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Sample records for antimicrobial chemotherapy pact

  1. Development of Photodynamic Antimicrobial Chemotherapy (PACT) for Clostridium difficile

    PubMed Central

    Pye, Hayley; Kohoutova, Darina; Mosse, Charles A.; Yahioglu, Gokhan; Stamati, Ioanna; Deonarain, Mahendra; Battah, Sinan; Ready, Derren; Allan, Elaine; Mullany, Peter; Lovat, Laurence B.

    2015-01-01

    Background Clostridium difficile is the leading cause of antibiotic-associated diarrhoea and pseudo membranous colitis in the developed world. The aim of this study was to explore whether Photodynamic Antimicrobial Chemotherapy (PACT) could be used as a novel approach to treating C. difficile infections. Methods PACT utilises the ability of light-activated photosensitisers (PS) to produce reactive oxygen species (ROS) such as free radical species and singlet oxygen, which are lethal to cells. We screened thirteen PS against C. difficile planktonic cells, biofilm and germinating spores in vitro, and cytotoxicity of effective compounds was tested on the colorectal adenocarcinoma cell-line HT-29. Results Three PS were able to kill 99.9% of bacteria in both aerobic and anaerobic conditions, both in the planktonic state and in a biofilm, after exposure to red laser light (0.2 J/cm2) without harming model colon cells. The applicability of PACT to eradicate C. difficile germinative spores indirectly was also shown, by first inducing germination with the bile salt taurocholate, followed by PACT. Conclusion This innovative and simple approach offers the prospect of a new antimicrobial therapy using light to treat C. difficile infection of the colon. PMID:26313448

  2. Photodynamic antimicrobial chemotherapy (PACT) inhibits biofilm formation by Candida albicans, increasing both ROS production and membrane permeability.

    PubMed

    Rosseti, Isabela Bueno; Chagas, Luciene Reginato; Costa, Maricilia Silva

    2014-05-01

    The opportunistic fungal Candida albicans is able to produce both superficial and systemic infections in immunocompromised patients. Photodynamic antimicrobial chemotherapy (PACT) is a process that combines visible light and a photosensitizer, producing reactive oxygen species (ROS) that can kill the treated cells and has been presented as a potential antimicrobial therapy. In this work, we study the effects of PACT, using toluidine blue (TB) as a photosensitizer drug, on ROS production and cell damage and the ability of C. albicans to form biofilm. A significant decrease was observed in the cell growth after PACT in a TB concentration-dependent manner. This effect was dependent on the incubation time after PACT. In addition, an increase in both the ROS production and cell permeability, after PACT, in a TB concentration-dependent manner was observed. PACT, using 0.1 mg/ml TB was able to reduce biofilm formation in 30, 50, and 62%, in cells submitted to incubation times of 1, 2, and 3 h, respectively. These results suggested that PACT, using TB, is able to decrease both growth and biofilm formation by C. albicans, possibly by a mechanism evolving both ROS production and the increase in the cell permeability.

  3. Photodynamic antimicrobial chemotherapy (PACT) using phenothiazines derivatives associated with the red laser against staphylococcus aureus

    NASA Astrophysics Data System (ADS)

    Oliveira, Susana C. P. S.; Santos, Gustavo M. P.; Monteiro, Juliana S. C.; Miranda, Anderson F. S.; Sampaio, Fernando J. P.; Gesteira, Maria F. M.; Zanin, Fátima A. A.; Santos, Marcos A. V.; Pinheiro, Antônio L. B.

    2013-03-01

    The objective of this study was to evaluate the bactericidal effect of photodynamic antimicrobial chemotherapy (PACT) using phenothiazinium dye (Toluidine blue O and methylene blue) at a low concentration of 1μg/mL irradiated with the red laser at doses of 2.4 e 4.8 J/cm² on strain of Staphylococcus aureus (ATCC 23529) in vitro. For this research, tests were performed in triplicate and the samples were distributed into six test groups: (L-P-) Negative control (L1+P-) and (L2+P-) bacterial suspensions were irradiated with laser energy 2.4 and 4.8 J/cm2 respectively in the absence of photosensitizer; (L1+P+) and (L2+P+) bacterial suspensions were irradiated with laser in the presence of 1μg/ml of photosensitizer and finally (L-P+) bacterial suspensions only in the presence of phenothiazinium dye. Therefore, were analyzed the potential bactericidal PACT by counting of colony-forming units and analyzed statistically (ANOVA, Tukey test, p<0.05). The results showed that the negative control group when compared with laser group (L2+P-) it was observed a statistically significant increase (p<0.01) which L2+P- showed a higher number of CFU, on the other hand when compared to L1+P- no statistically significant difference was found, relation to the groups submitted to PACT, only showed a statistically significant reduction relative to the group irradiated L2+P+ (p<0.01) that showed a decrease in the number of CFU. There was no statistically significant difference between the groups submitted to PDT (L1+P+ and L2+P+). Although the results of this study have shown a reduction in average number of colony forming units by the appropriate laser-dye treatment combination, it needs further investigation.

  4. Photodynamic antimicrobial chemotherapy (PACT) against oral microorganisms with the use of blue LED associated to curcumin

    NASA Astrophysics Data System (ADS)

    Sampaio, Fernando José P.; Pires-Santos, Gustavo M.; de Oliveira, Susana C. P. S.; Monteiro, Juliana S. C.; Bagnato, Vanderlei S.; Pinheiro, Antônio L. B.

    2016-03-01

    The use of curcumin as antimicrobial agent has been suggested and this effect may be potentialized by appropriate light. This study evaluated the effect of PACT using blue LED (λ450ηm +/- 5ηm, 220mW and spot of 0.785 cm2) associated to Curcumin at different concentrations (75, 37.5, 18.75, 9.37 and 4.68 μg /mL). Microorganisms from the oral mucosa and the posterior region of the tongue were collected and inoculated into test tubes containing 8mL of TSB medium. For these assays were performed 16 readings. In the assays were used culture plate of 24 wells. To each well was added 400 μL of the suspension containing the microorganisms. Suspensions without curcumin were placed in eight wells. Elsewhere, curcumin was applied varying concentrations with pre-irradiation time of 5 min. After stirring, 200 μL aliquot was taken from each well and the readings were immediately carried out by a spectrophotometer (SPECTRA MAX). Assessments of turbidity were performed following CLSI standard methods. After 1 hour of incubation in a bacteriological oven, 200 μL aliquot was removed from the remaining wells for a second reading. The results showed a decrease of total microorganisms in the most of test groups. The best result of the PACT was with 75 μg/mL, showing 81% of inhibition. It is concluded that PACT with blue LED associated to Curcumin could be a potential mechanism for controlling microorganism proliferation on the oral cavity.

  5. Investigation into the susceptibility of Burkholderia cepacia complex isolates to photodynamic antimicrobial chemotherapy (PACT)

    NASA Astrophysics Data System (ADS)

    Cassidy, C. M.; Watters, A. L.; Donnelly, R. F.; Tunney, M. M.

    2009-06-01

    The main cause of morbidity and mortality in cystic fibrosis (CF) sufferers is progressive pulmonary damage caused by recurrent and often unremitting respiratory tract infection. Causative organisms include Pseudomonas aeruginosa and Haemophilus influenzae, but in recent years the Burkholderia cepacia complex has come to the fore. This group of highly drug-resistant Gram-negative bacteria are associated with a rapid decline in lung function and the often fatal cepacia syndrome, with treatment limited to patient segregation and marginally effective antibacterial regimens. Thus, development of an effective treatment is of the upmost importance. PACT, a non-target specific therapy, has proven successful in killing both Gram-positive and Gram-negative bacteria. In this study, planktonic cultures of six strains of the B. cepacia complex were irradiated (635 nm, 200 J cm-2,10 minutes irradiation) following 30 seconds incubation with methylene blue (MB) or meso-tetra (N-methyl-4-pyridyl) porphine tetra tosylate (TMP). Rates of kill of > 99 % were achieved with MB- and TMP-PACT. A MB concentration of 50 μg ml-1 and TMP concentration of 500 μg ml-1 were associated with highest percentage kills for each photosensitizer. PACT is an attractive option for treatment of B.cepacia complex infection. Further study, involving biofilm culture susceptibility, delivery of light to the target and in vivo testing will be necessary before it PACT becomes a viable treatment option for CF patients who are colonised or infected with B. cepacia complex.

  6. Bactericidal Action of Photodynamic Antimicrobial Chemotherapy (PACT) with Photosensitizers Used as Plaque-Disclosing Agents against Experimental Biofilm.

    PubMed

    Ishiyama, Kirika; Nakamura, Keisuke; Kanno, Taro; Niwano, Yoshimi

    2016-01-01

    Our previous study revealed that the photo-irradiation of rose bengal, erythrosine, and phloxine, xanthene photosensitizers, used as dental plaque disclosing agents, could exert bactericidal action on planktonic Streptococcus mutans via the singlet oxygen. In the present study, the photo-irradiation induced bactericidal activity of the three xanthene compounds against the experimental biofilm of S. mutans was investigated in combination with acid electrolyzed water (AcEW) and alkaline electrolyzed water (AlEW). As a result, only the photo-irradiated rose bengal in AlEW showed prominent bactericidal activity with a >3-log reduction of the viable bacterial count. Since our previous study showed that the affinity of rose bengal to bacterial cells was superior to that of erythrosine and phloxine, it was speculated that AlEW damaged the extracellular matrix of the experimental biofilm, which would let the rose bengal easily be bound to the bacterial cells. From these results, it is strongly suggested that rose bengal is a suitable photosensitizer for use as a plaque disclosing agent in photodynamic antimicrobial chemotherapy to treat dental plaque. PMID:27667525

  7. Investigation into the potential of sub-lethal photodynamic antimicrobial chemotherapy (PACT) to reduce susceptibility of meticillin-resistant Staphylococcus aureus (MRSA) to antibiotics

    NASA Astrophysics Data System (ADS)

    Cassidy, C. M.; Donnelly, R. F.; Tunney, M. M.

    2009-06-01

    In PACT, a combination of a sensitising drug and visible light cause the selective destruction of microbial cells via singlet oxygen production. As singlet oxygen is a non-specific oxidizing agent and is only present during illumination, development of resistance to this treatment is thought to be unlikely. However, in response to oxidative stress, bacteria can up-regulate oxidative stress genes and associated antibiotic resistance genes. The up-regulation of these genes and potential transfer of genetic material may result in a resistant bacterial population. This study determined whether treatment of clinically isolated meticillin resistant Staphylococcus aureus (MRSA) strains with sub-lethal doses of methylene blue (MB) and meso-tetra (N-methyl-4-pyridyl) porphine tetra tosylate (TMP)-PACT resulted in reduced susceptibility to antibiotics and previously lethal PACT. Exposure of strains to sub-lethal doses of photosensitizer in combination with light had no effect on susceptibility to previously lethal photosensitization. Furthermore, exposure to sub-lethal concentrations of both photosensitizers caused no significant changes in the minimum inhibitory concentration (MIC) for each strain tested. Any differences in susceptibility were not significant as they did not cross breakpoints between resistant and susceptible for any organism or antibiotic tested. Therefore, PACT remains an attractive alternative option for treatment of MRSA infections.

  8. Photodynamic antimicrobial chemotherapy using zinc phthalocyanine derivatives in treatment of bacterial skin infection

    NASA Astrophysics Data System (ADS)

    Chen, Zhuo; Zhang, Yaxin; Wang, Dong; Li, Linsen; Zhou, Shanyong; Huang, Joy H.; Chen, Jincan; Hu, Ping; Huang, Mingdong

    2016-01-01

    Photodynamic antimicrobial chemotherapy (PACT) is an effective method for killing bacterial cells in view of the increasing problem of multiantibiotic resistance. We herein reported the PACT effect on bacteria involved in skin infections using a zinc phthalocyanine derivative, pentalysine β-carbonylphthalocyanine zinc (ZnPc-Lys). Compared with its anionic ZnPc counterpart, ZnPc-Lys showed an enhanced antibacterial efficacy in vitro and in an animal model of localized infection. Meanwhile, ZnPc-Lys was observed to significantly reduce the wound skin blood flow during wound healing, indicating an anti-inflammation activity. This study provides new insight on the mechanisms of PACT in bacterial skin infection.

  9. Oxidative stress of photodynamic antimicrobial chemotherapy inhibits Candida albicans virulence

    NASA Astrophysics Data System (ADS)

    Kato, Ilka Tiemy; Prates, Renato Araujo; Tegos, George P.; Hamblin, Michael R.; Simões Ribeiro, Martha

    2011-03-01

    Photodynamic antimicrobial chemotherapy (PACT) is based on the principal that microorganisms will be inactivated using a light source combined to a photosensitizing agent in the presence of oxygen. Oxidative damage of cell components occurs by the action of reactive oxygen species leading to cell death for microbial species. It has been demonstrated that PACT is highly efficient in vitro against a wide range of pathogens, however, there is limited information for its in vivo potential. In addition, it has been demonstrated that sublethal photodynamic inactivation may alter the virulence determinants of microorganisms. In this study, we explored the effect of sublethal photodynamic inactivation to the virulence factors of Candida albicans. Methylene Blue (MB) was used as photosensitizer for sublethal photodynamic challenge on C. albicans associated with a diode laser irradiation (λ=660nm). The parameters of irradiation were selected in causing no reduction of viable cells. The potential effects of PACT on virulence determinants of C. albicans cells were investigated by analysis of germ tube formation and in vivo pathogenicity assays. Systemic infection was induced in mice by the injection of fungal suspension in the lateral caudal vein. C. albicans exposed to sublethal photodynamic inactivation formed significantly less germ tube than untreated cells. In addition, mice infected with C. albicans submitted to sublethal PACT survived for a longer period of time than mice infected with untreated cells. The oxidative damage promoted by sublethal photodynamic inactivation inhibited virulence determinants and reduced in vivo pathogenicity of C. albicans.

  10. Antimicrobial peptide-modified liposomes for bacteria targeted delivery of temoporfin in photodynamic antimicrobial chemotherapy.

    PubMed

    Yang, Kewei; Gitter, Burkhard; Rüger, Ronny; Wieland, Gerhard D; Chen, Ming; Liu, Xiangli; Albrecht, Volker; Fahr, Alfred

    2011-10-01

    Photodynamic antimicrobial chemotherapy (PACT) and antimicrobial peptides (AMPs) are two promising strategies to combat the increasing prevalence of antibiotic-resistant bacteria. To take advantage of these two strategies, we integrated a novel antimicrobial peptide (WLBU2) and a potent generation II photosensitizer (temoporfin) into liposomes by preparing WLBU2-modified liposomes, aiming at bacteria targeted delivery of temoporfin for PACT. WLBU2 was successfully coupled to temoporfin-loaded liposomes using a functional phospholipid. The delivery of temoporfin to bacteria was confirmed by fluorescence microscopy and flow cytometry, thus demonstrating that more temoporfin was delivered to bacteria by WLBU2-modified liposomes than by unmodified liposomes. Consequently, the WLBU2-modified liposomes eradicated all methicillin-resistant Staphylococcus aureus (MRSA) and induced a 3.3 log(10) reduction of Pseudomonas aeruginosa in the in vitro photodynamic inactivation test. These findings demonstrate that the use of AMP-modified liposomes is promising for bacteria-targeted delivery of photosensitizers and for improving the PACT efficiency against both gram-positive and gram-negative bacteria in the local infections.

  11. Pioneers in Antimicrobial Chemotherapy.

    PubMed

    Gupta, Neha; Rodrigues, Camilla; Soman, Rajeev

    2015-09-01

    "If we are not careful, we soon will be in the post-antibiotic era, and for some patients and some microbes we are already there"- Tom Friedan Antibiotics revolutionized medicine in the 20th century. The era of antibacterial chemotherapy began in 1907 with the discovery of arsphenamine, first synthesized by Alferd Bertheim and Paul Ehrlich in 1907, used to treat syphilis. The first systemically active antibiotic, Prontosil was discovered in 1933 by Gerhard Domagk, for which he was awarded the 1939 Nobel Prize. Fleming's accidental discovery and isolation of penicillin in September 1928 marked the start of modern antibiotics. It was a discovery that changed the course of history and saved millions of lives. PMID:27608881

  12. Pioneers in Antimicrobial Chemotherapy.

    PubMed

    Gupta, Neha; Rodrigues, Camilla; Soman, Rajeev

    2015-09-01

    "If we are not careful, we soon will be in the post-antibiotic era, and for some patients and some microbes we are already there"- Tom Friedan Antibiotics revolutionized medicine in the 20th century. The era of antibacterial chemotherapy began in 1907 with the discovery of arsphenamine, first synthesized by Alferd Bertheim and Paul Ehrlich in 1907, used to treat syphilis. The first systemically active antibiotic, Prontosil was discovered in 1933 by Gerhard Domagk, for which he was awarded the 1939 Nobel Prize. Fleming's accidental discovery and isolation of penicillin in September 1928 marked the start of modern antibiotics. It was a discovery that changed the course of history and saved millions of lives.

  13. Antimicrobial action from a novel porphyrin derivative in photodynamic antimicrobial chemotherapy in vitro.

    PubMed

    Latief, Miftahul Akhyar; Chikama, Taiichiro; Shibasaki, Momoko; Sasaki, Takaaki; Ko, Ji-Ae; Kiuchi, Yoshiaki; Sakaguchi, Takemasa; Obana, Akira

    2015-01-01

    Efforts to identify improved treatments for corneal infection include the development of photodynamic antimicrobial chemotherapy (PACT). We evaluated the antimicrobial effect of PACT with a novel porphyrin derivative, TONS 504, and a novel light system on methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA). Bacteria were irradiated with a light-emitting diode (LED) at energies of 10, 20, or 30 J/cm(2) in the presence of various concentrations of TONS 504. Bacterial viability was assessed at 30 min and 24 h after irradiation by determination of colony formation on agar plates. PACT inhibited the growth of both MSSA and MRSA as early as 30 min after light exposure. Complete inhibition of bacterial growth was apparent at 24 h after irradiation at a TONS 504 concentration of 1 mg/L and LED energies of ≥10 J/cm(2) or a TONS 504 concentration of 0.5 mg/L and LED energies of ≥20 J/cm(2) for MSSA, and at a TONS 504 concentration of 10 mg/L and LED energies of ≥10 J/cm(2) or of a TONS 504 concentration of 1 mg/L and LED energies of ≥20 J/cm(2) for MRSA. Bacterial growth was unaffected by TONS 504 in the absence of irradiation or by irradiation in the absence of TONS 504. Our results thus demonstrate the antimicrobial efficacy of PACT with TONS 504 and a LED against both MSSA and MRSA in vitro, and they therefore provide a basis for further investigation of this system as a potential treatment for corneal infection.

  14. Photodynamic Antimicrobial Chemotherapy in Aquaculture: Photoinactivation Studies of Vibrio fischeri

    PubMed Central

    Alves, Eliana; Faustino, Maria A. F.; Tomé, João P. C.; Neves, Maria G. P. M. S.; Tomé, Augusto C.; Cavaleiro, José A. S.; Cunha, Ângela; Gomes, Newton C. M.; Almeida, Adelaide

    2011-01-01

    Background Photodynamic antimicrobial chemotherapy (PACT) combines light, a light-absorbing molecule that initiates a photochemical or photophysical reaction, and oxygen. The combined action of these three components originates reactive oxygen species that lead to microorganisms' destruction. The aim was to evaluate the efficiency of PACT on Vibrio fischeri: 1) with buffer solution, varying temperature, pH, salinity and oxygen concentration values; 2) with aquaculture water, to reproduce photoinactivation (PI) conditions in situ. Methodology/Principal Findings To monitor the PI kinetics, the bioluminescence of V. fischeri was measured during the experiments. A tricationic meso-substituted porphyrin (Tri-Py+-Me-PF) was used as photosensitizer (5 µM in the studies with buffer solution and 10–50 µM in the studies with aquaculture water); artificial white light (4 mW cm−2) and solar irradiation (40 mW cm−2) were used as light sources; and the bacterial concentration used for all experiments was ≈107 CFU mL−1 (corresponding to a bioluminescence level of 105 relative light units - RLU). The variations in pH (6.5–8.5), temperature (10–25°C), salinity (20–40 g L−1) and oxygen concentration did not significantly affect the PI of V. fischeri, once in all tested conditions the bioluminescent signal decreased to the detection limit of the method (≈7 log reduction). The assays using aquaculture water showed that the efficiency of the process is affected by the suspended matter. Total PI of V. fischeri in aquaculture water was achieved under solar light in the presence of 20 µM of Tri-Py+-Me-PF. Conclusions/Significance If PACT is to be used in environmental applications, the matrix containing target microbial communities should be previously characterized in order to establish an efficient protocol having into account the photosensitizer concentration, the light source and the total light dose delivered. The possibility of using solar light in PACT to

  15. Randomized in vivo evaluation of photodynamic antimicrobial chemotherapy on deciduous carious dentin.

    PubMed

    Steiner-Oliveira, Carolina; Longo, Priscila Larcher; Aranha, Ana Cecília Corrêa; Ramalho, Karen Müller; Mayer, Marcia Pinto Alves; de Paula Eduardo, Carlos

    2015-10-01

    The aim of this randomized in vivo study was to compare antimicrobial chemotherapies in primary carious dentin. Thirty-two participants ages 5 to 7 years underwent partial caries removal from deep carious dentin lesions in primary molars and were subsequently divided into three groups: control [chlorhexidine and resin-modified glass ionomer cement (RMGIC)], LEDTB [photodynamic antimicrobial chemotherapy (PACT) with light-emitting diode associated with toluidine blue solution and RMGIC], and LMB [PACT with laser associated with methylene blue solution and RMGIC]. The participants were submitted to initial clinical and radiographic examinations. Demographic features and biofilm, gingival, and DMFT/DMFS indexes were evaluated, in addition to clinical and radiographic followups at 6 and 12 months after treatments. Carious dentin was collected before and after each treatment, and the number of Streptococcus mutans, Streptococcus sobrinus, Lactobacillus casei, Fusobacterium nucleatum, Atopobium rimae, and total bacteria was established by quantitative polymerase chain reaction. No signs of pain or restoration failure were observed. All therapies were effective in reducing the number of microorganisms, except for S. sobrinus. No statistical differences were observed among the protocols used. All therapies may be considered as effective modern approaches to minimal intervention for the management of deep primary caries treatment. PMID:26502235

  16. Randomized in vivo evaluation of photodynamic antimicrobial chemotherapy on deciduous carious dentin

    NASA Astrophysics Data System (ADS)

    Steiner-Oliveira, Carolina; Longo, Priscila Larcher; Aranha, Ana Cecília Corrêa; Ramalho, Karen Müller; Mayer, Marcia Pinto Alves; de Paula Eduardo, Carlos

    2015-10-01

    The aim of this randomized in vivo study was to compare antimicrobial chemotherapies in primary carious dentin. Thirty-two participants ages 5 to 7 years underwent partial caries removal from deep carious dentin lesions in primary molars and were subsequently divided into three groups: control [chlorhexidine and resin-modified glass ionomer cement (RMGIC)], LEDTB [photodynamic antimicrobial chemotherapy (PACT) with light-emitting diode associated with toluidine blue solution and RMGIC], and LMB [PACT with laser associated with methylene blue solution and RMGIC]. The participants were submitted to initial clinical and radiographic examinations. Demographic features and biofilm, gingival, and DMFT/DMFS indexes were evaluated, in addition to clinical and radiographic followups at 6 and 12 months after treatments. Carious dentin was collected before and after each treatment, and the number of Streptococcus mutans, Streptococcus sobrinus, Lactobacillus casei, Fusobacterium nucleatum, Atopobium rimae, and total bacteria was established by quantitative polymerase chain reaction. No signs of pain or restoration failure were observed. All therapies were effective in reducing the number of microorganisms, except for S. sobrinus. No statistical differences were observed among the protocols used. All therapies may be considered as effective modern approaches to minimal intervention for the management of deep primary caries treatment.

  17. Clinical use of photodynamic antimicrobial chemotherapy for the treatment of deep carious lesions

    NASA Astrophysics Data System (ADS)

    Guglielmi, Camila De Almeida B.; Simionato, Maria Regina L.; Ramalho, Karen Müller; Imparato, José Carlos P.; Pinheiro, Sérgio Luiz; Luz, Maria A. A. C.

    2011-08-01

    The purpose of this study was to assess photodynamic antimicrobial chemotherapy (PACT) via irradiation, using a low power laser associated with a photosensitization dye, as an alternative to remove cariogenic microorganisms by drilling. Remaining dentinal samples in deep carious lesions on permanent molars (n = 26) were treated with 0.01% methylene blue dye and irradiated with a low power laser (InGaAIP - indium gallium aluminum phosphide; λ = 660 nm; 100 mW; 320 Jcm-2 90 s; 9J). Samples of dentin from the pulpal wall region were collected with a micropunch before and immediately after PACT and kept in a transport medium for microbiological analysis. Samples were cultured in plates of Brucella blood agar, Mitis Salivarius Bacitracin agar and Rogosa SL agar to determine the total viable bacteria, mutans streptococci and Lactobacillus spp. counts, respectively. After incubation, colony-forming units were counted and microbial reduction was calculated for each group of bacteria. PACT led to statistically significant reductions in mutans streptococci (1.38 log), Lactobacillus spp. (0.93 log), and total viable bacteria (0.91 log). This therapy may be an appropriate approach for the treatment of deep carious lesions using minimally invasive procedures.

  18. Photodynamic antimicrobial chemotherapy using zinc phthalocyanine derivative for bacterial skin infection

    NASA Astrophysics Data System (ADS)

    Chen, Zhuo; Zhang, Yaxin; Li, Linsen; Zhou, Shanyong; Chen, Jincan; Hu, Ping; Huang, Mingdong

    2014-09-01

    Folliculitis, furunculosis and acne vulgaris are very common skin disorders of the hair follicles and are associated with large grease-producing (sebaceous) glands. Although the detailed mechanisms involved these skin disorders are not fully understood, it is believed that the bacteria Propionibacterium acnes and Staphylococcus aureus are the key pathogenic factors involved. Conventional treatments targeting the pathogenic factors include a variety of topical and oral medications such as antibiotics. The wide use of antibiotics leads to bacterial resistance, and hence there is a need for new alternatives in above bacterial skin treatment. Photodynamic antimicrobial chemotherapy (PACT) is based on an initial photosensitization of the infected area, followed by irradiation with visible light, producing singlet oxygen which is cytotoxic to bacteria. Herein we reported a zinc phthalocyanine derivative, pentalysine β-carbonylphthalocyanine zinc (ZnPc-(Lys)5) and its PACT effect for the bacteria involved in these skin infections. Our results demonstrated strong bactericidal effects of this photosensitizer on both strains of the bacteria, suggesting ZnPc-(Lys)5 as a promising antimicrobial photosensitizer for the treatment of infectious diseases caused by these bacteria.

  19. Photodynamic antimicrobial chemotherapy on Streptococcus mutans using curcumin and toluidine blue activated by a novel LED device.

    PubMed

    Paschoal, Marco Aurelio; Lin, Meng; Santos-Pinto, Lourdes; Duarte, Simone

    2015-02-01

    Photodynamic antimicrobial chemotherapy (PACT) is an antimicrobial approach that uses photosensitizers (PS) in combination with light sources at specific wavelengths aiming the production of reactive oxygen species. The long illumination time necessary to active PS is a challenge in PACT. Thus, this study investigated the antimicrobial effect of a novel single source of light-emitting diode (LED) light that covers the entire spectrum of visible light beyond interchangeable probes at high power intensity. Blue and red LED probes were used into different exposure times to active different concentrations of curcumin (C) and toluidine blue (T) on planktonic suspensions of Streptococcus mutans UA 159 (S. mutans). S. mutans were standardized and submitted to (1) PACT treatment at three concentrations of C and T exposure at three radiant exposures of a blue LED (BL) (C+BL+) and a red LED (RL) (T+RL+), (2) C (C+BL-) or T alone (T+RL-), (3) both LED lights (C-BL+ and T-RL+), and (4) neither PS nor LED illumination (control group: C-BL- and T-RL-). Aliquots of the suspensions were diluted and cultured on blood agar plates. The number of colony-forming units was calculated after 48 h. The groups submitted to PACT presented a lethal photokilling rate to all PS concentrations at tested dosimetries. The comparison to control group when PS and LED lights used alone demonstrated no decrease in the number of viable bacterial counts. The novel LED device in combination with curcumin and toluidine blue promoted an effective photoinactivation of S. mutans suspensions at ultrashort light illumination times.

  20. Inactivation of acyclovir-sensitive and -resistant strains of herpes simplex virus type 1 in vitro by photodynamic antimicrobial chemotherapy

    PubMed Central

    Latief, Miftahul Akhyar; Ko, Ji-Ae; Kiuchi, Yoshiaki; Sakaguchi, Takemasa; Obana, Akira

    2015-01-01

    Purpose To evaluate the efficacy of photodynamic antimicrobial chemotherapy (PACT) with the new porphyrin derivative TONS 504 and a light-emitting diode (LED) against acyclovir (ACV)-sensitive and -resistant herpes simplex virus type 1 (HSV-1). Methods Human FL cells infected with the viral strains were subjected to PACT with TONS 504 at various concentrations (0.01 to 10 mg/l) and irradiation at various light energies (10 to 30 J/cm2) and were then incubated for 24 h before analysis. Results Immunocytofluorescence analysis with antibodies to HSV-1 revealed that PACT eliminated HSV-1 and ACV-resistant HSV-1 in a manner dependent on the TONS 504 concentration and light energy. Complete eradication of both viruses was apparent at a TONS 504 concentration of 10 mg/l and light energy of 10 to 30 J/cm2 as well as at a TONS 504 concentration of 1 mg/l and light energy of 20 or 30 J/cm2. No antiviral effect was apparent with TONS 504 in the absence of irradiation or with irradiation in the absence of TONS 504. Staining of cell nuclei with 4′, 6-diamidino-2-phenylindole revealed no apparent cytotoxicity of the PACT system, a finding that was confirmed by the system’s failure to induce the release of lactate dehydrogenase from the host cells. Conclusions We conclude that our PACT system based on TONS 504 and an LED is effective for eliminating HSV-1 and ACV-resistant HSV-1 without a harmful effect on host cells. PMID:25999680

  1. Evaluation of Photodynamic Antimicrobial Therapy (PACT) against Trypomastigotes of Trypanosoma cruzi: In Vitro Study

    NASA Astrophysics Data System (ADS)

    Barbosa, Artur F. S.; Soares, Luiz G. P.; Aciole, Jouber M. S.; Aciole, Gilberth T. S.; Pitta, Ivan R.; Galdino, Suely L.; Pinheiro, Antonio L. B.

    2011-08-01

    Policies to combat Chagas disease presents a considerable degree of negligence and is classified at level III by TDR, where the focus of research is based on the improvement and wider dissemination of existing tools and strategies for combating them. The PACT is based on topical or systemic administration of a nontoxic dye sensitive to light, followed by low dose irradiation with visible light of wavelength appropriate. In the presence of oxygen found in the cells, the photosensitizer (FS) enabled may react with molecules in its vicinity by electron transfer or hydrogen, leading to production of free radicals (type I reaction) or by energy transfer to oxygen (type II reaction), leading to production of singlet oxygen. Both paths can lead to cell death and the destruction of diseased tissue. In this work, we verify the effectiveness of PACT associated with a semiconductor laser InGaAlP, a wavelength (λ) equal to 660 nm±10 nm, 30 mW optical power, emitting red light in the visible spectrum, with a dose of 4 J/cm2 in continuous mode, using methylene blue in five differents concentrations on the infective trypomastigote forms of Trypanosoma cruzi. To determine the viability of the parasites, one sample from each treatment group at each concentration was removed and analyzed in a hemocytometer, observing the decrease in the number of live parasites for the solution without treatment. The results demonstrated significant percentage of parasite lysis (up to 86% lethality), what can not be observed in the groups treated with laser or with the FS.

  2. Methylene Blue-Loaded Dissolving Microneedles: Potential Use in Photodynamic Antimicrobial Chemotherapy of Infected Wounds.

    PubMed

    Caffarel-Salvador, Ester; Kearney, Mary-Carmel; Mairs, Rachel; Gallo, Luigi; Stewart, Sarah A; Brady, Aaron J; Donnelly, Ryan F

    2015-01-01

    Photodynamic therapy involves delivery of a photosensitising drug that is activated by light of a specific wavelength, resulting in generation of highly reactive radicals. This activated species can cause destruction of targeted cells. Application of this process for treatment of microbial infections has been termed "photodynamic antimicrobial chemotherapy" (PACT). In the treatment of chronic wounds, the delivery of photosensitising agents is often impeded by the presence of a thick hyperkeratotic/necrotic tissue layer, reducing their therapeutic efficacy. Microneedles (MNs) are an emerging drug delivery technology that have been demonstrated to successfully penetrate the outer layers of the skin, whilst minimising damage to skin barrier function. Delivering photosensitising drugs using this platform has been demonstrated to have several advantages over conventional photodynamic therapy, such as, painless application, reduced erythema, enhanced cosmetic results and improved intradermal delivery. The aim of this study was to physically characterise dissolving MNs loaded with the photosensitising agent, methylene blue and assess their photodynamic antimicrobial activity. Dissolving MNs were fabricated from aqueous blends of Gantrez(®) AN-139 co-polymer containing varying loadings of methylene blue. A height reduction of 29.8% was observed for MNs prepared from blends containing 0.5% w/w methylene blue following application of a total force of 70.56 N/array. A previously validated insertion test was used to assess the effect of drug loading on MN insertion into a wound model. Staphylococcus aureus, Escherichia coli and Candida albicans biofilms were incubated with various methylene blue concentrations within the range delivered by MNs in vitro (0.1-2.5 mg/mL) and either irradiated at 635 nm using a Paterson Lamp or subjected to a dark period. Microbial susceptibility to PACT was determined by assessing the total viable count. Kill rates of >96%, were achieved for S

  3. Photodynamic antimicrobial chemotherapy activity of (5,10,15,20-tetrakis(4-(4-carboxyphenycarbonoimidoyl)phenyl)porphyrinato) chloro gallium(III).

    PubMed

    Managa, Muthumuni; Amuhaya, Edith K; Nyokong, Tebello

    2015-12-01

    (5,10,15,20-Tetrakis(4-(4-carboxyphenycarbonoimidoyl)phenyl)porphyrinato) chloro gallium(III) (complex 1) was conjugated to platinum nanoparticles (PtNPs) (represented as 1-PtNPs). The resulting conjugate showed 18 nm red shift in the Soret band when compared to 1 alone. Complex 1 and 1-PtNPs showed promising photodynamic antimicrobial chemotherapy (PACT) activity against Staphylococcus aureus, Escherichia coli and Candida albicans in solution where the log reductions obtained were 4.92, 3.76, and 3.95, respectively for 1-PtNPs. The singlet oxygen quantum yields obtained were higher at 0.56 for 1-PtNPs in DMF while that of 1 was 0.52 in the same solvent. This resulted in improved PACT activity for 1-PtNPs compared to 1 alone.

  4. Electrically-responsive anti-adherent hydrogels for photodynamic antimicrobial chemotherapy.

    PubMed

    Fallows, Steven J; Garland, Martin J; Cassidy, Corona M; Tunney, Michael M; Singh, Thakur Raghu Raj; Donnelly, Ryan F

    2012-09-01

    The loading of the photosensitisers meso-Tetra (N-methyl-4-pyridyl) porphine tetra tosylate (TMP), methylene blue (MB) and TMP with sodium dodecyl sulphate (SDS) into and release from hydrogels composed of the polyelectrolyte poly(methyl vinyl ether-co-maleic acid) crosslinked in a 2:1 ratio with PEG 10,000 were investigated as a potential rapid photodynamic antimicrobial chemotherapy (PACT) treatment for infected wounds using iontophoresis as a novel delivery method. Photosensitiser uptake was very high; (% TMP uptake; 95.53-96.72%) (% MB uptake; 90.58-93.26%) and was PMVE/MA concentration independent, whilst SDS severely limited TMP uptake (5.93-8.75%). Hydrogel hardness, compressibility and adhesiveness on the dermal surface of neonate porcine skin increased with PMVE/MA concentration and were significantly increased with SDS. The ionic conductivities of the hydrogels increased with PMVE/MA concentration. Drug release was PMVE/MA concentration independent, except for drug release under iontophoteric conditions for MB and TMP (without SDS). In just 15 min, the mean% drug concentrations released of TMP, TMP (with SDS) and MB using an electric current ranged from 22.30 to 64.72 μg ml(-1), 6.37-4.59 μg ml(-1) and 11.73-36.57 μg ml(-1) respectively. These concentrations were in excess of those required to induce complete kill of clinical strains of meticillin-resistant Staphylococcus aureus and Burkholderia cepacia. Thus these results support our contention that the iontophoteric delivery of TMP and MB using anti-adherent, electrically-responsive, PEG-crosslinked PMVE/MA hydrogels are a potential option in the rapid PACT treatment of infected wounds.

  5. Photodynamic antimicrobial chemotherapy (PACT) for the treatment of malaria, leishmaniasis and trypanosomiasis.

    PubMed

    Baptista, M S; Wainwright, M

    2011-01-01

    A photodynamic effect occurs when photosensitiser molecules absorb light and dissipate the absorbed energy by transferring it to biological acceptors (usually oxygen), generating an excess of reactive species that are able to force cells into death pathways. Several tropical diseases present physiopathological aspects that are accessible to the application of a photosensitiser and local illumination. In addition, disease may be transmitted through infected blood donations, and many of the aetiological agents associated with tropical diseases have been shown to be susceptible to the photodynamic approach. However, there has been no systematic investigation of the application of photoantimicrobial agents in the various presentations, whether to human disease or to the disinfection of blood products or even as photo-insecticides. We aim in this review to report the advances in the photoantimicrobial approach that are beneficial to the field of anti-parasite therapy and also have the potential to facilitate the development of low-cost/high-efficiency protocols for underserved populations.

  6. Evaluation of photodynamic antimicrobial therapy (PACT) against promastigotes form of the Leishmania (Viannia) braziliensis: in vitro study

    NASA Astrophysics Data System (ADS)

    Barbosa, Artur F. S.; Sangiorgi, Bruno B.; Galdino, Suely L.; Pitta, Ivan R.; Barral Netto, Manoel; Correia, Neandder A.; Pinheiro, Antônio L. B.

    2012-03-01

    Leishmaniasis is a complex disease that affects more than 12 million people in 88 countries worldwide. Leishmania (Viannia) braziliensis is the most common species in the Americas and the most important causative agent of cutaneous and mucocutaneous leishmaniasis in Brazil. The therapeutic arsenal routinely employed to treat patients with leishmaniasis is limited and unsatisfactory. For cutaneous leishmaniasis, pentavalent antimonials are the first line therapeutic scheme recommended by the WHO. These compounds are highly toxic, poorly tolerated and their effectiveness highly variable. In this work, a technique with, so far, an unknown disadvantage is discussed. The aim of this study was to verify the effectiveness of PACT in vitro, as a new technique for the treatment of Leishmaniasis. For this, semiconductor laser (λ = 660nm, 40mW, 4.2J/cm2, CW) associated to phenothiazine's derivatives (5 and 10 μg/ml, TBO, Methylene Blue or Phenothiazine) on the promastigotes form of Leishmania braziliensis in a single session was used. Viability of the parasites was assessed in quadruplicates of each group. The samples were removed and analyzed in a hemocytometer 72h after PACT. We found an important decrease in the number of viable parasites on all treated groups in comparison to their controls. The results of present study showed significant percentage of lethality (above 95%) of the protocol. The 99.23% of lethality was achieved with 10 μg/ml of TBO. No lethality was seen on groups treated neither with laser nor with each compounds separately. The results are promising and indicative that the use of PACT may be a powerful treatment of leishmaniasis when compared to already available ones.

  7. In vitro study of the photodynamic antimicrobial therapy (PACT) against promastigotes form of the leishmania (viannia) braziliensis: in vitro study

    NASA Astrophysics Data System (ADS)

    Barbosa, Artur F. S.; Sangiorgi, Bruno B.; Galdino, Suely L.; Pitta, Ivan R.; Barral-Netto, Manoel; Pinheiro, Antônio L. B.

    2013-03-01

    Leishmaniasis, a protozoan parasitic disease that remains a major worldwide health problem with high endemicity in developing countries. Treatment of cutaneous Leishmaniasis (CL) should be decided by the clinical lesions, etiological species and its potential to develop into mucosal Leishmaniasis. High cost, systemic toxicity, and diminished efficacy due to development of parasite resistance are the serious drawbacks of current treatment options. Thus, identifying new, effective, and safer anti-leishmanial drug(s) is of paramount importance. The aim of this study was to verify the effectiveness of PACT in vitro, as a new technique for the treatment of Leishmaniasis. For this, semiconductor laser (λ = 660nm, 40mW, 8.4J/cm2, CW) associated to phenothiazine's derivatives (5 and 10 μg/ml, TBO, Methylene Blue or Phenothiazine) on the promastigotes form of Leishmania braziliensis in a single session was used. Viability of the parasites was assessed in quadruplicates of each group. The samples were removed and analyzed in a hemocytometer 72h after PACT. We found an important decrease in the number of viable parasites on all treated groups in comparison to their controls. The results of present study showed significant percentage of lethality (above 92%) of the protocol. The 98.33% of lethality was achieved with 10 μg/ml of FTZ. No lethality was seen on groups treated neither with laser nor with each compounds separately. The results are promising and indicative that the use of PACT may be a powerful treatment of Leishmaniasis when compared to already available ones.

  8. Resistance in antimicrobial photodynamic inactivation of bacteria.

    PubMed

    Maisch, Tim

    2015-08-01

    Antibiotics have increasingly lost their impact to kill bacteria efficiently during the last 10 years. The emergence and dissemination of superbugs with resistance to multiple antibiotic classes have occurred among Gram-positive and Gram-negative strains including Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter strains. These six superbugs can "escape" more or less any single kind of antibiotic treatment. That means bacteria are very good at developing resistance against antibiotics in a short time. One new approach is called photodynamic antimicrobial chemotherapy (PACT) which already has demonstrated an efficient antimicrobial efficacy among multi-resistant bacteria. Until now it has been questionable if bacteria can develop resistance against PACT. This perspective summarises the current knowledge about the susceptibility of bacteria towards oxidative stress and sheds some light on possible strategies of the development of photodynamic inactivation of bacteria (PACT)-induced oxidative stress resistance by bacteria.

  9. Methylene Blue-Loaded Dissolving Microneedles: Potential Use in Photodynamic Antimicrobial Chemotherapy of Infected Wounds

    PubMed Central

    Caffarel-Salvador, Ester; Kearney, Mary-Carmel; Mairs, Rachel; Gallo, Luigi; Stewart, Sarah A.; Brady, Aaron J.; Donnelly, Ryan F.

    2015-01-01

    Photodynamic therapy involves delivery of a photosensitising drug that is activated by light of a specific wavelength, resulting in generation of highly reactive radicals. This activated species can cause destruction of targeted cells. Application of this process for treatment of microbial infections has been termed “photodynamic antimicrobial chemotherapy” (PACT). In the treatment of chronic wounds, the delivery of photosensitising agents is often impeded by the presence of a thick hyperkeratotic/necrotic tissue layer, reducing their therapeutic efficacy. Microneedles (MNs) are an emerging drug delivery technology that have been demonstrated to successfully penetrate the outer layers of the skin, whilst minimising damage to skin barrier function. Delivering photosensitising drugs using this platform has been demonstrated to have several advantages over conventional photodynamic therapy, such as, painless application, reduced erythema, enhanced cosmetic results and improved intradermal delivery. The aim of this study was to physically characterise dissolving MNs loaded with the photosensitising agent, methylene blue and assess their photodynamic antimicrobial activity. Dissolving MNs were fabricated from aqueous blends of Gantrez® AN-139 co-polymer containing varying loadings of methylene blue. A height reduction of 29.8% was observed for MNs prepared from blends containing 0.5% w/w methylene blue following application of a total force of 70.56 N/array. A previously validated insertion test was used to assess the effect of drug loading on MN insertion into a wound model. Staphylococcus aureus, Escherichia coli and Candida albicans biofilms were incubated with various methylene blue concentrations within the range delivered by MNs in vitro (0.1–2.5 mg/mL) and either irradiated at 635 nm using a Paterson Lamp or subjected to a dark period. Microbial susceptibility to PACT was determined by assessing the total viable count. Kill rates of >96%, were achieved for

  10. Longitudinal effect of curcumin-photodynamic antimicrobial chemotherapy in adolescents during fixed orthodontic treatment: a single-blind randomized clinical trial study.

    PubMed

    Paschoal, Marco Aurélio; Moura, Cíntia Maria Zanin; Jeremias, Fabiano; Souza, Juliana Feltrin; Bagnato, Vanderlei S; Giusti, Juçaíra S M; Santos-Pinto, Lourdes

    2015-11-01

    White spot lesions are one of the concerns during the fixed orthodontic treatment. Thus, the aim of the present study was to evaluate the antimicrobial/anti-inflammatory effect of curcumin-photodynamic antimicrobial chemotherapy (c-PACT) and chlorhexidine varnish on the plaque accumulation and gingival bleeding in adolescents under fixed orthodontic treatment. A randomized clinical trial was performed with an initial number of 45 patients being distributed into three groups: group I-chlorhexidine varnish 2%, group II-placebo varnish, and group III-c-PACT (curcumin at 1.5 mg.mL(-1)) exposed to blue Light-emitting diode (LED) light at 450 nm (power density = 165 mW.cm(-2), fluency = 96 J.cm(-2), total dose = 150.7 J). The treatments were performed for four consecutive times with an interval of 1 week each. After the interventions, two calibrated examiners (Kappa value = 0.75) analyzed the dental plaque accumulation by plaque index (PI) and gingivitis condition by gingival bleeding index (GBI) with 1 and 3 months of follow-up after the treatments comprised a final sample of 35 patients. No significant difference was found to PI between the groups during baseline and 1-month period. Group III (1.52 ± 0.51) presented significance difference from group I (0.91 ± 0.75) and group II (1.03 ± 0.51) at 3 months of follow-up. In this same period, there was more plaque accumulation with significant statistical difference (P ≤ 0.05) in comparison to the other periods to all studied groups. There was a GBI reduction statistically significant to groups I and III at 1-month follow-up in comparison to other periods. No effect was verified to dental plaque accumulation after the photodynamic application mediated with curcumin activated with a blue LED light.

  11. Longitudinal effect of curcumin-photodynamic antimicrobial chemotherapy in adolescents during fixed orthodontic treatment: a single-blind randomized clinical trial study.

    PubMed

    Paschoal, Marco Aurélio; Moura, Cíntia Maria Zanin; Jeremias, Fabiano; Souza, Juliana Feltrin; Bagnato, Vanderlei S; Giusti, Juçaíra S M; Santos-Pinto, Lourdes

    2015-11-01

    White spot lesions are one of the concerns during the fixed orthodontic treatment. Thus, the aim of the present study was to evaluate the antimicrobial/anti-inflammatory effect of curcumin-photodynamic antimicrobial chemotherapy (c-PACT) and chlorhexidine varnish on the plaque accumulation and gingival bleeding in adolescents under fixed orthodontic treatment. A randomized clinical trial was performed with an initial number of 45 patients being distributed into three groups: group I-chlorhexidine varnish 2%, group II-placebo varnish, and group III-c-PACT (curcumin at 1.5 mg.mL(-1)) exposed to blue Light-emitting diode (LED) light at 450 nm (power density = 165 mW.cm(-2), fluency = 96 J.cm(-2), total dose = 150.7 J). The treatments were performed for four consecutive times with an interval of 1 week each. After the interventions, two calibrated examiners (Kappa value = 0.75) analyzed the dental plaque accumulation by plaque index (PI) and gingivitis condition by gingival bleeding index (GBI) with 1 and 3 months of follow-up after the treatments comprised a final sample of 35 patients. No significant difference was found to PI between the groups during baseline and 1-month period. Group III (1.52 ± 0.51) presented significance difference from group I (0.91 ± 0.75) and group II (1.03 ± 0.51) at 3 months of follow-up. In this same period, there was more plaque accumulation with significant statistical difference (P ≤ 0.05) in comparison to the other periods to all studied groups. There was a GBI reduction statistically significant to groups I and III at 1-month follow-up in comparison to other periods. No effect was verified to dental plaque accumulation after the photodynamic application mediated with curcumin activated with a blue LED light. PMID:25543296

  12. New criteria for selecting the proper antimicrobial chemotherapy for severe sepsis and septic shock.

    PubMed

    Periti, P; Mazzei, T

    1999-07-01

    The mortality rate resulting from severe bacterial sepsis, particularly that associated with shock, still approaches 50% in spite of appropriate antimicrobial therapy and optimum supportive care. Bacterial endotoxins that are part of the cell wall are one of the cofactors in the pathogenesis of sepsis and septic shock and are often induced by antimicrobial chemotherapy even if it is administered rationally. Not all antimicrobial agents are equally capable of inducing septic shock; this is dependant on their mechanism of action rather than on the causative pathogen species. The quantity of endotoxin released depends on the drug dose and whether filaments or spheroplast formation predominates. Some antibiotics such as carbapenems, ceftriaxone, cefepime, glycopeptides, aminoglycosides and quinolones do not have the propensity to provoke septic shock because their rapid bactericidal activity induces mainly spheroplast or fragile spheroplast-like bacterial forms.

  13. Host immune modulation by antimicrobial drugs: current knowledge and implications for antimicrobial chemotherapy.

    PubMed

    Banche, Giuliana; Allizond, Valeria; Mandras, Narcisa; Tullio, Vivian; Cuffini, Anna Maria

    2014-10-01

    It is known that antimicrobial agents possess several, beneficial, secondary properties which complement their primary antimicrobial activity like the immunomodulatory capacity that enforces host defense mechanisms or reduces host inflammatory response. In this review the current state of our recent research about the interaction between some antimicrobial agents and the immune system as complex pyramid of redundant cellular factors, humoral effectors and mediators against various microbial pathogens, will be presented and compared with recent literature data. The nature of such interactions is diverse and depends on the drug, the host immunological status and the microorganism. A more complete understanding of the host immune modulation by antimicrobial drugs may guide the selection of appropriate regimens for given clinical situations.

  14. NATO-Warsaw Pact

    SciTech Connect

    Not Available

    1988-12-01

    The North Atlantic Treaty Organization's peacetime deterrent position is good, and its conventional capabilities have improved over the last decade but they should be better says the Conventional Defense Study Group. It discussed the many factors NATO's success or failure would depend on and concluded that neither side has such an overwhelming advantage that victory is assured for one or the other. Although most scenarios favor the Warsaw Pact as the victor rather than NATO, group participants believe that Warsaw Pact forces might not have a substantial advantage in manpower or division strength in a short-preparation or medium warning attack. Some suggested solutions to improving NATO's conventional capabilities are discussed. They include the following: encouraging Europeans to assume greater responsibility for their defense, such as creating physical barriers to delay a Warsaw Pact advance; increasing emphasis on conventional war-fighting in Nato planning; using dumb weapons to conserve limited stocks of smart munitions; and using arms control measures, either reciprocal or negotiated, to reduce troop size.

  15. Chemotherapy

    MedlinePlus

    ... getting chemotherapy. Chemotherapy is most often given in cycles. These cycles may last one day, several days, or a ... period when no chemotherapy is given between each cycle. A rest period may last for days, weeks, ...

  16. The 2016 Garrod Lecture: The role of the healthcare epidemiologist in antimicrobial chemotherapy-a view from the USA.

    PubMed

    McGowan, John E

    2016-09-01

    Antimicrobial chemotherapy now spans 80 years and four generations. The healthcare epidemiologist has an important role to play in this field. Efforts focus in three areas: (i) minimizing the transmission of antimicrobial-resistant bacteria in healthcare settings (infection control); (ii) optimizing use of currently available antibacterial drugs (antibiotic stewardship); and (iii) recognizing and responding to opportunities for new drug development. For each area, the epidemiologist provides data that address four practical questions-'What is the problem?', 'What should be done?', 'Is it being done?' and 'Is it working?'. A team approach is crucial to acting on the epidemiological data. Examples are presented to illustrate different roles of the epidemiologist, and tools and measures that have been developed to address some problems of current importance. Monitoring of quality, integrity and security of data remains a major focus. The epidemiologist will continue to have a key role in antimicrobial chemotherapy. PMID:27550989

  17. Clofazimine Contributes Sustained Antimicrobial Activity after Treatment Cessation in a Mouse Model of Tuberculosis Chemotherapy

    PubMed Central

    Swanson, Rosemary V.; Ammerman, Nicole C.; Ngcobo, Bongani; Adamson, John; Moodley, Chivonne; Dorasamy, Afton; Moodley, Sashen; Mgaga, Zinhle; Bester, Linda A.; Singh, Sanil D.; Almeida, Deepak V.

    2016-01-01

    Experimental and clinical studies have indicated that the antileprosy drug clofazimine may contribute treatment-shortening activity when included in tuberculosis treatment regimens. Clofazimine accumulates to high levels in tissues, has a long half-life, and remains in the body for months after administration is stopped. We hypothesized that in tuberculosis treatment, accumulated clofazimine may contribute sustained antimicrobial activity after treatment cessation, and we used the BALB/c mouse model of chronic tuberculosis chemotherapy to address this hypothesis. Mycobacterium tuberculosis-infected mice were treated for 4 weeks or 8 weeks with either isoniazid alone, clofazimine alone, the first-line regimen rifampin-isoniazid-pyrazinamide-ethambutol, or a first-line regimen where clofazimine was administered in place of ethambutol. To evaluate posttreatment antimicrobial activity, bacterial regrowth in the lungs and spleens was assessed at the day of treatment cessation and 2, 4, 6, and 8 weeks after treatment was stopped. Bacterial regrowth was delayed in all mice receiving clofazimine, either alone or in combination, compared to the mice that did not receive clofazimine. This effect was especially evident in mice receiving multidrug therapy. In mice not receiving clofazimine, bacterial regrowth began almost immediately after treatment was stopped, while in mice receiving clofazimine, bacterial regrowth was delayed for up to 6 weeks, with the duration of sustained antimicrobial activity being positively associated with the time that serum clofazimine levels remained at or above the 0.25-μg/ml MIC for M. tuberculosis. Thus, sustained activity of clofazimine may be important in the treatment-shortening effect associated with this drug. PMID:26926638

  18. NATO-Warsaw Pact

    SciTech Connect

    Not Available

    1990-04-01

    If proposals to reduce conventional forces and equipment in Europe are adopted, how much of a peace dividend will the United States and its NATO allies reap This report discussed how GAO looked at the savings associated with a conventional forces reduction treaty and found that only a limited NATO peace dividend will result directly from the treaty proposals. Further, this dividend will not be shared equally by all NATO allies. Under the treaty, only the United States and the Soviet Union are required to make troop cuts. U.S. savings would result from the DOD decision to reduce the total number of its forces rather than simply relocate personnel from Europe. Implementing a Conventional Armed Forces in Europe treaty will be a complex task that will result in all NATO allies incurring certain costs. For example, verifying compliance with the treaty may require extensive NATO inspection and monitoring of Warsaw Pact force levels and treaty-limited equipment. NATO will incur additional costs in complying with treaty provisions that require the destruction of many conventional weapons.

  19. Factors Determining Staphylococcus aureus Susceptibility to Photoantimicrobial Chemotherapy: RsbU Activity, Staphyloxanthin Level, and Membrane Fluidity.

    PubMed

    Kossakowska-Zwierucho, Monika; Kaźmierkiewicz, Rajmund; Bielawski, Krzysztof P; Nakonieczna, Joanna

    2016-01-01

    Photoantimicrobial chemotherapy (PACT) constitutes a particular type of stress condition, in which bacterial cells induce a pleiotropic and as yet unexplored effect. In light of this, the key master regulators are of putative significance to the overall phototoxic outcome. In Staphylococcus aureus, the alternative sigma factor σ(B) controls the expression of genes involved in the response to environmental stress. We show that aberration of any sigB operon genes in S. aureus USA300 isogenic mutants causes a pronounced sensitization (>5 log10 reduction in CFU drop) to PACT with selected photosensitizers, namely protoporphyrin diarginate, zinc phthalocyanine and rose bengal. This effect is partly due to aberration-coupled staphyloxanthin synthesis inhibition. We identified frequent mutations in RsbU, a σ(B) activator, in PACT-vulnerable clinical isolates of S. aureus, resulting in σ(B) activity impairment. Locations of significant changes in protein structure (IS256 insertion, early STOP codon occurrence, substitutions A230T and A276D) were shown in a theoretical model of S. aureus RsbU. As a phenotypic hallmark of PACT-vulnerable S. aureus strains, we observed an increased fluidity of bacterial cell membrane, which is a result of staphyloxanthin content and other yet unidentified factors. Our research indicates σ(B) as a promising target of adjunctive antimicrobial therapy and suggests that enhanced cell membrane fluidity may be an adjuvant strategy in PACT. PMID:27486456

  20. Factors Determining Staphylococcus aureus Susceptibility to Photoantimicrobial Chemotherapy: RsbU Activity, Staphyloxanthin Level, and Membrane Fluidity

    PubMed Central

    Kossakowska-Zwierucho, Monika; Kaźmierkiewicz, Rajmund; Bielawski, Krzysztof P.; Nakonieczna, Joanna

    2016-01-01

    Photoantimicrobial chemotherapy (PACT) constitutes a particular type of stress condition, in which bacterial cells induce a pleiotropic and as yet unexplored effect. In light of this, the key master regulators are of putative significance to the overall phototoxic outcome. In Staphylococcus aureus, the alternative sigma factor σB controls the expression of genes involved in the response to environmental stress. We show that aberration of any sigB operon genes in S. aureus USA300 isogenic mutants causes a pronounced sensitization (>5 log10 reduction in CFU drop) to PACT with selected photosensitizers, namely protoporphyrin diarginate, zinc phthalocyanine and rose bengal. This effect is partly due to aberration-coupled staphyloxanthin synthesis inhibition. We identified frequent mutations in RsbU, a σB activator, in PACT-vulnerable clinical isolates of S. aureus, resulting in σB activity impairment. Locations of significant changes in protein structure (IS256 insertion, early STOP codon occurrence, substitutions A230T and A276D) were shown in a theoretical model of S. aureus RsbU. As a phenotypic hallmark of PACT-vulnerable S. aureus strains, we observed an increased fluidity of bacterial cell membrane, which is a result of staphyloxanthin content and other yet unidentified factors. Our research indicates σB as a promising target of adjunctive antimicrobial therapy and suggests that enhanced cell membrane fluidity may be an adjuvant strategy in PACT. PMID:27486456

  1. Positive Adolescent Choices Training (PACT).

    ERIC Educational Resources Information Center

    Hammond, W. Rodney; And Others

    Positive Adolescent Choices Training (PACT) is a health promotion program providing violence prevention programming targeted at black youth, at high risk for becoming either perpetrators or victims of violence. Conducted by the School of Professional Psychology of Wright State University in Dayton, Ohio, in cooperation with Dayton Public Schools,…

  2. [Chemotherapy].

    PubMed

    Aiba, Keisuke

    2004-05-01

    Cancer chemotherapy in the treatment of colorectal cancer has been evolving so extensively than ever. 5-fluorouracil (5-FU) has been a pivotal and a single active agent in the treatment of colorectal cancer. Reproducing and consistent better response rate has been shown since the introduction of the concept of biochemical modulation of 5-FU by leucovorin, a reduced folate, to the clinic and a combination chemotherapy of 5-FU and leucovorin (FL) has enable us to obtain a response rate around 20-30% and a median survival time ranging from 10 to 12 months. IFL regimen combing CPT-11 with FL showed a better MST ranging from 14 to 15 months, but now serious toxicity precludes general use outside of clinical trials. In the Europe, de Gramont regimen, an unique dose and schedule of 5-FU using a combination of continuous intravenous infusion of 5-FU with leucovorin over two days and bolus infusion of 5-FU twice over the same period, has been developed and shown improved antitumor activity and toxic profiles. FOLFOX 4, a combination chemotherapy of de Gramont regimen and oxaliplatin which is a third generation of cisplatin and a uniqe toxic profile with neuropathy, has demonstrated improved MST over a year and acceptable toxic profiles. Now FOLFOX 4 is considered to be a standard chemotherapy for the patients with advanced colorectal cancer, since a large phase III randomized study has shown that FOLFOX 4 was the most active and less toxic treatment regimen among active regimens such as IFL and IROX (CPT-11 and oxaliplatin). More recently, a combination of IFL and bevacizumab which is one of the molecular target agents and a antibody agent against vascular endothelial growth factor (VEGF), has demonstrated better MST reaching 20 months. Future large scale trials will attempt to develop more active regimen incorporating so-called molecular target agents.

  3. PACT: Parents and Children Together. Program Manual.

    ERIC Educational Resources Information Center

    Whitney, Loralyn; Hager, Elizabeth A.

    The Parent and Children Together (PACT) project, developed by the Arkansas Valley and High Plain Regional Library Services in Colorado, is aimed at promoting lifelong interest in reading among today's children. PACT services include: (1) sponsoring workshops that will train librarians and volunteers to plan and present parents' programs; (2)…

  4. Synthesis, characterization and in vitro photodynamic antimicrobial activity of basic amino acid-porphyrin conjugates.

    PubMed

    Meng, Shuai; Xu, Zengping; Hong, Ge; Zhao, Lihui; Zhao, Zhanjuan; Guo, Jianghong; Ji, Haiying; Liu, Tianjun

    2015-03-01

    Photodynamic antimicrobial chemotherapy (PACT), as a novel and effective modality for the treatment of infection with the advantage of circumventing multidrug resistance, receives great attention in recent years. The photosensitizer is the crucial element in PACT, and cationic porphyrins have been demonstrated to usually be more efficient than neutral and negatively charged analogues towards bacteria in PACT. In this work, three native basic amino acids, l-lysine, l-histidine and l-arginine, were conjugated with amino porphyrins as cationic auxiliary groups, and 13 target compounds were synthesized. This paper reports their syntheses, structural characterizations, oil-water partition coefficients, singlet oxygen generation yields, photo-stability, as well as their photo inactivation efficacies against methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli and Pseudomonas aeruginosa in vitro. The preliminary structure-activity relationship was discussed. Compound 4i, with porphyrin bearing four lysine moieties, displays the highest photo inactivation efficacy against the tested bacterial strains at 3.91 μM with a low light dose (6 J/cm(2)), and it is stable in serum and lower cytotoxicity to A929 cells. These basic amino acid-porphyrin conjugates are potential photosensitizers for PACT.

  5. Photodynamic antimicrobial chemotherapy activity of gallium tetra-(4-carboxyphenyl) porphyrin when conjugated to differently shaped platinum nanoparticles

    NASA Astrophysics Data System (ADS)

    Managa, Muthumuni; Nyokong, Tebello

    2015-11-01

    This work reports on the conjugation of differently shaped Pt nanoparticles (PtNPs) with ClGa(III) 5,10,15,20-tetrakis-(4-carboxyphenyl) porphyrin (ClGaTCPP). The resulting conjugates were used for photodynamic antimicrobial chemotherapy against Staphylococcus aureus. The degree of photo-inactivation is dependent on concentration of the conjugates, light dose (fluence) and illumination time. The log reduction obtained for ClGaTCPP when conjugated to cubic PtNPs was 4.64 log (which indicate 99.99% of the bacteria have been killed), which is much higher than 3.94 log unit for ClGaTCPP-Hexagonal PtNPs and 3.31 log units for ClGaTCPP-Unshaped PtNPs. ClGaTCPP alone gave a log unit reduction of less than 3, showing the importance of conjugation to PtNPs.

  6. Payload crew training scheduler (PACTS) user's manual

    NASA Technical Reports Server (NTRS)

    Shipman, D. L.

    1980-01-01

    The operation of the payload specialist training scheduler (PACTS) is discussed in this user's manual which is used to schedule payload specialists for mission training on the Spacelab experiments. The PACTS program is a fully automated interactive, computerized scheduling program equipped with tutorial displays. The tutorial displays are sufficiently detailed for use by a program analyst having no computer experience. The PACTS program is designed to operate on the UNIVAC 1108 computer system, and has the capability to load output into a PDP 11/45 Interactive Graphics Display System for printing schedules. The program has the capacity to handle up to three overlapping Spacelab missions.

  7. Does High-Dose Antimicrobial Chemotherapy Prevent the Evolution of Resistance?

    PubMed Central

    Day, Troy; Read, Andrew F.

    2016-01-01

    High-dose chemotherapy has long been advocated as a means of controlling drug resistance in infectious diseases but recent empirical studies have begun to challenge this view. We develop a very general framework for modeling and understanding resistance emergence based on principles from evolutionary biology. We use this framework to show how high-dose chemotherapy engenders opposing evolutionary processes involving the mutational input of resistant strains and their release from ecological competition. Whether such therapy provides the best approach for controlling resistance therefore depends on the relative strengths of these processes. These opposing processes typically lead to a unimodal relationship between drug pressure and resistance emergence. As a result, the optimal drug dose lies at either end of the therapeutic window of clinically acceptable concentrations. We illustrate our findings with a simple model that shows how a seemingly minor change in parameter values can alter the outcome from one where high-dose chemotherapy is optimal to one where using the smallest clinically effective dose is best. A review of the available empirical evidence provides broad support for these general conclusions. Our analysis opens up treatment options not currently considered as resistance management strategies, and it also simplifies the experiments required to determine the drug doses which best retard resistance emergence in patients. PMID:26820986

  8. NATO-Warsaw Pact. Force mobilization

    SciTech Connect

    Simon, J.

    1988-01-01

    Recent demographic and economic trends present mobilization problems for both the North Atlantic Treaty Organization and the Warsaw Pact. When the United States and the Soviet Union agreed to rid Europe of intermediate-range nuclear weapons, their agreement increased the emphasis on conventional force balances-thus creating anew strains within and between the alliances. These developments make the time ripe for a comprehensive study of NATO and Warsaw Pact capabilities to mobilize their conventional forces. This book draws upon essays prepared for the NATO-Warsaw Pact conference. In these essays, Us and European specialists discuss developments and vulnerabilities in the blocs. They address four issues: (1) mobilization and reinforcement, (2) developments in front-line states, (3) communications and transportation problems, and (4) difficulties on the flanks. These individual studies and the book as a whole represent the most current and thorough examination of NATO-Warsaw Pact capabilities available today.

