The Effect of Prednisolone? upon the Metabolism and Action of 25-Hydroxy and 1,25-Dihydroxyvitamin D3

Treatment of vitamin D-deficient rats with Prednisolone(R) does not alter the rate of conversion of [(3)H]25-hydroxyvitamin D(3) to [(3)H]1,25-dihydroxyvitamin D(3), but the further conversion of [(3)H]1,25-dihydroxyvitamin D(3) to a more polar metabolite is more rapid in the Prednisolone(R)-treated animals. This more polar metabolite is biologically inactive, periodate-insensitive, and persists in the intestine as long as 1,25-dihydroxyvitamin D(3). Also, the time course of action of 1,25-dihydroxyvitamin D(3) upon intestinal calcium transport is altered by Prednisolone(R) treatment. Treatment with Prednisolone(R) did not change the magnitude of the initial response to 1,25-dihydroxyvitamin D(3) at 7 hr, but did decrease the response at 24 and 48 hr after a single dose of 1,25-dihydroxyvitamin D(3). The present results show that one of the means by which large doses of adrenal corticoids alter intestinal calcium transport is by stimulating the further metabolism of 1,25-dihydroxyvitamin D(3) to a more polar, biologically inactive intestinal metabolite.     

Response to: Human papillomavirus (HPV) vaccine safety concerning POTS,CRPS and related conditions

Clinical Autonomic Research -     

Reciprocal potentiating action of depolarizing drugs on the isolated frog rectus abdominis muscle

Subthreshold concentrations of the depolarizing agents, acetylcholine and decamethonium, potentiated isotonic contractures of the isolated frog rectus abdominis muscle elicited by effective doses of either of these drugs or by choline in the absence of the anticholinesterases, sarin, or dyflos. Comparable potentiation of the contracture produced by decamethonium or choline could be obtained by alternate stimulation with acetylcholine in the absence of dyflos or sarin. Furthermore, dyflos alone did not effect potentiation in the absence of alternate stimulation with acetylcholine. Finally, the inhibitory action of tubocurarine, as measured by depression of the contracture elicited by decamethonium and acetylcholine, was not antagonized by sarin. It was concluded that the enhancement of the response to acetylcholine produced by dyflos and by sarin was brought about exclusively by their action as inhibitors of cholinesterase. The ability of dyflos and of sarin to potentiate contractures elicited by decamethonium or by choline may be attributed to a facilitation of the action of the depolarizing compounds by subthreshold concentrations of acetylcholine available in the presence of these anticholinesterases.     

Pluripotent stem cells engrafted into the normal or lesioned adult rat spinal cord are restricted to a glial lineage

Proliferating populations of undifferentiated neural stem cells were isolated from the embryonic day 14 rat cerebral cortex or the adult rat subventricular zone. These cells were pluripotent through multiple passages, retaining the ability to differentiate in vitro into neurons, astrocytes, and oligodendrocytes. Two weeks to 2 months after engraftment of undifferentiated, BrdU-labeled stem cells into the normal adult spinal cord, large numbers of surviving cells were seen. The majority of the cells differentiated with astrocytic phenotype, although some oligodendrocytes and undifferentiated, nestin-positive cells were detected; NeuN-positive neurons were not seen. Labeled cells were also engrafted into the contused adult rat spinal cord (moderate NYU Impactor injury), either into the lesion cavity or into the white or gray matter both rostral and caudal to the injury epicenter. Up to 2 months postgrafting, the majority of cells either differentiated into GFAP-positive astrocytes or remained nestin positive. No BrdU-positive neurons or oligodendrocytes were observed. These results show robust survival of engrafted stem cells, but a differentiated phenotype restricted to glial lineages. We suggest that in vitro induction prior to transplantation will be necessary for these cells to differentiate into neurons or large numbers of oligodendrocytes.     

Evaluation of Sagittal Spinopelvic Balance in Spinal Cord Stimulator Patients

ObjectiveSpinal cord stimulation (SCS) has become a popular nonopioid pain intervention. However, the treatment failure rate for SCS remains significantly high and many of these patients have poor sagittal spinopelvic balance, which has been found to correlate with increased pain and decreased quality of life. The purpose of this study was to determine if poor sagittal alignment is correlated with SCS treatment failure.Materials and MethodsComparative retrospective analysis was performed between two cohorts of patients who had undergone SCS placement, those who had either subsequent removal of their SCS system (representing a treatment failure cohort) and those that underwent generator replacement (representing a successful treatment cohort). The electronic medical record was used to collect demographic and surgical characteristics, which included radiographic measurements of lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS). Also included were data on pain medication usage including opioid and nonopioid therapies.ResultsEighty-one patients met inclusion criteria, 31 had complete removal, and 50 had generator replacements. Measurement of sagittal balance parameters demonstrated that many patients had poor alignment, with 34 outside normal range for LL (10 vs 24 in removal and replacement cohorts, respectively), 30 for PI (12 [38.7%] vs 18 [36.0%]), 46 for PT (18 [58.1%] vs 28 [56.0%]), 38 for SS (18 [58.1%] vs 20 [40.0%]), and 39 for PI-LL mismatch (14 [45.2%] vs 25 [50.0%]). There were no significant differences in sagittal alignment parameters between the two cohorts.ConclusionsThis retrospective cohort analysis of SCS patients did not demonstrate any relationship between poor sagittal alignment and failure of SCS therapy. Further studies of larger databases should be performed to determine how many patients ultimately go on to have additional structural spinal surgery after failure of SCS and whether or not those patients go on to have positive outcomes.