Thrombolysis in stroke patients with elevated inflammatory markers.

OBJECTIVE To investigate the prognostic value of white blood cell count (WBC) on functional outcome, mortality and bleeding risk in stroke patients treated with intravenous thrombolysis (IVT). METHODS In this prospective multicenter study from the TRISP registry, we assessed the association between WBC on admission and 3-month poor outcome (modified Rankin Scale 3-6), mortality and occurrence of symptomatic intracranial hemorrhage (sICH; ECASS-II-criteria) in IVT-treated stroke patients. WBC was used as continuous and categorical variable distinguishing leukocytosis (WBC > 10 × 109/l) and leukopenia (WBC  10 mg/l) on outcomes. RESULTS Of 10,813 IVT-treated patients, 2527 had leukocytosis, 112 leukopenia and 8174 normal WBC. Increasing WBC (by 1 × 109/l) predicted poor outcome (ORadjusted 1.04[1.02-1.06]) but not mortality and sICH. Leukocytosis was independently associated with poor outcome (ORadjusted 1.48[1.29-1.69]) and mortality (ORadjusted 1.60[1.35-1.89]) but not with sICH (ORadjusted 1.17[0.94-1.45]). Leukopenia did not predict any outcome. In a subgroup, combined leukocytosis and elevated CRP had the strongest association with poor outcome (ORadjusted 2.26[1.76-2.91]) and mortality (ORadjusted 2.43[1.86-3.16]) when compared to combined normal WBC and CRP. CONCLUSION In IVT-treated patients, leukocytosis independently predicted poor functional outcome and death. Bleeding complications after IVT were not independently associated with leukocytosis

Differential Expression between Human Dermal Papilla Cells from Balding and Non-Balding Scalps Reveals New Candidate Genes for Androgenetic Alopecia

Agency for Science, Technology and Research (A*STAR). EC is supported by the A*STAR Graduate Scholarship program

Does corporate reputation matter? Role of social media in consumer intention to purchase innovative food product

The exponential growth of the corporate reputation in food industry has resulted in innovations in every link of its supply chain. There have been studies that have characterized innovation in various industries from the perspective of technology, but far fewer in the area of corporate reputation, consumer perception, and intention towards innovations in food products. This research analyses the innovations in the food industry from the perspective of the consumer and provides a conceptual framework of food innovation stages. The study also investigates the relationship between corporate reputation and intention towards food innovation along with the other components of TPB model with an extension of social media engagement. The results from India and US samples confirm that social media engagement have a significant role to play in creating intention to purchase innovative food products. The study compares the US and Indian samples and identifies differences in subjective norms and perceived behavioural control

Opioids and the skin--where do we stand?

International audienceThe common ectodermal origin of the skin and nervous systems can be expected to predict likely interactions in the adult. Over the last couple of decades much progress has been made to elucidate the nature of these interactions, which provide multidirectional controls between the centrally located brain and the peripherally located skin and immune system. The opioid system is an excellent example of such an interaction and there is growing evidence that opioid receptors (OR) and their endogenous opioid agonists are functional in different skin structures, including peripheral nerve fibres, keratinocytes, melanocytes, hair follicles and immune cells. Greater knowledge of these skin-associated opioid interactions will be important for the treatment of chronic and acute pain and pruritus. Topical treatment of the skin with opioid ligands is particularly attractive as they are active with few side effects, especially if they cannot cross the blood-brain barrier. Moreover, cutaneous activation of the opioid system (e.g. by peripheral nerves, cutaneous and immune cells, especially in inflamed and damaged skin) can influence cell differentiation and apoptosis, and thus may be important for the repair of damaged skin. While many of the pieces of this intriguing puzzle remain to be found, we attempt in this review to weave a thread around available data to discuss how the peripheral opioid system may impact on different key players in skin physiology and pathology

The Role of Skin Opioid Receptor System in Itch

Opioid receptors are key players in induction of chronic itch. This could be confirmed using opiate receptor knockout mice experiments and clinical studies on patients with chronic itch. We have induced a dry skin dermatitis as a model for chronic itching on -(MOR) and -(KOR) opioid receptor knockout (KO) mice. MOR KO mice scratched significantly less than wild type (WT). Additionally the epidermal hypertrophy caused by chronic dermatitis and the amount of epidermal nerve endings in MOR KO mice were significantly decreased than in WT mice. KOR KO mice showed similar scratching behavior as MOR KO mice; however the changes were less significant. In addition, we performed a double blind, placebo controlled, cross over study using topically applied opioid receptor antagonist, Naltrexone, on patients with pruritus in atopic dermatitis. The results revealed significant effects of the topical application of Naltrexone in patients with chronic pruritus (45% improvement of pruritus by VAS compared to placebo, n=24), but not in patients with acute pruritus (7%, n=15). These studies establish the clinical relevance of MOR system and the peripheral, epidermal nerve endings in chronic pruritus and warrant further research and therapeutic potential for such research

Specific Targeting of Melanotic Cells with Peptide Ligated Photosensitizers for Photodynamic Therapy

A strategy combining covalent conjugation of photosensitizers to a peptide ligand directed to the melanocortin 1 (MC1) receptor with the application of sequential LED light dosage at near-IR wavelengths was developed to achieve specific cytotoxicity to melanocytes and melanoma (MEL) with minimal collateral damage to surrounding cells such as keratinocytes (KER). The specific killing of melanotic cells by targeted photodynamic therapy (PDT) described in this study holds promise as a potentially effective adjuvant therapeutic method to control benign skin hyperpigmentation or superficial melanotic malignancy such as Lentigo Maligna Melanoma (LMM).ISSN:2045-232

Investigating endogenous µ-opioid receptors in human keratinocytes as pharmacological targets using novel fluorescent ligand

<div><p>Opioids in skin function during stress response, regeneration, ageing and, particularly in regulating sensation. In chronic pruritus, topical treatment with Naltrexone changes μ-opioid receptor (μ-OR) localization to relieve itch. The molecular mechanisms behind the effects of Naltrexone on μ-OR function in reduction of itching behavior has not been studied. There is an immediate need to understand the endogenous complexity of μ-OR dynamics in normal and pathological skin conditions. Here we evaluate real-time behavior of μ-OR-Endomorphine complexes in the presence of agonist and antagonists. The μ-OR ligand Endomorphine-1 (EM) was conjugated to the fluorescent dye Tetramethylrhodamine (TAMRA) to investigate the effects of agonist and antagonists in N/TERT-1 keratinocytes. The cellular localization of the EM-TAMRA was followed through time resolved confocal microscopy and population analysis was performed by flow cytometry. The <i>in vitro</i> analyses demonstrate fast internalization and trafficking of the endogenous EM-TAMRA-μ-OR interactions in a qualitative manner. Competition with Endomorphine-1, Naltrexone and CTOP show both canonical and non-canonical effects in basal and differentiated keratinocytes. Acute and chronic treatment with Naltrexone and Endomorphine-1 increases EM-TAMRA binding to skin cells. Although Naltrexone is clinically effective in relieving itch, the mechanisms behind re-distribution of μ-ORs during clinical treatments are not known. Our study has given insight into cellular mechanisms of μ-OR ligand-receptor interactions after opioid agonist and antagonist treatments <i>in vitro</i>. These findings potentially offer opportunities in using novel treatment strategies for skin and peripheral sensory disorders.</p></div

HPLC parameters.

<p>HPLC parameters.</p