  9. Interference of bacterial cell-to-cell communication: a new concept of antimicrobial chemotherapy breaks antibiotic resistance

    PubMed Central

    Hirakawa, Hidetada; Tomita, Haruyoshi

    2013-01-01

    Bacteria use a cell-to-cell communication activity termed “quorum sensing” to coordinate group behaviors in a cell density dependent manner. Quorum sensing influences the expression profile of diverse genes, including antibiotic tolerance and virulence determinants, via specific chemical compounds called “autoinducers”. During quorum sensing, Gram-negative bacteria typically use an acylated homoserine lactone (AHL) called autoinducer 1. Since the first discovery of quorum sensing in a marine bacterium, it has been recognized that more than 100 species possess this mechanism of cell-to-cell communication. In addition to being of interest from a biological standpoint, quorum sensing is a potential target for antimicrobial chemotherapy. This unique concept of antimicrobial control relies on reducing the burden of virulence rather than killing the bacteria. It is believed that this approach will not only suppress the development of antibiotic resistance, but will also improve the treatment of refractory infections triggered by multi-drug resistant pathogens. In this paper, we review and track recent progress in studies on AHL inhibitors/modulators from a biological standpoint. It has been discovered that both natural and synthetic compounds can disrupt quorum sensing by a variety of means, such as jamming signal transduction, inhibition of signal production and break-down and trapping of signal compounds. We also focus on the regulatory elements that attenuate quorum sensing activities and discuss their unique properties. Understanding the biological roles of regulatory elements might be useful in developing inhibitor applications and understanding how quorum sensing is controlled. PMID:23720655

  10. Bacterial bloodstream infections and antimicrobial susceptibility pattern in pediatric hematology/oncology patients after anticancer chemotherapy

    PubMed Central

    Al-Mulla, Naima A; Taj-Aldeen, Saad J; El Shafie, Sittana; Janahi, Mohammed; Al-Nasser, Abdullah A; Chandra, Prem

    2014-01-01

    Purpose Bloodstream infections in pediatric hematology and oncology represent a major problem worldwide, but this has not been studied in Qatar. In this study, we investigated the burden of infection and the resistance pattern in the bacterial etiology, in the only tertiary pediatric hematology and oncology center in Qatar. Methods All pediatric cancer patients (n=185) were evaluated retrospectively during the period 2004–2011; a total of 70 (38%) patients were diagnosed with bloodstream infections. Bacterial etiology was determined, along with their susceptibility patterns. Neutropenia, duration of neutropenia, fever, duration of fever, and C-reactive protein (CRP) were evaluated throughout the study. Results A total of 70 patients (38%) were diagnosed with acute leukemias, lymphomas, solid tumors, or brain tumors; those patients experienced 111 episodes of bacteremia. The most common Gram-positive (n=64 [55%]) isolates were Staphylococcus epidermidis (n=26), Staphylococcus hominis (n=9), and Staphylococcus haemolyticus (n=7), and the common Gram-negative (n=52 [45%]) isolates were Klebsiella pneumoniae (n=14), Pseudomonas aeruginosa (n=10), and Escherichia coli (n=7). There was a significant association observed between fever with positive blood culture and different types of cancer (P=0.035). The majority of bacteremia (n=68 [61.3%]) occurred in nonneutropenic episodes. Elevated values of CRP (≥5 mg/L) were detected in 82 (95.3%) episodes and were negatively correlated with absolute neutrophil count (ANC) (r=−0.18; P=0.248) among all cases. However, the infection-related fatality rate was 2.2% (n=4), with three caused by Gram-negative pathogens. Multidrug resistant organisms were implicated in 33 (28.4%) cases and caused three of the mortality cases. Conclusion Multidrug resistant organisms cause mortality in pediatric cancer patients. Investigation of antimicrobial susceptibility of these organisms may guide successful antimicrobial therapy and improve

  11. Photodynamic Antimicrobial Chemotherapy for Root Canal System Asepsis: A Narrative Literature Review

    PubMed Central

    Diogo, P.; Gonçalves, T.; Palma, P.; Santos, J. M.

    2015-01-01

    Aim. The aim of this comprehensive literature review was to address the question: Does photodynamic therapy (PDT) improve root canal disinfection through significant bacterial reduction in the root canal system? Methodology. A comprehensive narrative literature review was performed to compare PDT effect with sodium hypochlorite as the comparative classical irrigant. Two reviewers independently conducted literature searches using a combination of medical subject heading terms and key words to identify relevant studies comparing information found in 7 electronic databases from January 2000 to May 2015. A manual search was performed on bibliography of articles collected on electronic databases. Authors were contacted to ask for references of more research not detected on the prior electronic and manual searches. Results. The literature search provided 62 titles and abstracts, from which 29 studies were related directly to the search theme. Considering all publications, 14 (48%) showed PDT to be more efficient in antimicrobial outcome than NaOCl (0.5–6% concentration) used alone and 2 (7%) revealed similar effects between them. Toluidine blue and methylene blue are the most used photosensitizers and most commonly laser has 660 nm of wavelength with a 400 nm diameter of intracanal fiber. Conclusions. PDT has been used without a well-defined protocol and still remains at an experimental stage waiting for further optimization. The level of evidence available in clinical studies to answer this question is low and at high risk of bias. PMID:26783392

  12. Photodynamic Antimicrobial Chemotherapy for Root Canal System Asepsis: A Narrative Literature Review.

    PubMed

    Diogo, P; Gonçalves, T; Palma, P; Santos, J M

    2015-01-01

    Aim. The aim of this comprehensive literature review was to address the question: Does photodynamic therapy (PDT) improve root canal disinfection through significant bacterial reduction in the root canal system? Methodology. A comprehensive narrative literature review was performed to compare PDT effect with sodium hypochlorite as the comparative classical irrigant. Two reviewers independently conducted literature searches using a combination of medical subject heading terms and key words to identify relevant studies comparing information found in 7 electronic databases from January 2000 to May 2015. A manual search was performed on bibliography of articles collected on electronic databases. Authors were contacted to ask for references of more research not detected on the prior electronic and manual searches. Results. The literature search provided 62 titles and abstracts, from which 29 studies were related directly to the search theme. Considering all publications, 14 (48%) showed PDT to be more efficient in antimicrobial outcome than NaOCl (0.5-6% concentration) used alone and 2 (7%) revealed similar effects between them. Toluidine blue and methylene blue are the most used photosensitizers and most commonly laser has 660 nm of wavelength with a 400 nm diameter of intracanal fiber. Conclusions. PDT has been used without a well-defined protocol and still remains at an experimental stage waiting for further optimization. The level of evidence available in clinical studies to answer this question is low and at high risk of bias.

  13. Antimicrobial chemotherapy of septicemia due to methicillin-resistant Staphylococcus aureus.

    PubMed Central

    Cafferkey, M T; Hone, R; Keane, C T

    1985-01-01

    The outcome of treatment of 48 episodes of septicemia due to methicillin-resistant Staphylococcus aureus (MRSA) in 44 patients was assessed. Twenty-six of the patients died; nineteen of them died of infection, and infection was a major contributing factor to the deaths of the remaining seven patients. Fourteen of fifteen patients treated with inadequate antibiotic therapy died, and the other patient developed a mycotic aneurysm of the femoral artery, for which amputation was necessary. Eight of eleven patients treated with amikacin (alone or combined with another antimicrobial) died, and three recovered slowly; only one recovered fully without sequelae. In an additional two patients who failed to respond to amikacin, treatment was changed to vancomycin. Vancomycin was used to treat 18 episodes of MRSA septicemia in 17 patients. In 14 of these episodes the patients recovered fully. One patient died of uncontrolled infection, and in three, infection was a contributing factor but not the major cause of death. Vancomycin was confirmed as antibiotic of choice in treating MRSA septicemia. PMID:3878691

  14. Applicability of photodynamic antimicrobial chemotherapy as an alternative to inactivate fish pathogenic bacteria in aquaculture systems.

    PubMed

    Arrojado, Cátia; Pereira, Carla; Tomé, João P C; Faustino, Maria A F; Neves, Maria G P M S; Tomé, Augusto C; Cavaleiro, José A S; Cunha, Angela; Calado, Ricardo; Gomes, Newton C M; Almeida, Adelaide

    2011-10-01

    Aquaculture activities are increasing worldwide, stimulated by the progressive reduction of natural fish stocks in the oceans. However, these activities also suffer heavy production and financial losses resulting from fish infections caused by microbial pathogens, including multidrug resistant bacteria. Therefore, strategies to control fish infections are urgently needed, in order to make aquaculture industry more sustainable. Antimicrobial photodynamic therapy (aPDT) has emerged as an alternative to treat diseases and prevent the development of antibiotic resistance by pathogenic bacteria. The aim of this work was to evaluate the applicability of aPDT to inactivate pathogenic fish bacteria. To reach this objective a cationic porphyrin Tri-Py(+)-Me-PF was tested against nine pathogenic bacteria isolated from a semi-intensive aquaculture system and against the cultivable bacteria of the aquaculture system. The ecological impact of aPDT in the aquatic environment was also tested on the natural bacterial community, using the overall bacterial community structure and the cultivable bacteria as indicators. Photodynamic inactivation of bacterial isolates and of cultivable bacteria was assessed counting the number of colonies. The impact of aPDT in the overall bacterial community structure of the aquaculture water was evaluated by denaturing gel gradient electrophoresis (DGGE). The results showed that, in the presence of Tri-Py(+)-Me-PF, the growth of bacterial isolates was inhibited, resulting in a decrease of ≈7-8 log after 60-270 min of irradiation. Cultivable bacteria were also considerably affected, showing decreases up to the detection limit (≈2 log decrease on cell survival), but the inactivation rate varied significantly with the sampling period. The DGGE fingerprint analyses revealed changes in the bacterial community structure caused by the combination of aPDT and light. The results indicate that aPDT can be regarded as a new approach to control fish

  15. Young Children Create Partner-Specific Referential Pacts with Peers

    ERIC Educational Resources Information Center

    Köymen, Bahar; Schmerse, Daniel; Lieven, Elena; Tomasello, Michael

    2014-01-01

    In 2 studies, we investigated how peers establish a "referential pact" to call something, for example, a "cushion" versus a "pillow" (both equally felicitous). In Study 1, pairs of 4-and 6-year-old German-speaking peers established a referential pact for an artifact, for example, a "woman's shoe," in a…

  16. [Sociodemographic indicators of the Andean Pact countries].

    PubMed

    1991-12-01

    The Andean Pact, also known as the Cartagena Accord, was signed on May 26, 1969, with the goal of promoting the socioeconomic integration of the countries of the subregion (Venezuela, Colombia, Ecuador, Peru, and Bolivia). 1992 marked a new stage in the Andean Pact by the consolidation of the integration process with the establishment of the Andean Free Trade Zone, allowing the uninhibited flow of goods. The subregion's population was 91.8 million in 1990, the most populous being Colombia with 32.9 million people. 71.5% of the total population (65 million people) live in cities with a high level of urban growth. During the period of 1990-95 the average rate of population growth was the highest in Bolivia with 2.8% and the lowest in Colombia with 1.95%. By comparison, the rate of growth was 0.2% in western Europe and 0.7% in the US. According to projections of the UN, approximately 113 million people will be living in the subregion in the year 2000. The indices of life expectancy and infant mortality have improved in recent decades; however, they are still poor compared to those of developed countries. The highest rate of infant mortality was registered in Bolivia with 93/1000 live births, followed by Peru with 76/1000, Ecuador with 53/1000, Colombia with 37/1000, and Venezuela with 33/1000 live births. The average rate of European countries is 7/1000 live births. Life expectancy increased from an average of 50 years in 1950 to 65.4 years in 1990. In 1990, average life expectancy was 76 years in the US, indicating that there are significant differences in medical care and social security between the countries of the region and developed countries.

  17. Mechanism and In Vivo Evaluation: Photodynamic Antibacterial Chemotherapy of Lysine-Porphyrin Conjugate

    PubMed Central

    Xu, Zengping; Gao, Yuxiang; Meng, Shuai; Yang, Baochen; Pang, Liyun; Wang, Chen; Liu, Tianjun

    2016-01-01

    Lysine-porphyrin conjugate 4i has potent photosensitive antibacterial effect on clinical isolated bacterial strains such as Methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli, and Pseudomonas aeruginosa. The mechanism of photodynamic antibacterial chemotherapy of 4i (4i-PACT) in vitro and the treatment effect in vivo was investigated in this paper. Atomic force microscopy (AFM) revealed that 4i-PACT can effectively destroy membrane and wall of bacteria, resulting in leakage of its content. This was confirmed by dual fluorescent staining with acridine orange/ethidium bromide and measuring materials absorption at 260 nm. Agarose gel electrophoresis measurement showed that 4i-PACT can damage genomic DNA. Healing of wound in rat infected by mixed bacteria showed that the efficiency of 4i-PACT is dependent on the dose of light. These results showed that 4i-PACT has promising bactericidal effect both in vitro and in vivo. PMID:26973620

  18. Ten key points for the appropriate use of antibiotics in hospitalised patients: a consensus from the Antimicrobial Stewardship and Resistance Working Groups of the International Society of Chemotherapy.

    PubMed

    Levy Hara, Gabriel; Kanj, Souha S; Pagani, Leonardo; Abbo, Lilian; Endimiani, Andrea; Wertheim, Heiman F L; Amábile-Cuevas, Carlos; Tattevin, Pierre; Mehtar, Shaheen; Lopes Cardoso, Fernando; Unal, Serhat; Gould, Ian

    2016-09-01

    The Antibiotic Stewardship and Resistance Working Groups of the International Society for Chemotherapy propose ten key points for the appropriate use of antibiotics in hospital settings. (i) Get appropriate microbiological samples before antibiotic administration and carefully interpret the results: in the absence of clinical signs of infection, colonisation rarely requires antimicrobial treatment. (ii) Avoid the use of antibiotics to 'treat' fever: use them to treat infections, and investigate the root cause of fever prior to starting treatment. (iii) Start empirical antibiotic treatment after taking cultures, tailoring it to the site of infection, risk factors for multidrug-resistant bacteria, and the local microbiology and susceptibility patterns. (iv) Prescribe drugs at their optimal dosing and for an appropriate duration, adapted to each clinical situation and patient characteristics. (v) Use antibiotic combinations only where the current evidence suggests some benefit. (vi) When possible, avoid antibiotics with a higher likelihood of promoting drug resistance or hospital-acquired infections, or use them only as a last resort. (vii) Drain the infected foci quickly and remove all potentially or proven infected devices: control the infection source. (viii) Always try to de-escalate/streamline antibiotic treatment according to the clinical situation and the microbiological results. (ix) Stop unnecessarily prescribed antibiotics once the absence of infection is likely. And (x) Do not work alone: set up local teams with an infectious diseases specialist, clinical microbiologist, hospital pharmacist, infection control practitioner or hospital epidemiologist, and comply with hospital antibiotic policies and guidelines. PMID:27502752

  19. X-Ray Psoralen Activated Cancer Therapy (X-PACT)

    PubMed Central

    Oldham, Mark; Yoon, Paul; Fathi, Zak; Beyer, Wayne F.; Adamson, Justus; Liu, Leihua; Alcorta, David; Xia, Wenle; Osada, Takuya; Liu, Congxiao; Yang, Xiao Y.; Dodd, Rebecca D.; Herndon, James E.; Meng, Boyu; Kirsch, David G.; Lyerly, H. Kim; Dewhirst, Mark W.; Fecci, Peter; Walder, Harold; Spector, Neil L.

    2016-01-01

    This work investigates X-PACT (X-ray Psoralen Activated Cancer Therapy): a new approach for the treatment of solid cancer. X-PACT utilizes psoralen, a potent anti-cancer therapeutic with current application to proliferative disease and extracorporeal photopheresis (ECP) of cutaneous T Cell Lymphoma. An immunogenic role for light-activated psoralen has been reported, contributing to long-term clinical responses. Psoralen therapies have to-date been limited to superficial or extracorporeal scenarios due to the requirement for psoralen activation by UVA light, which has limited penetration in tissue. X-PACT solves this challenge by activating psoralen with UV light emitted from novel non-tethered phosphors (co-incubated with psoralen) that absorb x-rays and re-radiate (phosphoresce) at UV wavelengths. The efficacy of X-PACT was evaluated in both in-vitro and in-vivo settings. In-vitro studies utilized breast (4T1), glioma (CT2A) and sarcoma (KP-B) cell lines. Cells were exposed to X-PACT treatments where the concentrations of drug (psoralen and phosphor) and radiation parameters (energy, dose, and dose rate) were varied. Efficacy was evaluated primarily using flow cell cytometry in combination with complimentary assays, and the in-vivo mouse study. In an in-vitro study, we show that X-PACT induces significant tumor cell apoptosis and cytotoxicity, unlike psoralen or phosphor alone (p<0.0001). We also show that apoptosis increases as doses of phosphor, psoralen, or radiation increase. Finally, in an in-vivo pilot study of BALBc mice with syngeneic 4T1 tumors, we show that the rate of tumor growth is slower with X-PACT than with saline or AMT + X-ray (p<0.0001). Overall these studies demonstrate a potential therapeutic effect for X-PACT, and provide a foundation and rationale for future studies. In summary, X-PACT represents a novel treatment approach in which well-tolerated low doses of x-ray radiation are delivered to a specific tumor site to generate UVA light which

  20. X-Ray Psoralen Activated Cancer Therapy (X-PACT).

    PubMed

    Oldham, Mark; Yoon, Paul; Fathi, Zak; Beyer, Wayne F; Adamson, Justus; Liu, Leihua; Alcorta, David; Xia, Wenle; Osada, Takuya; Liu, Congxiao; Yang, Xiao Y; Dodd, Rebecca D; Herndon, James E; Meng, Boyu; Kirsch, David G; Lyerly, H Kim; Dewhirst, Mark W; Fecci, Peter; Walder, Harold; Spector, Neil L

    2016-01-01

    This work investigates X-PACT (X-ray Psoralen Activated Cancer Therapy): a new approach for the treatment of solid cancer. X-PACT utilizes psoralen, a potent anti-cancer therapeutic with current application to proliferative disease and extracorporeal photopheresis (ECP) of cutaneous T Cell Lymphoma. An immunogenic role for light-activated psoralen has been reported, contributing to long-term clinical responses. Psoralen therapies have to-date been limited to superficial or extracorporeal scenarios due to the requirement for psoralen activation by UVA light, which has limited penetration in tissue. X-PACT solves this challenge by activating psoralen with UV light emitted from novel non-tethered phosphors (co-incubated with psoralen) that absorb x-rays and re-radiate (phosphoresce) at UV wavelengths. The efficacy of X-PACT was evaluated in both in-vitro and in-vivo settings. In-vitro studies utilized breast (4T1), glioma (CT2A) and sarcoma (KP-B) cell lines. Cells were exposed to X-PACT treatments where the concentrations of drug (psoralen and phosphor) and radiation parameters (energy, dose, and dose rate) were varied. Efficacy was evaluated primarily using flow cell cytometry in combination with complimentary assays, and the in-vivo mouse study. In an in-vitro study, we show that X-PACT induces significant tumor cell apoptosis and cytotoxicity, unlike psoralen or phosphor alone (p<0.0001). We also show that apoptosis increases as doses of phosphor, psoralen, or radiation increase. Finally, in an in-vivo pilot study of BALBc mice with syngeneic 4T1 tumors, we show that the rate of tumor growth is slower with X-PACT than with saline or AMT + X-ray (p<0.0001). Overall these studies demonstrate a potential therapeutic effect for X-PACT, and provide a foundation and rationale for future studies. In summary, X-PACT represents a novel treatment approach in which well-tolerated low doses of x-ray radiation are delivered to a specific tumor site to generate UVA light which

  1. [Migration and integration policies within the Andean Pact].

    PubMed

    Kratochwil, H

    1993-04-01

    "After a review of the institutions belonging to the 1969 Andean Pact, migration topics within this context are analyzed, considering three main issues: labor migration,...circulation of persons, where a series of agreements tending to simplify procedures at bordersites are still not practically in force for reasons concerning internal safety, drug traffic and unemployment, and migration across borders as related to borderline integration, which was dealt with in the Macchu Picchu Summit in 1990 and in a Decision Project in 1991." The five pact countries are Bolivia, Chile, Colombia, Ecuador, and Peru. (SUMMARY IN ENG) PMID:12344968

  2. (Relatively) Smooth Sailing: How a Large State University Successfully Adopted the PACT Teaching Event

    ERIC Educational Resources Information Center

    Gainsburg, Julie; Ericson, Bonnie

    2015-01-01

    In this article, the PACT Coordinator and former Department Chair of the Department of Secondary Education at a large state university describe how the PACT Teaching Event was introduced, piloted and implemented in their department. Despite the size and complexity of this department, PACT implementation went relatively smoothly, with widespread…

  3. Adolescent Subtest Norms for the ImPACT Neurocognitive Battery.

    PubMed

    Henry, Luke C; Sandel, Natalie

    2015-01-01

    The neurocognitive testing of sports concussion for injury management and return-to-play decisions has long been considered the gold standard in evaluation of the injury. Computerized testing batteries are frequently employed, with the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) being the most used of all the current testing platforms to evaluate concussion. ImPACT's clinical report yields four normed composite scores (Verbal Memory, Visual Memory, Visual Motor Speed, and Reaction Time) and another composite score that is not normed but is used as a validity measure (Impulse Control), as well as their corresponding subtest scores, which are not normed. The current study provides normative data on each of the subtests used to calculate the composite scores. Normative data are separated by gender for athletes aged 13 to 21 years old and are stratified by the norm age brackets already employed by the ImPACT. These norms may be helpful in the interpretation of the ImPACT clinical report and further delineation of areas of neurocognitive dysfunction. PMID:25412432

  4. Patient's Anastrozole Compliance to Therapy (PACT) Program: Baseline Data and Patient Characteristics from a Population-Based, Randomized Study Evaluating Compliance to Aromatase Inhibitor Therapy in Postmenopausal Women with Hormone-Sensitive Early Breast Cancer

    PubMed Central

    Harbeck, Nadia; Blettner, Maria; Hadji, Peyman; Jackisch, Christian; Lück, Hans-Joachim; Windemuth-Kieselbach, Christine; Zaun, Silke; Haidinger, Renate; Schmitt, Doris; Schulte, Hilde; Nitz, Ulrike; Kreienberg, Rolf

    2013-01-01

    Summary Background The Patient's Anastrozole Compliance to Therapy (PACT) program is a large randomized study designed to assess whether the provision of educational materials (EM) could improve compliance with aromatase inhibitor therapy in postmenopausal women with early, hormone receptor-positive breast cancer. Patients and Methods The PACT study presented a large, homogeneous dataset. The baseline analysis included patient demographics and initial treatments and patient perceptions about treatment and quality of life. Results Overall, 4,923 patients were enrolled at 109 German breast cancer centers/clinics in cooperation with 1,361 office-based gynecologists/oncologists. 4,844 women were randomized 1:1 to standard therapy (n = 2,402) or standard therapy plus EM (n = 2,442). Prior breast-conserving surgery and mastectomy had been received by 76% and 24% of the patients, respectively. Radiotherapy was scheduled for 85% of the patients, adjuvant chemotherapy for 38%. Reflecting the postmenopausal, hormone-sensitive nature of this population, only 285 patients (7%) had received neoadjuvant chemotherapy. Conclusions A comparison with epidemiological data from the West German Breast Center suggests that the patients in the PACT study are representative of a general postmenopausal early breast cancer population and that the findings may be applicable to ‘real-world’ Germany and beyond. Compliance data from PACT are eagerly anticipated. PMID:24419247

  5. Methodologies used by Warsaw Pact countries (except USSR) in obtaining US technologies. Student report

    SciTech Connect

    Cheeseman, R.J.

    1987-04-01

    The Warsaw Pact countries obtain U.S. technologies by legal and illegal means. Methods of collection include espionage, overt collection, acquisition by scientific and educational exchange participants, and illegal trade activities. Examples of methods used by the Warsaw Pact countries (except the USSR) are provided. The US faces barriers to preventing loss of its technologies. Among these are resistance from US business interests, insufficient cooperation between US government agencies and overseas allies, lack of US counterintelligence personnel, and the openess of American society. The study concludes that the Warsaw Pact's countries have narrowed NATO's qualitative lead in weaponry as a result of the Warsaw Pact's acquisition effort.

  6. 77 FR 50548 - Agency Information Collection: (PACT Qualitative Evaluation: Patient & Caregiver Interviews...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-21

    ... needed to evaluate the universal Patient Aligned Care Teams (PACT) Systems Redesign, document patients... information on patient characteristics and their experiences with self-managing chronic conditions,...

  7. Why perversion?: 'False love' and the perverse pact.

    PubMed

    Stein, Ruth

    2005-06-01

    In this paper, the author works with the awareness that perversion is a socially, historically and theologically loaded term, at the same time as it may be the latest frontier in psychoanalysis, both clinically, and in relation to contemporary art and culture which emphasize the perverse. Positioning itself against tendencies to deny the existence of a category of 'perversion' or, inversely, to abuse it for the power that accrues from the act of diagnosing, she also points to other liabilities in the history of the treatment of this term, such as the narrowing down of perversion to the exclusively sexual domain, or, alternatively, the overextension of it to polymorphously erotic practices that enhance sexual excitement. The paradoxes of perversion and the difficulties of distinguishing the perverse from the non-perverse are addressed. The case is also made that, in order to understand perversion, one must unlink it from the narrow notion of sexual practice and see what is involved on a deeper level--an approach initiated when psychoanalysis turned to perversion as a defense against psychotic anxieties, and began considering the necessary place of perversion in the transference--countertransference. Two features common to both sexual and non-sexual perverse relations are the seductive and bribing aspects of perversion, and its means-ends reversal. Perversion is a haven for the disguising of hatred and suspicion as excitement and (false) love. Displaced child and beating father, entitled child and seductive mother, are both prototypes of psychoanalytic reflection on parents who excite, deceive and corrupt their children and establish perverse pacts with them. The notion of the perverse pact is foregrounded in Alice's analysis, where first the resurrection and then the dismantling of such a pact were effected through various analytic means. PMID:16096075

  8. 77 FR 50551 - Agency Information Collection: Emergency Submission for OMB Review (PACT VISN20 Health Care...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-21

    ... AFFAIRS Agency Information Collection: Emergency Submission for OMB Review (PACT VISN20 Health Care... No. 2900-New (VA Form 10-0535). SUPPLEMENTARY INFORMATION: Title: PACT VISN20 Health Care Experiences...); Comment Request AGENCY: Veterans Health Administration, Department of Veterans Affairs. ACTION:...

  9. Novel Formulations for Antimicrobial Peptides

    PubMed Central

    Carmona-Ribeiro, Ana Maria; Carrasco, Letícia Dias de Melo

    2014-01-01

    Peptides in general hold much promise as a major ingredient in novel supramolecular assemblies. They may become essential in vaccine design, antimicrobial chemotherapy, cancer immunotherapy, food preservation, organs transplants, design of novel materials for dentistry, formulations against diabetes and other important strategical applications. This review discusses how novel formulations may improve the therapeutic index of antimicrobial peptides by protecting their activity and improving their bioavailability. The diversity of novel formulations using lipids, liposomes, nanoparticles, polymers, micelles, etc., within the limits of nanotechnology may also provide novel applications going beyond antimicrobial chemotherapy. PMID:25302615

  10. Thick silicon microstrip detectors simulation for PACT: Pair and Compton Telescope

    NASA Astrophysics Data System (ADS)

    Khalil, M.; Laurent, P.; Lebrun, F.; Tatischeff, V.; Dolgorouky, Y.; Bertoli, W.; Breelle, E.

    2016-11-01

    PACT is a space borne Pair and Compton Telescope that aims to make a sensitive survey of the gamma-ray sky between 100 keV and 100 MeV. It is based upon two main components: a silicon-based gamma-ray tracker and a crystal-based calorimeter. In this paper we will explain the imaging technique of PACT as a Multi-layered Compton telescope (0.1-10 MeV) and its major improvements over its predecessor COMPTEL. Then we will present a simulation study to optimize the silicon tracker of PACT. This tracker is formed of thousands of identical silicon double sided strip detectors (DSSDs). We have developed a simulation model (using SILVACO) to simulate the DSSD performance while varying its thickness, impurity concentration of the bulk material, electrode pitch, and electrode width. We will present a comprehensive overview of the impact of each varied parameter on the DSSD performance, in view of the application to PACT. The considered DSSD parameters are its depletion voltage, capacitance, and leakage current. After the selection of the PACT DSSD, we will present a simulation of the performance of the PACT telescope in the 0.1-10 MeV range.

  11. Alternative Antimicrobial Approach: Nano-Antimicrobial Materials

    PubMed Central

    Beyth, Nurit; Houri-Haddad, Yael; Domb, Avi; Khan, Wahid; Hazan, Ronen

    2015-01-01

    Despite numerous existing potent antibiotics and other antimicrobial means, bacterial infections are still a major cause of morbidity and mortality. Moreover, the need to develop additional bactericidal means has significantly increased due to the growing concern regarding multidrug-resistant bacterial strains and biofilm associated infections. Consequently, attention has been especially devoted to new and emerging nanoparticle-based materials in the field of antimicrobial chemotherapy. The present review discusses the activities of nanoparticles as an antimicrobial means, their mode of action, nanoparticle effect on drug-resistant bacteria, and the risks attendant on their use as antibacterial agents. Factors contributing to nanoparticle performance in the clinical setting, their unique properties, and mechanism of action as antibacterial agents are discussed in detail. PMID:25861355

  12. Anticancer chemotherapy

    SciTech Connect

    Weller, R.E.

    1988-10-01

    Despite troubled beginnings, anticancer chemotherapy has made significant contribution to the control of cancer in man, particularly within the last two decades. Early conceptual observations awakened the scientific community to the potentials of cancer chemotherapy. There are now more than 50 agents that are active in causing regression of clinical cancer. Chemotherapy's major conceptual contributions are two-fold. First, there is now proof that patients with overt metastatic disease can be cured, and second, to provide a strategy for control of occult metastases. In man, chemotherapy has resulted in normal life expectancy for some patients who have several types of metastatic cancers, including choriocarcinoma, Burkitt's lymphomas, Wilm's tumor, acute lymphocytic leukemia, Hodgkins disease, diffuse histiocytic lymphoma and others. Anticancer chemotherapy in Veterinary medicine has evolved from the use of single agents, which produce only limited remissions, to the concept of combination chemotherapy. Three basic principles underline the design of combination chemotherapy protocols; the fraction of tumor cell killed by one drug is independent of the fraction killed by another drug; drugs with different mechanisms of action should be chosen so that the antitumor effects will be additive; and since different classes of drugs have different toxicities the toxic effects will not be additive.

  13. Chemotherapy and Your Mouth

    MedlinePlus

    ... Health > Chemotherapy and Your Mouth Chemotherapy and Your Mouth Main Content Are You Being Treated With Chemotherapy ... Back to Top How Does Chemotherapy Affect the Mouth? Chemotherapy is the use of drugs to treat ...

  14. Physiotherapy informed by Acceptance and Commitment Therapy (PACT): protocol for a randomised controlled trial of PACT versus usual physiotherapy care for adults with chronic low back pain

    PubMed Central

    Godfrey, Emma; Galea Holmes, Melissa; Wileman, Vari; McCracken, Lance; Moss-Morris, Rona; Pallet, John; Sanders, Duncan; Barcellona, Massimo; Critchley, Duncan

    2016-01-01

    Introduction Chronic low back pain (CLBP) is a common condition and source of significant suffering, disability and healthcare costs. Current physiotherapy treatment is moderately effective. Combining theory-based psychological methods with physiotherapy could improve outcomes for people with CLBP. The primary aim of this randomised controlled trial (RCT) is to evaluate the efficacy of Physiotherapy informed by Acceptance and Commitment Therapy (PACT) on functioning in patients with CLBP. Methods and analysis The PACT trial is a two-armed, parallel-group, multicentre RCT to assess the efficacy of PACT in comparison with usual physiotherapy care (UC). 240 patients referred to physiotherapy with CLBP will be recruited from three National Health Service (NHS) hospitals trusts. Inclusion criteria are: age ≥18 years, CLBP ≥12-week duration, scoring ≥3 points on the Roland-Morris Disability Questionnaire (RMDQ) and adequate understanding of spoken and written English to participate. Patients will be randomised to PACT or UC (120 per arm stratified by centre) by an independent randomisation service and followed up at 3 and 12 months post randomisation. The sample size of 240 will provide adequate power to detect a standardised mean difference of 0.40 in the primary outcome (RMDQ; 5% significance, 80% power) assuming attrition of 20%. Analysis will be by intention to treat conducted by the trial statistician, blind to treatment group, following a prespecified analysis plan. Estimates of treatment effect at the follow-up assessments will use an intention-to-treat framework, implemented using a linear mixed-effects model. Ethics and dissemination This trial has full ethical approval (14/SC/0277). It will be disseminated via peer-reviewed publications and conference presentations. The results will enable clinicians, patients and health service managers to make informed decisions regarding the efficacy of PACT for patients with CLBP. Trial registration number ISRCTN

  15. Intracavitary chemotherapy

    SciTech Connect

    Markman, M.

    1985-01-01

    Pharmacokinetic modeling has suggested, and clinical investigations have confirmed, that intracavitary drug administration can result in a much greater drug exposure for the cavity into which the agent is instilled compared to the plasma. Both the safety and the efficacy of several agents administered individually or in combination have now been demonstrated. Several malignancies, in particular ovarian carcinoma and malignant mesothelioma, which remain confined to body cavities for much of their natural history, might be most rationally treated by the intracavitary treatment approach. Early clinical trials have demonstrated significant activity of intracavitary chemotherapy in both of these malignancies. Optimal drugs and dosages as well as appropriate scheduling for the various tumors involving body cavities remain to be defined. Whether or not combination intracavitary chemotherapy will significantly improve survival of patients with malignant disease confined to body cavities must await carefully controlled clinical trials comparing this treatment approach to standard systemically administered chemotherapy. 144 references.

  16. Altered Activation of Protein Kinase PKR and Enhanced Apoptosis in Dystonia Cells Carrying a Mutation in PKR Activator Protein PACT*

    PubMed Central

    Vaughn, Lauren S; Bragg, D. Cristopher; Sharma, Nutan; Camargos, Sarah; Cardoso, Francisco; Patel, Rekha C

    2015-01-01

    PACT is a stress-modulated activator of the interferon-induced double-stranded RNA-activated protein kinase (PKR). Stress-induced phosphorylation of PACT is essential for PACT's association with PKR leading to PKR activation. PKR activation leads to phosphorylation of translation initiation factor eIF2α inhibition of protein synthesis and apoptosis. A recessively inherited form of early-onset dystonia DYT16 has been recently identified to arise due to a homozygous missense mutation P222L in PACT. To examine if the mutant P222L protein alters the stress-response pathway, we examined the ability of mutant P222L to interact with and activate PKR. Our results indicate that the substitution mutant P222L activates PKR more robustly and for longer duration albeit with slower kinetics in response to the endoplasmic reticulum stress. In addition, the affinity of PACT-PACT and PACT-PKR interactions is enhanced in dystonia patient lymphoblasts, thereby leading to intensified PKR activation and enhanced cellular death. P222L mutation also changes the affinity of PACT-TRBP interaction after cellular stress, thereby offering a mechanism for the delayed PKR activation in response to stress. Our results demonstrate the impact of a dystonia-causing substitution mutation on stress-induced cellular apoptosis. PMID:26231208

  17. WindPACT Turbine Rotor Design Study: June 2000--June 2002 (Revised)

    SciTech Connect

    Malcolm, D. J.; Hansen, A. C.

    2006-04-01

    This report presents the results of the turbine rotor study completed by Global Energy Concepts (GEC) as part of the U.S. Department of Energy's WindPACT (Wind Partnership for Advanced Component Technologies) project. The purpose of the WindPACT project is to identify technology improvements that will enable the cost of energy from wind turbines to fall to a target of 3.0 cents/kilowatt-hour in low wind speed sites. The study focused on different rotor configurations and the effect of scale on those rotors.

  18. Understanding Chemotherapy

    MedlinePlus

    ... you may get chemotherapy before a peripheral blood stem cell transplant. Fill this section in with your doctor or nurse. I am getting chemo ... can be given in these forms: An IV (intravenously) A shot (injection) into a muscle or other part of your body A pill ...

  19. 77 FR 50546 - Agency Information Collection: (PACT Patient Experiences Survey); Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-21

    ... healthcare delivery through increasing access, coordination, communication, and continuity of care. The.... 3507(j)(1)). An emergency clearance is being requested for information needed to improve patient care... model, ``Patient Aligned Care Team'' or PACT at all Veterans Health Administration (VHA)...

  20. Probability and Confidence Trade-Space (PACT) Evaluation: Accounting for Uncertainty in Sparing Assessments

    NASA Technical Reports Server (NTRS)

    Anderson, Leif; Box, Neil; Carter-Journet, Katrina; DiFilippo, Denise; Harrington, Sean; Jackson, David; Lutomski, Michael

    2012-01-01

    Purpose of presentation: (1) Status update on the developing methodology to revise sub-system sparing targets. (2) To describe how to incorporate uncertainty into spare assessments and why it is important to do so (3) Demonstrate hardware risk postures through PACT evaluation

  1. The Flexibility of Conceptual Pacts: Referring Expressions Dynamically Shift to Accommodate New Conceptualizations.

    PubMed

    Ibarra, Alyssa; Tanenhaus, Michael K

    2016-01-01

    In a classic paper, Brennan and Clark argued that when interlocutors agree on a name for an object, they are forming a temporary agreement on how to conceptualize that object; that is, they are forming a conceptual pact. The literature on conceptual pacts has largely focused on the costs and benefits of breaking and maintaining lexical precedents, and the degree to which they might be partner-specific. The research presented here focuses on a question about conceptual pacts that has been largely neglected in the literature: To what extent are conceptual pacts specific to the local context of the interaction? If conceptual pacts are indeed temporary, then when the local context changes in ways that are accessible to participants, we would expect participants to seamlessly shift to referential expressions that reflect novel conceptualizations. Two experiments examined how referential forms change across context in collaborative, task-oriented dialog between naïve participants. In Experiment 1, names for parts of an unknown object were established in an "item" identification stage (e.g., a shape that looked like a wrench was called "the wrench"). In a second "build" stage, that name was often supplanted by an object-oriented name, e.g., the "leg." These changes happened abruptly and without negotiation. In Experiment 2, interlocutors manipulated clip art and more abstract tangram pictures in a "slider" puzzle to arrange the objects into a target configuration. On some trials moving an object revealed a picture that could be construed as a contrast competitor, e.g., a clip art picture of a camel after "the camel" had been negotiated as a name for a tangram shape, or vice versa. As would be expected, modification rates increased when a potential contrast was revealed. More strikingly, the degree to which a name had been negotiated or the frequency with which it had been used did not affect the likelihood that the revealed shape would be considered as a potential

  2. The Flexibility of Conceptual Pacts: Referring Expressions Dynamically Shift to Accommodate New Conceptualizations

    PubMed Central

    Ibarra, Alyssa; Tanenhaus, Michael K.

    2016-01-01

    In a classic paper, Brennan and Clark argued that when interlocutors agree on a name for an object, they are forming a temporary agreement on how to conceptualize that object; that is, they are forming a conceptual pact. The literature on conceptual pacts has largely focused on the costs and benefits of breaking and maintaining lexical precedents, and the degree to which they might be partner-specific. The research presented here focuses on a question about conceptual pacts that has been largely neglected in the literature: To what extent are conceptual pacts specific to the local context of the interaction? If conceptual pacts are indeed temporary, then when the local context changes in ways that are accessible to participants, we would expect participants to seamlessly shift to referential expressions that reflect novel conceptualizations. Two experiments examined how referential forms change across context in collaborative, task-oriented dialog between naïve participants. In Experiment 1, names for parts of an unknown object were established in an “item” identification stage (e.g., a shape that looked like a wrench was called “the wrench”). In a second “build” stage, that name was often supplanted by an object-oriented name, e.g., the “leg.” These changes happened abruptly and without negotiation. In Experiment 2, interlocutors manipulated clip art and more abstract tangram pictures in a “slider” puzzle to arrange the objects into a target configuration. On some trials moving an object revealed a picture that could be construed as a contrast competitor, e.g., a clip art picture of a camel after “the camel” had been negotiated as a name for a tangram shape, or vice versa. As would be expected, modification rates increased when a potential contrast was revealed. More strikingly, the degree to which a name had been negotiated or the frequency with which it had been used did not affect the likelihood that the revealed shape would be

  3. PACT - a bottom pressure based, compact deep-ocean tsunameter with acoustic surface coupling

    NASA Astrophysics Data System (ADS)

    Macrander, A.; Gouretski, V.; Boebel, O.

    2009-04-01

    The German-Indonsian Tsunami Early Warning System (GITEWS) processes a multitude of information to comprehensively and accurately evaluate the possible risks inherent to seismic events around Indonesia. Within just a few minutes, measurements of the vibration and horizontal movements off the coastal regions of Indonesia provide a clear picture of the location and intensity of a seaquake. However, not every seaquake causes a tsunami, nor is every tsunami caused by a seaquake. To avoid nerve-wrecking and costly false alarms and to protect against tsunamis caused by landslides, the oceanic sea-level must be measured directly. This goal is pursued in the GITEWS work package "ocean instrumentation", aiming at a a highest reliability and redundancy by developing a set of independent instruments, which measure the sea-level both offshore in the deep ocean and at the coast on the islands off Indonesia. Deep ocean sea-level changes less than a centimetre can be detected by pressure gauges deployed at the sea floor. Based on some of the concepts developed as part of the US DART system, a bottom pressure based, acoustically coupled tsunami detector (PACT) was developed under the auspices of the AWI in collaboration with two German SME and with support of University of Bremen and University of Rhode Island. The PACT system records ocean bottom pressure, performs on-board tsunami detection and acoustically relays the data to the surface buoy. However, employing computational powers and communication technologies of the new millennium, PACT integrates the entire sea-floor package (pressure gauge, data logger and analyzer, acoustic modem, acoustic release and relocation aids) into a single unit, i.e. a standard benthos sphere. PACT thereby reduces costs, minimizes the deployment efforts, while maximizing reliability and maintenance intervals. Several PACT systems are scheduled for their first deployment off Indonesia during 2009. In this presentation, the technical specifications

  4. Electrocardiogram-gated coronary CT angiography dose estimates using ImPACT.

    PubMed

    Kobayashi, Masanao; Asada, Yasuki; Matsubara, Kosuke; Suzuki, Shouichi; Koshida, Kichiro; Matsunaga, Yuta; Haba, Tomonobu; Kawaguchi, Ai; Toyama, Hiroshi; Kato, Ryouichi

    2016-07-08

    The primary study objective was to assess radiation doses using a modified form of the Imaging Performance Assessment of Computed Tomography (CT) scanner (ImPACT) patient dosimetry for cardiac applications on an Aquilion ONE ViSION Edition scanner, including the Ca score, target computed tomography angiography (CTA), prospective CTA, continuous CTA/cardiac function analysis (CFA), and CTA/CFA modulation. Accordingly, we clarified the CT dose index (CTDI) to determine the relationship between heart rate (HR) and X-ray exposure. As a secondary objective, we compared radiation doses using modified ImPACT, a whole-body dosimetry phantom study, and the k-factor method to verify the validity of the dose results obtained with modified ImPACT. The effective dose determined for the reference person (4.66 mSv at 60 beats per minute (bpm) and 33.43 mSv at 90bpm) were approximately 10% less than those determined for the phantom study (5.28 mSv and 36.68 mSv). The effective doses according to the k-factor (0.014 mSv•mGy-1•cm-1; 2.57 mSv and 17.10 mSv) were significantly lower than those obtained with the other two methods. In the present study, we have shown that ImPACT, when modified for cardiac applications, can assess both absorbed and effective doses. The results of our dose comparison indicate that modified ImPACT dose assessment is a promising and practical method for evaluating coronary CTA.

  5. Automation of PCXMC and ImPACT for NASA Astronaut Medical Imaging Dose and Risk Tracking

    NASA Technical Reports Server (NTRS)

    Bahadori, Amir; Picco, Charles; Flores-McLaughlin, John; Shavers, Mark; Semones, Edward

    2011-01-01

    To automate astronaut organ and effective dose calculations from occupational X-ray and computed tomography (CT) examinations incorporating PCXMC and ImPACT tools and to estimate the associated lifetime cancer risk per the National Council on Radiation Protection & Measurements (NCRP) using MATLAB(R). Methods: NASA follows guidance from the NCRP on its operational radiation safety program for astronauts. NCRP Report 142 recommends that astronauts be informed of the cancer risks from reported exposures to ionizing radiation from medical imaging. MATLAB(R) code was written to retrieve exam parameters for medical imaging procedures from a NASA database, calculate associated dose and risk, and return results to the database, using the Microsoft .NET Framework. This code interfaces with the PCXMC executable and emulates the ImPACT Excel spreadsheet to calculate organ doses from X-rays and CTs, respectively, eliminating the need to utilize the PCXMC graphical user interface (except for a few special cases) and the ImPACT spreadsheet. Results: Using MATLAB(R) code to interface with PCXMC and replicate ImPACT dose calculation allowed for rapid evaluation of multiple medical imaging exams. The user inputs the exam parameter data into the database and runs the code. Based on the imaging modality and input parameters, the organ doses are calculated. Output files are created for record, and organ doses, effective dose, and cancer risks associated with each exam are written to the database. Annual and post-flight exposure reports, which are used by the flight surgeon to brief the astronaut, are generated from the database. Conclusions: Automating PCXMC and ImPACT for evaluation of NASA astronaut medical imaging radiation procedures allowed for a traceable and rapid method for tracking projected cancer risks associated with over 12,000 exposures. This code will be used to evaluate future medical radiation exposures, and can easily be modified to accommodate changes to the risk

  6. Electrocardiogram-gated coronary CT angiography dose estimates using ImPACT.

    PubMed

    Kobayashi, Masanao; Asada, Yasuki; Matsubara, Kosuke; Suzuki, Shouichi; Koshida, Kichiro; Matsunaga, Yuta; Haba, Tomonobu; Kawaguchi, Ai; Toyama, Hiroshi; Kato, Ryouichi

    2016-01-01

    The primary study objective was to assess radiation doses using a modified form of the Imaging Performance Assessment of Computed Tomography (CT) scanner (ImPACT) patient dosimetry for cardiac applications on an Aquilion ONE ViSION Edition scanner, including the Ca score, target computed tomography angiography (CTA), prospective CTA, continuous CTA/cardiac function analysis (CFA), and CTA/CFA modulation. Accordingly, we clarified the CT dose index (CTDI) to determine the relationship between heart rate (HR) and X-ray exposure. As a secondary objective, we compared radiation doses using modified ImPACT, a whole-body dosimetry phantom study, and the k-factor method to verify the validity of the dose results obtained with modified ImPACT. The effective dose determined for the reference person (4.66 mSv at 60 beats per minute (bpm) and 33.43 mSv at 90bpm) were approximately 10% less than those determined for the phantom study (5.28 mSv and 36.68 mSv). The effective doses according to the k-factor (0.014 mSv•mGy-1•cm-1; 2.57 mSv and 17.10 mSv) were significantly lower than those obtained with the other two methods. In the present study, we have shown that ImPACT, when modified for cardiac applications, can assess both absorbed and effective doses. The results of our dose comparison indicate that modified ImPACT dose assessment is a promising and practical method for evaluating coronary CTA. PMID:27455500

  7. HIV chemotherapy

    NASA Astrophysics Data System (ADS)

    Richman, Douglas D.

    2001-04-01

    The use of chemotherapy to suppress replication of the human immunodeficiency virus (HIV) has transformed the face of AIDS in the developed world. Pronounced reductions in illness and death have been achieved and healthcare utilization has diminished. HIV therapy has also provided many new insights into the pathogenesis and the viral and cellular dynamics of HIV infection. But challenges remain. Treatment does not suppress HIV replication in all patients, and the emergence of drug-resistant virus hinders subsequent treatment. Chronic therapy can also result in toxicity. These challenges prompt the search for new drugs and new therapeutic strategies to control chronic viral replication.

  8. UTILIZATION OF ImPACT TESTING TO MEASURE INJURY RISK IN ALPINE SKI AND SNOWBOARD ATHLETES

    PubMed Central

    Huntimer, Brittney; Kernozek, Thomas; Cole, John

    2016-01-01

    ABSTRACT Background While studies that have examined the prevalence of musculoskeletal injuries in alpine skiing and snowboarding exist, there has been no discussion of how neurocognitive deficits may influence such injuries. Recent authors have identified a possible link between Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) testing results and the prevalence of musculoskeletal injury in athletic populations. However, no study has specifically examined this in the alpine skiing and snowboard athletes who sustain injury and those that do not. Hypothesis/Purpose The purpose was to review injury data and ImPACT test results within the local ski/snowboard population to determine if there was a difference in components of ImPACT test scores between injured and non-injured athletes. It was hypothesized that differences would exist in component scores on ImPACT testing between injured and non-injured athletes. Study design Retrospective cohort study Methods Injury records and baseline ImPACT testing scores for 93 athletes aged 14-17 participating in a local ski and snowboard club during the 2009-2012 seasons were gathered retrospectively. Injuries documented for the lower and upper extremity included ligament sprains, muscle strains, contusions, dislocation/subluxation, fractures and concussions. Athletes who sustained any of these listed injuries were categorized within the injured athlete group. Each component of ImPACT test scores was compared between gender and for injury status within skiing and snowboarding disciplines using a series of two-way analysis of variance tests. Results There was no difference between non-injured and injured females as well as non-injured and injured males in reaction time and visual motor speed (VMS), however there was an interaction between gender and injury status on composite reaction time and visual motor speed, or VMS. The composite reaction time for females was 4.7% faster with injury while males without injury

  9. Evaluation of the effect of photodynamic antimicrobial therapy in dentin caries: a pilot in vivo study

    NASA Astrophysics Data System (ADS)

    Borges, F. M. C.; de-Melo, M. A. S.; Lima, J. M. P.; Zanin, I. C. J.; Rodrigues, L. K. A.; Nobre-dos-Santos, M.

    2010-02-01

    In vitro and in situ studies have demonstrated that the photodynamic antimicrobial therapy (PACT) is effective in reducing Streptococcus mutans population in artificially carious dentin. This pilot in vivo study evaluated the antimicrobial effect of PACT using toluidine blue O (TBO) and a light-emitting diode (LED) in carious dentin lesions. Five healthy adult volunteers (19-36 yr), with at least 4 active carious cavities each, participated in this study. Teeth of each volunteer were randomly divided into four groups: (1) without TBO and without light (Control); (2) with TBO alone (TBO); (3) with LED at 94/J cm2 alone (LED); and (4) with TBO plus LED at 94 J/cm2 (PACT). Each cavity was divided into two halves. The baseline carious dentin sample was collected from half of each cavity. Following, the treatments were performed using a random distribution of tooth into treatments. Then, the second collection of carious dentin samples was performed. Before and after treatments, dentin samples were analyzed with regard to the counts of total viable microorganisms, total streptococci, mutans streptococci, and lactobacilli. The data were statistically analyzed by Kruskal-Wallis and Student-Newman-Keuls tests (α=5%). Log reductions ranged from -0.12 to 2.68 and significant reductions were observed for PACT (group 4) when compared to the other groups (1, 2, and 3) for total streptococci and mutans streptococci. Concluding, PACT was effective in killing oral microorganisms present in in vivo carious dentin lesions and may be a promising technique for eliminating bacteria from dentin before restoration.

  10. Antimicrobials Treatment

    NASA Astrophysics Data System (ADS)

    Drosinos, Eleftherios H.; Skandamis, Panagiotis N.; Mataragas, Marios

    The use of antimicrobials is a common practice for preservation of foods. Incorporation, in a food recipe, of chemical antimicrobials towards inhibition of spoilage and pathogenic micro-organisms results in the compositional modification of food. This treatment is nowadays undesirable for the consumer, who likes natural products. Scientific community reflecting consumers demand for natural antimicrobials has made efforts to investigate the possibility to use natural antimicrobials such us bacteriocins and essential oils of plant origin to inhibit microbial growth.

  11. Assessing implicit motivational orientations in couple relationships: the Partner-Related Agency and Communion Test (PACT).

    PubMed

    Hagemeyer, Birk; Neyer, Franz J

    2012-03-01

    The Partner-Related Agency and Communion Test (PACT) was developed to measure implicit agentic and communal needs in the domain of couple relationships through content analyses of fantasy stories. Study 1 (N = 125) confirmed that the new thematic coding system captured experimentally induced differences in partner-related motivation and showed expected relations with D. G. Winter's (1994) motive scoring system. Study 2 confirmed the discriminant and incremental validity of the implicit partner-related needs compared with self-report measures of the Big Five traits and adult attachment in a sample of 499 couples. In addition, dyadic analyses revealed expected associations of the partner-related needs with relationship satisfaction as experienced by oneself and by one's partner. The studies lend initial support to the validity of the relationship-specific needs for agency and communion as assessed by the PACT and introduce dyadic data analyses to the study of implicit motives. PMID:21787092

  12. [Decentralization and regionalization: dynamics and conditioning factors for the implementation of the Health Pact in Brazil].

    PubMed

    de Lima, Luciana Dias; de Queiroz, Lúcia F N; Machado, Cristiani Vieira; Viana, Ana Luiza d'Ávila

    2012-07-01

    Decentralization and regionalization represent constitutional guidelines for the organization of the Unified Health System, which in the last 20 years has required the adoption of mechanisms to coordinate and accommodate federative tensions in Brazil's healthcare sector. This paper analyzes the national implementation of the Health Pact between 2006 and 2010 involving a strategy that reconfigures intergovernmental relations in the sector. The study involved the analysis of documents, official data and interviews with federal, state and municipal managers in the Brazilian states. The content of the national proposal is initially discussed, including its implications for health policy. The different rhythms and degrees of implementation of the Health Pact are then reviewed, with respect to adherence by states and municipalities and the formation of Regional Management Boards. Lastly, the conditioning factors for the multiplicity of experiences observed in the country are identified and the challenges facing progress toward a decentralized and regionalized health system in Brazil are discussed.

  13. Assessing implicit motivational orientations in couple relationships: the Partner-Related Agency and Communion Test (PACT).

    PubMed

    Hagemeyer, Birk; Neyer, Franz J

    2012-03-01

    The Partner-Related Agency and Communion Test (PACT) was developed to measure implicit agentic and communal needs in the domain of couple relationships through content analyses of fantasy stories. Study 1 (N = 125) confirmed that the new thematic coding system captured experimentally induced differences in partner-related motivation and showed expected relations with D. G. Winter's (1994) motive scoring system. Study 2 confirmed the discriminant and incremental validity of the implicit partner-related needs compared with self-report measures of the Big Five traits and adult attachment in a sample of 499 couples. In addition, dyadic analyses revealed expected associations of the partner-related needs with relationship satisfaction as experienced by oneself and by one's partner. The studies lend initial support to the validity of the relationship-specific needs for agency and communion as assessed by the PACT and introduce dyadic data analyses to the study of implicit motives.

  14. A psychochemical weapon considered by the Warsaw Pact: a research note.

    PubMed

    Rózsa, Lajos

    2009-01-01

    Contrary to widespread rumours during the Cold War era, little, if any, evidence existed in the scientific literature to support the view that the Soviet Union or its Warsaw Pact allies considered the use of psychochemical weapons militarily. The Hungarian State Archives have recently opened up declassified records of Hungary's State Defence Council meetings held between 1962 and 1978. Materials submitted to the Council include reports about the coordinative meetings of the Warsaw Pact military medical services. Research into possible countermeasures against psychotropic drugs is listed as a research priority assigned to Hungary in 1962. Hungary rejected this task in 1963, but joined the ongoing project again in 1965. Methylamphetamine was produced in Budapest for use as an experimental model of such weapons. Within the context of contemporary western research, this drug was considered to be an effective interrogation tool. Similarly to the CIA, Hungary also failed to develop an antidote against it and the project was terminated, fruitlessly, in 1972. These documents serve as evidence that a Warsaw Pact forum had, in fact, been considering a psychochemical weapon as a "warfare agent."

  15. A psychochemical weapon considered by the Warsaw Pact: a research note.

    PubMed

    Rózsa, Lajos

    2009-01-01

    Contrary to widespread rumours during the Cold War era, little, if any, evidence existed in the scientific literature to support the view that the Soviet Union or its Warsaw Pact allies considered the use of psychochemical weapons militarily. The Hungarian State Archives have recently opened up declassified records of Hungary's State Defence Council meetings held between 1962 and 1978. Materials submitted to the Council include reports about the coordinative meetings of the Warsaw Pact military medical services. Research into possible countermeasures against psychotropic drugs is listed as a research priority assigned to Hungary in 1962. Hungary rejected this task in 1963, but joined the ongoing project again in 1965. Methylamphetamine was produced in Budapest for use as an experimental model of such weapons. Within the context of contemporary western research, this drug was considered to be an effective interrogation tool. Similarly to the CIA, Hungary also failed to develop an antidote against it and the project was terminated, fruitlessly, in 1972. These documents serve as evidence that a Warsaw Pact forum had, in fact, been considering a psychochemical weapon as a "warfare agent." PMID:19142819

  16. 1 year test-retest reliability of ImPACT in professional ice hockey players.

    PubMed

    Bruce, Jared; Echemendia, Ruben; Meeuwisse, Willem; Comper, Paul; Sisco, Amber

    2014-01-01

    The Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) battery is widely used to assess neurocognitive outcomes following sports-related concussion. The purpose of this study was to examine the 1 year test-retest reliability of ImPACT in a multilingual sample of professional hockey players. A total of 305 professional hockey players were tested 1 year apart using ImPACT. Reliable change confidence intervals were calculated and test-retest reliability was measured using Pearson and Intraclass correlation coefficients. Results indicated that the 1-year test-retest reliabilities for the Visual Motor and Reaction Time Composites ranged from low to high (.52 to .81). In contrast, 1-year test-retest reliabilities for the Verbal and Visual Memory Composites were low (.22 to .58). The 1-year test-retest results provided mixed support for the use of Visual Motor and Reaction Time Composites in select samples; in contrast, the Verbal and Visual Memory Composites may not be sensitive to clinical change.

  17. Antimicrobial peptides

    PubMed Central

    2014-01-01

    With increasing antibiotics resistance, there is an urgent need for novel infection therapeutics. Since antimicrobial peptides provide opportunities for this, identification and optimization of such peptides have attracted much interest during recent years. Here, a brief overview of antimicrobial peptides is provided, with focus placed on how selected hydrophobic modifications of antimicrobial peptides can be employed to combat also more demanding pathogens, including multi-resistant strains, without conferring unacceptable toxicity. PMID:24758244

  18. Politics of Policy: Assessing the Implementation, Impact, and Evolution of the Performance Assessment for California Teachers (PACT) and edTPA

    ERIC Educational Resources Information Center

    Reagan, Emilie Mitescu; Schram, Thomas; McCurdy, Kathryn; Chang, Te-Hsin; Evans, Carla M.

    2016-01-01

    Summative performance assessments in teacher education, such as the Performance Assessment for California Teachers (PACT) and the edTPA, have been heralded through polices intended to enhance the quality of the teaching profession and raise its stature among other professions. However, the development and implementation of the PACT, and…

  19. Antimicrobial Polymer

    DOEpatents

    McDonald, William F.; Wright, Stacy C.; Taylor, Andrew C.

    2004-09-28

    A polymeric composition having antimicrobial properties and a process for rendering the surface of a substrate antimicrobial are disclosed. The polymeric composition comprises a crosslinked chemical combination of (i) a polymer having amino group-containing side chains along a backbone forming the polymer, (ii) an antimicrobial agent selected from metals, metal alloys, metal salts, metal complexes and mixtures thereof, and (iii) a crosslinking agent containing functional groups capable of reacting with the amino groups. In one example embodiment, the polymer is a polyamide formed from a maleic anhydride or maleic acid ester monomer and alkylamines thereby producing a polyamide having amino substituted alkyl chains on one side of the polyamide backbone; the crosslinking agent is a phosphine having the general formula (A).sub.3 P wherein A is hydroxyalkyl; and the metallic antimicrobial agent is selected from chelated silver ions, silver metal, chelated copper ions, copper metal, chelated zinc ions, zinc metal and mixtures thereof.

  20. Antimicrobial Resistance

    MedlinePlus

    ... antibiotic are known as methicillin-resistant S. aureus or MRSA. Antibiotics and other antimicrobial drugs first became widely ... factors for infection are known as community-associated MRSA (CA-MRSA). Recently, several cases overseas and in ...

  1. PACT Act

    THOMAS, 113th Congress

    Rep. Peters, Scott H. [D-CA-52

    2014-07-09

    09/08/2014 Referred to the Subcommittee on Africa, Global Health, Global Human Rights and International Organizations. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  2. Identification of contaminants during primary isolation of mycobacteria in the BACTEC system with the antimicrobial supplement PACT.

    PubMed

    Salfinger, M; Kafader, F M; Hardegger, U; Wüst, J

    1988-04-01

    1500 sputum specimens and bronchial washings were cultured for mycobacteria. One half of the specimen was treated with N-acetyl-L-cysteine--sodium hydroxide (3%) (NALC) and the other with sodium dodecyl (lauryl) sulfate--sodium hydroxide (1%) (SDS). The different species of contaminants found with each pretreatment method with the BACTEC radiometric system were identified. Contamination occurred in 6% by using SDS and in 10% by using NALC. The SDS method was more effective against Bacillus ssp. and Streptomyces ssp., the major contaminants. However, the growth of Pseudomonas ssp. was a problem in both methods. PMID:3394450

  3. International Psychological Applications Conference and Trends (InPACT) Proceedings (Ljubljana, Slovenia, May 2-4, 2015)

    ERIC Educational Resources Information Center

    Pracana, Clara, Ed.

    2015-01-01

    We are delighted to welcome you to the International Psychological Applications Conference and Trends (InPACT) 2015, taking place in Ljubljana, Slovenia, from 2 to 4 of May. Psychology, nowadays, offers a large range of scientific fields where it can be applied. The goal of understanding individuals and groups (mental functions and behavioral…

  4. Initial Efficacy of Project ImPACT: A Parent-Mediated Social Communication Intervention for Young Children with ASD

    ERIC Educational Resources Information Center

    Ingersoll, Brooke; Wainer, Allison

    2013-01-01

    Project ImPACT is a parent-mediated social communication intervention for young children with ASD that was developed in community settings to encourage dissemination. A single-subject, multiple-baseline design was conducted across 8 preschoolers with ASD and their mothers to examine the efficacy of the model for improving parent intervention…

  5. Assessing Pre-Service Teachers Prior to Certification: Perspectives on the Performance Assessment for California Teachers (PACT)

    ERIC Educational Resources Information Center

    Okhremtchouk, Irina S.; Newell, Patrick A.; Rosa, Rebecca

    2013-01-01

    This study focuses on pre-service teachers' perspectives regarding how the process of completing the Performance Assessment for California Teachers (PACT) affected them academically, professionally, and personally. Two cohorts participated in this year-two study. Pre-service teachers' perspectives were acquired using a survey instrument…

  6. Secondary Students' Understanding of NATO and the Warsaw Pact: The Educational Implications of Research Conducted in Three NATO Nations.

    ERIC Educational Resources Information Center

    Galfo, Armand J.

    Three research projects were conducted over a three year period among secondary school students in the United Kingdom, the United States (Virginia), and West Germany in order to determine students' understanding the 40-year confrontation between the North Atlantic Treaty Organization (NATO) and the Warsaw Pact. These studies included 1991 students…

  7. PACT: the actuator to support the primary mirror of the ELT

    NASA Astrophysics Data System (ADS)

    Kamphues, F.; Nijenhuis, J.; den Breeje, R.; van den Dool, T. C.; Ponsioen, J.

    2008-07-01

    The European Southern Observatory (ESO) has started technology development for their next generation optical telescope. Due to its ultra large collecting area, The European Extremely Large Telescope (E-ELT) will require a paradigm shift in telescope design to keep the overall program cost at an acceptable level. The E-ELT will feature a 42 meter segmented primary mirror and will make extensive use of active and adaptive optics. Each primary mirror segment will be supported by three actuators that control piston and tilt. TNO has developed a low cost nanopositioning actuator (PACT) for the primary mirror segments. The actuators will be tested by IAC and ESO, with support from TNO, under operational conditions in a Wind Evaluation Breadboard (WEB) at the Roque de Los Muchachos observatory in La Palma.

  8. Probability and Confidence Trade-space (PACT) Evaluation: Accounting for Uncertainty in Sparing Assessments

    NASA Technical Reports Server (NTRS)

    Anderson, Leif; Box, Neil; Carter, Katrina; DiFilippo, Denise; Harrington, Sean; Jackson, David; Lutomski, Michael

    2012-01-01

    There are two general shortcomings to the current annual sparing assessment: 1. The vehicle functions are currently assessed according to confidence targets, which can be misleading- overly conservative or optimistic. 2. The current confidence levels are arbitrarily determined and do not account for epistemic uncertainty (lack of knowledge) in the ORU failure rate. There are two major categories of uncertainty that impact Sparing Assessment: (a) Aleatory Uncertainty: Natural variability in distribution of actual failures around an Mean Time Between Failure (MTBF) (b) Epistemic Uncertainty : Lack of knowledge about the true value of an Orbital Replacement Unit's (ORU) MTBF We propose an approach to revise confidence targets and account for both categories of uncertainty, an approach we call Probability and Confidence Trade-space (PACT) evaluation.

