Peran Pemerintah dalam Program Pembangunan Desa Wonosari Kecamatan Tutur Kabupaten Pasuruan

This study aims to describe the role of government in building of Wonosari village, Tutur sub district, Pasuruan regency and how the implementation program of the building of Wonosari village. This study uses qualitative descriptive. The informants of this study are head of department, head of compiling program, head and members of local gov- ernment, BPD and societies. Collecting data technique doing by triangulation, inductive data analysis, and the result of the qualitative study emphasize to the good meaning of the study. this study showed that the role of government in building of Wonosari village is good enough and balance. The cooperation is mutual where the involved knowing each the position and role in build the village. The local government has role to facilitate the societies and give good guidance about the purpose of the building. People play the role in giving the ideas, energy and wealth to the success of build. Whereas, the support fac- tor is cooperation of government – society is the approach of government to the society. And the society has understood about their position and their role in study. In addition to, the inhibit factor is minimal awareness of society to the program and there is still opinion from the government that society is the object of supervision build.

The salivary transcriptome of Limnobdella mexicana (Annelida: Clitellata: Praobdellidae) and orthology determination of major leech anticoagulants

Bloodfeeding requires several adaptations that allow the parasite to feed efficiently. Leeches and other hematophagous animals have developed different mechanisms to inhibit hemostasis, one of the main barriers imposed by their hosts. Limnobdella mexicana is a member of the leech family Praobdellidae, a family of host generalists known for their preference to attach on mucosal membranes of mammals, such as those in nasopharyngeal cavities, bladders and ocular orbits. Previous studies have hypothesized a positive relationship between diversity of anticoagulants and diversity of hosts in bloodfeeding leeches. However, orthology determination of putative anticoagulants and the lack of standardization of sequencing effort and method hinder comparisons between publicly available transcriptomes generated in different laboratories. In the present study, we examine the first transcriptome of a praobdellid leech and identify 15 putative anticoagulants using a phylogeny-based inference approach, amino-acid conservation, Pfam domains and BLAST searches. Our phylogenetic analyses suggest that the ancestral leech was able to inhibit factor Xa and that some hirudins that have been reported in previous studies on leech anticoagulants may not be orthologous with the archetypal hirudin.

The Non-Vitamin K Antagonist Oral Anticoagulants in Heart Disease: Section V—Special Situations

Non-vitamin K antagonist oral anticoagulants (NOACs) include dabigatran, which inhibits thrombin, and apixaban, betrixaban, edoxaban and rivaroxaban, which inhibit factor Xa. In large clinical trials comparing the NOACs with the vitamin K antagonist (VKA) warfarin, dabigatran, apixaban, rivaroxaban and edoxaban were at least as effective for stroke prevention in atrial fibrillation and for treatment of venous thromboembolism, but were associated with less intracranial bleeding. In addition, the NOACs are more convenient to administer than VKAs because they can be given in fixed doses without routine coagulation monitoring. Consequently, the NOACs are now replacing VKAs for these indications, and their use is increasing. Although, as a class, the NOACs have a favourable benefit–risk profile compared with VKAs, choosing among them is complicated because they have not been compared in head-to-head trials. Therefore, selection depends on the results of the individual trials, renal function, the potential for drug–drug interactions and preference for once- or twice-daily dosing. In addition, several ‘special situations’ were not adequately studied in the dedicated clinical trials. For these situations, knowledge of the unique pharmacological features of the various NOACs and judicious cross-trial comparison can help inform prescription choices. The purpose of this position article is therefore to help clinicians choose the right anticoagulant for the right patient at the right dose by reviewing a variety of special situations not widely studied in clinical trials.

Reversing anti–factor Xa agents and the unmet needs in trauma patients

Andexanet alfa, a reversing agent for anticoagulants that inhibit factor Xa, has recently been licensed in the United States. We discuss the impact of this licensure on current practice and review in detail the problems of a neglected and growing clinical area: reversing the anticoagulation effect of factor Xa inhibitors in bleeding trauma patients. We identify areas of practice that need research so that care of bleeding trauma patients receiving direct factor Xa inhibitors can be improved.

