Haemanthus coccineus extract and its main bioactive component narciclasine display profound anti-inflammatory activities in vitro and in vivo

Haemanthus coccineus extracts (HCE) have traditionally been used to treat a variety of diseases, like febrile colds or asthma. Since new therapeutic options against inflammatory processes are still urgently needed, we aimed to pharmacologically characterise the anti-inflammatory potential of HCEin vitro and in vivo and to identify the underlying bioactive component(s). The action of HCE on oedema formation and leucocyte infiltration were analysed in two murine models of inflammation (dermal oedema induced by arachidonic acid and croton oil;kidney injury caused by unilateral ureteral obstruction). The interaction of leucocytes with endothelial cells (ECs) as well as the activation parameters of these two cell types were analysed. Moreover, the nuclear factor B (NFB) pathway was investigated in detail in ECs. Using different fractions of HCE, the bioactive principle was identified. In vivo, HCE (450mg/kg orally or 2mg/kg intraperitoneally) inhibited oedema formation, leucocyte infiltration and cytokine synthesis. In vitro, HCE (100-300ng/ml) blocked leucocyte-EC interaction as well as the activation of isolated leucocytes (cytokine synthesis and proliferation) and of primary ECs (adhesion molecule expression). HCE suppressed NFB-dependent gene transcription in the endothelium, but did not interfere with the NFB activation cascade (IB degradation, p65 nuclear translocation and NFB DNA-binding activity). The alkaloid narciclasine was elucidated as the bioactive compound responsible for the anti-inflammatory action of HCE. Our study highlights HCE and its main alkaloid narciclasine as novel interesting approach for the treatment of inflammation-related disorders

Dynamics of UF[6] Desublimation with the Influence of Tank Geometry for Various Coolant Temperature

Mathematical model of UF[6] desublimation in a vertical immersion tank is presented in the article. Results of calculations of the filling dynamics of the tanks with 1m3 volume at various coolant temperatures, with and without ellipticity of the end walls are given. It is shown that allowance for the ellipticity of the end walls of the tanks leads to a significant increase in the time of desublimation of UF[6]

Haemanthus coccineus extract and its main bioactive component narciclasine display profound anti-inflammatory activities in vitro and in vivo

Haemanthus coccineus extracts (HCE) have traditionally been used to treat a variety of diseases, like febrile colds or asthma. Since new therapeutic options against inflammatory processes are still urgently needed, we aimed to pharmacologically characterise the anti-inflammatory potential of HCEin vitro and in vivo and to identify the underlying bioactive component(s). The action of HCE on oedema formation and leucocyte infiltration were analysed in two murine models of inflammation (dermal oedema induced by arachidonic acid and croton oil;kidney injury caused by unilateral ureteral obstruction). The interaction of leucocytes with endothelial cells (ECs) as well as the activation parameters of these two cell types were analysed. Moreover, the nuclear factor B (NFB) pathway was investigated in detail in ECs. Using different fractions of HCE, the bioactive principle was identified. In vivo, HCE (450mg/kg orally or 2mg/kg intraperitoneally) inhibited oedema formation, leucocyte infiltration and cytokine synthesis. In vitro, HCE (100-300ng/ml) blocked leucocyte-EC interaction as well as the activation of isolated leucocytes (cytokine synthesis and proliferation) and of primary ECs (adhesion molecule expression). HCE suppressed NFB-dependent gene transcription in the endothelium, but did not interfere with the NFB activation cascade (IB degradation, p65 nuclear translocation and NFB DNA-binding activity). The alkaloid narciclasine was elucidated as the bioactive compound responsible for the anti-inflammatory action of HCE. Our study highlights HCE and its main alkaloid narciclasine as novel interesting approach for the treatment of inflammation-related disorders

Elevated prevalence of multidrug-resistant gram-negative organisms in HIV positive men

Background: Routes of transmission of multidrug-resistant gram-negative organisms (MDRGN) are not completely understood. Since sexual transmission of MDRGN might represent a potential mode that has not been noticed so far, this study evaluated transmission of MDRGN in HIV positive men. Methods: Between November 2014 and March 2016, we retrospectively investigated the MDRGN prevalence in rectal swabs of n = 109 males tested positive for HIV (HP). These findings were compared to the MDRGN prevalence in n = 109 rectal swabs in age-matched males tested negative for HIV (HN) within the same period. According to the infection control protocol of University Hospital Frankfurt, Germany (UHF), patients admitted to intensive/intermediate care units have to be screened for MDRGN on day of admittance. Patients without HIV testing or MDRGN screening were excluded. Results: MDRGN prevalence in rectal swabs was significantly higher (p = 0.002) in male HP (23.9%;95% confidence interval 16.2-32.9%) than in age-matched male HN (8.3%;3.8-15.1%). In total, 35 MDRGN species were detected. The most frequent MDRGN species was Escherichia coli with resistance due to ESBL expression and additional resistance to fluoroquinolones with n = 25/35 (71.4%;53.7-85.4%). Thereof, n = 19/26 (73.1%;52.2-88.4%) were detected in HP and n = 6/9 (66.7%;29.9-92.5%) in HN, respectively. Conclusions: Prevalence of MDRGN is significantly higher in male HIV positive than in male HIV negative individuals. This might indicate sexual transmission of MDRGN within the male HIV positive population. As treatment options in case of MRGN infections are limited, prevention of MDRGN transmission is strongly emphasized