  9. Regulation of PACT-Mediated Protein Kinase Activation by the OV20.0 Protein of Orf Virus

    PubMed Central

    Tseng, Yeu-Yang; Liao, Guan-Ru; Sen, Ganes C.; Lin, Fong-Yuan

    2015-01-01

    ABSTRACT Double-stranded RNA (dsRNA)-activated protein kinase (PKR), a major component of the cellular antiviral system, is activated by the binding of either dsRNA or the cellular PKR activator, the PACT protein. The suppression of PKR activation is one of the main strategies that viruses employ to circumvent interferon signaling. Orf virus (ORFV), a parapoxvirus from the Poxviridae family, causes contagious pustular dermatitis in small ruminants. Previous studies have demonstrated that various OV20.0 isoforms, encoded by the OV20.0L gene, are able to inhibit PKR activation both by sequestering dsRNA and by physically interacting with PKR in vitro. Thus, this gene acts as a virulence factor of ORFV when tested using a mouse infection model. In the present study, the regions within OV20.0 that interact with dsRNA and with PKR have been mapped. Furthermore, this study demonstrates for the first time that OV20.0 is also able to interact with the dsRNA binding domain of PACT and that the presence of dsRNA strengthened the interaction of these two molecules. The presence of OV20.0 diminishes PKR phosphorylation when this is stimulated by PACT. Nevertheless, the association of OV20.0 with PKR, rather than with PACT, was found to be essential for reducing PACT-mediated PKR phosphorylation. These observations elucidate a new strategy whereby innate immunity can be evaded by ORFV. IMPORTANCE Our previous study indicated that ORFV's two OV20.0 isoforms act as a PKR antagonist via sequestering the PKR activator, dsRNA, and by interacting with PKR, leading to an inhibition of PKR activation (Y. Y. Tseng, F. Y. Lin, S. F. Cheng, D. Tscharke, S. Chulakasian, C. C. Chou, Y. F. Liu, W. S. Chang, M. L. Wong, and W. L. Hsu, J Virol 89:4966–4979, 2015, doi:10.1128/JVI.03714-14). In the current study, the possible mechanisms by which OV20.0 protein counteracts PKR activation were studied in depth. OV20.0 is able to bind PKR and its two activators, dsRNA and PACT. In addition, OV20

  10. Regulation of PACT-Mediated Protein Kinase Activation by the OV20.0 Protein of Orf Virus.

    PubMed

    Tseng, Yeu-Yang; Liao, Guan-Ru; Sen, Ganes C; Lin, Fong-Yuan; Hsu, Wei-Li

    2015-11-01

    Double-stranded RNA (dsRNA)-activated protein kinase (PKR), a major component of the cellular antiviral system, is activated by the binding of either dsRNA or the cellular PKR activator, the PACT protein. The suppression of PKR activation is one of the main strategies that viruses employ to circumvent interferon signaling. Orf virus (ORFV), a parapoxvirus from the Poxviridae family, causes contagious pustular dermatitis in small ruminants. Previous studies have demonstrated that various OV20.0 isoforms, encoded by the OV20.0L gene, are able to inhibit PKR activation both by sequestering dsRNA and by physically interacting with PKR in vitro. Thus, this gene acts as a virulence factor of ORFV when tested using a mouse infection model. In the present study, the regions within OV20.0 that interact with dsRNA and with PKR have been mapped. Furthermore, this study demonstrates for the first time that OV20.0 is also able to interact with the dsRNA binding domain of PACT and that the presence of dsRNA strengthened the interaction of these two molecules. The presence of OV20.0 diminishes PKR phosphorylation when this is stimulated by PACT. Nevertheless, the association of OV20.0 with PKR, rather than with PACT, was found to be essential for reducing PACT-mediated PKR phosphorylation. These observations elucidate a new strategy whereby innate immunity can be evaded by ORFV.IMPORTANCE Our previous study indicated that ORFV's two OV20.0 isoforms act as a PKR antagonist via sequestering the PKR activator, dsRNA, and by interacting with PKR, leading to an inhibition of PKR activation (Y. Y. Tseng, F. Y. Lin, S. F. Cheng, D. Tscharke, S. Chulakasian, C. C. Chou, Y. F. Liu, W. S. Chang, M. L. Wong, and W. L. Hsu, J Virol 89:4966-4979, 2015, doi:10.1128/JVI.03714-14). In the current study, the possible mechanisms by which OV20.0 protein counteracts PKR activation were studied in depth. OV20.0 is able to bind PKR and its two activators, dsRNA and PACT. In addition, OV20.0 binds

  11. Chemotherapy-Related Neurotoxicity.

    PubMed

    Taillibert, Sophie; Le Rhun, Emilie; Chamberlain, Marc C

    2016-09-01

    Chemotherapy may have detrimental effects on either the central or peripheral nervous system. Central nervous system neurotoxicity resulting from chemotherapy manifests as a wide range of clinical syndromes including acute, subacute, and chronic encephalopathies, posterior reversible encephalopathy, acute cerebellar dysfunction, chronic cognitive impairment, myelopathy, meningitis, and neurovascular syndromes. These clinical entities vary by causative agent, degree of severity, evolution, and timing of occurrence. In the peripheral nervous system, chemotherapy-induced peripheral neuropathy (CIPN) and myopathy are the two main complications of chemotherapy. CIPN is the most common complication, and the majority manifest as a dose-dependent length-dependent sensory axonopathy. In severe cases of CIPN, the dose of chemotherapy is reduced, the administration delayed, or the treatment discontinued. Few treatments are available for CIPN and based on meta-analysis, duloxetine is the preferred symptomatic treatment. Myopathy due to corticosteroid use is the most frequent cause of muscle disorders in patients with cancer. PMID:27443648

  12. Antimicrobial Peptides

    PubMed Central

    Bahar, Ali Adem; Ren, Dacheng

    2013-01-01

    The rapid increase in drug-resistant infections has presented a serious challenge to antimicrobial therapies. The failure of the most potent antibiotics to kill “superbugs” emphasizes the urgent need to develop other control agents. Here we review the history and new development of antimicrobial peptides (AMPs), a growing class of natural and synthetic peptides with a wide spectrum of targets including viruses, bacteria, fungi, and parasites. We summarize the major types of AMPs, their modes of action, and the common mechanisms of AMP resistance. In addition, we discuss the principles for designing effective AMPs and the potential of using AMPs to control biofilms (multicellular structures of bacteria embedded in extracellular matrixes) and persister cells (dormant phenotypic variants of bacterial cells that are highly tolerant to antibiotics). PMID:24287494

  13. Antimicrobial peptides.

    PubMed

    Bahar, Ali Adem; Ren, Dacheng

    2013-11-28

    The rapid increase in drug-resistant infections has presented a serious challenge to antimicrobial therapies. The failure of the most potent antibiotics to kill "superbugs" emphasizes the urgent need to develop other control agents. Here we review the history and new development of antimicrobial peptides (AMPs), a growing class of natural and synthetic peptides with a wide spectrum of targets including viruses, bacteria, fungi, and parasites. We summarize the major types of AMPs, their modes of action, and the common mechanisms of AMP resistance. In addition, we discuss the principles for designing effective AMPs and the potential of using AMPs to control biofilms (multicellular structures of bacteria embedded in extracellular matrixes) and persister cells (dormant phenotypic variants of bacterial cells that are highly tolerant to antibiotics).

  14. DOE NCSP Review of TRUPACT-II/HalfPACT Fissile Limits

    SciTech Connect

    Goluoglu, S.

    2002-03-28

    The U.S. Department of Energy (DOE) Environmental Management (EM) Office of Nuclear Material & Spent Fuel, EM-21, tasked the CSSG to perform a scoping study to determine the feasibility of increasing the fissile mass loading limits for specified TRUPACT-II and HalfPACT packages and containers. The results of the scoping study may provide insights and technical guidance for establishing fissile mass loading limits at waste generator sites and at the waste repository. The goal is to reduce costs of transporting fissile material to the WIPP from EM's various closure sites. This report documents the results of the scoping study and demonstrates that it is feasible to significantly increase the fissile mass loading limits in the TRUPACT-II and HalfPACT packages and containers. Depending upon the particular payload containers used, the number of shipments to WIPP could be reduced by at least a factor of 2 and as much as a factor of 16 and the number of total payload containers required ''down-hole'' at WIPP could be reduced by at least a factor of 2 and as much as about 6. These cost savings result simply from applying a more realistic criticality analysis model rather than the very conservative, hypothetical, bounding analysis used to support the existing fissile mass loading limits. However, the applications of existing and developmental computational tools, nuclear data, and experiments from the DOE Nuclear Criticality Safety Program have the potential to further reduce transportation and disposal container costs on the order of 7% to 17%. It is suggested that EM proceed with an effort to do the required formal analyses and pursue SARP supplements to take advantage of these savings. The success of these analyses are dependent upon the availability of the majority of the infrastructure supported by the DOE Nuclear Criticality Safety Program as defined in the Five-Year Plan for the program. Finally, it should be noted that these potential cost savings are based only on

  15. Neurocognitive performance and symptom profiles of Spanish-speaking Hispanic athletes on the ImPACT test.

    PubMed

    Ott, Summer; Schatz, Philip; Solomon, Gary; Ryan, Joseph J

    2014-03-01

    This study documented baseline neurocognitive performance of 23,815 athletes on the Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) test. Specifically, 9,733 Hispanic, Spanish-speaking athletes who completed the ImPACT test in English and 2,087 Hispanic, Spanish-speaking athletes who completed the test in Spanish were compared with 11,955 English-speaking athletes who completed the test in English. Athletes were assigned to age groups (13-15, 16-18). Results revealed a significant effect of language group (p < .001; partial η(2) = 0.06) and age (p < .001; partial η(2) = 0.01) on test performance. Younger athletes performed more poorly than older athletes, and Spanish-speaking athletes completing the test in Spanish scored more poorly than Spanish-speaking and English-speaking athletes completing the test in English, on all Composite scores and Total Symptom scores. Spanish-speaking athletes completing the test in English also performed more poorly than English-speaking athletes completing the test in English on three Composite scores. These differences in performance and reported symptoms highlight the need for caution in interpreting ImPACT test data for Hispanic Americans.

  16. Animation of Antimicrobial Resistance

    MedlinePlus

    ... 08 Animation of Antimicrobial Resistance (text version) Arabic Translation - Animation of Antimicrobial Resistance (WMV - 19.2MB) Chinese Translation - Animation of Antimicrobial Resistance (WMV - 19.2MB) French ...

  17. Chemotherapy (For Parents)

    MedlinePlus

    ... sample before beginning chemotherapy to evaluate kidney function. Giving your child plenty of fluids to drink will ... eating, after using the bathroom, and after touching animals. They shouldn't share cups or utensils with ...

  18. Chemotherapy in metastatic retinoblastoma.

    PubMed

    Kingston, J E; Hungerford, J L; Plowman, P N

    1987-03-01

    Eleven children with metastatic retinoblastoma diagnosed during the period 1970-1984 were treated with chemotherapy. Short-term complete responses were observed in three children treated with a four-drug combination which included cisplatinum, and in one child treated with vincristine and cyclophosphamide. The median duration of survival of the 11 children receiving chemotherapy was nine months, whilst the median survival of 13 children with metastatic retinoblastoma who were not given chemotherapy was only 2.3 months (p = 0.06). This suggests that retinoblastoma is a chemosensitive tumour and therefore adjuvant chemotherapy may have a role in children with retinoblastoma who at diagnosis are thought to be at high risk of developing metastatic disease. PMID:3587892

  19. Large-scale tissue clearing (PACT): Technical evaluation and new perspectives in immunofluorescence, histology, and ultrastructure

    PubMed Central

    Neckel, Peter H.; Mattheus, Ulrich; Hirt, Bernhard; Just, Lothar; Mack, Andreas F.

    2016-01-01

    Novel techniques, like CLARITY and PACT, render large tissue specimens transparent and thereby suitable for microscopic analysis. We used these techniques to evaluate their potential in the intestine as an exemplary organ with a complex tissue composition. Immunohistochemistry, light sheet-, and confocal scanning-microscopy enabled us to follow complex three-dimensional structures, like nerve fibers, vessels, and epithelial barriers throughout the entire organ. Moreover, in a systematic electron microscopic study, we analyzed the morphology and preservation of tissue on ultrastructural level during the clearing process. We also connect tissue clearing with classical histology and demonstrate that cleared tissues can be stained with Hematoxylin-Eosin and Heidenhain’s Azan stain, suggesting potential use in histopathology. These experiments showed that a neutral pH during the clearing process results in much better preservation of tissue ultrastructure and standard stainability. Volume changes of specimens were monitored and quantified during the course of the protocol. Additionally, we employed the technique to visualize the enteric nervous system and the epithelial barrier in post mortem human gut preparations. Our data show the high potential of tissue clearing throughout different tissue types supporting its usefulness in research and diagnosis, and contribute to the technical discussion of ultrastructural tissue-retention. PMID:27680942

  20. Bulgarian military neurosurgery: from Warsaw Pact to the North Atlantic Treaty Organization.

    PubMed

    Enchev, Yavor; Eftimov, Tihomir

    2010-05-01

    After 45 years as a closest ally of the Soviet Union in the Warsaw Pact, founded mainly against the US and the Western Europe countries, and 15 years of democratic changes, since 2004 Bulgaria has been a full member of NATO and an equal and trusted partner of its former enemies. The unprecedented transformation has affected all aspects of the Bulgarian society. As a function of the Bulgarian Armed Forces, Bulgarian military medicine and in particular Bulgarian military neurosurgery is indivisibly connected with their development. The history of Bulgarian military neurosurgery is the history of the transition from the Union of Soviet Socialist Republics military system and military medicine to NATO standards in every aspect. The career of the military neurosurgeon in Bulgaria is in many ways similar to that of the civilian neurosurgeon, but there are also many peculiarities. The purpose of this study was to outline the background and the history of Bulgarian military neurosurgery as well as its future trends in the conditions of world globalization.

  1. Chemotherapy for Melanoma.

    PubMed

    Wilson, Melissa A; Schuchter, Lynn M

    2016-01-01

    Prior to the recent therapeutic advances, chemotherapy was the mainstay of treatment options for advanced-stage melanoma. A number of studies have investigated various chemotherapy combinations in order to expand on the clinical responses achieved with single-agent dacarbazine, but these have not demonstrated an improvement in overall survival. Similar objective responses were observed with the combination of carboplatin and paclitaxel as were seen with single-agent dacarbazine. The combination of chemotherapy and immunotherapy, known as biochemo-therapy, has shown high clinical responses; however, biochemo-therapy has not been shown to improve overall survival and resulted in increased toxicities. In contrast, palliation and long-term responses have been observed with localized treatment with isolated limb perfusion or infusion in limb-isolated disease. Although new, improved therapeutic options exist for first-line management of advanced-stage melanoma, chemotherapy may still be important in the palliative treatment of refractory, progressive, and relapsed melanoma. We review the various chemotherapy options available for use in the treatment and palliation of advanced-stage melanoma, discuss the important clinical trials supporting the treatment recommendations, and focus on the clinical circumstances in which treatment with chemotherapy is useful.

  2. [Efficacy of Levofloxacin Hydrate in Febrile Neutropenia for Outpatient Chemotherapy].

    PubMed

    Inagaki, Manato; Sato, Junya; Nihei, Satoru; Kashiwaba, Masahiro; Kudo, Kenzo

    2016-05-01

    Management of febrile neutropenia (FN) is important for the safety of patients undergoing outpatient chemotherapy. Oral antimicrobials are usually prescribed as the initial treatment for FN, and outpatients are instructed to begin medication prior to chemotherapy. However, the effectiveness and safety of the use of these oral antibiotics have not yet been established. In this study, we investigated the effectiveness and safety of levofloxacin hydrate (LVFX) for breast cancer patients with FN, and the factors associated with the onset of FN in 134 breast cancer patients who underwent chemotherapy including the anticancer drug anthracycline (total, 513 courses), in an outpatient chemotherapy department. The effectiveness and safety of LVFX were defined respectively as defervescence within 5 days, and the appearance of side effects such as diarrhea and rashes. Fever was observed in 89 (66%) of the 134 patients, and during 164 (32%) of 513 courses. Defervescence was observed with the LVFX medication in 149 (93%) of 160 courses. The primary side effect was the development of rashes, and only 2 (1%) of the 160 courses were discontinued. Onset of stomatitis during chemotherapy was observed as a factor of FN (odds ratio: 1.36, p<0.05). Our results suggest that the use of LVFX according to the patients' discretion might be an effective and safe option for the management of FN during outpatient chemotherapy.

  3. [Efficacy of Levofloxacin Hydrate in Febrile Neutropenia for Outpatient Chemotherapy].

    PubMed

    Inagaki, Manato; Sato, Junya; Nihei, Satoru; Kashiwaba, Masahiro; Kudo, Kenzo

    2016-05-01

    Management of febrile neutropenia (FN) is important for the safety of patients undergoing outpatient chemotherapy. Oral antimicrobials are usually prescribed as the initial treatment for FN, and outpatients are instructed to begin medication prior to chemotherapy. However, the effectiveness and safety of the use of these oral antibiotics have not yet been established. In this study, we investigated the effectiveness and safety of levofloxacin hydrate (LVFX) for breast cancer patients with FN, and the factors associated with the onset of FN in 134 breast cancer patients who underwent chemotherapy including the anticancer drug anthracycline (total, 513 courses), in an outpatient chemotherapy department. The effectiveness and safety of LVFX were defined respectively as defervescence within 5 days, and the appearance of side effects such as diarrhea and rashes. Fever was observed in 89 (66%) of the 134 patients, and during 164 (32%) of 513 courses. Defervescence was observed with the LVFX medication in 149 (93%) of 160 courses. The primary side effect was the development of rashes, and only 2 (1%) of the 160 courses were discontinued. Onset of stomatitis during chemotherapy was observed as a factor of FN (odds ratio: 1.36, p<0.05). Our results suggest that the use of LVFX according to the patients' discretion might be an effective and safe option for the management of FN during outpatient chemotherapy. PMID:27210089

  4. Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Methodology, Drugs and Bidirectional Chemotherapy.

    PubMed

    Valle, S J; Alzahrani, N A; Liauw, W; Sugarbaker, P H; Bhatt, A; Morris, D L

    2016-06-01

    Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) combined have been recognized as standard of care for treatment of a subset of patients with peritoneal carcinomatosis (PC). The aim of CRS is to eliminate all macroscopic disease through a series of visceral resections followed by targeting any residual microscopic disease with intraperitoneal chemotherapy, exposing the peritoneal surfaces to a high concentration of chemotherapy with a lower systemic toxicity. Different regimes of intraperitoneal chemotherapy include HIPEC, early postoperative intraperitoneal chemotherapy (EPIC) and bidirectional chemotherapy. The efficacy and modality of treatment with intraperitoneal chemotherapy is dependent on multiple factors including the chosen cytotoxic agent and its pharmacokinetics and pharmacodynamics. There is no standardized methodology for intraperitoneal chemotherapy administration. This review will discuss the pharmacological principles of the various intraperitoneal chemotherapy techniques. PMID:27065705

  5. Food Antimicrobials Nanocarriers

    PubMed Central

    Blanco-Padilla, Adriana; Soto, Karen M.; Hernández Iturriaga, Montserrat

    2014-01-01

    Natural food antimicrobials are bioactive compounds that inhibit the growth of microorganisms involved in food spoilage or food-borne illness. However, stability issues result in degradation and loss of antimicrobial activity. Nanoencapsulation allows protection of antimicrobial food agents from unfavorable environmental conditions and incompatibilities. Encapsulation of food antimicrobials control delivery increasing the concentration of the antimicrobials in specific areas and the improvement of passive cellular absorption mechanisms resulted in higher antimicrobial activity. This paper reviews the present state of the art of the nanostructures used as food antimicrobial carriers including nanoemulsions, nanoliposomes, nanoparticles, and nanofibers. PMID:24995363

  6. Antimicrobial peptides.

    PubMed

    Zhang, Ling-Juan; Gallo, Richard L

    2016-01-11

    Antimicrobial peptides and proteins (AMPs) are a diverse class of naturally occurring molecules that are produced as a first line of defense by all multicellular organisms. These proteins can have broad activity to directly kill bacteria, yeasts, fungi, viruses and even cancer cells. Insects and plants primarily deploy AMPs as an antibiotic to protect against potential pathogenic microbes, but microbes also produce AMPs to defend their environmental niche. In higher eukaryotic organisms, AMPs can also be referred to as 'host defense peptides', emphasizing their additional immunomodulatory activities. These activities are diverse, specific to the type of AMP, and include a variety of cytokine and growth factor-like effects that are relevant to normal immune homeostasis. In some instances, the inappropriate expression of AMPs can also induce autoimmune diseases, thus further highlighting the importance of understanding these molecules and their complex activities. This Primer will provide an update of our current understanding of AMPs. PMID:26766224

  7. Curative cancer chemotherapy.

    PubMed

    Frei, E

    1985-12-01

    Cancer chemotherapy provides variably effective treatment for the majority of forms of human cancer and curative treatment for some 12 categories of cancer. Curative treatment is defined as the proportion of patients who survive beyond the time after which the risk of treatment failure approaches zero, i.e., the disease-free survival plateau. This progress has resulted from a closely integrated scientific effort, including drug development, pharmacology, preclinical modeling, experimental design with respect to clinical trials, quantitative criteria for response, and a series of clinical trials (initially in children with acute lymphocytic leukemia) in which the importance of complete remission, of dose and schedule, of sequencing chemotherapeutic agents, of pharmacological sanctuaries, and particularly of combination chemotherapy was studied. The principles derived from these studies, particularly those relating to combination chemotherapy, resulted in curative treatment for disseminated Hodgkin's disease, non-Hodgkin's lymphoma, pediatric solid tumors, testicular cancer, and limited small cell lung cancer. Many patients with certain stages of solid tumors, such as breast cancer and osteogenic sarcoma, are at high risk of having disseminated microscopic disease. Experimental studies indicate that treatment which is only partially effective against macroscopic disease is much more effective against microscopic tumors. Therefore chemotherapy is administered immediately following control of the primary tumor in patients at high risk of having disseminated microscopic disease, a treatment known as adjuvant chemotherapy. This program has been highly successful in increasing the cure rate in patients with pediatric solid tumors and in prolonging disease-free survival in patients with premenopausal breast cancer. Given dissemination of the technology, it is estimated that 15,000-30,000 patients per year are potentially curable in the United States. Curability of cancer

  8. WindPACT Turbine Design Scaling Studies Technical Area 3 -- Self-Erecting Tower and Nacelle Feasibility: March 2000--March 2001

    SciTech Connect

    Global Energy Concepts, LLC

    2001-05-31

    The United States Department of Energy (DOE), through the National Renewable Energy Laboratory (NREL), has implemented the Wind Partnerships for Advanced Component Technologies (WindPACT) program to explore advanced technologies for improving the reliability and cost-effectiveness of wind energy technology. Global Energy Concepts (GEC) prepared this report on self-erecting towers as part of the WindPACT program. The objectives of the work were to identify potential methods for erecting wind turbine towers without the use of large conventional cranes, establish the most promising methods, and compare the costs of the most promising methods to the costs of conventional cranes.

  9. PACT- and RIG-I-Dependent Activation of Type I Interferon Production by a Defective Interfering RNA Derived from Measles Virus Vaccine

    PubMed Central

    Ho, Ting-Hin; Kew, Chun; Lui, Pak-Yin; Chan, Chi-Ping; Satoh, Takashi; Akira, Shizuo

    2015-01-01

    ABSTRACT The live attenuated measles virus vaccine is highly immunostimulatory. Identification and characterization of its components that activate the innate immune response might provide new strategies and agents for the rational design and development of chemically defined adjuvants. In this study, we report on the activation of type I interferon (IFN) production by a defective interfering (DI) RNA isolated from the Hu-191 vaccine strain of measles virus. We found that the Hu-191 virus induced IFN-β much more potently than the Edmonston strain. In the search for IFN-inducing species in Hu-191, we identified a DI RNA specifically expressed by this strain. This DI RNA, which was of the copy-back type, was predicted to fold into a hairpin structure with a long double-stranded stem region of 206 bp, and it potently induced the expression of IFN-β. Its IFN-β-inducing activity was further enhanced when both cytoplasmic RNA sensor RIG-I and its partner, PACT, were overexpressed. On the contrary, this activity was abrogated in cells deficient in PACT or RIG-I. The DI RNA was found to be associated with PACT in infected cells. In addition, both the 5′-di/triphosphate end and the double-stranded stem region on the DI RNA were essential for its activation of PACT and RIG-I. Taken together, our findings support a model in which a viral DI RNA is sensed by PACT and RIG-I to initiate an innate antiviral response. Our work might also provide a foundation for identifying physiological PACT ligands and developing novel adjuvants or antivirals. IMPORTANCE The live attenuated measles virus vaccine is one of the most successful human vaccines and has largely contained the devastating impact of a highly contagious virus. Identifying the components in this vaccine that stimulate the host immune response and understanding their mechanism of action might help to design and develop better adjuvants, vaccines, antivirals, and immunotherapeutic agents. We identified and characterized

  10. Antimicrobial Drugs in Fighting against Antimicrobial Resistance

    PubMed Central

    Cheng, Guyue; Dai, Menghong; Ahmed, Saeed; Hao, Haihong; Wang, Xu; Yuan, Zonghui

    2016-01-01

    The outbreak of antimicrobial resistance, together with the lack of newly developed antimicrobial drugs, represents an alarming signal for both human and animal healthcare worldwide. Selection of rational dosage regimens for traditional antimicrobial drugs based on pharmacokinetic/pharmacodynamic principles as well as development of novel antimicrobials targeting new bacterial targets or resistance mechanisms are key approaches in tackling AMR. In addition to the cellular level resistance (i.e., mutation and horizontal gene transfer of resistance determinants), the community level resistance (i.e., bilofilms and persisters) is also an issue causing antimicrobial therapy difficulties. Therefore, anti-resistance and antibiofilm strategies have currently become research hotspot to combat antimicrobial resistance. Although metallic nanoparticles can both kill bacteria and inhibit biofilm formation, the toxicity is still a big challenge for their clinical applications. In conclusion, rational use of the existing antimicrobials and combinational use of new strategies fighting against antimicrobial resistance are powerful warranties to preserve potent antimicrobial drugs for both humans and animals. PMID:27092125

  11. Antimicrobial Drugs in Fighting against Antimicrobial Resistance.

    PubMed

    Cheng, Guyue; Dai, Menghong; Ahmed, Saeed; Hao, Haihong; Wang, Xu; Yuan, Zonghui

    2016-01-01

    The outbreak of antimicrobial resistance, together with the lack of newly developed antimicrobial drugs, represents an alarming signal for both human and animal healthcare worldwide. Selection of rational dosage regimens for traditional antimicrobial drugs based on pharmacokinetic/pharmacodynamic principles as well as development of novel antimicrobials targeting new bacterial targets or resistance mechanisms are key approaches in tackling AMR. In addition to the cellular level resistance (i.e., mutation and horizontal gene transfer of resistance determinants), the community level resistance (i.e., bilofilms and persisters) is also an issue causing antimicrobial therapy difficulties. Therefore, anti-resistance and antibiofilm strategies have currently become research hotspot to combat antimicrobial resistance. Although metallic nanoparticles can both kill bacteria and inhibit biofilm formation, the toxicity is still a big challenge for their clinical applications. In conclusion, rational use of the existing antimicrobials and combinational use of new strategies fighting against antimicrobial resistance are powerful warranties to preserve potent antimicrobial drugs for both humans and animals. PMID:27092125

  12. CLARITY and PACT-based imaging of adult zebrafish and mouse for whole-animal analysis of infections.

    PubMed

    Cronan, Mark R; Rosenberg, Allison F; Oehlers, Stefan H; Saelens, Joseph W; Sisk, Dana M; Jurcic Smith, Kristen L; Lee, Sunhee; Tobin, David M

    2015-12-01

    Visualization of infection and the associated host response has been challenging in adult vertebrates. Owing to their transparency, zebrafish larvae have been used to directly observe infection in vivo; however, such larvae have not yet developed a functional adaptive immune system. Cells involved in adaptive immunity mature later and have therefore been difficult to access optically in intact animals. Thus, the study of many aspects of vertebrate infection requires dissection of adult organs or ex vivo isolation of immune cells. Recently, CLARITY and PACT (passive clarity technique) methodologies have enabled clearing and direct visualization of dissected organs. Here, we show that these techniques can be applied to image host-pathogen interactions directly in whole animals. CLARITY and PACT-based clearing of whole adult zebrafish and Mycobacterium tuberculosis-infected mouse lungs enables imaging of mycobacterial granulomas deep within tissue to a depth of more than 1 mm. Using established transgenic lines, we were able to image normal and pathogenic structures and their surrounding host context at high resolution. We identified the three-dimensional organization of granuloma-associated angiogenesis, an important feature of mycobacterial infection, and characterized the induction of the cytokine tumor necrosis factor (TNF) within the granuloma using an established fluorescent reporter line. We observed heterogeneity in TNF induction within granuloma macrophages, consistent with an evolving view of the tuberculous granuloma as a non-uniform, heterogeneous structure. Broad application of this technique will enable new understanding of host-pathogen interactions in situ. PMID:26449262

  13. Antimicrobial Treatments and Efficacy

    EPA Science Inventory

    To limit exposure to indoor biological contamination a risk-management approach which employs various antimicrobial treatments can effectively control contaminants and reduce exposure. Antimicrobial treatment of biological contaminants, especially mold in buildings, it is often n...

  14. [Chemotherapy of brain tumors].

    PubMed

    Kuratsu, J; Ushio, Y

    1994-10-01

    Despite recent attempts to improve chemotherapeutic approaches for the treatment of malignant gliomas, results remain limited and palliative. The development of effective chemotherapy for tumors of the central nervous system (CNS) is complicated in that the blood-brain barrier (B.B.B.) hampers the penetration of most drugs into the brain and cerebrospinal fluid. The factors governing delivery in the brain are the drug's molecular weight, lipophilicity and degree of ionization. Now the standard therapy for malignant glioma is maximal tumor resection followed by combination radiotherapy plus chemotherapy. Nitrosoureas are representative drugs which easily cross the B.B.B.. It has been shown that nitrosourea compounds have an additive effect to radiotherapy. The toxicity profile of nitrosoureas is leukocytopenia and thrombocytopenia as a dose-limiting factor. Furthermore, the great heterogeneity of malignant glioma tissues offered a rationale for the use of multiple drugs. Many studies were reported to show a substantial advantage for the multidrug regimen over control series utilizing single drugs alone. Despite clear examples of the effectiveness of chemotherapy, we are still far from improving the cure rate for the vast majority of patients with primary malignancies of the CNS. Further improvement in patient survival may depend upon understanding and manipulating the pathways that regulate aberrant growth in these tumors. The development of new anticancer agents, which are sensitive to malignant glioma and can reach a high concentration in glioma tissue, is warranted. PMID:7986118

  15. Integrating a Focus on Academic Language, English Learners, and Mathematics: Teacher Candidates' Responses on the Performance Assessment for California Teachers (PACT)

    ERIC Educational Resources Information Center

    Bunch, George C.; Aguirre, Julia M.; Téllez, Kip

    2015-01-01

    Throughout the United States, teacher educators are developing new strategies to improve the preparation of mainstream teachers for linguistic diversity. In this article, we explore teacher candidates' responses to the Performance Assessment for California Teachers (PACT), a preservice assessment required for credentialing that requires…

  16. Building the Interest of High School Students for Science- A PACT Ambassador Program To Investigate Soap Manufacturing and Industrial Chemistry

    NASA Astrophysics Data System (ADS)

    Lynch, Matthew; Geary, Nicholas; Hagaman, Karen; Munson, Anne; Sabo, Mark

    1999-02-01

    The Ambassador Program of the Partnership for the Advancement of Chemical Technology (PACT) brings industrial applications of technology into high schools to enhance the student's perception of the chemical industry and industrial careers in chemistry. This article details a two-year effort (1996 and 1997) in which ambassadors from the Procter and Gamble Company and Miami University-Middletown worked with Finneytown High School students. The program entailed following a typical product development cycle for fabricating commercially viable soap products. It exposed students to as many aspects of science and science careers as possible, from traditional research and development to product research. The objective of the article is to inform the reader about the program with sufficient detail to encourage similar efforts. Thus, it includes a discussion of the initiation, organization, and curriculum of the program and also provides a critique as an evaluation of its effectiveness.

  17. Chemotherapy in Retinoblastoma: Current Approaches

    PubMed Central

    Yanık, Özge; Gündüz, Kaan; Yavuz, Kıvılcım; Taçyıldız, Nurdan; Ünal, Emel

    2015-01-01

    Retinoblastoma (RB) is the most common childhood malignant intraocular tumor. Although enucleation and external beam radiotherapy have been historically used, today the most commonly used eye-sparing approach is chemotherapy. Chemotherapy can be used in both intraocular and extraocular RB cases. Chemotherapeutic agents may be applied in different ways, including systemic, subconjunctival, intra-arterial and intravitreal routes. The main purposes of application of systemic therapy are to reduce the tumor size for local treatment (chemoreduction), or to reduce the risk of metastasis after enucleation surgery (adjuvant therapy). Intra-arterial chemotherapy with the current name “super-selective intra-arterial infusion therapy” could be applied as primary therapy in tumors confined to the retina or as a secondary method in tumor recurrence. The most important advantage of intra-arterial therapy is the prevention of systemic chemotherapy complications. Intravitreal chemotherapy is administered in the presence of persistent or recurrent vitreous seeding. The term “extraocular RB” includes orbital invasion and metastatic disease. Current treatment for orbital invasion is neoadjuvant chemotherapy followed by surgical enucleation and adjuvant chemotherapy and radiotherapy after surgery. In metastatic disease, regional lymph node involvement, distant metastases, and/or central nervous system (CNS) involvement may occur. Among them, CNS involvement has the worst prognosis, remaining at almost 100% mortality. In metastatic disease, high-dose salvage chemotherapy and autologous hematopoietic stem cell rescue therapy are the possible treatment options; radiotherapy could also be added to the protocol according to the side of involvement. PMID:27800245

  18. Antimicrobials in beekeeping.

    PubMed

    Reybroeck, Wim; Daeseleire, Els; De Brabander, Hubert F; Herman, Lieve

    2012-07-01

    The bee diseases American and European foulbrood and nosemosis can be treated with anti-infectious agents. However, in the EU and the USA the use of these agents in beekeeping is strictly regulated due to the lack of tolerance (e.g. Maximum Residue Limit) for residues of antibiotics and chemotherapeutics in honey. This article reviews the literature dealing with antimicrobials of interest in apiculture, stability of these antimicrobials in honey, and disposition of the antimicrobials in honeybee hives.

  19. Chemotherapy targeting cancer stem cells.

    PubMed

    Liu, Haiguang; Lv, Lin; Yang, Kai

    2015-01-01

    Conventional chemotherapy is the main treatment for cancer and benefits patients in the form of decreased relapse and metastasis and longer overall survival. However, as the target therapy drugs and delivery systems are not wholly precise, it also results in quite a few side effects, and is less efficient in many cancers due to the spared cancer stem cells, which are considered the reason for chemotherapy resistance, relapse, and metastasis. Conventional chemotherapy limitations and the cancer stem cell hypothesis inspired our search for a novel chemotherapy targeting cancer stem cells. In this review, we summarize cancer stem cell enrichment methods, the search for new efficient drugs, and the delivery of drugs targeting cancer stem cells. We also discuss cancer stem cell hierarchy complexity and the corresponding combination therapy for both cancer stem and non-stem cells. Learning from cancer stem cells may reveal novel strategies for chemotherapy in the future.

  20. Chemotherapy targeting cancer stem cells

    PubMed Central

    Liu, Haiguang; Lv, Lin; Yang, Kai

    2015-01-01

    Conventional chemotherapy is the main treatment for cancer and benefits patients in the form of decreased relapse and metastasis and longer overall survival. However, as the target therapy drugs and delivery systems are not wholly precise, it also results in quite a few side effects, and is less efficient in many cancers due to the spared cancer stem cells, which are considered the reason for chemotherapy resistance, relapse, and metastasis. Conventional chemotherapy limitations and the cancer stem cell hypothesis inspired our search for a novel chemotherapy targeting cancer stem cells. In this review, we summarize cancer stem cell enrichment methods, the search for new efficient drugs, and the delivery of drugs targeting cancer stem cells. We also discuss cancer stem cell hierarchy complexity and the corresponding combination therapy for both cancer stem and non-stem cells. Learning from cancer stem cells may reveal novel strategies for chemotherapy in the future. PMID:26045975

  1. Antimicrobial (Drug) Resistance

    MedlinePlus

    ... Antimicrobial (Drug) Resistance Antibiotic-Resistant Mycobacterium tuberculosis (TB) Methicillin-Resistant Staphylococcus aureus (MRSA) Vancomycin-Resistant Enterococci (VRE) Multidrug-Resistant Neisseria ...

  2. Carotidynia after anticancer chemotherapy

    PubMed Central

    Hayashi, Shinichi; Maruoka, Shuichiro; Takahashi, Noriaki; Hashimoto, Shu

    2014-01-01

    Carotidynia is characterised by inflammation limited to the common carotid artery, which has been recognised as a distinct disease entity by advanced vascular imaging. Although most cases of carotidynia are idiopathic, we herein present a case of carotidynia after anticancer chemotherapy. A 64-year-old male patient received docetaxel followed by granulocyte-colony stimulating factor (G-CSF) for the treatment of lung squamous carcinoma. After the treatment, bilateral cervical pain developed. Vascular imaging, including magnetic resonance imaging, computed tomography and ultrasonography, showed characteristics specific for carotidynia. Although there was no strong confirmation using tests such as a challenge test, our observations suggest that docetaxel or G-CSF could be a causative drug triggering carotidynia. PMID:25273942

  3. Adult medulloblastoma: multiagent chemotherapy.

    PubMed Central

    Greenberg, H. S.; Chamberlain, M. C.; Glantz, M. J.; Wang, S.

    2001-01-01

    In this study, the records of 17 adult patients with medulloblastoma treated with craniospinal radiation and 1 of 2 multiagent chemotherapy protocols were reviewed for progression-free survival, overall survival, and toxicity, and the patients were compared with each other and with similarly treated children and adults. Records of patients treated at 3 institutions were reviewed. Seventeen medulloblastoma patients (11 female, 6 male) with a median age of 23 years (range, 18-47 years) were treated with surgery, craniospinal radiation (CSRT) plus local boost, and 1 of 2 adjuvant chemotherapy regimens. All tumors were infratentorial (10 in 4th ventricle and 7 in left or right hemisphere). Ten patients presented with hydrocephalus, and 7 of them were shunted. Eight patients had gross total resection, 7 had subtotal resection (>50% removed), and 2 had partial resection (<50% removed). Postoperatively, 3 patients had positive cytology and 3 had positive spinal MRI. Five patients were classified as good risk and 12 were classified as poor risk (Chang staging system). Ten patients were treated with the "Packer protocol," consisting of CSRT plus weekly vincristine followed by 8 cycles of cisplatin, lomustine, and vincristine. Seven patients were treated with the Pediatric Oncology Group (POG) protocol, consisting of alternating courses of cisplatin/etoposide and cyclophosphamide/vincristine, followed by CSRT. Eight of 17 patients relapsed, with all 8 relapsing at the primary site. Other relapse sites included the leptomeninges (5), bone (1), and brain (1). The estimated median relapse-free survival (Kaplan-Meier) for all patients was 48 months (95% confidence interval, >26 months to infinity). Median relapse-free survival for patients on the Packer protocol was 26 months, and for those on the POG regimen was 48 months (P = 0.410). Five of 10 on the Packer protocol were relapse-free, while 4 of 7 were relapse-free on the POG regimen. Two patients relapsed during chemotherapy

  4. Antimicrobial Peptides in 2014

    PubMed Central

    Wang, Guangshun; Mishra, Biswajit; Lau, Kyle; Lushnikova, Tamara; Golla, Radha; Wang, Xiuqing

    2015-01-01

    This article highlights new members, novel mechanisms of action, new functions, and interesting applications of antimicrobial peptides reported in 2014. As of December 2014, over 100 new peptides were registered into the Antimicrobial Peptide Database, increasing the total number of entries to 2493. Unique antimicrobial peptides have been identified from marine bacteria, fungi, and plants. Environmental conditions clearly influence peptide activity or function. Human α-defensin HD-6 is only antimicrobial under reduced conditions. The pH-dependent oligomerization of human cathelicidin LL-37 is linked to double-stranded RNA delivery to endosomes, where the acidic pH triggers the dissociation of the peptide aggregate to release its cargo. Proline-rich peptides, previously known to bind to heat shock proteins, are shown to inhibit protein synthesis. A model antimicrobial peptide is demonstrated to have multiple hits on bacteria, including surface protein delocalization. While cell surface modification to decrease cationic peptide binding is a recognized resistance mechanism for pathogenic bacteria, it is also used as a survival strategy for commensal bacteria. The year 2014 also witnessed continued efforts in exploiting potential applications of antimicrobial peptides. We highlight 3D structure-based design of peptide antimicrobials and vaccines, surface coating, delivery systems, and microbial detection devices involving antimicrobial peptides. The 2014 results also support that combination therapy is preferred over monotherapy in treating biofilms. PMID:25806720

  5. Efficacy of the photodynamic antimicrobial therapy (PACT) with the use of methylene blue associated with the λ660nm laser in Leishmania (Leishmania) amazonesis: in vitro study

    NASA Astrophysics Data System (ADS)

    Pires-Santos, Gustavo M.; Marques, Aparecida M. C.; Alves, Eliomara S. S.; Oliveira, Susana C. P. S.; Monteiro, Juliana S. C.; Rosa, Cristiane B.; Colombo, Fabio; Pinheiro, Antônio L. B.; Vannier-Santos, Marcos A.

    2012-03-01

    The present studied evaluated the in vitro effects of PDT on Leishmania (Leishmania) amazonensis promastigotes. For this examination L. amazonensis promastigotes, stain Josefa, were used and maintained in Warren media supplement with fetal bovine serum at 26°C for 96 hours. A viability curve was accomplished using different concentrations of methylene blue photosensitizer associated to red laser light in order to obtain the most effective interaction to inhibit the parasite's growth. Two pre-irradiation periods, 5 and 30 minutes, were evaluated and the promastigotes were counted by colorimetry. On fluorescence microscopy the autophagic processes and reactive oxygen species were detected. Promastigotes treated with Photodynamic Therapy (PDT) by concentrations of 5 and 0,315ug/mL, presented cellular proliferation inhibition when compared to the control. In the first condition, the cells had structural alterations such as truncated cells, cells with two flagella, bleb formation and cells body deformation, while none of these modifications could be visualized in the control group. When analyzed through fluorescence microscopy, the promastigotes treated were positives for free radicals immediately after light application and also 1 hour after treatment presenting signs of autophagia. PDT on L. (L.) amazonensis is effective causing alterations that can help elucidate the mechanisms of the parasite's death when treated with methilene

  6. MicroRNA-122 Inhibits the Production of Inflammatory Cytokines by Targeting the PKR Activator PACT in Human Hepatic Stellate Cells.

    PubMed

    Nakamura, Masato; Kanda, Tatsuo; Sasaki, Reina; Haga, Yuki; Jiang, Xia; Wu, Shuang; Nakamoto, Shingo; Yokosuka, Osamu

    2015-01-01

    MicroRNA-122 (miR-122) is one of the most abundant miRs in the liver. Previous studies have demonstrated that miR-122 plays a role in inflammation in the liver and functions in hepatic stellate cells (HSCs), which reside in the space of Disse. Here, we showed that the transient inhibition of PKR-activating protein (PACT) expression, by miR-122 or siRNA targeting of PACT, suppressed the production of proinflammatory cytokines, such as interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1) and IL-1β, in human HSC LX-2. Sequence and functional analyses confirmed that miR-122 directly targeted the 3'-untranslated region of PACT. Immunofluorescence analysis revealed that miR-122 blocked NF-κB-nuclear translocation in LX-2 cells. We also showed that conditioned medium from miR-122-transfected LX-2 cells suppressed human monocyte-derived THP-1 cell migration. Taken together, our study indicates that miR-122 may downregulate cytokine production in HSCs and macrophage chemotaxis and that the targeting of miR-122 may have therapeutic potential for preventing the progression of liver diseases. PMID:26636761

  7. Chemotherapy for Soft Tissue Sarcomas

    MedlinePlus

    ... drugs may be used as well, including cisplatin, dacarbazine (DTIC), docetaxel (Taxotere ® ), gemcitabine (Gemzar ® ), methotrexate, oxaliplatin, paclitaxel (Taxol ® ), ... such as: MAID (mesna, Adriamycin [doxorubicin], ifosfamide, and dacarbazine). Chemotherapy drugs kill cancer cells but also damage ...

  8. [Chemotherapy for prostate cancer].

    PubMed

    Rauchenwald, Michael; De Santis, Maria; Fink, Eleonore; Höltl, Wolfgang; Kramer, Gero; Marei, Isabella-Carolina; Neumann, Hans-Jörg; Reissigl, Andreas; Schmeller, Nikolaus; Stackl, Walter; Hobisch, Alfred; Krainer, Michael

    2008-01-01

    For many years the benefit of chemotherapy in patients with prostate cancer was thought to be limited to palliation of late-stage disease, and thus this treatment option only became involved in patient care towards the end of the disease process, if at all. However, two landmark phase-III trials with docetaxel-based therapy (TAX 327 and Southwest Oncology Group, SWOG, 9916) have shown a survival benefit for patients with hormone refractory prostate cancer (HRPC) thus prompting a change in patterns of care. With raising interest for chemotherapeutic options and clinical trials for new drugs and new indications (neoadjuvant therapy, adjuvant therapy, increasing PSA levels after local treatment, and hormone sensitive cancer) under way our goal was to review within the context of a multidisciplinary team the available evidence and explore the standard for the medical treatment of prostate cancer outside of clinical trials. We are carefully evaluating the current treatment recommendations based on the available evidence and highlight potential future treatment options but also discuss important clinical topics (treatment until progression versus the advantage of chemo holidays, definition of particular patient subgroups and potential second line options) for which there are no clear cut answers to date. The role and importance of radiotherapy, biphosphonate treatment and the medical management of pain and side effects is also discussed. The multitude of treatment options for patients with advanced prostate cancer clearly asks for a close collaboration between urologists, medical oncologists and radiation therapists. PMID:18726672

  9. Global Similarities and Multifaceted Differences in the Production of Partner-Specific Referential Pacts by Adults with Autism Spectrum Disorders.

    PubMed

    Nadig, Aparna; Seth, Shivani; Sasson, Michelle

    2015-01-01

    Over repeated reference conversational partners tend to converge on preferred terms or referential pacts. Autism spectrum disorders (ASD) are characterized by pragmatic difficulties that are best captured by less structured tasks. To this end we tested adults with ASD who did not have language or intellectual impairments, and neurotypical comparison participants in a referential communication task. Participants were directors, describing unlexicalized, complex novel stimuli over repeated rounds of interaction. Group comparisons with respect to referential efficiency showed that directors with ASD demonstrated typical lexical entrainment: they became faster over repeated rounds and used shortened referential forms. ASD and neurotypical groups did not differ with respect to the number of descriptors they provided or the number of exchanges needed for matchers to identify figures. Despite these similarities the ASD group was slightly slower overall. We examined partner-specific effects by manipulating the common ground shared with the matcher. As expected, neurotypical directors maintained referential precedents when speaking to the same matcher but not with a new matcher. Directors with ASD were qualitatively similar but displayed a less pronounced distinction between matchers. However, significant differences and different patterns of reference emerged over time; neurotypical directors incorporated the new matcher's contributions into descriptions, whereas directors with ASD were less likely to do so. PMID:26733897

  10. Mathematical modeling of COD removal via the combined treatment of domestic wastewater and landfill leachate based on the PACT process.

    PubMed

    Fernández Bou, Ángel S; Nascentes, Alexandre Lioi; Costa Pereira, Barbara; Da Silva, Leonardo Duarte Batista; Alberto Ferreira, João; Campos, Juacyara Carbonelli

    2015-01-01

    The experiments performed in this study consisted of 16 batch reactors fed different mixtures of landfill leachate combined with synthetic wastewater treated using the Powdered Activated Carbon Treatment (PACT) process. The objective was to measure the COD mass removal per liter each day for each reactor using two models: the first model combined the variables PAC concentration (0 g·L(-1), 2 g·L(-1), 4 g·L(-1), and 6 g·L(-1)) and leachate rate in the wastewater (0%, 2%, 5%, and 10%), and the second model combined the PAC concentration and the influent COD. The Response Surface Methodology with Central Composite Design was used to describe the response surface of both models considered in this study. Domestic wastewater was produced under controlled conditions in the laboratory where the experiments were performed. The results indicated that the PAC effect was null when the influent did not contain leachate; however, as the concentration of leachate applied to the mixture was increased, the addition of a higher PAC concentration resulted in a better COD mass removal in the reactors. The adjusted R(2) values of the two models were greater than 0.95, and the predicted R(2) values were greater than 0.93. The models may be useful for wastewater treatment companies to calculate PAC requirements in order to meet COD mass removal objectives in combined treatment. PMID:25723064

  11. Mathematical modeling of COD removal via the combined treatment of domestic wastewater and landfill leachate based on the PACT process.

    PubMed

    Fernández Bou, Ángel S; Nascentes, Alexandre Lioi; Costa Pereira, Barbara; Da Silva, Leonardo Duarte Batista; Alberto Ferreira, João; Campos, Juacyara Carbonelli

    2015-01-01

    The experiments performed in this study consisted of 16 batch reactors fed different mixtures of landfill leachate combined with synthetic wastewater treated using the Powdered Activated Carbon Treatment (PACT) process. The objective was to measure the COD mass removal per liter each day for each reactor using two models: the first model combined the variables PAC concentration (0 g·L(-1), 2 g·L(-1), 4 g·L(-1), and 6 g·L(-1)) and leachate rate in the wastewater (0%, 2%, 5%, and 10%), and the second model combined the PAC concentration and the influent COD. The Response Surface Methodology with Central Composite Design was used to describe the response surface of both models considered in this study. Domestic wastewater was produced under controlled conditions in the laboratory where the experiments were performed. The results indicated that the PAC effect was null when the influent did not contain leachate; however, as the concentration of leachate applied to the mixture was increased, the addition of a higher PAC concentration resulted in a better COD mass removal in the reactors. The adjusted R(2) values of the two models were greater than 0.95, and the predicted R(2) values were greater than 0.93. The models may be useful for wastewater treatment companies to calculate PAC requirements in order to meet COD mass removal objectives in combined treatment.

  12. Global Similarities and Multifaceted Differences in the Production of Partner-Specific Referential Pacts by Adults with Autism Spectrum Disorders

    PubMed Central

    Nadig, Aparna; Seth, Shivani; Sasson, Michelle

    2015-01-01

    Over repeated reference conversational partners tend to converge on preferred terms or referential pacts. Autism spectrum disorders (ASD) are characterized by pragmatic difficulties that are best captured by less structured tasks. To this end we tested adults with ASD who did not have language or intellectual impairments, and neurotypical comparison participants in a referential communication task. Participants were directors, describing unlexicalized, complex novel stimuli over repeated rounds of interaction. Group comparisons with respect to referential efficiency showed that directors with ASD demonstrated typical lexical entrainment: they became faster over repeated rounds and used shortened referential forms. ASD and neurotypical groups did not differ with respect to the number of descriptors they provided or the number of exchanges needed for matchers to identify figures. Despite these similarities the ASD group was slightly slower overall. We examined partner-specific effects by manipulating the common ground shared with the matcher. As expected, neurotypical directors maintained referential precedents when speaking to the same matcher but not with a new matcher. Directors with ASD were qualitatively similar but displayed a less pronounced distinction between matchers. However, significant differences and different patterns of reference emerged over time; neurotypical directors incorporated the new matcher's contributions into descriptions, whereas directors with ASD were less likely to do so. PMID:26733897

  13. Prevention of Alcohol-Related Crime and Trauma (PACT): brief interventions in routine care pathway – a study protocol

    PubMed Central

    2013-01-01

    Background Globally, alcohol-related injuries cause millions of deaths and huge economic loss each year . The incidence of facial (jawbone) fractures in the Northern Territory of Australia is second only to Greenland, due to a strong involvement of alcohol in its aetiology, and high levels of alcohol consumption. The highest incidences of alcohol-related trauma in the Territory are observed amongst patients in the Maxillofacial Surgery Unit of the Royal Darwin Hospital. Accordingly, this project aims to introduce screening and brief interventions into this unit, with the aims of changing health service provider practice, improving access to care, and improving patient outcomes. Methods Establishment of Project Governance: The project governance team includes a project manager, project leader, an Indigenous Reference Group (IRG) and an Expert Reference Group (ERG). Development of a best practice pathway: PACT project researchers collaborate with clinical staff to develop a best practice pathway suited to the setting of the surgical unit. The pathway provides clear guidelines for screening, assessment, intervention and referral. Implementation: The developed pathway is introduced to the unit through staff training workshops and associate resources and adapted in response to staff feedback. Evaluation: File audits, post workshop questionnaires and semi-structured interviews are administered. Discussion This project allows direct transfer of research findings into clinical practice and can inform future hospital-based injury prevention strategies. PMID:23331868

  14. Antimicrobial Peptides in Reptiles

    PubMed Central

    van Hoek, Monique L.

    2014-01-01

    Reptiles are among the oldest known amniotes and are highly diverse in their morphology and ecological niches. These animals have an evolutionarily ancient innate-immune system that is of great interest to scientists trying to identify new and useful antimicrobial peptides. Significant work in the last decade in the fields of biochemistry, proteomics and genomics has begun to reveal the complexity of reptilian antimicrobial peptides. Here, the current knowledge about antimicrobial peptides in reptiles is reviewed, with specific examples in each of the four orders: Testudines (turtles and tortosises), Sphenodontia (tuataras), Squamata (snakes and lizards), and Crocodilia (crocodilans). Examples are presented of the major classes of antimicrobial peptides expressed by reptiles including defensins, cathelicidins, liver-expressed peptides (hepcidin and LEAP-2), lysozyme, crotamine, and others. Some of these peptides have been identified and tested for their antibacterial or antiviral activity; others are only predicted as possible genes from genomic sequencing. Bioinformatic analysis of the reptile genomes is presented, revealing many predicted candidate antimicrobial peptides genes across this diverse class. The study of how these ancient creatures use antimicrobial peptides within their innate immune systems may reveal new understandings of our mammalian innate immune system and may also provide new and powerful antimicrobial peptides as scaffolds for potential therapeutic development. PMID:24918867

  15. Fast Disinfecting Antimicrobial Surfaces

    PubMed Central

    Madkour, Ahmad E.; Dabkowski, Jeffery M.; Nüsslein, Klaus; Tew, Gregory N.

    2013-01-01

    Silicon wafers and glass surfaces were functionalized with facially amphiphilic antimicrobial copolymers using the “grafting from” technique. Surface initiated atom transfer radical polymerization (ATRP) was used to grow poly(butylmethacrylate)-co-poly(Boc-aminoethyl methacrylate) from the surfaces. Upon Boc-deprotection, these surfaces became highly antimicrobial and killed S. aureus and E. coli 100% in less than 5 min. The molecular weight and grafting density of the polymer were controlled by varying the polymerization time and initiator surface density. Antimicrobial studies showed that the killing efficiency of these surfaces was independent of polymer layer thickness or grafting density within the range of surfaces studied. PMID:19177651

  16. Pharmacogenomics of antimicrobial agents.

    PubMed

    Aung, Ar Kar; Haas, David W; Hulgan, Todd; Phillips, Elizabeth J

    2014-01-01

    Antimicrobial efficacy and toxicity varies between individuals owing to multiple factors. Genetic variants that affect drug-metabolizing enzymes may influence antimicrobial pharmacokinetics and pharmacodynamics, thereby determining efficacy and/or toxicity. In addition, many severe immune-mediated reactions have been associated with HLA class I and class II genes. In the last two decades, understanding of pharmacogenomic factors that influence antimicrobial efficacy and toxicity has rapidly evolved, leading to translational success such as the routine use of HLA-B*57:01 screening to prevent abacavir hypersensitivity reactions. This article examines recent advances in the field of antimicrobial pharmacogenomics that potentially affect treatment efficacy and toxicity, and challenges that exist between pharmacogenomic discovery and translation into clinical use.

  17. Pharmacogenomics of antimicrobial agents

    PubMed Central

    Aung, Ar Kar; Haas, David W; Hulgan, Todd; Phillips, Elizabeth J

    2015-01-01

    Antimicrobial efficacy and toxicity varies between individuals owing to multiple factors. Genetic variants that affect drug-metabolizing enzymes may influence antimicrobial pharmacokinetics and pharmacodynamics, thereby determining efficacy and/or toxicity. In addition, many severe immune-mediated reactions have been associated with HLA class I and class II genes. In the last two decades, understanding of pharmacogenomic factors that influence antimicrobial efficacy and toxicity has rapidly evolved, leading to translational success such as the routine use of HLA-B*57:01 screening to prevent abacavir hypersensitivity reactions. This article examines recent advances in the field of antimicrobial pharmacogenomics that potentially affect treatment efficacy and toxicity, and challenges that exist between pharmacogenomic discovery and translation into clinical use. PMID:25495412

  18. Novel antimicrobial textiles

    NASA Astrophysics Data System (ADS)

    Cho, Unchin

    2003-10-01

    Many microorganisms can survive, and perhaps proliferate on textiles, generating adverse effects such as: disease transmission, odor generation, pH changes, staining, discoloration and loss of performance. These adverse effects may threaten users' health, deteriorate textile properties and degrade service quality. It may, therefore, be desirable to incorporate antimicrobials on textiles for controlling the growth of microorganisms. This dissertation focuses on the development of antimicrobial fibers and fabrics by integration of antimicrobials with these textiles. The applications of hydantoin-based halamines were mainly investigated in the research. The typical process is that hydantoin containing compounds are grafted onto textiles and transformed to halamine by chlorination. Hydantoin-based halamines are usually chloramines that release chlorine (Cl+) via cleavage of the -NCl functional group which attacks and kills microbes. The antimicrobial behavior is rechargeable many times by rinsing the fiber or fabric with chlorine-containing solution. Some quaternary ammonium type antimicrobials were also investigated in this research. The choice of integrating techniques is dependant on both the textile and antimicrobial compounds. In this dissertation, the nine approaches were studied for incorporating antimicrobial with various textiles: (1) co-extrusion of fibers with halamine precursor additive; (2) grafting of the quaternary ammonium compounds onto ethylene-co-acrylic acid fiber for creating quaternary ammonium type antimicrobial fiber; (3) entrapment of the additives in thermally bonded bicomponent nonwoven fabrics; (4) attaching antimicrobial additives to surfaces with latex adhesive coating; (5) grafting of antimicrobial compounds onto rubber latex via UV exposure; (6) reaction of halamine with needle-punched melamine formaldehyde nonwoven fabric and laminates; (7) coating melamine resin onto tent fabrics and laminates; (8) synthesis of super absorbent polymer

  19. Antimicrobial compounds in tears.

    PubMed

    McDermott, Alison M

    2013-12-01

    The tear film coats the cornea and conjunctiva and serves several important functions. It provides lubrication, prevents drying of the ocular surface epithelia, helps provide a smooth surface for refracting light, supplies oxygen and is an important component of the innate defense system of the eye providing protection against a range of potential pathogens. This review describes both classic antimicrobial compounds found in tears such as lysozyme and some more recently identified such as members of the cationic antimicrobial peptide family and surfactant protein-D as well as potential new candidate molecules that may contribute to antimicrobial protection. As is readily evident from the literature review herein, tears, like all mucosal fluids, contain a plethora of molecules with known antimicrobial effects. That all of these are active in vivo is debatable as many are present in low concentrations, may be influenced by other tear components such as the ionic environment, and antimicrobial action may be only one of several activities ascribed to the molecule. However, there are many studies showing synergistic/additive interactions between several of the tear antimicrobials and it is highly likely that cooperativity between molecules is the primary way tears are able to afford significant antimicrobial protection to the ocular surface in vivo. In addition to effects on pathogen growth and survival some tear components prevent epithelial cell invasion and promote the epithelial expression of innate defense molecules. Given the protective role of tears a number of scenarios can be envisaged that may affect the amount and/or activity of tear antimicrobials and hence compromise tear immunity. Two such situations, dry eye disease and contact lens wear, are discussed here.

  20. Antimicrobial Compounds in Tears

    PubMed Central

    McDermott, Alison M.

    2013-01-01

    The tear film coats the cornea and conjunctiva and serves several important functions. It provides lubrication, prevents drying of the ocular surface epithelia, helps provide a smooth surface for refracting light, supplies oxygen and is an important component of the innate defense system of the eye providing protection against a range of potential pathogens. This review describes both classic antimicrobial compounds found in tears such as lysozyme and some more recently identified such as members of the cationic antimicrobial peptide family and surfactant protein-D as well as potential new candidate molecules that may contribute to antimicrobial protection. As is readily evident from the literature review herein, tears, like all mucosal fluids, contain a plethora of molecules with known antimicrobial effects. That all of these are active in vivo is debatable as many are present in low concentrations, may be influenced by other tear components such as the ionic environment, and antimicrobial action may be only one of several activities ascribed to the molecule. However, there are many studies showing synergistic/additive interactions between several of the tear antimicrobials and it is highly likely that cooperativity between molecules is the primary way tears are able to afford significant antimicrobial protection to the ocular surface in vivo. In addition to effects on pathogen growth and survival some tear components prevent epithelial cell invasion and promote the epithelial expression of innate defense molecules. Given the protective role of tears a number of scenarios can be envisaged that may affect the amount and/or activity of tear antimicrobials and hence compromise tear immunity. Two such situations, dry eye disease and contact lens wear, are discussed here. PMID:23880529

  1. Eradication of Helicobacter mustelae from the ferret stomach: an animal model of Helicobacter (Campylobacter) pylori chemotherapy.

    PubMed Central

    Otto, G; Fox, J G; Wu, P Y; Taylor, N S

    1990-01-01

    Colonization of the ferret stomach by Helicobacter mustelae has been suggested as a possible animal model for Helicobacter pylori-associated gastroduodenal disease of humans. Our study was designed to determine whether antimicrobial chemotherapy could eradicate H. mustelae from ferrets. Triple antimicrobial therapy combining amoxicillin, metronidazole, and bismuth subsalicylate was successful in eradicating the organism from 5 of 7 (71%) adult ferrets. Despite apparent in vitro susceptibility, neither chloramphenicol monotherapy nor a polytherapeutic regimen combining tetracycline, metronidazole, and bismuth subsalicylate proved effective in the eradication of H. mustelae. Several strains isolated after unsuccessful polytherapy showed markedly increased resistance to metronidazole. These preliminary findings are similar to results of H. pylori treatment trials with humans and suggest that the ferret may be a useful model for evaluating and comparing potential antimicrobial modalities for the eradication of H. pylori. PMID:2393285

  2. Antimicrobial resistance in livestock.

    PubMed

    Catry, B; Laevens, H; Devriese, L A; Opsomer, G; De Kruif, A

    2003-04-01

    Antimicrobial resistance may become a major problem in veterinary medicine as a consequence of the intensive use and misuse of antimicrobial drugs. Related problems are now arising in human medicine, such as the appearance of multi-resistant food-borne pathogens. Product characteristics, dose, treatment interval and duration of treatment influence the selection pressure for antimicrobial drug resistance. There are theoretical, experimental and clinical indications that the emergence of de novo resistance in a pathogenic population can be prevented by minimizing the time that suboptimal drug levels are present in the infected tissue compartment. Until recently, attention has been focused on target pathogens. However, it should be kept in mind that when antimicrobial drugs are used in an individual, resistance selection mainly affects the normal body flora. In the long term, this is at least equally important as resistance selection in the target pathogens, as the horizontal transfer of resistance genes converts almost all pathogenic bacteria into potential recipients for antimicrobial resistance. Other factors contributing to the epidemiology of antimicrobial resistance are the localization and size of the microbial population, and the age, immunity and contact intensity of the host. In livestock, dynamic herd-related resistance patterns have been observed in different animal species.

  3. A bivalent cationic dye enabling selective photo-inactivation against Gram-negative bacteria.

    PubMed

    Li, Ke; Zhang, Yang-Yang; Jiang, Guo-Yu; Hou, Yuan-Jun; Zhang, Bao-Wen; Zhou, Qian-Xiong; Wang, Xue-Song

    2015-05-01

    A piperazine-modified Crystal Violet was found to be able to selectively inactivate Gram-negative bacteria upon visible light irradiation but left Gram-positive bacteria less damaged, which can serve as a blueprint for the development of novel narrow-spectrum agents to replenish the current arsenal of photodynamic antimicrobial chemotherapy (PACT).

  4. Lumbar reservoir for intrathecal chemotherapy.

    PubMed

    Dyck, P

    1985-06-15

    The Ommaya ventricular reservoir has been the standby of intrathecal chemotherapy for more than a decade, in spite of some specific drawbacks. A general anaesthetic is often required. The scalp must be shaven. Ventricular puncture may not always be easy and keeping the ventricular catheter patent is sometimes difficult. Hence the author has adapted a commercially available lumbar peritoneal shunt system to function as a lumbar intrathecal reservoir. The procedure is simple and can be performed expeditiously under local anaesthesia. To date, eight cases have received intrathecal chemotherapy by this means. PMID:3838918

  5. IN.PACT Amphirion paclitaxel eluting balloon versus standard percutaneous transluminal angioplasty for infrapopliteal revascularization of critical limb ischemia: rationale and protocol for an ongoing randomized controlled trial

    PubMed Central

    2014-01-01

    Background The effectiveness and durability of endovascular revascularization therapies for chronic critical limb ischemia (CLI) are challenged by the extensive burden of infrapopliteal arterial disease and lesion-related characteristics (e.g., severe calcification, chronic total occlusions), which frequently result in poor clinical outcomes. While infrapopliteal vessel patency directly affects pain relief and wound healing, sustained patency and extravascular care both contribute to the ultimate “patient-centric” outcomes of functional limb preservation, mobility and quality of life (QoL). Methods/Design IN.PACT DEEP is a 2:1 randomized controlled trial designed to assess the efficacy and safety of infrapopliteal arterial revascularization between the IN.PACT Amphirion™ paclitaxel drug-eluting balloon (IA-DEB) and standard balloon angioplasty (PTA) in patients with Rutherford Class 4-5-6 CLI. Discussion This multicenter trial has enrolled 358 patients at 13 European centers with independent angiographic core lab adjudication of the primary efficacy endpoint of target lesion late luminal loss (LLL) and clinically driven target lesion revascularization (TLR) in major amputation-free surviving patients through 12-months. An independent wound core lab will evaluate all ischemic wounds to assess the extent of healing and time to healing at 1, 6, and 12 months. A QoL questionnaire including a pain scale will assess changes from baseline scores through 12 months. A Clinical Events Committee and Data Safety Monitoring Board will adjudicate the composite primary safety endpoints of all-cause death, major amputation, and clinically driven TLR at 6 months and other trial endpoints and supervise patient safety throughout the study. All patients will be followed for 5 years. A literature review is presented of the current status of endovascular treatment of CLI with drug-eluting balloon and standard PTA. The rationale and design of the IN.PACT DEEP Trial are

  6. The Professionalism Assessment of Clinical Teachers (PACT): the reliability and validity of a novel tool to evaluate professional and clinical teaching behaviors.

    PubMed

    Young, Meredith E; Cruess, Sylvia R; Cruess, Richard L; Steinert, Yvonne

    2014-03-01

    Physicians function as clinicians, teachers, and role models within the clinical environment. Negative learning environments have been shown to be due to many factors, including the presence of unprofessional behaviors among clinical teachers. Reliable and valid assessments of clinical teacher performance, including professional behaviors, may provide a foundation for evidence-based feedback to clinical teachers, enable targeted remediation or recognition, and help to improve the learning environment. However, few tools exist for the evaluation of clinical teachers that include a focus on both professional and clinical teaching behaviors. The Professionalism Assessment of Clinical Teachers (PACT) was developed and implemented at one Canadian institution and was assessed for evidence of reliability and validity. Following each clerkship rotation, students in the 2009-2010 third-year undergraduate clerkship cohort (n = 178) anonymously evaluated a minimum of two clinical teachers using the PACT. 4,715 forms on 567 faculty members were completed. Reliability, validity, and free text comments (present in 45 % of the forms) were examined. An average of 8.6 PACT forms were completed per faculty (range 1-60), with a reliability of 0.31 for 2.9 forms (harmonic mean); 12 forms were necessary for a reliability of 0.65. Global evaluations of teachers aligned with ratings of free-text comments (r = 0.77, p < 0.001). Comment length related negatively with overall rating (r = -0.19, p < 0.001). Mean performance related negatively with variability of performance (r = -0.72, p < 0.001), although this may be related to a ceiling effect. Most faculty members were rated highly; however 'provided constructive feedback' was the least well-rated item. Respectful interactions with students appeared to be the most influential item in the global rating of faculty performance. The PACT is a moderately reliable tool for the assessment of professional behaviors of clinical

  7. The Professionalism Assessment of Clinical Teachers (PACT): the reliability and validity of a novel tool to evaluate professional and clinical teaching behaviors.

