Chemical allergy: new science,new understanding and new opportunities

Chemicalallergycantakeavarietyofforms.Thoseofgreatestrelevancetotoxicologyareskinsensitisationresul tinginallergiccontactdermatitis,andsensitisationoftherespiratorytractassociatedwithallergicrhinitisandasthma.Bothrepresentimportanthealthissuesandthereisaneedforeffectivehazardcharacterisationandriskassessment.Thelocallymphnodeassay(LLNA)isusedincreasinglyfortheidentificationofchemicalsthathavethepo tentialtocauseskinsensitisation.Thismethodisnowemployedalsofordeterminationofrelativeskinsensit…     

Monocyclic β-lactams: new structures for new biological activities

The azetidinone core-structure offers a unique approach to the design and synthesis of new derivatives with unique biological properties. During the last two decades researches convincingly demonstrated that the prospect of structural modifications of monocyclic β-lactams with specific substituents is an effective procedure for the detection and improvement of important pharmacological effects different from antibacterial activity. As a matter of fact, new β-lactam compounds demonstrated biological activity as inhibitors of a wide range of enzymes. This review reports the latest developments on monocyclic β-lactam compounds activity as anticancer, antitubercular, HFAAH inhibitors, HDAC inhibitors, anti-inflammatory drugs (tryptase inhibitors), Cathepsin K inhibitors, and vasopressin inhibitors. We attempted to highlight the intertwined relationships between structural features and biological activities, by analysing groups anchored on the three positions of the azetidinone ring as sources of molecular diversity.     

A new producer of mevastatin

Mevastatin (compactin)was isolated form culture broth of a fungal strain SIIA-F3933,The strain SIIA-F3933 was isolated from a soil sample collected in Putuo mountain,Zhejiang Province,P,R.China,It was identified as Penicillium janczewskii Zaleski based on its cultural and morphological characteristics and was regarded as a new producer of mevastatin，。     

Pompholyx: what's new?

Background: Pompholyx is a chronic relapsing inflammatory vesicobullous skin disease of the hands and feet belonging to the spectrum of eczema. Established treatments, both topical and systemic, are limited in efficacy, risk:benefit ratio and prevention of further relapses. New treatment options are needed. Objective: The article will discuss new treatment options, in particular for cheiropompholyx. Methods: A MEDLINE^® and ClinicalTrials.gov^® research has been conducted and publications about new and emerging treatments for pompholyx have been analysed. Results/conclusions: Among the recent developments, topical calcineurin inhibitors (TCI) and botulinum toxin A (BTXA) seem to be effective against pompholyx. The major disadvantage of BTXA is the need for injections, but efforts are being made to develop a topical form of application. Bexaroten gel has been used for chronic hand dermatitis, with good efficacy in the hyperkeratotic type. Further studies on pompholyx are needed. There is currently widespread interest in plant-based pharmaceuticals. Studies involving such topical drugs are on the way. In systemic treatment, retinoid alitretinoin has been most extensively studied in hand dermatitis. However, experiences relating to pompholyx are more limited. New types of anti-inflammatory oral drugs such as leukotriene inhibitors and phosphodiesterase-4 (PDE4) inhibitors have become available. These seem to have potential in the adjuvant treatment of pompholyx. Monoclonal antibodies of various types have been investigated in small series, but have failed to demonstrate consistent efficacy. Further investigations with new monoclonals are needed. Phototherapy of pompholyx is a cornerstone in treatment. High-dose UVA1 has been established as an effective modality in centres where the rather expensive equipment is available. Recently, UV-free phototherapy has been introduced, but more data are needed before final conclusions can be drawn.     

What's new in fillers?

This article is an in-depth review of various materials and products that have been used for the augmentation of soft tissue in the past, and covers several new products, methods, and techniques that may provide new options for dermatologists who use fillers in their practice. Pros and cons of each are discussed, along with mechanisms of action, dosages, approved and off-label uses, as well as a look ahead at some prospective technology.     

TAT-based drug delivery system – new directions in protein delivery for new hopes?

There has been great progress in the use of TAT-based drug delivery systems for the delivery of different macromolecules into cells in vitro and in vivo, thus circumventing the bioavailability barrier that is a problem for so many drugs. There are many advantages to using this system, such as the ability to deliver these cargoes into all types of cells in culture and into all organs in vivo. This system can even deliver cargoes into the brain across the blood–brain barrier. In addition, the ability to target specific intracellular sub-localizations such as the nuclei, the mitochondria and lysosomes further expands the possibilities of this drug delivery system to the development of sub-cellular organelle-targeted therapy. The therapeutic applications seem almost unlimited, and the use of the TAT-based delivery system has extended from proteins to a large variety of cargoes such as oligonucleotides, imaging agents, low molecular mass drugs, nanoparticles, micelles and liposomes. In this review the most recent advances in the use of the TAT-based drug delivery system will be described, mainly discussing TAT-mediated protein delivery and the use of the TAT system for enzyme replacement therapy.     

Clues for new therapeutics in osteoporosis and periodontal disease: new roles for lipoxygenases?

Lipoxygenase (LOX) pathways are well appreciated for their ability to regulate key events contributing to the cardinal signs of inflammation. Recent evidence indicates that LOX genes are associated with osteoporosis. Also, overexpression of the 15-LOX Type 1 in transgenic rabbits leads to a reduced inflammatory phenotype and protection from periodontal disease, as well as atherosclerosis. Osteoporosis and inflammation-associated bone degradation, such as periodontitis, affect many individuals worldwide and are known to have pathogenesis that involves local mediators via communication between osteoclasts and osteoblasts during osteogenesis. Evidence has emerged indicating that LOX gene expression is associated with reduced bone strength in murine models of osteoporosis. Overexpression of the 15-LOX gene and its products, such as lipoxins, confers endogenous anti-inflammation. This article discusses the recent findings that may link aberrant LOX pathway expression in these diseases, suggesting new avenues for therapeutic approaches via activation of endogenous pathways for resolution of local inflammation.     

