Anastomotic stoma coated with chitosan film as a betamethasone dipropionate carrier for peripheral nerve regeneration

Scar hyperplasia at the suture site is an important reason for hindering the repair effect of peripheral nerve injury anastomosis. To address this issue, two repair methods are often used. Biological agents are used to block nerve sutures and the surrounding tissue to achieve phys- ical anti-adhesion effects. Another agent is glucocorticosteroid, which can prevent scar growth by inhibiting inflammation. However, the overall effect of promoting regeneration of the injured nerve is not satisfactory. In this regard, we envision that these two methods can be combined and lead to shared understanding for achieving improved nerve repair. In this study, the right tibial nerve was transected 1 cm above the knee to establish a rat tibial nerve injury model. The incision was directly sutured after nerve transection. The anastomotic stoma was coated with 0.5 × 0.5 cm^2 chitosan sheets with betamethasone dipropionate. At 12 weeks after injury, compared with the con- trol and poly （D, L-lactic acid） groups, chitosan-betamethasone dipropionate film slowly degraded with the shape of the membrane still intact. Further, scar hyperplasia and the degree of adhesion at anastomotic stoma were obviously reduced, while the regenerated nerve fiber structure was complete and arranged in a good order in model rats. Electrophysiological study showed enhanced compound muscle action potential. Our results confirm that chitosan-betamethasone dipropionate film can effectively prevent local scar hyperplasia after tibial nerve repair and promote nerve regeneration.

Development of a topical ointment of betamethasone dipropionate loaded nanostructured lipid carrier

The purpose of this study was to design an innovative topical ointment containing betamethasone dipropionate loaded nanostructured lipid carrier (BD-NLC) for the treatment of atopic dermatitis (AD). BD-loaded NLC was produced with precirol ATO 5 and oleic oil (OA) by melt emulsification method. Effects of surfactant concentration, amount of solid lipid and liquid lipid on skin retention and skin penetration were investigated by in vitro percutaneous permeation experiment. The optimized BD-NLC showed a homogeneous particle size of 169.1 nm (with PI = 0.195), negatively charged surface (-23.4 mV) and high encapsulation efficiency (85%). Particle morphology assessed by TEM revealed a spherical shape. In vitro skin permeation study was carried out to investigate the percutaneous behaviors of W/O ointment with BD-NLC and Carbopol emulgel ointment with BD-NLC. W/O ointment with BDNLC showed high skin retention (35.43 μg/g) and low penetration (0.87 μg/ml). In vitro drug release studies were carried out to demonstrate the drug releasing properties of the two ointments. W/O ointment with BD-NLC showed an advantage for skin retention as it was better for drug release. The tissue distribution test suggested that BD distribution was skin > muscle > blood. Self-made topical ointment in mice showed no skin irritation. The animal experiments indicated that BD-loaded NLC ointment was effective and safe for topical use.

Efficacy and safety of low dose compound betamethasone in the treatment of mild knee osteoarthritis

Objective:To investigate the efficacy and safety of intra-articular injection of low-dose compound betamethasone in the treatment of mild knee osteoarthritis.Methods:From September 2018 to December 2019,90 patients with mild knee osteoarthritis were divided into complete dose group and low dose group according to the treatment sequence,45 cases in each group.The complete dose group was treated with intra-artiular injection of betamethasone(1ml)and sodium hyaluronate(2ml),once a week,three times as a course of treatment.The low dose group was treated with intra-artiular injection of betamethasone(0.3ml)and sodium hyaluronate(2ml),once a week,three times as a course of treatment.Lysholm scores、the Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)and visual analogue scale(VAS)were compared between the two groups before and after treatment,and the efficacy and safety of the two groups were evaluated.Results:80 patients were followed up with an average of(4.96±1.50)months ranging from 3 to 8 months,and 10 cases(11.11%)were dropped out,including 2 cases in the complete dose group,2 cases in the midway withdrawal group,and 1 case in the treatment course less than the treatment course;3 cases in the low dose group lost the follow-up,and 2 cases dropped out.Compared with that before treatment,Lysholm scores were significantly improved,WOMAC scores and VAS scores were significantly decreased in the two groups at 3 weeks,6 weeks and 12 weeks after treatment(P<0.001).The Lysholm scores of low dose group were78.10±2.16,86.78±2.55,80.90±2.26,WOMAC scores were 61.00±1.38,39.03±1.98,45.76±1.66 and VAS scores were 2.23±0.89,0.78±0.73 and 1.05±0.85 in low dose group at 3 weeks,6 weeks and 12 weeks after treatment.There was no significant difference between the two groups(P>0.05).No drugrelated adverse reactions occurred in both groups.Conclusion:The curative effect of low dose compound betamethasone intra-articular injection in the treatment of mild knee osteoarthritis is equivalent to that of complete dose compound betamethasone.It can improve the function and symptoms of knee joint,and is safe and effective.

