The effect of choline-stabilized orthosilicic acid in patients with peri-implantitis: an exploratory randomized, double-blind, placebo controlled study.

BACKGROUND: Choline-stabilized orthosilicic acid (CS-OSA) was previously found to stimulate bone collagen formation in osteopenia and to improve biomarkers of cartilage degradation in knee osteoarthritis. The aim of the present study was to investigate the effect of oral administration of CS-OSA on clinical symptoms of peri-implantitis and the associated bone loss. METHODS: Twenty-one patients with peri-implantitis were randomized in CS-OSA or placebo groups. After initial clinical and cone beam computed tomography (CBCT) measurements [probing pocket depth (PPD), bleeding on probing (BOP), mucosal recession (REC), distance from implant shoulder to alveolar crest (IS-AC) and distance from implant shoulder to first bone-to-implant contact (IS-BIC)], flap operations were performed at the peri-implantitis sites. All patients were instructed to use either placebo or CS-OSA capsules twice a day for 1 year. Measurements were repeated 6 and 12 months after randomization. RESULTS: The data of 18 patients (36 implants) were used in the per protocol analysis. PPD and BOP improved significantly (p < 0.05) compared to baseline for both groups after 6 and 12 months. However, REC significantly increased in the placebo group but not in the CS-OSA group. The change in REC over 6 and 12 months was significantly different between groups (p < 0.01). IS-BIC and IS-AC measurements remained stable in the CS-OSA group whereas in the placebo group, both parameters increased significantly after 6 and 12 months. The change in IS-BIC over 12 months was significantly different between groups (p < 0.05). CONCLUSION: The results of this preliminary study suggest that CS-OSA may stabilize and even prevent further bone loss after surgical peri-implantitis treatment and support mucosal tissue healing. Trial registration The trial was retrospectively registered at ISRCTN registry, registration number: ISRCTN14348802, registration date: 24/06/2020.

Adrenergic signaling elements in the bladder wall of the adult rat.

A growing body of work is describing the absence of a significant sympathetic innervation of the detrusor implying little sympathetic regulation of bladder contractility. However, low doses of adrenergic agonists are capable of relaxing the bladder smooth muscle. If these effects underpin a physiological response then the cellular nature and operation of this system are currently unknown. The present immunohistochemistry study was done to explore the existence of alternative adrenergic signaling elements in the rat bladder wall. Using antibodies to tyrosine hydroxylase (TH) and vesicular mono-amine transporter (vmat), few adrenergic nerves were found in the detrusor although TH immunoreactive (IR) nerves were apparent in the bladder neck. TH-IR and vmat-IR nerves were however abundant surrounding blood vessels. A population of vmat-IR cells was found within the network of interstitial cells that surround the detrusor muscle bundles. These vmat-IR cells were not or only weakly TH-IR. This suggests that these interstitial cells have the capacity to store and release catecholamines that may involve noradrenaline. Cells expressing the ß1-adrenoceptor (ß1AR-IR) were also detected within the interstitial cell network. Double staining with antibodies to ß1AR and vmat suggests that the majority of vmat-IR interstitial cells show ß1AR-IR indicative of an autocrine signaling system. In conclusion, a population of interstitial cells has the machinery to store, release and respond to catecholamines. Thus, there might exist a non-neuronal ß-adrenergic system operating in the bladder wall possibly linked to one component of motor activity, micro-contractions, a system that may be involved in mechanisms underpinning bladder sensation.

The actions of isoprenaline and mirabegron in the isolated whole rat and guinea pig bladder.