Benzene risk assessment: does new evidence on myelodysplastic syndrome justify a new approach?

Epidemiologic findings play an important role in benzene risk assessment, which is utilized to guide the selection of recommended benzene exposure levels to prevent adverse health effects. For decades, excess leukemia risk, especially that in the Pliofilm^® cohort, has been the focus of benzene risk assessment. While more stringent benzene standards, often ≤1?ppm, have been promulgated to protect workers from developing leukemia, recent epidemiologic studies have reported elevated risk of myelodysplastic syndrome (MDS). This report aims to examine whether the use of new data on MDS is scientifically warranted in future benzene risk assessments. First, we reviewed current benzene guidelines, regulations, and underlying risk assessments in developed countries. Second, we examined current epidemiologic literature on benzene and MDS, which identified seven studies with simultaneous measures of MDS risk and benzene exposure and 17 studies on MDS in populations potentially exposed to benzene. Next, we examined the potential of the MDS data to serve as the basis of future benzene risk assessments, by comparing its quality and risk estimates with those used in current benzene standards. We conclude from the current literature that there is strong evidence that MDS can be caused by benzene, and the MDS data from the pooled petroleum study should be further examined in future benzene risk assessments. We recommend that future MDS-based benzene risk assessment use total MDS as the endpoint, take into consideration the full exposure period, and examine a range of benzene exposure metrics, including the role of peak, intermittent benzene exposures.     

Glucosamine for knee osteoarthritis--what's new?

Glucosamine is a natural substance that has been widely used for several years as a food supplement to treat people with osteoarthritis.1 One formulation of black triangle downglucosamine hydrochloride (Alateris - Ransom) has recently become the first (and is currently the only) glucosamine product to be licensed as a medicine in the UK for symptomatic relief of mild to moderate osteoarthritis of the knee. In 2002, we concluded that unlicensed "oral glucosamine sulphate 1,500 mg [daily] probably provides modest symptom relief in patients with osteoarthritis of the knee and its efficacy appears similar to that of NSAIDs".1 Here we update our advice in the light of new evidence and assess the place of the licensed glucosamine hydrochloride tablets.     

Several new targets of antitumor agents

甲胎蛋白作为肝癌生长的促进因子，是抗肝癌药的新靶点．用药物抑制或封闭癌基因表达为治疗肿瘤开辟了新途径．诱导肿瘤细胞向正常细胞分化已成为肿瘤药物治疗的又一崭新策略．诱导肿瘤细胞凋亡是许多抗肿瘤药的共同作用方式；用自杀基因靶向治疗肿瘤优化了目前的化学治疗，具有广阔的应用前景．     

Is urotensin-II the new endothelin?

Urotensin-II (U-II), a peptide isolated from the urophysis of teleost fish 35 years ago, is the endogenous ligand of the mammalian orphan receptor GPR14/SENR. Recently, human homologues of both the receptor (UT-II) and the peptide (hU-II) have been discovered. Following de-orphanization, hU-II was declared the 'new endothelin' as initial studies suggested similarities between the peptides, and in isolated arteries of cynomolgus monkey U-II was a more potent constrictor than endothelin-1 (ET-1), with equal efficacy. However, effects of U-II in vascular tissue from other mammalian species are variable and although potent, U-II exhibits a lesser maximal response than ET-1. In contrast, in humans U-II has emerged as a ubiquitious constrictor of both arteries and veins in vitro and elicits a reduction in blood flow in the forearm and skin microcirculation in vivo. In addition to direct vasoconstrictor activity on smooth muscle receptors, endothelium-dependent U-II-mediated vasodilatation has also been observed. Non-vascular, peripheral actions of U-II include potent inotropy and airway smooth muscle constriction and U-II and its receptor are present throughout rat brain implying a possible neurotransmitter or neuromodulatory role in the central nervous system. U-II is proposed to contribute to human diseases including atherosclerosis, cardiac hypertrophy, pulmonary hypertension and tumour growth. The development of selective receptor antagonists should help to clarify the relative importance of hU-II as a multifunctional peptide in mammalian systems and its role in disease. What is clear is that U-II is emerging as a new and potentially important mammalian transmitter.     

Clues for new therapeutics in osteoporosis and periodontal disease: new roles for lipoxygenases?

Lipoxygenase (LOX) pathways are well appreciated for their ability to regulate key events contributing to the cardinal signs of inflammation. Recent evidence indicates that LOX genes are associated with osteoporosis. Also, overexpression of the 15-LOX Type 1 in transgenic rabbits leads to a reduced inflammatory phenotype and protection from periodontal disease, as well as atherosclerosis. Osteoporosis and inflammation-associated bone degradation, such as periodontitis, affect many individuals worldwide and are known to have pathogenesis that involves local mediators via communication between osteoclasts and osteoblasts during osteogenesis. Evidence has emerged indicating that LOX gene expression is associated with reduced bone strength in murine models of osteoporosis. Overexpression of the 15-LOX gene and its products, such as lipoxins, confers endogenous anti-inflammation. This article discusses the recent findings that may link aberrant LOX pathway expression in these diseases, suggesting new avenues for therapeutic approaches via activation of endogenous pathways for resolution of local inflammation.     

Superior efficacy of new medicines?

Purpose  

To provide an overview of and discuss newly authorised medicines with an improved efficacy.