C-C Bond formation in the purine 8-position by addition of allylmetals

8-Substituted purines have been extensively studied as for example anticancer or antiviral drugs. C-C Bond formation at the purine 8-position has been most commonly done via 8-halopurines, e.g. Pd-catalyzed coupling reactions. Meanwhile, direct conversion of purines not substituted at C-8 to 8-alkylpurines seems to be promising but there are few reports in the literature. In this thesis, addition of an allylmetallic reagent to 8-unsustituted purines followed by oxidation of the adduct to form 8-allylated purines will be discussed

SECONDARY METABOLITES FROM MICROMONOSPORA SP. (G044)

In the course of our screening program, the EtOAc extract of a Micromonospora sp. (strain G044) from sponge Tethya aurantium of the sea of Côtô - Thanh Lân exhibited antimicrobial activity against Enterococcus faecalis, Bacillus cereus and Candida albicans. In this paper, we reported the isolation and structural elucidation of six secondary metabolites Cyclo-(Pro-Trp) (1), Cyclo-(Pro-Met) (2), Cyclo-(Pro-Val) (4), N-acetyltryptamine (3), uridine (5), and 2-phenylacetic acid (6) from the cultures broth of Micromonospora sp. (strain G044). The structures of 1 – 6 were determined by analyses of MS and 2D NMR data. All compounds were evaluated for their antimicrobial activity against a panel of clinically significant microorganisms. Compound 1 inhibited Escherichia coli with a MIC value of 128 µg/ml

Penetrating Keratoplasty for Keratoconus in Vietnamese Patients

BACKGROUND: Keratoconus is an ectatic corneal disorder that can impair the visual acuity. Up to now, penetrating keratoplasty (PK) remains the most common surgical procedure to treat severe keratoconus. In Vietnam, most keratoconus patients come to visit doctor at severe stage and were treated by PK, so we conduct this study. AIM: To evaluate the results of PK for keratoconus in Vietnamese patients. METHODS: This was a retrospective study of 31 eyes with keratoconus who underwent PK in VNIO from January 2005 to December 2014. RESULTS: The average visual acuity was 0.86 ± 0.37 logMAR (20/145). In the group of patients without amblyopia, best spectacle-corrected visual acuity of 20/60 or better was recorded in 75.9% of eyes and 93.1% of eyes achieved a best corrected visual acuity with hard contact lenses of 20/40 or better. Mean postoperative corneal power was 43.8 ± 4.5D. Mean corneal astigmatism was 5.9 ± 2.7D. 94.6% of grafts remained clear. Posterior subcapsular cataract developed in 22.6% of eyes. Graft rejection was recognized in 12.9% of eyes. CONCLUSION: PK is an effective procedure with high rate of graft survival for keratoconus patients. However, patients should be aware of the necessary of optical correction to gain the best VA after surgery

Chemical constituents from fruits of Hydnocarpus hainanensis Merr. (Flacourtiaceae) in Vietnam

Five compounds were isolated from the fruits of Hydnocarpus hainanensis Merr. Sleum. (Flacourtiaceae). Their structures were determined by spectroscopic analysis including MS and NMR. The isolates were identified as taraktophyllin (1), hydnocarpic acid (2), 3,4-dihydroxybenzyl alcohol (3), 3,4-dihydroxybenzoic acid (4) and 3-hydroxy-4-methoxybenzoic acid (5)

Secondary metabolites from Micromonospora ectrinospora G017

Eight  compounds, cyclo-(Pro-Tryp) (1), N-[2-(1H-indol-3-yl)-2-oxo-ethyl] acetamide (2), cyclo-(Pro-Tyr) (3), cyclo-(Pro-Phe) (4), cyclo-trans-4-OH-(Pro-Phe) (5), cyclo-(Pro-Leu) (6), cyclo-(Pro-Val) (7), and  uracil (8) were isolated from the culture broth of the marine Micromonospora ectrinospora G017 strain. The structures of the isolated compounds were established on the basis of their spectral data, including mass spectrometry and NMR

Terpenoids from leaves of Viburnum sambucinum Reinw. ex. Blume (Caprifoliaceae)

Six compounds were isolated from the leaves of Viburnum sambucinum Reinw. ex Blume (Caprifoliaceae).  The structures of the isolates were determined by spectroscopic analysis including MS and NMR. Accordingly, the isolated compounds were identified as a-amyrin (1), ursolic acid (2), 3β,28-dihydroxy-urs-12-ene (3), oleanolic acid (4), 16β-hydroxylup-20(29)-ene-3-one (5) and trans-2-phyten-1-ol (6)

Discrepancies in Infectivity of Flavivirus and SARS-CoV-2 Clinical Samples: An Improved Assay for Infectious Virus Shedding and Viremia Assessment

Infectivity and neutralizing antibody titers of flavivirus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are frequently measured using the conventional plaque assay. While the assay is useful in the determination of infectivity, conventional plaque assays generally possess lower sensitivity and are time-consuming compared to nucleic acid amplification tests. In this study, a microcrystalline cellulose (MCC), Avicel, was evaluated as an alternative to the conventional virus overlay medium, methylcellulose, for a plaque assay. The plaque assay was performed using dengue and COVID-19 clinical samples and laboratory-established flavivirus and SARS-CoV-2 strains. In virus titration of clinical samples, the plaques were significantly larger, and the virus titers were higher when Avicel MCC-containing overlay medium was used than with conventional methylcellulose overlay medium. In addition, for some clinical samples and laboratory virus strains, infectious particles were detected as plaques in the Avicel MCC-containing medium, but not in the conventional methylcellulose medium. The results suggest that the viremia titer determined using the new overlay medium containing Avicel MCC may better reflect the innate infectious and plaque-forming capabilities of clinical samples and better reflect virus infectivity

