Objective: To investigate the association between the gene polymorphisms of rs774320676, rs768437857, rs928508030, and rs2275235 loci of Cathepsin S (CTSS) and risk of acute atherosclerotic cerebral infarction. Methods: A total of 315 patients with acute atherosclerotic cerebral infarction (study group) and 220 healthy subjects (control group) were enrolled in the present study. The genetic polymorphism of rs774320676, rs768437857, rs928508030, and rs2275235 loci of CTSS of subjects was analyzed by PCR-Sanger sequencing. Results: The proportion of carriers with mutant T allele at rs774320676 locus and mutant G allele at rs928508030 locus of CTSS in study group was significantly higher than the proportion in control group (P=0.000, adjusted odds ratio (OR) = 1.332, 95% confidence interval (CI) = 1.200-1.460; P<0.001, adjusted OR = 1.185, 95% CI = 1.055-1.314; P=0.002). The T allele at rs774320676 locus and the G allele at rs928508030 locus of CTSS were independent risk factors for acute atherosclerotic cerebral infarction (OR = 2.534, 95% CI = 1.020-4.652, P=0.006; OR = 2.016, 95% CI = 1.031-4.385, P=0.031). Conclusion: The single nucleotide polymorphisms (SNPs) of rs774320676 and rs928508030 of CTSS gene were related with risk for acute atherosclerotic cerebral infarction. The T allele at rs774320676 locus and G allele at rs928508030 locus of CTSS were genetic susceptibility genes of acute atherosclerotic cerebral infarction.

Drug-induced scleroderma has been rarely reported, mostly with the features of diffuse scleroderma or acrosclerosis, and exceptionally with the characteristics of morphea. We report the case of an adult white woman, enrolled in a double-blind, placebo-controlled, multicentric trial evaluating the efficacy and safety of the cathepsin K inhibitor balicatib for osteoporosis. Typical morphea lesions developed on the patient\'s trunk 9 months after the beginning of therapy. Lesions completely resolved after drug withdrawal and a single brief course of systemic steroids. No recurrence occurred in a 2-year follow-up. Fifteen cases of drug-induced morphea could be retrieved from the literature. Drug withdrawal determined complete remission in only a few patients. Different drug classes have been implicated. Some of these, including balicatib, alter directly connective tissue metabolism.

OBJECTIVE: Cysteine proteases as cathepsins K and L as well as matrix metalloproteases are considered to be basically involved in collagen turnover. Degenerative joint diseases such as gonarthrosis are characterised by massive cartilage degradation mediated by increased activities of these proteases. These enzymes are, therefore, interesting targets for the treatment of painful arthritic joint diseases. The aim of these studies was to reconsider the hypothesis that cathepsin activities are enhanced in patients suffering from osteoarthritis.
RESULTS: We report on a 69-year-old female suffering from severe pain due to predominant retropatellar arthrosis. The clinical symptoms of this patient did not significantly differ from that of 30 other patients who were involved in this study. All patients undergone an endoprosthetic knee joint replacement. During the operation we harvested cartilage probes and isolated the chondrocytes from the joint cartilage for determination of the mRNA and the activities of cathepsins B, H, K and L. Compared to chondrocytes isolated from the control patients we found the activity of cysteine proteases to be extremely enhanced in chondrocytes of this patient. Moreover, the concentration of cystatin c, an endogenous inhibitor of cathepsins, was not detectable.
CONCLUSIONS: The results raise doubts on the predominant role of cysteine proteases in severe cartilage destruction.

Tracking the impurity profile of an active pharmaceutical ingredient (API) is a very important task for all stages of drug development. A systematic approach for tracking impurity profile of API is described. Various real pharmaceutical applications are presented through successful examples of impurity profile tracking for three different novel APIs. These include MK-0969, an M3 antagonist; MK-0677, an oral-active growth hormone secretagogue and API-A, a cathepsin K inhibitor. A general strategy including selection of a reversed phase high performance liquid chromatographic (RP-HPLC) impurity profile method based on screening various stationary phases and changing the pH of the mobile phase and elucidation of impurity structures through the utilization of LC-MS, preparative-LC and NMR is demonstrated. A series of studies were conducted on the peak purity check by using the LC-UV diode-array and LC-MS detections. The advantages and disadvantages of each technique in the evaluation of peak purity are discussed.

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Biological diversity--or biodiversity--is the term given to the variety of life on Earth and the natural patterns it forms. The biodiversity we see today is the fruit of billions of years of evolution, shaped by natural processes and, increasingly, by the influence of humans. It forms the web of life of which we are an integral part and upon which we so fully depend. The research on molecular biodiversity tries to lay the scientific foundation of a rational conservation policy that has its roots in various disciplines including systematics/taxonomy (species richness), present day ecology (diversity of ecological systems), and functional genetics (genetic diversity). The results of ongoing genome analyses (genome projects and expressed sequence tag projects) and the achievements of molecular evolution may allow us not only to quantitate the diversity of the present biota but also to extrapolate to their diversification in the future. A link between biodiversity and genomics/molecular evolution will create a platform which we hope may facilitate a sustainable management of organismic life and ensure its exploitation for human benefit. In the present review we outline possible strategies, using the Porifera (sponges) as a prominent example. On the basis of solid taxonomy and ecological data, the high value of this phylum for human application becomes obvious, especially with regard to the field of chemical ecology and the desire to find novel potential drugs for clinical use. In addition, the benefit of trying to make sense of molecular biodiversity using sponges as an example can be seen in the fact that the study of these animals, which are \"living fossils\", gives us a good insight into the history of our planet, especially with respect to the evolution of Metazoa.

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Osteopetrosis is a disease in which a disturbance in the resorption of bone formed by endochondral ossification takes place. The cause of the osteoclast insufficiency is unknown. In the literature, the etiology of the disease is discussed in relation to the complete absence of cathepsin K synthesis, a cysteine protease. In our case report, we demonstrated cathepsin K expression in the osteoclast cells of the benign form of osteopetrosis. We also found the macrophage marker CD 68 in these osteoclast cells, whereas other mononuclear phagocytic cells were not present in the vicinity of osteoclasts. The inhibition of osteoclast cells by phagocytes is unlikely.

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The prolonged administration of epsilon-aminocaproic acid (EACA) resulted in the development of severe proximal myopathy associated with high plasma creatine kinase values, rhabdomyolysis, myoglobinuria, and mild hyperbilirubinaemia. Withdrawal of the drug led to spontaneous resolution of the clinical and biochemical syndrome. Structural and enzyme studies of a biopsy specimen of the involved skeletal muscle supported the presence of subclinical myopathy. The mechanism whereby EACA produces its toxicity in muscle may in part be due to inhibition of cathepsin D, but the possibility that other proteases are involved has not been excluded. The fact that this clinical syndrome is rare despite the widespread use of EACA may be because it only occurs in subjects with a subclinical skeletal muscle disorder which is unmasked by the drug.