ß3-adrenoceptor agonists influence overactive bladder in humans and animal models. However, data is emerging that the mode of action of these drugs is complex. The present study explored the actions of the ß3-adrenergic agonist mirabegron and the non-selective agonist isoprenaline on the contractile systems in the rat and guinea pig bladder. Intravesical pressure was measured in isolated whole bladders from female adult animals. In both species spontaneous contractile activity was observed. The muscarinic agonist arecaidine produced complex responses consisting of an initial transient pressure rise followed by complex phasic activity. Three contractile elements were identified: intrinsic micro-contractile activity, initial transient response and steady state phasic activity. The intrinsic and steady state activity could be further divided into a baseline pressure with superimposed phasic activity. The effects of isoprenaline and mirabegron were investigated on these elements. In the rat, the micro-contractile activity could be completely inhibited by isoprenaline (full agonist). The arecaidine-induced initial and steady state baseline pressures were partially reduced, while the phasic activity was little affected. In the guinea pig, both the arecaidine-induced baseline pressure and the phasic activity were affected by isoprenaline. Mirabegron didn't produce significant inhibitory effects in any of the contractile elements in either species. These results show that complex contractile systems operate in the rat and guinea pig bladder that can be modulated by ß1/ß2-adrenoceptor mechanisms. No evidence was obtained for any ß3-dependent regulation of contraction. These data support similar data in humans. Therefore the primary site of therapeutic action of ß3-adrenergic agonists remains unknown.

Possible role of the major pelvic ganglion in the modulation of non-voiding activity in rats.

AIMS: The existence of a motor-sensory system contributing to bladder sensation is now becoming widely accepted. Although it is clear that the motor component of this system appears to be generated within the bladder wall, recent observations suggest that the mechanisms involved in its modulation may lie outside the wall. The present study was undertaken to gain more insights into the peripheral modulation of non-voiding activity and the role of the major pelvic ganglion. METHODS: Male Sprague-Dawley rats anesthetized with urethane were used. The bladder was filled till 60% of the micturition threshold volume. The baseline pressure and the superimposed non-voiding activity were observed before and after consecutive bilateral transections of the hypogastric and pelvic nerves and bilateral ablation of the major pelvic ganglia. RESULTS: Hypogastric and pelvic nerve transection didn't significantly change the baseline pressure and superimposed non-voiding activity. Removal of the major pelvic ganglia resulted into an increased baseline pressure when compared with the control and increased amplitude of the non-voiding contractions when compared with both the decentralized condition (both hypogastric and pelvic nerves transected) and the control. The frequency of the non-voiding contractions wasn't affected. CONCLUSIONS: Non-voiding activity during the urine storage phase seems to be modulated at the level of the major pelvic ganglion. This suggests the possibility of local circuits between the bladder and the peripheral ganglia that may be responsible for an inhibitory component influencing non-voiding activity.

Mechanisms of pelvic organ cross-talk: impact of urethral ligation on the inhibitory rectovesical reflex.

PURPOSE: The existence of an inhibitory rectovesical reflex elicited by noxious colorectal afferent input was previously documented in an isovolumetric cystometry model with a ligated urethra. We compared the effect of noxious colorectal distension on bladder cystometry with an open and a ligated urethra. MATERIALS AND METHODS: We used female Sprague Dawley® rats anesthetized with urethane. The effect of noxious (60 mm Hg) colorectal distension on intermittent and continuous cystometry with an open urethra was studied and then compared to inhibiting isovolumetric bladder contractions in the same rat after ligating the urethra. We evaluated volume, the pressure micturition threshold, the intercontraction interval, bladder contraction frequency and amplitude of micturition contractions. RESULTS: Noxious colorectal distension at 60 mm Hg did not significantly influence volume or the pressure micturition threshold during intermittent cystometry. It also did not influence the pressure micturition threshold, the intercontraction interval or bladder contraction frequency during continuous cystometry. After urethral ligation 60 mm Hg colorectal distension inhibited isovolumetric bladder contraction frequency in the same rat (mean ± SEM 0.363 ± 0.207 vs 0.886 ± 0.106 contractions per minute, p <0.05). This inhibition persisted a mean of 289.08 ± 91.24 seconds after deflating the rectal balloon. CONCLUSIONS: The inhibitory rectovesical reflex elicited by noxious colorectal distension clearly occurred in an isovolumetric bladder model with a ligated urethra but only to a negligible extent in filling related voiding contractions. Our results suggest that the inhibitory rectovesical reflex, most likely at the level of the lumbosacral spinal cord, is the result of an additive noxious urethral and colonic afferent stimulus.