    PubMed

    Young, Meredith E; Cruess, Sylvia R; Cruess, Richard L; Steinert, Yvonne

    2014-03-01

    Physicians function as clinicians, teachers, and role models within the clinical environment. Negative learning environments have been shown to be due to many factors, including the presence of unprofessional behaviors among clinical teachers. Reliable and valid assessments of clinical teacher performance, including professional behaviors, may provide a foundation for evidence-based feedback to clinical teachers, enable targeted remediation or recognition, and help to improve the learning environment. However, few tools exist for the evaluation of clinical teachers that include a focus on both professional and clinical teaching behaviors. The Professionalism Assessment of Clinical Teachers (PACT) was developed and implemented at one Canadian institution and was assessed for evidence of reliability and validity. Following each clerkship rotation, students in the 2009-2010 third-year undergraduate clerkship cohort (n = 178) anonymously evaluated a minimum of two clinical teachers using the PACT. 4,715 forms on 567 faculty members were completed. Reliability, validity, and free text comments (present in 45 % of the forms) were examined. An average of 8.6 PACT forms were completed per faculty (range 1-60), with a reliability of 0.31 for 2.9 forms (harmonic mean); 12 forms were necessary for a reliability of 0.65. Global evaluations of teachers aligned with ratings of free-text comments (r = 0.77, p < 0.001). Comment length related negatively with overall rating (r = -0.19, p < 0.001). Mean performance related negatively with variability of performance (r = -0.72, p < 0.001), although this may be related to a ceiling effect. Most faculty members were rated highly; however 'provided constructive feedback' was the least well-rated item. Respectful interactions with students appeared to be the most influential item in the global rating of faculty performance. The PACT is a moderately reliable tool for the assessment of professional behaviors of clinical

  8. Managing Chemotherapy Side Effects: Memory Changes

    MedlinePlus

    ... C ancer I nstitute Managing Chemotherapy Side Effects Memory Changes What is causing these changes? Your doctor ... thinking or remembering things Managing Chemotherapy Side Effects: Memory Changes Get help to remember things. Write down ...

  9. Managing Chemotherapy Side Effects: Swelling (Fluid Retention)

    MedlinePlus

    ... ancer I nstitute Managing Chemotherapy Side Effects Swelling (Fluid retention) “My hands and feet were swollen and ... at one time. Managing Chemotherapy Side Effects: Swelling (Fluid retention) Weigh yourself. l Weigh yourself at the ...

  10. General principles of antimicrobial therapy.

    PubMed

    Leekha, Surbhi; Terrell, Christine L; Edson, Randall S

    2011-02-01

    Antimicrobial agents are some of the most widely, and often injudiciously, used therapeutic drugs worldwide. Important considerations when prescribing antimicrobial therapy include obtaining an accurate diagnosis of infection; understanding the difference between empiric and definitive therapy; identifying opportunities to switch to narrow-spectrum, cost-effective oral agents for the shortest duration necessary; understanding drug characteristics that are peculiar to antimicrobial agents (such as pharmacodynamics and efficacy at the site of infection); accounting for host characteristics that influence antimicrobial activity; and in turn, recognizing the adverse effects of antimicrobial agents on the host. It is also important to understand the importance of antimicrobial stewardship, to know when to consult infectious disease specialists for guidance, and to be able to identify situations when antimicrobial therapy is not needed. By following these general principles, all practicing physicians should be able to use antimicrobial agents in a responsible manner that benefits both the individual patient and the community.

  11. General principles of antimicrobial therapy.

    PubMed

    Leekha, Surbhi; Terrell, Christine L; Edson, Randall S

    2011-02-01

    Antimicrobial agents are some of the most widely, and often injudiciously, used therapeutic drugs worldwide. Important considerations when prescribing antimicrobial therapy include obtaining an accurate diagnosis of infection; understanding the difference between empiric and definitive therapy; identifying opportunities to switch to narrow-spectrum, cost-effective oral agents for the shortest duration necessary; understanding drug characteristics that are peculiar to antimicrobial agents (such as pharmacodynamics and efficacy at the site of infection); accounting for host characteristics that influence antimicrobial activity; and in turn, recognizing the adverse effects of antimicrobial agents on the host. It is also important to understand the importance of antimicrobial stewardship, to know when to consult infectious disease specialists for guidance, and to be able to identify situations when antimicrobial therapy is not needed. By following these general principles, all practicing physicians should be able to use antimicrobial agents in a responsible manner that benefits both the individual patient and the community. PMID:21282489

  12. Chemotherapy of human african trypanosomiasis.

    PubMed

    Bacchi, Cyrus J

    2009-01-01

    Human Africa trypanosomiasis is a centuries-old disease which has disrupted sub-Saharan Africa in both physical suffering and economic loss. This article presents an update of classic chemotherapeutic agents, in use for >50 years and the recent development of promising non-toxic combination chemotherapy suitable for use in rural clinics.

  13. Pancreatic cancer: chemotherapy and radiotherapy

    PubMed Central

    Andrén-Sandberg, Åke

    2011-01-01

    Pancreatic cancer in many cases appears in a non-curatively resectable stage when the diagnosis is made. Palliative treatment become an option in the patients with advanced stage. The present article reviewed chemotherapy and radiotherapy in various advanced stage of pancreatic cancer. PMID:22540056

  14. Granulomatous Amebic Encephalitis in a Child with Acute Lymphoblastic Leukemia Successfully Treated with Multimodal Antimicrobial Therapy and Hyperbaric Oxygen▿

    PubMed Central

    Maritschnegg, P.; Sovinz, P.; Lackner, H.; Benesch, M.; Nebl, A.; Schwinger, W.; Walochnik, J.; Urban, C.

    2011-01-01

    Acanthamoeba is the causative agent of granulomatous amebic encephalitis, a rare and usually fatal disease. We report a child with acute lymphoblastic leukemia who developed brain abscesses caused by Acanthamoeba during induction therapy. Multimodal antimicrobial chemotherapy and hyperbaric oxygen therapy resulted in complete resolution of symptoms and of pathology as seen by magnetic resonance imaging. PMID:21084511

  15. [Growth promoting antimicrobials].

    PubMed

    Hoogkamp-Korstanje, J A

    1999-06-19

    The committee 'Growth promoting antimicrobials' of the Health Council of the Netherlands in 1998 advised immediate prohibition of all growth promoting antimicrobials related to human drugs and decrease of use of other growth promoting antimicrobials during the next three years in Europe. It is clear that frequent use of antibiotics is associated with development of resistance by selection in animals (and man), but it is not proven that this is an explanation of resistance in the human community. We know only little about the mechanisms and conditions of transfer of bacteria to man. Other questions raised are: what about the resulting possible increase of therapeutic application of antibiotics in animals, how to handle the increase of dung, nitrogen and phosphate in the environment and how farmers can survive with a decrease in income, sometimes by as much as 50%? Although many will feel sympathy for the report and its recommendations, implementing them will be difficult and possibly premature. PMID:10416481

  16. Antimicrobial Peptides from Fish

    PubMed Central

    Masso-Silva, Jorge A.; Diamond, Gill

    2014-01-01

    Antimicrobial peptides (AMPs) are found widely distributed through Nature, and participate in the innate host defense of each species. Fish are a great source of these peptides, as they express all of the major classes of AMPs, including defensins, cathelicidins, hepcidins, histone-derived peptides, and a fish-specific class of the cecropin family, called piscidins. As with other species, the fish peptides exhibit broad-spectrum antimicrobial activity, killing both fish and human pathogens. They are also immunomodulatory, and their genes are highly responsive to microbes and innate immuno-stimulatory molecules. Recent research has demonstrated that some of the unique properties of fish peptides, including their ability to act even in very high salt concentrations, make them good potential targets for development as therapeutic antimicrobials. Further, the stimulation of their gene expression by exogenous factors could be useful in preventing pathogenic microbes in aquaculture. PMID:24594555

  17. [REACTIVATION OF TUBERCULOSIS PRESENTING WITH EMPYEMA DUE TO ANTICANCER CHEMOTHERAPY FOR DIFFUSE LARGE B CELL LYMPHOMA].

    PubMed

    Yuba, Tatsuya; Hatsuse, Mayumi; Kodama, Mai; Uda, Sayaka; Yoshimura, Akihiro; Kurisu, Naoko

    2016-04-01

    A 79-year-old man with a history of tuberculosis was found to have chronic empyema in the right lung and was diagnosed with malignant diffuse large-cell lymphoma (Ann Arbor stage IIE). After completion of one course of rituximab plus cyclophosphamide, pirarubicin, vincristine, and prednisolone (R-CHOP) chemotherapy, the patient developed lung abscess and sepsis caused by Streptococcus intermedius. This condition was treated with antimicrobial agents, and chemotherapy was resumed. After the second course, the chemotherapy regimen was continued without prednisolone, and after administration of the third course, a chest wall mass was found in the right lung. An acid-fast bacillus smear test of the abscess aspirate was positive, and Mycobacterium tuberculosis was detected in a polymerase chain reaction assay, leading to a diagnosis of perithoracic tuberculosis. Chemotherapy for the lymphoma was discontinued, and treatment with four oral antitubercular agents was started. This treatment led to remission of perithoracic tuberculosis. In Japan, tuberculous scar and chronic empyema are relatively common findings, and relapse of tuberculosis should always be considered for patients with these findings during chemotherapy and immunosuppressive therapy. PMID:27530021

  18. Efficacy of HPA Lanolin® in treatment of lip alterations related to chemotherapy

    PubMed Central

    SANTOS, Paulo Sérgio da Silva; TINÔCO-ARAÚJO, José Endrigo; de SOUZA, Lucas Monteiro de Vasconcelos Alves; FERREIRA, Rafael; IKOMA, Maura Rosane Valério; RAZERA, Ana Paula Ribeiro; SANTOS, Márcia Mirolde Magno de Carvalho

    2013-01-01

    The side effects of chemotherapy on the lips may cause esthetic and functional impact and increase the risk of infection. HPA Lanolin® is an option for supportive therapy because it has anti-inflammatory, antimicrobial and moisturizing properties. Objective: To evaluate the efficacy of this product in the prevention of lip alterations in a population of patients undergoing chemotherapy. Material and Methods: Patients undergoing chemotherapy (n=57) were examined and distributed into two groups: study (used HPA Lanolin®) and control (without supportive therapy on the lips). We evaluated the patients two weeks after chemotherapy, registering oral alterations, symptoms of pain, discomfort, limitation of mouth opening and dehydration, classified according to a visual analogue scale. Results: Patients who used HPA Lanolin® had lower dehydration and experienced improvement of lip dryness (p<0.001). The main symptoms were dehydration, discomfort, limitation of mouth opening, pain. The main clinical signs were dry lips, mucositis, cheilitis, hematoma, swelling and cracking. We found no difference concerning the variables of pain, discomfort, and limitation of mouth opening between the study and control group. Conclusions: We suggest that HPA Lanolin® is effective in reducing the symptoms of dehydration and the signs of lip dryness resulting from toxicity of chemotherapy, proving to be an interesting alternative supportive therapy for cancer patients. PMID:23739860

  19. Antimicrobial Graft Copolymer Gels.

    PubMed

    Harvey, Amanda C; Madsen, Jeppe; Douglas, C W Ian; MacNeil, Sheila; Armes, Steven P

    2016-08-01

    In view of the growing worldwide rise in microbial resistance, there is considerable interest in designing new antimicrobial copolymers. The aim of the current study was to investigate the relationship between antimicrobial activity and copolymer composition/architecture to gain a better understanding of their mechanism of action. Specifically, the antibacterial activity of several copolymers based on 2-(methacryloyloxy)ethyl phosphorylcholine [MPC] and 2-hydroxypropyl methacrylate (HPMA) toward Staphylococcus aureus was examined. Both block and graft copolymers were synthesized using either atom transfer radical polymerization or reversible addition-fragmentation chain transfer polymerization and characterized via (1)H NMR, gel permeation chromatography, rheology, and surface tensiometry. Antimicrobial activity was assessed using a range of well-known assays, including direct contact, live/dead staining, and the release of lactate dehydrogenase (LDH), while transmission electron microscopy was used to study the morphology of the bacteria before and after the addition of various copolymers. As expected, PMPC homopolymer was biocompatible but possessed no discernible antimicrobial activity. PMPC-based graft copolymers comprising PHPMA side chains (i.e. PMPC-g-PHPMA) significantly reduced both bacterial growth and viability. In contrast, a PMPC-PHPMA diblock copolymer comprising a PMPC stabilizer block and a hydrophobic core-forming PHPMA block did not exhibit any antimicrobial activity, although it did form a biocompatible worm gel. Surface tensiometry studies and LDH release assays suggest that the PMPC-g-PHPMA graft copolymer exhibits surfactant-like activity. Thus, the observed antimicrobial activity is likely to be the result of the weakly hydrophobic PHPMA chains penetrating (and hence rupturing) the bacterial membrane. PMID:27409712

  20. Treatment of Nausea and Vomiting During Chemotherapy

    PubMed Central

    Mustian, Karen M; Devine, Katie; Ryan, Julie L; Janelsins, Michelle C; Sprod, Lisa K; Peppone, Luke J; Candelario, Grace D; Mohile, Supriya G; Morrow, Gary R

    2014-01-01

    Nausea and vomiting are two of the most troubling side effects patients experience during chemotherapy. While newly available treatments have improved our ability to manage nausea and vomiting, anticipatory and delayed nausea and vomiting are still a major problem for patients receiving chemotherapy. Many cancer patients will delay or refuse future chemotherapy treatments and contemplate stopping chemotherapy altogether because of their fear of experiencing further nausea and vomiting. The purpose of this article is to provide an overview of the patho-psychophysiology of chemotherapy-induced nausea and vomiting and the recommended guidelines for treatment. PMID:24466408

  1. Chemotherapy against cancer during pregnancy

    PubMed Central

    Esposito, Susanna; Tenconi, Rossana; Preti, Valentina; Groppali, Elena; Principi, Nicola

    2016-01-01

    Abstract Background: The concomitant incidence of cancer and pregnancy has increased in recent years because of the increase in maternal age at the time of the 1st pregnancy. The diagnosis of cancer in a pregnant woman causes ethical and therapeutic problems for both the patient and the physician. The main aim of this paper is to describe the available evidence concerning the short- and long-term neonatal impact of chemotherapy given to pregnant women. Methods: The relevant publications in English were identified by a systematic review of MEDLINE and PubMed for the last 15 years. The search strategy included “cancer[Title/Abstract] OR tumor[Title/Abstract] AND pregnancy[Title/Abstract] OR pregnant[Title/Abstract] AND embryo[Title/Abstract] or fetus[Title/Abstract] or neonate[Title/Abstract] or newborn[Title/Abstract] or pediatric[Title/Abstract] or child[Title/Abstract] AND English[lang].” Results: An analysis of the literature showed that only the administration of chemotherapy during the embryonic stage of conceptus is dangerous and can lead to the termination of the pregnancy. When the disease is diagnosed in the 2nd or 3rd trimester of gestation or when it is possible to delay the initiation of chemotherapy beyond the 14th week, the risk of severe problems for the fetus are low, and pregnancy termination is not required. Conclusion: Data regarding the final outcome of children who have received in utero chemotherapy seem reassuring. Only the administration in the embryonal stage of conceptus is dangerous and can lead to the termination of pregnancy. When the disease is diagnosed in the 2nd or 3rd trimester of gestation or when it is possible to delay the initiation of chemotherapy beyond the 14th week, the risk of severe problems for the fetus are low and pregnancy termination is not needed. Increased knowledge of how to minimize the risks of chemotherapy can reduce improper management including unnecessary termination of pregnancy, delayed maternal

  2. Antimicrobial properties of honey.

    PubMed

    Israili, Zafar H

    2014-01-01

    Honey has been widely accepted as food and medicine by all generations, traditions, and civilizations, both ancient and modern. For at least 2700 years, honey has been used by humans to treat a variety of ailments through topical application, but only recently have the antiseptic and antimicrobial properties of honey been discovered. Honey has been reported to be effective in a number of human pathologies. Clinical studies have demonstrated that application of honey to severely infected cutaneous wounds rapidly clears infection from the wound and improves tissue healing. A large number of in vitro and limited clinical studies have confirmed the broad-spectrum antimicrobial (antibacterial, antifungal, antiviral, and antimycobacterial) properties of honey, which may be attributed to the acidity (low pH), osmotic effect, high sugar concentration, presence of bacteriostatic and bactericidal factors (hydrogen peroxide, antioxidants, lysozyme, polyphenols, phenolic acids, flavonoids, methylglyoxal, and bee peptides), and increase in cytokine release, and to immune modulating and anti-inflammatory properties of honey; the antimicrobial action involves several mechanisms. Despite a large amount of data confirming the antimicrobial activity of honey, there are no studies that support the systemic use of honey as an antibacterial agent. PMID:23782759

  3. Triclosan antimicrobial polymers

    PubMed Central

    Petersen, Richard C.

    2016-01-01

    Triclosan antimicrobial molecular fluctuating energies of nonbonding electron pairs for the oxygen atom by ether bond rotations are reviewed with conformational computational chemistry analyses. Subsequent understanding of triclosan alternating ether bond rotations is able to help explain several material properties in Polymer Science. Unique bond rotation entanglements between triclosan and the polymer chains increase both the mechanical properties of polymer toughness and strength that are enhanced even better through secondary bonding relationships. Further, polymer blend compatibilization is considered due to similar molecular relationships and polarities. With compatibilization of triclosan in polymers a more uniform stability for nonpolar triclosan in the polymer solid state is retained by the antimicrobial for extremely low release with minimum solubility into aqueous solution. As a result, triclosan is projected for long extended lifetimes as an antimicrobial polymer additive. Further, triclosan rapid alternating ether bond rotations disrupt secondary bonding between chain monomers in the resin state to reduce viscosity and enhance polymer blending. Thus, triclosan is considered for a polymer additive with multiple properties to be an antimicrobial with additional benefits as a nonpolar toughening agent and a hydrophobic wetting agent. The triclosan material relationships with alternating ether bond rotations are described through a complete different form of medium by comparisons with known antimicrobial properties that upset bacterial cell membranes through rapid fluctuating mechanomolecular energies. Also, triclosan bond entanglements with secondary bonding can produce structural defects in weak bacterial lipid membranes requiring pliability that can then interfere with cell division. Regarding applications with polymers, triclosan can be incorporated by mixing into a resin system before cure, melt mixed with thermoplastic polymers that set on cooling

  4. Keep Our PACT Act

    THOMAS, 112th Congress

    Rep. Van Hollen, Chris [D-MD-8

    2011-03-01

    03/21/2011 Referred to the Subcommittee on Early Childhood, Elementary, and Secondary Education. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  5. Keep Our PACT Act

    THOMAS, 113th Congress

    Rep. Van Hollen, Chris [D-MD-8

    2014-09-18

    11/17/2014 Referred to the Subcommittee on Early Childhood, Elementary, and Secondary Education. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  6. Rates and predictors of invalid baseline test performance in high school and collegiate athletes for three computerized neurocognitive tests (CNTs): ANAM, Axon, and ImPACT

    PubMed Central

    Nelson, Lindsay D.; Pfaller, Adam Y.; Rein, Lisa E.; McCrea, Michael A.

    2015-01-01

    Background Preseason baseline testing is increasingly performed on athletes using computerized neurocognitive tests (CNTs). Adequate effort is critical to establish valid estimates of ability, yet many users do not evaluate performance validity, and the conditions that impact validity are not well understood across the available CNTs. Purpose We examined the rates and predictors of invalid baseline performance for three popular CNTs: ANAM (Automated Neuropsychological Assessment Metrics), Axon Sports, and ImPACT (Immediate Post-Concussion Cognitive Assessment and Testing). Study Design Cross-sectional study. Methods High school and collegiate athletes (N = 2,063) completed two of three CNTs each during pre-season evaluations. All possible pairings were present across the sample, and order of administration was randomized. Examiners gave one-on-one, scripted pre-test instructions emphasizing the importance of good effort. Profile validity was determined by the manufacturers’ standard criteria. Results The overall percentage of tests flagged as of questionable validity was lowest for ImPACT (2.7%) and higher for ANAM and Axon (10.8% and 11.3%, respectively). The majority of invalid baselines were flagged as such due to failure on only one validity criterion. Several athlete and testing factors (e.g., attention deficit-hyperactivity disorder/ADHD, estimated general intellectual ability, administration order) predicted validity status for one or more CNTs. Considering only first CNT administrations and participants without ADHD and/or learning disability (n = 1,835) brought the rates of invalid baselines to 2.1%, 8.8%, and 7.0%, for ImPACT, ANAM, and Axon, respectively. Invalid profiles on the Medical Symptom Validity Test (MSVT) were rare (1.8% of subjects) and demonstrated poor correspondence to CNT validity outcomes. Conclusion These CNTs’ validity criteria may not identify the same causes of invalidity or be equally sensitive to effort. The validity indicators

  7. Can we prevent antimicrobial resistance by using antimicrobials better?

    PubMed

    Soothill, Germander; Hu, Yanmin; Coates, Anthony

    2013-06-10

    Since their development over 60 years ago, antimicrobials have become an integral part of healthcare practice worldwide. Recently, this has been put in jeopardy by the emergence of widespread antimicrobial resistance, which is one of the major problems facing modern medicine. In the past, the development of new antimicrobials kept us one step ahead of the problem of resistance, but only three new classes of antimicrobials have reached the market in the last thirty years. A time is therefore approaching when we may not have effective treatment against bacterial infections, particularly for those that are caused by Gram-negative organisms. An important strategy to reduce the development of antimicrobial resistance is to use antimicrobials more appropriately, in ways that will prevent resistance. This involves a consideration of the pharmacokinetic and pharmacodynamics properties of antimicrobials, the possible use of combinations, and more appropriate choice of antimicrobials, which may include rapid diagnostic testing and antimicrobial cycling. Examples given in this review include Mycobacterium tuberculosis, Gram-negative and Gram-positive organisms. We shall summarise the current evidence for these strategies and outline areas for future development.

  8. Antimicrobial Resistance in Agriculture

    PubMed Central

    Thanner, Sophie; Drissner, David

    2016-01-01

    ABSTRACT In this article, the current knowledge and knowledge gaps in the emergence and spread of antimicrobial resistance (AMR) in livestock and plants and importance in terms of animal and human health are discussed. Some recommendations are provided for generation of the data required in order to develop risk assessments for AMR within agriculture and for risks through the food chain to animals and humans. PMID:27094336

  9. Substandard/Counterfeit Antimicrobial Drugs

    PubMed Central

    Kelesidis, Theodoros

    2015-01-01

    SUMMARY Substandard/counterfeit antimicrobial drugs are a growing global problem. The most common substandard/counterfeit antimicrobials include beta-lactams (among antibiotics) and chloroquine and artemisin derivatives (among antimalarials). The most common type of substandard/counterfeit antimicrobial drugs have a reduced amount of the active drug, and the majority of them are manufactured in Southeast Asia and Africa. Counterfeit antimicrobial drugs may cause increased mortality and morbidity and pose a danger to patients. Here we review the literature with regard to the issue of substandard/counterfeit antimicrobials and describe the prevalence of this problem, the different types of substandard/counterfeit antimicrobial drugs, and the consequences for the individuals and global public health. Local, national, and international initiatives are required to combat this very important public health issue. PMID:25788516

  10. Substandard/counterfeit antimicrobial drugs.

    PubMed

    Kelesidis, Theodoros; Falagas, Matthew E

    2015-04-01

    Substandard/counterfeit antimicrobial drugs are a growing global problem. The most common substandard/counterfeit antimicrobials include beta-lactams (among antibiotics) and chloroquine and artemisin derivatives (among antimalarials). The most common type of substandard/counterfeit antimicrobial drugs have a reduced amount of the active drug, and the majority of them are manufactured in Southeast Asia and Africa. Counterfeit antimicrobial drugs may cause increased mortality and morbidity and pose a danger to patients. Here we review the literature with regard to the issue of substandard/counterfeit antimicrobials and describe the prevalence of this problem, the different types of substandard/counterfeit antimicrobial drugs, and the consequences for the individuals and global public health. Local, national, and international initiatives are required to combat this very important public health issue. PMID:25788516

  11. Bridging the gap: the Virtual Chemotherapy Unit.

    PubMed

    Scavuzzo, Jennifer; Gamba, Nicole

    2004-01-01

    Due to the complexity of pediatric chemotherapy administration, systems promoting safety must be utilized. Computerized order entry has been proven to reduce errors in the ordering of chemotherapeutic agents. A task force (the Breakthrough Committee) at The Children's Hospital of Philadelphia (CHOP) evaluated systems and identified the need to streamline the chemotherapy admission process from the outpatient clinic to the inpatient unit. In the outpatient setting chemotherapy orders were handwritten, whereas inpatient orders were computerized. Patients due for chemotherapy admissions were unable to start chemotherapy until they were physically admitted to an inpatient bed. In many cases, patients would not start receiving chemotherapy until late in the evening or even overnight. The Breakthrough Committee created the Virtual Chemotherapy Unit (Virtual Unit), which standardizes the ordering and documentation for all chemotherapy admissions. As per its name, the Virtual Unit is not an actual hospital unit but merely a location in the computer system where the patient is admitted prior to having a bed on the inpatient unit. Patients are now able to start chemotherapy infusions in the outpatient setting early in the day, rather than waiting until arrival to the inpatient unit. The nurses in the outpatient clinic are able to document chemotherapy administration online, giving the inpatient staff the ability to view the medications that were given. The Virtual Unit bridges the gap in chemotherapy ordering and documentation by utilizing 1 online episode per patient admission. Oncology nurses at CHOP played a fundamental role in the creation of the Virtual Unit. Nurses identified situations with potential for error in the ordering and administration of chemotherapy. These scenarios were analyzed and used in creating a safer system.

  12. [Neruda and antimicrobial resistance].

    PubMed

    Cotera, Alejandro

    2011-07-01

    Antimicrobial resistance has been a problem in medicine, since their incorporation to clinical practice. Numerous papers have been written on the subject. The analysis of two poems by Pablo Neruda "How much does a man live" and "Larynx", included in the volume "Estravagario" and published for the first time in 1957 and 1958, give us an incredible revelation about the concept of resistance. In these poems aureomycin, the first antimicrobial of the family of tetracyclines, was included as a poetic figure and the therapeutic action of antimicrobials was described. "Never so much bugs died I tons of them fell I but the few that remained olive I manifested their perversity". These writings incorporated novel concepts, even for physicians of that time and described the closeness of death that a patient may perceive during the course of a given disease. The capacity of Pablo Neruda to extract the essence of situations and to anticipate to conditions that only years later became clinically relevant problems, is noteworthy. PMID:22051837

  13. [Neruda and antimicrobial resistance].

    PubMed

    Cotera, Alejandro

    2011-07-01

    Antimicrobial resistance has been a problem in medicine, since their incorporation to clinical practice. Numerous papers have been written on the subject. The analysis of two poems by Pablo Neruda "How much does a man live" and "Larynx", included in the volume "Estravagario" and published for the first time in 1957 and 1958, give us an incredible revelation about the concept of resistance. In these poems aureomycin, the first antimicrobial of the family of tetracyclines, was included as a poetic figure and the therapeutic action of antimicrobials was described. "Never so much bugs died I tons of them fell I but the few that remained olive I manifested their perversity". These writings incorporated novel concepts, even for physicians of that time and described the closeness of death that a patient may perceive during the course of a given disease. The capacity of Pablo Neruda to extract the essence of situations and to anticipate to conditions that only years later became clinically relevant problems, is noteworthy.

  14. Immunotherapy and chemotherapy in children with neuroblastoma.

    PubMed

    Nesbit, M E; Kersey, J; Finklestein, J; Weiner, J; Simmons, R

    1976-09-01

    Recent advances with immunotherapy in animal tumors suggested that trials with a combination of chemotherapy and immunotherapy in human malignant tumors might be worthwhile. A pilot program with Vibrio cholera neuraminidase-treated tumor cells plus BCG was tested in 3 patients who had had chemotherapy for disseminated neuroblastoma. Two of these children were in "complete remission" after radiation therapy and chemotherapy before the administration of immunotherapy. Relapse occurred in 5-6 months in all 3 patients. These disappointing results are discussed in relation to problems of current chemotherapy in disseminated neuroblastoma including results obtained at second-look operations in patients obtaining "complete remission."

  15. Rationale for combining immunotherapy with chemotherapy.

    PubMed

    Dalgleish, Angus G

    2015-01-01

    Immunotherapy has usually been considered as an alternative to more traditional modalities. Moreover, it has previously been felt that chemotherapy is inherently immunosuppressive and not suitable for combining with immunotherapy. In this review, the concept of combining different modalities that result in cell death, such as radiotherapy and chemotherapy, with immunotherapy is explored. Tumors actively cause immune suppression which can be reversed by their removal but when this is not possible, enhancing the immune response with nonspecific immune stimulation can enhance the response to other modalities, such as radiotherapy and chemotherapy. Additionally, several chemotherapy agents at low doses selectively inhibit regulatory and suppressor cells.

  16. [Primary systemic chemotherapy for breast cancer].

    PubMed

    Takada, Masahiro; Toi, Masakazu

    2007-11-01

    Neoadjuvant chemotherapy for breast cancer has achieved a higher response rate with the combination of anthracycline and taxane. Molecular targeted agents, such as trastuzumab, are expected to enhance the effectiveness of treatment. The main objectives of neoadjuvant chemotherapy are to reduce tumor size, increase breast conserving rate, identify treatment response, adjust the following treatment strategy, and develop a new treatment using biological specimens. Recently, there has been an increasing demand to provide a tailored treatment in neoadjuvant chemotherapy with establishment of genetic testing for biological markers and adjustment of therapeutic strategy following identification of the early treatment response. We reviewed recent advances in neoadjuvant chemotherapy for breast cancer.

  17. Northern Power Systems WindPACT Drive Train Alternative Design Study Report; Period of Performance: April 12, 2001 to January 31, 2005

    SciTech Connect

    Bywaters, G.; John, V.; Lynch, J.; Mattila, P.; Norton, G.; Stowell, J.; Salata, M.; Labath, O.; Chertok, A.; Hablanian, D.

    2004-10-01

    The National Renewable Energy Laboratory (NREL) Wind Partnerships for Advanced Component Technologies (WindPACT) project seeks to advance wind turbine technology by exploring innovative concepts in drivetrain design. A team led by Northern Power Systems (Northern) of Waitsfield, Vermont, was chosen to perform this work. Conducted under subcontract YCX-1-30209-02, project objectives are to identify, design, and test a megawatt (MW)-scale drivetrain with the lowest overall life cycle cost. The project entails three phases: preliminary study of alternative drivetrain designs (Phase I), detailed design development (Phase II), and proof of concept fabrication and test (Phase III). This report summarizes the results of the preliminary design study (Phase I).

  18. Preliminary Effectiveness of Project ImPACT: A Parent-Mediated Intervention for Children with Autism Spectrum Disorder Delivered in a Community Program

    PubMed Central

    Stadnick, Nicole A.; Stahmer, Aubyn; Brookman-Frazee, Lauren

    2015-01-01

    This is a pilot study of the effectiveness of Project ImPACT, a parent-mediated intervention for ASD delivered in a community program. The primary aim was to compare child and parent outcomes between the intervention group and a community comparison for 30 young children with ASD at baseline and 12 weeks. The secondary aim was to identify parent factors associated with changes in child outcomes. Results indicated significant improvement in child communication skills and a strong trend for parent intervention adherence for the intervention group from baseline to 12 weeks. Higher baseline parenting stress was negatively related to child social gains from baseline to 12 weeks. Findings provide further support for delivering parent-mediated interventions in community settings to children with ASD. PMID:25633920

  19. Strategies to Combat Antimicrobial Resistance

    PubMed Central

    Uchil, Rajesh R; Kohli, Gurdeep Singh; Katekhaye, Vijay M

    2014-01-01

    The global burden of antimicrobial resistance is rising and is associated with increased morbidity and mortality in clinical and community setting. Spread of antibiotic resistance to different environmental niches and development of superbugs have further complicated the effective control strategies. International, national and local approaches have been advised for control and prevention of antimicrobial resistance. Rational use of antimicrobials, regulation on over-the-counter availability of antibiotics, improving hand hygiene and improving infection prevention and control are the major recommended approaches. Thorough understanding of resistance mechanism and innovation in new drugs and vaccines is the need. A multidisciplinary, collaborative, regulatory approach is demanded for combating antimicrobial resistance. PMID:25177596

  20. Chemotherapy

    MedlinePlus

    ... or get an injection (shot). Another way of giving chemo is through an IV line, which is ... eating, after using the bathroom, and after touching animals. This helps to prevent infection. Do not share ...

  1. Chemotherapy

    MedlinePlus

    ... En Español Making a Change – Your Personal Plan Hot Topics Meningitis Choosing Your Mood Prescription Drug Abuse ... temperature beverages may be easier to drink than hot or cold liquids. Get on a medication schedule. ...

  2. Chemotherapy

    MedlinePlus

    ... Brain Tumor Treatment Locations Treatment Side Effects & their Management Support and Resources Caregiver Resource Center Pediatric Caregiver Resource Center About Us Our Founders Board of Directors Staff Leadership Strategic Plan Financials News Careers Brain Tumor Information ...

  3. [Infection control in neutropenia induced by high-dose cytarabine chemotherapy].

    PubMed

    Miyazaki, Masayuki; Senzaki, Kouji; Kiyoi, Hitoshi; Kohno, Shigekatu; Noda, Yukihiro; Nabeshima, Toshitaka

    2004-11-01

    A high-dose cytarabine (Cylocide; Ara-C: HDAC) chemotherapy has been successfully used as a postremission consolidation therapy for acute myeloid leukemia (AML). Although this chemotherapy has been estimated to cause severe myelosuppression, there has been no report about infection risk relating to HDAC chemotherapy. The purpose of this retrospective study is to evaluate the infection risk in AML patients treated with HDAC (n = 18) compared to those treated with standard-dose Ara-C (SDAC, n = 18). The mean duration of severe neutropenia (neutrophils < 500/microl) in HDAC group and SDAC was 14.8 days and 10.4 days, respectively, indicating a significant prolongation in the HDAC group (p < 0.05). The frequency of febrile neutropenia in the HDAC group tended to increase compared to that in the SDAC group (p = 0.093). The average days of usage of quinolone antimicrobial prophylaxis and aminoglycoside antibiotic injection in febrile neutropenia in the HDAC group were significantly longer than those of the SDAC group (quinolone; p < 0.01, aminoglycoside; p < 0.05). The frequency of Streptococcus infection isolated from pharyngeal mucus in the HDAC group was significantly higher than that in the SDAC group (100% versus 75%; p < 0.05). These results suggest that HDAC chemotherapy increased the infection risk compared to SDAC, and especially patients who received HDAC need a further prevention plan against gram-positive bacteria.

  4. Chemotherapy-induced peripheral neuropathy.

    PubMed

    Fehrenbacher, Jill C

    2015-01-01

    Chemotherapy-induced peripheral neuropathy (CIPN) is common in patients receiving anticancer treatment and can affect survivability and long-term quality of life of the patient following treatment. The symptoms of CIPN primarily include abnormal sensory discrimination of touch, vibration, thermal information, and pain. There is currently a paucity of pharmacological agents to prevent or treat CIPN. The lack of efficacious therapeutics is due, at least in part, to an incomplete understanding of the mechanisms by which chemotherapies alter the sensitivity of sensory neurons. Although the clinical presentation of CIPN can be similar with the various classes of chemotherapeutic agents, there are subtle differences, suggesting that each class of drugs might induce neuropathy via different mechanisms. Multiple mechanisms have been proposed to underlie the development and maintenance of neuropathy; however, most pharmacological agents generated from preclinical experiments have failed to alleviate the symptoms of CIPN in the clinic. Further research is necessary to identify the specific mechanisms by which each class of chemotherapeutics induces neuropathy.

  5. Chemotherapy for intraperitoneal use: a review of hyperthermic intraperitoneal chemotherapy and early post-operative intraperitoneal chemotherapy

    PubMed Central

    McPartland, Sarah; Detelich, Danielle; Saif, Muhammad Wasif

    2016-01-01

    Peritoneal spread of tumors is a major problem in cancer management. Patients develop a marked deterioration in quality of life and shortened survival. This is in part due to bowel obstructions, marked ascites, and overall increase debilitation. Standard medical management has shown to be inadequate for the treatment of these problems. Surgery can palliate symptoms, however, it is unable to be complete at the microscopic level by a significant spillage of tumor cells throughout the abdomen. Chemotherapy can have some improvement in symptoms however it is short lived due to poor penetration into the peritoneal cavity. The role of intraperitoneal chemotherapy is to maximize tumor penetration and optimize cell death while minimizing systemic toxicity. Hyperthermic intraperitoneal chemotherapy (HIPEC) and early post-operative intraperitoneal chemotherapy (EPIC) are two treatment methods that serve this role and have been shown to improve survival. This review will discuss different chemotherapies used for both of these treatment options. PMID:26941983

  6. Carboranyl-Chlorin e6 as a Potent Antimicrobial Photosensitizer.

    PubMed

    Omarova, Elena O; Nazarov, Pavel A; Firsov, Alexander M; Strakhovskaya, Marina G; Arkhipova, Anastasia Yu; Moisenovich, Mikhail M; Agapov, Igor I; Ol'shevskaya, Valentina A; Zaitsev, Andrey V; Kalinin, Valery N; Kotova, Elena A; Antonenko, Yuri N

    2015-01-01

    Antimicrobial photodynamic inactivation is currently being widely considered as alternative to antibiotic chemotherapy of infective diseases, attracting much attention to design of novel effective photosensitizers. Carboranyl-chlorin-e6 (the conjugate of chlorin e6 with carborane), applied here for the first time for antimicrobial photodynamic inactivation, appeared to be much stronger than chlorin e6 against Gram-positive bacteria, such as Bacillus subtilis, Staphyllococcus aureus and Mycobacterium sp. Confocal fluorescence spectroscopy and membrane leakage experiments indicated that bacteria cell death upon photodynamic treatment with carboranyl-chlorin-e6 is caused by loss of cell membrane integrity. The enhanced photobactericidal activity was attributed to the increased accumulation of the conjugate by bacterial cells, as evaluated both by centrifugation and fluorescence correlation spectroscopy. Gram-negative bacteria were rather resistant to antimicrobial photodynamic inactivation mediated by carboranyl-chlorin-e6. Unlike chlorin e6, the conjugate showed higher (compared to the wild-type strain) dark toxicity with Escherichia coli ΔtolC mutant, deficient in TolC-requiring multidrug efflux transporters. PMID:26535905

  7. Carboranyl-Chlorin e6 as a Potent Antimicrobial Photosensitizer

    PubMed Central

    Omarova, Elena O.; Nazarov, Pavel A.; Firsov, Alexander M.; Strakhovskaya, Marina G.; Arkhipova, Anastasia Yu.; Moisenovich, Mikhail M.; Agapov, Igor I.; Ol’shevskaya, Valentina A.; Zaitsev, Andrey V.; Kalinin, Valery N.; Kotova, Elena A.; Antonenko, Yuri N.

    2015-01-01

    Antimicrobial photodynamic inactivation is currently being widely considered as alternative to antibiotic chemotherapy of infective diseases, attracting much attention to design of novel effective photosensitizers. Carboranyl-chlorin-e6 (the conjugate of chlorin e6 with carborane), applied here for the first time for antimicrobial photodynamic inactivation, appeared to be much stronger than chlorin e6 against Gram-positive bacteria, such as Bacillus subtilis, Staphyllococcus aureus and Mycobacterium sp. Confocal fluorescence spectroscopy and membrane leakage experiments indicated that bacteria cell death upon photodynamic treatment with carboranyl-chlorin-e6 is caused by loss of cell membrane integrity. The enhanced photobactericidal activity was attributed to the increased accumulation of the conjugate by bacterial cells, as evaluated both by centrifugation and fluorescence correlation spectroscopy. Gram-negative bacteria were rather resistant to antimicrobial photodynamic inactivation mediated by carboranyl-chlorin-e6. Unlike chlorin e6, the conjugate showed higher (compared to the wild-type strain) dark toxicity with Escherichia coli ΔtolC mutant, deficient in TolC-requiring multidrug efflux transporters. PMID:26535905

  8. Managing Chemotherapy Side Effects: Hair Loss (Alopecia)

    MedlinePlus

    ... C ancer I nstitute Managing Chemotherapy Side Effects Hair Loss (Alopecia) “Losing my hair was hard at first. Then I got used ... uncovered.” Questions other people have asked: Why does hair fall out? Chemotherapy can harm the cells that ...

  9. Engineering Antimicrobials Refractory to Resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Multi-drug resistant superbugs are a persistent problem in modern health care, demonstrating the need for a new class of antimicrobials that can address this concern. Triple-acting peptidoglycan hydrolase fusions are a novel class of antimicrobials which have qualities well suited to avoiding resis...

  10. Antimicrobial stewardship: philosophy versus practice.

    PubMed

    Dodds Ashley, Elizabeth S; Kaye, Keith S; DePestel, Daryl D; Hermsen, Elizabeth D

    2014-10-15

    To promote the judicious use of antimicrobials and preserve their usefulness in the setting of growing resistance, a number of policy-making bodies and professional societies have advocated the development of antimicrobial stewardship programs. Although these programs have been implemented at many institutions in the United States, their impact has been difficult to measure. Current recommendations advocate the use of both outcome and process measures as metrics for antimicrobial stewardship. Although patient outcome metrics have the greatest impact on the quality of care, the literature shows that antimicrobial use and costs are the indicators measured most frequently by institutions to justify the effectiveness of antimicrobial stewardship programs. The measurement of more meaningful outcomes has been constrained by difficulties inherent to these measures, lack of funding and resources, and inadequate study designs. Antimicrobial stewardship can be made more credible by refocusing the antimicrobial review process to target specific disease states, reassessing the usefulness of current metrics, and integrating antimicrobial stewardship program initiatives into institutional quality and safety efforts.

  11. Improving Systemic Chemotherapy for Bladder Cancer.

    PubMed

    Rose, Tracy L; Milowsky, Matthew I

    2016-05-01

    Systemic chemotherapy is integral to the management of muscle-invasive and metastatic bladder cancer (BCa). Neoadjuvant chemotherapy has been increasingly utilized for muscle-invasive BCa over the past several years, and several options for cisplatin-based regimens have emerged. Adjuvant chemotherapy may be considered for select patients who did not receive neoadjuvant therapy. Systemic chemotherapy added to radiotherapy is a critical component of a bladder-preserving approach and superior to radiotherapy alone. Cisplatin-based chemotherapy has been the mainstay for metastatic BCa for more than three decades. Novel targeted agents are in development fueled by the recent molecular characterization of BCa. Recent trials of immunotherapy have demonstrated the possibility of a less toxic and potentially more effective treatment for metastatic disease. It is an extremely exciting time for BCa research, and much needed improvements in systemic treatment are most certainly on the horizon. PMID:26984414

  12. How to fight antimicrobial resistance.

    PubMed

    Foucault, Cédric; Brouqui, Philippe

    2007-03-01

    Antimicrobial misuse results in the development of resistance and superbugs. Over recent decades, resistance has been increasing despite continuing efforts to control it, resulting in increased mortality and cost. Many authorities have proposed local, regional and national guidelines to fight against this phenomenon, and the usefulness of these programmes has been evaluated. Multifaceted intervention seems to be the most efficient method to control antimicrobial resistance. Monitoring of bacterial resistance and antibiotic use is essential, and the methodology has now been homogenized. The implementation of guidelines and infection control measures does not control antimicrobial resistance and needs to be reinforced by associated measures. Educational programmes and rotation policies have not been evaluated sufficiently in the literature. Combination antimicrobial therapy is inefficient in controlling antimicrobial resistance.

  13. Chemotherapy plus interferon-alpha2b versus chemotherapy in the treatment of follicular lymphoma.

    PubMed

    Neri, N; Avilés, A; Cleto, S; Díaz, N; Talavera, A; García, E L; Díaz-Maqueo, J C

    2001-10-01

    The best treatment of follicular lymphoma remains to be determined because the long natural history of follicular lymphoma requires mature data for accurate analysis. Although the goal of primary treatment remains durable remission, the sequential application of effective treatments may also result in a prolongation of median survival time. The use of interferon (IFN) with doxorubicin-based chemotherapy has demonstrated an increase of event-free survival but not in overall survival; however, its acute and late cardiac toxicity limits its use. For this reason, we began a controlled clinical trial to assess the efficacy and toxicity of chemotherapy: COPP (cyclophosphamide, vincristine, prednisone, and procarbazine) + IFN alternating every month for six cycles compared to six cycles of chemotherapy. In an intent-to treat analysis, 55 patients were enrolled (median age 61 years). Most cases (91%) with advanced disease were randomly assigned to chemotherapy + IFN (28 cases) or chemotherapy (27 cases). Complete remission was observed in 16 patients: 59% (95% CI, 53-70%) in the chemotherapy arm compared to 20 patients 71% (95% CI, 58-79%) in the chemotherapy + IFN arm; total responses were 74% and 86%, respectively. At a median follow-up of 60 months, event-free survival was 100% for patients treated with chemotherapy + IFN, which was statistically different from patients treated with chemotherapy 70%. At 7 years, median survival has not yet been reached; 72% of patients chemotherapy + IFN remain alive without disease (95% CI, 59-81%), which is not statistically different from 72% (95%CI, 50-73%) in the chemotherapy arm. Non-hematological toxicity was most frequent and severe in the chemotherapy arm; hematological toxicity was similar in both groups. Thus, it appears that chemotherapy + IFN, as described herein, improves event-free survival but the overall survival rates remain unchanged. The use of COPP appears to be better that anthracycline-based chemotherapy because

  14. Modification of chemotherapy by nitroimidazoles

    SciTech Connect

    Siemann, D.W.

    1984-09-01

    The potentiation of chemotherapeutic agents by radiation sensitizers has been extensively studied for several years. There is little doubt that the effectiveness of certain anti-cancer drugs, primarily alkylating agents, can readily be enhanced both in vitro and in vivo through the addition of a sensitizer. While enhanced effects have been observed in certain critical normal tissues, in general most animal model studies have demonstrated a therapeutic gain at large sensitizer doses. This approach to combination therapies therefore appears promising. Yet many questions concerning the interaction between chemotherapeutic agents and radiosensitizers, particularly in the aspects of modification of chemotherapy by nitroimidazoles are reviewed and discussed. These address the importance in chemopotentiation of (i) hypoxia, (ii) alterations in DNA damage and/or repair, (iii) depletion of intracellular sulfhydryls and (iv) modification of drug pharmacokinetics.

  15. Trace Elements and Chemotherapy Sensitivity.

    PubMed

    Liu, Zhihui; Yang, Weiping; Long, Gang; Wei, Changyuan

    2016-10-01

    Trace elements might be associated with the development of hepatocellular carcinoma (HCC) and the efficacy of chemotherapy against HCC. Therefore, this study aimed to explore the association between trace elements and efficacy of chemotherapy in patients with HCC. Cancer, cancer-adjacent, and cancer-free tissues were collected intraoperatively from 55 patients with HCC between January 2001 and April 2004 at the Affiliated Tumor Hospital of Guangxi Medical University in Guangxi (China), a high HCC incidence area in the world. Trace element levels were analyzed by atomic absorption spectrophotometry. In vitro sensitivity of cancer cells to five chemotherapeutic drugs (5-fluorouracil, doxorubicin, cisplatin, carboplatin, and mitomycin) was tested using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in cancer cells from 32 patients. Zinc, copper, manganese, and selenium levels had the same gradient distribution in different liver tissues: cancer < cancer-adjacent < cancer-free tissues. Copper levels of cancer tissues were negatively correlated with body weight (r = -0.278, P = 0.027), while manganese and selenium levels were negatively correlated with age (r = -0.297, P = 0.015; r = -0.285, P = 0.018, respectively). Simple correlation analyses revealed that the carboplatin sensitivity was negatively correlated with selenium levels of cancer tissues, while doxorubicin sensitivity was negatively correlated with manganese levels (r = -0.497, P = 0.004). Partial correlation analyses showed that doxorubicin sensitivity only was negatively correlated with manganese levels (r = -0.450, P = 0.014). These results suggest that the selenium and manganese content in primary HCC tissues could influence the response of the HCC cells to carboplatin and doxorubicin. These preliminary results provide a basis for future studies. PMID:26961293

  16. Antimicrobial resistance in Canada

    PubMed Central

    Conly, John

    2002-01-01

    Antibiotic resistance has increased rapidly during the last decade, creating a serious threat to the treatment of infectious diseases. Canada is no exception to this worldwide phenomenon. Data from the Canadian Nosocomial Infection Surveillance Program have revealed that the incidence of methicillin-resistant Staphylococcus aureus, as a proportion of S. aureus isolates, increased from 1% in 1995 to 8% by the end of 2000, and vancomycin-resistant enterococcus has been documented in all 10 provinces since the first reported outbreak in 1995. The prevalence of nonsusceptible Streptococcus pneumoniae in Canada in 2000 was found to be 12%. Human antimicrobial prescriptions, adjusted for differences in the population, declined 11% based on the total number of prescriptions dispensed between 1995 and 2000. There was also a 21% decrease in β-lactam prescriptions during this same period. These data suggest that systematic efforts to reduce unnecessary prescribing of antimicrobials to outpatients in Canada, beginning after a national consensus conference in 1997, may be having an impact. There is, however, still a need for continued concerted efforts on a national, provincial and regional level to quell the rising tide of antibiotic resistance. PMID:12406948

  17. The Relationship between Antimicrobial Use and Antimicrobial Resistance in Europe

    PubMed Central

    Cars, Otto; Buchholz, Udo; Mölstad, Sigvard; Goettsch, Wim; Veldhuijzen, Irene K.; Kool, Jacob L.; Sprenger, Marc J.W.; Degener, John E.

    2002-01-01

    In Europe, antimicrobial resistance has been monitored since 1998 by the European Antimicrobial Resistance Surveillance System (EARSS). We examined the relationship between penicillin nonsusceptibility of invasive isolates of Streptococcus pneumoniae (an indicator organism) and antibiotic sales. Information was collected on 1998-99 resistance data for invasive isolates of S. pneumoniae to penicillin, based on surveillance data from EARSS and on outpatient sales during 1997 for beta-lactam antibiotics and macrolides. Our results show that in Europe antimicrobial resistance is correlated with use of beta-lactam antibiotics and macrolides. PMID:11927025

  18. Administration of chemotherapy in patients on dialysis.

    PubMed

    Kuo, James C; Craft, Paul S

    2015-08-01

    The prevalence of patients on dialysis has increased and these patients present a challenge for chemotherapy administration when diagnosed with cancer. A consensus on the dosage and timing of different chemotherapeutic agents in relation to dialysis has not been established. We describe the pattern of care and treatment outcome for cancer patients on dialysis in our institution. The dataset from the Australia and New Zealand Dialysis and Transplant Registry of patients on dialysis who had a diagnosis of cancer was obtained and matched to the pharmacy records in our institution to identify patients who had received chemotherapy while on dialysis. Relevant clinical information including details of the dialysis regimen, chemotherapy administration and adverse events was extracted for analysis. Between July 1999 and July 2014, 21 patients on dialysis were included for analysis. Five (23.8%) received chemotherapy, most of which was administered before dialysis sessions. As a result of adverse events, one patient discontinued treatment; two other patients required dose reduction or treatment delay. Chemotherapy administration was feasible in cancer patients on dialysis, but chemotherapy usage was low. Better understanding of the altered pharmacokinetics in patients on dialysis may improve chemotherapy access and practice.

  19. Comparison of bevacizumab plus chemotherapy with chemotherapy alone in advanced non-small-lung cancer patients.

    PubMed

    Tang, Ning; Wang, Zhehai

    2016-01-01

    Bevacizumab plus chemotherapy was approved by the US Food and Drug Administration (FDA) as a first-line treatment for advanced nonsquamous, non-small-cell lung cancer (NSCLC) in 2006. This study retrospectively compared the efficacy of bevacizumab plus chemotherapy with chemotherapy alone as the first-line and second-line treatment as well as the maintenance treatment for advanced NSCLC patients. A total of 1,352 patients were included and we analyzed the efficacy evaluation according to the criteria of the Response Evaluation Criteria In Solid Tumors (RECIST), survival, and adverse reactions. The data showed that for bevacizumab plus chemotherapy as the first-line treatment, the median progression-free survival (mPFS) and median overall survival (mOS) were 11.5 and 17.0 months, respectively, compared to 7.0 and 14 months, respectively, in patients who received chemotherapy alone (P<0.01). With bevacizumab plus chemotherapy as maintenance treatment, the mPFS and mOS were 6.0 and 17.4 months, respectively, compared to 3.0 and 15.0 months, respectively, with chemotherapy alone (P<0.01). With bevacizumab plus chemotherapy as the second-line treatment, the mPFS was 3.0 months compared to only 2.0 months with chemotherapy alone (P<0.01). The overall responses to the different regimens showed that the remission rate with bevacizumab plus chemotherapy was higher than that with chemotherapy alone (31.8% vs 25.5%, P<0.05), although there was no statistical difference in the disease control rate with either first- or second-line treatment. In conclusion, chemotherapy plus bevacizumab as the first-line and maintenance treatment, led to better curative rates and tolerable adverse reactions compared with chemotherapy alone in advanced NSCLC patients. Bevacizumab combined with cytotoxic drugs was suitable as the second-line treatment for such patients.

  20. Comparison of bevacizumab plus chemotherapy with chemotherapy alone in advanced non-small-lung cancer patients.

    PubMed

    Tang, Ning; Wang, Zhehai

    2016-01-01

    Bevacizumab plus chemotherapy was approved by the US Food and Drug Administration (FDA) as a first-line treatment for advanced nonsquamous, non-small-cell lung cancer (NSCLC) in 2006. This study retrospectively compared the efficacy of bevacizumab plus chemotherapy with chemotherapy alone as the first-line and second-line treatment as well as the maintenance treatment for advanced NSCLC patients. A total of 1,352 patients were included and we analyzed the efficacy evaluation according to the criteria of the Response Evaluation Criteria In Solid Tumors (RECIST), survival, and adverse reactions. The data showed that for bevacizumab plus chemotherapy as the first-line treatment, the median progression-free survival (mPFS) and median overall survival (mOS) were 11.5 and 17.0 months, respectively, compared to 7.0 and 14 months, respectively, in patients who received chemotherapy alone (P<0.01). With bevacizumab plus chemotherapy as maintenance treatment, the mPFS and mOS were 6.0 and 17.4 months, respectively, compared to 3.0 and 15.0 months, respectively, with chemotherapy alone (P<0.01). With bevacizumab plus chemotherapy as the second-line treatment, the mPFS was 3.0 months compared to only 2.0 months with chemotherapy alone (P<0.01). The overall responses to the different regimens showed that the remission rate with bevacizumab plus chemotherapy was higher than that with chemotherapy alone (31.8% vs 25.5%, P<0.05), although there was no statistical difference in the disease control rate with either first- or second-line treatment. In conclusion, chemotherapy plus bevacizumab as the first-line and maintenance treatment, led to better curative rates and tolerable adverse reactions compared with chemotherapy alone in advanced NSCLC patients. Bevacizumab combined with cytotoxic drugs was suitable as the second-line treatment for such patients. PMID:27536131

  1. Comparison of bevacizumab plus chemotherapy with chemotherapy alone in advanced non-small-lung cancer patients

    PubMed Central

    Tang, Ning; Wang, Zhehai

    2016-01-01

    Bevacizumab plus chemotherapy was approved by the US Food and Drug Administration (FDA) as a first-line treatment for advanced nonsquamous, non-small-cell lung cancer (NSCLC) in 2006. This study retrospectively compared the efficacy of bevacizumab plus chemotherapy with chemotherapy alone as the first-line and second-line treatment as well as the maintenance treatment for advanced NSCLC patients. A total of 1,352 patients were included and we analyzed the efficacy evaluation according to the criteria of the Response Evaluation Criteria In Solid Tumors (RECIST), survival, and adverse reactions. The data showed that for bevacizumab plus chemotherapy as the first-line treatment, the median progression-free survival (mPFS) and median overall survival (mOS) were 11.5 and 17.0 months, respectively, compared to 7.0 and 14 months, respectively, in patients who received chemotherapy alone (P<0.01). With bevacizumab plus chemotherapy as maintenance treatment, the mPFS and mOS were 6.0 and 17.4 months, respectively, compared to 3.0 and 15.0 months, respectively, with chemotherapy alone (P<0.01). With bevacizumab plus chemotherapy as the second-line treatment, the mPFS was 3.0 months compared to only 2.0 months with chemotherapy alone (P<0.01). The overall responses to the different regimens showed that the remission rate with bevacizumab plus chemotherapy was higher than that with chemotherapy alone (31.8% vs 25.5%, P<0.05), although there was no statistical difference in the disease control rate with either first- or second-line treatment. In conclusion, chemotherapy plus bevacizumab as the first-line and maintenance treatment, led to better curative rates and tolerable adverse reactions compared with chemotherapy alone in advanced NSCLC patients. Bevacizumab combined with cytotoxic drugs was suitable as the second-line treatment for such patients. PMID:27536131

  2. Virtual Reality: A Distraction Intervention for Chemotherapy

    PubMed Central

    Schneider, Susan M.; Hood, Linda E.

    2007-01-01

    Purpose/Objectives To explore virtual reality (VR) as a distraction intervention to relieve symptom distress in adults receiving chemotherapy treatments for breast, colon, and lung cancer. Design Crossover design in which participants served as their own control. Setting Outpatient clinic at a comprehensive cancer center in the southeastern United States. Sample 123 adults receiving initial chemotherapy treatments. Methods Participants were randomly assigned to receive the VR distraction intervention during one chemotherapy treatment and then received no intervention (control) during an alternate matched chemotherapy treatment. The Adapted Symptom Distress Scale–2, Revised Piper Fatigue Scale, and State Anxiety Inventory were used to measure symptom distress. The Presence Questionnaire and an open-ended questionnaire were used to evaluate the subjects’ VR experience. The influence of type of cancer, age, and gender on symptom outcomes was explored. Mixed models were used to test for differences in levels of symptom distress. Main Research Variables Virtual reality and symptom distress. Findings Patients had an altered perception of time (p < 0.001) when using VR, which validates the distracting capacity of the intervention. Evaluation of the intervention indicated that patients believed the head-mounted device was easy to use, they experienced no cybersickness, and 82% would use VR again. However, analysis demonstrated no significant differences in symptom distress immediately or two days following chemotherapy treatments. Conclusions Patients stated that using VR made the treatment seem shorter and that chemotherapy treatments with VR were better than treatments without the distraction intervention. However, positive experiences did not result in a decrease in symptom distress. The findings support the idea that using VR can help to make chemotherapy treatments more tolerable, but clinicians should not assume that use of VR will improve chemotherapy

  3. Prevention of chemotherapy-induced ovarian damage.

    PubMed

    Roness, Hadassa; Kashi, Oren; Meirow, Dror

    2016-01-01

    Recent advances in our understanding of the mechanisms underlying the impact of cytotoxic drugs on the ovary have opened up new directions for the protection of the ovary from chemotherapy-induced damage. These advances have spurred the investigation of pharmacological agents to prevent ovarian damage at the time of treatment. Prevention of ovarian damage and follicle loss would provide significant advantages over existing fertility preservation techniques. This manuscript reviews new methods for the prevention of chemotherapy-induced ovarian damage, including agents that act on the PI3K/PTEN/Akt follicle activation pathway, apoptotic pathways, the vascular system, and other potential methods of reducing chemotherapy-induced ovotoxicity.

  4. Overview, prevention and management of chemotherapy extravasation

    PubMed Central

    Kreidieh, Firas Y; Moukadem, Hiba A; El Saghir, Nagi S

    2016-01-01

    Chemotherapy extravasation remains an accidental complication of chemotherapy administration and may result in serious damage to patients. We review in this article the clinical aspects of chemotherapy extravasation and latest advances in definitions, classification, prevention, management and guidelines. We review the grading of extravasation and tissue damage according to various chemotherapeutic drugs and present an update on treatment and new antidotes including dexrazoxane for anthracyclines extravasation. We highlight the importance of education and training of the oncology team for prevention and prompt pharmacological and non-pharmacological management and stress the availability of new antidotes like dexrazoxane wherever anthracyclines are being infused. PMID:26862492

  5. Safe chemotherapy in the home environment.

    PubMed

    Chavis-Parker, Paula

    2015-05-01

    The Oncology Nursing Society and the American Society of Clinical Oncology have established guidelines for the safe and effective use of chemotherapeutic medications in the acute and outpatient care settings. A review of literature was performed to determine the safe and effective administration of chemotherapy in the home environment. The administration of oral and intravenous chemotherapy in the home has become a common intervention for patients being treated for cancer based on patient preference, cost-effectiveness of healthcare delivery, and increasing demand for oncology services. Home healthcare nurses can greatly impact the management of adverse effects of chemotherapy in the home, increasing the quality of life and improving patient outcomes.

  6. [Antimicrobial susceptibility in Chile 2012].

    PubMed

    Cifuentes-D, Marcela; Silva, Francisco; García, Patricia; Bello, Helia; Briceño, Isabel; Calvo-A, Mario; Labarca, Jaime

    2014-04-01

    Bacteria antimicrobial resistance is an uncontrolled public health problem that progressively increases its magnitude and complexity. The Grupo Colaborativo de Resistencia, formed by a join of experts that represent 39 Chilean health institutions has been concerned with bacteria antimicrobial susceptibility in our country since 2008. In this document we present in vitro bacterial susceptibility accumulated during year 2012 belonging to 28 national health institutions that represent about 36% of hospital discharges in Chile. We consider of major importance to report periodically bacteria susceptibility so to keep the medical community updated to achieve target the empirical antimicrobial therapies and the control measures and prevention of the dissemination of multiresistant strains.

  7. Antimicrobial properties of hemoglobin.

    PubMed

    Sheshadri, Preethi; Abraham, Jayanthi

    2012-12-01

    Hemoglobin consists of a heme containing component and a globin unit. It exists as a tetramer with 2 α subunits and 2 β subunits in adults and with 2 α subunits and 2 γ chains in infants. On proteolytic cleavage, hemoglobin breaks down to produce many biologically active compounds, among which are hemocidins, those which exhibit antimicrobial property. The generation of these peptides does not depend on the blood group, Rhesus factor, age and sex of the healthy donors. The microbicidal activity has been observed against a variety of gram positive and Gram-negative bacteria, and against filamentous fungi, yeast and even certain parasites. The discovery of hemocidins opens a new field for research into the details of the peptides acting as second line of defence in boosting the innate immune system of the organisms.

  8. Native Brazilian plants against nosocomial infections: a critical review on their potential and the antimicrobial methodology.

    PubMed

    H Moreno, Paulo Roberto; da Costa-Issa, Fabiana Inácio; Rajca-Ferreira, Agnieszka K; Pereira, Marcos A A; Kaneko, Telma M

    2013-01-01

    The growing incidences of drug-resistant pathogens have increased the attention on several medicinal plants and their metabolites for antimicrobial properties. These pathogens are the main cause of nosocomial infections which led to an increasing mortality among hospitalized patients. Taking into consideration those factors, this paper reviews the state-of-the-art of the research on antibacterial agents from native Brazilian plant species related to nosocomial infections as well as the current methods used in the investigations of the antimicrobial activity and points out the differences in techniques employed by the authors. The antimicrobial assays most frequently used were broth microdilution, agar diffusion, agar dilution and bioautography. The broth microdilution method should be the method of choice for testing new antimicrobial agents from plant extracts or isolated compounds due to its advantages. At the moment, only a small part of the rich Brazilian flora has been investigated for antimicrobial activity, mostly with unfractionated extracts presenting a weak or moderate antibacterial activity. The combination of crude extract with conventional antibiotics represents a largely unexploited new form of chemotherapy with novel and multiple mechanisms of action that can overcome microbial resistance that needs to be further investigated. The antibacterial activity of essential oil vapours might also be an interesting alternative treatment of hospital environment due to their ability in preventing biofilm formation. However, in both alternatives more studies should be done on their mode of action and toxicological effects in order to optimize their use. PMID:24200361

  9. Chemotherapy for cholangiocarcinoma: An update.

    PubMed

    Ramírez-Merino, Natalia; Aix, Santiago Ponce; Cortés-Funes, Hernán

    2013-07-15

    Cholangiocarcinomas (bile duct cancers) are a heterogeneous group of malignancies arising from the epithelial cells of the intrahepatic, perihilar and extrahepatic bile ducts. Patients diagnosed with cholangiocarcinoma must be evaluated by a multidisciplinary team and be treated with individualized management. First of all, it is very important to define the potential resectability of the tumor because surgery is the main therapeutic option for these patients. Overall, cholangiocarcinomas have a very poor prognosis. The 5-year survival rate is 5%-10%. In cases with a potentially curative surgery, 5-year survival rates of 25%-30% are reported. Therefore, it is necessary to increase the cure rate from surgery, exploring the survival benefit of any adjuvant strategy. It is difficult to clarify the role of adjuvant treatment in localized and locally advanced cholangiocarcinomas. There are limited data and the role of adjuvant chemotherapy/chemoradiation in patients with resected biliary tract cancer is poorly defined. The most relevant studies in the adjuvant setting are one from Japan, the well known ESPAC-3 and BILCAP from the United Kingdom and a meta-analysis. We show the results of these trials. According to medical oncology guidelines, postoperative adjuvant therapy is widely recommended for all patients with intrahepatic or extrahepatic cholangiocarcinoma who have microscopically positive resection margins, as well as for those with a complete resection but node-positive disease. Clinical trials are ongoing. The locally advanced cholangiocarcinoma setting includes a heterogeneous mix of patients: (1) patients who have had surgery but with macroscopic residual disease; (2) patients with locally recurrent disease after potentially curative treatment; and (3) patients with locally unresectable disease at presentation. In these patients, surgery is not an option and chemoradiation therapy can prolong overall survival and provide control of symptoms due to local

  10. Chemotherapy for cholangiocarcinoma: An update

    PubMed Central

    Ramírez-Merino, Natalia; Aix, Santiago Ponce; Cortés-Funes, Hernán

    2013-01-01

    Cholangiocarcinomas (bile duct cancers) are a heterogeneous group of malignancies arising from the epithelial cells of the intrahepatic, perihilar and extrahepatic bile ducts. Patients diagnosed with cholangiocarcinoma must be evaluated by a multidisciplinary team and be treated with individualized management. First of all, it is very important to define the potential resectability of the tumor because surgery is the main therapeutic option for these patients. Overall, cholangiocarcinomas have a very poor prognosis. The 5-year survival rate is 5%-10%. In cases with a potentially curative surgery, 5-year survival rates of 25%-30% are reported. Therefore, it is necessary to increase the cure rate from surgery, exploring the survival benefit of any adjuvant strategy. It is difficult to clarify the role of adjuvant treatment in localized and locally advanced cholangiocarcinomas. There are limited data and the role of adjuvant chemotherapy/chemoradiation in patients with resected biliary tract cancer is poorly defined. The most relevant studies in the adjuvant setting are one from Japan, the well known ESPAC-3 and BILCAP from the United Kingdom and a meta-analysis. We show the results of these trials. According to medical oncology guidelines, postoperative adjuvant therapy is widely recommended for all patients with intrahepatic or extrahepatic cholangiocarcinoma who have microscopically positive resection margins, as well as for those with a complete resection but node-positive disease. Clinical trials are ongoing. The locally advanced cholangiocarcinoma setting includes a heterogeneous mix of patients: (1) patients who have had surgery but with macroscopic residual disease; (2) patients with locally recurrent disease after potentially curative treatment; and (3) patients with locally unresectable disease at presentation. In these patients, surgery is not an option and chemoradiation therapy can prolong overall survival and provide control of symptoms due to local

  11. Breast Cancer Chemotherapy and Your Heart

    MedlinePlus

    ... of the American Heart Association Cardiology Patient Page Breast Cancer Chemotherapy and Your Heart Christine Unitt , Kamaneh Montazeri , ... Disclosures Footnotes Figures & Tables Info & Metrics eLetters Introduction Breast cancer is the most commonly diagnosed cancer in women. ...

