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Enhance Cancer Cell Recognition and Overcome Drug Resistance Using Hyaluronic Acid and α-Tocopheryl Succinate Based Multifunctional Nanoparticles.

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Enhance Cancer Cell Recognition and Overcome Drug Resistance Using Hyaluronic Acid and α-Tocopheryl Succinate Based Multifunctional Nanoparticles.

Mol Pharm. 2015 May 6;

Authors: Liang S, Wang AT, Yang ZZ, Liu YJ, Qi XR

Abstract
Multidrug resistance (MDR) presents a clinical obstacle to cancer chemotherapy. The main purpose of this study was to evaluate the potential of a hyaluronic acid (HA) and α-tocopheryl succinate (α-TOS) based nanoparticle to enhance cancer cell recognition and overcome MDR, and to explore the underlying mechanisms. A multifunctional nanoparticle, HTTP-50 NP, consisted of HA-α-TOS (HT) conjugate and D-α-tocopheryl polyethylene glycol succinate (TPGS) with docetaxel loaded in its hydrophobic core. The promoted tumor cell recognition and accumulation, cytotocicity, mitochondria-specific apoptotic pathways for the HTTP-50 NP were confirmed in MCF-7/Adr cells (P-gp-overexpressing cancer model), indicating that the formulated DTX and the conjugated α-TOS in the HTTP-50 NP could synergistically circumvent the acquired and intrinsic MDR in MCF-7/Adr cells. In vivo investigation on the MCF-7/Adr xenografted nude mice models confirmed that HTTP-50 NP possessed much higher tumor tissue accumulation and exhibited pronouncedly enhanced anti-resistance tumor efficacy with reduced systemic toxicity compared with HTTP-0 NP and Taxotere. The mechanisms of the multifunctional HTTP-50 NP to overcome MDR and enhance anti-resistance efficacy may be contributed by CD44 receptor-targeted delivery, P-gp efflux inhibition, and meanwhile to maximize antitumor efficacy by synergism of DTX and mitocan of α-TOS killing tumor cells.

PMID: 25945733 [PubMed – as supplied by publisher]

Biofilm production by multiresistant Corynebacterium striatum associated with nosocomial outbreak.

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Biofilm production by multiresistant Corynebacterium striatum associated with nosocomial outbreak.

Mem Inst Oswaldo Cruz. 2015 Apr;110(2):242-8

Authors: Souza Cd, Faria YV, Sant’Anna Lde O, Viana VG, Seabra SH, Souza MC, Vieira VV, Hirata Júnior R, Moreira Lde O, Mattos-Guaraldi AL

Abstract
Corynebacterium striatum is a potentially pathogenic microorganism that causes nosocomial outbreaks. However, little is known about its virulence factors that may contribute to healthcare-associated infections (HAIs). We investigated the biofilm production on abiotic surfaces of multidrug-resistant (MDR) and multidrug-susceptible (MDS) strains of C. striatum of pulsed-field gel electrophoresis types I-MDR, II-MDR, III-MDS and IV-MDS isolated during a nosocomial outbreak in Rio de Janeiro, Brazil. The results showed that C. striatum was able to adhere to hydrophilic and hydrophobic abiotic surfaces. The C. striatum 1987/I-MDR strain, predominantly isolated from patients undergoing endotracheal intubation procedures, showed the greatest ability to adhere to all surfaces. C. striatum bound fibrinogen to its surface, which contributed to biofilm formation. Scanning electron microscopy showed the production of mature biofilms on polyurethane catheters by all pulsotypes. In conclusion, biofilm production may contribute to the establishment of HAIs caused by C. striatum.

PMID: 25946249 [PubMed – in process]

Diabetes mellitus is associated with cavities, smear grade, and multidrug-resistant tuberculosis in Georgia.

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Diabetes mellitus is associated with cavities, smear grade, and multidrug-resistant tuberculosis in Georgia.

Int J Tuberc Lung Dis. 2015 Jun;19(6):685-92

Authors: Magee MJ, Kempker RR, Kipiani M, Gandhi NR, Darchia L, Tukvadze N, Howards PP, Narayan KM, Blumberg HM

Abstract
SETTING: National tuberculosis (TB) treatment facility in the country of Georgia.
OBJECTIVE: To determine the prevalence of diabetes mellitus (DM) and pre-DM among patients with TB using glycosylated-hemoglobin (HbA1c), and to estimate the association between DM and clinical characteristics and response to anti-tuberculosis treatment.
DESIGN: A cohort study was conducted from 2011 to 2014 at the National Centre for TB and Lung Disease in Tbilisi. Patients aged ⩾35 years with pulmonary TB were included. HbA1c was used to define DM (⩾6.5%), pre-DM (⩾5.7-6.4%), and no DM (<5.7%). Interviews and medical chart abstraction were performed. Regression analyses estimated associations between DM and 1) baseline TB characteristics and 2) anti-tuberculosis treatment outcomes.
RESULTS: A total of 318 newly diagnosed patients with TB were enrolled. The prevalence of DM and pre-DM was 11.6% and 16.4%, respectively. In multivariable analyses, patients with TB-DM had more cavitation (adjusted OR [aOR] 2.26), higher smear grade (aOR 2.37), and more multidrug-resistant TB (MDR-TB) (aOR 2.27) than patients without DM. The risk of poor anti-tuberculosis treatment outcomes was similar among patients with and those without DM (28.1% vs. 23.6%).
CONCLUSION: DM and pre-DM were common among adults with newly diagnosed pulmonary TB in Tbilisi, Georgia, and DM was associated with more clinical symptoms, and MDR-TB, at presentation.

