Efficacy of the New Neuraminidase Inhibitor CS-8958 against H5N1 Influenza Viruses

Currently, two neuraminidase (NA) inhibitors, oseltamivir and zanamivir, which must be administrated twice daily for 5 days for maximum therapeutic effect, are licensed for the treatment of influenza. However, oseltamivir-resistant mutants of seasonal H1N1 and highly pathogenic H5N1 avian influenza A viruses have emerged. Therefore, alternative antiviral agents are needed. Recently, a new neuraminidase inhibitor, R-125489, and its prodrug, CS-8958, have been developed. CS-8958 functions as a long-acting NA inhibitor in vivo (mice) and is efficacious against seasonal influenza strains following a single intranasal dose. Here, we tested the efficacy of this compound against H5N1 influenza viruses, which have spread across several continents and caused epidemics with high morbidity and mortality. We demonstrated that R-125489 interferes with the NA activity of H5N1 viruses, including oseltamivir-resistant and different clade strains. A single dose of CS-8958 (1,500 µg/kg) given to mice 2 h post-infection with H5N1 influenza viruses produced a higher survival rate than did continuous five-day administration of oseltamivir (50 mg/kg twice daily). Virus titers in lungs and brain were substantially lower in infected mice treated with a single dose of CS-8958 than in those treated with the five-day course of oseltamivir. CS-8958 was also highly efficacious against highly pathogenic H5N1 influenza virus and oseltamivir-resistant variants. A single dose of CS-8958 given seven days prior to virus infection also protected mice against H5N1 virus lethal infection. To evaluate the improved efficacy of CS-8958 over oseltamivir, the binding stability of R-125489 to various subtypes of influenza virus was assessed and compared with that of other NA inhibitors. We found that R-125489 bound to NA more tightly than did any other NA inhibitor tested. Our results indicate that CS-8958 is highly effective for the treatment and prophylaxis of infection with H5N1 influenza viruses, including oseltamivir-resistant mutants

Experimental Models Point Mutations in Plasmodium Falciparum Pfatpase6 Gene Exposed to Recuring Artemisinin in Vitro

The aims of this research to prove that repeated exposure of artemisinin can cause pfatpase6 gene mutation on Plasmodium falciparum in vitro. The research methods used culture In Vitro Plasmodium falciparum of strain 2300 IC50 value determination test artemisinin, artemisinin repeated exposure test (PO1, PO2, PO3 dan PO4) dose IC50, DNA extraction, gene amplification of pfatpase6 using Polymerase Chain Reaction (PCR) technique, electrophoresis, PCR product purification, labeling DNA from PCR results, DNA precipitation of PCR product, application of product labeling on the sequencing machines, analysis of the results of sequencing, and Data Analysis. The results of PCR pfatpase6 gene amplification include region 6 – 3216 for codon 89-1031 located in exon 1 and 2 Plasmodium falciparum 2300 by using five pairs of primers. Primer pair 1FR produce a long amplicon of 737 bp which covers of codon 89; primer pair 2FR produce a long amplicon of 813 bp which covers of codon 263, 431; primer pair 4FR produce a long amplicon of 700 bp which covers of codon 460, 465, 623; primer pair 5FR produce a long amplicon of 550 bp which includes of codon 683, 769; and primer pair 6FR produce a long amplicon of 876 bp which covers of codon 898, 1031.Multialigment pfatpase6 gene Plasmodium falciparum of strains Papua 2300 point mutations are obtained in the form of transition and transversion in treatment groups at the same nucleotide region 123, 2035, 2043, 2138 dan 2148. Conclusion of this research Artemisinin repeated exposure can cause point mutations in pfatpase6 genes Plasmodium falciparum of strains 2300 in vitr

The Steroid Hormone Profile in Etawah Crossbreed Goat While Ovulation Induced Using the Selectsynch Method

This study aimed to provide alternative information and solutions in an effort to increase reproductive productivity in etawah crossbreed goats (PE). The sample used in this study was 10 female PE with an average age of 2.5 - 3 years and primiparous at least . Ovulation induction was performed using 0.1 mg intra-muscular Gonadotropin-Releasing Hormone (GnRH), after seven days injection of Prostaglandin F2α (PGF2α) was given as much as 2.5 mg submucosa of the vulva, followed by a second injection of GnRH as much as 0,2 mg intramuscular in samples that have really experienced heat and selected selectively according to the signs of natural heat shown by the sample and followed by insemination as much as 2 doses or 0.50 ml of frozen semen. Blood sampling was performed at H0, H7th, H14th and H21th after insemination. All blood samples were collected and progesterone and estrogen hormone profiles were examined using the ELISA method. From the results of the ELISA test, the mean progesterone hormone profile H0 = 4.798 ng / ml, H7th = 4.887 ng / ml, H14th = 4.824 ng / ml, H21th = 5.148 ng / ml. The profile of the hormone estrogen at H0 = 19,461 pg / ml, H7th = 17,457 pg / ml, H14th = 18,248 pg / ml, H21th = 17,515 pg / ml. This study showed an increase in the levels of the progesterone hormone at H0 to H7th, then slightly decreased in H14th and a significant increase in H21th. For the estrogen hormone, there is a decrease from H0 to H7th then there is a slight increase in H14th and decreases again in H21th

Produksi dan Kualitas Telur Itik Alabio di Daerah Sentra Peternakan Desa Sungai Pandan, Kabupaten Hulu Sungai Utara, Kalimantan Selatan

Penelitian ini merupakan penelitian deskriptif dengan menggunakan 20 itik Alabio betina siap bertelur dengan rentang usia 6 bulan dan untuk pemeriksaan kualitas telur untuk masing-masing kelompok 10 sampel. Pengamatan tingkat produksi telur dilakukan selama tiga bulan dengan 10 pengulangan, kualitas telur (ketebalan kulit telur, persentase kulit telur, persentase kulit telur, persentase albumin, persentase kuning telur, huagh unit, warna kuning telur, kadar protein dan lemak kandungan). Data produksi telur dan kualitas telur diuji menggunakan uji Anova. Hasil pengamatan rata-rata produksi harian telur 15.45 ± 0.12, 14.72 ± 0.10, 14.91 ± 0.09; produksi berat harian (kg/hari) 925.27 ± 7.50, 875.40 ± 6.32, 884 ± 5.03; hasil dari ketebalan kulit telur kualitas 0.33 ± 0.01, 0.33 ± 0.12, 0.33 ± 0.12; persentase kulit telur 11.32 ± 0.93, 11.28 ± 0.10, 11.36 ± 0.05; persentase albumin 55.70 ± 1.08, 56.66 ± 1.22, 56.12 ± 1.00; persen kuning telur 32.07 ± 1.24, 31.55 ± 1.48, 31.64 ± 1.20; Haugh unit 88.70 ± 6.21, 91.41 ± 6.70, 94.51 ± 5.06. Warna kuning masing-masing memiliki skor 15. Dapat disimpulkan bahwa produksi dan kualitas telur itik Alabio baik