  12. Novel Combination Chemotherapy for Localized Ewing Sarcoma

    Cancer.gov

    In this clinical trial, researchers will test whether the addition of the drug combination vincristine, topotecan, and cyclophosphamide to a standard chemotherapy regimen improves overall survival in patients with extracranial Ewing

  13. Management of Chemotherapy Induced Nausea and Vomiting in Patients on Multiday Cisplatin Based Combination Chemotherapy.

    PubMed

    Ranganath, Praveen; Einhorn, Lawrence; Albany, Costantine

    2015-01-01

    Introduction of cisplatin based chemotherapy has revolutionized the treatment of germ cell tumors. A common side effect of multiday cisplatin chemotherapy is severe nausea and vomiting. Considerable progress has been made in the control of these side effects since the introduction of cisplatin based chemotherapy in the 1970s. Germ cell tumor which is a model for a curable neoplasm has also turned into an excellent testing ground to develop effective strategies to prevent chemotherapy induced nausea and vomiting (CINV) in multiday cisplatin based regimens. The use of combination of a 5-hydroxytryptamine (HT)3 receptor antagonist, a neurokinin-1 (NK1) antagonist, and dexamethasone has greatly improved our ability to prevent and control acute and delayed CINV. Mechanism and pattern of CINV with multiday chemotherapy may differ from those in single day chemotherapy and therefore efficacy of antiemetic drugs as observed in single day chemotherapy may not be applicable. There are only few randomized clinical trials with special emphasis on multiday chemotherapy. Further studies are essential to determine the efficacy, optimal dose, and duration of the newer agents and combinations in multiday cisplatin based chemotherapy. PMID:26425563

  14. Management of Chemotherapy Induced Nausea and Vomiting in Patients on Multiday Cisplatin Based Combination Chemotherapy

    PubMed Central

    Ranganath, Praveen; Einhorn, Lawrence; Albany, Costantine

    2015-01-01

    Introduction of cisplatin based chemotherapy has revolutionized the treatment of germ cell tumors. A common side effect of multiday cisplatin chemotherapy is severe nausea and vomiting. Considerable progress has been made in the control of these side effects since the introduction of cisplatin based chemotherapy in the 1970s. Germ cell tumor which is a model for a curable neoplasm has also turned into an excellent testing ground to develop effective strategies to prevent chemotherapy induced nausea and vomiting (CINV) in multiday cisplatin based regimens. The use of combination of a 5-hydroxytryptamine (HT)3 receptor antagonist, a neurokinin-1 (NK1) antagonist, and dexamethasone has greatly improved our ability to prevent and control acute and delayed CINV. Mechanism and pattern of CINV with multiday chemotherapy may differ from those in single day chemotherapy and therefore efficacy of antiemetic drugs as observed in single day chemotherapy may not be applicable. There are only few randomized clinical trials with special emphasis on multiday chemotherapy. Further studies are essential to determine the efficacy, optimal dose, and duration of the newer agents and combinations in multiday cisplatin based chemotherapy. PMID:26425563

  15. Antimicrobial seafood packaging: a review.

    PubMed

    Singh, Suman; Ho Lee, Myung; Park, Lnsik; Shin, Yangjai; Lee, Youn Suk

    2016-06-01

    Microorganisms are the major cause of spoilage in most seafood products; however, only few microbes, called the specific spoilage organisms (SSOs), contribute to the offensive off-flavors associated with seafood spoilage. In food, microbial degradation manifests itself as spoilage, or changes in the sensory properties of a food product, rendering it unsuitable for human consumption. The use of antimicrobial substances can control the general microflora as well as specific microorganisms related to spoilage to provide products with higher safety and better quality. Many antimicrobial compounds have been evaluated in film structures for use in seafood, especially organic acids and their salts, enzymes, bacteriocins; some studies have considered inorganic compounds such as AgSiO2, zinc oxide, silver zeolite, and titanium oxide. The characteristics of some organic antimicrobial packaging systems for seafood and their antimicrobial efficiency in film structures are reviewed in this article. PMID:27478206

  16. Prodrug strategies in anticancer chemotherapy.

    PubMed

    Kratz, Felix; Müller, Ivonne A; Ryppa, Claudia; Warnecke, André

    2008-01-01

    The majority of clinically approved anticancer drugs are characterized by a narrow therapeutic window that results mainly from a high systemic toxicity of the drugs in combination with an evident lack of tumor selectivity. Besides the development of suitable galenic formulations such as liposomes or micelles, several promising prodrug approaches have been followed in the last decades with the aim of improving chemotherapy. In this review we elucidate the two main concepts that underlie the design of most anticancer prodrugs: drug targeting and controlled release of the drug at the tumor site. Consequently, active and passive targeting using tumor-specific ligands or macromolecular carriers are discussed as well as release strategies that are based on tumor-specific characteristics such as low pH or the expression of tumor-associated enzymes. Furthermore, other strategies such as ADEPT (antibody-directed enzyme prodrug therapy) and the design of self-eliminating structures are introduced. Chemical realization of prodrug approaches is illustrated by drug candidates that have or may have clinical importance.

  17. Natural products for cancer chemotherapy

    PubMed Central

    Demain, Arnold L.; Vaishnav, Preeti

    2011-01-01

    Summary For over 40 years, natural products have served us well in combating cancer. The main sources of these successful compounds are microbes and plants from the terrestrial and marine environments. The microbes serve as a major source of natural products with anti‐tumour activity. A number of these products were first discovered as antibiotics. Another major contribution comes from plant alkaloids, taxoids and podophyllotoxins. A vast array of biological metabolites can be obtained from the marine world, which can be used for effective cancer treatment. The search for novel drugs is still a priority goal for cancer therapy, due to the rapid development of resistance to chemotherapeutic drugs. In addition, the high toxicity usually associated with some cancer chemotherapy drugs and their undesirable side‐effects increase the demand for novel anti‐tumour drugs active against untreatable tumours, with fewer side‐effects and/or with greater therapeutic efficiency. This review points out those technologies needed to produce the anti‐tumour compounds of the future. PMID:21375717

  18. Chemotherapy-induced Spontaneous Pneumothorax: Case Series.

    PubMed

    Hendarsih, Een; Fadjari, Trinugroho H; Oehadian, Amaylia

    2016-04-01

    We present 2 patients who developed spontaneous pneumothorax (SP) following rapid regression of lymphoma and rhabdomyosarcoma with lung metastases. Case 1, a 43-year old man was admitted to our hospital with dyspnea 10 days before admission. He denied any recent trauma or previous treatment for lung tuberculosis. Three weeks prior to admission, he received first cycle of CHOP for non-Hodgkin's lymphoma stage II BE. Chest X-ray consistent with right pneumothorax. After treatment with chest tube drainage for about 1 month, the patient recovered and chemotherapy could be continued without further complications. Case 2, a 35- year old man was admitted to other hospital with dyspnea and chest pain on day 4 after second cycle of systemic combined chemotherapy for rhabdomyosarcoma stage IV (lung metastases) with doxorubicin, ifosfamide, mesna, and dacarbazine. Chest X-ray showed hydropneumothorax on right and left lung. After treatment with chest tube drainage about 2 weeks, the patient recovered and chemotherapy could be continued without further complications. The mechanism of pneumothorax following chemotherapy is not clearly understood yet, however, several hypotheses have been considered: 1) the rupture of a subpleural bulla after chemotherapy; 2) the rupture of an emphysematous bulla in an over expanded portion of the lung which is partially obstructed by a neoplasm; 3) tumor lyses or necrosis due to cytotoxic chemotherapy directly induces the formation of fistula. Dyspnea and chest pain suddenly appear during successful chemotherapy for metastatic chemosensitive tumors should alert the physician to the possibility of SP. The treatment is directed toward lung re-expansion. Chemotherapy induced pneumothorax should be considered as oncologic emergency. PMID:27550883

  19. Mechanisms of chemotherapy-induced behavioral toxicities

    PubMed Central

    Vichaya, Elisabeth G.; Chiu, Gabriel S.; Krukowski, Karen; Lacourt, Tamara E.; Kavelaars, Annemieke; Dantzer, Robert; Heijnen, Cobi J.; Walker, Adam K.

    2015-01-01

    While chemotherapeutic agents have yielded relative success in the treatment of cancer, patients are often plagued with unwanted and even debilitating side-effects from the treatment which can lead to dose reduction or even cessation of treatment. Common side effects (symptoms) of chemotherapy include (i) cognitive deficiencies such as problems with attention, memory and executive functioning; (ii) fatigue and motivational deficit; and (iii) neuropathy. These symptoms often develop during treatment but can remain even after cessation of chemotherapy, severely impacting long-term quality of life. Little is known about the underlying mechanisms responsible for the development of these behavioral toxicities, however, neuroinflammation is widely considered to be one of the major mechanisms responsible for chemotherapy-induced symptoms. Here, we critically assess what is known in regards to the role of neuroinflammation in chemotherapy-induced symptoms. We also argue that, based on the available evidence, neuroinflammation is unlikely the only mechanism involved in the pathogenesis of chemotherapy-induced behavioral toxicities. We evaluate two other putative candidate mechanisms. To this end we discuss the mediating role of damage-associated molecular patterns (DAMPs) activated in response to chemotherapy-induced cellular damage. We also review the literature with respect to possible alternative mechanisms such as a chemotherapy-induced change in the bioenergetic status of the tissue involving changes in mitochondrial function in relation to chemotherapy-induced behavioral toxicities. Understanding the mechanisms that underlie the emergence of fatigue, neuropathy, and cognitive difficulties is vital to better treatment and long-term survival of cancer patients. PMID:25954147

  20. Antimicrobials for bacterial bioterrorism agents.

    PubMed

    Sarkar-Tyson, Mitali; Atkins, Helen S

    2011-06-01

    The limitations of current antimicrobials for highly virulent pathogens considered as potential bioterrorism agents drives the requirement for new antimicrobials that are suitable for use in populations in the event of a deliberate release. Strategies targeting bacterial virulence offer the potential for new countermeasures to combat bacterial bioterrorism agents, including those active against a broad spectrum of pathogens. Although early in the development of antivirulence approaches, inhibitors of bacterial type III secretion systems and cell division mechanisms show promise for the future.

  1. Economic impact of antimicrobial resistance.

    PubMed Central

    McGowan, J. E.

    2001-01-01

    One reason antimicrobial-drug resistance is of concern is its economic impact on physicians, patients, health-care administrators, pharmaceutical producers, and the public. Measurement of cost and economic impact of programs to minimize antimicrobial-drug resistance is imprecise and incomplete. Studies to describe and evaluate the problem will have to employ new methods and be of large scale to produce information that is broadly applicable. PMID:11294725

  2. Chemotherapy for Stage II Colon Cancer.

    PubMed

    Varghese, Anna

    2015-12-01

    The adjuvant treatment of patients with stage II colon cancer is an area of controversy in medical oncology. Adjuvant chemotherapy aims to eradicate micrometastatic disease present at the time of surgery, preventing the development of distant metastatic disease and thereby curing those patients of their cancer. National and international guidelines for the adjuvant treatment of stage II colon cancer recommend a range of treatment options from observation to chemotherapy with single-agent or combination regimens, depending on the presence or absence of high-risk features (poorly differentiated histology, presence of lymphovascular invasion, presence of perineural invasion, report of < 12 lymph nodes, bowel obstruction, localized perforation, or positive margins). In the one prospective study designed to address the role of adjuvant chemotherapy in stage II colon cancer, a small but statistically significant benefit in overall survival was seen for those patients who received adjuvant chemotherapy; however, multiple meta-analyses and retrospective subgroup analyses have called these findings into question. Though there may be a role for adjuvant chemotherapy in the treatment of patients with stage II colon cancer, its incremental benefit is small, at best, and comes with the risks of real and rarely fatal complications of chemotherapy. PMID:26648796

  3. Adjuvant chemotherapy in head and neck cancer.

    PubMed Central

    Stell, P. M.; Rawson, N. S.

    1990-01-01

    An overview is presented of 23 trials of adjuvant chemotherapy in squamous cell carcinoma of the head and neck. These were reviewed from the point of view of design of the trial, analysis of survival, response rates, meta-analysis, site of failure, toxicity and cost. The minimal increase in survival that could be detected ranged from 11 to 51%, with a median of 25%. No trial was big enough to detect the likely increase of survival, which is 5%. Many trials excluded some eligible patients before randomisation, the proportion being 21% in those series with details. A further 9% of treated patients were excluded from analysis. A response rate in four induction studies of 47% equated with a 6% increase in cancer mortality. Meta-analysis showed an insignificant overall improvement in cancer mortality of 0.5%. Induction chemotherapy, synchronous chemotherapy and induction/maintenance chemotherapy did not affect cancer mortality whereas synchronous/maintenance therapy did. Cisplatinum, methotrexate, bleomycin, 5-FU and a variety of other regimens did not affect the death rate from cancer, but the combination of VBM significantly increased it. Neither single agent nor combination chemotherapy produced a significant reduction of cancer deaths. The rate of locoregional failure was significantly lower in the treated arms, whereas the metastatic rate was similar in both arms. Only three papers gave full details of toxicity with grading: these showed a high toxicity rate. The mortality rate from chemotherapy in nine series averaged 6.5%. PMID:2140045

  4. [Chemotherapy selection through the process of gastric cancer].

    PubMed

    Liu, Tian-Shu

    2012-02-01

    The role of chemotherapy has become more and more important in the whole process of gastric cancer. S-1 or XELOX regimen is regarded as the standard treatment option in adjuvant chemotherapy. First-line chemotherapy in advanced gastric cancer has been established to improve survival, and the benefit from second-line chemotherapy is being acknowledged. More studies are needed to assess the neoadjuvant chemotherapy.

  5. Test-retest, retest, and retest: Growth curve models of repeat testing with Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT).

    PubMed

    Maerlender, Arthur C; Masterson, Caitlin J; James, Tiffany D; Beckwith, Jonathan; Brolinson, Per Gunner; Crisco, Joe; Duma, Stefan; Flashman, Laura A; Greenwald, Rick; Rowson, Steven; Wilcox, Beth; McAllister, Tom W

    2016-10-01

    Computerized neuropsychological testing has become an important tool in the identification and management of sports-related concussions; however, the psychometric effect of repeat testing has not been studied extensively beyond test-retest statistics. The current study analyzed data from Division I collegiate athletes who completed Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) baseline assessments at four sequential time points that varied over the course of their athletic careers. Administrations were part of a larger National Institutes of Health (NIH) study. Growth curve modeling showed that the two memory composite scores increased significantly with successive administrations: Change in Verbal Memory was best represented with a quadratic model, while a linear model best fit Visual Memory. Visual Motor Speed and Reaction Time composites showed no significant linear or quadratic growth. The results demonstrate the effect of repeated test administrations for memory composite scores, while speed composites were not significantly impacted by repeat testing. Acceptable test-retest reliability was demonstrated for all four composites as well.

  6. Test-retest, retest, and retest: Growth curve models of repeat testing with Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT).

    PubMed

    Maerlender, Arthur C; Masterson, Caitlin J; James, Tiffany D; Beckwith, Jonathan; Brolinson, Per Gunner; Crisco, Joe; Duma, Stefan; Flashman, Laura A; Greenwald, Rick; Rowson, Steven; Wilcox, Beth; McAllister, Tom W

    2016-10-01

    Computerized neuropsychological testing has become an important tool in the identification and management of sports-related concussions; however, the psychometric effect of repeat testing has not been studied extensively beyond test-retest statistics. The current study analyzed data from Division I collegiate athletes who completed Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) baseline assessments at four sequential time points that varied over the course of their athletic careers. Administrations were part of a larger National Institutes of Health (NIH) study. Growth curve modeling showed that the two memory composite scores increased significantly with successive administrations: Change in Verbal Memory was best represented with a quadratic model, while a linear model best fit Visual Memory. Visual Motor Speed and Reaction Time composites showed no significant linear or quadratic growth. The results demonstrate the effect of repeated test administrations for memory composite scores, while speed composites were not significantly impacted by repeat testing. Acceptable test-retest reliability was demonstrated for all four composites as well. PMID:27266563

  7. Estimating peak skin and eye lens dose from neuroperfusion examinations: Use of Monte Carlo based simulations and comparisons to CTDIvol, AAPM Report No. 111, and ImPACT dosimetry tool values

    PubMed Central

    Zhang, Di; Cagnon, Chris H.; Villablanca, J. Pablo; McCollough, Cynthia H.; Cody, Dianna D.; Zankl, Maria; Demarco, John J.; McNitt-Gray, Michael F.

    2013-01-01

    Purpose: CT neuroperfusion examinations are capable of delivering high radiation dose to the skin or lens of the eyes of a patient and can possibly cause deterministic radiation injury. The purpose of this study is to: (a) estimate peak skin dose and eye lens dose from CT neuroperfusion examinations based on several voxelized adult patient models of different head size and (b) investigate how well those doses can be approximated by some commonly used CT dose metrics or tools, such as CTDIvol, American Association of Physicists in Medicine (AAPM) Report No. 111 style peak dose measurements, and the ImPACT organ dose calculator spreadsheet. Methods: Monte Carlo simulation methods were used to estimate peak skin and eye lens dose on voxelized patient models, including GSF's Irene, Frank, Donna, and Golem, on four scanners from the major manufacturers at the widest collimation under all available tube potentials. Doses were reported on a per 100 mAs basis. CTDIvol measurements for a 16 cm CTDI phantom, AAPM Report No. 111 style peak dose measurements, and ImPACT calculations were performed for available scanners at all tube potentials. These were then compared with results from Monte Carlo simulations. Results: The dose variations across the different voxelized patient models were small. Dependent on the tube potential and scanner and patient model, CTDIvol values overestimated peak skin dose by 26%–65%, and overestimated eye lens dose by 33%–106%, when compared to Monte Carlo simulations. AAPM Report No. 111 style measurements were much closer to peak skin estimates ranging from a 14% underestimate to a 33% overestimate, and with eye lens dose estimates ranging from a 9% underestimate to a 66% overestimate. The ImPACT spreadsheet overestimated eye lens dose by 2%–82% relative to voxelized model simulations. Conclusions: CTDIvol consistently overestimates dose to eye lens and skin. The ImPACT tool also overestimated dose to eye lenses. As such they are still

  8. Outpatient parenteral antimicrobial therapy and antimicrobial stewardship: challenges and checklists.

    PubMed

    Gilchrist, M; Seaton, R A

    2015-04-01

    Outpatient parenteral antimicrobial therapy (OPAT) has become, for many countries, an established form of healthcare delivery. At the same time, there have been calls to ensure the prudent use of the existing antimicrobial armamentarium. For OPAT, this presents a dilemma. On one hand, stewardship principles look for the most effective agent with minimal collateral effects. In OPAT, whilst the aims of the service are similar, convenience of dosing to optimize early hospital discharge or admission avoidance may take precedence over an agent's spectrum of activity. This brief article aims to highlight the importance and explore the challenges of antimicrobial stewardship in the context of OPAT. Within the UK, the safe and effective use of antimicrobials is modelled around the IDSA/Society for Healthcare Epidemiology of America stewardship practice guidelines with local customization where appropriate. Current UK stewardship practice principles were compared with published good practice recommendations for OPAT to identify how OPAT could support the broader antimicrobial stewardship agenda. It is essential that antimicrobial stewardship teams should understand the challenges faced in the non-inpatient setting and the potential benefits/lower risks associated with avoided admission or shortened hospital stay in this population. Within its limitations, OPAT should practise stewardship principles, including optimization of intravenous to oral switch and the reporting of outcomes, healthcare-associated infections and re-admission rates. OPAT should report to the antimicrobial stewardship team. Ideally the OPAT team should be formally represented within the stewardship framework. A checklist has been proposed to aid OPAT services in ensuring they meet their stewardship agenda.

  9. Peptides and Peptidomimetics for Antimicrobial Drug Design

    PubMed Central

    Mojsoska, Biljana; Jenssen, Håvard

    2015-01-01

    The purpose of this paper is to introduce and highlight a few classes of traditional antimicrobial peptides with a focus on structure-activity relationship studies. After first dissecting the important physiochemical properties that influence the antimicrobial and toxic properties of antimicrobial peptides, the contributions of individual amino acids with respect to the peptides antibacterial properties are presented. A brief discussion of the mechanisms of action of different antimicrobials as well as the development of bacterial resistance towards antimicrobial peptides follows. Finally, current efforts on novel design strategies and peptidomimetics are introduced to illustrate the importance of antimicrobial peptide research in the development of future antibiotics. PMID:26184232

  10. Editorial of the Special Issue Antimicrobial Polymers

    PubMed Central

    Piozzi, Antonella; Francolini, Iolanda

    2013-01-01

    The special issue “Antimicrobial Polymers” includes research and review papers concerning the recent advances on preparation of antimicrobial polymers and their relevance to industrial settings and biomedical field. Antimicrobial polymers have recently emerged as promising candidates to fight microbial contamination onto surfaces thanks to their interesting properties. In this special issue, the main strategies pursued for developing antimicrobial polymers, including polymer impregnation with antimicrobial agents or synthesis of polymers bearing antimicrobial moieties, were discussed. The future application of these polymers either in industrial or healthcare settings could result in an extremely positive impact not only at the economic level but also for the improvement of quality of life. PMID:24005863

  11. Hospital antimicrobial stewardship in the nonuniversity setting.

    PubMed

    Trivedi, Kavita K; Kuper, Kristi

    2014-06-01

    Inappropriate antimicrobial use and antimicrobial resistance persist across the healthcare continuum. Antimicrobial stewardship guidelines assist healthcare institutions in establishing antimicrobial stewardship programs but rely on infectious diseases expertise and leadership, which are not available in all settings. Despite this, many institutions have found ways to use available resources to perform stewardship activities, with improvements in antimicrobial use and reductions in resistance and cost. This article highlights success stories in nonuniversity hospital settings and proposes antimicrobial stewardship strategies that may be more feasible in settings with limited infectious diseases expertise, information technology, or financial resources.

  12. Antimicrobial resistance in bacteria from horses: Epidemiology of antimicrobial resistance.

    PubMed

    Maddox, T W; Clegg, P D; Williams, N J; Pinchbeck, G L

    2015-11-01

    Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections. While the epidemiology of antimicrobial resistance in bacteria from man has been studied extensively, less work has been undertaken in companion animals, particularly horses. Methicillin-resistant Staphylococcus aureus has been identified as a cause of infections, with a low prevalence of nasal carriage by horses in the community but higher for hospitalised horses. Molecular characterisation has shown methicillin-resistant Staphylococcus aureus strains either to be predominantly of types associated with horses or of sequence type ST398. Antimicrobial-resistant Escherichia coli (including multidrug-resistant and extended spectrum β-lactamase-producing isolates) have caused infections and been documented in faecal carriage by horses, with many significant resistance mechanisms identified. More sporadic reports and molecular characterisation exist for resistance in other bacteria such as enterococci, Salmonella, Acinetobacter and Pseudomonas species. Limited work has been undertaken evaluating risk factors and much of the epidemiology of antimicrobial resistance in bacteria from horses remains to be determined.

  13. Antimicrobial action of sanguinarine.

    PubMed

    Godowski, K C

    1989-01-01

    Sanguinarine is a benzophenanthridine alkaloid derived from rhizomes of Sanguinaria canadensis L. (bloodroot). It is a cationic molecule which converts from an iminium ion form at pH less than 6 to an alkanolamine form at pH greater than 7. Sanguinaria extract is composed of sanguinarine and five other closely related alkaloids. The safety profile of both sanguinarine and sanguinaria extract provide a broad margin for their safe use in oral health products. Sanguinarine has broad antimicrobial activity as well as antiinflammatory properties. In vitro studies indicate that the anti-plaque action of sanguinaria is due to its ability to inhibit bacterial adherence to newly formed pellicle, its retention in plaque being 10-100 times its saliva concentration, and due to its antimicrobic properties. The MIC of sanguinarine ranges from 1 to 32 micrograms/mL for most species of plaque bacteria. Long term use of sanguinaria-containing toothpaste and oral rinse products does not predispose users to detrimental shifts in oral flora. Electron microscopic studies of bacteria exposed to sanguinarine demonstrate that bacteria aggregate and become morphologically irregular. Sanguinarine-containing slow release polymer systems are currently being developed for use in periodontitis treatment applications.

  14. Antimicrobial Peptides from Plants.

    PubMed

    Tam, James P; Wang, Shujing; Wong, Ka H; Tan, Wei Liang

    2015-01-01

    Plant antimicrobial peptides (AMPs) have evolved differently from AMPs from other life forms. They are generally rich in cysteine residues which form multiple disulfides. In turn, the disulfides cross-braced plant AMPs as cystine-rich peptides to confer them with extraordinary high chemical, thermal and proteolytic stability. The cystine-rich or commonly known as cysteine-rich peptides (CRPs) of plant AMPs are classified into families based on their sequence similarity, cysteine motifs that determine their distinctive disulfide bond patterns and tertiary structure fold. Cystine-rich plant AMP families include thionins, defensins, hevein-like peptides, knottin-type peptides (linear and cyclic), lipid transfer proteins, α-hairpinin and snakins family. In addition, there are AMPs which are rich in other amino acids. The ability of plant AMPs to organize into specific families with conserved structural folds that enable sequence variation of non-Cys residues encased in the same scaffold within a particular family to play multiple functions. Furthermore, the ability of plant AMPs to tolerate hypervariable sequences using a conserved scaffold provides diversity to recognize different targets by varying the sequence of the non-cysteine residues. These properties bode well for developing plant AMPs as potential therapeutics and for protection of crops through transgenic methods. This review provides an overview of the major families of plant AMPs, including their structures, functions, and putative mechanisms. PMID:26580629

  15. Antimicrobial Peptides from Plants

    PubMed Central

    Tam, James P.; Wang, Shujing; Wong, Ka H.; Tan, Wei Liang

    2015-01-01

    Plant antimicrobial peptides (AMPs) have evolved differently from AMPs from other life forms. They are generally rich in cysteine residues which form multiple disulfides. In turn, the disulfides cross-braced plant AMPs as cystine-rich peptides to confer them with extraordinary high chemical, thermal and proteolytic stability. The cystine-rich or commonly known as cysteine-rich peptides (CRPs) of plant AMPs are classified into families based on their sequence similarity, cysteine motifs that determine their distinctive disulfide bond patterns and tertiary structure fold. Cystine-rich plant AMP families include thionins, defensins, hevein-like peptides, knottin-type peptides (linear and cyclic), lipid transfer proteins, α-hairpinin and snakins family. In addition, there are AMPs which are rich in other amino acids. The ability of plant AMPs to organize into specific families with conserved structural folds that enable sequence variation of non-Cys residues encased in the same scaffold within a particular family to play multiple functions. Furthermore, the ability of plant AMPs to tolerate hypervariable sequences using a conserved scaffold provides diversity to recognize different targets by varying the sequence of the non-cysteine residues. These properties bode well for developing plant AMPs as potential therapeutics and for protection of crops through transgenic methods. This review provides an overview of the major families of plant AMPs, including their structures, functions, and putative mechanisms. PMID:26580629

  16. Chemotherapy, cognitive impairment and hippocampal toxicity.

    PubMed

    Dietrich, J; Prust, M; Kaiser, J

    2015-11-19

    Cancer therapies can be associated with significant central nervous system (CNS) toxicity. While radiation-induced brain damage has been long recognized both in pediatric and adult cancer patients, CNS toxicity from chemotherapy has only recently been acknowledged. Clinical studies suggest that the most frequent neurotoxic adverse effects associated with chemotherapy include memory and learning deficits, alterations of attention, concentration, processing speed and executive function. Preclinical studies have started to shed light on how chemotherapy targets the CNS both on cellular and molecular levels to disrupt neural function and brain plasticity. Potential mechanisms include direct cellular toxicity, alterations in cellular metabolism, oxidative stress, and induction of pro-inflammatory processes with subsequent disruption of normal cellular and neurological function. Damage to neural progenitor cell populations within germinal zones of the adult CNS has been identified as one of the key mechanisms by which chemotherapy might exert long-lasting and progressive neurotoxic effects. Based on the important role of the hippocampus for maintenance of brain plasticity throughout life, several experimental studies have focused on the study of chemotherapy effects on hippocampal neurogenesis and associated learning and memory. An increasing body of literature from both animal studies and neuroimaging studies in cancer patients suggests a possible relationship between chemotherapy induced hippocampal damage and the spectrum of neurocognitive deficits and mood alterations observed in cancer patients. This review aims to briefly summarize current preclinical and neuroimaging studies that are providing a potential link between the neurotoxic effects of chemotherapy and hippocampal dysfunction, highlighting challenges and future directions in this field of investigation.

  17. Chemotherapy, cognitive impairment and hippocampal toxicity.

    PubMed

    Dietrich, J; Prust, M; Kaiser, J

    2015-11-19

    Cancer therapies can be associated with significant central nervous system (CNS) toxicity. While radiation-induced brain damage has been long recognized both in pediatric and adult cancer patients, CNS toxicity from chemotherapy has only recently been acknowledged. Clinical studies suggest that the most frequent neurotoxic adverse effects associated with chemotherapy include memory and learning deficits, alterations of attention, concentration, processing speed and executive function. Preclinical studies have started to shed light on how chemotherapy targets the CNS both on cellular and molecular levels to disrupt neural function and brain plasticity. Potential mechanisms include direct cellular toxicity, alterations in cellular metabolism, oxidative stress, and induction of pro-inflammatory processes with subsequent disruption of normal cellular and neurological function. Damage to neural progenitor cell populations within germinal zones of the adult CNS has been identified as one of the key mechanisms by which chemotherapy might exert long-lasting and progressive neurotoxic effects. Based on the important role of the hippocampus for maintenance of brain plasticity throughout life, several experimental studies have focused on the study of chemotherapy effects on hippocampal neurogenesis and associated learning and memory. An increasing body of literature from both animal studies and neuroimaging studies in cancer patients suggests a possible relationship between chemotherapy induced hippocampal damage and the spectrum of neurocognitive deficits and mood alterations observed in cancer patients. This review aims to briefly summarize current preclinical and neuroimaging studies that are providing a potential link between the neurotoxic effects of chemotherapy and hippocampal dysfunction, highlighting challenges and future directions in this field of investigation. PMID:26086545

  18. Bevacizumab with preoperative chemotherapy versus preoperative chemotherapy alone for colorectal cancer liver metastases

    PubMed Central

    Lu, Zhen-Hai; Peng, Jian-Hong; Wang, Fu-Long; Yuan, Yun-Fei; Jiang, Wu; Li, Yu-Hong; Wu, Xiao-Jun; Chen, Gong; Ding, Pei-Rong; Li, Li-Ren; Kong, Ling-Heng; Lin, Jun-Zhong; Zhang, Rong-Xin; Wan, De-Sen; Pan, Zhi-Zhong

    2016-01-01

    Abstract This study aimed to assess the efficacy and safety of bevacizumab plus preoperative chemotherapy as first-line treatment for liver-only metastatic colorectal cancer in Chinese patients compared with those of preoperative chemotherapy alone. Patients with histologically confirmed liver-only metastatic colorectal cancer were sequentially reviewed, and received either preoperative chemotherapy plus bevacizumab (bevacizumab group, n = 32) or preoperative chemotherapy alone (chemotherapy group, n = 57). Progression-free survival, response rate, liver resection rate, conversion rate, and safety were analyzed. With median follow-up of 28.7 months, progression-free survival was 10.9 months (95% confidence interval: 8.7–13.1 months) in bevacizumab group and 9.9 months (95% confidence interval: 6.8–13.1 months) in chemotherapy group (P = 0.472). Response rates were 59.4% in bevacizumab group and 38.6% in chemotherapy group (P = 0.059). Overall liver resection (R0, R1, and R2) rate was 68.8% in bevacizumab group and 54.4% in chemotherapy group (P = 0.185). Conversion rate was 51.9% in bevacizumab group and 40.4% in chemotherapy group (P = 0.341). No postoperative complication was observed in all patients. Bevacizumab plus preoperative chemotherapy as first-line treatment for liver-only metastatic colorectal cancer tends to achieve better clinical benefit with controllable safety in Chinese patients. PMID:27583930

  19. Antimicrobial resistance in Scandinavia after ban of antimicrobial growth promoters.

    PubMed

    Bengtsson, Björn; Wierup, Martin

    2006-01-01

    The banned use of antimicrobial growth promoters resulted in a considerably decreased use of antimicrobials in food animal production in Sweden (65%), Denmark (47%), Norway (40%) and Finland (27%). The current prevalence of antimicrobial resistance in animal bacterial populations is also considerably lower than in some other countries in the EU. In the swine production, no or limited effect was found in the finisher production (>25 to 30 kg). Temporary negative effects occurred during the post weaning period (7-30 kg). In Denmark, the cost of production from birth to slaughter per pig produced increased by approximately 1.0 euro with a high variability between pig producers. In the broiler production the termination had no significant negative effect on animal health and welfare or on production economy. PMID:17127526

  20. Pathobiology of chemotherapy-induced hair loss.

    PubMed

    Paus, Ralf; Haslam, Iain S; Sharov, Andrey A; Botchkarev, Vladimir A

    2013-02-01

    Hair loss can be a psychologically devastating adverse effect of chemotherapy, but satisfactory management strategies for chemotherapy-induced alopecia remain elusive. In this Review we focus on the complex pathobiology of this side-effect. We discuss the clinical features and current management approaches, then draw upon evidence from mouse models and human hair-follicle organ-culture studies to explore the main pathobiology principles and explain why chemotherapy-induced alopecia is so challenging to manage. P53-dependent apoptosis of hair-matrix keratinocytes and chemotherapy-induced hair-cycle abnormalities, driven by the dystrophic anagen or dystrophic catagen pathway, play important parts in the degree of hair-follicle damage, alopecia phenotype, and hair-regrowth pattern. Additionally, the degree of hair-follicle stem-cell damage determines whether chemotherapy-induced alopecia is reversible. We highlight the need for carefully designed preclinical research models to generate novel, clinically relevant pointers to how this condition may be overcome.

  1. Chemotherapy in Elderly Patients with Gastric Cancer

    PubMed Central

    Kim, Hyeong Su; Kim, Jung Han; Kim, Ji Won; Kim, Byung Chun

    2016-01-01

    Gastric cancer (GC) is one of the most frequent malignant diseases in the elderly. Systemic chemotherapy showed an improvement of quality of life and survival benefit compared to supportive care alone in patients with advanced GC. Because comorbidities or age-related changes in pharmacokinetics and pharmacodynamics may lead to higher toxicity, however, many oncologists hesitate to recommend elderly patients to receive chemotherapy. Available data suggest that elderly patients with GC are able to tolerate and benefit from systemic chemotherapy to the same extent as younger patients. The age alone should not be the only criteria to preclude effective chemotherapy. However, proper patient selection is extremely important to deliver effective treatment safely. A comprehensive geriatric assessment (CGA) is a useful method to assess life expectancy and risk of morbidity in older patients and to guide providing optimal treatment. Treatment should be personalized based on the nature of the disease, the life expectancy, the risk of complication, and the patient's preference. Combination chemotherapy can be considered for older patients with metastatic GC who are classified as non-frail patients by CGA. For frail or vulnerable patients, however, monotherapy or only symptomatic treatment may be desirable. Targeted agents seem to be promising treatment options for elderly patients with GC considering their better efficacy and less toxicity. PMID:26722364

  2. [Chemotherapy of chiasmal gliomas in children].

    PubMed

    Helcl, F

    1995-04-01

    Chiasmal gliomas are rare tumors occurring predominantly in childhood. Their optimal treatment is still controversial. In the past only neurosurgeons (performing partial or subtotal removal of the tumor, biopsy or shunting procedure in hydrocephalus) and radiotherapeutists participated in their treatment. In the middle of the eighties there was only a single article dealing with chemotherapy of these tumors (Rosenstock, 1985). Since that time there was an increased number of articles about harmful effects of radiotherapy on the developing child's brain. Neurosurgeons are aware that they will not solve this problem alone. During the past 7 years we have observed gradual retreat from radiotherapy and an inclination to combined chemotherapy of the chiasmal gliomas in children. The author has been engaged in the research of this clinical entity for more than 10 years and he offers to readers a summary of the contemporary knowledge about chemotherapy of chiasmal gliomas in children. Despite the fact that there is lacking experience with long-term survivors after chemotherapy, which is extremely important especially in this disease, the preliminary short-term results of combined chemotherapy of chiasmal gliomas in children are promising. Rapid development of chemistry and pharmacology in the last few years is promising for the discovery of further, more effective anti-tumor drugs. Their new combinations could improve present non-satisfactory results of treatment of chiasmal gliomas in children. (Ref. 25.)

  3. Innovative therapies: intraoperative intracavitary chemotherapy.

    PubMed

    Chang, Michael Y; Sugarbaker, David J

    2004-11-01

    Both phase I studies demonstrated that high-dose cisplatin can be delivered safely with acceptable complication rates. The maximum tolerated doses of 225 mg/m2 and 250 mg/m2 cisplatin, respectively, are higher than any other published report of intrapleural cisplatin. The intrapleural cisplatin doses reported in other trials have been 80 mg/m2, 100 mg/m2, and 200 mg/m2. Despite the use of high-dose intraoperative chemotherapy, the group of 50 patients who underwent EPP experienced mortality and morbidity comparable to the contemporaneous group of 41 patients who did not participate in the protocol, except for increased rates of deep venous thrombosis and diaphragmatic patch failure. The 44 patients who underwent P/D experienced a slightly higher mortality rate and creatinine toxicity rate than the first phase I trial. Given the demographics of this patient cohort (higher age, lower FEV1, and inability to withstand pneumonectomy because of limited cardiopulmonary reserve), however, the mortality and morbidity rates seem acceptable. The pharmacologic data from both studies support our hypothesis that high regional doses of cisplatin can be delivered with less systemic absorption than can be achieved with intravenous administration (data not shown). With the maximum tolerated dose of intracavitary cisplatin and safety of intraoperative administration after surgical resection firmly established by these phase I trials, we are prepared to implement phase II and III studies of EPP and P/D with intraoperative cisplatin lavage. We aim to monitor tumor recurrence and patient survival prospectively and compare these results with historic controls. We also intend to document prospectively the morbidity and mortality of the treatment protocols. Finally, we plan to evaluate the pharmacokinetics of cisplatin by measuring tissue and perfusate levels of active and inactive cisplatin. By approaching the problem of local recurrence after resection of MPM in a careful and methodical

  4. Antimicrobial Resistance Mechanisms among Campylobacter

    PubMed Central

    2013-01-01

    Campylobacter jejuni and Campylobacter coli are recognized as the most common causative agents of bacterial gastroenteritis in the world. Humans most often become infected by ingesting contaminated food, especially undercooked chicken, but also other sources of bacteria have been described. Campylobacteriosis is normally a self-limiting disease. Antimicrobial treatment is needed only in patients with more severe disease and in those who are immunologically compromised. The most common antimicrobial agents used in the treatment of Campylobacter infections are macrolides, such as erythromycin, and fluoroquinolones, such as ciprofloxacin. Tetracyclines have been suggested as an alternative choice in the treatment of clinical campylobacteriosis but in practice are not often used. However, during the past few decades an increasing number of resistant Campylobacter isolates have developed resistance to fluoroquinolones and other antimicrobials such as macrolides, aminoglycosides, and beta-lactams. Trends in antimicrobial resistance have shown a clear correlation between use of antibiotics in the veterinary medicine and animal production and resistant isolates of Campylobacter in humans. In this review, the patterns of emerging resistance to the antimicrobial agents useful in treatment of the disease are presented and the mechanisms of resistance to these drugs in Campylobacter are discussed. PMID:23865047

  5. Antimicrobial implications of vitamin D

    PubMed Central

    Youssef, Dima A; Miller, Christopher WT; El-Abbassi, Adel M; Cutchins, Della C; Cutchins, Coleman; Grant, William B

    2011-01-01

    Evidence exists that vitamin D has a potential antimicrobial activity and its deficiency has deleterious effects on general well-being and longevity. Vitamin D may reduce the risk of infection through multiple mechanisms. Vitamin D boosts innate immunity by modulating production of anti-microbial peptides (AMPs) and cytokine response. Vitamin D and its analogues via these mechanisms are playing an increasing role in the management of atopic dermatitis, psoriasis, vitiligo, acne and rosacea. Vitamin D may reduce susceptibility to infection in patients with atopic dermatitis and the ability to regulate local immune and inflammatory responses offers exciting potential for understanding and treating chronic inflammatory dermatitides. Moreover, B and T cell activation as well as boosting the activity of monocytes and macrophages also contribute to a potent systemic anti-microbial effect. The direct invasion by pathogenic organisms may be minimized at sites such as the respiratory tract by enhancing clearance of invading organisms. A vitamin D replete state appears to benefit most infections, with the possible noteworthy exception of Leishmaniasis. Antibiotics remain an expensive option and misuse of these agents results in significant antibiotic resistance and contributes to escalating health care costs. Vitamin D constitutes an inexpensive prophylactic option and possibly therapeutic product either by itself or as a synergistic agent to traditional antimicrobial agents. This review outlines the specific antimicrobial properties of vitamin D in combating a wide range of organisms. We discuss the possible mechanisms by which vitamin D may have a therapeutic role in managing a variety of infections. PMID:22259647

  6. Antimicrobial activities of squalamine mimics.

    PubMed

    Kikuchi, K; Bernard, E M; Sadownik, A; Regen, S L; Armstrong, D

    1997-07-01

    We investigated the antimicrobial properties of compounds with structural features that were designed to mimic those of squalamine, an antibiotic isolated from the stomach of the dogfish shark. The mimics, like squalamine, are sterol-polyamine conjugates. Unlike squalamine, the mimics were simple to prepare, at high yield, from readily available starting materials. Several squalamine mimics showed activity against gram-negative rods, gram-positive cocci including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, and fungi. Some had little or no hemolytic activity. The hydrophobicity of the sterol backbone and the length and the cationic charge of the side chains appeared to be critical determinants of activity. One of the squalamine mimics, SM-7, was bactericidal against Escherichia coli, Pseudomonas aeruginosa, and S. aureus; its activity was decreased by divalent or monovalent cations and by bovine serum albumin. Subinhibitory concentrations of SM-7 markedly enhanced the antimicrobial activity of rifampin against gram-negative rods. These results suggest that the compounds may disrupt an outer membrane of gram-negative rods. Squalamine mimics are a new class of broad-spectrum antimicrobial agents. The antagonism of their activity by serum and albumin and their hemolytic properties may limit their use as systemic agents. The squalamine mimics, because of their potencies, broad spectra of antimicrobial activity, and potential for systemic toxicity, appear to be good candidates for development as topical antimicrobial agents. PMID:9210661

  7. ACVIM consensus statement on therapeutic antimicrobial use in animals and antimicrobial resistance.

    PubMed

    Weese, J S; Giguère, S; Guardabassi, L; Morley, P S; Papich, M; Ricciuto, D R; Sykes, J E

    2015-01-01

    The epidemic of antimicrobial resistant infections continues to challenge, compromising animal care, complicating food animal production and posing zoonotic disease risks. While the overall role of therapeutic antimicrobial use in animals in the development AMR in animal and human pathogens is poorly defined, veterinarians must consider the impacts of antimicrobial use in animal and take steps to optimize antimicrobial use, so as to maximize the health benefits to animals while minimizing the likelihood of antimicrobial resistance and other adverse effects. This consensus statement aims to provide guidance on the therapeutic use of antimicrobials in animals, balancing the need for effective therapy with minimizing development of antimicrobial resistance in bacteria from animals and humans.

  8. [THE TOXIC EFFECTS OF CHEMOTHERAPY ON THE GASTROINTESTINAL TRACT].

    PubMed

    Sivak, L A; Maidanevich, N N; Lyalkin, S A; Aleksik, E M; Askolskiy, A V; Klimanov, M Y; Kasap, N V

    2015-01-01

    Chemotherapy in modern oncology is one of the main methods of treatment, along with surgery and radiotherapy techniques. More than 60% of patients receiving chemotherapy at different stages of treatment. Recently, modern chemotherapy has become more urgent personal approach to the choice of drugs and their doses, aimed at reducing the toxicity of chemotherapy. Complications of chemotherapy significantly degrade the effectiveness of the treatment of patients with malignant tumors, because they require lower doses of anticancer drug, or lengthening the intervals between cycles of chemotherapy, which affects treatment outcomes and quality of life. PMID:26118038

  9. Automated plan-recognition of chemotherapy protocols

    PubMed Central

    Bhatia, Haresh; Levy, Mia

    2011-01-01

    Cancer patients are often treated with multiple sequential chemotherapy protocols ranging in complexity from simple to highly complex patterns of multiple repeating drugs. Clinical documentation procedures that focus on details of single drug events, however, make it difficult for providers and systems to efficiently abstract the sequence and nature of treatment protocols. We have developed a data driven method for cancer treatment plan recognition that takes as input pharmacy chemotherapy dispensing records and produces the sequence of identified chemotherapy protocols. Compared to a manually annotated gold standard, our method was 75% accurate and 80% precise for a breast cancer testing set (110 patients, 2,029 drug events), and 54% accurate and 63% precise for a lung cancer testing set (53 patients, 670 drug events). This method for cancer treatment plan recognition may provide clinicians and systems an abstracted view of the patient’s treatment history. PMID:22195061

  10. Pharmacokinetics and pharmacogenomics in gastric cancer chemotherapy.

    PubMed

    Nishiyama, Masahiko; Eguchi, Hidetaka

    2009-05-20

    Despite extensive efforts, treatment of gastric cancer by chemotherapy, the globally accepted standard, is yet undetermined, and uncertainty remains regarding the optimal regimen. Recent introduction of active "new generation agents" offers hope for improving patient outcomes. Current chemotherapeutic trials provided several regimens that may become a possible standard treatment, including docetaxel/cisplatin/5-FU (TCF) and cisplatin/S-1 for advanced and metastatic cancer and S-1 monotherapy in the adjuvant setting. Along with the development of novel active regimens, individual optimization of cancer chemotherapy has been attempted in order to reduce toxicity and enhance tumor response. Unlike the rare and limited contribution of pharmacokinetic studies, pharmacogenomic studies are increasing the potential to realize the therapeutics against gastric cancer. Despite the limited data, pharmacogenomics in gastric cancer have provided a number of putative biomarkers for the prediction of tumor response to chemotherapies and of toxicity.

  11. Oncotherapy: A System for Requesting Chemotherapy Protocols.

    PubMed

    Righi, Laura Vera

    2015-01-01

    A clinical decision support system is able to provide oncologists with suitable treatment options at the moment of decision making regarding which chemotherapy protocol is the best to apply to a particular oncological case. The National Cancer Institute has created a Guidelines Committee that establishes therapeutical options for each clinical case. The Health Informatics Department has developed Oncotherapy, a knowledge database that incorporates information provided by the Guidelines Committee. Oncotherapy includes a tailored information repository to provide oncologists in the public health system with the chemotherapy protocols available given three types of data: clinical diagnosis, clinical stage and therapy criteria. The protocol selected by the treating oncologist is sent back to Oncotherapy, which may create new knowledge that can be incorporated into the knowledge database. In this way, the system supports making the best decision according to the chemotherapy protocol options available. Furthermore, it can warn of errors that could result from mistakenly chosen therapies. PMID:26262420

  12. Antimicrobial susceptibility of Mycoplasma hyorhinis.

    PubMed

    Wu, C C; Shryock, T R; Lin, T L; Faderan, M; Veenhuizen, M F

    2000-09-15

    A broth microdilution technique was used to determine the antimicrobial susceptibility of 15 field isolates of Mycoplasma hyorhinis to 10 antimicrobial agents, representative of different classes, and contrasting newer agents to existing ones. For the macrolides, the MIC(90) for tylosin and tilmicosin was 1 and 4 microg/ml, respectively, but was > or = 16 microg/ml for erythromycin. Tetracycline, lincomycin and enrofloxacin each had an MIC(90) of 2 microg/ml. The mycoplasma had similar levels of susceptibility to the aminoglycoside and aminocyclictol classes exhibiting an MIC(90) of 4 microg/ml for gentamicin and 2 microg/ml for spectinomycin. The isolates exhibited high MICs to trimethoprim/sulfamethoxazole with an MIC(90) > or = 16/304 microg/ml. In summary, M. hyorhinis isolates from the US had low MICs against a variety of antimicrobials tested, with the exception of erythromycin and trimethoprim/sulfamethoxazole. PMID:10925038

  13. Synthetic biology of antimicrobial discovery.

    PubMed

    Zakeri, Bijan; Lu, Timothy K

    2013-07-19

    Antibiotic discovery has a storied history. From the discovery of penicillin by Sir Alexander Fleming to the relentless quest for antibiotics by Selman Waksman, the stories have become like folklore used to inspire future generations of scientists. However, recent discovery pipelines have run dry at a time when multidrug-resistant pathogens are on the rise. Nature has proven to be a valuable reservoir of antimicrobial agents, which are primarily produced by modularized biochemical pathways. Such modularization is well suited to remodeling by an interdisciplinary approach that spans science and engineering. Herein, we discuss the biological engineering of small molecules, peptides, and non-traditional antimicrobials and provide an overview of the growing applicability of synthetic biology to antimicrobials discovery.

  14. Synthetic biology of antimicrobial discovery

    PubMed Central

    Zakeri, Bijan; Lu, Timothy K.

    2012-01-01

    Antibiotic discovery has a storied history. From the discovery of penicillin by Sir Alexander Fleming to the relentless quest for antibiotics by Selman Waksman, the stories have become like folklore, used to inspire future generations of scientists. However, recent discovery pipelines have run dry at a time when multidrug resistant pathogens are on the rise. Nature has proven to be a valuable reservoir of antimicrobial agents, which are primarily produced by modularized biochemical pathways. Such modularization is well suited to remodeling by an interdisciplinary approach that spans science and engineering. Herein, we discuss the biological engineering of small molecules, peptides, and non-traditional antimicrobials and provide an overview of the growing applicability of synthetic biology to antimicrobials discovery. PMID:23654251

  15. Antifungal proteins: More than antimicrobials?

    PubMed Central

    Hegedüs, Nikoletta; Marx, Florentine

    2013-01-01

    Antimicrobial proteins (AMPs) are widely distributed in nature. In higher eukaryotes, AMPs provide the host with an important defence mechanism against invading pathogens. AMPs of lower eukaryotes and prokaryotes may support successful competition for nutrients with other microorganisms of the same ecological niche. AMPs show a vast variety in structure, function, antimicrobial spectrum and mechanism of action. Most interestingly, there is growing evidence that AMPs also fulfil important biological functions other than antimicrobial activity. The present review focuses on the mechanistic function of small, cationic, cysteine-rich AMPs of mammals, insects, plants and fungi with antifungal activity and specifically aims at summarizing current knowledge concerning additional biological properties which opens novel aspects for their future use in medicine, agriculture and biotechnology. PMID:23412850

  16. In vitro photodynamic antimicrobial chemotherapy in dentine contaminated by cariogenic bacteria

    NASA Astrophysics Data System (ADS)

    Melo, M. A. S.; de-Paula, D. M.; Lima, J. P. M.; Borges, F. M. C.; Steiner-Oliveira, C.; Nobre-Dos-Santos, M.; Zanin, I. C. J.; Barros, E. B.; Rodrigues, L. K. A.

    2010-06-01

    The development of a method to ensure bacterial-free substrates without extensive cavity preparation would be highly useful to dentistry, since there is no currently available effective method for killing residual bacteria in dentinal tissue. This randomized in vitro study determined parameters for using toluidine blue O (TBO) with a light-emitting diode (LED) for dentine caries disinfection and monitored intrapulpal/periodontal temperatures during irradiation. Occlusal human dentine slabs were immersed in Streptococcus mutans culture for demineralization induction. Slabs were allocated to 10 groups ( n = 15), which were treated with 0.1 mg ml-1 TBO with 5 min of incubation time or 0.9% NaCl solution for 5, 10 or 15 min, and submitted or not to irradiation for 5, 10 or 15 min (47, 94, and 144 J/cm2). Before and after treatments, dentine samples were analyzed with regard to S. mutans counts. In whole teeth, temperature in pulp and periodontium was measured by thermocouples during irradiation. Kruskal-Wallis/Student-Newman-Keuls, and ANOVA/Tukey test were respectively utilized to compare log reductions and temperature rises between groups. Bacterial reduction was observed when dentine was exposed to both TBO and LED at all irradiation times, as well as to LED alone for 10 and 15 min. Temperature increases lower than 2°C were observed for either pulp or periodontium. Concluding, LED combined with TBO is a safe and effective approach for dentine caries disinfection. Nevertheless, additional studies should be conducted to determine the influence of the irradiation in S. mutans viability in dentinal surface/tubules.

  17. An evaluation of Neisseria gonorrhoeae antimicrobial susceptibility testing in the UK.

    PubMed

    Jain, Anu; Cole, Michelle J; Planche, Tim; Ison, Catherine A

    2014-11-01

    The only method currently available to perform Neisseria gonorrhoeae antimicrobial susceptibility testing (Ng-AST) requires a viable organism obtained by culture. Reports of in vitro resistance to extended-spectrum cephalosporins, the treatment of choice for gonorrhoea, coupled with increasing gonorrhoea diagnoses is worrying. The aim of this study was to identify various methodologies employed by the UK microbiology laboratories to perform Ng-AST. Of the 118 laboratories that responded, 114 offered Ng-AST; the majority (82.5%, 94/114) of the laboratories used British Society for Antimicrobial Chemotherapy methodology for Ng-AST. The other main findings were infrequent use of quality control procedures and inconsistent susceptibility testing of the antibiotics used routinely for treatment.

  18. Uses of antimicrobial genes from microbial genome

    DOEpatents

    Sorek, Rotem; Rubin, Edward M.

    2013-08-20

    We describe a method for mining microbial genomes to discover antimicrobial genes and proteins having broad spectrum of activity. Also described are antimicrobial genes and their expression products from various microbial genomes that were found using this method. The products of such genes can be used as antimicrobial agents or as tools for molecular biology.

  19. Intrathecal chemotherapy. Selection of cytostatic agents.

    PubMed

    Hayakawa, T; Yamada, R; Kanai, N; Kuroda, R; Ushio, Y; Higashi, H; Mogami, H

    1970-09-01

    Selection of cytostatic agents for intrathecal administration is the subject of this paper.Both the toxic side effects-destruction of blood-brain barrier and change of body weight-and the cytostatic effects on intracranially transplanted Yoshida ascites sarcoma were investigated of intrathecal administration of various cytostatic agents. As a result, it may be concluded that Methotrexate and Endoxan and lower dose of mitomycin C are suitable drugs for intrathecal chemotherapy.Based on these findings, clinical cases of malignant brain tumours were treated with intrathecal chemotherapy.Grateful acknowledgement is made to Professor Dennosuke Jinnai for his constant interest and guidance in this investigation.

  20. Optimizing initial chemotherapy for metastatic pancreatic cancer.

    PubMed

    Mantripragada, Kalyan C; Safran, Howard

    2016-05-01

    The two combination chemotherapy regimens FOLFIRINOX and gemcitabine plus nab-paclitaxel represent major breakthroughs in the management of metastatic pancreatic cancer. Both regimens showed unprecedented survival advantage in the setting of front-line therapy. However, their application for treatment of patients in the community is challenging because of significant toxicities, thus limiting potential benefits to a narrow population of patients. Modifications to the dose intensity or schedule of those regimens improve their tolerability, while likely retaining survival advantage over single-agent chemotherapy. Newer strategies to optimize these two active regimens in advanced pancreatic cancer are being explored that can help personalize treatment to individual patients.

  1. [Induction chemotherapy for locally advanced cervical cancer].

    PubMed

    Morkhov, K Yu; Nechushkina, V M; Kuznetsov, V V

    2015-01-01

    The main methods of treatment for cervical cancer are surgery, radiotherapy or their combination. During past two decades chemotherapy are increasingly being used not only in patients with disseminated forms of this disease but also in patients undergoing chemoradiotherapy or as induction therapy. Possibilities of adjuvant chemotherapy for cervical cancer are being studied. According to A.D.Kaprin and V.V. Starinskiy in 2013 in Russia, 32% of patients with newly diagnosed cervical cancer underwent only radiation therapy, 32%--combined or complex treatment, 27.3%--only surgery, and just 8.7%--chemoradiotherapy. PMID:26087600

  2. Cancer Chemotherapy - Multiple Languages: MedlinePlus

    MedlinePlus

    ... العربية) Chemotherapy (Arabic) العربية Bilingual PDF Health Information Translations Handling Chemotherapy Safely (Arabic) التعامل الآمن مع العلاج الكيماوي - العربية Bilingual PDF Health Information Translations Nausea and Vomiting with Cancer Treatment (Arabic) العربية ...

  3. Fluoroquinolone antimicrobial agents.

    PubMed Central

    Wolfson, J S; Hooper, D C

    1989-01-01

    The fluoroquinolones, a new class of potent orally absorbed antimicrobial agents, are reviewed, considering structure, mechanisms of action and resistance, spectrum, variables affecting activity in vitro, pharmacokinetic properties, clinical efficacy, emergence of resistance, and tolerability. The primary bacterial target is the enzyme deoxyribonucleic acid gyrase. Bacterial resistance occurs by chromosomal mutations altering deoxyribonucleic acid gyrase and decreasing drug permeation. The drugs are bactericidal and potent in vitro against members of the family Enterobacteriaceae, Haemophilus spp., and Neisseria spp., have good activity against Pseudomonas aeruginosa and staphylococci, and (with several exceptions) are less potent against streptococci and have fair to poor activity against anaerobic species. Potency in vitro decreases in the presence of low pH, magnesium ions, or urine but is little affected by different media, increased inoculum, or serum. The effects of the drugs in combination with a beta-lactam or aminoglycoside are often additive, occasionally synergistic, and rarely antagonistic. The agents are orally absorbed, require at most twice-daily dosing, and achieve high concentrations in urine, feces, and kidney and good concentrations in lung, bone, prostate, and other tissues. The drugs are efficacious in treatment of a variety of bacterial infections, including uncomplicated and complicated urinary tract infections, bacterial gastroenteritis, and gonorrhea, and show promise for therapy of prostatitis, respiratory tract infections, osteomyelitis, and cutaneous infections, particularly when caused by aerobic gram-negative bacilli. Fluoroquinolones have also proved to be efficacious for prophylaxis against travelers' diarrhea and infection with gram-negative bacilli in neutropenic patients. The drugs are effective in eliminating carriage of Neisseria meningitidis. Patient tolerability appears acceptable, with gastrointestinal or central nervous

  4. Antimicrobial drugs for treating cholera

    PubMed Central

    Leibovici-Weissman, Ya'ara; Neuberger, Ami; Bitterman, Roni; Sinclair, David; Salam, Mohammed Abdus; Paul, Mical

    2014-01-01

    Background Cholera is an acute watery diarrhoea caused by infection with the bacterium Vibrio cholerae, which if severe can cause rapid dehydration and death. Effective management requires early diagnosis and rehydration using oral rehydration salts or intravenous fluids. In this review, we evaluate the additional benefits of treating cholera with antimicrobial drugs. Objectives To quantify the benefit of antimicrobial treatment for patients with cholera, and determine whether there are differences between classes of antimicrobials or dosing schedules. Search methods We searched the Cochrane Infectious Disease Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; African Index Medicus; LILACS; Science Citation Index; metaRegister of Controlled Trials; WHO International Clinical Trials Registry Platform; conference proceedings; and reference lists to March 2014. Selection criteria Randomized and quasi-randomized controlled clinical trials in adults and children with cholera that compared: 1) any antimicrobial treatment with placebo or no treatment; 2) different antimicrobials head-to-head; or 3) different dosing schedules or different durations of treatment with the same antimicrobial. Data collection and analysis Two reviewers independently applied inclusion and exclusion criteria, and extracted data from included trials. Diarrhoea duration and stool volume were defined as primary outcomes. We calculated mean difference (MD) or ratio of means (ROM) for continuous outcomes, with 95% confidence intervals (CI), and pooled data using a random-effects meta-analysis. The quality of evidence was assessed using the GRADE approach. Main results Thirty-nine trials were included in this review with 4623 participants. Antimicrobials versus placebo or no treatment Overall, antimicrobial therapy shortened the mean duration of diarrhoea by about a day and a half compared to placebo or no treatment (MD -36.77 hours, 95% CI -43

  5. Expression levels of the microRNA maturing microprocessor complex component DGCR8 and the RNA-induced silencing complex (RISC) components argonaute-1, argonaute-2, PACT, TARBP1, and TARBP2 in epithelial skin cancer.

    PubMed

    Sand, Michael; Skrygan, Marina; Georgas, Dimitrios; Arenz, Christoph; Gambichler, Thilo; Sand, Daniel; Altmeyer, Peter; Bechara, Falk G

    2012-11-01

    The microprocessor complex mediates intranuclear biogenesis of precursor microRNAs from the primary microRNA transcript. Extranuclear, mature microRNAs are incorporated into the RNA-induced silencing complex (RISC) before interaction with complementary target mRNA leads to transcriptional repression or cleavage. In this study, we investigated the expression profiles of the microprocessor complex subunit DiGeorge syndrome critical region gene 8 (DGCR8) and the RISC components argonaute-1 (AGO1), argonaute-2 (AGO2), as well as double-stranded RNA-binding proteins PACT, TARBP1, and TARBP2 in epithelial skin cancer and its premalignant stage. Patients with premalignant actinic keratoses (AK, n = 6), basal cell carcinomas (BCC, n = 15), and squamous cell carcinomas (SCC, n = 7) were included in the study. Punch biopsies were harvested from the center of the tumors (lesional), from healthy skin sites (intraindividual controls), and from healthy skin sites in a healthy control group (n = 16; interindividual control). The DGCR8, AGO1, AGO2, PACT, TARBP1, and TARBP2 mRNA expression levels were detected by quantitative real-time reverse transcriptase polymerase chain reaction. The DGCR8, AGO1, AGO2, PACT, and TARBP1 expression levels were significantly higher in the AK, BCC, and SCC groups than the healthy controls (P < 0.05). There was no significant difference in the TARBP2 expression levels between groups (P > 0.05). This study indicates that major components of the miRNA pathway, such as the microprocessor complex and RISC, are dysregulated in epithelial skin cancer.

  6. How antimicrobial peptides disrupt lipid bilayers?

    NASA Astrophysics Data System (ADS)

    Sengupta, Durba

    2011-03-01

    The molecular basis for the activity of cyclic and linear antimicrobial peptides is analysed. We performed multi-scale molecular dynamics simulations and biophysical measurements to probe the interaction of antimicrobial peptides with model membranes. Two linear antimicrobial peptides, magainin and melittin and a cyclic one, BPC194 have been studied. We test different models to determine the generic and specific forces that lead to bilayer disruption. We probe whether interfacial stress or local membrane perturbation is more likely to lead to the porated state. We further analyse the reasons that determine specificity and increase of activity in antimicrobial peptides. The results provide detailed insight in the mode of action of antimicrobial peptides.

  7. Radiation recall supraglottitis. A hazard in head and neck chemotherapy

    SciTech Connect

    Wallenborn, P.A.; Postma, D.S.

    1984-09-01

    The enhanced effects of chemotherapy on previously irradiated tissue have been well demonstrated. When chemotherapy is given some time after irradiation and elicits a tissue reaction in the radiation field, the reaction is termed radiation recall. We review known interactions between chemotherapy and radiotherapy and report, to our knowledge, the first case of a supraglottitis radiation recall reaction. Familiarity with this phenomenon and potential complications of chemotherapy following head and neck irradiation may expedite early diagnosis and appropriate lifesaving treatment.

  8. Helical Antimicrobial Sulfono- {gamma} -AApeptides

    SciTech Connect

    Li, Yaqiong; Wu, Haifan; Teng, Peng; Bai, Ge; Lin, Xiaoyang; Zuo, Xiaobing; Cao, Chuanhai; Cai, Jianfeng

    2015-06-11

    Host-defense peptides (HDPs) such as magainin 2 have emerged as potential therapeutic agents combating antibiotic resistance. Inspired by their structures and mechanism of action, herein we report the fi rst example of antimicrobial helical sulfono- γ - AApeptide foldamers. The lead molecule displays broad-spectrum and potent antimicrobial activity against multi-drug-resistant Gram- positive and Gram-negative bacterial pathogens. Time-kill studies and fl uorescence microscopy suggest that sulfono- γ -AApeptides eradicate bacteria by taking a mode of action analogous to that of HDPs. Clear structure - function relationships exist in the studied sequences. Longer sequences, presumably adopting more-de fi ned helical structures, are more potent than shorter ones. Interestingly, the sequence with less helical propensity in solution could be more selective than the stronger helix-forming sequences. Moreover, this class of antimicrobial agents are resistant to proteolytic degradation. These results may lead to the development of a new class of antimicrobial foldamers combating emerging antibiotic-resistant pathogens.

  9. Antimicrobial activity of Pseudognaphalium moritzianum.

    PubMed

    Rangel, D; Garcia, I; Velasco, J; Buitrago, D; Velazco, E

    2002-12-01

    The antimicrobial activity of ethanol, acetone and aqueous extracts of the aerial parts of Pseudognaphalium moritzianum was evaluated. Ethanol and acetone extracts showed activity against Staphlococcus aureus, Enterococcus faecalis and Pseudomonas aeruginosa. The aqueous extract was active against S. aureus and P. aeruginosa.

  10. Antimicrobial resistance: a global response.

    PubMed Central

    Smith, Richard D.; Coast, Joanna

    2002-01-01

    Resistance to antimicrobial therapies reduces the effectiveness of these drugs, leading to increased morbidity, mortality, and health care expenditure. Because globalization increases the vulnerability of any country to diseases occurring in other countries, resistance presents a major threat to global public health, and no country acting on its own can adequately protect the health of its population against it. International collective action is therefore essential. Nevertheless, responsibility for health remains predominantly national. Consequently, there is a potentially significant disparity between the problems and solutions related to antimicrobial resistance and the institutions and mechanisms that are available to deal with them. This paper considers the capacity of national and international institutions and mechanisms to generate a collective response to antimicrobial resistance. Strategies for containing resistance are outlined, with particular reference to globally coordinated activities of countries. The adequacy of national and international responses to resistance is assessed, and the actions that international bodies could take to solve difficulties associated with present responses are highlighted. Approaches are suggested for securing international collective action for the containment of antimicrobial resistance. PMID:11953791

  11. Antimicrobial activity of resveratrol analogues.

    PubMed

    Chalal, Malik; Klinguer, Agnès; Echairi, Abdelwahad; Meunier, Philippe; Vervandier-Fasseur, Dominique; Adrian, Marielle

    2014-01-01

    Stilbenes, especially resveratrol and its derivatives, have become famous for their positive effects on a wide range of medical disorders, as indicated by a huge number of published studies. A less investigated area of research is their antimicrobial properties. A series of 13 trans-resveratrol analogues was synthesized via Wittig or Heck reactions, and their antimicrobial activity assessed on two different grapevine pathogens responsible for severe diseases in the vineyard. The entire series, together with resveratrol, was first evaluated on the zoospore mobility and sporulation level of Plasmopara viticola (the oomycete responsible for downy mildew). Stilbenes displayed a spectrum of activity ranging from low to high. Six of them, including the most active ones, were subsequently tested on the development of Botrytis cinerea (fungus responsible for grey mold). The results obtained allowed us to identify the most active stilbenes against both grapevine pathogens, to compare the antimicrobial activity of the evaluated series of stilbenes, and to discuss the relationship between their chemical structure (number and position of methoxy and hydroxy groups) and antimicrobial activity. PMID:24918540

  12. Molecular Detection of Antimicrobial Resistance

    PubMed Central

    Fluit, Ad C.; Visser, Maarten R.; Schmitz, Franz-Josef

    2001-01-01

    The determination of antimicrobial susceptibility of a clinical isolate, especially with increasing resistance, is often crucial for the optimal antimicrobial therapy of infected patients. Nucleic acid-based assays for the detection of resistance may offer advantages over phenotypic assays. Examples are the detection of the methicillin resistance-encoding mecA gene in staphylococci, rifampin resistance in Mycobacterium tuberculosis, and the spread of resistance determinants across the globe. However, molecular assays for the detection of resistance have a number of limitations. New resistance mechanisms may be missed, and in some cases the number of different genes makes generating an assay too costly to compete with phenotypic assays. In addition, proper quality control for molecular assays poses a problem for many laboratories, and this results in questionable results at best. The development of new molecular techniques, e.g., PCR using molecular beacons and DNA chips, expands the possibilities for monitoring resistance. Although molecular techniques for the detection of antimicrobial resistance clearly are winning a place in routine diagnostics, phenotypic assays are still the method of choice for most resistance determinations. In this review, we describe the applications of molecular techniques for the detection of antimicrobial resistance and the current state of the art. PMID:11585788

  13. Investigational Antimicrobial Agents of 2013

    PubMed Central

    Pucci, Michael J.

