OBJECTIVETo observe whether bladder controller can restore bladder function in paraplegic dogs.

METHODSFour dogs were studied after their T(10) spinal cord was transected. Electrodes implanted around S(2) bilaterally were connected to subcutaneous recievers. Microsurgical techniques were employed in dorsal rhizotomy at S(1 - 3) intradural segment. After daily stimulation, the results of bladder controller were evaluated by micturition and vesicography.

RESULTSMicturition was given under electrical stimulation with a urine volume of 80 - 140 ml per time. The mode of micturition was post-stimulus voiding. Vesicography showed that the bladder was filled and bladder neck was open in the micturition course of electric stimulation. Residual urine volume was 15 - 20 ml.

CONCLUSIONBladder controller together with a sacral deafferentation procedure can restore bladder function of paraplegic dogs.

Animals ; Disease Models, Animal ; Dogs ; Electric Stimulation ; Male ; Spinal Cord Injuries ; physiopathology ; surgery ; Urinary Bladder ; physiopathology ; surgery ; Urination

BACKGROUND: Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD. METHODS: This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied. RESULTS: At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs . placebo, 95% CI 31%-69%) and 45% (low vs . placebo, 95% CI 26%-64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator's Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. CONCLUSION CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.
Adult ; Humans ; Dermatitis, Atopic/drug therapy* ; Treatment Outcome ; Severity of Illness Index ; Antibodies, Monoclonal, Humanized/therapeutic use* ; Injections, Subcutaneous ; Double-Blind Method