Orphan Three-Finger Toxins Bind at Tissue Factor–Factor VIIa Interface to Inhibit Factor X Activation: Identification of Functional Site by Docking

Three-finger toxins (3FTxs) contribute to toxicity of venomous snakes belonging to the family Elapidae. Currently, functions of a considerable proportion of 3FTxs are still unknown. Here, we describe the function of orphan group I 3FTxs consisting of four members. We also identified a new member of this group by sequencing a transcript isolated from Naja naja venom. This transcript, named najalexin, is identical to that previously described 3FTx from Naja atra venom gland, and shared high sequence identity with ringhalexin from Hemachatus haemachatus and a hypothetical protein from Ophiophagus hannah (here named as ophiolexin). The three-dimensional structure, as predicted by molecular modeling, showed that najalexin and ophiolexin share the same conserved structural organization as ringhalexin and other 3FTxs. Since ringhalexin inhibits the activation of factor X by the tissue factor–factor VIIa complex (TF-FVIIa), we evaluated the interaction of this group of 3FTxs with all components using in silico protein–protein docking studies. The binding of orphan group I 3FTxs to TF-FVIIa complex appears to be driven by their interaction with TF. They bind to fibronectin domain closer to the 170-loop of the FVIIa heavy chain to inhibit factor X activation. The docking studies reveal that functional site residues Tyr7, Lys9, Glu12, Lys26, Arg34, Leu35, Arg40, Val55, Asp56, Cys57, Cys58, and Arg65 on these 3FTxs are crucial for interaction. In silico replacement of these residues by Ala resulted in significant effects in the binding energies. Furthermore, these functional residues are not found in other groups of 3FTxs, which exhibit distinct pharmacological properties.

Mechanistic Basis for the Differential Effects of Rivaroxaban and Apixaban on Global Tests of Coagulation

Rivaroxaban and apixaban are both small molecules that reversibly inhibit factor Xa. Compared with rivaroxaban, apixaban has minimal effects on the prothrombin time and activated partial thromboplastin time. To investigate this phenomenon, we used a factor Xa-directed substrate in a buffer system. Although rivaroxaban and apixaban inhibited factor Xa with similar Ki values at equilibrium, kinetic measurements revealed that rivaroxaban inhibited factor Xa up to 4-fold faster than apixaban (p < 0.001). Using a discontinuous chromogenic assay to monitor thrombin production by prothrombinase in a purified system, rivaroxaban was 4-fold more potent than apixaban (Ki values of 0.7 ± 0.3 and 2.9 ± 0.5 nM, respectively; p = 0.02). Likewise, in thrombin generation assays in plasma, rivaroxaban prolonged the lag time and suppressed endogenous thrombin potential to a greater extent than apixaban. To characterize how the two inhibitors differ in recognizing factor Xa, inhibition of prothrombinase was monitored in real-time using a fluorescent probe for thrombin. The data were fit using a mixed-inhibition model and the individual association and dissociation rate constants were determined. The association rates for the binding of rivaroxaban to either free factor Xa or factor Xa incorporated into the prothrombinase complex were 10- and 1,193-fold faster than those for apixaban, respectively, whereas dissociation rates were about 3-fold faster. Collectively, these findings suggest that rivaroxaban and apixaban differ in their capacity to inhibit factor Xa and provide a plausible explanation for the observation that rivaroxaban has a greater effect on global tests of coagulation than apixaban.

Recent advances in the treatment of venous thromboembolism in the era of the direct oral anticoagulants

The direct oral anticoagulants (DOACs) have now supplanted vitamin K antagonists (VKAs) for the treatment of venous thromboembolism (VTE). The DOACs include dabigatran, which inhibits thrombin, and rivaroxaban, apixaban, and edoxaban, which inhibit factor Xa. The DOACs are as effective for the prevention of recurrence as conventional VTE treatment, consisting of a parenteral anticoagulant followed by a VKA, and are associated with less bleeding. Because of these properties and the convenience of fixed dosing without the need for routine coagulation monitoring, guidelines now recommend DOACs over VKAs for VTE treatment in patients without active cancer. This paper examines the increasing role of the DOACs for VTE treatment.

Acylcarnitines are anticoagulants that inhibit factor Xa and are reduced in venous thrombosis, based on metabolomics data

Key PointsUntargeted and targeted metabolomics showed association of low plasma acylcarnitines levels with venous thrombosis risk. Long-chain acylcarnitines are anticoagulants that inhibit factor Xa by binding to factor Xa outside the γ-carboxy glutamic acid domain.

Effects of Two Trypsin Inhibitors on Trypsin in Activity and Structure

Two reversible trypsin inhibitors, Kunitz trypsin inhibitor (KTI) and Bowman-Birk trypsin inhibitor (BBI) were compared to find the more optimal one as the inhibit factor during trypsin immobilization. Fluorescence spectroscopy, UV–visible absorption spectroscopy and circular dichroism (CD) spectroscopy were used to explore the effects of the two inhibitors on trypsin in activity and structure. The results showed that both inhibitors combined with trypsin in 1:1. CD circular dichroism spectroscopy showed that KTI and BBI led to different changes in trypsin second structure. The results can help us find out the mechanism between the two inhibitors and trypsin and select the more optimal inhibitor in trypsin immobilization.