    2013-01-01

    SUMMARY New antimicrobial agents are always needed to counteract the resistant pathogens that continue to be selected by current therapeutic regimens. This review provides a survey of known antimicrobial agents that were currently in clinical development in the fall of 2012 and spring of 2013. Data were collected from published literature primarily from 2010 to 2012, meeting abstracts (2011 to 2012), government websites, and company websites when appropriate. Compared to what was reported in previous surveys, a surprising number of new agents are currently in company pipelines, particularly in phase 3 clinical development. Familiar antibacterial classes of the quinolones, tetracyclines, oxazolidinones, glycopeptides, and cephalosporins are represented by entities with enhanced antimicrobial or pharmacological properties. More importantly, compounds of novel chemical structures targeting bacterial pathways not previously exploited are under development. Some of the most promising compounds include novel β-lactamase inhibitor combinations that target many multidrug-resistant Gram-negative bacteria, a critical medical need. Although new antimicrobial agents will continue to be needed to address increasing antibiotic resistance, there are novel agents in development to tackle at least some of the more worrisome pathogens in the current nosocomial setting. PMID:24092856

  14. Antimicrobial Polymers with Metal Nanoparticles

    PubMed Central

    Palza, Humberto

    2015-01-01

    Metals, such as copper and silver, can be extremely toxic to bacteria at exceptionally low concentrations. Because of this biocidal activity, metals have been widely used as antimicrobial agents in a multitude of applications related with agriculture, healthcare, and the industry in general. Unlike other antimicrobial agents, metals are stable under conditions currently found in the industry allowing their use as additives. Today these metal based additives are found as: particles, ions absorbed/exchanged in different carriers, salts, hybrid structures, etc. One recent route to further extend the antimicrobial applications of these metals is by their incorporation as nanoparticles into polymer matrices. These polymer/metal nanocomposites can be prepared by several routes such as in situ synthesis of the nanoparticle within a hydrogel or direct addition of the metal nanofiller into a thermoplastic matrix. The objective of the present review is to show examples of polymer/metal composites designed to have antimicrobial activities, with a special focus on copper and silver metal nanoparticles and their mechanisms. PMID:25607734

  15. Antimicrobial activity of quaternized heteroxylans.

    PubMed

    Ebringerová, A; Belicová, A; Ebringer, L

    1994-11-01

    A series of quaternized D-xylan polysaccharides, differing in the structural features of their macromolecular backbone, were tested for antimicrobial activity against Staphylococcus aureus, Enterococcus faecalis, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, Serratia marcescens and Saccharomyces cerevisiae. Activity was comparable with that of the cationic surfactant, cetyltrimethylammonium bromide, and depended on the degree of quaternization and the structural backbone of the derivatives.

  16. Antimicrobial activity of resveratrol analogues.

    PubMed

    Chalal, Malik; Klinguer, Agnès; Echairi, Abdelwahad; Meunier, Philippe; Vervandier-Fasseur, Dominique; Adrian, Marielle

    2014-06-10

    Stilbenes, especially resveratrol and its derivatives, have become famous for their positive effects on a wide range of medical disorders, as indicated by a huge number of published studies. A less investigated area of research is their antimicrobial properties. A series of 13 trans-resveratrol analogues was synthesized via Wittig or Heck reactions, and their antimicrobial activity assessed on two different grapevine pathogens responsible for severe diseases in the vineyard. The entire series, together with resveratrol, was first evaluated on the zoospore mobility and sporulation level of Plasmopara viticola (the oomycete responsible for downy mildew). Stilbenes displayed a spectrum of activity ranging from low to high. Six of them, including the most active ones, were subsequently tested on the development of Botrytis cinerea (fungus responsible for grey mold). The results obtained allowed us to identify the most active stilbenes against both grapevine pathogens, to compare the antimicrobial activity of the evaluated series of stilbenes, and to discuss the relationship between their chemical structure (number and position of methoxy and hydroxy groups) and antimicrobial activity.

  17. Antimicrobial activity of Securidaca longipedunculata.

    PubMed

    Ajali, U; Chukwurah, B K C

    2004-11-01

    The folk herbal uses of Securidaca longipedunculata in the treatment of diarrhea, boils, gonorrhea, and cough prompted phytochemical analyses and antimicrobial activity screening of extracts of the root. Some flavonoids isolated showed activity against many micro-organisms. These flavonoids were isolated using chromatographic methods. PMID:15636189

  18. Circumventing Tumor Resistance to Chemotherapy by Nanotechnology

    PubMed Central

    Liang, Xing-Jie; Chen, Chunying; Zhao, Yuliang; Wang, Paul C.

    2011-01-01

    Patient relapse and metastasis of malignant cells is very common after standard cancer treatment with surgery, radiation, and/or chemotherapy. Chemotherapy, a cornerstone in the development of present day cancer therapy, is one of the most effective and potent strategies to treat malignant tumors. However, the resistance of cancer cells to the drugs remains a significant impediment to successful chemotherapy. An additional obstacle is the inability of chemotherapeutic drugs to selectively target tumor cells. Almost all the anticancer agents have severe side effects on normal tissues and organs. The toxicity of currently available anticancer drugs and the inefficiency of chemotherapeutic treatments, especially for advanced stages of the disease, have limited the optimization of clinical drug combinations and effective chemotherapeutic protocols. Nanomedicine allows the release of drugs by biodegradation and self-regulation of nanomaterials in vitro and in vivo. Nanotechnologies are characterized by effective drug encapsulation, controllable self-assembly, specificity and biocompatibility as a result of their own material properties. Nanotechnology has the potential to overcome current chemotherapeutic barriers in cancer treatment, because of the unique nanoscale size and distinctive bioeffects of nanomaterials. Nanotechnology may help to solve the problems associated with traditional chemotherapy and multidrug resistance. PMID:19949937

  19. The curability of advanced cancers with chemotherapy.

    PubMed

    Boh-Seng, Y

    1981-07-01

    The tremendous progress that has been made in the chemotherapy of malignant diseases since the early 1950's has enabled the cure of a significant number of cancers such as chloriocarcinoma, Burkitt's lymphoma, Hodgkin's disease, non-Hodgkin's lymphoma, the acute leukaemias, testicular carcinoma, and many childhood cancers such as rhabdomyosarcoma, Wilm's tumor, Ewing's sarcoma, ovarian cancer, and retinoblastoma. As a result, the mortality from cancers has dropped by 15% for persons under the age of 45 years and even more for those under 30 years of age. Many other metastatic cancers can now be successfully controlled with chemotherapy and, ultimately, more will be added to the growing list of curable cancers. The chemotherapeutic agents responsible for the cures of some cancers include asparaginase, actinomycin D, Adriamycin, bleomycin, cisplatin, cyclophosphamide, cytosine arabinoside, 5-fluorouracil, 6-mercaptopurine, methotrexate, nitrogen mustard, prednisone, procarbazine, and vincristine. The discovery of new effective drugs such as AMSA and anthracenedione promises to improve the success rates obtained with present therapy. Chemotherapy is indicated for every patient who has metastatic cancer, since virtually every patient can receive some palliation from such therapy, while for some patients chemotherapy holds the promise of prolongation of life or even cure.

  20. [Nurse telephone support at home during chemotherapy].

    PubMed

    Despiau, Frédéric; Bombail, Marie; Leches, Céline; Montastruc, Marion; Gladieff, Laurence; Delord, Jean-Pierre

    2015-01-01

    An innovative scheme has been operational since 2013 at the Institut Claudius Regaud in Toulouse, aimed at patients undergoing chemotherapy. After an initial consultation, patients receive regular telephone support at home from expert nurses between treatments. The scheme helps to improve patient management and reinforce the community-hospital link. PMID:26365645

  1. Glossodynia after radiation therapy and chemotherapy

    SciTech Connect

    Naylor, G.D.; Marino, G.G.; Shumway, R.C.

    1989-10-01

    Radiation therapy and chemotherapy have decreased the mortality rates of cancer patients, but the morbidity associated with oral complications is high in many cases. A pretreatment oral evaluation and institution of a preventive care program reduce oral symptoms such as glossodynia considerably. When oral symptoms are minimized, the dentist can improve the patient's quality of life.40 references.

  2. Neoadjuvant and Adjuvant Chemotherapy of Cervical Cancer.

    PubMed

    Mallmann, Peter; Mallmann, Christoph

    2016-01-01

    Neoadjuvant chemotherapy is indicated in patients who can tolerate the side effects of a chemotherapy and with preoperative presentation of one of the following clinical risk situations: bulky disease with a maximal tumor diameter of > 4 cm, suspicious lymph nodes in magnetic resonance imaging (MRI), computed tomography (CT) scan or endosonography, histopathologically confirmed lymph node metastasis, or histopathologically documented risk factors such as G3 and L1V1. A neoadjuvant chemotherapy followed by surgery should be performed with cisplatin at a dosage of > 25 mg/m2 per week and an application interval of < 14 days. The previously published data suggests an improved rate of complete resection and reduced incidences of positive lymph nodes and parametric infiltration. Accordingly, the percentage of patients in need for adjuvant radiochemotherapy after operation can be significantly reduced. Some studies demonstrated a prolongation of progression-free and overall survival. Following the previously published studies, adjuvant chemotherapy after operation or after radiochemotherapy has no significant effect on the overall survival and, following the current guidelines, should be avoided. PMID:27614740

  3. Adjuvant Chemotherapy in Rectal Cancer after Chemoradiotherapy.

    PubMed

    Boustani, J; Caubet, M; Bosset, J-F

    2016-02-01

    The aim of this overview was to investigate whether adjuvant chemotherapy has a favourable effect on the outcome of patients with rectal cancer who had preoperative (chemo)radiotherapy. A review of randomised clinical trials that allocated patients between fluorouracil-based and observation or between fluorouracil-based and oxaliplatin-based adjuvant chemotherapy after preoperative (chemo)radiotherapy was carried out, including their corresponding meta-analyses. None of the five randomised trials has shown a significant benefit of fluorouracil-based adjuvant chemotherapy for overall survival or disease-free survival. Also, the three corresponding meta-analyses failed to show a benefit of adjuvant treatment. Of three randomised trials - two phase III and one phase II with a 3-year disease-free survival end point - two showed a small benefit of adding oxaliplatin to fluorouracil, one failed. The corresponding meta-analyses showed that the pooled difference was not significant. In conclusion, the use of postoperative 5-fluorouracil-based chemotherapy with or without oxaliplatin in patients with rectal cancer after preoperative (chemo)radiotherapy is not scientifically proven.

  4. Bacillary angiomatosis in a child undergoing chemotherapy.

    PubMed

    Myers, S A; Prose, N S; Garcia, J A; Wilson, K H; Dunsmore, K P; Kamino, H

    1992-10-01

    Bacillary angiomatosis is an infectious disease of the skin and viscera characterized by vascular lesions, originally described in patients with human immunodeficiency virus infection. There are also case reports of bacillary angiomatosis occurring in immunocompetent patients and in noninfected patients with suppressed immune function. We report a case of bacillary angiomatosis in a child undergoing chemotherapy for acute leukemia.

  5. How to calculate the dose of chemotherapy

    PubMed Central

    Gurney, H

    2002-01-01

    Body surface area-dosing does not account for the complex processes of cytotoxic drug elimination. This leads to an unpredictable variation in effect. Overdosing is easily recognised but it is possible that unrecognised underdosing is more common and may occur in 30% or more of patients receiving standard regimen. Those patients who are inadvertently underdosed are at risk of a significantly reduced anticancer effect. Using published data, it can be calculated that there is an almost 20% relative reduction in survival for women receiving adjuvant chemotherapy for breast cancer as a result of unrecognised underdosing. Similarly, the cure rate of cisplatin-based chemotherapy for advanced testicular cancer may be reduced by as much as 10%. The inaccuracy of body surface area-dosing is more than an inconvenience and it is important that methods for more accurate dose calculation are determined, based on the known drug elimination processes for cytotoxic chemotherapy. Twelve rules for dose calculation of chemotherapy are given that can be used as a guideline until better dose-calculation methods become available. Consideration should be given to using fixed dose guidelines independent of body surface area and based on drug elimination capability, both as a starting dose and for dose adjustment, which may have accuracy, safety and financial advantages. British Journal of Cancer (2002) 86, 1297–1302. DOI: 10.1038/sj/bjc/6600139 www.bjcancer.com © 2002 Cancer Research UK PMID:11953888

  6. Prolonged remission of recurrent cervical carcinoma following paclitaxel and carboplatin chemotherapy with paclitaxel maintenance chemotherapy.

    PubMed

    Micha, John P; Sassoon, Aaron F; Wong, Humberto; Goldstein, Bram H

    2015-08-01

    Cervical cancer recurs in ~30% of cases, for which a favorable prognosis is often unattainable. We describe a cervical cancer patient who developed metastatic disease ~5 years after her initial diagnosis. She was subsequently treated with six cycles of paclitaxel (175 mg/m) and carboplatin area under the curve (AUC) 5 chemotherapy every 21 days, and paclitaxel (135 mg/m) maintenance therapy every 21 days; the patient has remained in clinical remission after more than 5 years of follow-up. Chemotherapy has not historically been effective in managing recurrent, persistent, or metastatic cervical cancer. However, our case study involving paclitaxel and carboplatin chemotherapy with maintenance chemotherapy represents one of the longest documented remission rates in association with the management of recurrent cervical cancer.

  7. Combating Antimicrobial Resistance in Foodborne Microorganisms.

    PubMed

    Lai, Edward P C; Iqbal, Zafar; Avis, Tyler J

    2016-02-01

    This review addresses an important public health hazard affecting food safety. Antimicrobial agents are used in foods to reduce or eliminate microorganisms that cause disease. Many traditional organic compounds, novel synthetic organic agents, natural products, peptides, and proteins have been extensively studied for their effectiveness as antimicrobial agents against foodborne Campylobacter spp., Escherichia coli, Listeria spp. and Salmonella. However, antimicrobial resistance can develop in microorganisms, enhancing their ability to withstand the inhibiting or killing action of antimicrobial agents. Knowledge gaps still exist with regard to the actual chemical and microbiological mechanisms that must be identified to facilitate the search for new antimicrobial agents. Technical implementation of antimicrobial active packing films and coatings against target microorganisms must also be improved for extended product shelf life. Recent advances in antimicrobial susceptibility testing can provide researchers with new momentum to pursue their quest for a resistance panacea.

  8. Access to effective antimicrobials: a worldwide challenge.

    PubMed

    Laxminarayan, Ramanan; Matsoso, Precious; Pant, Suraj; Brower, Charles; Røttingen, John-Arne; Klugman, Keith; Davies, Sally

    2016-01-01

    Recent years have seen substantial improvements in life expectancy and access to antimicrobials, especially in low-income and lower-middle-income countries, but increasing pathogen resistance to antimicrobials threatens to roll back this progress. Resistant organisms in health-care and community settings pose a threat to survival rates from serious infections, including neonatal sepsis and health-care-associated infections, and limit the potential health benefits from surgeries, transplants, and cancer treatment. The challenge of simultaneously expanding appropriate access to antimicrobials, while restricting inappropriate access, particularly to expensive, newer generation antimicrobials, is unique in global health and requires new approaches to financing and delivering health care and a one-health perspective on the connections between pathogen transmission in animals and humans. Here, we describe the importance of effective antimicrobials. We assess the disease burden caused by limited access to antimicrobials, attributable to resistance to antimicrobials, and the potential effect of vaccines in restricting the need for antibiotics.

  9. Access to effective antimicrobials: a worldwide challenge.

    PubMed

    Laxminarayan, Ramanan; Matsoso, Precious; Pant, Suraj; Brower, Charles; Røttingen, John-Arne; Klugman, Keith; Davies, Sally

    2016-01-01

    Recent years have seen substantial improvements in life expectancy and access to antimicrobials, especially in low-income and lower-middle-income countries, but increasing pathogen resistance to antimicrobials threatens to roll back this progress. Resistant organisms in health-care and community settings pose a threat to survival rates from serious infections, including neonatal sepsis and health-care-associated infections, and limit the potential health benefits from surgeries, transplants, and cancer treatment. The challenge of simultaneously expanding appropriate access to antimicrobials, while restricting inappropriate access, particularly to expensive, newer generation antimicrobials, is unique in global health and requires new approaches to financing and delivering health care and a one-health perspective on the connections between pathogen transmission in animals and humans. Here, we describe the importance of effective antimicrobials. We assess the disease burden caused by limited access to antimicrobials, attributable to resistance to antimicrobials, and the potential effect of vaccines in restricting the need for antibiotics. PMID:26603918

  10. Conditioned Emotional Distress in Women Receiving Chemotherapy for Breast Cancer.

    ERIC Educational Resources Information Center

    Jacobsen, Paul B.; And Others

    1995-01-01

    Investigated whether women undergoing outpatient chemotherapy for breast cancer can develop classically conditioned emotional distress. Patients' responses to a distinctive stimulus were assessed in a location not associated with chemotherapy administration. Results supported hypothesis that pairing a distinctive stimulus with chemotherapy would…

  11. Palliative communications: addressing chemotherapy in patients with advanced cancer.

    PubMed

    Kadakia, K C; Moynihan, T J; Smith, T J; Loprinzi, C L

    2012-04-01

    Patients with advanced cancers often endure chemotherapy late in their disease course leading to unnecessary adverse effects, loss of quality of life, and delay in hospice referral. Compassionate and honest communication about the use of chemotherapy can facilitate better patient care. This manuscript will explore communication issues regarding palliative-intent chemotherapy.

  12. Antimicrobial activity of trout hepcidin.

    PubMed

    Alvarez, Claudio A; Guzmán, Fanny; Cárdenas, Constanza; Marshall, Sergio H; Mercado, Luis

    2014-11-01

    Hepcidin is an antimicrobial peptide and a hormone produced mostly the liver. It is a cysteine-rich peptide with a highly conserved β-sheet structure. Recently, we described the hepcidin expression in liver of rainbow trout and its inducibility by iron overloading and lipopolysaccharide (LPS). Thus, in this work, we focused in analyzing the importance of the peptide conformation associated to its oxidative state in the antimicrobial activity. This peptide showed a α-helix conformation in reduced state and the characteristic β-sheet conformation in the oxidized state. Antimicrobial activity assays showed that the oxidized peptide is more effective than the reduced peptide against Escherichia coli and the important salmon fish pathogen Piscirickettsia salmonis. In addition, confocal analysis of P. salmonis culture exposed to trout hepcidin coupled with rhodamine revealed the intracellular location of this peptide and Sytox permeation assay showed that membrane disruption is not the mechanism of its antimicrobial action. Moreover, a conserved ATCUN motif was detected in the N-terminus of this peptide. This sequence has been described as a small metal-binding site that has been implicated in DNA cleavage. In this work we proved that this peptide is able to induce DNA hydrolysis in the presence of ascorbate and CuCl2. When the same experiments were carried out using a variant with truncated N-terminus no DNA hydrolysis was observed. Our results suggest that correct folding of hepcidin is required for its antimicrobial activity and most likely the metal-binding site (ATCUN motif) present in its N-terminus is involved in the oxidative damage to macromolecules. PMID:24794583

  13. [Hypomagnesemia following chemotherapy of disseminated testicular tumors].

    PubMed

    Hida, S; Nishimura, K; Nishio, Y; Okada, Y; Okada, K; Yoshida, O

    1988-01-01

    Sixteen patients with metastatic testicular cancer were treated with combination chemotherapy including cisplatin (CDDP) at 3- to 4-week intervals for two to five courses. There was a sequential fall in serum magnesium with each course of therapy: 13 of the 16 patients (81%) became hypomagnesemic, and the median magnesium nadir was 1.67 mg/dl. Serum magnesium nadir levels gradually decreased according to the cumulative CDDP dose. Acute clinical effects of the hypomagnesemia were observed in 4 patients, 2 of them complained of neuromuscular disturbance in the extremities, one of cardiac arrhythmia, and the other of Raynaud's phenomenon. The median time to the onset of hypomagnesemia was 67 days and the duration of hypomagnesemia was 24 days. The creatinine clearance (Ccr) decreased gradually according to the cumulative CDDP dose, and the mean Ccr declined from 87.2 ml/min before therapy to 55.8 ml/min. In 3 out of 16 patients, an irreversible decrease to below 50 ml/min was seen after chemotherapy. In patients with normal renal function treated by VAB-6 regimen, creatinine clearance (Ccr) decreased transiently during each course of chemotherapy and returned to the pretreatment level during the interval. The mean creatinine clearance declined from 90.7 ml/min before therapy to 82.9 ml/min after three courses of induction chemotherapy. Urinary excretion of beta 2 microglobulin (beta 2MG) increased transiently before Ccr began to decrease during each course of chemotherapy. Serum potassium and calcium concentrations decreased transiently probably due to urinary losses but there was no significant relationship between hypopotassemia, hypocalcemia and hypomagnesemia.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Prognostic nutritional index before adjuvant chemotherapy predicts chemotherapy compliance and survival among patients with non-small-cell lung cancer

    PubMed Central

    Shimizu, Katsuhiko; Okita, Riki; Saisho, Shinsuke; Yukawa, Takuro; Maeda, Ai; Nojima, Yuji; Nakata, Masao

    2015-01-01

    Background Adjuvant chemotherapy after the complete resection of non-small-cell lung cancer (NSCLC) is now the standard of care. To improve survival, it is important to identify risk factors for the continuation of adjuvant chemotherapy. In this study, we analyzed chemotherapy compliance and magnitude of the prognostic impact of the prognostic nutritional index (PNI) before adjuvant chemotherapy. Methods We conducted a retrospective review of data from 106 patients who had received adjuvant chemotherapy. The adjuvant chemotherapy consisted of an oral tegafur agent (OT) or platinum-based chemotherapy (PB). The correlations between the PNI values and recurrence-free survival (RFS) were then evaluated. Results In the PB group, the percentage of patients who completed the four planned cycles of chemotherapy was not correlated with the PNI. In the OT group, however, a significant difference was observed in the percentage of patients who completed the planned chemotherapy according to the PNI before adjuvant chemotherapy. The RFS of patients with a PNI <50 before adjuvant chemotherapy was significantly poorer than that of the patients with a PNI ≥50. A multivariate analysis showed that nodal metastasis and PNI before chemotherapy were independent predictors of the RFS. However, PNI before surgery was not a predictor of the RFS. In the subgroup analysis, PNI before chemotherapy was independent predictor of the RFS in the OT group (P=0.019), but not in the PB group (P=0.095). Conclusion The PNI before adjuvant chemotherapy influenced the treatment compliance with the planned chemotherapy in the OT group, but not the PB group. In addition, a low PNI before adjuvant chemotherapy was associated with a poor RFS in a multivariate analysis, especially in the OT group. PMID:26504397

  15. Is there liability with chemotherapy following immediate breast construction?

    PubMed

    Yule, G J; Concannon, M J; Croll, G; Puckett, C L

    1996-04-01

    Review of 46 consecutive patients undergoing immediate breast reconstruction with tissue expanders and subsequent implant placement was conducted to assess the potential liability of adjuvant chemotherapy. Twenty-three patients required chemotherapy, while 23 did not. Critical comparison of complications and outcome of the two groups revealed no significant differences. Within the parameters of the study (avoidance of expansion or surgery during the period of chemotherapy), there appeared to be no disadvantage posed to the immediate reconstruction patient by adjuvant chemotherapy. We feel that this option can continue to be offered despite the anticipation of probable chemotherapy.

  16. Chemotherapy: Does Neoadjuvant or Adjuvant Therapy Improve Outcomes?

    PubMed

    Canter, Robert J

    2016-10-01

    Since preoperative chemotherapy has been clearly shown to improve outcomes for patients with Ewing sarcoma, rhabdomyosarcoma, and osteosarcoma, practitioners have attempted to extend the use of adjuvant/neoadjuvant chemotherapy to other types of adult soft tissue sarcoma. Given the high risk of distant recurrence and disease-specific death for patients with soft tissue sarcoma tumors larger than 10 cm, these patients should be considered candidates for neoadjuvant chemotherapy as well as investigational therapies. Yet, potential toxicity from cytotoxic chemotherapy is substantial, and there remains little consensus and wide variation regarding the indications for use of chemotherapy in the adjuvant/neoadjuvant setting. PMID:27591503

  17. Antimicrobial Stewardship and Urinary Tract Infections

    PubMed Central

    Abbo, Lilian M.; Hooton, Thomas M.

    2014-01-01

    Urinary tract infections are the most common bacterial infections encountered in ambulatory and long-term care settings in the United States. Urine samples are the largest single category of specimens received by most microbiology laboratories and many such cultures are collected from patients who have no or questionable urinary symptoms. Unfortunately, antimicrobials are often prescribed inappropriately in such patients. Antimicrobial use, whether appropriate or inappropriate, is associated with the selection for antimicrobial-resistant organisms colonizing or infecting the urinary tract. Infections caused by antimicrobial-resistant organisms are associated with higher rates of treatment failures, prolonged hospitalizations, increased costs and mortality. Antimicrobial stewardship consists of avoidance of antimicrobials when appropriate and, when antimicrobials are indicated, use of strategies to optimize the selection, dosing, route of administration, duration and timing of antimicrobial therapy to maximize clinical cure while limiting the unintended consequences of antimicrobial use, including toxicity and selection of resistant microorganisms. This article reviews successful antimicrobial stewardship strategies in the diagnosis and treatment of urinary tract infections. PMID:27025743

  18. Cognitive effects of chemotherapy-induced menopause in breast cancer.

    PubMed

    Vearncombe, Katharine J; Rolfe, Margaret; Andrew, Brooke; Pachana, Nancy A; Wright, Margaret; Beadle, Geoffrey

    2011-11-01

    This study examined whether chemotherapy-induced menopause affects cognitive functioning in women with early breast cancer. The neuropsychological performance of 121 breast cancer patients (age M=49.62, SD=8.11, range=25.25-67.92) treated with chemotherapy was assessed pre-chemotherapy, as well as 1, 6, and 18 months post-chemotherapy completion. Linear mixed modeling was used to evaluate the data. Type of menopause (pre, chemotherapy-induced, and post menopause) was found to significantly interact with cognitive performance on two cognitive variables. Specifically, chemotherapy-induced menopausal women did not show any significant changes in performance on an abstract reasoning task, while the pre-menopausal and post-menopausal groups significantly improved over time. A significant interaction on a test of finger dexterity and coordination was also found, although inspection of the results indicated that this was due to a significant improvement in the pre-menopausal groups at 6 months post chemotherapy. After chemotherapy most cognitive variables showed improvements over time, although two indicators of verbal memory showed significant declines immediately after chemotherapy, with improvement by 18 months post completion. The current study found little evidence to suggest that chemotherapy-induced menopause broadly affects cognitive functioning after treatment administration. However, longer follow-up assessments are warranted to assess the long-term effects of combined chemotherapy and endocrine treatment.

  19. Relationship of gonadal activity and chemotherapy-induced gonadal damage

    SciTech Connect

    Rivkees, S.A.; Crawford, J.D.

    1988-04-08

    The authors tested the hypothesis that chemotherapy-induced gonadal damage is proportional to the degree of gonadal activity during treatment. Thirty studies that evaluated gonadal function after cyclophosphamide therapy for renal disease or combination chemotherapy for Hodgkin's disease or acute lymphocytic leukemia provided data for analysis. Data were stratified according to sex, illness, chemotherapeutic regimen and dose, and pubertal stage at the time of treatment. Chemotherapy-induced damage was more likely to occur in patients who were treated when sexually mature compared with those who were treated when prepubertal. Males were significantly more frequently affected than females when treated for renal disease of Hodgkin's disease. Chemotherapy-induced damage was also more likely to occur when patients were treated with large doses of alkylating agents. These data suggest that chemotherapy-induced damage is proportional to gonadal activity. Further efforts are needed to test whether induced gonadal quiescence during chemotherapy will reduce the strikingly high incidence of gonadal failure following chemotherapy.

  20. Management of Breast Cancer Patients with Chemotherapy-Induced Neutropenia or Febrile Neutropenia

    PubMed Central

    Fontanella, Caterina; Bolzonello, Silvia; Lederer, Bianca; Aprile, Giuseppe

    2014-01-01

    Summary Chemotherapy-induced neutropenia (CIN) is a common toxicity caused by the administration of anticancer drugs. This side effect is associated with life-threatening infections and may alter the chemotherapy schedule, thus impacting on early and long-term outcomes. Elderly breast cancer patients with impaired health status or advanced disease as well as patients undergoing dose-dense anthracycline/taxane- or docetaxel-based regimens have the highest risk of CIN. A careful assessment of the baseline risk for CIN allows the selection of patients who need primary prophylaxis with granulocyte colony-stimulating factor (G-CSF) and/or antimicrobial agents. Neutropenic cancer patients may develop febrile neutropenia and CIN-related severe medical complications. Specific risk assessment scores, along with comprehensive clinical evaluation, are able to define a group of febrile patients with low risk for complications who can be safely treated as outpatients. Conversely, patients with higher risk of severe complications should be hospitalized and should receive intravenous antibiotic therapy with or without G-CSF. PMID:25404882

  1. Antimicrobial peptides in the brain.

    PubMed

    Su, Yanhua; Zhang, Kai; Schluesener, Hermann J

    2010-10-01

    Antimicrobial peptides (AMPs) are an evolutionarily conserved component of the innate immune system of many species. The brain is an immunologically privileged organ but can produce a robust immune response against pathogens and cell debris, promoting rapid and efficient clearance. AMPs may be critically involved in the innate immune system of the brain. Though the mechanisms of AMPs' action in the brain still need further elucidation, many studies have shown that AMPs are multifunctional molecules in the brain. In addition to antimicrobial action, they take part in congenital and adaptive immune reactions (immunoregulation), function as signaling molecules in tissue repair, inflammation and other important processes through different mechanisms, and they might, in addition, become diagnostic markers of brain disease.

  2. Antimicrobial resistance of mastitis pathogens.

    PubMed

    Oliver, Stephen P; Murinda, Shelton E

    2012-07-01

    Antibiotics are used extensively in the dairy industry to combat disease and to improve animal performance. Antibiotics such as penicillin, cephalosporin, streptomycin, and tetracycline are used for the treatment and prevention of diseases affecting dairy cows caused by a variety of gram-positive and gram-negative bacteria. Antibiotics are often administrated routinely to entire herds to prevent mastitis during the dry period. An increase in the incidence of disease in a herd generally results in increased use of antimicrobials, which in turn increases the potential for antibiotic residues in milk and the potential for increased bacterial resistance to antimicrobials. Continued use of antibiotics in the treatment and prevention of diseases of dairy cows will continue to be scrutinized. It is clear that strategies employing the prudent use of antimicrobials are needed. This clearly illustrates the importance of effective herd disease prevention and control programs. Based on studies published to date, scientific evidence does not support widespread, emerging resistance among mastitis pathogens to antibacterial drugs even though many of these antibiotics have been used in the dairy industry for treatment and prevention of disease for several decades. However, it is clear that use of antibiotics in dairy cows can contribute to increased antimicrobial resistance. While antimicrobial resistance does occur, we are of the opinion that the advantages of using antibiotics for the treatment of mastitis far outweigh the disadvantages. The clinical consequences of antimicrobial resistance of dairy pathogens affecting humans appear small. Antimicrobial resistance among dairy pathogens, particularly those found in milk, is likely not a human health concern as long as the milk is pasteurized. However, there are an increasing number of people who choose to consume raw milk. Transmission of an antimicrobial-resistant mastitis pathogen and/or foodborne pathogen to humans could occur

  3. Antimicrobial resistance in Saudi Arabia

    PubMed Central

    Zowawi, Hosam M.

    2016-01-01

    Antimicrobial resistance (AMR) is increasingly being highlighted as an urgent public and animal health issue worldwide. This issue is well demonstrated in bacteria that are resistant to last-line antibiotics, suggesting a future with untreatable infections. International agencies have suggested combating strategies against AMR. Saudi Arabia has several challenges that can stimulate the emergence and spread of multidrug-resistant bacteria. Tackling these challenges need efforts from multiple sectors to successfully control the spread and emergence of AMR in the country. Actions should include active surveillance to monitor the emergence and spread of AMR. Infection prevention and control precautions should also be optimized to limit further spread. Raising awareness is essential to limit inappropriate antibiotics use, and the antibiotic stewardship programs in hospital settings, outpatients, and community pharmacies, should regulate the ongoing use of antimicrobials. PMID:27570847

  4. Bacteriophage endolysins as novel antimicrobials

    PubMed Central

    Schmelcher, Mathias; Donovan, David M; Loessner, Martin J

    2013-01-01

    Endolysins are enzymes used by bacteriophages at the end of their replication cycle to degrade the peptidoglycan of the bacterial host from within, resulting in cell lysis and release of progeny virions. Due to the absence of an outer membrane in the Gram-positive bacterial cell wall, endolysins can access the peptidoglycan and destroy these organisms when applied externally, making them interesting antimicrobial candidates, particularly in light of increasing bacterial drug resistance. This article reviews the modular structure of these enzymes, in which cell wall binding and catalytic functions are separated, as well as their mechanism of action, lytic activity and potential as antimicrobials. It particularly focuses on molecular engineering as a means of optimizing endolysins for specific applications, highlights new developments that may render these proteins active against Gram-negative and intracellular pathogens and summarizes the most recent applications of endolysins in the fields of medicine, food safety, agriculture and biotechnology. PMID:23030422

  5. Antimicrobial Peptides from Marine Proteobacteria

    PubMed Central

    Desriac, Florie; Jégou, Camille; Balnois, Eric; Brillet, Benjamin; Le Chevalier, Patrick; Fleury, Yannick

    2013-01-01

    After years of inadequate use and the emergence of multidrug resistant (MDR) strains, the efficiency of “classical” antibiotics has decreased significantly. New drugs to fight MDR strains are urgently needed. Bacteria hold much promise as a source of unusual bioactive metabolites. However, the potential of marine bacteria, except for Actinomycetes and Cyanobacteria, has been largely underexplored. In the past two decades, the structures of several antimicrobial compounds have been elucidated in marine Proteobacteria. Of these compounds, polyketides (PKs), synthesised by condensation of malonyl-coenzyme A and/or acetyl-coenzyme A, and non-ribosomal peptides (NRPs), obtained through the linkage of (unusual) amino acids, have recently generated particular interest. NRPs are good examples of naturally modified peptides. Here, we review and compile the data on the antimicrobial peptides isolated from marine Proteobacteria, especially NRPs. PMID:24084784

  6. Cholic acid derivatives: novel antimicrobials.

    PubMed

    Savage, P B; Li, C

    2000-02-01

    Mimics of squalamine and polymyxin B (PMB) have been prepared from cholic acid in hope of finding new antimicrobial agents. The squalamine mimics include the polyamine and sulphate functionalities found in the parent antibiotic, however, the positions relative to the steroid nucleus have been exchanged. The PMB mimics include the conservation of functionality among the polymyxin family of antibiotics, the primary amine groups and a hydrophobic chain. Although the squalamine and PMB mimics are morphologically dissimilar, they display similar activities. Both are simple to prepare and demonstrate broad spectrum antimicrobial activity against Gram-negative and Gram-positive organisms. Specific examples may be inactive alone, yet effectively permeabilise the outer membranes of Gram-negative bacteria rendering them sensitive to hydrophobic antibiotics. Problems associated with some of the squalamine and PMB mimics stem from their haemolytic activity and interactions with serum proteins, however, examples exist without these side effects which can sensitise Gram-negative bacteria to hydrophobic antibiotics. PMID:11060676

  7. Cytotoxic drug: towards safer chemotherapy practices.

    PubMed

    Joshi, M C

    2007-01-01

    Health care is nearly 10 years behind other industries in its efforts to reduce the errors. Medication error may be nobody's baby, but when it happens, it could well turn out to be everyone's worry and the reasons given for medication error range from silly to the downright serious. The anticancer drugs are known to be mutagenic, teratogenic and carcinogenic, so extra precaution should be taken while storing, diluting, administering the drugs and disposing the waste. The objectives of this article are to define the standards for using cancer chemotherapy in hospitals; to tackle any spillage of drug and how to dispose of the waste of anticancer drugs. This could be beneficial to any hospital where chemotherapy is given without any defined standard operating procedure. The information furnished in this article is collected from the mentioned references and also from websites- The American Cancer Society: Cancer Facts and Figures 2002, www.cancer.org and www.cancersourceRN.com. PMID:17401222

  8. Using Epigenetic Therapy to Overcome Chemotherapy Resistance.

    PubMed

    Strauss, Julius; Figg, William D

    2016-01-01

    It has been known for decades that as cancer progresses, tumors develop genetic alterations, making them highly prone to developing resistance to therapies. Classically, it has been thought that these acquired genetic changes are fixed. This has led to the paradigm of moving from one cancer therapy to the next while avoiding past therapies. However, emerging data on epigenetic changes during tumor progression and use of epigenetic therapies have shown that epigenetic modifications leading to chemotherapy resistance have the potential to be reversible with epigenetic therapy. In fact, promising clinical data exist that treatment with epigenetic agents can diminish chemotherapy resistance in a number of tumor types including chronic myelogenous leukemia, colorectal, ovarian, lung and breast cancer. The potential for epigenetic-modifying drugs to allow for treatment of resistant disease is exciting and clinical trials have just begun to evaluate this area.

  9. Chemotherapy-Induced Amenorrhea – An Update

    PubMed Central

    Liedtke, C.; Kiesel, L.

    2012-01-01

    Because of the heterogeneity in the definition of chemotherapy-induced amenorrhea (CIA) there are distinct differences in the literature with regard to its incidence as well as its dependence on various influencing factors. The occurrence of CIA varies greatly depending on the applied chemotherapy. The pathogenesis of CIA is especially based on a reduction of ovarian reserves. Various sonographic and biochemical factors can be used to exclude or confirm CIA. This is particularly important when an endocrine therapy with tamoxifen is not possible and the use of aromatase inhibitors is under consideration. CIA and especially the frequently thereby resulting early menopause can lead to pronounced restrictions in the quality of life of the affected patients, not least due to the resulting infertility. On the other hand, various studies have shown that CIA may have a positive prognostic significance. Thus, the identification of measures to prevent CIA (for example, through the use of GnRH analogues) is of particular importance. PMID:26640289

  10. [Scalp cooling for chemotherapy-induced alopecia].

    PubMed

    Komen, Marion M C; Smorenburg, Carolien H; van den Hurk, Corina J G; Nortier, J W R Hans

    2011-01-01

    Alopecia is a very common side effect of cytostatic therapy and is considered one of the most emotionally distressing effects. To prevent alopecia scalp cooling is currently used in some indications in medical oncology in 59 hospitals in the Netherlands. The success of scalp cooling depends on various factors such as type of chemotherapy, dose, infusion time, number of treatment cycles and combinations of drugs. In general, scalp cooling is well tolerated. The reported side-effects are headache, coldness, dizziness and sometimes claustrophobia. An increase in the risk of scalp metastases has not been demonstrated. Proceeding from the South Netherlands Comprehensive Cancer Centre a national working group is put together in order to draw up a national guideline for chemotherapy-induced alopecia. PMID:22085565

  11. Computed tomography of osteosarcoma after intraarterial chemotherapy

    SciTech Connect

    Shirkhoda, A.; Jaffe, N.; Wallace, S.; Ayala, A.; Lindell, M.M.; Zornoza, J.

    1985-01-01

    The response to intraarterial cis-diamminedichloroplatinum II (CDP) chemotherapy was evaluated by computed tomography (CT) in 33 patients with pathologically proved osteosarcoma of the long or flat bones. Twenty-one of the 33 patients had a CT scan before chemotherapy was started. In the other 12 patients, a CT scan was obtained after at least two courses of treatment, and additional studies were performed during the course of therapy. In those patients responding to treatment, the posttherapy scan revealed a remarkable decrease or complete disappearance of the associated soft-tissue mass and clear reestablishment of the fat planes between the muscle bundles that had been obscured. There was sharp definition of the peripheral margins of the calcified healing neoplasm, and the calcification in the healing tumor could be differentiated easily from that of the original bone neoplasm. CT was more accurate than conventional studies in detecting healing process and diagnosis of remission.

  12. Antimicrobials & cholera: are we stranded?

    PubMed

    Ghosh, Amit; Ramamurthy, T

    2011-02-01

    Antimicrobial resistance poses a major threat in the treatment of infectious diseases. Though significant progress in the management of diarrhoeal diseases has been achieved by improved hygiene, development of new antimicrobials and vaccines, the burden remains the same, especially in children below 5 yr of age. In the case of cholera, though oral rehydration treatment is the mainstay, antimicrobial therapy is mandatory at times to reduce the volume of stool and shorten the duration of the disease. Though for many pathogens, antimicrobial resistance emerged soon after the introduction of antibiotics, Vibrio cholerae remained sensitive to most of the antibiotics for quite a long period. However, the scenario changed over the years and today, V. cholerae strains isolated world over are resistant to multiple antibiotics. A myriad number of mechanisms underlie this phenomenon. These include production of extended-spectrum beta-lactamases, enhanced multi-drug efflux pump activity, plasmid-mediated quinolone and fluoroquinolone resistance, and chromosomal mutations. Horizontal transfer of resistance determinants with mobile genetic elements like integrons and the integrating conjugative elements (ICEs), SXTs help in the dissemination of drug resistance. Though all strains isolated are not resistant to all antibiotics and we are not as yet "stranded", expanding spectrum of drug resistance is a definite cause for concern. Pipelines of discovery of new antibiotics are drying up as major pharmaceutical companies are losing interest in investing money in this endeavour, mainly due to the short shelf-life of the antibiotics and also due to the fast emergence of drug resistance. To address this issue, attempts are now being made to discover drugs which are pathogen specific and target their "virulence mechanisms". It is expected that development of resistance against such antibiotics would take much longer. This review briefly focuses on all these issues.

  13. Magic bullets and moving targets: antibiotic resistance and experimental chemotherapy, 1900-1940.

    PubMed

    Gradmann, Christoph

    2011-01-01

    It was in the 1940s that antibiotic resistance arose as an object of study for clinical medicine. Somewhat earlier it had become an important analytical tool for bacterial geneticists. However, the concept of antibiotic resistance as an induced and inheritable trait of microbial species was introduced a generation earlier in the years preceding the First World War. The paper reconstructs the concept that was put forward by the German immunologist Paul Ehrlich in 1907. He came across the phenomenon when trying to develop chemotherapies for trypanosomiasis, the best known of which is African sleeping sickness. However, resistance was studied by him for other than therapy-related purposes. It provided a productive laboratory model for the study of cell functions. Induced resistance to chemicals facilitated the development of ideas on the relation of a parasite's cellular metabolism and of drug action, i.e. by providing a negative proof for the existence of chemoreceptors on the surfaces of parasite cells. This approach does also serve to explain why British and German researchers continued to study the phenomenon of induced resistance in microbes for decades -despite it being absent from clinical medicine. After all, there existed very few chemotherapies of infectious diseases prior to the arrival of the sulfa drugs. Moreover, resistance to such medicines was rarely observed. However, being part and parcel of Ehrlich's theories, his views on resistance were also criticised together with these. It was in particular Henry Dale who would challenge Ehrlich's views of resistance being an inheritable and stable trait of microbes. Instead he insisted that understanding this "wholly mysterious phenomenon" required taking into account some host interaction. Induced resistance, which had come into being as a chance discovery on the chemotherapy of sleeping sickness, thus became one of the more important laboratory models of twentieth-century immunological research. Its early

  14. Benchmarking antimicrobial drug use in hospitals.

    PubMed

    Ibrahim, Omar M; Polk, Ron E

    2012-04-01

    Measuring and monitoring antibiotic use in hospitals is believed to be an important component of the strategies available to antimicrobial stewardship programs to address acquired antimicrobial resistance. Recent efforts to organize large numbers of hospitals into networks allow for interhospital comparisons of a variety of healthcare processes and outcomes, a process often called 'benchmarking'. For comparisons of antimicrobial use to be valid, usage figures must be risk-adjusted to account for differences in patient mix and hospital characteristics. The purpose of this review is to describe recent methods to benchmark antimicrobial drug use and to critically assess the potential advantages and the remaining challenges. While many methodological challenges remain, and the clinical outcomes resulting from benchmarking programs have yet to be determined, recent developments suggest that benchmarking antimicrobial drug use will become an important component of antimicrobial stewardship program activities.

  15. Antimicrobial hydrogels for the treatment of infection

    PubMed Central

    Veiga, Ana Salomé; Schneider, Joel P.

    2014-01-01

    The increasing prevalence of microbial infections, especially those associated with impaired wound healing and biomedical implant failure has spurred the development of new materials having antimicrobial activity. Hydrogels are a class of highly hydrated material finding use in diverse medical applications such as drug delivery, tissue engineering, as wound fillers and as implant coatings, to name a few. The biocompatible nature of many gels make them a convenient starting platform to develop selectively active antimicrobial materials. Hydrogels with antimicrobial properties can be obtained through the encapsulation or covalent immobilization of known antimicrobial agents, or the material itself can be designed to possess inherent antimicrobial activity. In this review we present an overview of antimicrobial hydrogels that have recently been developed and when possible provide a discussion relevant to their mechanism of action. PMID:24122459

  16. Antimicrobial hydrogels for the treatment of infection.

    PubMed

    Veiga, Ana Salomé; Schneider, Joel P

    2013-11-01

    The increasing prevalence of microbial infections, especially those associated with impaired wound healing and biomedical implant failure has spurred the development of new materials having antimicrobial activity. Hydrogels are a class of highly hydrated material finding use in diverse medical applications such as drug delivery, tissue engineering, as wound fillers, and as implant coatings, to name a few. The biocompatible nature of many gels make them a convenient starting platform to develop selectively active antimicrobial materials. Hydrogels with antimicrobial properties can be obtained through the encapsulation or covalent immobilization of known antimicrobial agents, or the material itself can be designed to possess inherent antimicrobial activity. In this review we present an overview of antimicrobial hydrogels that have recently been developed and when possible provide a discussion relevant to their mechanism of action.

  17. Use of antimicrobial agents in aquaculture.

    PubMed

    Park, Y H; Hwang, S Y; Hong, M K; Kwon, K H

    2012-04-01

    The aquaculture industry has grown dramatically, and plays an important role in the world's food supply chain. Antimicrobial resistance in bacteria associated with food animals receives much attention, and drug use in aquaculture is also an important issue. There are many differences between aquatic and terrestrial management systems, such as the methods used for administration of drugs. Unique problems are related to the application of drugs in aquatic environments. Residual drugs in fish products can affect people who consume them, and antimicrobials released into aquatic environments can select for resistant bacteria. Moreover, these antimicrobial-resistant bacteria, or their resistance genes, can be transferred to humans. To decrease the risks associated with the use of antimicrobials, various regulations have been developed. In addition, it is necessary to prevent bacterial diseases in aquatic animals by vaccination, to improve culture systems, and to monitor the amount of antimicrobial drugs used and the prevalence of antimicrobial-resistant bacteria.

  18. Psychosocial and Physical Effects of Adjuvant Chemotherapy

    PubMed Central

    Hislop, Thomas Gregory; Elwood, J. Mark; Waxler-Morrison, Nancy; Ragaz, Joseph; Skippen, Diane Hazel; Turner, I.D.

    1991-01-01

    Breast cancer patients younger than 55 completed a questionnaire on psychosocial factors and physical side effects shortly after diagnosis and 9 to 15 months after diagnosis. Those who had used adjuvant chemotherapy were more likely than those who had not to report physical side effects; there was little difference in psychosocial factors. Recent users were more likely than ex-users to report physical side effects, difficulties with domestic chores, and improvement in psychosocial factors. PMID:21229020

  19. [Continuous ambulatory chemotherapy with elastomer pump].

    PubMed

    Cabrera Figueroa, J; Arias Hernández, M

    2001-09-01

    Continuous perfusion administration of chemotherapy can be performed by means of various devices known as pumps. There are syringe pumps, elastomeric pumps, peristaltic pumps and pumps which can be implanted. In our hospital environment, the elastomeric pump enjoys a high degree of acceptance since it permits a cancer patient to maintain a large degree of autonomy while he/she carries on his/her activities. PMID:12150128

  20. Chemotherapy or radiation-induced oral mucositis.

    PubMed

    Lalla, Rajesh V; Saunders, Deborah P; Peterson, Douglas E

    2014-04-01

    Oral mucositis is a significant toxicity of systemic chemotherapy and of radiation therapy to the head and neck region. The morbidity of oral mucositis can include pain, nutritional compromise, impact on quality of life, alteration in cancer therapy, risk for infection, and economic costs. Management includes general symptomatic support and targeted therapeutic interventions for the prevention or treatment of oral mucositis. Evidence-based clinical practice guidelines are available to guide clinicians in the selection of effective management strategies.

  1. A New mouthwash for Chemotherapy Induced Stomatitis

    PubMed Central

    Miranzadeh, Sedigheh; Adib-Hajbaghery, Mohsen; Soleymanpoor, Leyla; Ehsani, Majid

    2014-01-01

    Background: Stomatitis is a disturbing side-effect of chemotherapy that disturbs patients and causes difficulties in patient’s drinking, eating and talking, and may results in infection and bleeding. Objectives: This study aimed to investigate the effect of Yarrow distillate in the treatment of chemotherapy-induced stomatitis. Patients and Methods: This randomized controlled trial study was conducted during 2013. The study population consisted of all cancer patients with chemotherapy-induced oral stomatitis referred to Shahid Beheshti Medical Center, Kashan, Iran. The data collection instrument had two-part; a demographic part and another part recording the severity of the stomatitis at the first, seventh, and 14th days of the intervention based on a WHO criteria checklist in 2005. In this study, 56 patients diagnosed with cancer were randomly assigned into control and experimental groups in similar blocks according to their stomatitis severity. The experimental group gargled 15 mL of a routine solution mixed with Yarrow distillate 4 times a day for 14 days while the control group gargled 15 mL of routine solution. The severity of stomatitis was assessed at the beginning of the intervention, and then after 7 and 14 days of the study. Data were analyzed using chi-square and Fisher exact test, Mann-Whitney U, Kruskal-Wallis, and Friedman tests using SPSS 11.5 software. Results: At first, the median score of stomatitis in the experimental group was 2.50 that significantly reduced to 1 and 0 in days 7 and 14 of the intervention, respectively (P value < 0.001). However, in the control group, the median score of stomatitis was 2.50, which significantly increased to 3 in days 7 and 14 (P value < 0.001). Conclusions: Yarrow distillate-contained solution reduced stomatitis severity more than the routine solution. Therefore, we suggest using it in patients with chemotherapy-induced stomatitis. PMID:25699281

  2. Collagen-like antimicrobial peptides.

    PubMed

    Masuda, Ryo; Kudo, Masakazu; Dazai, Yui; Mima, Takehiko; Koide, Takaki

    2016-11-01

    Combinatorial library composed of rigid rod-like peptides with a triple-helical scaffold was constructed. The component peptides were designed to have various combinations of basic and neutral (or hydrophobic) amino acid residues based on collagen-like (Gly-Pro-Yaa)-repeating sequences, inspired from the basic and amphiphilic nature of naturally occurring antimicrobial peptides. Screening of the peptide pools resulted in identification of antimicrobial peptides. A structure-activity relationship study revealed that the position of Arg-cluster at N-terminus and cystine knots at C-terminus in the triple helix significantly contributed to the antimicrobial activity. The most potent peptide RO-A showed activity against Gram-negative Escherichia coli and Gram-positive Bacillus subtilis. In addition, Escherichia coli exposed to RO-A resulted in abnormal elongation of the cells. RO-A was also shown to have remarkable stability in human serum and low cytotoxicity to mammalian cells. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 453-459, 2016. PMID:27271210

  3. Plant Products as Antimicrobial Agents

    PubMed Central

    Cowan, Marjorie Murphy

    1999-01-01

    The use of and search for drugs and dietary supplements derived from plants have accelerated in recent years. Ethnopharmacologists, botanists, microbiologists, and natural-products chemists are combing the Earth for phytochemicals and “leads” which could be developed for treatment of infectious diseases. While 25 to 50% of current pharmaceuticals are derived from plants, none are used as antimicrobials. Traditional healers have long used plants to prevent or cure infectious conditions; Western medicine is trying to duplicate their successes. Plants are rich in a wide variety of secondary metabolites, such as tannins, terpenoids, alkaloids, and flavonoids, which have been found in vitro to have antimicrobial properties. This review attempts to summarize the current status of botanical screening efforts, as well as in vivo studies of their effectiveness and toxicity. The structure and antimicrobial properties of phytochemicals are also addressed. Since many of these compounds are currently available as unregulated botanical preparations and their use by the public is increasing rapidly, clinicians need to consider the consequences of patients self-medicating with these preparations. PMID:10515903

  4. Antimicrobial Properties of Amyloid Peptides

    PubMed Central

    Kagan, Bruce L.; Jang, Hyunbum; Capone, Ricardo; Arce, Fernando Teran; Ramachandran, Srinivasan; Lal, Ratnesh; Nussinov, Ruth

    2011-01-01

    More than two dozen clinical syndromes known as amyloid diseases are characterized by the buildup of extended insoluble fibrillar deposits in tissues. These amorphous Congo red staining deposits known as amyloids exhibit a characteristic green birefringence and cross-β structure. Substantial evidence implicates oligomeric intermediates of amyloids as toxic species in the pathogenesis of these chronic disease states. A growing body of data has suggested that these toxic species form ion channels in cellular membranes causing disruption of calcium homeostasis, membrane depolarization, energy drainage, and in some cases apoptosis. Amyloid peptide channels exhibit a number of common biological properties including the universal U-shape β-strand-turn-β-strand structure, irreversible and spontaneous insertion into membranes, production of large heterogeneous single-channel conductances, relatively poor ion selectivity, inhibition by Congo red, and channel blockade by zinc. Recent evidence has suggested that increased amounts of amyloids are not only toxic to its host target cells but also possess antimicrobial activity. Furthermore, at least one human antimicrobial peptide, protegrin-1, which kills microbes by a channel-forming mechanism, has been shown to possess the ability to form extended amyloid fibrils very similar to those of classic disease-forming amyloids. In this paper, we will review the reported antimicrobial properties of amyloids and the implications of these discoveries for our understanding of amyloid structure and function. PMID:22081976

  5. [Experimental study on chemotherapy of acute glanders].

    PubMed

    Iliukhin, V I; Rotov, K A; Senina, T V; Snatenkov, E A; Tikhonov, S N; Plekhanova, N G; Kulikova, A S; Shubnikova, E V; Korol', E V; Nekhezina, M O

    2012-01-01

    Glanders is a zoonotic infection inducing acute forms of the disease (pneumonia, sepsis) in humans and animals under certain conditions, which even with the use of modern chemotherapy have unfavourable prognosis. Insufficient of efficacy of antibiotics with in vitro low MIC for planktonic bacterial suspension of Burkholderia mallei in chemotherapy of acute forms of glanders was due to the capacity of the pathogen for intracellular survival and formation of biofilms. Under such conditions the susceptibility of B. mallei to antibiotics lowered by several orders of magnitude. Chemotherapy of the glanders acute forms in animals usually provided only an increase of the lifespan, while among the survivors there was recorded a high relapse rate. More favourable outcomes were observed with the use of in vitro effective antibiotics in the form of clathrate compounds or especially liposomal forms. In the experiments with golden hamsters the survival rate reached 100% in 1000 Dlm infection even with the treatment onset by meropenem liposomal form 48 hours after the infection. Chemotherapeutics in the liposomal form significantly lowered resistance of B. mallei in both the experiments with a suspension of planktonic organisms and the use of bacteria interned in eukaryotic cells (Tetrahymena pyriformis).

  6. Systemic Treatment Safety Symposium 2014: Oral Chemotherapy

    PubMed Central

    Simanovski, V.; Kaizer, L.; Wright, M.; Rae, E.; Ahmad, N.; Creber, K.; Green, E.; Vu, K.; Kukreti, V.; Krzyzanowska, M.K.

    2014-01-01

    The second Systemic Treatment Safety Symposium, which took place February 21, 2014, in Toronto, aimed to identify opportunities for improving the delivery of systemic cancer treatment in Ontario based on regional needs, while providing a venue for collaboration and knowledge-sharing. The agenda included a series of panel sessions followed by discussions, presentations of regional improvement projects and results, and breakout sessions. Based on the discussion that took place at the symposium, a provincial goal of zero handwritten or verbal oral chemotherapy orders by June 30, 2015, has now been established, and regions will be provided with funding for safe prescribing initiatives to support achievement of that aim. Building on the lessons learned from the 2014 System Treatment Safety Symposium, a common measurement strategy will be identified, and Cancer Care Ontario (cco) will also support the work by identifying the recommended key elements of a safe oral chemotherapy prescription. Additionally, cco will identify areas for improving systemic treatment computerized prescriber order entry systems to better enable prescribing of oral agents within such systems. Among the most prominent of the lessons learned during the symposium was the importance of having a focused topic (such as oral chemotherapy) while maintaining a province-wide scope. Another significant takeaway was that attendees appreciate the opportunity to hear from colleagues across the province about the work underway in various regions. Future safety symposia will also explore opportunities for enhanced engagement with participants through greater use of technology.

  7. Treatment of oral mucositis due to chemotherapy

    PubMed Central

    Bagán-Sebastián, José V

    2016-01-01

    Introduction The management of oral mucositis is a challenge, due to its complex biological nature. Over the last 10 years, different strategies have been developed for the management of oral mucositis caused by chemotherapy in cancer patients. Material and Methods An exhaustive search was made of the PubMed-Medline, Cochrane Library and Scopus databases, crossing the key words “oral mucositis”, “prevention” and “treatment” with the terms “chemotherapy” and “radiotherapy” by means of the boolean operators “AND” and “NOT”. A total of 268 articles were obtained, of which 96 met the inclusion criteria. Results Several interventions for the prevention of oral mucositis, such as oral hygiene protocols, amifostine, benzidamine, calcium phosphate, cryotherapy and iseganan, among others, were found to yield only limited benefits. Other studies have reported a decrease in the appearance and severity of mucositis with the use of cytoprotectors (sucralfate, oral glutamine, hyaluronic acid), growth factors, topical polyvinylpyrrolidone, and low power laser irradiation. Conclusions Very few interventions of confirmed efficacy are available for the management of oral mucositis due to chemotherapy. However, according to the reviewed literature, the use of palifermin, cryotherapy and low power laser offers benefits, reducing the incidence and severity of oral mucositis – though further studies are needed to confirm the results obtained. Key words:Chemotherapy-Induced Oral Mucositis Treatment. PMID:27034762

  8. Fertility preservation after chemotherapy for Hodgkin lymphoma.

    PubMed

    van der Kaaij, Marleen A E; van Echten-Arends, Jannie; Simons, Arnold H M; Kluin-Nelemans, Hanneke C

    2010-12-01

    Treatment for Hodgkin lymphoma can negatively affect fertility. This review summarizes data on fertility after chemotherapy in adult patients. Alkylating chemotherapy, especially if containing procarbazine and/or cyclophosphamide, is most harmful to gonadal functioning. Alkylating regimens cause prolonged azoospermia in 90-100% of men and ovarian failure in 5-25% of women under the age of 30. Non-alkylating chemotherapy, like ABVD, is much less harmful: one-third of male patients develop transient azoospermia, and almost no female patients experience ovarian failure. Age is an important factor for women: females over 30 years have a much higher risk of acute ovarian failure. However, with long-term follow-up the cumulative risk of menopause before the age of 40 becomes the same irrespective of treatment age. In males, semen cryopreservation before start of treatment should be offered to all (post)pubertal patients. For females with a partner, IVF followed by embryo cryopreservation is a widely available method, but this necessitates postponement of lymphoma therapy for at least a month. Oocyte cryopreservation and ovarian tissue cryopreservation are experimental techniques showing great promise. GnRH-analogues are being investigated as possible means to preserve fertility in women, but effectiveness has not yet been proven conclusively.

  9. Insect inducible antimicrobial peptides and their applications.

    PubMed

    Ezzati-Tabrizi, Reyhaneh; Farrokhi, Naser; Talaei-Hassanloui, Reza; Alavi, Seyed Mehdi; Hosseininaveh, Vahid

    2013-12-01

    Antimicrobial peptides (AMPs) are found as important components of the innate immune system (host defense) of all invertebrates. These peptides can be constitutively expressed or induced in response to microbial infections. Indeed, they vary in their amino acid sequences, potency and antimicrobial activity spectra. The smaller AMPs act greatly by disrupting the structure or function of microbial cell membranes. Here, the insect innate immune system with emphasis on inducible antimicrobial peptide properties against microbial invaders has been discussed.

  10. Correlations between Income Inequality and Antimicrobial Resistance

    PubMed Central

    Kirby, Andrew; Herbert, Annie

    2013-01-01

    Objectives The aim of this study is to investigate if correlations exist between income inequality and antimicrobial resistance. This study’s hypothesis is that income inequality at the national level is positively correlated with antimicrobial resistance within developed countries. Data collection and analysis Income inequality data were obtained from the Standardized World Income Inequality Database. Antimicrobial resistance data were obtained from the European antimicrobial Resistance Surveillance Network and outpatient antimicrobial consumption data, measured by Defined daily Doses per 1000 inhabitants per day, from the European Surveillance of antimicrobial Consumption group. Spearman’s correlation coefficient (r) defined strengths of correlations of: > 0.8 as strong, > 0.5 as moderate and > 0.2 as weak. Confidence intervals and p values were defined for all r values. Correlations were calculated for the time period 2003-10, for 15 European countries. Results Income inequality and antimicrobial resistance correlations which were moderate or strong, with 95% confidence intervals > 0, included the following. Enterococcus faecalis resistance to aminopenicillins, vancomycin and high level gentamicin was moderately associated with income inequality (r= ≥0.54 for all three antimicrobials). Escherichia coli resistance to aminoglycosides, aminopenicillins, third generation cephalosporins and fluoroquinolones was moderately-strongly associated with income inequality (r= ≥0.7 for all four antimicrobials). Klebsiella pneumoniae resistance to third generation cephalosporins, aminoglycosides and fluoroquinolones was moderately associated with income inequality (r= ≥0.5 for all three antimicrobials). Staphylococcus aureus methicillin resistance and income inequality were strongly associated (r=0.87). Conclusion As income inequality increases in European countries so do the rates of antimicrobial resistance for bacteria including E. faecalis, E. coli, K. pneumoniae

  11. Antimicrobial technology in orthopedic and spinal implants

    PubMed Central

    Eltorai, Adam EM; Haglin, Jack; Perera, Sudheesha; Brea, Bielinsky A; Ruttiman, Roy; Garcia, Dioscaris R; Born, Christopher T; Daniels, Alan H

    2016-01-01

    Infections can hinder orthopedic implant function and retention. Current implant-based antimicrobial strategies largely utilize coating-based approaches in order to reduce biofilm formation and bacterial adhesion. Several emerging antimicrobial technologies that integrate a multidisciplinary combination of drug delivery systems, material science, immunology, and polymer chemistry are in development and early clinical use. This review outlines orthopedic implant antimicrobial technology, its current applications and supporting evidence, and clinically promising future directions. PMID:27335811

  12. Antimicrobial polymer films for food packaging

    NASA Astrophysics Data System (ADS)

    Concilio, S.; Piotto, S.; Sessa, L.; Iannelli, P.; Porta, A.; Calabrese, E. C.; Galdi, M. R.; Incarnato, L.

    2012-07-01

    New antimicrobial polymeric systems were realized introducing new antimicrobial azo compounds in PP and LDPE matrices. The polymeric materials containing different percentage of azo compounds were mold-casted and the obtained film were tested in vitro against Gram+ and Gram- bacteria and fungi. These results hold promise for the fabrication of bacteria-resistant polymer films by means of simple melt processing with antimicrobial azo-dyes.

  13. Outpatient parenteral antimicrobial therapy in pediatrics: an opportunity to expand antimicrobial stewardship.

    PubMed

    Knackstedt, Elizabeth D; Stockmann, Chris; Davis, Carly R; Thorell, Emily A; Pavia, Andrew T; Hersh, Adam L

    2015-02-01

    We reviewed patient discharges with outpatient parenteral antimicrobial therapy (OPAT) to determine whether outpatient parenteral antimicrobial therapy was modifiable or unnecessary at a large tertiary care children's hospital. At least one modification definitely or possibly would have been recommended for 78% of episodes. For more than 40% of episodes, outpatient parenteral antimicrobial therapy was potentially not indicated. PMID:25633007

  14. Promoting antimicrobial stewardship: using video tools for junior doctors' induction.

    PubMed

    Hadjiphilippou, Savvas; Odogwu, Sarah-Elizabeth; Jeyaratnam, Dakshika

    2014-02-01

    Antimicrobial prescribing is linked to key issues in infection control and patient safety. This article presents a novel video tool for junior doctors promoting antimicrobial stewardship, and thus safe antimicrobial prescribing, through improved awareness of local information technology systems.

  15. Antimicrobial use and resistance in animals.

    PubMed

    McEwen, Scott A; Fedorka-Cray, Paula J

    2002-06-01

    Food animals in the United States are often exposed to antimicrobials to treat and prevent infectious disease or to promote growth. Many of these antimicrobials are identical to or closely resemble drugs used in humans. Precise figures for the quantity of antimicrobials used in animals are not publicly available in the United States, and estimates vary widely. Antimicrobial resistance has emerged in zoonotic enteropathogens (e.g., Salmonella spp., Campylobacter spp.), commensal bacteria (e.g., Escherichia coli, enterococci), and bacterial pathogens of animals (e.g., Pasteurella, Actinobacillus spp.), but the prevalence of resistance varies. Antimicrobial resistance emerges from the use of antimicrobials in animals and the subsequent transfer of resistance genes and bacteria among animals and animal products and the environment. To slow the development of resistance, some countries have restricted antimicrobial use in feed, and some groups advocate similar measures in the United States. Alternatives to growth-promoting and prophylactic uses of antimicrobials in agriculture include improved management practices, wider use of vaccines, and introduction of probiotics. Monitoring programs, prudent use guidelines, and educational campaigns provide approaches to minimize the further development of antimicrobial resistance. PMID:11988879

  16. The Potential of Antimicrobial Peptides as Biocides

    PubMed Central

    Laverty, Garry; Gorman, Sean P.; Gilmore, Brendan F.