Novel Riboswitch Ligand Analogs as Selective Inhibitors of Guanine-Related Metabolic Pathways

Riboswitches are regulatory elements modulating gene expression in response to specific metabolite binding. It has been recently reported that riboswitch agonists may exhibit antimicrobial properties by binding to the riboswitch domain. Guanine riboswitches are involved in the regulation of transport and biosynthesis of purine metabolites, which are critical for the nucleotides cellular pool. Upon guanine binding, these riboswitches stabilize a 5′-untranslated mRNA structure that causes transcription attenuation of the downstream open reading frame. In principle, any agonistic compound targeting a guanine riboswitch could cause gene repression even when the cell is starved for guanine. Antibiotics binding to riboswitches provide novel antimicrobial compounds that can be rationally designed from riboswitch crystal structures. Using this, we have identified a pyrimidine compound (PC1) binding guanine riboswitches that shows bactericidal activity against a subgroup of bacterial species including well-known nosocomial pathogens. This selective bacterial killing is only achieved when guaA, a gene coding for a GMP synthetase, is under the control of the riboswitch. Among the bacterial strains tested, several clinical strains exhibiting multiple drug resistance were inhibited suggesting that PC1 targets a different metabolic pathway. As a proof of principle, we have used a mouse model to show a direct correlation between the administration of PC1 and the reduction of Staphylococcus aureus infection in mammary glands. This work establishes the possibility of using existing structural knowledge to design novel guanine riboswitch-targeting antibiotics as powerful and selective antimicrobial compounds. Particularly, the finding of this new guanine riboswitch target is crucial as community-acquired bacterial infections have recently started to emerge

Antimicrobial susceptibility patterns and characterization of clinical isolates of Staphylococcus aureus in KwaZulu-Natal province, South Africa

BACKGROUND: Antimicrobial resistance of Staphylococcus aureus especially methicillin-resistant S. aureus (MRSA) continues to be a problem for clinicians worldwide. However, few data on the antibiotic susceptibility patterns of S. aureus isolates in South Africa have been reported and the prevalence of MRSA in the KwaZulu-Natal (KZN) province is unknown. In addition, information on the characterization of S. aureus in this province is unavailable. This study investigated the susceptibility pattern of 227 S. aureus isolates from the KZN province, South Africa. In addition, characterization of methicillin-sensitive S. aureus (MSSA) and MRSA are reported in this survey. METHODS: The in-vitro activities of 20 antibiotics against 227 consecutive non-duplicate S. aureus isolates from clinical samples in KZN province, South Africa were determined by the disk-diffusion technique. Isolates resistant to oxacillin and mupirocin were confirmed by PCR detection of the mecA and mup genes respectively. PCR-RFLP of the coagulase gene was employed in the characterization of MSSA and MRSA. RESULTS: All the isolates were susceptible to vancomycin, teicoplanin and fusidic acid, and 26.9% of isolates studied were confirmed as MRSA. More than 80% of MRSA were resistant to at least four classes of antibiotics and isolates grouped in antibiotype 8 appears to be widespread in the province. The MSSA were also susceptible to streptomycin, neomycin and minocycline, while less than 1% was resistant to chloramphenicol, ciprofloxacin, rifampicin and mupirocin. The inducible MLS(B )phenotype was detected in 10.8% of MSSA and 82% of MRSA respectively, and one MSSA and one MRSA exhibited high-level resistance to mupirocin. There was good correlation between antibiotyping and PCR-RFLP of the coagulase gene in the characterization of MRSA in antibiotypes 1, 5 and 12. CONCLUSION: In view of the high resistance rates of MRSA to gentamicin, erythromycin, clindamycin, rifampicin and trimethoprim, treatment of MRSA infections in this province with these antibacterial agents would be unreliable. There is an emerging trend of mupirocin resistance among S. aureus isolates in the province. PCR-RFLP of the coagulase gene was able to distinguish MSSA from MRSA and offers an attractive option to be considered in the rapid epidemiological analysis of S. aureus in South Africa. Continuous surveillance on resistance patterns and characterization of S. aureus in understanding new and emerging trends in South Africa is of utmost importance