Objective Probiotics are beneficial in human health. In this study, we investigated the effect of probiotics on absorption of amlodipine, a dihydropyridine calcium antagonist used in the treatment of angina and hypertension, in a rabbit model. Methods Lactobacillus plantarum IS-10506 probiotic was administered for 14 days to male New Zealand rabbits. Blood samples were collected before and after probiotic supplementation. Amlodipine (10 mg) was then administered to all groups. Blood samples from a marginal vein were withdrawn at 5, 15, 30, 60, and 120 minutes to determine amlodipine concentrations in rabbit plasma. Results Amlodipine concentrations in the L. plantarum IS-10506 group were 4.95 ± 1.22, 8.71 ± 0.69, and 12.48 ± 2.53 ng/ml, and those in the control group were 1.69 ± 0.31, 3.89 ± 1.23, and 7.17 ± 1.85 ng/ml at 30, 60, and 120 minutes, respectively after administration of amlodipine. Amlodipine concentrations in the L. plantarum IS-10506 group were significantly higher than those in the control group at 30, 60, and 120 minutes after amlodipine administration. Conclusion Our results suggested that supplementation of L. plantarum IS-10506 significantly increases amlodipine plasma concentrations in rabbits.
Rapid resistance development of HIV-1 and Plasmodium falciparum parasite requires discovery of more potent new drugs. Aspartic protease enzymes expressed by HIV-1 and P. falciparum could be used as important drug targets. The catalytic site is located at the bottom of a cleft in the enzyme surface and consists of triad Asp25, Thr26, Gly27. Important aspartic acids are Asp32 and Asp215. Aspartic proteases are inhibited by pepstatin-A, a naturally occurring peptide containing two statins, which replace the amino acids. The hydroxyl group of the statin binds tightly to the catalytically-active aspartic acid residues in the active site of protease, thereby mimicking the transition state of the peptide cleavage. Previous study proved that ganoderiol-F, a triterpenoid isolated from the stem of Ganoderma sinense showed higher affinity towards HIV-1 protease (binding energy= -11.40 kcal/mol and K i = 4.68 nM) than to plasmepsin I (binding energy= -9.96 kcal/mol and K i = 50.94 nM). In this paper, computational studies of G. lucidum triterpenoids with aspartic protease enzymes of HIV-1 and plasmepsin I, were performed using AutoDock 4.2. Nelfinavir and KNI-10006 were used as the standards for HIV-1 protease and plasmepsin I, respectively. The four triterpenoids are able to interact with both enzymes. Ganoderat acid-B showed the best affinity to HIV-1 protease (binding energy= -7.49 kcal/mol and Ki= 0.001 mM) which is better than nelfinavir. Furthermore, the best affinity to Plasmepsin I is showed by ganodermanondiol (binding energy= -7.14 kcal/mol and Ki= 0.005 mM which is better than KNI-10006. According to the values of binding energy and inhibition constant, triterpenoids of G. lucidum could be developed further as both anti-HIV and anti-malaria.
Saat ini, lebih dari setengah antibiotik yang digunakan di dunia merupakan kelompok β-laktam namun efektivitas klinis antibiotik tersebut kini terbatas karena resistensi antibiotik terhadap mikroorganisme penyebab penyakit infeksius. Beberapa mekanisme resistensi terhadap Enterobacteriaceae terutama disebabkan hidrolisis antibiotik oleh enzim spesifik, yang disebut dengan β-laktamase. Enzim β-laktamase menunjukkan kelompok besar enzim yang berbeda secara genetik dan fungsional yaitu extended-spectrum β-lactamase (ESBL) yang diketahui menimbulkan ancaman resistensi yang serius. Lokalisasi plasmid dari gen yang disandi terhadap distribusi enzim pada patogen meningkat setiap tahunnya. ESBL yang memiliki penyebaran yang luas dan relevan secara klinis adalah ESBL kelas A yaitu jenis Temoniera (TEM), Sulphydryl variable (SHV) dan Cefotaxime (CTX-M). Tujuan penulisan review ini adalah untuk mengkaji varian gen bla CTX-M yang banyak menyebabkan peningkatan resistensi antibiotik. Metode yang digunakan pada review ini yaitu penelusuran data berbasis Pubmed, Scopus dan Google Scholar tanpa pembatasan indeks faktor dengan kata kunci "bla CTX-M ", "Extended-spectrum β-lactamase", dan "antibiotic resistance". Ssimpulan dari review ini yaitu ESBL jenis CTX-M telah menggantikan jenis TEM dan SHV secara dominan pada dekade terakhir. ESBL yang dihasilkan oleh Klebsiella pneumoniae diketahui muncul sebagai salah satu patogen nosokomial utama. Infeksi nosokomial yang disebabkan oleh CTX-M-15 pada Klebsiella pneumoniae mengalami peningkatan dalam beberapa tahun terakhir ini.
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