    2011-01-01

    Antimicrobial peptides constitute a diverse class of naturally occurring antimicrobial molecules which have activity against a wide range of pathogenic microorganisms. Antimicrobial peptides are exciting leads in the development of novel biocidal agents at a time when classical antibiotics are under intense pressure from emerging resistance, and the global industry in antibiotic research and development stagnates. This review will examine the potential of antimicrobial peptides, both natural and synthetic, as novel biocidal agents in the battle against multi-drug resistant pathogen infections. PMID:22072905

  17. [Pattern of antimicrobial susceptibility of enterococci strains].

    PubMed

    Hoyos, A; Gutiérrez, J; Piédrola, G

    1995-04-01

    Enterococci resistance to antimicrobials has increased lately. We studied the susceptibility to 12 antimicrobials of 150 enterococci strains coming from hospitalized and outpatients, using the agar dilution method. Teicoplanin, followed by imipenem and amoxicilin-clavulanic acid had the lower minimal inhibitory concentrations. No strains of E faecalis was resistant to ampicillin, whereas 14% of E faecium had minimal inhibitory concentrations over 8 micrograms/ml. The high minimal inhibitory concentrations of cefpirome (64 micrograms/ml) renders this antimicrobial useless in the treatment of enterococcal infections. Betalactamase production and resistance to glucopeptides were not detected. Antimicrobial susceptibility of strains coming for hospitalized or outpatients were similar.

  18. Antimicrobial Resistance: Is the World UNprepared?

    PubMed

    2016-09-01

    Long Blurb: On September 21st 2016 the United Nations General Assembly convenes in New York, United States to tackle a looming and seemingly inevitable global challenge with the potential to threaten the health and wellbeing of all people: antimicrobial resistance. In an Editorial, the PLOS Medicine Editors reflect on the challenge of coordinating the response to antimicrobial resistance in order to ensure the viability of current antimicrobials and the development of new therapies against resistant pathogens. Short Blurb: In this month's Editorial, the PLOS Medicine Editors reflect on the upcoming United Nations General Assembly meeting which convenes to discuss the global challenge of antimicrobial resistance. PMID:27618631

  19. Randomized Trial of Two Dosages of Prophylactic Granulocyte Colony-Stimulating Factor after Induction Chemotherapy in Pediatric Acute Myeloid Leukemia

    PubMed Central

    Inaba, Hiroto; Cao, Xueyuan; Pounds, Stanley; Pui, Ching-Hon; Rubnit, Jeffrey E.; Ribeiro, Raul C.; Razzouk, Bassem I.

    2010-01-01

    Background Granulocyte colony-stimulating factor (G-CSF) is effective in accelerating neutrophil recovery after intensive chemotherapy for acute myeloid leukemia (AML). However, the optimal G-CSF dosage for patients with AML has not been determined. To our knowledge, G-CSF dosages have not been compared in a randomized AML study. Methods Patients enrolled on the St. Jude AML97 protocol who remained on study after window therapy were eligible to participate. The effect of the dosage of G-CSF given after induction chemotherapy courses 1 and 2 was analyzed in 46 patients randomly assigned in a double-blinded manner to receive 5 or 10 μg/kg/day of G-CSF. The number of days of G-CSF treatment, neutropenia (absolute neutrophil count < 0.5 × 109/L), and hospitalization; the number of episodes of febrile neutropenia, grade 2-4 infection, and antimicrobial therapy; transfusion requirements; the cost of supportive care; and survival were compared between the two study arms. Results We found no statistically significant difference between the two arms in any of the endpoints measured. Conclusions The higher G-CSF dosage (10 μg/kg/day) offers no greater benefit than the lower dosage (5 μg/kg/day) in patients undergoing intensive chemotherapy for AML. PMID:21381017

  20. Presence of antimicrobial resistance and antimicrobial use in sows are risk factors for antimicrobial resistance in their offspring.

    PubMed

    Callens, Bénédicte; Faes, Christel; Maes, Dominiek; Catry, Boudewijn; Boyen, Filip; Francoys, Delphine; de Jong, Ellen; Haesebrouck, Freddy; Dewulf, Jeroen

    2015-02-01

    This study investigated whether antimicrobial-resistant Escherichia coli in apparently healthy sows and antimicrobial administration to sows and piglets influenced antimicrobial resistance in fecal commensal E. coli from piglets. Sixty sows from three herds and three of their piglets were sampled at several time points. Antimicrobial usage data during parturition and farrowing were collected. Clinical resistance was determined for two isolates per sampling time point for sows and piglets using disk diffusion. Only 27.4% of E. coli isolates from newborn piglets showed no resistance. Resistance to one or two antimicrobial classes equaled 41.2% and 46.8% in isolates from sows and piglets, respectively, for the overall farrowing period. Multiresistance to at least four classes was found as frequently in sows (15.6%) as in piglets (15.2%). Antimicrobial resistance in piglets was influenced by antimicrobial use in sows and piglets and by the sow resistance level (p≤0.05). Using aminopenicillins and third-generation cephalosporins in piglets affected resistance levels in piglets (odds ratios [OR] >1; p≤0.05). Using enrofloxacin in piglets increased the odds for enrofloxacin resistance in piglets (OR=26.78; p≤0.0001) and sows at weaning (OR=4.04; p≤0.05). For sows, antimicrobial exposure to lincomycin-spectinomycin around parturition increased the resistance to ampicillin, streptomycin, trimethoprim-sulfadiazine in sows (OR=21.33, OR=142.74, OR=18.03; p≤0.05) and additionally to enrofloxacin in piglets (OR=7.50; p≤0.05). This study demonstrates that antimicrobial use in sows and piglets is a risk factor for antimicrobial resistance in the respective animals. Moreover, resistance determinants in E. coli from piglets are selected by using antimicrobials in their dam around parturition.

  1. Antimicrobial drugs for treating cholera

    PubMed Central

    Leibovici-Weissman, Ya'ara; Neuberger, Ami; Bitterman, Roni; Sinclair, David; Salam, Mohammed Abdus; Paul, Mical

    2014-01-01

    Background Cholera is an acute watery diarrhoea caused by infection with the bacterium Vibrio cholerae, which if severe can cause rapid dehydration and death. Effective management requires early diagnosis and rehydration using oral rehydration salts or intravenous fluids. In this review, we evaluate the additional benefits of treating cholera with antimicrobial drugs. Objectives To quantify the benefit of antimicrobial treatment for patients with cholera, and determine whether there are differences between classes of antimicrobials or dosing schedules. Search methods We searched the Cochrane Infectious Disease Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE; African Index Medicus; LILACS; Science Citation Index; metaRegister of Controlled Trials; WHO International Clinical Trials Registry Platform; conference proceedings; and reference lists to March 2014. Selection criteria Randomized and quasi-randomized controlled clinical trials in adults and children with cholera that compared: 1) any antimicrobial treatment with placebo or no treatment; 2) different antimicrobials head-to-head; or 3) different dosing schedules or different durations of treatment with the same antimicrobial. Data collection and analysis Two reviewers independently applied inclusion and exclusion criteria, and extracted data from included trials. Diarrhoea duration and stool volume were defined as primary outcomes. We calculated mean difference (MD) or ratio of means (ROM) for continuous outcomes, with 95% confidence intervals (CI), and pooled data using a random-effects meta-analysis. The quality of evidence was assessed using the GRADE approach. Main results Thirty-nine trials were included in this review with 4623 participants. Antimicrobials versus placebo or no treatment Overall, antimicrobial therapy shortened the mean duration of diarrhoea by about a day and a half compared to placebo or no treatment (MD -36.77 hours, 95% CI -43

  2. Antimicrobial susceptibility and molecular epidemiology of Neisseria gonorrhoeae in Germany.

    PubMed

    Horn, Nicole Nari; Kresken, Michael; Körber-Irrgang, Barbara; Göttig, Stephan; Wichelhaus, Cornelia; Wichelhaus, Thomas A

    2014-07-01

    Antimicrobial drug resistance in Neisseria gonorrhoeae has become an increasing public health problem. Hence, surveillance of resistance development is of crucial importance to implement adequate treatment guidelines. Data on the spread of antibiotic resistance among gonococcal isolates in Germany, however, is scarce. In a resistance surveillance study conducted by the Paul Ehrlich Society for Chemotherapy between October 2010 and December 2011, 23 laboratories all over Germany were requested to send N. gonorrhoeae isolates to the study laboratory in Frankfurt am Main. Species verification was performed biochemically using ApiNH and with Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS). Antimicrobial susceptibility testing was performed using the Etest method. For molecular epidemiological analysis, N. gonorrhoeae strains were genotyped by means of N. gonorrhoeae multi-antigen sequence typing. A total of 213 consecutive gonococcal isolates were analyzed in this nationwide study. Applying EUCAST breakpoints, high resistance rates were found for ciprofloxacin (74%) and tetracycline (41%). Penicillin non-susceptibility was detected in 80% of isolates. The rate of azithromycin resistance was 6%, while all strains were susceptible to spectinomycin, cefixime, and ceftriaxone. Molecular typing of gonococcal isolates revealed a great heterogeneity of 99 different sequence types (ST), but ST1407 predominated (n=39). This is the first comprehensive German multi-centre surveillance study on antibiotic susceptibility and molecular epidemiology of N. gonorrhoeae with implications for antibiotic choice for treatment of gonorrhoea. The World Health Organization supports the concept that an efficacious treatment of gonorrhoea results in at least 95% of infections being cured. Accordingly, as spectinomycin is not available on the German market, only the third generation cephalosporins cefixime and ceftriaxone are regarded as valuable drugs

  3. Role of Chemotherapy and Mechanisms of Resistance to Chemotherapy in Metastatic Castration-Resistant Prostate Cancer

    PubMed Central

    Lohiya, Vipin; Aragon-Ching, Jeanny B.; Sonpavde, Guru

    2016-01-01

    Chemotherapy using the taxanes, docetaxel and cabazitaxel, remains an important therapeutic option in metastatic castration-resistant prostate cancer (CRPC). However, despite the survival benefits afforded by these agents, the survival increments are modest and resistance occurs universally. Efforts to overcome resistance to docetaxel by combining with biologic agents have heretofore been unsuccessful. Indeed, resistance to these taxanes is also associated with cross-resistance to the antiandrogen drugs, abiraterone and enzalutamide. Here, we discuss the various mechanisms of resistance to chemotherapy in metastatic CRPC and the potential role of emerging regimens and agents in varying clinical phases of development. PMID:27773999

  4. Update on Adjuvant Chemotherapy for Early Breast Cancer

    PubMed Central

    Rampurwala, Murtuza M; Rocque, Gabrielle B; Burkard, Mark E

    2014-01-01

    Breast cancer is the second most common cancer in women worldwide. Although most women are diagnosed with early breast cancer, a substantial number recur due to persistent micro-metastatic disease. Systemic adjuvant chemotherapy improves outcomes and has advanced from first-generation regimens to modern dose-dense combinations. Although chemotherapy is the cornerstone of adjuvant therapy, new biomarkers are identifying patients who can forego such treatment. Neo-adjuvant therapy is a promising platform for drug development, but investigators should recognize the limitations of surrogate endpoints and clinical trials. Previous decades have focused on discovering, developing, and intensifying adjuvant chemotherapy. Future efforts should focus on customizing therapy and reducing chemotherapy for patients unlikely to benefit. In some cases, it may be possible to replace chemotherapy with treatments directed at specific genetic or molecular breast cancer subtypes. Yet, we anticipate that chemotherapy will remain a critical component of adjuvant therapy for years to come. PMID:25336961

  5. Inhaled chemotherapy in lung cancer: future concept of nanomedicine

    PubMed Central

    Zarogoulidis, Paul; Chatzaki, Ekaterini; Porpodis, Konstantinos; Domvri, Kalliopi; Hohenforst-Schmidt, Wolfgang; Goldberg, Eugene P; Karamanos, Nikos; Zarogoulidis, Konstantinos

    2012-01-01

    Regional chemotherapy was first used for lung cancer 30 years ago. Since then, new methods of drug delivery and pharmaceuticals have been investigated in vitro, and in animals and humans. An extensive review of drug delivery systems, pharmaceuticals, patient monitoring, methods of enhancing inhaled drug deposition, safety and efficacy, and also additional applications of inhaled chemotherapy and its advantages and disadvantages are presented. Regional chemotherapy to the lung parenchyma for lung cancer is feasible and efficient. Safety depends on the chemotherapy agent delivered to the lungs and is dose-dependent and time-dependent. Further evaluation is needed to provide data regarding early lung cancer stages, and whether regional chemotherapy can be used as neoadjuvant or adjuvant treatment. Finally, inhaled chemotherapy could one day be administered at home with fewer systemic adverse effects. PMID:22619512

  6. Adjuvant chemotherapy for rectal cancer: Is it needed?

    PubMed Central

    Milinis, Kristijonas; Thornton, Michael; Montazeri, Amir; Rooney, Paul S

    2015-01-01

    Adjuvant chemotherapy has become a standard treatment of advanced rectal cancer in the West. The benefits of adjuvant chemotherapy after surgery alone have been well established. However, controversy surrounds the use adjuvant chemotherapy in patients who received preoperative chemoradiotherapy, despite it being recommended by a number of international guidelines. Results of recent multicentre randomised control trials showed no benefit of adjuvant chemotherapy in terms of survival and rates of distant metastases. However, concerns exist regarding the quality of the studies including inadequate staging modalities, out-dated chemotherapeutic regimens and surgical approaches and small sample sizes. It has become evident that not all the patients respond to adjuvant chemotherapy and more personalised approach should be employed when considering the benefits of adjuvant chemotherapy. The present review discusses the strengths and weaknesses of the current evidence-base and suggests improvements for future studies. PMID:26677436

  7. The Interplay of Immunotherapy and Chemotherapy: Harnessing Potential Synergies

    PubMed Central

    Emens, Leisha A.; Middleton, Gary

    2016-01-01

    Although cancer chemotherapy has historically been considered immune suppressive, it is now accepted that certain chemotherapies can augment tumor immunity. The recent success of immune checkpoint inhibitors has renewed interest in immunotherapies, and in combining them with chemotherapy to achieve additive or synergistic clinical activity. Two major ways that chemotherapy promotes tumor immunity are by inducing immunogenic cell death as part of its intended therapeutic effect, and by disrupting strategies that tumors use to evade immune recognition. This second strategy in particular is dependent on the drug, its dose, and the schedule of chemotherapy administration in relation to antigen exposure or release. In this Cancer Immunology at the Crossroads article we focus on cancer vaccines and immune checkpoint blockade as a forum for reviewing preclinical and clinical data demonstrating the interplay between immunotherapy and chemotherapy. PMID:25941355

  8. Antimicrobial use in swine production and its effect on the swine gut microbiota and antimicrobial resistance.

    PubMed

    Holman, Devin B; Chénier, Martin R

    2015-11-01

    Antimicrobials have been used in swine production at subtherapeutic levels since the early 1950s to increase feed efficiency and promote growth. In North America, a number of antimicrobials are available for use in swine. However, the continuous administration of subtherapeutic, low concentrations of antimicrobials to pigs also provides selective pressure for antimicrobial-resistant bacteria and resistance determinants. For this reason, subtherapeutic antimicrobial use in livestock remains a source of controversy and concern. The swine gut microbiota demonstrates a number of changes in response to antimicrobial administration depending on the dosage, duration of treatment, age of the pigs, and gut location that is sampled. Both culture-independent and -dependent studies have also shown that the swine gut microbiota contains a large number of antimicrobial resistance determinants even in the absence of antimicrobial exposure. Heavy metals, such as zinc and copper, which are often added at relatively high doses to swine feed, may also play a role in maintaining antimicrobial resistance and in the stability of the swine gut microbiota. This review focuses on the use of antimicrobials in swine production, with an emphasis on the North American regulatory context, and their effect on the swine gut microbiota and on antimicrobial resistance determinants in the gut microbiota. PMID:26414105

  9. Creating and standardizing annual chemotherapy competencies throughout a healthcare system.

    PubMed

    Carreon, Nancy; Sugarman, Cathleen; Beener, Elizabeth; Agan, Donna

    2015-01-01

    Changes in chemotherapy delivery from inpatient to outpatient settings and transition from intravenous to oral administration threaten the competency level of chemotherapy nurses. To standardize care and demonstrate competency across five hospital campuses and four outpatient infusion centers, one health system developed a hands-on competency evaluation for chemotherapy nurses based on a scenario approach. Results included improved confidence, competence, identification of variation, and standardization of equipment, process, and policy. PMID:25608095

  10. Antimicrobial peptides: premises and promises.

    PubMed

    Reddy, K V R; Yedery, R D; Aranha, C

    2004-12-01

    Antimicrobial peptides (AMPs) are an important component of the natural defences of most living organisms against invading pathogens. These are relatively small (< 10kDa), cationic and amphipathic peptides of variable length, sequence and structure. During the past two decades several AMPs have been isolated from a wide variety of animals, both vertebrates and invertebrates, and plants as well as from bacteria and fungi. Most of these peptides are obtained from different sources like macrophages, neutrophils, epithelial cells, haemocytes, fat body, reproductive tract, etc. These peptides exhibit broad-spectrum activity against a wide range of microorganisms including Gram-positive and Gram-negative bacteria, protozoa, yeast, fungi and viruses. A few peptides have also been found to be cytotoxic to sperm and tumour cells. AMPs are classified based on the three dimensional structural studies carried out with the help of NMR. The peptides are broadly classified into five major groups namely (a) peptides that form alpha-helical structures, (b) peptides rich in cysteine residues, (c) peptides that form beta-sheet, (d) peptides rich in regular amino acids namely histatin, arginine and proline and (e) peptides composed of rare and modified amino acids. Most of these peptides are believed to act by disrupting the plasma membrane leading to the lysis of the cell. AMPs have been found to be excellent candidates for developing novel antimicrobial agents and a few of these peptides show antimicrobial activity against pathogens causing sexually transmitted infection (STI), including HIV/HSV. Peptides, namely magainin and nisin have been shown to demonstrate contraceptive properties in vitro and in vivo. A few peptides have already entered clinical trials for the treatment of impetigo, diabetic foot ulcers and gastric helicobacter infections. In this review, we discuss the source, structures and mode of action with special reference to therapeutic considerations of various AMPs

  11. Antimicrobial edible films and coatings.

    PubMed

    Cagri, Arzu; Ustunol, Zeynep; Ryser, Elliot T

    2004-04-01

    Increasing consumer demand for microbiologically safer foods, greater convenience, smaller packages, and longer product shelf life is forcing the industry to develop new food-processing, cooking, handling, and packaging strategies. Nonfluid ready-to-eat foods are frequently exposed to postprocess surface contamination, leading to a reduction in shelf life. The food industry has at its disposal a wide range of nonedible polypropylene- and polyethylene-based packaging materials and various biodegradable protein- and polysaccharide-based edible films that can potentially serve as packaging materials. Research on the use of edible films as packaging materials continues because of the potential for these films to enhance food quality, food safety, and product shelf life. Besides acting as a barrier against mass diffusion (moisture, gases, and volatiles), edible films can serve as carriers for a wide range of food additives, including flavoring agents, antioxidants, vitamins, and colorants. When antimicrobial agents such as benzoic acid, sorbic acid, propionic acid, lactic acid, nisin, and lysozyme have been incorporated into edible films, such films retarded surface growth of bacteria, yeasts, and molds on a wide range of products, including meats and cheeses. Various antimicrobial edible films have been developed to minimize growth of spoilage and pathogenic microorganisms, including Listeria monocytogenes, which may contaminate the surface of cooked ready-to-eat foods after processing. Here, we review the various types of protein-based (wheat gluten, collagen, corn zein, soy, casein, and whey protein), polysaccharide-based (cellulose, chitosan, alginate, starch, pectin, and dextrin), and lipid-based (waxes, acylglycerols, and fatty acids) edible films and a wide range of antimicrobial agents that have been or could potentially be incorporated into such films during manufacture to enhance the safety and shelf life of ready-to-eat foods.

  12. Antimicrobial and biofilm inhibiting diketopiperazines.

    PubMed

    de Carvalho, M P; Abraham, W-R

    2012-01-01

    Diketopiperazines are the smallest cyclic peptides known. 90% of Gram-negative bacteria produce diketopiperazines and they have also been isolated from Gram-positive bacteria, fungi and higher organisms. Biosynthesis of cyclodipeptides can be achieved by dedicated nonribosomal peptide synthetases or by a novel type of synthetases named cyclopeptide synthases. Since the first report in 1924 a large number of bioactive diketopiperazines was discovered spanning activities as antitumor, antiviral, antifungal, antibacterial, antiprion, antihyperglycemic or glycosidase inhibitor agents. As infections are of increasing concern for human health and resistances against existing antibiotics are growing this review focuses on the antimicrobial activities of diketopiperazines. The antibiotic bicyclomycin is a diketopiperazine and structure activity studies revealed the unique nature of this compound which was finally developed for clinical applications. The antimicrobial activities of a number of other diketopiperazines along with structure activity relationships are discussed. Here a special focus is on the activity-toxicity problem of many compounds setting tight limitations to their application as drugs. Not only these classical antimicrobial activities but also proposed action in modulating bacterial communication as a new target to control biofilms will be evaluated. Pathogens organized in biofilms are difficult to eradicate because of the increase of their tolerance for antibiotics for several orders. Diketopiperazines were reported to modulate LuxR-mediated quorum-sensing systems of bacteria, and they are considered to influence cell-cell signaling offering alternative ways of biofilm control by interfering with microbial communication. Concluding the review we will finally discuss the potential of diketopiperazines in the clinic to erase biofilm infections.

  13. A Clinical Prediction Model to Assess Risk for Chemotherapy-Related Hospitalization in Patients Initiating Palliative Chemotherapy

    PubMed Central

    Brooks, Gabriel A.; Kansagra, Ankit J.; Rao, Sowmya R.; Weitzman, James I.; Linden, Erica A.; Jacobson, Joseph O.

    2015-01-01

    IMPORTANCE Chemotherapy-related hospitalizations in patients with advanced cancer are common, distressing, and costly. Methods to identify patients at high risk of chemotherapy toxic effects will permit development of targeted strategies to prevent chemotherapy-related hospitalizations. OBJECTIVE To demonstrate the feasibility of using readily available clinical data to assess patient-specific risk of chemotherapy-related hospitalization. DESIGN, SETTING, AND PARTICIPANTS Nested case-control study conducted from January 2003 through December 2011 at the Mass General/North Shore Cancer Center, a community-based cancer center in north eastern Massachusetts. The parent cohort included 1579 consecutive patients with advanced solid-tumor cancer receiving palliative-intent chemotherapy. Case patients (n = 146) included all patients from the parent cohort who experienced a chemotherapy-related hospitalization. Controls (n = 292) were randomly selected from 1433 patients who did not experience a chemotherapy-related hospitalization. EXPOSURES Putative risk factors for chemotherapy-related hospitalization—including patient characteristics, treatment characteristics, and pretreatment laboratory values—were abstracted from medical records. Multivariable logistic regression was used to model the patient-specific risk of chemotherapy-related hospitalization. MAIN OUTCOMES AND MEASURES Chemotherapy-related hospitalization, as adjudicated by the oncology clinical care team within a systematic quality-assessment program. RESULTS A total of 146 (9.2%) of 1579 patients from the parent cohort experienced a chemotherapy-related hospitalization. In multivariate regression, 7 variables were significantly associated with chemotherapy-related hospitalization: age, Charlson comorbidity score, creatinine clearance, calcium level, below-normal white blood cell and/or platelet count, polychemotherapy (vs monotherapy), and receipt of camptothecin chemotherapy. The median predicted risk of

  14. TESTING ANTIMICROBIAL EFFICACY ON POROUS MATERIALS

    EPA Science Inventory

    The efficacy of antimicrobial treatments to eliminate or control biological growth in the indoor environment can easily be tested on nonporous surfaces. However, the testing of antimicrobial efficacy on porous surfaces, such as those found in the indoor environment [i.e., gypsum ...

  15. Legal issues associated with antimicrobial drug resistance.

    PubMed Central

    Fidler, D. P.

    1998-01-01

    An effective public health strategy against the development of antimicrobial drug resistance needs to be informed by legal as well as scientific analysis. This article describes some legal issues arising from current efforts against antimicrobial resistance and underscores the interdependence between law and public health in these efforts. PMID:9621187

  16. Antimicrobial Constituents from Allium hookeri Root.

    PubMed

    Kima, Jung-Eun; Seo, Ji-Hye; Bae, Min-Suk; Bae, Chun-Sik; Yoo, Jin-Cheol; Bang, Mi-Ae; Cho, Seung-Sik; Park, Dae-Hun

    2016-02-01

    In this study, we partially purified the ethyl acetate soluble fraction of the ethanol extract of the root of Allum hookeri. We identified seven compounds, benzoic acid, tetradecanoic acid, hexadecanoic acid, ferulic acid, cinnamic acid, octadecanoic acid and hexanedioic acid, that have antimicrobial activity using GC-MS, and evaluated the antimicrobial susceptibility and MIC (minimum inhibitory concentration) against multidrug-resistant bacteria.

  17. Antimicrobial resistance issues in beef production

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antimicrobial resistance threats to human health as identified have been recognized as a critical global public health concern. Linkage of some threats to beef production is discussed. The relevance to beef production of recent government actions will be examined. Prominent antimicrobial resistance ...

  18. Antimicrobial food packaging: potential and pitfalls

    PubMed Central

    Malhotra, Bhanu; Keshwani, Anu; Kharkwal, Harsha

    2015-01-01

    Nowadays food preservation, quality maintenance, and safety are major growing concerns of the food industry. It is evident that over time consumers’ demand for natural and safe food products with stringent regulations to prevent food-borne infectious diseases. Antimicrobial packaging which is thought to be a subset of active packaging and controlled release packaging is one such promising technology which effectively impregnates the antimicrobial into the food packaging film material and subsequently delivers it over the stipulated period of time to kill the pathogenic microorganisms affecting food products thereby increasing the shelf life to severe folds. This paper presents a picture of the recent research on antimicrobial agents that are aimed at enhancing and improving food quality and safety by reduction of pathogen growth and extension of shelf life, in a form of a comprehensive review. Examination of the available antimicrobial packaging technologies is also presented along with their significant impact on food safety. This article entails various antimicrobial agents for commercial applications, as well as the difference between the use of antimicrobials under laboratory scale and real time applications. Development of resistance amongst microorganisms is considered as a future implication of antimicrobials with an aim to come up with actual efficacies in extension of shelf life as well as reduction in bacterial growth through the upcoming and promising use of antimicrobials in food packaging for the forthcoming research down the line. PMID:26136740

  19. Cationic Antimicrobial Polymers and Their Assemblies

    PubMed Central

    Carmona-Ribeiro, Ana Maria; de Melo Carrasco, Letícia Dias

    2013-01-01

    Cationic compounds are promising candidates for development of antimicrobial agents. Positive charges attached to surfaces, particles, polymers, peptides or bilayers have been used as antimicrobial agents by themselves or in sophisticated formulations. The main positively charged moieties in these natural or synthetic structures are quaternary ammonium groups, resulting in quaternary ammonium compounds (QACs). The advantage of amphiphilic cationic polymers when compared to small amphiphilic molecules is their enhanced microbicidal activity. Besides, many of these polymeric structures also show low toxicity to human cells; a major requirement for biomedical applications. Determination of the specific elements in polymers, which affect their antimicrobial activity, has been previously difficult due to broad molecular weight distributions and random sequences characteristic of radical polymerization. With the advances in polymerization control, selection of well defined polymers and structures are allowing greater insight into their structure-antimicrobial activity relationship. On the other hand, antimicrobial polymers grafted or self-assembled to inert or non inert vehicles can yield hybrid antimicrobial nanostructures or films, which can act as antimicrobials by themselves or deliver bioactive molecules for a variety of applications, such as wound dressing, photodynamic antimicrobial therapy, food packing and preservation and antifouling applications. PMID:23665898

  20. Synthesis and antimicrobial activity of squalamine analogue.

    PubMed

    Kim, H S; Choi, B S; Kwon, K C; Lee, S O; Kwak, H J; Lee, C H

    2000-08-01

    Synthesis and antimicrobial activity of squalamine analogue 2 are reported. The synthesis of 2 was accomplished from bisnoralcohol 3. The spermidine moiety was introduced via reductive amination of an appropriately functionalized 3beta-aminosterol with spermidinyl aldehyde 17 utilizing sodium triacetoxyborohydride as the reducing agent. Compound 2 shows weaker antimicrobial activity than squalamine. PMID:11003150

  1. Antimicrobial Resistance in the Environment.

    PubMed

    Williams, Maggie R; Stedtfeld, Robert D; Guo, Xueping; Hashsham, Syed A

    2016-10-01

    This review summarizes important publications from 2015 pertaining to the occurrence of antimicrobial resistance (AMR) in the environment. Emphasis is placed on sources of antibiotic resistance in the aquatic environment including wastewater treatment plants, hospitals, and agriculture, treatment and mitigation techniques, and surveillance and analysis methodologies for characterizing abundance data. As such, this review is organized into the following sections: i) occurrence of AMR in the environment, including surface waters, aquaculture, and wastewater ii) treatment technologies, and iii) technologies for rapid surveillance of AMR, iv) transmission between matrices, v) databases and analysis methods, and vi) gaps in AMR understanding. PMID:27620115

  2. [Antimicrobial sensitive of Morganella morganii].

    PubMed

    Zalas-Wiecek, Patrycja; Michalska, Anna; Sielska, Barbara; Gospodarek, Eugenia

    2011-01-01

    The aim of this study was the evaluation of the antimicrobial sensitive of Morganella morganii rods isolated from clinical samples. This study included 50 of M. morganii strains isolated in the Clinical Microbiology Department of dr. A. Jurasz University Hospital in 2008-2009. All of strains were sensitive to carbapenems (imipenem, meropenem, ertapenem, doripenem) and piperacillin/tazobactam and most of them to beta-lactam antibiotics, aminoglycosides and fluorochinolons. Resistance to tetracyclines demonstrated 38,0% strains and to doxycycline - 40,0%. One out of 6 strains isolated from urine samples were sensitive to nitrofurantoin. Extended Spectrum Beta-Lactamases were produced by 5 (10,0%) strains.

  3. Preventing medication errors in cancer chemotherapy.

    PubMed

    Cohen, M R; Anderson, R W; Attilio, R M; Green, L; Muller, R J; Pruemer, J M

    1996-04-01

    Recommendations for preventing medication errors in cancer chemotherapy are made. Before a health care provider is granted privileges to prescribe, dispense, or administer antineoplastic agents, he or she should undergo a tailored educational program and possibly testing or certification. Appropriate reference materials should be developed. Each institution should develop a dose-verification process with as many independent checks as possible. A detailed checklist covering prescribing, transcribing, dispensing, and administration should be used. Oral orders are not acceptable. All doses should be calculated independently by the physician, the pharmacist, and the nurse. Dosage limits should be established and a review process set up for doses that exceed the limits. These limits should be entered into pharmacy computer systems, listed on preprinted order forms, stated on the product packaging, placed in strategic locations in the institution, and communicated to employees. The prescribing vocabulary must be standardized. Acronyms, abbreviations, and brand names must be avoided and steps taken to avoid other sources of confusion in the written orders, such as trailing zeros. Preprinted antineoplastic drug order forms containing checklists can help avoid errors. Manufacturers should be encouraged to avoid or eliminate ambiguities in drug names and dosing information. Patients must be educated about all aspects of their cancer chemotherapy, as patients represent a last line of defense against errors. An interdisciplinary team at each practice site should review every medication error reported. Pharmacists should be involved at all sites where antineoplastic agents are dispensed. Although it may not be possible to eliminate all medication errors in cancer chemotherapy, the risk can be minimized through specific steps. Because of their training and experience, pharmacists should take the lead in this effort. PMID:8697025

  4. Preexisting antitumor immunity augments the antitumor effects of chemotherapy.

    PubMed

    Zhang, Lingbing; Feng, Dongdong; Yu, Lynda X; Tsung, Kangla; Norton, Jeffrey A

    2013-06-01

    Efficacy of cancer chemotherapy is generally believed to be the result of direct drug killing of tumor cells. However, increased tumor cell killing does not always lead to improved efficacy. Herein, we demonstrate that the status of antitumor immunity at the time of chemotherapy treatment is a critical factor affecting the therapeutic outcome in that tumor-bearing mice that possess preexisting antitumor immunity respond to chemotherapy much better than those that do not. Enhancing antitumor immunity before or at the time of chemotherapy-induced antigen release increases subsequent response to chemotherapy significantly. By in vitro and in vivo measurements of antitumor immunity, we found a close correlation between the intensity of antitumor immunity activated by chemotherapy and the efficacy of treatment. Immune intervention with interleukin-12 during the early phase of chemotherapy-induced immune activation greatly amplifies the antitumor response, often resulting in complete tumor eradication not only at the chemo-treated local site, but also systemically. These findings provide additional evidence for an immune-mediated antitumor response to chemotherapy. Further, our results show that timely immune modification of chemotherapy-activated antitumor immunity can result in enhanced antitumor-immune response and complete tumor eradication.

  5. Preexisting antitumor immunity augments the antitumor effects of chemotherapy.

    PubMed

    Zhang, Lingbing; Feng, Dongdong; Yu, Lynda X; Tsung, Kangla; Norton, Jeffrey A

    2013-06-01

    Efficacy of cancer chemotherapy is generally believed to be the result of direct drug killing of tumor cells. However, increased tumor cell killing does not always lead to improved efficacy. Herein, we demonstrate that the status of antitumor immunity at the time of chemotherapy treatment is a critical factor affecting the therapeutic outcome in that tumor-bearing mice that possess preexisting antitumor immunity respond to chemotherapy much better than those that do not. Enhancing antitumor immunity before or at the time of chemotherapy-induced antigen release increases subsequent response to chemotherapy significantly. By in vitro and in vivo measurements of antitumor immunity, we found a close correlation between the intensity of antitumor immunity activated by chemotherapy and the efficacy of treatment. Immune intervention with interleukin-12 during the early phase of chemotherapy-induced immune activation greatly amplifies the antitumor response, often resulting in complete tumor eradication not only at the chemo-treated local site, but also systemically. These findings provide additional evidence for an immune-mediated antitumor response to chemotherapy. Further, our results show that timely immune modification of chemotherapy-activated antitumor immunity can result in enhanced antitumor-immune response and complete tumor eradication. PMID:23595208

  6. [Salivation in children during anticancer chemotherapy].

    PubMed

    Popruzhenko, T V; Boris, S P

    2016-01-01

    The study aimed to assess the needs and options for salivation management in children treated with antileukemic chemotherapy. In a preliminary cross-sectional study the saliva flow rate and viscosity were evaluated in 75 leukemic children that received chemotherapy with methotrexate in low dose (44 people, 44 episode, group 1), or in high-dose (31 people, 42 episode, group 2), and in 25 healthy children (group 3). Then, 26 children were randomly divided into two groups in the 70 episodes course of high-dosed chemotherapy, and received acetylcysteine (A) or only standard oral management (S) for 1-10 day of treatment. Parameters of salivation and children performance (Lansky et al.) were evaluated. Mann-Whitney U-test was used for analysis. In group 1, 2 and 3 the flow rate (Me [LQ/HQ]) was 0.5 [0.3; 0.8]; 0.9 [0.6; 1.2] and 0.5 [0.3; 0.6] ml/min respectively (p1-3>0.05; p<0.01; p1-2<0.05). Viscosity levels in group 1, 2 and 3 were 2.75 [3.67; 3.67], 10.05 [5.3; 26.0] and 3.9 [2.7; 6.5] unites respectively (p1-3>0.05; p2, 3<0.01; p1, 2<0.01). In group A and S the flow rate was 2.7 [0.5; 4.1] and 0.4 [0.1; 2.2] ml/min (р<0.05); viscosity was 1.5 [1.2; 4.1] and 6.4 [5.3; 8.1] unites (р<0.001), performance Lansky index was 80 [65; 90] and 70 [60; 80] (р<0.01) respectively. Salivation dysfunction complicates the chemotherapy with high-dosed methotrexate in children: it is indicated by high viscosity combined with elevated flow rate. Acetylcysteine normalizes saliva viscosity and improves children's performance.

  7. Intestinal lymphangiectasia secondary to radiotherapy and chemotherapy

    SciTech Connect

    Rao, S.S.; Dundas, S.; Holdsworth, C.D.

    1987-08-01

    We report a case of intestinal lymphangiectasia secondary to radiotherapy and chemotherapy. The patient also had small bowel bacterial overgrowth and pancreatic insufficiency. Lymphatic ectasia as a histological feature has been described previously in association with postradiotherapy malabsorption, but radiation-induced lymphangiectasia producing clinical manifestations has hitherto not been reported. Replacement of dietary long-chain fats with medium-chain triglycerides, pancreatic enzyme supplements, and a short course of oxytetracycline, resulted in dramatic clinical improvement. The possibility of intestinal lymphangiectasia should be borne in mind in patients with postradiotherapy malabsorption. A low serum albumin and lymphocyte count should draw attention to this possibility.

  8. Liposome-encapsulated actinomycin for cancer chemotherapy

    DOEpatents

    Rahman, Yueh-Erh; Cerny, Elizabeth A.

    1976-01-01

    An improved method is provided for chemotherapy of malignant tumors by injection of antitumor drugs. The antitumor drug is encapsulated within liposomes and the liposomes containing the encapsulated drug are injected into the body. The encapsulated drug penetrates into the tumor cells where the drug is slowly released and induces degeneration and death of the tumor cells, while any toxicity to the host body is reduced. Liposome encapsulation of actinomycin D has been found to be particularly effective in treating cancerous abdominal tumors, while drastically reducing the toxicity of actinomycin D to the host.

  9. Anaphylaxis to chemotherapy and monoclonal antibodies.

    PubMed

    Castells, Mariana C

    2015-05-01

    Hypersensitivity reactions are increasingly prevalent, although underrecognized and underreported. Platins induce immunoglobulin E-mediated sensitization; taxenes and some monoclonal antibodies can induce reactions at first exposure. Severe hypersensitivity can preclude first-line therapy. Tryptase level at the time of a reaction is a useful diagnostic tool. Skin testing provides a specific diagnosis. Newer tests are promising diagnostic tools to help identify patients at risk before first exposure. Safe management includes rapid drug desensitization. This review provides information regarding the scope of hypersensitivity and anaphylactic reactions induced by chemotherapy and biological drugs, as well as diagnosis, management, and treatment options. PMID:25841555

  10. Antimicrobial peptides important in innate immunity.

    PubMed

    Cederlund, Andreas; Gudmundsson, Gudmundur H; Agerberth, Birgitta

    2011-10-01

    Antimicrobial peptides are present in all walks of life, from plants to animals, and they are considered to be endogenous antibiotics. In general, antimicrobial peptides are determinants of the composition of the microbiota and they function to fend off microbes and prevent infections. Antimicrobial peptides eliminate micro-organisms through disruption of their cell membranes. Their importance in human immunity, and in health as well as disease, has only recently been appreciated. The present review provides an introduction to the field of antimicrobial peptides in general and discusses two of the major classes of mammalian antimicrobial peptides: the defensins and the cathelicidins. The review focuses on their structures, their main modes of action and their regulation.

  11. Methods of Antimicrobial Coating of Diverse Materials

    NASA Technical Reports Server (NTRS)

    Akse, James R.; Holtsnider, John T.; Kliestik, Helen

    2011-01-01

    Methods of coating diverse substrate materials with antimicrobial agents have been developed. Originally intended to reduce health risks to astronauts posed by pathogenic microorganisms that can grow on surfaces in spacecraft, these methods could also be used on Earth for example, to ensure sterility of surgical inserts and other medical equipment. The methods involve, generally, chemical preparation of substrate surfaces to enable attachment of antimicrobial molecules to the substrate surfaces via covalent bonds. Substrate materials that have been treated successfully include aluminum, glass, a corrosion-resistant nickel alloy, stainless steel, titanium, and poly(tetrafluoroethylene). Antimicrobial agents that have been successfully immobilized include antibiotics, enzymes, bacteriocins, bactericides, and fungicides. A variety of linkage chem istries were employed. Activity of antimicrobial coatings against gram-positive bacteria, gram-negative bacteria, and fungi was demonstrated. Results of investigations indicate that the most suitable combination of antimicrobial agent, substrate, and coating method depends upon the intended application.

  12. Epidemiology of antimicrobial resistance in bloodstream infections.

    PubMed

    Akova, Murat

    2016-04-01

    Antimicrobial resistance in bacterial pathogens is a worldwide challenge leading high morbidity and mortality in clinical settings. Multidrug resistant patterns in gram-positive and -negative bacteria have resulted in difficult-to-treat or even untreatable infections with conventional antimicrobials. Since the early identification of causative microorganisms and their antimicrobial susceptibility patterns in patients with bacteremia and other serious infections is lacking in many healthcare institutions, broad spectrum antibiotics are liberally and mostly unnecessarily used. Such practice has, in turn, caused dramatic increases in emerging resistance and when coupled with poor practice of infection control, resistant bacteria can easily be disseminated to the other patients and the environment. Thus, availability of updated epidemiological data on antimicrobial resistance in frequently encountered bacterial pathogens will be useful not only for deciding on empirical treatment strategies, but also devising an effective antimicrobial stewardship program in hospitals. PMID:26984779

  13. Application of natural antimicrobials for food preservation.

    PubMed

    Tiwari, Brijesh K; Valdramidis, Vasilis P; O'Donnell, Colm P; Muthukumarappan, Kasiviswanathan; Bourke, Paula; Cullen, P J

    2009-07-22

    In this review, antimicrobials from a range of plant, animal, and microbial sources are reviewed along with their potential applications in food systems. Chemical and biochemical antimicrobial compounds derived from these natural sources and their activity against a range of pathogenic and spoilage microorganisms pertinent to food, together with their effects on food organoleptic properties, are outlined. Factors influencing the antimicrobial activity of such agents are discussed including extraction methods, molecular weight, and agent origin. These issues are considered in conjunction with the latest developments in the quantification of the minimum inhibitory (and noninhibitory) concentration of antimicrobials and/or their components. Natural antimicrobials can be used alone or in combination with other novel preservation technologies to facilitate the replacement of traditional approaches. Research priorities and future trends focusing on the impact of product formulation, intrinsic product parameters, and extrinsic storage parameters on the design of efficient food preservation systems are also presented. PMID:19548681

  14. Clinical pharmacology of antimicrobial use in humans and animals.

    PubMed

    Lathers, Claire M

    2002-06-01

    bacterial targets. Bacterial resistance and its selection may be evaluated by comparing the relationship to antibiotic pharmacokinetic (PK) values obtained from serum concentrations and organism MICs (minimum inhibitory concentrations; concentration-dependent killing) to reveal culture and sensitivity tests in patients. Pharmacodynamic (PD) models may be developed to identify factors associated with the probability that bacterial resistance will develop. Thomas et al (Antimicrobial Agents Chemotherapy 1998;42:521) used this combined approach of PK/PD and MICs to examine data retrospectively. The role of clinical pharmacology is to work with PK/PD models such as these to determine the best use of antibiotics in humans to minimize the development of resistance. The role of any regulatory body responsible for the protection of the public health and food safety for consumers is to assess risk and to then communicate and manage the risk. Scientific uncertainty must be interpreted to propose sound policy options. The conversion of sound science into an appropriate regulatory policy to protect the public health is most important.

  15. Clinical pharmacology of antimicrobial use in humans and animals.

    PubMed

    Lathers, Claire M

    2002-06-01

    bacterial targets. Bacterial resistance and its selection may be evaluated by comparing the relationship to antibiotic pharmacokinetic (PK) values obtained from serum concentrations and organism MICs (minimum inhibitory concentrations; concentration-dependent killing) to reveal culture and sensitivity tests in patients. Pharmacodynamic (PD) models may be developed to identify factors associated with the probability that bacterial resistance will develop. Thomas et al (Antimicrobial Agents Chemotherapy 1998;42:521) used this combined approach of PK/PD and MICs to examine data retrospectively. The role of clinical pharmacology is to work with PK/PD models such as these to determine the best use of antibiotics in humans to minimize the development of resistance. The role of any regulatory body responsible for the protection of the public health and food safety for consumers is to assess risk and to then communicate and manage the risk. Scientific uncertainty must be interpreted to propose sound policy options. The conversion of sound science into an appropriate regulatory policy to protect the public health is most important. PMID:12043947

  16. Antimicrobial outcomes in plasma medicine

    NASA Astrophysics Data System (ADS)

    Ryan, Thomas P.; Stalder, Kenneth R.; Woloszko, Jean

    2015-03-01

    Plasma is referred to as the fourth state of matter and is frequently generated in the environment of a strong electric field. The result consists of highly reactive species--ions, electrons, reactive atoms and molecules, and UV radiation. Plasma Medicine unites a number of fields, including Physics, Plasma Chemistry, Cell Biology, Biochemistry, and Medicine. The treatment modality utilizes Cold Atmospheric Plasma (CAP), which is able to sterilize and treat microbes in a nonthermal manner. These gas-based plasma systems operate at close to room temperature and atmospheric pressure, making them very practical for a range of potential treatments and are highly portable for clinical use throughout the health care system. The hypothesis is that gas based plasma kills bacteria, fungus, and viruses but spares mammalian cells. This paper will review systematic work which shows examples of systems and performance in regards to antimicrobial effects and the sparing of mammalian cells. The mechanism of action will be discussed, as well as dosing for the treatment of microbial targets, including sterilization processes, another important healthcare need. In addition, commercial systems will be overviewed and compared, along with evidence-based, patient results. The range of treatments cover wound treatment and biofilms, as well as antimicrobial treatment, with little chance for resistance and tolerance, as in drug regimens. Current clinical studies include applications in dentistry, food treatment, cancer treatment, wound treatment for bacteria and biofilms, and systems to combat health care related infections.

  17. Antimicrobial Peptides: Versatile Biological Properties

    PubMed Central

    Pushpanathan, Muthuirulan; Rajendhran, Jeyaprakash

    2013-01-01

    Antimicrobial peptides are diverse group of biologically active molecules with multidimensional properties. In recent past, a wide variety of AMPs with diverse structures have been reported from different sources such as plants, animals, mammals, and microorganisms. The presence of unusual amino acids and structural motifs in AMPs confers unique structural properties to the peptide that attribute for their specific mode of action. The ability of these active AMPs to act as multifunctional effector molecules such as signalling molecule, immune modulators, mitogen, antitumor, and contraceptive agent makes it an interesting candidate to study every aspect of their structural and biological properties for prophylactic and therapeutic applications. In addition, easy cloning and recombinant expression of AMPs in heterologous plant host systems provided a pipeline for production of disease resistant transgenic plants. Besides these properties, AMPs were also used as drug delivery vectors to deliver cell impermeable drugs to cell interior. The present review focuses on the diversity and broad spectrum antimicrobial activity of AMPs along with its multidimensional properties that could be exploited for the application of these bioactive peptides as a potential and promising drug candidate in pharmaceutical industries. PMID:23935642

  18. Combination Effects of Antimicrobial Peptides

    PubMed Central

    Yu, Guozhi; Baeder, Desiree Y.; Regoes, Roland R.

    2016-01-01

    Antimicrobial peptides (AMPs) are ancient and conserved across the tree of life. Their efficacy over evolutionary time has been largely attributed to their mechanisms of killing. Yet, the understanding of their pharmacodynamics both in vivo and in vitro is very limited. This is, however, crucial for applications of AMPs as drugs and also informs the understanding of the action of AMPs in natural immune systems. Here, we selected six different AMPs from different organisms to test their individual and combined effects in vitro. We analyzed their pharmacodynamics based on the Hill function and evaluated the interaction of combinations of two and three AMPs. Interactions of AMPs in our study were mostly synergistic, and three-AMP combinations displayed stronger synergism than two-AMP combinations. This suggests synergism to be a common phenomenon in AMP interaction. Additionally, AMPs displayed a sharp increase in killing within a narrow dose range, contrasting with those of antibiotics. We suggest that our results could lead a way toward better evaluation of AMP application in practice and shed some light on the evolutionary consequences of antimicrobial peptide interactions within the immune system of organisms. PMID:26729502

  19. WE-D-BRE-04: Modeling Optimal Concurrent Chemotherapy Schedules

    SciTech Connect

    Jeong, J; Deasy, J O

    2014-06-15

    Purpose: Concurrent chemo-radiation therapy (CCRT) has become a more common cancer treatment option with a better tumor control rate for several tumor sites, including head and neck and lung cancer. In this work, possible optimal chemotherapy schedules were investigated by implementing chemotherapy cell-kill into a tumor response model of RT. Methods: The chemotherapy effect has been added into a published model (Jeong et al., PMB (2013) 58:4897), in which the tumor response to RT can be simulated with the effects of hypoxia and proliferation. Based on the two-compartment pharmacokinetic model, the temporal concentration of chemotherapy agent was estimated. Log cell-kill was assumed and the cell-kill constant was estimated from the observed increase in local control due to concurrent chemotherapy. For a simplified two cycle CCRT regime, several different starting times and intervals were simulated with conventional RT regime (2Gy/fx, 5fx/wk). The effectiveness of CCRT was evaluated in terms of reduction in radiation dose required for 50% of control to find the optimal chemotherapy schedule. Results: Assuming the typical slope of dose response curve (γ50=2), the observed 10% increase in local control rate was evaluated to be equivalent to an extra RT dose of about 4 Gy, from which the cell-kill rate of chemotherapy was derived to be about 0.35. Best response was obtained when chemotherapy was started at about 3 weeks after RT began. As the interval between two cycles decreases, the efficacy of chemotherapy increases with broader range of optimal starting times. Conclusion: The effect of chemotherapy has been implemented into the resource-conservation tumor response model to investigate CCRT. The results suggest that the concurrent chemotherapy might be more effective when delayed for about 3 weeks, due to lower tumor burden and a larger fraction of proliferating cells after reoxygenation.

  20. Ambient noise levels in the chemotherapy clinic

    PubMed Central

    Gladd, Dana K.; Saunders, Gabrielle H.

    2016-01-01

    Many of the drugs used for chemotherapy treatments are known to be ototoxic, and can result in permanent hearing threshold shifts. The degree of ototoxic damage can be influenced by many factors including dosage, duration of exposure, genetics, and coadministration with other ototoxic agents. Cisplatin is known for its ototoxic effects on hearing thresholds, particularly in the high frequencies. Recent studies have indicated a synergistic relationship between Cisplatin administration and moderate to high noise level exposure starting between 70–85 dB SPL. This study measured the noise levels in the Portland Veteran’s Affairs Medical Center’s outpatient chemotherapy clinic. Average (LAeq) and peak (LCpeak) noise measures were recorded every minute from 7 am until 6 pm on the two busiest clinic days. Patients, visitors, and staff members filled out anonymous surveys regarding their reactions to noise levels. Cumulative noise levels were not at levels known to interact with Cisplatin for a significant period of time. Noise measurement analysis indicated that levels were at or above 70 dB SPL for less than ten minutes during the 11-hour recording window. The patient and visitor surveys indicated that both groups were unbothered by noise in the clinic. However, most staff members were bothered by or concerned about noise levels, and many felt that it caused stress and difficulty communicating on the phone. PMID:22122961

  1. Drug Cocktail Optimization in Chemotherapy of Cancer

    PubMed Central

    Preissner, Saskia; Dunkel, Mathias; Hoffmann, Michael F.; Preissner, Sarah C.; Genov, Nikolai; Rong, Wen Wei; Preissner, Robert; Seeger, Karlheinz

    2012-01-01

    Background In general, drug metabolism has to be considered to avoid adverse effects and ineffective therapy. In particular, chemotherapeutic drug cocktails strain drug metabolizing enzymes especially the cytochrome P450 family (CYP). Furthermore, a number of important chemotherapeutic drugs such as cyclophosphamide, ifosfamide, tamoxifen or procarbazine are administered as prodrugs and have to be activated by CYP. Therefore, the genetic variability of these enzymes should be taken into account to design appropriate therapeutic regimens to avoid inadequate drug administration, toxicity and inefficiency. Objective The aim of this work was to find drug interactions and to avoid side effects or ineffective therapy in chemotherapy. Data sources and methods Information on drug administration in the therapy of leukemia and their drug metabolism was collected from scientific literature and various web resources. We carried out an automated textmining approach. Abstracts of PubMed were filtered for relevant articles using specific keywords. Abstracts were automatically screened for antineoplastic drugs and their synonyms in combination with a set of human CYPs in title or abstract. Results We present a comprehensive analysis of over 100 common cancer treatment regimens regarding drug-drug interactions and present alternatives avoiding CYP overload. Typical concomitant medication, e.g. antiemetics or antibiotics is a preferred subject to improvement. A webtool, which allows drug cocktail optimization was developed and is publicly available on http://bioinformatics.charite.de/chemotherapy. PMID:23236419

  2. Cancer chemotherapy and cardiac arrhythmias: a review.

    PubMed

    Tamargo, Juan; Caballero, Ricardo; Delpón, Eva

    2015-02-01

    Cardiovascular toxicity is a potential complication of cancer chemotherapy (CC) that increases the morbidity and mortality of cancer patients. Cardiac arrhythmias have been reported as an adverse effect of many chemotherapeutic drugs, including novel targeted therapies. The relationship between chemotherapy and arrhythmias has not been well-established and the proarrhythmogenic mechanisms remain uncertain as they can be the result of a direct electrophysiological effect or of changes in cardiac structure and function, including myocardial ischaemia and heart failure, which create an arrhythmogenic substrate. In this review we summarise available evidence of proarrhythmia induced by CC, discuss the possible mechanisms involved in this adverse effect and emphasise the importance of cardiac monitoring for the early diagnosis, intervention and surveillance of those patients more susceptible to develop proarrhythmia in an attempt to reduce the morbidity and mortality. Oncologists should be fully aware of proarrhythmia and the close collaboration between cardiologists and oncologists would result in a better cardiovascular assessment, risk stratification, cardiac monitoring and treatment during CC and during the follow-up. The final objective is to understand the mechanisms of proarrhythmia and evaluate its real incidence and clinical relevance so as to select the safest and most effective treatment for cancer patients.

  3. Light protection of chemotherapy drugs for infusion.

    PubMed

    Clarkson, Douglas McG; Harvey, Roger; Sheepy, Dave

    2015-02-01

    Specific chemotherapy drugs which require to be delivered by continuous infusion over time can have their effectiveness impaired by exposure to optical radiation. Mechanisms and processes of drug preparation and patient administration associated with light sensitive drugs were monitored within a Chemotherapy Unit. Levels of ambient light at locations of drug preparation/administration and levels of protection afforded by optical filter elements such as infusion lines were determined using a double grating Bentham Dmc150 spectroradiometer. Models of light exposure were developed for separate components of drug preparation and infusion delivery systems where the latter included the fluid bag with protective light cover, drip chamber and giving set line. In addition, the attenuation coefficient of Dacarbazine at the concentration typically used in patient treatments was determined using specially manufactured measurement cells. The relative contributions to light absorption of the drug bag, drip chamber and patient line were identified for specific types of giving sets, spectral content/intensity of light exposure and specific drug light absorption profiles. This indicated significant differences in the level of light protection afforded by specific giving sets and either single or double layer protection of the drug bag reservoir. It is not clear, however, if these variations could lead to significant differences of levels of drug de-activation and/or creation of undesirable photo-products such as in the case of Dacarbazine. Such techniques, however, provide a means of identifying how light exposure can be maintained at levels as low as reasonably possible as a precautionary measure.

  4. Adjuvant chemotherapy for soft tissue sarcoma.

    PubMed

    Casali, Paolo G

    2015-01-01

    Adjuvant chemotherapy is not standard treatment in soft tissue sarcoma (STS). However, when the risk of relapse is high, it is an option for shared decision making with the patient in conditions of uncertainty. This is because available evidence is conflicting, even if several randomized clinical trials have been performed for 4 decades and also have been pooled into meta-analyses. Indeed, available meta-analyses point to a benefit in the 5% to 10% range in terms of survival and distant relapse rate. Some local benefit also was suggested by some trials. Placing chemotherapy in the preoperative setting may help gain a local advantage in terms of the quality of surgical margins or decreased sequelae. This may be done within a personalized approach according to the clinical presentation. Attempts to personalize treatment on the basis of the variegated pathology and molecular biology of STS subgroups are ongoing as well, according to what is done in the medical treatment of advanced STS. Thus, decision making for adjuvant and neoadjuvant indications deserves personalization in clinical research and in clinical practice, taking profit from all multidisciplinary clinical skills available at a sarcoma reference center, though with a degree of subjectivity because of the limitations of available evidence. PMID:25993233

  5. Thermotherapy, chemotherapy, and meristem culture in banana.

    PubMed

    Lassois, Ludivine; Lepoivre, Philippe; Swennen, Rony; van den Houwe, Ines; Panis, Bart

    2013-01-01

    Bananas that provide a staple food to the millions of people are adversely affected by several viruses such as Banana bunchy Top Virus (BBTV), Banana Streak Virus (BSV), and Cucumber Mosaic Virus (CMV). These viruses are known to have a devastating effect on crop production and constraint to the international exchange and conservation of banana germplasm-a cornerstone for breeding new cultivars. The viruses are particularly problematic in vegetative propagated crops, like bananas, because of their transmission in the planting material. Different virus eradication techniques have been developed, such as thermotherapy, chemotherapy, and meristem culture for providing virus-free planting material. Meristem culture proved to be the most effective procedure to eradicate phloem-associated viruses. This method requires isolation of meristematic dome of plant under the aseptic conditions and culture in an appropriate nutrient medium to develop new virus-free plants. Thermotherapy is another widely used virus eradication technique, which is initially carried out on in vivo or in vitro plants and eventually combined with meristem culture technique. The plantlets are initially grown at 28°C day temperature and increase it by 2°C per day until reaches 40°C and the night temperature at 28°C; maintain plants at 40°C for 4 weeks; excise meristem and culture onto the regeneration medium. In chemotherapy technique, antiviral chemical compound Virazole(®) is applied on meristem culture. Combination of these techniques is also applied to improve the eradication rate.

  6. Antimicrobial use and antimicrobial resistance in nosocomial pathogens at a tertiary care hospital in Pune

    PubMed Central

    Nair, Velu; Sharma, Dinesh; Sahni, A.K.; Grover, Naveen; Shankar, S.; Jaiswal, S.S.; Dalal, S.S.; Basannar, D.R.; Phutane, Vivek S.; Kotwal, Atul; Gopal Rao, G.; Batura, Deepak; Venkatesh, M.D.; Sinha, Tapan; Kumar, Sushil; Joshi, D.P.

    2015-01-01

    Background Resistance to antimicrobial agents is emerging in wide variety of nosocomial and community acquired pathogens. Widespread and often inappropriate use of broad spectrum antimicrobial agents is recognized as a significant contributing factor to the development and spread of bacterial resistance. This study was conducted to gain insight into the prevalent antimicrobial prescribing practices, and antimicrobial resistance pattern in nosocomial pathogens at a tertiary care hospital in Pune, India. Methods Series of one day cross sectional point prevalence surveys were carried out on four days between March and August 2014. All eligible in patients were included in the study. A structured data entry form was used to collect the data for each patient. Relevant samples were collected for microbiological examination from all the clinically identified hospital acquired infection cases. Results 41.73% of the eligible patients (95% CI: 39.52–43.97) had been prescribed at least one antimicrobial during their stay in the hospital. Beta-lactams (38%) were the most prescribed antimicrobials, followed by Protein synthesis inhibitors (24%). Majority of the organisms isolated from Hospital acquired infection (HAI cases) were found to be resistant to the commonly used antimicrobials viz: Cefotaxime, Ceftriaxone, Amikacin, Gentamicin and Monobactams. Conclusion There is need to have regular antimicrobial susceptibility surveillance and dissemination of this information to the clinicians. In addition, emphasis on the rational use of antimicrobials, antimicrobial rotation and strict adherence to the standard treatment guidelines is very essential. PMID:25859071

  7. Remote Antimicrobial Stewardship in Community Hospitals.

    PubMed

    Wood, Zachary H; Nicolsen, Nicole C; Allen, Nichole; Cook, Paul P

    2015-11-13

    Antimicrobial stewardship has become standard practice at university medical centers, but the practice is more difficult to implement in remote community hospitals that lack infectious diseases trained practitioners. Starting in 2011, six community hospitals within the Vidant Health system began an antimicrobial stewardship program utilizing pharmacists who reviewed charts remotely from Vidant Medical Center. Pharmacists made recommendations within the electronic medical record (EMR) to streamline, discontinue, or switch antimicrobial agents. Totals of charts reviewed, recommendations made, recommendations accepted, and categories of intervention were recorded. Linear regression was utilized to measure changes in antimicrobial use over time. For the four larger hospitals, recommendations for changes were made in an average of 45 charts per month per hospital and physician acceptance of the pharmacists' recommendations varied between 83% and 88%. There was no significant decrease in total antimicrobial use, but much of the use was outside of the stewardship program's review. Quinolone use decreased by more than 50% in two of the four larger hospitals. Remote antimicrobial stewardship utilizing an EMR is feasible in community hospitals and is generally received favorably by physicians. As more community hospitals adopt EMRs, there is an opportunity to expand antimicrobial stewardship beyond the academic medical center.

  8. Recent Advances in Antimicrobial Polymers: A Mini-Review

    PubMed Central

    Huang, Keng-Shiang; Yang, Chih-Hui; Huang, Shu-Ling; Chen, Cheng-You; Lu, Yuan-Yi; Lin, Yung-Sheng

    2016-01-01

    Human safety and well-being is threatened by microbes causing numerous infectious diseases resulting in a large number of deaths every year. Despite substantial progress in antimicrobial drugs, many infectious diseases remain difficult to treat. Antimicrobial polymers offer a promising antimicrobial strategy for fighting pathogens and have received considerable attention in both academic and industrial research. This mini-review presents the advances made in antimicrobial polymers since 2013. Antimicrobial mechanisms exhibiting either passive or active action and polymer material types containing bound or leaching antimicrobials are introduced. This article also addresses the applications of these antimicrobial polymers in the medical, food, and textile industries. PMID:27657043

  9. Danish Integrated Antimicrobial Resistance Monitoring and Research Program

    PubMed Central

    Heuer, Ole E.; Emborg, Hanne-Dorthe; Bagger-Skjøt, Line; Jensen, Vibeke F.; Rogues, Anne-Marie; Skov, Robert L.; Agersø, Yvonne; Brandt, Christian T.; Seyfarth, Anne Mette; Muller, Arno; Hovgaard, Karin; Ajufo, Justin; Bager, Flemming; Aarestrup, Frank M.; Frimodt-Møller, Niels; Wegener, Henrik C.; Monnet, Dominique L.

    2007-01-01

    Resistance to antimicrobial agents is an emerging problem worldwide. Awareness of the undesirable consequences of its widespread occurrence has led to the initiation of antimicrobial agent resistance monitoring programs in several countries. In 1995, Denmark was the first country to establish a systematic and continuous monitoring program of antimicrobial drug consumption and antimicrobial agent resistance in animals, food, and humans, the Danish Integrated Antimicrobial Resistance Monitoring and Research Program (DANMAP). Monitoring of antimicrobial drug resistance and a range of research activities related to DANMAP have contributed to restrictions or bans of use of several antimicrobial agents in food animals in Denmark and other European Union countries. PMID:18217544

  10. [Principles of managing chemotherapy-induced nausea and vomiting].

    PubMed

    Takiuchi, Hiroya; Kawabe, Shinichiro; Goto, Masahiro; Ota, Syunsuke; Kii, Takayuki; Tanaka, Toshimitsu; Nishitani, Hitoshi; Kuwakado, Shin; Katsu, Ken-ichi

    2006-01-01

    Chemotherapy-induced nausea and vomiting (emesis) can significantly affect a patient's quality of life, leading to poor compliance with further chemotherapy treatment. For patients treated with emetogenic chemotherapy, it is very important to prevent nausea and vomiting completely. The incidence and severity of nausea and/or vomiting in patients receiving chemotherapy are affected by numerous factors, including: 1) the specific chemotherapeutic agents used; 2) their dosage; 3) the schedule and route of administration; and 4) individual patient variability. Approximately 70 to 80% of all cancer patients receiving chemotherapy experience emesis, whereas 10% to 44% experience anticipatory emesis. The following general principles are recommended. 1) A 5-HT3 receptor antagonist should be administered prior to each day's 1st dose of moderately or highly emetogenic chemotherapy. 2) Dexamethasone should be administered once daily either orally or intravenously for every day of moderately or highly-emetogenic chemotherapy and for 2-3 days after chemotherapy for regimens that are likely to cause significant delayed-emesis. 3) The most effective way to treat anticipatory nausea and/or vomiting is to prevent it by using optimal antiemetic therapy during every cycle of treatment.

  11. Pegfilgrastim use during chemotherapy: current and future applications.

    PubMed

    Wolf, Todd; Densmore, John J

    2004-11-01

    Chemotherapy-induced myelosuppression is the most common dose-limiting side effect of cancer chemotherapy. Neutropenia is a serious risk with chemotherapy, associated with infectious complications, use of intravenous antibiotics, hospitalization, and even death. The occurrence of febrile neutropenia can lead to dose reductions and delay in subsequent cycles of chemotherapy that may have a detrimental affect on overall survival and disease-free survival. Granulocyte colony-stimulating factors (G-CSF) can reduce the duration of severe neutropenia, the incidence of febrile neutropenia, and allow planned dosing and timing of chemotherapy. Filgrastim is a G-CSF that has demonstrated benefit for the treatment and prophylaxis of chemotherapy-induced neutropenia (CIN), but its short half-life requires repeated daily subcutaneous injection. Pegfilgrastim is a recombinant G-CSF created by attaching a polyethylene glycol (PEG) molecule to the filgrastim protein. Once-per-cycle dosing of pegfilgrastim has been evaluated in clinical trials using myelosuppressive chemotherapy in breast cancer, Hodgkin's lymphoma, and non-Hodgkin's lymphoma. Trials have demonstrated that pegfilgrastim is comparable in safety and efficacy to filgrastim for decreasing the duration of severe neutropenia after chemotherapy in patients with nonmyeloid malignancy. This review will summarize recent clinical trial results and novel uses of pegfilgrastim.

  12. Effects of chemotherapy on osseointegration of implants: a case report.

    PubMed

    McDonald, A R; Pogrel, M A; Sharma, A

    1998-01-01

    A patient underwent mandibular resection for high-grade osteosarcoma with immediate reconstruction with a microvascular fibula free bone graft and simultaneous placement of osseointegrated implants. Following initial healing, she underwent six cycles of chemotherapy and had further revision surgery prior to implant exposure and construction of a prosthesis. The chemotherapy appears to have had no deleterious effects on implant osseointegration or survival.

  13. [The second-line chemotherapy for urological cancers].