Direct Viral RNA Detection of SARS-CoV-2 and DENV in Inactivated Samples by Real-Time RT-qPCR: Implications for Diagnosis in Resource Limited Settings with Flavivirus Co-Circulation

The RT-qPCR method remains the gold standard and first-line diagnostic method for the detection of SARS-CoV-2 and flaviviruses, especially in the early stage of viral infection. Rapid and accurate viral detection is a starting point in the containment of the COVID-19 pandemic and flavivirus outbreaks. However, the shortage of diagnostic reagents and supplies, especially in resource-limited countries that experience co-circulation of SARS-CoV-2 and flaviviruses, are limitations that may result in lesser availability of RT-qPCR-based diagnostic tests. In this study, the utility of RNA-free extraction methods was assessed for the direct detection of SARS-CoV-2 and DENV-2 in heat-inactivated or chemical-inactivated samples. The findings demonstrate that direct real-time RT-qPCR is a feasible option in comparison to conventional real-time RT-qPCR based on viral genome extraction-based methods. The utility of heat-inactivation and direct real-time RT-qPCR for SARS-CoV-2, DENV-2 viral RNA detection was demonstrated by using clinical samples of SARS-CoV-2 and DENV-2 and spiked cell culture samples of SARS-CoV-2 and DENV-2. This study provides a simple alternative workflow for flavivirus and SARS-CoV-2 detection that includes heat inactivation and viral RNA extraction-free protocols, with aims to reduce the risk of exposure during processing of SARS-CoV-2 biological specimens and to overcome the supply-chain bottleneck, particularly in resource limited settings with flavivirus co-circulation

Risk factors for cannula-associated arterial thrombosis following extracorporeal membrane oxygenation support: a retrospective study

Background Hemostatic dysfunction during extracorporeal membrane oxygenation (ECMO) due to blood-circuit interaction and the consequences of shear stress imposed by flow rates lead to rapid coagulation cascade and thrombus formation in the ECMO system and blood vessels. We aimed to identify the incidence and risk factors for cannula-associated arterial thrombosis (CaAT) post-decannulation. Methods A retrospective study of patients undergoing arterial cannula removal following ECMO was performed. We evaluated the incidence of CaAT and compared the characteristics, ECMO machine parameters, cannula sizes, number of blood products transfused during ECMO, and daily hemostasis parameters in patients with and without CaAT. Multivariate analysis identified the risk factors for CaAT. Results Forty-seven patients requiring venoarterial ECMO (VA-ECMO) or hybrid methods were recruited for thrombosis screening. The median Sequential Organ Failure Assessment score was 11 (interquartile range, 8–13). CaAT occurred in 29 patients (61.7%), with thrombosis in the superficial femoral artery accounting for 51.7% of cases. The rate of limb ischemia complications in the CaAT group was 17.2%. Multivariate analysis determined that the ECMO flow rate–body surface area (BSA) ratio (100 ml/min/m2) was an independent factor for CaAT, with an odds ratio of 0.79 (95% confidence interval, 0.66–0.95; P=0.014). Conclusions We found that the incidence of CaAT was 61.7% following successful decannulation from VA-ECMO or hybrid modes, and the ECMO flow rate–BSA ratio was an independent risk factor for CaAT. We suggest screening for arterial thrombosis following VA-ECMO, and further research is needed to determine the risks and benefits of such screening

Differential Infectivity of Human Neural Cell Lines by a Dengue Virus Serotype-3 Genotype-III with a Distinct Nonstructural Protein 2A (NS2A) Amino Acid Substitution Isolated from the Cerebrospinal Fluid of a Dengue Encephalitis Patient

Dengue encephalitis is considered as a severe but unusual clinical presentation of dengue infection. Limited molecular information is available on the neurotropism of dengue virus (DENV), highlighting the need for further research. During a dengue outbreak in Vietnam in 2013, two DENV-3 strains were isolated, in which one was isolated from cerebrospinal fluid (CSF) samples from a dengue encephalitis patient and another strain was isolated from a patient with classical dengue fever in Hai Phong, Vietnam. DENV serotype-3 (DENV-3) isolated from these samples belonged to genotype III, marking the first report of this genotype in the country at that time. Genetic variation between both strains was elucidated by using a full genome sequencing by next-generation sequencing (NGS). The infectivity of the isolated DENV-3 strains was further characterized using human and mouse neuronal cell lines. Phylogenetic analysis of the isolates demonstrated high homogeneity between the CSF-derived and serum-derived DENV-3, in which the full genome sequences of the CSF-derived DENV-3 presented a Thr-1339-Ile mutation in the nonstructural 2A (NS2A) protein. The CSF-derived DENV-3 isolate grew preferentially in human neuronal cells, with a significant proportion of cells that were positive for nonstructural 1 (NS1), nonstructural 4B (NS4B), and nonstructural 5 (NS5) antigens. These results suggest that NS2A may be a crucial region in the neuropathogenesis of DENV-3 and its growth in human neuronal cells. Taken together, our results demonstrate that a CSF-derived DENV-3 has unique infectivity characteristics for human neuronal cells, which might play a crucial role in the neuropathogenesis of DENV infection