Pruritus is a common symptom that can significantly reduce quality of life through sleep disruption. To examine features of disturbed sleep in patients with chronic pruritic dermatoses and test the hypothesis that systemic inflammation may serve as a biomarker for impaired sleep in these patients. Cross-sectional analysis of the National Health and Nutrition Examination Survey investigating systemic inflammation using C-reactive protein (CRP) levels. Logistic regression was used to compare patients with and without sleep disturbances adjusting for demographics (model 1) and medical comorbidities (model 2). Chronic pruritic dermatoses were associated with multiple sleep disturbances including nighttime awakenings (Model 1OR=1.646, 95%CI[1.031-2.627]; Model 2OR=1.329, 95%CI[0.888-1.989]) and early morning awakening (Model 1OR=1.669, 95%CI[1.118-2.493]; Model 2OR=1.582, 95%CI[1.008-2.481]). Mean CRP levels were 52.8% higher among pruritic dermatoses patients reporting trouble sleeping compared to those who did not (0.663 vs 0.434 mg/dL; p=0.034). Trouble sleeping was also positively correlated with CRP levels (β=0.142, p=0.025). Potential recall bias among participants. In addition to confirming sleep disturbances with pruritic dermatoses, we found these disturbances are more likely to present with elevated CRP levels. Clinicians should consider the potential risk for sleep-related and cardiac comorbidities in patients diagnosed with itchy skin conditions.In addition to confirming sleep disturbances with pruritic dermatoses, we found these disturbances are more likely to present with elevated CRP levels. Clinicians should consider the potential risk for sleep-related and cardiac comorbidities in patients diagnosed with itchy skin conditions.The early identification of teratogens in humans and animals is mandatory for drug discovery and development. Zebrafish has emerged as an alternative model to traditional preclinical models for predicting teratogenicity and other potential chemical-induced toxicity hazards. To prove its predictivity, we exposed zebrafish embryos from 0 to 96 h post fertilization to a battery of 31 compounds classified as teratogens or non-teratogens in mammals. The teratogenicity score was based on the measurement of 16 phenotypical parameters, namely heart edema, pigmentation, body length, eye size, yolk size, yolk sac edema, otic vesicle defects, otoliths defects, body axis defects, developmental delay, tail bending, scoliosis, lateral fins absence, hatching ratio, lower jaw malformations and tissue necrosis. Among the 31 compounds, 20 were detected as teratogens and 11 as non-teratogens, resulting in 94.44 % sensitivity, 90.91 % specificity and 87.10 % accuracy compared to rodents. These percentages decreased slightly when referred to humans, with 87.50 % sensitivity, 81.82 % specificity and 74.19 % accuracy, but allowed an increase in the prediction levels reported by rodents for the same compounds. Positive compounds showed a high correlation among teratogenic parameters, pointing out at general developmental delay as major cause to explain the physiological/morphological malformations. A more detailed analysis based on deviations from main trends revealed potential specific modes of action for some compounds such as retinoic acid, DEAB, ochratoxin A, haloperidol, warfarin, valproic acid, acetaminophen, dasatinib, imatinib, dexamethasone, 6-aminonicotinamide and bisphenol A. The high degree of predictivity and the possibility of applying mechanistic approaches makes zebrafish a powerful model for screening teratogenicity.We report the pharmaceutical stability of trastuzumab stored for a short time (12 h) at room temperature (RT; 20-25 °C) compared to trastuzumab stored at 2-8 °C. The physicochemical properties were evaluated by UV-visible and FTIR spectroscopy, SDS-PAGE and size-exclusion HPLC (SE-HPLC). Trastuzumab was reacted with benzylisothiocyanate diethylenetriaminepentaacetic acid (BzDTPA) to complex 111In. The HER2-binding affinity of 111In-BzDTPA-trastuzumab synthesised from trastuzumab stored at RT or at 2-8 °C was measured using HER2-positive SK-Br-3 human breast cancer (BC) cells. The tumour and normal tissue uptake of 111In-BzDTPA-trastuzumab was studied by microSPECT/CT imaging and biodistribution studies in CD1 athymic mice with s.c. HER2-positive SK-Ov-3 human ovarian cancer xenografts. There were no differences in λmax or molar absorptivity (ε) values in the UV-visible spectra of trastuzumab stored at RT or at 2-8 °C. FTIR spectroscopy suggested no differences in secondary structure. SDS-PAGE revealed protein bands corresponding to the expected molecular weights. SE-HPLC showed identical properties for trastuzumab stored at RT or at 2-8 °C. The dissociation constant (Kd) for binding of 111In-BzDTPA-trastuzumab to HER2 on SK-Br-3 cells (2.2-4.4 nM) was not significantly different when the radioimmunoconjugates were synthesised from trastuzumab stored at RT or at 2-8 °C. MicroSPECT/CT demonstrated high uptake in SK-Ov-3 tumours in mice that was not significantly different using trastuzumab stored at RT or at 2-8 °C (33.7 ± 8.8% vs. 22.2 ± 8.1% i.d./g, respectively; P = 0.36). https://www.selleckchem.com/products/debio-0123.html There were no significant differences in normal tissue uptake or in tumour/normal tissue (T/NT) ratios. We conclude that short-term storage of trastuzumab at RT for 12 h did not affect the physicochemical or biological properties of the drug.This paper reports a detailed characterization of laser-induced micro-jets, including ex vivo experiments using skin as a target substrate to check the feasibility in terms of needle-free jet injection. The actuation technique comprised a Nd-YAG based laser system to superheat the liquid locally, which creates a pressure wave actuating the motion of the liquid as a jet. Typical jet speeds were ~O(102) m/s and diameters ~O(101-102) μm and Re ~O(102-104). We studied the effect of various system parameters related to both geometry (e.g., capillary diameter, laser focal point) and fluid properties (e.g., viscosity). To advance the understanding of liquid delivery into tissue, transient penetration dynamics and dispersion patterns were studied. Stand-off distance, mechanical strength of the proxy gel, and laser pulse energy were also found to affect the penetration of liquid jets into the skin models. |