Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The scabies mite (Sarcoptes scabiei) is a parasite responsible for major morbidity in disadvantaged communities and immuno-compromised patients worldwide. In addition to the physical discomfort caused by the disease, scabies infestations facilitate infection by Streptococcal species via skin lesions, resulting in a high prevalence of rheumatic fever/heart disease in affected communities. The scabies mite produces 33 proteins that are closely related to those in the dust mite group 3 allergen and belong to the S1-like protease family (chymotrypsin-like). However, all but one of these molecules contain mutations in the conserved active-site catalytic triad that are predicted to render them catalytically inactive. These molecules are thus termed scabies mite inactivated protease paralogues (SMIPPs). The precise function of SMIPPs is unclear; however, it has been suggested that these proteins might function by binding and protecting target substrates from cleavage by host immune proteases, thus preventing the host from mounting an effective immune challenge. In order to begin to understand the structural basis for SMIPP function, we solved the crystal structures of SMIPP-S-I1 and SMIPP-S-D1 at 1.85 A and 2.0 A resolution, respectively. Both structures adopt the characteristic serine protease fold, albeit with large structural variations over much of the molecule. In both structures, mutations in the catalytic triad together with occlusion of the S1 subsite by a conserved Tyr200 residue is predicted to block substrate ingress. Accordingly, we show that both proteases lack catalytic function. Attempts to restore function (via site-directed mutagenesis of catalytic residues as well as Tyr200) were unsuccessful. Taken together, these data suggest that SMIPPs have lost the ability to bind substrates in a classical "canonical" fashion, and instead have evolved alternative functions in the lifecycle of the scabies mite.
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PMID:Structural mechanisms of inactivation in scabies mite serine protease paralogues. 1942 18

In 2004, we reviewed the status of disease caused by the scabies mite Sarcoptes scabiei at the time and pointed out that very little basic research had ever been done. The reason for this was largely the lack of availability of mites for experimental purposes and, to a degree, a consequent lack of understanding of its importance, resulting in the trivial name 'itch mite'. Scabies is responsible for major morbidity in disadvantaged communities and immunocompromised patients worldwide. In addition to the physical discomfort caused by the disease, scabies infestations facilitate infection by bacterial pathogens such as Streptococcus pyogenes and Staphylococcus aureus via skin lesions, resulting in severe downstream disease such as in a high prevalence of rheumatic fever/heart disease in affected communities. We now have further evidence that in disadvantaged populations living in tropical climates, scabies rather than 'Strep throat' is an important source of S. pyogenes causing rheumatic fever and eventually rheumatic heart disease. In addition, our work has resulted in two fundamental research tools that facilitate much of the current biomedical research efforts on scabies, namely a public database containing ~45,000 scabies mite expressed sequence tags and a porcine in vivo model. Here we will discuss novel and unexpected proteins encountered in the database that appear crucial to mite survival with regard to digestion and evasion of host defence. The mode(s) of action of some of these have been at least partially revealed. Further, newly discovered molecules that may well have a similar role, such as a family of inactivated cysteine proteases, are yet to be investigated. Hence, there are now whole families of potential targets for chemical inhibitors of S. scabiei. These efforts put today's scabies research in a unique position to design and test small molecules that may specifically interfere with mite-derived molecules, such as digestive proteases and mite complement inhibitors. The porcine scabies model will be available to trial in vivo treatment with potential inhibitors. New therapies for scabies may be developed from these studies and may contribute to reduce the spread of scabies and the subsequent prevalence of bacterial skin infections and their devastating sequelae in the community.
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PMID:Scabies: important clinical consequences explained by new molecular studies. 2272 46

Sarcoptes scabiei (S. scabiei), a parasite mite which causes scabies disease resulting in serious public health concern. The long-term scabies disease can lead to complications such as septicemia, acute post-streptococcal glomerulonephritis, heart disease, and secondary infections. Timely treatment to the affected patients is required to control the disease and get rid of the causative agent. Delayed diagnosis and inappropriate treatment can lead to serious consequences. The most common treatment strategy is the use of allopathic medicines which can immediately relieve the patient but have the drawback of side effects. The safe and cost-effective alternative treatment strategy is the use of medicinal plants which have beneficial therapeutic potential against variety of diseases due to the presence of many bioactive phytoconstituents with no or minimal side effects. For the present review, the published articles describing scabies disease and its phytotherapeutic modalities were searched through different data bases including Google Scholar, PubMed, Medline, and ScienceDirect using the keywords like S. scabiei, prevalence of scabies disease, and phytotherapy of scabies. A large number of medicinal plants, such as Melaleuca alternifolia, Curcuma longa, Azadirachta indica, Rosmarinus officinalis, Capsicum annuum, Cinnamomum camphor, Solanum nigrum, and Eupatorium perfoliatum, have been reviewed for the promising future treatments of scabies. All the studied plants have many bioactive compounds with potential therapeutic effects against scabies and can be utilized for therapeutic purposes for this disease. This literature study has limitations because of the lack of sufficient data due to limited pre-clinical trials in this particular area. This review provides a baseline to explore the therapeutic potential of these medicinal plants against skin diseases. However, extensive studies are required to identify, authenticate, and characterize the bioactive compounds present in these plants which may lead to value addition in pharmaceutical industries providing the cost-effective way of treatment with minimal side effects.
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PMID:Therapeutic potential of medicinal plants for the management of scabies. 3183 Mar 56