Clinical pharmacokinetics and pharmacodynamics of oral systemic nonbiologic therapies for psoriasis patients.

INTRODUCTION: Psoriasis is a chronic inflammatory immune condition. Treatments for psoriasis vary with disease severity, ranging from topicals to systemic biologic agents. The pharmacokinetic (PK) and pharmacodynamic (PD) properties of these therapies establish drug efficacy, toxicity, and optimal dosing to ensure therapeutic drug levels are sustained and adverse effects are minimized. AREAS COVERED: A literature search was performed on PubMed, Google Scholar, and Ovid MEDLINE for PK and PD, efficacy, and safety data regarding oral systemic nonbiologic therapies utilized for moderate-to-severe plaque psoriasis. The findings were organized into sections for each drug: oral acitretin, methotrexate, cyclosporine, apremilast, tofacitinib, and deucravacitinib. EXPERT OPINION: Some psoriasis patients may not respond to initial therapy. Ongoing research is evaluating genetic polymorphisms that may predict an improved response to specific medications. However, financial and insurance barriers, as well as limited genetic polymorphisms correlated with treatment response, may restrict the implementation of genetic testing necessary to personalize treatments. How well psoriasis patients adhere to treatment may contribute greatly to variation in response. Therapeutic drug monitoring may help patients adhere to treatment, improve clinical response, and sustain disease control.

Organization of the ectodermal nervous structures in jellyfish: scyphomedusae.

Antibodies to α- or ß-tubulin and to the bioactive peptide FMRFamide were used to investigate the organization of the ectodermal nervous structures in five species of scyphomedusae. Within the swim system, morphological evidence, including a developmental sequence, suggests that the tubulin-immunoreactive nerve net in the subumbrella is the Giant Fiber Nerve Net (Motor Nerve Net) that directly activates the swim musculature, and the FMRFamide-immunoreactive nerve net is the Diffuse Nerve Net that serves a sensory function and also enhances swim muscle activity. Similar dual labeling was found in other structures, including those involved in feeding and protective reactions (pedalia and tentacles, radial strips of smooth muscle), and in the exumbrella, where the networks were associated with batteries of nematocysts. In addition, FMRFamide immuno-staining in the rhopalia and rhopalial niches suggests that sensory components of these networks may aid in the gravitational sense of scyphomedusae.

Organization of the ectodermal nervous structures in medusae: cubomedusae.

At least two conducting systems are well documented in cubomedusae. A variably diffuse network of large neurons innervates the swim musculature and can be visualized immunohistochemically using antibodies against α- or ß-tubulin. Despite the non-specificity of these antibodies, multiple lines of evidence suggest that staining highlights the primary motor networks. These networks exhibit unique neurite distributions among the muscle sheets in that network density is greatest in the perradial frenula, where neurites are oriented in parallel with radial muscle fibers. This highly innervated, buttress-like muscle sheet may serve a critical role in the cubomedusan mechanism of turning. In scyphomedusae, a second subumbrellar network immunoreactive to antibodies against the neuropeptide FMRFamide innervates the swim musculature, but it is absent in cubomedusae. Immunoreactivity to FMRFamide in cubomedusae is mostly limited to a small network of neurons in the pacemaker region of the rhopalia, the pedalial apex at the nerve ring junction, and a few neuron tracts in the nerve ring. However, FMRFamide-immunoreactive networks, as well as tubulin-immunoreactive networks, are nearly ubiquitous outside of the swim muscle sheets in the perradial smooth muscle bands, manubrium, pedalia, and tentacles. Here we describe in detail the peripheral nerve nets of box jellyfish on the basis of immunoreactivity to the antibodies above. Our results offer insight into how the peripheral nerve nets are organized to produce the complex swimming, feeding, and defensive behaviors observed in cubomedusae.