PMID: 25946360 [PubMed – in process]

Klebsiella Pneumoniae in Septicemic Neonates with Special Reference to Extended Spectrum β-lactamase, AmpC, Metallo β-lactamase Production and Multiple Drug Resistance in Tertiary Care Hospital.

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Klebsiella Pneumoniae in Septicemic Neonates with Special Reference to Extended Spectrum β-lactamase, AmpC, Metallo β-lactamase Production and Multiple Drug Resistance in Tertiary Care Hospital.

J Lab Physicians. 2015 Jan-Jun;7(1):32-7

Authors: Gajul SV, Mohite ST, Mangalgi SS, Wavare SM, Kakade SV

Abstract
BACKGROUND: β-lactamases viz., extended spectrum β-lactamase (ESBL), AmpC, and metallo β-lactamase (MBL) production in Klebsiella pneumoniae has led to a serious concern about septicemic neonates in Neonatal Intensive Care Units due to high resistance against commonly used antimicrobials.
PURPOSE: To study the prevalence of ESBL, AmpC, and MBL production in K. pneumoniae isolates in neonatal septicemia, to check antimicrobial susceptibility to various drugs including tigecycline; and to assess burden of multiple drug resistance (MDR).
MATERIALS AND METHODS: Total 24 clinical isolates of K. pneumoniae isolated from 318 blood samples of suspected cases of neonatal septicemia were studied. Isolates were screened for ESBL, AmpC, and MBL production by Clinical and Laboratory Standards Institute (CLSI) disk method, AmpC cefoxitin screen, and imipenem, meropenem, ceftazidime disk screen respectively; and confirmation was done by CLSI phenotypic disk confirmatory test, AmpC sterile disk method, and imipenem ethylenediamine tetracetic acid double disk synergy test respectively. Antimicrobial susceptibility was determined by Kirby-Bauer’s disk diffusion method. Efficacy of tigecycline was evaluated using United States Food and Drug Administration guidelines.
RESULTS: Of the 24 K. pneumoniae isolates, co-production of AmpC + MBL was found in more number of isolates (67%) (P < 0.0001) compared to single enzyme production (ESBL and MBL 8% both, AmpC 12.5%). Rate of resistance for penicillins and cephalosporins was highest. Susceptibility was more for imipenem, co-trimoxazole, and meropenem. Nonsusceptibility to tigecycline was low (21%). A total of 23 (96%) isolates were MDR.
CONCLUSIONS: Routine detection of ESBL, AmpC, and MBL is required in laboratories. Carbapenems should be kept as a last resort drugs. Trend of tigecycline susceptibility has been noted in the study. Continued monitoring of susceptibility pattern is necessary to detect true burden of resistance for proper management.

PMID: 25949057 [PubMed]

Antimycobacterial and Anti-Inflammatory Activities of Substituted Chalcones Focusing on an Anti-Tuberculosis Dual Treatment Approach.

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Antimycobacterial and Anti-Inflammatory Activities of Substituted Chalcones Focusing on an Anti-Tuberculosis Dual Treatment Approach.

Molecules. 2015;20(5):8072-8093

Authors: Ventura TL, Calixto SD, de Azevedo Abrahim-Vieira B, de Souza AM, Mello MV, Rodrigues CR, Soter de Mariz E Miranda L, Alves de Souza RO, Leal IC, Lasunskaia EB, Muzitano MF

Abstract
Tuberculosis (TB) remains a serious public health problem aggravated by the emergence of M. tuberculosis (Mtb) strains resistant to multiple drugs (MDR). Delay in TB treatment, common in the MDR-TB cases, can lead to deleterious life-threatening inflammation in susceptible hyper-reactive individuals, encouraging the discovery of new anti-Mtb drugs and the use of adjunctive therapy based on anti-inflammatory interventions. In this study, a series of forty synthetic chalcones was evaluated in vitro for their anti-inflammatory and antimycobacterial properties and in silico for pharmacokinetic parameters. Seven compounds strongly inhibited NO and PGE2 production by LPS-stimulated macrophages through the specific inhibition of iNOS and COX-2 expression, respectively, with compounds 4 and 5 standing out in this respect. Four of the seven most active compounds were able to inhibit production of TNF-α and IL-1β. Chalcones that were not toxic to cultured macrophages were tested for antimycobacterial activity. Eight compounds were able to inhibit growth of the M. bovis BCG and Mtb H37Rv strains in bacterial cultures and in infected macrophages. Four of them, including compounds 4 and 5, were active against a hypervirulent clinical Mtb isolate as well. In silico analysis of ADMET properties showed that the evaluated chalcones displayed satisfactory pharmacokinetic parameters. In conclusion, the obtained data demonstrate that at least two of the studied chalcones, compounds 4 and 5, are promising antimycobacterial and anti-inflammatory agents, especially focusing on an anti-tuberculosis dual treatment approach.

PMID: 25951004 [PubMed – as supplied by publisher]