Drug utilization and medical expenses in psoriasis treatment at a dermatology hospital in Vietnam, 2019-2021.

Introduction: Psoriasis is a persistent, chronic, inflammatory cutaneous disorder that recurs frequently and has negative impacts on the living quality of sufferers. Methods: Data from the Inpatient and Outpatient Department medical records at Can Tho dermatology hospital were used to generate a descriptive statistics report on medicines and medical costs for psoriasis therapy in 2019-2021. Results: The average number of prescription medications varied annually, averaging roughly 0.62±85.4% per prescription. Corticosteroids and calcipotriol were the most commonly recommended drugs for psoriasis. Antihistamines were the most often used medication, with over 12,000 instances among the 28,397 individuals studied. The peak in average per-treatment expenses occurred in 2021 when they fluctuated between US $120 and US $160. In contrast, examination expenses were the most costly, ranging from US $93-$107. Conclusion: The bulk of psoriasis therapy treatments were topical agents, whose quantities rose progressively. Direct examination expenses accounted for the greatest proportion.

Proteolytic activation of the cell death protease Yama/CPP32 by granzyme B.

The serine protease granzyme B, which is secreted by cytotoxic cells, is one of the major effectors of apoptosis in susceptible targets. To examine the apoptotic mechanism of granzyme B, we have analyzed its effect on purified proteins that are thought to be components of death pathways inherent to cells. We demonstrate that granzyme B processes interleukin 1beta-converting enzyme (ICE) and the ICE-related protease Yama (also known as CPP32 or apopain) by limited proteolysis. Processing of ICE does not lead to activation. However, processing by granzyme B leads directly to the activation of Yama, which is now able to bind inhibitors and cleave the substrate poly(ADP-ribose) polymerase whose proteolysis is a marker of apoptosis initiated by several other stimuli. Thus ICE-related proteases can be activated by serine proteases that possess the correct specificity. Activation of pro-Yama by granzyme B is within the physiologic range. Thus the cytotoxic effect of granzyme B can be explained by its activation of an endogenous protease component of a programmed cell death pathway.

Yama/CPP32 beta, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase.

Although the mechanism of mammalian apoptosis has not been elucidated, a protease of the CED-3/ICE family is anticipated to be a component of the death machinery. Several lines of evidence predict that this protease cleaves the death substrate poly(ADP-ribose) polymerase (PARP) to a specific 85 kDa form observed during apoptosis, is inhibitable by the CrmA protein, and is distinct from ICE. We cloned a ced-3/ICE-related gene, designated Yama, that encodes a protein identical to CPP32 beta. Purified Yama was a zymogen that, when activated, cleaved PARP to generate the 85 kDa apoptotic fragment. Cleavage of PARP by Yama was inhibited by CrmA but not by an inactive point mutant of CrmA. Furthermore, CrmA blocked cleavage of PARP in cells undergoing apoptosis. We propose that Yama may represent an effector component of the mammalian cell death pathway and suggest that CrmA blocks apoptosis by inhibiting Yama.

Granzyme B is inhibited by the cowpox virus serpin cytokine response modifier A.

The ability of cytolytic cells to cause apoptosis in target cells is in part due to the action of the serine proteinase granzyme B. We demonstrate that granzyme B is inhibited, with an association rate constant of 2.9 x 10(5) M-1 s-1, by the cowpox viral serpin cytokine response modifier A (CrmA). Previously we have shown CrmA to be an inhibitor of the cysteine proteinase interleukin-1 beta-converting enzyme (ICE). Thus the mechanism of CrmA involves the unusual ability to efficiently inhibit proteinases from two distinct catalytic classes, in this case serine and cysteine proteinases. Granzyme B and ICE are both used to combat viral infection, and we propose that cowpox virus uses CrmA to evade the contribution of these two proteinases. Thus, through CrmA, the virus may influence two of the pathways normally used to kill virus-infected cells: acting on endogenous proteinases such as ICE and on exogenous proteinases delivered by cytotoxic lymphocytes to infected cells.

Expression of a functional alpha-macroglobulin receptor binding domain in Escherichia coli.

We have expressed receptor-binding domains of human alpha 2-macroglobulin and rat alpha 1-macroglobulin in Escherichia coli. Expression levels of both recombinants were quite high, but the human one was insoluble, probably forming inclusion bodies. The rat domain, which lacks the human disulfide, was produced in a soluble form and readily purified by two simple chromatographic steps. Purified recombinant rat alpha 1-macroglobulin receptor-binding domain was fully functional in binding to the alpha-macroglobulin receptor on human fibroblasts. This 142 residue domain should serve as an excellent template for analyzing the structural requirements for alpha-macroglobulin receptor ligation and dissecting the varied biological functions resulting from such ligation.