Impact of Prophylactic Betamethasone Indication on the Neonatal Outcome in 38-Week Pregnancies Prior to Elective Cesarean Section

Objective: To assess whether the use of prenatal betamethasone in pregnancies with elective Caesarean section (C-section) at 38 weeks has a similar risk of adverse neonatal respiratory outcomes than elective C-section at 39 weeks. Methods: Retrospective cohort study of pregnant patients with singleton pregnancies and elective C-section at term in a one-year period. Cases were C-section at 38 weeks of gestation with a complete course of betamethasone started 48-hours before. As a control group, pregnancies with a C-section at 39 weeks without betamethasone were included. Results: During the study period, 186 patients were included. Of these, 91 were delivered at 38 weeks and 95 at 39 weeks. There were no significant differences in maternal age and parity. Moreover, there were no significant differences in respiratory complications (respiratory distress syndrome [RDS] = 0% vs 1.1%;p = 1.0, transitory tachypnea [TT] = 0% vs 0%) and admission to Neonatal Intensive Care Unit (NICU) (8.8% vs 6.3%;p = 0.7) between deliveries at 38 weeks and 39 weeks, respectively. Conclusion: Prophylactic use of betamethasone in early term pregnancies who undergo an elective C-section at 38 weeks is associated with similar adverse neonatal respiratory outcomes than patients with C-section at 39 weeks without corticosteroids.

A Formal Synthesis of Betamethasone

A formal synthesis of betamethasone from 5α-pregnane-3β,16β,20S-triol is described.Key transformations are a bromination-acetylation of triol,an SN2 reaction of the resulting C16α-bromide with dimethylcopperlithium to get the required C16β-methyl group,and a double hydroxylation to prepare the dihydroxyacetone side chain.

Rinderon(Betamethasone)点眼药的使用经验

自从皮质素合成以来,相继发现许多副作用少,且有效的合成肾上腺皮质激素,目前已成为眼科治疗不可缺少的药物。Betamethasone(商品名 Rinderon)为最新的制剂,其抗炎症作用为去氢氧化考地松的8～10倍,且其副作用较所有的皮质素制剂均少。作者等应用0.1%Betamethasone

Analgesic Effect of Diprospan in Rats with Trigeminal Neuralgia

This study examined the analgesic effect of diprospan in rats with trigeminal neuralgia.Rat model of trigeminal neuralgic pain was established by loosely ligating the left infraorbital branch of the trigeminal nerve.After allodynia developed,the rats were randomly divided into 2 groups（n=20 in each）：diprospan group,in which the rats received diprospan（7 mg/mL,0.1 mL） injected to the left infraorbital foramen area;control group,in which saline（0.1 mL） was administered as the same manner as the diprospan group.The pain threshold（PT） in the left infraorbital area was measured before and 2,6,and 8 weeks after the administration.The expression of neuropeptides [substance P,preprotachykinin A（PPTA）,calcitonin gene-related peptide（CGRP）] in the trigeminal nerve was detected at the same time points as the PT measurement by immunohistochemistry or in situ hybridization method.The results showed that in the diprospan group,the PT was 10.65±1.26,10.77±1.19 and 14.13±1.34 g 2,6,and 8 weeks after the administration respectively,significantly higher than that before the administration（PT value：0.36±0.11）（P0.05 for each）.In the saline group,the PT was 0.37±0.13,0.66±0.09,4.45±1.29 and 13.72±1.72 g before and 2,6,and 8 weeks after the administration respectively with differences being significant between before and 6,8 weeks after the administration（P0.01）.No significant difference existed in the PT between the diprospan group and the saline group at pre-administration（P0.05）.The PT in the diprospan group was significantly greater than that in the saline group 2 and 6 weeks post-administration（P0.05）.In the diprospan group,the expression levels of neuropeptides were significantly reduced as compared with those in the saline group 2 and 6 weeks post-administration（P0.05）.It was concluded that diprospan has an obvious analgesic effect on the trigeminal neuropathic pain partly by reducing the expression of neuropeptides in the trigeminal ganglia.

