonstrated that the extracellular matrix (ECM) protein elastin was specifically induced in undifferentiated fibroblasts when they were grown on ligament ECM isolated from animals at later stages of development (Mecham, R.P., Madaras, J.G., and Senior, R.M., 1984. J. Cell Biol. 98:1804-1812). To investigate the expression of FCL-1 as a function of developmental age, we grew fetal calf ligament fibroblasts from an 85 d (first trimester) animal (FCL 85d) on three different substrata: ligament from a 120 d (second trimester) animal, ligament from a 270 d (term) animal, and unmodified plastic tissue culture dishes. FCL 270d fibroblasts were grown on plastic substrata and served as a differentiated cellular control. Analysis of metabolically radiolabeled proteins from both the culture media and the cell layers showed that the synthesis of FCL-1 was selectively increased in those cells cultured on ligament ECM. For FCL 85d fibroblasts grown on 120 d and 270 d ligaments, FCL-1 comprised 17% and 22%, respectively, of the culture medium proteins that precipitated at concentrations of ammonium sulfate from 20-50%. FCL 85d and 270d fibroblasts grown on plastic substrata yielded values of 2.5% and 1.0%, respectively. This effect appeared to be specific for this collagen and did not reflect a general increase in the synthesis of connective tissue proteins of the ECM (e.g., types I and III procollagen). As percent of total newly-synthesized cellular protein, the output of FCL-1 was 10-fold higher by FCL 85d cells grown on 270d ligament ECM (5.8%) as compared to that of the same cellular population grown on a plastic surface (0.56%). The presence of the ligament ECM also altered the levels and distribution of secreted proteins between the culture medium and the cell layer. These studies provide evidence for differential expression of the novel collagen FCL-1 by FCL fibroblasts during development and suggest that such expression is affected, at least in part, by interaction of the cell with a ligament ECM.     

U-80816: A novel partial muscarinic agonist

U-80816 (1-(4-(5-methyl-1H-imidazol-1-yl)-2-butynyl)-2-pyrrolidinone is an acetylenic amine which has been investigated as a partial agonist of muscarinic receptors. In vitro U-80816 inhibited binding of (³H)-N-methylscopolamine [(³H)-NMS] and (methyl-³H) oxotremorine-M acetate [³H)-Oxo-M] to the cortical membrance preparation with Ki's of 75 and 3.24 nM, respectively. In the M1 cell line, U-80816 increased phosphatidylinositol (Pl) hydrolysis. However, the maximum increase in the Pl hydrolysis was significantly (P < 0.01) less than oxotremorine and RS 86. Intraperitoneal administration of U-80816 dose-dependently increased striatal acetylcholine (ACh) concentration, and the effect was significant (P < 0.01) at 30 mg/kg. In the presence of hemicholinium-3 (HC-3), U-80816 inhibited the release of (³H)-ACh from hippocampal slices. On the other hand, in the presence of eserine, U-80816 increased the release of (³H)-ACh. In in vivo pharmacological tests, U-80816 produced hypothermia and tremors in mice. This compound failed to produce lacrimation or salivation in mice when administered up to 100 mg/kg. U-80816 antagonized oxotremorine-induced salivation. It is bioavailable to the brain in a significant amount after oral administration and has a sufficiently long duration of action. The in vitro and in vivo pharmacological investigations indicate that U-80816 is a partial agonist of muscarinic receptors.     

Teleophthalmology and the digital divide: inequities highlighted by the COVID-19 pandemic

The COVID-19 pandemic has brought an unprecedented change in the way we deliver eye care to our patients, most notably with the rapid addition of telehealth technology into our practices. We have welcomed telehealth with open arms in hopes that it would improve access to care for our patients; however, one question remains: Does it improve health equity?Subject terms: Public health, Risk factors     

Transurethral electrostimulation in the therapy of postoperative disorders of bladder emptying following extended hysterectomy

As a suitable method of the treatment of postoperative voiding disturbance following gynaecological surgery (hysterectomy) the indirect electrostimulation of detrusor vesicae is presented. It is possible with this method to treat the congenital (myelomeningocele) and the obtained (spinal cord dysfunction) but also the disturbances following hysterectomy successfully. In cases with such a hypotonic bladder the stimulation of the bladder wall is made with an intermittent application of exponential current so that sufficient contractions to the voiding will occur after the treatment.     

Hydralazine does not Ameliorate Nitric Oxide Resistance in Chronic Heart Failure

Purpose  

The A-HeFT trial demonstrated incremental survival with hydralazine/isosorbide dinitrate combination in African–American patients with chronic heart failure (CHF). It has been suggested that hydralazine might enhance nitric oxide (NO)—mediated effects of organic nitrates by decreasing superoxide (O₂⁻) formation, one of the factors inducing NO resistance. We evaluated whether hydralazine therapy potentiates nitrate-induced vasodilation and inhibition of platelet aggregation by ameliorating NO resistance.