97 research outputs found
Patient-Reported Ocular Disorders and Symptoms in Adults with Moderate-to-Severe Atopic Dermatitis: Screening and Baseline Survey Data from a Clinical Trial
Introduction: Patients with atopic dermatitis
(AD) have a greater risk of conjunctivitis and
other ocular surface disorders than the general
population. We evaluated the burden of ocular
surface disorders and related symptoms prior to
treatment initiation in adults with moderate-tosevere AD.
Methods: Patients were enrolled in a randomized, placebo-controlled, double-blinded,
phase 3 trial of dupilumab administered with
concomitant topical corticosteroids. At the
beginning of the screening period, all enrolled
patients completed a survey of ocular disorder
diagnoses received in the past year; at baseline,
patients completed a survey of frequency and
severity of ocular symptoms (discomfort, itching, redness, and tearing) experienced in the
past month.
Results: A total of 712 of 740 patients enrolled
in the trial provided responses to the survey. At
screening, 286 of 740 patients (38.6%) reported
having at least one ocular disorder in the past
year. At baseline, 499 of 712 respondents
(70.1%) reported having at least one symptom
within the past month. Of these patients, 4.4%,
6.0%, 5.5%, and 4.4%, respectively, reported
h
Caspase-3 dependent nitrergic neuronal apoptosis following cavernous nerve injury is mediated via RhoA and ROCK activation in major pelvic ganglion
Axonal injury due to prostatectomy leads to Wallerian degeneration of the cavernous nerve (CN) and erectile dysfunction (ED). Return of potency is dependent on axonal regeneration and reinnervation of the penis. Following CN injury (CNI), RhoA and Rho-associated protein kinase (ROCK) increase
in penile endothelial and smooth muscle cells. Previous studies indicate that nerve regeneration is hampered by activation of RhoA/ROCK pathway. We evaluated the role of RhoA/ROCK pathway in CN regulation following CNI using a validated rat model. CNI upregulated gene and protein expression of RhoA/ROCK and caspase-3 mediated apoptosis in the major pelvic ganglion (MPG). ROCK inhibitor (ROCK-I) prevented upregulation of RhoA/ROCK pathway as well as activation of caspase-3 in the MPG. Following CNI, there was decrease in the dimer to monomer ratio of neuronal nitric oxide synthase (nNOS) protein and lowered NOS activity in the MPG, which were prevented by ROCK-I. CNI lowered intracavernous pressure and impaired non-adrenergic non-cholinergic-mediated relaxation in the penis, consistent with ED. ROCK-I maintained the intracavernous pressure and non-adrenergic non-cholinergic-mediated relaxation in the penis following CNI. These results suggest that activation of RhoA/ROCK pathway mediates caspase-3 dependent apoptosis of nitrergic neurons in the MPG following CNI and that ROCK-I can prevent post-prostatectomy ED
Intratunical injection of autologous adipose stromal vascular fraction reduces collagen III expression in a rat model of chronic penile fibrosis
Previous studies have shown that the injection of adipose stem cells and stromal vascular fraction(SVF) into the tunica albuginea (TA) during the inflammatory phase in a rat model of Peyronie’s disease(PD) prevented the development of TA fibrosis. Our aim was to investigate whether local injection of SVF can reduce established fibrosis in a rat model of chronic phase of PD. Eighteen-male 12-wk-old Sprague-Dawley rats were divided in three equal groups: sham, PD without treatment (PD) and PD treated with SVF(PD-SVF). Sham rats underwent 2 injections of vehicle into the TA one month apart. PD rats underwent TGF-β1 injection and injection of vehicle one month later. PD-SVF rats underwent TGF-β1 injection followed by SVF (1-million cells) one month later. One month after the last treatment, the animals, n = 6 rats per group, underwent measurement of intracorporal and mean arterial pressure during electrostimulation of the cavernous nerve. Following euthanasia, penises were harvested for in-vitro study. Erectile function was not statistically significantly different between groups. PD animals developed subtunical areas of fibrosis and elastosis with upregulation of collagen III protein. These fibrotic changes were reversed after injection of SVF. We provide evidence that local injection of SVF reverses TA fibrosis in a rat model of chronic phase of PD
Conjunctivitis in dupilumab clinical trials
Background Dupilumab blocks the shared receptor component for interleukin (IL)-4
and IL-13. It is approved in the U.S.A. for patients aged ≥ 12 years with moderate-tosevere atopic dermatitis (AD) uncontrolled by topical prescription medicines or who
cannot use topical medicines, for patients in Japan whose AD is uncontrolled with
existing therapies, for patients with moderate-to-severe AD in Europe who are candidates for systemic therapy and for patients aged ≥ 12 years for maintenance treatment
of moderate-to-severe asthma uncontrolled with their current medicines. AD trials
have reported increased incidence of conjunctivitis for dupilumab vs. placebo.
Objectives To characterize further the occurrence and risk factors of conjunctivitis
in dupilumab clinical trials.
Methods We evaluated randomized placebo-controlled trials of dupilumab in AD
(n = 2629), asthma (n = 2876), chronic rhinosinusitis with nasal polyps
(CRSwNP) (n = 60) and eosinophilic oesophagitis (EoE) (n = 47).
Results In most AD trials, dupilumab-treated patients had higher conjunctivitis incidence than placebo controls. Higher baseline AD severity and previous history of conjunctivitis were associated with increased conjunctivitis incidence. Conjunctivitis was
mostly mild to moderate. Most cases recovered or resolved during the treatment period; two patients permanently discontinued dupilumab due to conjunctivitis or keratitis. Common treatments included ophthalmic corticosteroids, antibiotics, and
antihistamines or mast cell stabilizers. Most cases were diagnosed by the investigators.
In asthma and CRSwNP trials, the incidence of conjunctivitis was lower for both
dupilumab and placebo than in AD trials; dupilumab did not increase the incidence
compared with placebo. In the EoE trial, no patients had conjunctivitis.
Conclusions Conjunctivitis was more frequent with dupilumab treatment in most
AD trials. In dupilumab trials in other type 2 diseases, incidence of conjunctivitis was overall very low, and was similar for dupilumab and placebo. In AD, the
incidence of conjunctivitis was associated with AD severity and prior history of
conjunctivitis. The aetiology and treatment of conjunctivitis in dupilumab-treated
patients require further study
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