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Objective To determine the supratentorial area associated with poststroke dysphagia, we assessed the diffusion tensor images (DTI) in subacute stroke patients with supratentorial lesions. Methods We included 31 patients with a first episode of infarction in the middle cerebral artery territory. Each subject underwent brain DTI as well as a videofluoroscopic swallowing study (VFSS) and patients divided were into the dysphagia and non-dysphagia groups. Clinical dysphagia scale (CDS) scores were compared between the two groups. The corticospinal tract volume (TV), fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were calculated for 11 regions of interest in the supratentorial area-primary motor cortex, primary somatosensory cortex, supplementary motor cortex, anterior cingulate cortex, orbitofrontal cortex, parietooccipital cortex, insular cortex, posterior limb of the internal capsule, thalamus, and basal ganglia (putamen and caudate nucleus). DTI parameters were compared between the two groups. Results Among the 31 subjects, 17 were diagnosed with dysphagia by VFSS. Mean TVs were similar across the two groups. Significant inter-group differences were observed in two DTI values: the FA value in the contra-lesional primary motor cortex and the ADC value in the bilateral posterior limbs of the internal capsule (all p<0.05). Conclusion The FA value in the primary motor cortex on the contra-lesional side and the ADC value in the bilateral PLIC can be associated with dysphagia in middle cerebral artery stroke. [ABSTRACT FROM AUTHOR]

Based on the hypothesis that skin barrier impairment is a contributor to side-effects associated with retinoic acid therapy, a double-blind, placebo-controlled pilot study examined the combined use of retinoic acid with myristyl nicotinate (MN), a lipophilic derivative of niacin that enhances skin barrier function, in female subjects with mild to moderate facial photodamage. The study involved a 1-month run-in period with placebo or MN prior to initiation of retinoic acid therapy for 3 months. Analysis of skin biopsies revealed that retinoic acid therapy resulted in stratum corneum thinning of approximately 25% ( P = 0.006 versus baseline) that was ameliorated by MN use ( P < 0.005). Therapy resulted in an increased rate of transepidermal water loss (TEWL) of approximately 45% ( P = 0.001 versus baseline) and use of MN protected against the increase in TEWL with the strongest protection provided by prior use of MN ( P = 0.056 versus placebo). MN use reduced the incidence of side-effects of the therapy and again prior use provided the greatest reduction of side-effects. Subjects showed statistically significant clinical improvement ( P < 0.05 versus baseline) during the study. MN use did not interfere with any clinical improvement parameters and improved effects on temple laxity ( P = 0.01 versus placebo). Analysis of changes in epidermal thickness, Ki67-positive cells and intensity of loricrin staining demonstrated that MN either improved or did not interfere with retinoic acid efficacy. These results show that prior and concurrent use of MN can mitigate barrier impairment and improve the tolerability of retinoic acid therapy for facial photodamage without interfering with efficacy. [ABSTRACT FROM AUTHOR]

Background Female pattern alopecia is a common dermatologic condition that manifests after puberty. The only approved drug treatment for this condition is 2% minoxidil for topical application. Aims This pilot study examined the effect of topical application of two niacin derivatives, octyl nicotinate and tetradecyl nicotinate, on hair fullness in female alopecia. Patients/methods Sixty female subjects with Ludwig types I–III female pattern hair loss were evaluated in a double-blinded, placebo-controlled (40 active, 20 placebo) design using standardized 35-mm photographic analyses for assessment of efficacy after 6 months of application. Results The niacin derivatives demonstrated a statistically significant increase in hair fullness ( P = 0.04 compared to the placebo). Conclusion Whereas evaluation of hair growth in women is challenging, this 6-month pilot study demonstrated statistically significant increase in hair fullness on blinded 35-mm photographic analysis. Long-term topical application of nicotinic acid derivatives offers promise for providing benefit in female alopecia and warrants further study. [ABSTRACT FROM AUTHOR]

Activation of CD38 in lymphokine-activated killer (LAK) cells involves interleukin-8 (IL8)-mediated protein kinase G (PKG) activation and results in an increase in the sustained intracellular Ca2+ concentration ([Ca2+]i), cADP-ribose, and LAK cell migration. However, direct phosphorylation or activation of CD38 by PKG has not been observed in vitro. In this study, we examined the molecular mechanism of PKG-mediated activation of CD38. Nonmuscle myosin heavy chain IIA (MHCIIA) was identified as a CD38-associated protein upon IL8 stimulation. The IL8-induced association of MHCIIA with CD38 was dependent on PKG-mediated phosphorylation of MHCIIA. Supporting these observations, IL8- or cell-permeable cGMP analog-induced formation of cADP-ribose, increase in [Ca2+]i, and migration of LAK cells were inhibited by treatment with the MHCIIA inhibitor blebbistatin. Binding studies using purified proteins revealed that the association of MHCIIA with CD38 occurred through Lck, a tyrosine kinase. Moreover, these three molecules co-immunoprecipitated upon IL8 stimulation of LAK cells. IL8 treatment of LAK cells resulted in internalization of CD 38, which co-localized with MHCIIA and Lck, and blebbistatin blocked internalization of CD38. These findings demonstrate that the association of phospho-MHCIIA with Lck and CD38 is a critical step in the internalization and activation of CD38. [ABSTRACT FROM AUTHOR]