A Survey among Texas Pain Society Physicians Regarding the Types and Dosages of Steroids Utilized Clinically in Epidural Steroid Injectates

Objective: Epidural steroid injections (ESI) are used extensively to treat radicular back pain. This study is designed to evaluate the types and dosages of steroids commonly used and understand prescribing habits of the Texas Pain Society pain management physicians. Method: From April to May 2014, we sent all 270 Texas Pain Society members a questionnaire to complete online. We collected 45 responses. Result: Type of steroid commonly used in injectate: Eighteen (41.9%) phy-sicians reported using methylprednisolone most. Fifteen (34.9%) physicians use triamcinolone, 9 (20.9%) physicians use dexamethasone, 1 (2.3%) uses betamethasone, and 2 skipped this question. Important factors influencing the type of steroid use in injectate: Half of the physicians reported that the location of the ESI was most important (19 responses, 48.7%). Ten (25.6%) reported that the approach of the ESI was most important. Another ten (25.6%) agreed that the potency of the steroid was most important. Dosage of steroid used in injectate: About half of the physicians use a fixed dose of steroid (22, 51.2%) while 21 (48.8%) use a variable dose of steroid. Of those who use a fixed dose of steroid, many use methylprednisolone 80 mg (9, 39.1%). Of those who use a variable dosage of steroid, the most important factor in their determination of the dosage is the patient’s comorbidities (20 responses, 58.8%). The use of depo-steroid in injectate: Thirty-two out of 43 (74.4%) use depo-steroid while 11 out of 43 (25.6%) wouldn’t use depo-steroid. Of those who use depo-steroid, the duration and availability in the epidural space is the most common reason for its use (23, 76.7%). Conclusion: By using a simple questionnaire detailing what types and dosages of steroids are used, compiling a list of best practices can help Texas Pain Society physicians tremendously in the treatment of radicular back pain.

Use of antenatal corticosteroids among infants with gestational age at 24 to 31 weeks in 57 neonatal intensive care units of China: a cross-sectional study

Background:Antenatal corticosteroids(ACS)can significantly improve the outcomes of preterm infants.This study aimed to describe the ACS use rates among preterm infants admitted to Chinese neonatal intensive care units(NICU)and to explore perinatal factors associated with ACS use,using the largest contemporary cohort of very preterm infants in China.Methods:This cross-sectional study enrolled all infants born at 24^(+0)to 31^(+6)weeks and admitted to 57 NICUs of the Chinese Neonatal Network from January 1st,2019 to December 30th,2019.The ACS administration was defined as at least one dose of dexamethasone and betamethasone given before delivery.Multiple logistic regressions were applied to determine the association between perinatal factors and ACS usage.Results:A total of 7828 infants were enrolled,among which 6103(78.0%)infants received ACS.ACS use rates increased with increasing gestational age(GA),from 177/259(68.3%)at 24 to 25 weeks’gestation to 3120/3960(78.8%)at 30 to 31 weeks’gestation.Among infants exposed to ACS,2999 of 6103(49.1%)infants received a single complete course,and 33.4%(2039/6103)infants received a partial course.ACS use rates varied from 30.2%to 100%among different hospitals.Multivariate regression showed that increasing GA,born in hospital(inborn),increasing maternal age,maternal hypertension and premature rupture of membranes were associated with higher likelihood to receive ACS.Conclusions:The use rate of ACS remained low for infants at 24 to 31 weeks’gestation admitted to Chinese NICUs,with fewer infants receiving a complete course.The use rates varied significantly among different hospitals.Efforts are urgently needed to propose improvement measures and thus improve the usage of ACS.