Sunscreening Agents: A Review.

Sunscreening agents: a review.

Filed under: Drug and Alcohol Rehabilitation

J Clin Aesthet Dermatol. 2013 Jan; 6(1): 16-26
Latha MS, Martis J, Shobha V, Sham Shinde R, Bangera S, Krishnankutty B, Bellary S, Varughese S, Rao P, Naveen Kumar BR

The increasing incidence of skin cancers and photodamaging effects caused by ultraviolet radiation has increased the use of sunscreening agents, which have shown beneficial effects in reducing the symptoms and reoccurrence of these problems. Many sunscreen compounds are in use, but their safety and efficacy are still in question. Efficacy is measured through indices, such as sun protection factor, persistent pigment darkening protection factor, and COLIPA guidelines. The United States Food and Drug Administration and European Union have incorporated changes in their guidelines to help consumers select products based on their sun protection factor and protection against ultraviolet radiation, whereas the Indian regulatory agency has not yet issued any special guidance on sunscreening agents, as they are classified under cosmetics. In this article, the authors discuss the pharmacological actions of sunscreening agents as well as the available formulations, their benefits, possible health hazards, safety, challenges, and proper application technique. New technologies and scope for the development of sunscreening agents are also discussed as well as the role of the physician in patient education about the use of these agents.
HubMed – drug

 

Nociceptive transmission to rat primary somatosensory cortex – comparison of sedative and analgesic effects.

Filed under: Drug and Alcohol Rehabilitation

PLoS One. 2013; 8(1): e53966
Granmo M, Jensen T, Schouenborg J

CO(2)-laser C-fibre evoked cortical potentials (LCEPs) is a potentially useful animal model for studies of pain mechanisms. A potential confounding factor when assessing analgesic effects of systemically administered drugs using LCEP is sedation. This study aims to clarify: 1) the relation between level of anaesthesia and magnitude of LCEP, 2) the effects of a sedative and an analgesic on LCEP and dominant EEG frequency 3) the effects of a sedative and analgesic on LCEP when dominant EEG frequency is kept stable. LCEP and EEG were recorded in isoflurane/nitrous-oxide anaesthetized rats. Increasing isoflurane level gradually reduced LCEPs and lowered dominant EEG frequencies. Systemic midazolam (10 ?mol/kg) profoundly reduced LCEP (19% of control) and lowered dominant EEG frequency. Similarly, morphine 1 and 3 mg/kg reduced LCEP (39%, 12% of control, respectively) and decreased EEG frequency. When keeping the dominant EEG frequency stable, midazolam caused no significant change of LCEP. Under these premises, morphine at 3 mg/kg, but not 1 mg/kg, caused a significant LCEP reduction (26% of control). In conclusion, the present data indicate that the sedative effects should be accounted for when assessing the analgesic effects of drug. Furthermore, it is suggested that LCEP, given that changes in EEG induced by sedation are compensated for, can provide information about the analgesic properties of systemically administrated drugs.
HubMed – drug

 

Epithelial-Mesenchymal Transition Markers and HER3 Expression Are Predictors of Elisidepsin Treatment Response in Breast and Pancreatic Cancer Cell Lines.

Filed under: Drug and Alcohol Rehabilitation

PLoS One. 2013; 8(1): e53645
Teixidó C, Marés R, Aracil M, Ramón Y Cajal S, Hernández-Losa J

Elisidepsin (elisidepsin trifluoroacetate, Irvalec®, PM02734) is a new synthetic depsipeptide, a result of the PharmaMar Development Program that seeks synthetic products of marine origin-derived compounds. Elisidepsin is a drug with antiproliferative activity in a wide range of tumors. In the present work we studied and characterized the mechanisms associated with sensitivity and resistance to elisidepsin treatment in a broad panel of tumor cell lines from breast and pancreas carcinomas, focusing on different factors involved in epithelial-mesenchymal transition (EMT) and the use of HER family receptors in predicting the in vitro drug response. Interestingly, we observed that the basal protein expression levels of EMT markers show a significant correlation with cell viability in response to elisidepsin treatment in a panel of 12 different breast and pancreatic cancer cell lines. In addition, we generated three elisidepsin treatment-resistant cell lines (MCF-7, HPAC and AsPC-1) and analyzed the pattern of expression of different EMT markers in these cells, confirming that acquired resistance to elisidepsin is associated with a switch to the EMT state. Furthermore, a direct correlation between basal HER3 expression and sensitivity to elisidepsin was observed; moreover, modulation of HER3 expression levels in different cancer cell lines alter their sensitivities to the drug, making them more resistant when HER3 expression is downregulated by a HER3-specific short hairpin RNA and more sensitive when the receptor is overexpressed. These results show that HER3 expression is an important marker of sensitivity to elisidepsin treatment.
HubMed – drug

 

AKT Signaling as a Novel Factor Associated with In Vitro Resistance of Human AML to Gemtuzumab Ozogamicin.

Filed under: Drug and Alcohol Rehabilitation

PLoS One. 2013; 8(1): e53518
Rosen DB, Harrington KH, Cordeiro JA, Leung LY, Putta S, Lacayo N, Laszlo GS, Gudgeon CJ, Hogge DE, Hawtin RE, Cesano A, Walter RB

Gemtuzumab ozogamicin (GO), an immunoconjugate between an anti-CD33 antibody and a calicheamicin-?(1) derivative, induces remissions and improves survival in a subset of patients with acute myeloid leukemia (AML). As the mechanisms underlying GO and calicheamicin-?(1) resistance are incompletely understood, we herein used flow cytometry-based single cell network profiling (SCNP) assays to study cellular responses of primary human AML cells to GO. Our data indicate that the extent of DNA damage is quantitatively impacted by CD33 expression and drug efflux activity. However, although DNA damage is required for GO-induced cytotoxicity, it is not sufficient for effective cell kill, suggesting that downstream anti-apoptotic pathways may function as relevant resistance mechanisms. Supporting this notion, we found activated PI3K/AKT signaling to be associated with GO resistance in vitro in primary AML cells. Consistently, the investigational AKT inhibitor MK-2206 significantly sensitized various human AML cells to GO or free calicheamicin-?(1) with particularly pronounced effects in otherwise GO or free calicheamicin-?(1) -resistant cells. Likewise, MK-2206 also sensitized primary AML cells to calicheamicin-?(1). Together, our findings illustrate the capacity of SCNP assays to discover chemotherapy-related biological pathways and signaling networks relevant to GO-induced genotoxic stress. The identification of AKT signaling as being associated with GO resistance in vitro may provide a novel approach to improve the in vivo efficacy of GO/calicheamicin-?(1) and, by extrapolation, other DNA damage-based therapeutics.
HubMed – drug

 

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