Pancreatic cancer is one of the most difficult types of cancer to treat because of its high mortality rate due to chemotherapy resistance. We previously reported that combined treatment with gefitinib (GEF) and clarithromycin (CAM) results in enhanced cytotoxicity of GEF along with endoplasmic reticulum (ER) stress loading in non-small cell lung cancer cell lines. An epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) such as GEF induces autophagy in a pro-survival role, whereas CAM inhibits autophagy flux in various cell lines. Pronounced GEF-induced cytotoxicity therefore appears to depend on the efficacy of autophagy inhibition. In the present study, we compared the effect on autophagy inhibition among such macrolides as CAM, azithromycin (AZM), and EM900, a novel 12-membered non-antibiotic macrolide. We then assessed the enhanced GEF-induced cytotoxic effect on pancreatic cancer cell lines BxPC-3 and PANC-1. Autophagy flux analysis indicated that AZM is the most effective autophagy inhibitor of the three macrolides. CAM exhibits an inhibitory effect but less than AZM and EM900. Notably, the enhancing effect of GEF-induced cytotoxicity by combining macrolides correlated well with their efficient autophagy inhibition. However, this pronounced cytotoxicity was not due to upregulation of apoptosis induction, but was at least partially mediated through necroptosis. Our data suggest the possibility of using macrolides as 'chemosensitizers' for EGFR-TKI therapy in pancreatic cancer patients to enhance non-apoptotic tumor cell death induction.
A total of 51 cases of Lymphadenitis due to NTM could be identified. The illness occurs typically in young children up to six years of age. The most frequent cause were species of the Mycobacterium avium-intracellulare-scrofulaceum complex. Except for the local diagnosis of a cervical Lymphadenitis other clinical symptoms are missing, just as specific laboratory parameters with a subacute or chronic course. The tuberculin skin test can be false positive. The diagnosis is confirmed by biopsy and histology as well as through microbiological tests.
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HCWs or patients may serve as the source of pertussis in nosocomial outbreaks, which can result in substantial morbidity and outlay of resources for control measures. Our review suggested that a diagnosis of pertussis should be an early consideration for HCWs with cough illness. Targeted pertussis immunization of HCWs, employee health policies that provide for testing and furlough of HCWs with prolonged cough, and monitoring of HCWs for compliance with infection control measures could reduce the morbidity and costs associated with pertussis outbreaks. These measures will require evaluation of their effectiveness.
sparse serum azithromycin concentration, MIC, efficacy and safety data were collected from three Japanese Phase 3 studies of a 2 g single dose of azithromycin-ER for respiratory tract infections. These sparse concentration data were combined with data from eight Phase 1 PK studies in Japanese and Western populations, to develop a robust population PK model using a non-linear mixed effects approach. The exposure-response relationships for efficacy and safety were evaluated using logistic regression.
Confluent human umbilical vein endothelial cells (HUVECs) were infected with Cp or CMV. After 48 h of infection, production of eNOS, cyclic guanosine monophosphate (cGMP) and reactive oxygen species (ROS) was measured. Detection of cGMP was used as a reporter assay for the bioavailability of NO. Subsequently, Cp- and CMV-infected HUVECs were coincubated with 0.016 mg L(-1) and 1 mg L(-1) azithromycin.
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Healthcare waste (HCW) might potentially harbor infective viable microorganisms in sanitary landfills. We investigated the antimicrobial susceptibility patterns and the occurrence of the mecA gene in coagulase-negative Staphylococcus strains (CoNS) recovered from the leachate of the HCW in an untreated sanitary landfill.
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The gram-negative soil bacillus Burkholderia pseudomallei is the causative agent of melioidosis, a severe and potentially fatal septicemic disease that is endemic to Southeast Asia and northern Australia. Its intrinsic resistance to many antibiotics is attributed mainly to the presence of several drug efflux pumps, and therefore, inhibitors of such pumps are expected to restore the activities of many clinically important antimicrobial agents that are the substrates of these pumps. The phenothiazine antipsychotic and antihistaminic drugs prochlorperazine, chlorpromazine, and promazine have a synergistic interaction with a wide spectrum of antimicrobial agents, thereby enhancing their antimicrobial potency against B. pseudomallei. Antimicrobial agents that interacted synergistically with the phenothiazines include streptomycin, erythromycin, oleandomycin, spectinomycin, levofloxacin, azithromycin, and amoxicillin-clavulanic acid. The MICs of these antibiotics were reduced as much as 8,000-fold in the presence of the phenothiazines. Antimicrobial agents which did not interact synergistically with the phenothiazines include gentamicin, amoxicillin, and ampicillin. Omeprazole, a proton pump inhibitor, provided an augmentation of antimicrobial activities similar to that of the phenothiazines, suggesting that the phenothiazines might have interfered with the proton gradient at the inner membrane. B. pseudomallei cells accumulated more erythromycin in the presence of the phenothiazines, an effect similar to that of carbonyl cyanide m-chlorophenylhydrazone, a proton gradient uncoupler. In the presence of the phenothiazines, a much reduced concentration of erythromycin (0.06x MIC) also protected human lung epithelial cells and macrophage cells from B. pseudomallei infection and attenuated its cytotoxicity.
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Thirty sites in patients with chronic periodontitis and probing depth (PD) 4-6 mm were categorized randomly into two treatment groups: Scaling and root planing (SRP) plus 0.5% AZM gel (group 1) and SRP only (group 2). Clinical evaluation was undertaken using the Gingival Index (GI) of Loe and Silness and plaque was assessed using the Turesky et al. modification of Quigley Hein Index at baseline and 21 days. Pocket PD and clinical attachment level (CAL) were also measured.
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These results suggest that azithromycin administration ameliorates induced inflammation effects in a rat model of acute conjunctivitis.
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Fourteen school-age children with active trachoma (one failed to complete the study).
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To evaluate the efficacy and safety of subconjunctival injections of clindamycin associated with oral corticotherapy in the treatment of toxoplasmic retinochoroiditis (TRC) and its effect on recurrence.
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Azithromycin is well absorbed and tolerated by ball pythons. On the basis of plasma pharmacokinetics and tissue concentration data, we suggest an azithromycin dosage in ball pythons of 10 mg/kg, orally, every 2 to 7 days, depending upon the site of infection and susceptibil ity of the infective organism.