    PubMed

    Miki, Tsuneharu; Mikami, Kazuya; Mizutani, Yoichi

    2005-01-01

    This review summarizes second-line chemotherapy for testicular cancer and urothelial cancer. For testicular cancer, the combination of bleomycin (BLM), etoposide (ETP), and cisplatin (CDDP) (BEP) is commonly used as an induction therapy. The combination of vinblastine (VLB), ifosfamide (IFM) and CDDP (VeIP) or ETP, IFM, and CDDP (VIP) is used for the second-line chemotherapy. When the efficacy of VeIP and VIP is not sufficient, high-dose chemotherapy or chemotherapy with new anticancer agents has been used for the second-line chemotherapy. High-dose chemotherapy showed long-term survival rates of 30-50%, but patients with testicular cancer resistance to CDDP have poor outcomes. Although new anticancer agents, such as paclitaxel (TXL), gemcitabine (GEM) and irinotecan have been introduced, further examinations are needed to evaluate these drugs. The combination of methotrexate, VLB, adriamycin, and CDDP (MVAC) is used as the standard chemotherapy for urothelial cancer. The outcomes of MVAC are favorable, but the duration of response is short and long-term survival cannot be expected. Recently, the efficacy of new anticancer agents including TXL and GEM against urothelial cancers has been demonstrated. Although TXL and GEM combination therapy as the second-line chemotherapy has some effects, more evidence needs to be accumulated to establish it as a second-line treatment.

  14. [Collateral effects of intraoperative hyperthermic chemotherapy in peritoneal carcinomatosis].

    PubMed

    Izzo, L; Galati, G; D'Aprile, M R; Stasolla, A; Kharrub, Z; Maccioni, F; Sassayannis, P G; D'Arielli, D; Marini, M; Gazzanelli, S; Caputo, M

    2004-01-01

    The association between chemotherapy and hypertermia produces a synergic effect. In this study the Authors present their experience, by the analysis of the results. From 1993 to 2000, 17 patients have been treated with surgery associated with hypertermic chemotherapy for peritoneal carcinomatosis. For the management of these patients a constant cooperation among surgeon, cardiologist and anaesthetist is very important. PMID:15112761

  15. Human antimicrobial peptides and proteins.

    PubMed

    Wang, Guangshun

    2014-05-13

    As the key components of innate immunity, human host defense antimicrobial peptides and proteins (AMPs) play a critical role in warding off invading microbial pathogens. In addition, AMPs can possess other biological functions such as apoptosis, wound healing, and immune modulation. This article provides an overview on the identification, activity, 3D structure, and mechanism of action of human AMPs selected from the antimicrobial peptide database. Over 100 such peptides have been identified from a variety of tissues and epithelial surfaces, including skin, eyes, ears, mouths, gut, immune, nervous and urinary systems. These peptides vary from 10 to 150 amino acids with a net charge between -3 and +20 and a hydrophobic content below 60%. The sequence diversity enables human AMPs to adopt various 3D structures and to attack pathogens by different mechanisms. While α-defensin HD-6 can self-assemble on the bacterial surface into nanonets to entangle bacteria, both HNP-1 and β-defensin hBD-3 are able to block cell wall biosynthesis by binding to lipid II. Lysozyme is well-characterized to cleave bacterial cell wall polysaccharides but can also kill bacteria by a non-catalytic mechanism. The two hydrophobic domains in the long amphipathic α-helix of human cathelicidin LL-37 lays the basis for binding and disrupting the curved anionic bacterial membrane surfaces by forming pores or via the carpet model. Furthermore, dermcidin may serve as ion channel by forming a long helix-bundle structure. In addition, the C-type lectin RegIIIα can initially recognize bacterial peptidoglycans followed by pore formation in the membrane. Finally, histatin 5 and GAPDH(2-32) can enter microbial cells to exert their effects. It appears that granulysin enters cells and kills intracellular pathogens with the aid of pore-forming perforin. This arsenal of human defense proteins not only keeps us healthy but also inspires the development of a new generation of personalized medicine to combat

  16. Human Antimicrobial Peptides and Proteins

    PubMed Central

    Wang, Guangshun

    2014-01-01

    As the key components of innate immunity, human host defense antimicrobial peptides and proteins (AMPs) play a critical role in warding off invading microbial pathogens. In addition, AMPs can possess other biological functions such as apoptosis, wound healing, and immune modulation. This article provides an overview on the identification, activity, 3D structure, and mechanism of action of human AMPs selected from the antimicrobial peptide database. Over 100 such peptides have been identified from a variety of tissues and epithelial surfaces, including skin, eyes, ears, mouths, gut, immune, nervous and urinary systems. These peptides vary from 10 to 150 amino acids with a net charge between −3 and +20 and a hydrophobic content below 60%. The sequence diversity enables human AMPs to adopt various 3D structures and to attack pathogens by different mechanisms. While α-defensin HD-6 can self-assemble on the bacterial surface into nanonets to entangle bacteria, both HNP-1 and β-defensin hBD-3 are able to block cell wall biosynthesis by binding to lipid II. Lysozyme is well-characterized to cleave bacterial cell wall polysaccharides but can also kill bacteria by a non-catalytic mechanism. The two hydrophobic domains in the long amphipathic α-helix of human cathelicidin LL-37 lays the basis for binding and disrupting the curved anionic bacterial membrane surfaces by forming pores or via the carpet model. Furthermore, dermcidin may serve as ion channel by forming a long helix-bundle structure. In addition, the C-type lectin RegIIIα can initially recognize bacterial peptidoglycans followed by pore formation in the membrane. Finally, histatin 5 and GAPDH(2-32) can enter microbial cells to exert their effects. It appears that granulysin enters cells and kills intracellular pathogens with the aid of pore-forming perforin. This arsenal of human defense proteins not only keeps us healthy but also inspires the development of a new generation of personalized medicine to

  17. Antimicrobial Dose in Obese Patient

    PubMed Central

    Kassab, Sawsan; Syed Sulaiman, Syed Azhar; Abdul Aziz, Noorizan

    2007-01-01

    Introduction Obesity is a chronic disease that has become one of major public health issue in Malaysia because of its association with other disease states including cardiovascular disease and diabetes. Despite continuous efforts to educate the public about the health risks associated with obesity, prevalence of the disease continues to increase. Dosing of many medications are based on weight, limited data are available on how antimicrobial agents should be dosed in obesity. The aim of this case presentation is to discuss dose of antibiotic in obese patient. Case report: Patient: GMN, Malay, Female, 45 year old, 150kg, transferred from medical ward to ICU with problems of fever, orthopnea, sepsis secondary to nosocomial pneumonia. She was admitted to hospital a week ago for SOB on exertion, cyanosis, mildly dyspneic, somasthenia, bilateral ankle swelling. There was no fever, cough, chest pain, clubbing, flapping tremor. Her grand father has pre-morbid history of obesity, HPT, DM and asthma. She was non alcoholic, smoker, and not on diet control. The diagnosis Pickwickian syndrome was made. Patient was treated with IV Dopamine 11mcg/kg/min, IV Morphine 4mg/h. IV GTN 15mcg/min, IV Ca gluconate 10g/24h for 3/7, IV Zantac 50mg tds, IV Augmentin 1.2g tds, IV Lasix 40mg od, IV Plasil 10mg tds, S.c heparin 5000IU bd. patient become stable and moved to medical ward to continue her treatment. Discussion: The altered physiologic function seen in obese patients is a concern in patients receiving antimicrobial agents because therapeutic outcomes depend on achieving a minimum inhibitory concentration (MIC). The therapeutic effect of any drug can be altered when any of the 4 pharmacokinetic processes (absorption, distribution, metabolism, or elimination) are altered. Decreased blood flow rates and increased renal clearance in obese patients can affect drug distribution and elimination. Changes in serum protein levels can change the metabolism and distribution of drugs that are

  18. Dietetic management in gastrointestinal complications from antimalignant chemotherapy.

    PubMed

    Calixto-Lima, L; Martins de Andrade, E; Gomes, A P; Geller, M; Siqueira-Batista, R

    2012-01-01

    Antineoplastic chemotherapy (CT) represents the systemic treatment of malignant tumors. It can be used alone or combined with surgery and / or radiotherapy. The cytotoxic agents used in chemotherapy work on both cancerous cells and noncancerous cells of the body, generally resulting in high toxicity. The biological aggressiveness of chemotherapy particularly affects rapidly replicating cells, such as those of the digestive tract, resulting in adverse effects that impair food intake, leading to compromised nutritional status and which may lead to cachexia. The main toxic effects of chemotherapy in the gastrointestinal tract include nausea, vomiting -these are the most frequent- constipation, diarrhea, xerostomia, mucositis, dysphagia and anorexia. Given the high frequency of such effects, nutritional intervention should be an integral part of cancer treatment, to maintain and/or improve the patient's nutritional status and reduce or minimize the side effects caused by treatment. Accordingly, the goal of this study is to review dietetic conduct in the process of caring for patients undergoing cancer chemotherapy.

  19. Management of HIV Infection in Patients With Cancer Receiving Chemotherapy

    PubMed Central

    Mayer, Kenneth H.; Torres, Harrys A.; Mulanovich, Victor

    2014-01-01

    The optimal antiretroviral therapy (ART) regimen for human immunodeficiency virus (HIV)–infected patients with cancer remains unknown, as clinical trials are lacking and published data are insufficient to guide recommendations. When concomitant use of chemotherapy and ART is anticipated, overlap of toxic effects and drug–drug interactions between chemotherapy and ART may alter the optimal choice of ART. Prospective studies are urgently needed to further define the toxic effects of combined chemotherapy and ART in HIV-positive cancer patients. Such studies should aid the development of guidelines for treatment of this population. For now, clinicians should individualize decisions regarding treatment of HIV according to clinical and laboratory findings, cancer treatment plan (chemotherapy, radiotherapy, or surgery), liver or renal disease, potential adverse drug effects (eg, rash, gastrointestinal intolerance, bone marrow suppression), and patient preference. This review focuses on what infectious disease specialists need to know to select the most appropriate ART regimens for patients receiving chemotherapy. PMID:24642555

  20. Case report: retinitis pigmentosa following cytotoxic chemotherapy in Usher's syndrome.

    PubMed

    Blanchet, P; Wellemeyer, M L; Burton, G V

    1992-05-01

    Ocular toxicity is an uncommon complication of cytotoxic chemotherapy. Retinitis pigmentosa complicating cancer chemotherapy has not been reported. A patient with probable Usher's syndrome (congenital sensorineural deafness) had apparent acceleration of retinitis pigmentosa with blindness following cytotoxic chemotherapy for non-Hodgkin's lymphoma. Retinitis pigmentosa, a feature of Usher's syndrome, usually develops as a slowly progressive process. The rapid acceleration of retinopathy following tumor therapy suggests a possible relationship to the cytotoxic chemotherapy. Lymphocytes and fibroblasts from patients with Usher's syndrome are hypersensitive to the x-ray type of DNA-damaging agents. The DNA-damaging effects of chemotherapy may have accelerated the progression of retinitis pigmentosa in this patient. PMID:1580321

  1. Ultrashort Antimicrobial Peptides with Antiendotoxin Properties

    PubMed Central

    Chih, Ya-Han; Lin, Yen-Shan; Yip, Bak-Sau; Wei, Hsiu-Ju; Chu, Hung-Lun; Yu, Hui-Yuan; Cheng, Hsi-Tsung

    2015-01-01

    Release of lipopolysaccharide (LPS) (endotoxin) from bacteria into the bloodstream may cause serious unwanted stimulation of the host immune system. Some but not all antimicrobial peptides can neutralize LPS-stimulated proinflammatory responses. Salt resistance and serum stability of short antimicrobial peptides can be boosted by adding β-naphthylalanine to their termini. Herein, significant antiendotoxin effects were observed in vitro and in vivo with the β-naphthylalanine end-tagged variants of the short antimicrobial peptides S1 and KWWK. PMID:26033727

  2. Comparative evaluation of antimicrobials for textile applications.

    PubMed

    Windler, Lena; Height, Murray; Nowack, Bernd

    2013-03-01

    Many antimicrobial technologies are available for textiles. They may be used in many different textile applications to prevent the growth of microorganisms. Due to the biological activity of the antimicrobial compounds, the assessment of the safety of these substances is an ongoing subject of research and regulatory scrutiny. This review aims to give an overview on the main compounds used today for antimicrobial textile functionalization. Based on an evaluation of scientific publications, market data as well as regulatory documents, the potential effects of antimicrobials on the environment and on human health were considered and also life cycle perspectives were taken into account. The characteristics of each compound were summarized according to technical, environmental and human health criteria. Triclosan, silane quaternary ammonium compounds, zinc pyrithione and silver-based compounds are the main antimicrobials used in textiles. The synthetic organic compounds dominate the antimicrobials market on a weight basis. On the technical side the application rates of the antimicrobials used to functionalize a textile product are an important parameter with treatments requiring lower dosage rates offering clear benefits in terms of less active substance required to achieve the functionality. The durability of the antimicrobial treatment has a strong influence on the potential for release and subsequent environmental effects. In terms of environmental criteria, all compounds were rated similarly in effective removal in wastewater treatment processes. The extent of published information about environmental behavior for each compound varies, limiting the possibility for an in-depth comparison of all textile-relevant parameters across the antimicrobials. Nevertheless the comparative evaluation showed that each antimicrobial technology has specific risks and benefits that should be taken into account in evaluating the suitability of different antimicrobial products. The

  3. Antimicrobial activity of Gentiana lutea L. extracts.

    PubMed

    Savikin, Katarina; Menković, Nebojsa; Zdunić, Gordana; Stević, Tatjana; Radanović, Dragoja; Janković, Teodora

    2009-01-01

    Methanolic extracts of flowers and leaves of Gentiana lutea L., together with the isolated compounds mangiferin, isogentisin and gentiopicrin, were used to investigate the antimicrobial activity of the plant. A variety of Gram-positive and Gram-negative bacteria as well as the yeast Candida albicans has been included in this study. Both extracts and isolated compounds showed antimicrobial activity with MIC values ranging from 0.12-0.31 mg/ml. Our study indicated that the synergistic activity of the pure compounds may be responsible for the good antimicrobial effect of the extracts. Quantification of the secondary metabolites was performed using HPLC.

  4. Naturally occurring antimicrobials for minimally processed foods.

    PubMed

    Davidson, P Michael; Critzer, Faith J; Taylor, T Matthew

    2013-01-01

    Natural antimicrobials are gaining increased interest from researchers and food manufacturers alike seeking to discover label-friendly alternatives to the widely implemented synthetic compounds. Naturally occurring antimicrobials can be applied directly to food to protect food quality, extend food shelf life by inhibiting or inactivating spoilage microorganisms, and improve food safety by inhibiting or inactivating food-borne pathogens. There are a great number of natural antimicrobials derived from animal, plant, and microbial sources. This manuscript reviews their efficacy against spoilage and pathogenic organisms, their methods of evaluation, and their application in various foods as well as the development of novel delivery systems and incorporation with other hurdles.

  5. [Antimicrobial peptide in dentisty. Literature review].

    PubMed

    Sato, F Simain; Rompen, E; Heinen, E

    2009-12-01

    The use of antimicrobial substances has contributed to the development of multiple antimicrobial resistances (1), challenging the pharmaceutical industry to develop with new, innovative, and effective molecules. Discovered around 1980, molecules called natural antimicrobial peptides (AMPs) appear to hold great potential for the treatment of infections. These cationic peptides are able to stop the bacterial development and to control infections. The purpose of this review is to help improve the understanding of the way AMPs operate in the context of the development of new cures against viruses, bacteria, and mushrooms found in the human body in general and in the oral cavity in particular. PMID:20143750

  6. Comparative evaluation of antimicrobials for textile applications.

    PubMed

    Windler, Lena; Height, Murray; Nowack, Bernd

    2013-03-01

    Many antimicrobial technologies are available for textiles. They may be used in many different textile applications to prevent the growth of microorganisms. Due to the biological activity of the antimicrobial compounds, the assessment of the safety of these substances is an ongoing subject of research and regulatory scrutiny. This review aims to give an overview on the main compounds used today for antimicrobial textile functionalization. Based on an evaluation of scientific publications, market data as well as regulatory documents, the potential effects of antimicrobials on the environment and on human health were considered and also life cycle perspectives were taken into account. The characteristics of each compound were summarized according to technical, environmental and human health criteria. Triclosan, silane quaternary ammonium compounds, zinc pyrithione and silver-based compounds are the main antimicrobials used in textiles. The synthetic organic compounds dominate the antimicrobials market on a weight basis. On the technical side the application rates of the antimicrobials used to functionalize a textile product are an important parameter with treatments requiring lower dosage rates offering clear benefits in terms of less active substance required to achieve the functionality. The durability of the antimicrobial treatment has a strong influence on the potential for release and subsequent environmental effects. In terms of environmental criteria, all compounds were rated similarly in effective removal in wastewater treatment processes. The extent of published information about environmental behavior for each compound varies, limiting the possibility for an in-depth comparison of all textile-relevant parameters across the antimicrobials. Nevertheless the comparative evaluation showed that each antimicrobial technology has specific risks and benefits that should be taken into account in evaluating the suitability of different antimicrobial products. The

  7. The role of public health in antimicrobial stewardship in healthcare.

    PubMed

    Trivedi, Kavita K; Pollack, Loria A

    2014-10-15

    Education, surveillance, and promotion of antimicrobial stewardship align with the goals of public health to prevent disease, promote health, and prolong life. Many US federal and state public health organizations are already engaged in antimicrobial stewardship activities. Healthcare providers are encouraged to work with public health officials on appropriate local antimicrobial stewardship strategies to attain the common goal of reducing antimicrobial resistance and preserving antimicrobials for future generations.

  8. Antimicrobial photodynamic therapy: An overview

    PubMed Central

    Rajesh, S.; Koshi, Elizabeth; Philip, Koshi; Mohan, Aparna

    2011-01-01

    Inflammatory periodontal disease caused by dental plaque is characterized by the clinical signs of inflammation and loss of periodontal tissue support. The mechanical removal of this biofilm and adjunctive use of antibacterial disinfectants and antibiotics have been the conventional methods of periodontal therapy. But the removal of plaque and the reduction in the number of infectious organisms can be impaired in sites with difficult access. The possibility of development of resistance to antibiotics by the target organism has led to the development of a new antimicrobial concept with fewer complications. Photodynamic therapy (PDT) involves the use of low power lasers with appropriate wavelength to kill micro organisms treated with a photosensitizer drug. PDT could be a useful adjunct to mechanical as well as antibiotics in eliminating periopathogenic bacteria. PMID:22368354

  9. Antimicrobial peptides of multicellular organisms

    NASA Astrophysics Data System (ADS)

    Zasloff, Michael

    2002-01-01

    Multicellular organisms live, by and large, harmoniously with microbes. The cornea of the eye of an animal is almost always free of signs of infection. The insect flourishes without lymphocytes or antibodies. A plant seed germinates successfully in the midst of soil microbes. How is this accomplished? Both animals and plants possess potent, broad-spectrum antimicrobial peptides, which they use to fend off a wide range of microbes, including bacteria, fungi, viruses and protozoa. What sorts of molecules are they? How are they employed by animals in their defence? As our need for new antibiotics becomes more pressing, could we design anti-infective drugs based on the design principles these molecules teach us?

  10. Antimicrobial activities of Barringtonia acutangula.

    PubMed

    Rahman, M Mukhlesur; Polfreman, David; MacGeachan, Jodie; Gray, Alexander I

    2005-06-01

    Crude extracts and VLC fractions from the stem bark of Barringtonia acutangula (L.) Gaertn (Fam. Lecythidaceae) were screened for their antimicrobial activities against two Gram-positive bacteria, two Gram-negative bacteria and two fungi using a microdilution titre assay. Among the crude extracts, petroleum ether extract showed good activity against all test organisms. The VLC fraction PE 16 was found to be very effective against Bacillus subtilis (MIC=25 microg/ml) and Aspergillus niger (MIC=12.5 microg/ml). The activities were compared to standard antibiotics-kanamycin and fluconazole. The major compound from PE16 was identified as 12, 20(29)-lupadien-3-ol by NMR spectroscopy. PMID:16114086

  11. Antimicrobial dihydroisocoumarins from Crassocephalum biafrae.

    PubMed

    Tabopda, Turibio K; Fotso, Gislain W; Ngoupayo, Joseph; Mitaine-Offer, Anne-Claire; Ngadjui, Bonaventure T; Lacaille-Dubois, Marie-Aleth

    2009-09-01

    Bioassay-guided fractionation of the CHCl (3)-soluble extract of the stem bark of Crassocephalum biafrae (Asteraceae) resulted in the isolation of three new dihydroisocoumarins, named biafraecoumarins A ( 1), B ( 2), and C ( 3); two known triterpenes ( 4 and 5); and a known ceramide ( 6). The structures of the new compounds were established as 7-but-15-enyl-6,8-dihydroxy-3( R)-penta-9,11-dienylisochroman-1-one ( 1), 7-butyl-6,8-dihydroxy-3( R)-penta-9,11-dienylisochroman-1-one ( 2), and 7-butyl-6,8-dihydroxy-3( R)-pent-10-enylisochroman-1-one ( 3) using spectroscopic data. Compounds 1- 3 exhibit low to significant antimicrobial activities against Escherichia coli, Bacillus subtilis, Staphylococcus aureus, Pseudomonas picketti, Trichphyton longifusus, Aspergillus flavus, Microsporum canis, Fusarium solani, Candida albicans, and Candida glabrata. PMID:19350487

  12. The in vitro effect of six antimicrobials against Mycoplasma putrefaciens, Mycoplasma mycoides subsp. mycoides LC and Mycoplasma capricolum subsp. capricolum isolated from sheep and goats in Jordan.

    PubMed

    Al-Momani, W; Nicholas, R A J; Janakat, S; Abu-Basha, E; Ayling, R D

    2006-01-01

    Respiratory disease in sheep and goats is a major problem in Jordan and is often associated with Mycoplasma species. Without effective vaccines, control is mainly by chemotherapy, but the uncontrolled use of antimicrobials has led to concerns about the potential development of antimicrobial resistance. The in vitro effect of chloramphenicol, florfenicol, enrofloxacin, tylosin, erythromycin and oxytetracycline was determined against 32 isolates of Mycoplasma species-M. mycoides subsp. mycoides LC (6), M. capricolum subsp. capricolum (8) and M. putrefaciens (18), all isolated from either nasal swabs or milk, from sheep and goats in different regions of Jordan. The antimicrobial susceptibility showed some Mycoplasma species-specific differences, with M. capricolum subsp. capricolum being more susceptible to tylosin and erythromycin. Chloramphenicol and florfenicol were the least effective for all three Mycoplasma species. No trends or significant differences in antimicrobial susceptibilities were observed between sheep and goat isolates, between milk or nasal swab isolates, or between isolates from different regions of Jordan. Some isolates of M. capricolum subsp. capricolum and M. putrefaciens showed higher MIC levels with oxytetracycline, as did two isolates of M. mycoides subsp. mycoides LC with tylosin, possibly indicating signs of development of antimicrobial resistance. PMID:17405622

  13. Antimicrobial Peptides in Human Sepsis

    PubMed Central

    Martin, Lukas; van Meegern, Anne; Doemming, Sabine; Schuerholz, Tobias

    2015-01-01

    Nearly 100 years ago, antimicrobial peptides (AMPs) were identified as an important part of innate immunity. They exist in species from bacteria to mammals and can be isolated in body fluids and on surfaces constitutively or induced by inflammation. Defensins have anti-bacterial effects against Gram-positive and Gram-negative bacteria as well as anti-viral and anti-yeast effects. Human neutrophil peptides (HNP) 1–3 and human beta-defensins (HBDs) 1–3 are some of the most important defensins in humans. Recent studies have demonstrated higher levels of HNP 1–3 and HBD-2 in sepsis. The bactericidal/permeability-increasing protein (BPI) attenuates local inflammatory response and decreases systemic toxicity of endotoxins. Moreover, BPI might reflect the severity of organ dysfunction in sepsis. Elevated plasma lactoferrin is detected in patients with organ failure. HNP 1–3, lactoferrin, BPI, and heparin-binding protein are increased in sepsis. Human lactoferrin peptide 1–11 (hLF 1–11) possesses antimicrobial activity and modulates inflammation. The recombinant form of lactoferrin [talactoferrin alpha (TLF)] has been shown to decrease mortality in critically ill patients. A phase II/III study with TLF in sepsis did not confirm this result. The growing number of multiresistant bacteria is an ongoing problem in sepsis therapy. Furthermore, antibiotics are known to promote the liberation of pro-inflammatory cell components and thus augment the severity of sepsis. Compared to antibiotics, AMPs kill bacteria but also neutralize pathogenic factors such as lipopolysaccharide. The obstacle to applying naturally occurring AMPs is their high nephro- and neurotoxicity. Therefore, the challenge is to develop peptides to treat septic patients effectively without causing harm. This overview focuses on natural and synthetic AMPs in human and experimental sepsis and their potential to provide significant improvements in the treatment of critically ill with severe infections

  14. Making a Case for Pediatric Antimicrobial Stewardship Programs.

    PubMed

    Magsarili, Heather K; Girotto, Jennifer E; Bennett, Nicholas J; Nicolau, David P

    2015-11-01

    Although antimicrobials are commonly used in children, it is important to remember that they can have a profound impact on this unique patient population. Inadvertent consequences of antiinfective use in children include antimicrobial resistance, infection caused by Clostridium difficile, increased risk of obesity, and adverse drug events. In addition, compared with adults, children have different dosing requirements, antimicrobial formulation needs, pharmacokinetics, and antimicrobial susceptibility profiles. Therefore, pediatric-specific antimicrobial stewardship efforts are needed to promote appropriate use of antimicrobials in children. The primary purposes of this review article are to provide a rationale behind pediatric-focused antimicrobial stewardship and to describe currently available evidence regarding the initiatives of pediatric antimicrobial stewardship programs (ASPs). A literature search of the Medline database was performed (from inception through March 2015). The studies included in this review focus on antimicrobial stewardship interventions in inpatient pediatric settings. Ten inpatient studies involving pediatric-focused antimicrobial stewardship interventions were identified from the published literature. Four studies used the core strategy of prospective audit with feedback; two used prior approval. The remaining four used supplemental antimicrobial stewardship strategies (guidelines, clinical pathways, and computerized decision support tools). In general, the interventions resulted in decreased antimicrobial use, reduced antimicrobial costs, and fewer prescribing errors. Children have unique medical needs related to antimicrobials and deserve focused ASP efforts. The literature regarding pediatric antimicrobial stewardship interventions is limited, but published interventions may serve as paradigms for developing pediatric ASPs as demonstrated by the general success of these interventions.

  15. Exploring novel chemotherapy treatments using the WWW.

    PubMed

    Boyle, J; Henderson, D; McCall, J; McLeod, H; Usher, J

    1997-11-01

    A JAVA application, The Oncologists Workbench, which allows oncologists to estimate the influence of new cancer treatment schedules is being developed. The requirement for a rational approach to the design of chemotherapeutic regimens is well established [1]. Our prototype allows oncologists using the World Wide Web (WWW) to graphically construct treatment regimens while considering various toxic side effects. A simulation engine makes predictions of tumour growth based on previous clinical knowledge of response to treatment. The oncologist can then examine the predicted tumour response information with a specially constructed interactive viewer. These interlinked tools allow oncologists to develop and predict the effectiveness of novel chemotherapeutic regimens. This work is part of an ongoing collaboration between oncologists, mathematicians and computer scientists to provide tools for improving cancer chemotherapy.

  16. Chemotherapy of prostate cancer: present and future.

    PubMed

    Trump, Donald; Lau, Yiu-Keung

    2003-06-01

    The role of chemotherapy in prostate cancer continues to evolve. In men with symptomatic androgen-independent prostate cancer, significant reduction in pain and analgesic requirements are achievable with mitoxantrone and glucocorticoid combinations compared with glucocorticoids alone. However, survival rates are not improved. Taxane-based combinations with estramustine phosphate or other new agents show promise. Prostate-specific antigen response rates with these combinations appear to be 1.5 to 2 times more frequent than with mitoxantrone-based combinations. Randomized trials of taxane versus mitoxantrone-based therapies are underway. New agents and applications of current agents in adjuvant settings should be explored if survival in men with prostate cancer is to be improved. PMID:12756087

  17. Photoswitchable nanoparticles for in vivo cancer chemotherapy.

    PubMed

    Tong, Rong; Chiang, Homer H; Kohane, Daniel S

    2013-11-19

    There are many obstacles to effective cancer chemotherapy, including drug penetration and accumulation in tumors and drug systemic toxicity. The penetration of therapies into tumors is limited by the dense tumor matrix and by compression of the tumor vasculature. We have developed spiropyran-based nanoparticles that shrink from 103 to 49 nm upon irradiation at 365 nm. That shrinkage enhanced tissue penetration and drug release. Irradiation of s.c. HT-1080 tumors in nude mice administered i.v. docetaxel-containing nanoparticles was more effective treatment than free docetaxel or encapsulated docetaxel without irradiation. Irradiation at the tumor site also resulted in less systemic toxicity than if the nanoparticles were irradiated before injection, presumably because of less systemically distributed free drug. The enhanced efficacy of nanoparticles in irradiated tumors may have been related to the observed enhanced tumor penetration by nanoparticles and decompression of tumor blood vessels, which may also increase nanoparticle delivery into tumors.

  18. Thermal potentiation of chemotherapy by magnetic nanoparticles

    PubMed Central

    Torres-Lugo, Madeline; Rinaldi, Carlos

    2014-01-01

    Clinical studies have demonstrated the effectiveness of hyperthermia as an adjuvant for chemotherapy and radiotherapy. However, significant clinical challenges have been encountered, such as a broader spectrum of toxicity, lack of patient tolerance, temperature control and significant invasiveness. Hyperthermia induced by magnetic nanoparticles in high-frequency oscillating magnetic fields, commonly termed magnetic fluid hyperthermia, is a promising form of heat delivery in which thermal energy is supplied at the nanoscale to the tumor. This review discusses the mechanisms of heat dissipation of iron oxide-based magnetic nanoparticles, current methods and challenges to deliver heat in the clinic, and the current work related to the use of magnetic nanoparticles for the thermal-chemopotentiation of therapeutic drugs. PMID:24074390

  19. Thermal potentiation of chemotherapy by magnetic nanoparticles.

    PubMed

    Torres-Lugo, Madeline; Rinaldi, Carlos

    2013-10-01

    Clinical studies have demonstrated the effectiveness of hyperthermia as an adjuvant for chemotherapy and radiotherapy. However, significant clinical challenges have been encountered, such as a broader spectrum of toxicity, lack of patient tolerance, temperature control and significant invasiveness. Hyperthermia induced by magnetic nanoparticles in high-frequency oscillating magnetic fields, commonly termed magnetic fluid hyperthermia, is a promising form of heat delivery in which thermal energy is supplied at the nanoscale to the tumor. This review discusses the mechanisms of heat dissipation of iron oxide-based magnetic nanoparticles, current methods and challenges to deliver heat in the clinic, and the current work related to the use of magnetic nanoparticles for the thermal-chemopotentiation of therapeutic drugs.

  20. Anticipatory nausea and vomiting due to chemotherapy.

    PubMed

    Kamen, Charles; Tejani, Mohamedtaki A; Chandwani, Kavita; Janelsins, Michelle; Peoples, Anita R; Roscoe, Joseph A; Morrow, Gary R

    2014-01-01

    As a specific variation of chemotherapy-induced nausea and vomiting, anticipatory nausea and vomiting (ANV) appears particularly linked to psychological processes. The three predominant factors related to ANV are classical conditioning; demographic and treatment-related factors; and anxiety or negative expectancies. Laboratory models have provided some support for these underlying mechanisms for ANV. ANV may be treated with medical or pharmacological interventions, including benzodiazepines and other psychotropic medications. However, behavioral treatments, including systematic desensitization, remain first line options for addressing ANV. Some complementary treatment approaches have shown promise in reducing ANV symptoms. Additional research into these approaches is needed. This review will address the underlying models of ANV and provide a discussion of these various treatment options.

  1. A case of Takotsubo cardiomyopathy after chemotherapy

    PubMed Central

    Malley, Tamir; Watson, Edmund

    2016-01-01

    Here we present the case of a patient with diffuse large B-cell lymphoma who was admitted to hospital for an elective autologous peripheral blood stem cell transplant after cytotoxic treatment with lomustine, cytarabine, cyclophosphomide and etoposide (LACE). On the final day of chemotherapeutic treatment, she developed sudden onset dyspnoea. Electrocardiography confirmed acute antero-lateral T-wave inversion. She went onto have coronary angiography that demonstrated unobstructed coronary arteries. Left ventriculography demonstrated apical ballooning, consistent with Takotsubo (stress) cardiomyopathy. The link between chemotherapy and Takotsubo cardiomyopathy has become increasingly recognized in recent years, although causality remains to be established and the mechanism of action is not yet fully understood. PMID:27066260

  2. Chemotherapy of prostate cancer: present and future.

    PubMed

    Trump, Donald; Lau, Yiu-Keung

    2003-06-01

    The role of chemotherapy in prostate cancer continues to evolve. In men with symptomatic androgen-independent prostate cancer, significant reduction in pain and analgesic requirements are achievable with mitoxantrone and glucocorticoid combinations compared with glucocorticoids alone. However, survival rates are not improved. Taxane-based combinations with estramustine phosphate or other new agents show promise. Prostate-specific antigen response rates with these combinations appear to be 1.5 to 2 times more frequent than with mitoxantrone-based combinations. Randomized trials of taxane versus mitoxantrone-based therapies are underway. New agents and applications of current agents in adjuvant settings should be explored if survival in men with prostate cancer is to be improved.

  3. Chemotherapy and Fingerprint Loss: Beyond Cosmetic

    PubMed Central

    2012-01-01

    Hand–foot syndrome (HFS) is a common adverse reaction to several chemotherapy drugs. Focus has been on the clinically relevant sequelae associated with this condition, with fingerprint loss receiving little attention. We report the case of a 53-year old male patient with terminal metastatic adenocarcinoma of the rectum involving the liver and lungs who developed grade 3 HFS while on capecitabine therapy. This resulted in his inability to process required government papers as a result of the loss of his fingerprints, imposing significant inconvenience and frustration on a person severely challenged by his deteriorating health. We believe clinicians should pay more attention to this possible outcome that can add additional stress in the lives of patients whose quality of life is already severely compromised. PMID:22298801

  4. Intrathecal chemotherapy with ACNU for meningeal gliomatosis.

    PubMed Central

    Yoshida, T. K.; Beuls, E.; Shimizu, K.; Koulousakis, A.; Sturm, V.

    1992-01-01

    ACNU [1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride], one of the chloroethylnitrosoureas (CENUs), is believed to be effective against malignant glioma when intravenously or intrathecally administered. A rat model with meningeal gliomatosis (MG) induced by an intracisternal inoculation of rat C6 or 9L glioma cells was intrathecally and intravenously treated with ACNU in order to test the feasibility of intrathecal chemotherapy with ACNU in the treatment of meningeal gliomatosis. The median survival time (MST) of the animals was significantly prolonged when ACNU was intrathecally administered at dosages of 0.5 to 1.5 mg kg-1 in the early stages of MG, i.e. within 3 days after the tumour inoculation, whereas intravenous therapy with ACNU at a dose of 15 mg kg-1 did not exhibit any efficacy in the rats inoculated with C6 glioma cells (C6-MG). Intrathecal ACNU, however, at dosages of up to 1.5 mg kg-1 failed to demonstrate any therapeutic effect in the late stage of MG, i.e. 5 days after the tumour inoculation, except in the rats inoculated with 9L brain tumour cells (9L-MG). Intravenous chemotherapy with ACNU at a dose of 15 mg kg-1 extended the MST of the 9L-MG rats more significantly in the late stage of MG than in its early stage. This points to the feasibility of intrathecal ACNU in the treatment of meningeal gliomatosis in its early stages, but not in its late stages in which intravenous ACNU might be more effective than intrathecal treatment against MG of which the parenchyma has already been deeply invaded by the tumour. Images Figure 5 PMID:1457369

  5. Bevacizumab with preoperative chemotherapy versus preoperative chemotherapy alone for colorectal cancer liver metastases: a retrospective cohort study.

    PubMed

    Lu, Zhen-Hai; Peng, Jian-Hong; Wang, Fu-Long; Yuan, Yun-Fei; Jiang, Wu; Li, Yu-Hong; Wu, Xiao-Jun; Chen, Gong; Ding, Pei-Rong; Li, Li-Ren; Kong, Ling-Heng; Lin, Jun-Zhong; Zhang, Rong-Xin; Wan, De-Sen; Pan, Zhi-Zhong

    2016-08-01

    This study aimed to assess the efficacy and safety of bevacizumab plus preoperative chemotherapy as first-line treatment for liver-only metastatic colorectal cancer in Chinese patients compared with those of preoperative chemotherapy alone.Patients with histologically confirmed liver-only metastatic colorectal cancer were sequentially reviewed, and received either preoperative chemotherapy plus bevacizumab (bevacizumab group, n = 32) or preoperative chemotherapy alone (chemotherapy group, n = 57). Progression-free survival, response rate, liver resection rate, conversion rate, and safety were analyzed.With median follow-up of 28.7 months, progression-free survival was 10.9 months (95% confidence interval: 8.7-13.1 months) in bevacizumab group and 9.9 months (95% confidence interval: 6.8-13.1 months) in chemotherapy group (P = 0.472). Response rates were 59.4% in bevacizumab group and 38.6% in chemotherapy group (P = 0.059). Overall liver resection (R0, R1, and R2) rate was 68.8% in bevacizumab group and 54.4% in chemotherapy group (P = 0.185). Conversion rate was 51.9% in bevacizumab group and 40.4% in chemotherapy group (P = 0.341). No postoperative complication was observed in all patients.Bevacizumab plus preoperative chemotherapy as first-line treatment for liver-only metastatic colorectal cancer tends to achieve better clinical benefit with controllable safety in Chinese patients. PMID:27583930

  6. Antimicrobial silver: an unprecedented anion effect.

    PubMed

    Swathy, J R; Sankar, M Udhaya; Chaudhary, Amrita; Aigal, Sahaja; Anshup; Pradeep, T

    2014-01-01

    Silver is an indispensable metal but its use has to be minimised for sustainable growth. Much of the silver lost during use is unrecoverable; an example being its use as an antimicrobial agent, a property known since ages. While developing methods to create an affordable drinking water purifier especially for the developing world, we discovered that 50 parts per billion (ppb) of Ag(+) released continuously from silver nanoparticles confined in nanoscale cages is enough to cause antimicrobial activity in conditions of normal water. Here we show that the antibacterial and antiviral activities of Ag(+) can be enhanced ~1,000 fold, selectively, in presence of carbonate ions whose concentration was maintained below the drinking water norms. The protective layers of the organisms were affected during the carbonate-assisted antimicrobial activity. It is estimated that ~1,300 tons of silver can be saved annually using this new way to enhance its antimicrobial activity. PMID:25418185

  7. Membrane disruption mechanism of antimicrobial peptides

    NASA Astrophysics Data System (ADS)

    Lee, Ka Yee

    2012-04-01

    Largely distributed among living organisms, antimicrobial peptides are a class of small (<100 residues) host defense peptides that induce selective membrane lytic activity against microbial pathogens. The permeabilizing behavior of these diverse peptides has been commonly attributed to the formation of pores, and such pore formation has been categorized as barrel-stave, toroidal, or carpet-like. With the continuing discovery of new peptide species, many are uncharacterized and the exact mechanism is unknown. Through the use of atomic force microscopy, the disruption of supported lipid bilayer patches by protegrin-1 is concentration-dependent. The intercalation of antimicrobial peptide into the bilayer results in structures beyond that of pore formation, but with the formation of worm-like micelles at high peptide concentration. Our results suggest that antimicrobial peptide acts to lower the interfacial energy of the bilayer in a way similar to detergents. Antimicrobial peptides with structural differences, magainin-1 and aurein 1.1, exhibit a mechanistic commonality.

  8. Antimicrobial-Coated Granules for Disinfecting Water

    NASA Technical Reports Server (NTRS)

    Akse, James R.; Holtsnider, John T.; Kliestik, Helen

    2011-01-01

    Methods of preparing antimicrobialcoated granules for disinfecting flowing potable water have been developed. Like the methods reported in the immediately preceding article, these methods involve chemical preparation of substrate surfaces (in this case, the surfaces of granules) to enable attachment of antimicrobial molecules to the surfaces via covalent bonds. A variety of granular materials have been coated with a variety of antimicrobial agents that include antibiotics, bacteriocins, enzymes, bactericides, and fungicides. When employed in packed beds in flowing water, these antimicrobial-coated granules have been proven effective against gram-positive bacteria, gram-negative bacteria, fungi, and viruses. Composite beds, consisting of multiple layers containing different granular antimicrobial media, have proven particularly effective against a broad spectrum of microorganisms. These media have also proven effective in enhancing or potentiating the biocidal effects of in-line iodinated resins and of very low levels of dissolved elemental iodine.

  9. Antimicrobial dispensing by Ontario dairy veterinarians

    PubMed Central

    Léger, David F.; Newby, Nathalie C.; Reid-Smith, Richard; Anderson, Neil; Pearl, David L.; Lissemore, Kerry D.; Kelton, David F.

    2015-01-01

    This questionnaire-based cross-sectional study was designed to capture the demographics of dairy practitioners in Ontario and to describe aspects of antimicrobial dispensing on-farm and over-the-counter by these veterinarians. The information collected revealed that the prescription status of a drug and the level of veterinary-client-patient relationship were important elements of dispensing policies. Over-the-counter dispensing records were incomplete, while only a small proportion of on-farm dispensing records contained pertinent information and directions as required by the Veterinarians Act. While respondents recognized that antimicrobial use in dairy herds could lead to resistance in cattle, few indicated that this was a significant public health issue. Veterinarians can play a key role in antimicrobial stewardship, part of which is the provision of complete written dispensing instructions to producers for antimicrobial use in dairy cattle. PMID:26130834

  10. Towards Self-regenerating Antimicrobial Polymer Surfaces

    PubMed Central

    Dorner, Franziska; Boschert, David; Schneider, Alexandra; Hartleb, Wibke; Al-Ahmad, Ali; Lienkamp, Karen

    2016-01-01

    Regeneration of functional polymer surfaces after damage or contamination is an unresolved scientific challenge, and also of practical importance. In this proof-of-concept study, we present a method to regenerate a functional surface property using a polymer multi-layer architecture. This is exemplified using antimicrobially active surfaces. The idea is to shed the top layer of the polymer layer stack, like a reptile shedding its skin. The proof-of-concept stack consists of two antimicrobial layers and a degradable interlayer. Shedding of the top layer is enabled by degrading that interlayer. The shedding process was analyzed by quantitative fluorescence microscopy, ellipsometry, and FTIR spectroscopy. Antimicrobial assays revealed that the functionality of the emerging antimicrobial layer was fully retained after shedding. PMID:27489747

  11. Antimicrobial dispensing by Ontario dairy veterinarians.

    PubMed

    Léger, David F; Newby, Nathalie C; Reid-Smith, Richard; Anderson, Neil; Pearl, David L; Lissemore, Kerry D; Kelton, David F

    2015-07-01

    This questionnaire-based cross-sectional study was designed to capture the demographics of dairy practitioners in Ontario and to describe aspects of antimicrobial dispensing on-farm and over-the-counter by these veterinarians. The information collected revealed that the prescription status of a drug and the level of veterinary-client-patient relationship were important elements of dispensing policies. Over-the-counter dispensing records were incomplete, while only a small proportion of on-farm dispensing records contained pertinent information and directions as required by the Veterinarians Act. While respondents recognized that antimicrobial use in dairy herds could lead to resistance in cattle, few indicated that this was a significant public health issue. Veterinarians can play a key role in antimicrobial stewardship, part of which is the provision of complete written dispensing instructions to producers for antimicrobial use in dairy cattle. PMID:26130834

  12. Antimicrobial silver: An unprecedented anion effect

    PubMed Central

    Swathy, J. R.; Sankar, M. Udhaya; Chaudhary, Amrita; Aigal, Sahaja; Anshup; Pradeep, T.

    2014-01-01

    Silver is an indispensable metal but its use has to be minimised for sustainable growth. Much of the silver lost during use is unrecoverable; an example being its use as an antimicrobial agent, a property known since ages. While developing methods to create an affordable drinking water purifier especially for the developing world, we discovered that 50 parts per billion (ppb) of Ag+ released continuously from silver nanoparticles confined in nanoscale cages is enough to cause antimicrobial activity in conditions of normal water. Here we show that the antibacterial and antiviral activities of Ag+ can be enhanced ~1,000 fold, selectively, in presence of carbonate ions whose concentration was maintained below the drinking water norms. The protective layers of the organisms were affected during the carbonate-assisted antimicrobial activity. It is estimated that ~1,300 tons of silver can be saved annually using this new way to enhance its antimicrobial activity. PMID:25418185

  13. Statistical metamodeling for revealing synergistic antimicrobial interactions.

    PubMed

    Chen, Hsiang Chia; Chen, Chia Hsiang; Gau, Vincent; Zhang, Donna D; Liao, Joseph C; Wang, Fei-Yue; Wong, Pak Kin

    2010-01-01

    Many bacterial pathogens are becoming drug resistant faster than we can develop new antimicrobials. To address this threat in public health, a metamodel antimicrobial cocktail optimization (MACO) scheme is demonstrated for rapid screening of potent antibiotic cocktails using uropathogenic clinical isolates as model systems. With the MACO scheme, only 18 parallel trials were required to determine a potent antimicrobial cocktail out of hundreds of possible combinations. In particular, trimethoprim and gentamicin were identified to work synergistically for inhibiting the bacterial growth. Sensitivity analysis indicated gentamicin functions as a synergist for trimethoprim, and reduces its minimum inhibitory concentration for 40-fold. Validation study also confirmed that the trimethoprim-gentamicin synergistic cocktail effectively inhibited the growths of multiple strains of uropathogenic clinical isolates. With its effectiveness and simplicity, the MACO scheme possesses the potential to serve as a generic platform for identifying synergistic antimicrobial cocktails toward management of bacterial infection in the future. PMID:21124958

  14. Statistical Metamodeling for Revealing Synergistic Antimicrobial Interactions

    PubMed Central

    Chen, Chia Hsiang; Gau, Vincent; Zhang, Donna D.; Liao, Joseph C.; Wang, Fei-Yue; Wong, Pak Kin

    2010-01-01

    Many bacterial pathogens are becoming drug resistant faster than we can develop new antimicrobials. To address this threat in public health, a metamodel antimicrobial cocktail optimization (MACO) scheme is demonstrated for rapid screening of potent antibiotic cocktails using uropathogenic clinical isolates as model systems. With the MACO scheme, only 18 parallel trials were required to determine a potent antimicrobial cocktail out of hundreds of possible combinations. In particular, trimethoprim and gentamicin were identified to work synergistically for inhibiting the bacterial growth. Sensitivity analysis indicated gentamicin functions as a synergist for trimethoprim, and reduces its minimum inhibitory concentration for 40-fold. Validation study also confirmed that the trimethoprim-gentamicin synergistic cocktail effectively inhibited the growths of multiple strains of uropathogenic clinical isolates. With its effectiveness and simplicity, the MACO scheme possesses the potential to serve as a generic platform for identifying synergistic antimicrobial cocktails toward management of bacterial infection in the future. PMID:21124958

  15. Antimicrobial defense and persistent infection in insects.

    PubMed

    Haine, Eleanor R; Moret, Yannick; Siva-Jothy, Michael T; Rolff, Jens

    2008-11-21

    During 400 million years of existence, insects have rarely succumbed to the evolution of microbial resistance against their potent antimicrobial immune defenses. We found that microbial clearance after infection is extremely fast and that induced antimicrobial activity starts to increase only when most of the bacteria (99.5%) have been removed. Our experiments showed that those bacteria that survived exposure to the insect's constitutive immune response were subsequently more resistant to it. These results imply that induced antimicrobial compounds function primarily to protect the insect against the bacteria that persist within their body, rather than to clear microbial infections. These findings suggest that understanding of the management of antimicrobial peptides in natural systems might inform medical treatment strategies that avoid the risk of drug resistance. PMID:19023083

  16. Antimicrobial activity of borate-buffered solutions.

    PubMed Central

    Houlsby, R D; Ghajar, M; Chavez, G O

    1986-01-01

    A minimal salts medium adjusted to physiological pH and osmolality was buffered with either 0.3% phosphate or 1.2% borate and evaluated for antimicrobial activity. The borate-buffered medium, either with or without a carbon source, exhibited significant antimicrobial activity against 15 Pseudomonas strains, 12 strains of enteric bacteria, and 7 strains of staphylococci. The borate-buffered system appears suitable for use as a generic vehicle for ophthalmic pharmaceutical agents. PMID:3729341

  17. The interpretation of antimicrobial susceptibility patterns.

    PubMed Central

    Martin, S W; Meek, A H

    1981-01-01

    The results of a computer model designed to demonstrate the effect of antimicrobial exposure (therapy) on the likelihood of isolating putative pathogens and on the proportion of successfully isolated organisms resistant to specific antimicrobials are presented. The results indicate that the observed percentage resistant is not a reliable indicator of the actual percentage resistant in the source population. Data from the Bruce County Beef Project in 1979-80 are used to verify some of the assumptions used in the model. PMID:7196279

  18. Antimicrobial prophylaxis in caesarean section delivery

    PubMed Central

    Liu, Ronghua; Lin, Lin; Wang, Dujuan

    2016-01-01

    Antimicrobial prophylaxis is used routinely for pre-, intra- and post-operative caesarean section. One of the most important risk factors for postpartum infection is caesarean delivery. Caesarean section shows a higher incidence of infection than vaginal delivery. It is complicated by surgical site infections, endometritis or urinary tract infection. The aim of the present study was to assess the usage of antimicrobials in women undergoing caesarean section at a Tertiary Care Hospital. A prospective study was conducted in 100 women during the period of February 2013 to August 2013 in the inpatient Department of Gynaecology and Obstetrics. Data collected included the age of the patient, gravidity, and type of caesarean section, which was analyzed for the nature and number of antimicrobials prescribed, duration of treatment, polypharmacy, fixed-dose combinations, generic/brand names used and failure of prophylaxis. Antimicrobial prophylaxis was administered to the patients. The most commonly prescribed antimicrobial was a combination of ceftriaxone and sulbactam. Of 100 patients, 87% were aged 20–35 years. The highest proportion of patients were primigravida 72%. Elective procedure was carried out in 38%, the remaining were emergency C-section in whom intra- and post-operative antimicrobial prophylaxis was given for a duration of 7 days. In total, 27% of patients were reported with infection even after the antimicrobial prophylaxis. In conclusion, pre-operative prophylaxis was given in the early rupture of membranes. Fixed-dose combinations were preferred. Incidence of infection even after antimicrobial prophylaxis was reported due to pre-existing infection, debilitating disease or prolonged rupture of membranes. Patients with recurrent infection were shifted to amoxicillin and clavulinic acid combination. Drugs were prescribed only by brand names which is of concern. PMID:27446303

  19. Report: Antimicrobial activity of Kalanchoe laciniata.

    PubMed

    Manan, Maria; Hussain, Liaqat; Ijaz, Hira; Qadir, Muhammad Imran

    2016-07-01

    This study was conducted to identify antimicrobial potential of Kalanchoe laciniata. The plants were extracted with 30-70% aqueous-methanol and n-hexane. The antimicrobial activities were examined using agar well diffusion method against bacteria (Staphylococcus aureus, Escherichia coli) and fungi (Candidaalbicans). Results showed that E. coli were more sensitive than Staphylococcus aureus and Candida albicans. The largest zone of inhibition (52 mm) was recorded against E. coli with the n-hexane extract of Kalanchoe laciniata.

  20. Patient Comprehension and Attitudes toward Maintenance Chemotherapy for Lung Cancer

    PubMed Central

    Gerber, David E.; Hamann, Heidi A.; Rasco, Drew W.; Woodruff, Sharon; Craddock Lee, Simon J.

    2012-01-01

    Objective Maintenance chemotherapy is a recently approved approach to the treatment of advanced non-small cell lung cancer (NSCLC). We sought to gain insight into patients’ perceptions of maintenance chemotherapy using qualitative methods. Methods We conducted thematic content analysis of focus groups at a freestanding cancer center and at an associated safety-net county hospital. Patients with advanced NSCLC who had started but not yet completed first-line platinum doublet chemotherapy were provided visual and written explanations of maintenance chemotherapy before being guided in group discussion. Results Key themes to emerge for consideration of maintenance chemotherapy included (1) survival benefits, disease control, and “buying time”; (2) the importance of “doing something”; (3) quality of life concerns; (4) the role of provider opinion/preference; and (5) the importance of logistics. Conclusions Patients undergoing first-line chemotherapy for advanced NSCLC were able to understand the concept of maintenance chemotherapy, distinguish it from traditional treatment paradigms, identify pros and cons of this approach, and convey reasons for considering it. Practice Implications Advances in oncology care that alter therapy modalities and delivery may significantly impact patient perceptions and treatment experiences. Clinical team members may wish to elicit treatment preferences of first-line patients through clinical discussions that anticipate these considerations. PMID:22632736

  1. Photodynamic antimicrobial effects of bis-indole alkaloid indigo from Indigofera truxillensis Kunth (Leguminosae).

    PubMed

    Andreazza, Nathalia Luiza; de Lourenço, Caroline C; Stefanello, Maria Élida Alves; Atvars, Teresa Dib Zambon; Salvador, Marcos José

    2015-05-01

    Multidrug-resistant microbial infections represent an exponentially growing problem affecting communities worldwide. Photodynamic therapy is a promising treatment based on the combination of light, oxygen, and a photosensitizer that leads to reactive oxygen species production, such as superoxide (type I mechanism) and singlet oxygen (type II mechanism) that cause massive oxidative damage and consequently the host cell death. Indigofera genus has gained considerable interest due its mutagenic, cytotoxic, and genotoxic activity. Therefore, this study was undertaken to investigate the effect of crude extracts, alkaloidal fraction, and isolated substance derived from Indigofera truxillensis in photodynamic antimicrobial chemotherapy on the viability of bacteria and yeast and evaluation of mechanisms involved. Our results showed that all samples resulted in microbial photoactivation in subinhibitory concentration, with indigo alkaloid presenting a predominant photodynamic action through type I mechanism. The use of CaCl2 and MgCl2 as cell permeabilizing additives also increased gram-negative bacteria susceptibility to indigo.

  2. Industrial food animal production, antimicrobial resistance, and human health.

    PubMed

    Silbergeld, Ellen K; Graham, Jay; Price, Lance B

    2008-01-01

    Antimicrobial resistance is a major public health crisis, eroding the discovery of antimicrobials and their application to clinical medicine. There is a general lack of knowledge of the importance of agricultural antimicrobial use as a factor in antimicrobial resistance even among experts in medicine and public health. This review focuses on agricultural antimicrobial drug use as a major driver of antimicrobial resistance worldwide for four reasons: It is the largest use of antimicrobials worldwide; much of the use of antimicrobials in agriculture results in subtherapeutic exposures of bacteria; drugs of every important clinical class are utilized in agriculture; and human populations are exposed to antimicrobial-resistant pathogens via consumption of animal products as well as through widespread release into the environment.

  3. Understanding the mechanisms and drivers of antimicrobial resistance.

    PubMed

    Holmes, Alison H; Moore, Luke S P; Sundsfjord, Arnfinn; Steinbakk, Martin; Regmi, Sadie; Karkey, Abhilasha; Guerin, Philippe J; Piddock, Laura J V

    2016-01-01

    To combat the threat to human health and biosecurity from antimicrobial resistance, an understanding of its mechanisms and drivers is needed. Emergence of antimicrobial resistance in microorganisms is a natural phenomenon, yet antimicrobial resistance selection has been driven by antimicrobial exposure in health care, agriculture, and the environment. Onward transmission is affected by standards of infection control, sanitation, access to clean water, access to assured quality antimicrobials and diagnostics, travel, and migration. Strategies to reduce antimicrobial resistance by removing antimicrobial selective pressure alone rely upon resistance imparting a fitness cost, an effect not always apparent. Minimising resistance should therefore be considered comprehensively, by resistance mechanism, microorganism, antimicrobial drug, host, and context; parallel to new drug discovery, broad ranging, multidisciplinary research is needed across these five levels, interlinked across the health-care, agriculture, and environment sectors. Intelligent, integrated approaches, mindful of potential unintended results, are needed to ensure sustained, worldwide access to effective antimicrobials. PMID:26603922

  4. Hypothyroid cardiomyopathy in a patient post-doxorubicin chemotherapy.

    PubMed

    Silver, Adam Jeffrey; Patel, Hena N; Okwuosa, Tochi

    2016-01-01

    Hypothyroidism may cause decreased cardiac output and heart failure-and when severe, bradycardia and pericardial effusions may develop. Chemotherapies, particularly doxorubicin, are known and often irreversible causes of cardiomyopathy. As such, when cardiomyopathy develops in patients who have been exposed to anthracycline chemotherapy, the importance of ruling out other reversible causes such as hypothyroidism cannot be overstated. We present a case of acute systolic heart failure in a patient post-doxorubicin chemotherapy and radiation therapy for alveolar rhabdomyosarcoma, found to have severe hypothyroidism as a reversible cause of cardiomyopathy. PMID:27053539

  5. [Personality and emesis in the patient treated with antineoplastic chemotherapy].

    PubMed

    Llorca, G; Martín, T; Derecho, J; Gómez, M J

    1991-01-01

    A sample of twenty cancer patients following chemotherapy realize MMPI questionnaire, and another one for valuation of emetic and anticipatory phenomena in relation to said therapy. The authors came to the conclusion that 36.8% of the sample had anticipatory nausea and vomiting, 63.6% anticipatory dysphoria, and 66% emetic incidents after chemotherapy. The conclusion, through comparison of personality variables, is that all patients showed neuroticism and depression scales increased, in relation to healthy population. Depression variable increased especially in patients that didn't present anticipatory nausea and vomiting. Likewise, patients with anticipatory symptoms or emetic incidents after chemotherapy present an increased social introversion variable.

  6. Cancer chemotherapy during pregnancy. Consortium of cancer in pregnancy evidence.

    PubMed Central

    Lishner, M.; Koren, G.

    2001-01-01

    QUESTION: I have an 8-weeks' pregnant patient who was diagnosed with stage III Hodgkin's disease last week. The oncologist suggests delaying chemotherapy until the second trimester. What are the effects of chemotherapy on a fetus after the first trimester? Where can I find reliable information on the subject? ANSWER: Available data suggest that exposure to chemotherapy during the first trimester of pregnancy is associated with increased risk of major malformations. Exposure during the second and third trimesters does not result in major malformations, but could have nonteratogenic effects, such as low birth weight. The brain develops throughout pregnancy, and it could be affected later in pregnancy. PMID:11212430

  7. Chemotherapy following radium‐223 dichloride treatment in ALSYMPCA

    PubMed Central

    Hoskin, Peter; Coleman, Robert E.; Nilsson, Sten; Vogelzang, Nicholas J.; Petrenciuc, Oana; Staudacher, Karin; Thuresson, Marcus; Parker, Christopher

    2016-01-01

    BACKGROUND Radium‐223 prolongs overall survival in patients with castration‐resistant prostate cancer (CRPC) and symptomatic bone metastases, regardless of prior docetaxel. Whether or not chemotherapy can be safely administered following radium‐223 treatment is of clinical importance. An exploratory analysis of prospectively collected data, from the ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) patient subgroup who received chemotherapy after radium‐223 or placebo treatment, was conducted to evaluate the safety and efficacy of chemotherapy following radium‐223. METHODS In ALSYMPCA, CRPC patients with symptomatic bone metastases and no visceral metastases were randomized 2:1 to receive six injections of radium‐223 (50 kBq/kg IV) or placebo plus best standard of care, stratified by prior docetaxel, baseline alkaline phosphatase, and current bisphosphonate use. In this exploratory analysis, chemotherapy agents administered following study treatment were identified; timing and duration were calculated. Hematologic safety was reviewed, and overall survival analyzed. RESULTS Overall, 142 radium‐223 and 64 placebo patients received subsequent chemotherapy; most common were docetaxel (70% radium‐223, 72% placebo) and mitoxantrone (16% radium‐223, 20% placebo). The majority of patients (61% radium‐223, 58% placebo) had received prior docetaxel. Radium‐223 patients started subsequent chemotherapy later than placebo patients; chemotherapy duration was similar between groups. In radium‐223 and placebo patients receiving subsequent chemotherapy, median hematologic values (hemoglobin, neutrophils, and platelets) remained nearly constant up to 18 months following start of chemotherapy, regardless of prior docetaxel treatment. A low percentage of patients in both groups had grades 3–4 hematologic values (<10%). Platelet count decline, from last measurement before chemotherapy, was numerically greater in radium‐223 versus placebo patients. Median

  8. [INTRAVENOUS CHEMOTHERAPY VERSUS INTRAPERITONEAL CHEMOTHERAPY IN ADVANCED OVARIAN CANCER: UPDATE ON THE SITUATION WORLDWIDE AND IN ISRAEL].

    PubMed

    Binyamin, Sivan; Segev, Yakir; Auslender, Ron; Bitterman, Arie; Lavie, Ofer

    2015-09-01

    Ovarian cancer is the second in incidence and the first cause of death. As much as 70% of ovarian cancer patients are diagnosed with advanced disease. The standard treatment of advanced ovarian cancer is a combination of primary optimal debulking (POD) followed by a combined adjuvant chemotherapy treatment. Another optional treatment includes neoadjuvant chemotherapy followed by optimal debulking and then adjuvant chemotherapy. The common adjuvant chemotherapy includes a combination of platinum and taxol compounds given intravenously. Other possible treatments which had been evaluated in the past decades include a combination of chemotherapy given intravenously and intraperitoneally. The rationale behind delivering the chemotherapy intraperitoneally is to provide a much higher concentrations of cytotoxic agents in the peritoneal cavity and to reduce the systemic side effects. A number of randomized trials have shown that the combination of IV and IP chemotherapy entails a survival advantage. Most studies included treatment based on cisplatin treatments with/ without taxol given intravenously versus a combined treatment (intravenously and intraperitoneally) of those agents. An advantage of up to 8 months in disease-free survival and 11 months in overall survival was noted in the IP group. On the other hand, this treatment led to a higher rate of side effects, including abdominal pain, electrolyte imbalance and catheter related complications. Despite the inconsistency in the treatment protocols between the different trials comparing intravenous and intra-peritoneal treatment, one cannot ignore the statistical significance between the groups, for disease-free survival and overall survival. That is why, when addressing patients who completed optimal surgery, one needs to conduct a thorough evaluation regarding the complementary chemotherapy treatment. Due to the broad side effect profile, special notice should be taken as to the patient's age, medical history, and

  9. Quaternized Chitosan as an Antimicrobial Agent: Antimicrobial Activity, Mechanism of Action and Biomedical Applications in Orthopedics

    PubMed Central

    Tan, Honglue; Ma, Rui; Lin, Chucheng; Liu, Ziwei; Tang, Tingting

    2013-01-01

    Chitosan (CS) is a linear polysaccharide with good biodegradability, biocompatibility and antimicrobial activity, which makes it potentially useful for biomedical applications, including an antimicrobial agent either alone or blended with other polymers. However, the poor solubility of CS in most solvents at neutral or high pH substantially limits its use. Quaternary ammonium CS, which was prepared by introducing a quaternary ammonium group on a dissociative hydroxyl group or amino group of the CS, exhibited improved water solubility and stronger antibacterial activity relative to CS over an entire range of pH values; thus, this quaternary modification increases the potential biomedical applications of CS in the field of anti-infection. This review discusses the current findings on the antimicrobial properties of quaternized CS synthesized using different methods and the mechanisms of its antimicrobial actions. The potential antimicrobial applications in the orthopedic field and perspectives regarding future studies in this field are also considered. PMID:23325051

  10. Characterization of Novel Antimicrobial Peptoids

    PubMed Central

    Goodson, Bob; Ehrhardt, Anton; Ng, Simon; Nuss, John; Johnson, Kirk; Giedlin, Marty; Yamamoto, Ralph; Moos, Walter H.; Krebber, Anke; Ladner, Martha; Giacona, Mary Beth; Vitt, Charles; Winter, Jill

    1999-01-01

    Peptoids differ from peptides in that peptoids are composed of N-substituted rather than alpha-carbon-substituted glycine units. In this paper we report the in vitro and in vivo antibacterial activities of several antibacterial peptoids discovered by screening combinatorial chemistry libraries for bacterial growth inhibition. In vitro, the peptoid CHIR29498 and some of its analogues were active in the range of 3 to 12 μg/ml against a panel of gram-positive and gram-negative bacteria which included isolates which were resistant to known antibiotics. Peptoid antimicrobial activity against Staphylococcus aureus was rapid, bactericidal, and independent of protein synthesis. β-Galactosidase and propidium iodide leakage assays indicated that the membrane is the most likely target of activity. Positional isomers of an active peptoid were also active, consistent with a mode of action, such as membrane disruption, that does not require a specific fit between the molecule and its target. In vivo, CHIR29498 protected S. aureus-infected mice in a simple infection model. PMID:10348765

  11. Infectious complications in 126 patients treated with high-dose chemotherapy and autologous peripheral blood stem cell transplantation.

    PubMed

    Salazar, R; Solá, C; Maroto, P; Tabernero, J M; Brunet, J; Verger, G; Valentí, V; Cancelas, J A; Ojeda, B; Mendoza, L; Rodríguez, M; Montesinos, J; López-López, J J

    1999-01-01

    The effect of an extensive prophylactic antimicrobial regimen was prospectively assessed in 126 patients after high-dose chemotherapy and autologous PBSC. They received ciprofloxacin (500 mg/12 h), acyclovir (200 mg/6 h), and itraconazole (200 mg/12 h) orally until neutrophil recovery. Febrile patients received i.v. imipenem (500 mg/6 h) to which vancomycin and amikacin were added if fever persisted for 2-3 and 5 days, respectively. Amphotericin B lipid complex was further given on day 7 or 8 of fever. Median times for a neutrophil count of >0.5 x 10(9)/l and a platelet count of >20 x 10(9)/l were 9 and 11 days. Severe neutropenia (<0.1 x 10(9)/l) lasted for a median of 5 days in which 72% of febrile episodes and 50% of cases of bacteremia occurred. Gram-positive bacteria were isolated in 30 of 40 episodes of bacteremia, 25 of which were caused by Staphylococcus epidermidis. Clinical foci were the intravascular catheter in 35 cases, respiratory infection in 11, cellulitis in two, anal abscess in one, and neutropenic enterocolitis in one. The high incidence of febrile episodes (94%) and bacteremias (31%) may be due to the lack of efficacy of antimicrobial prophylaxis and the persistence of a 5-day period of severe neutropenia.

  12. Oral administration of antimicrobials increase antimicrobial resistance in E. coli from chicken--a systematic review.

    PubMed

    Simoneit, C; Burow, E; Tenhagen, B-A; Käsbohrer, A

    2015-01-01

    Antimicrobials play an important role in animal and human health care. It was the aim of this systematic review to assess the effects of oral administration of antimicrobials on the development of antimicrobial resistance (AMR) in Escherichia coli (E. coli) from chickens. Moreover, the effects of the administration of more than one antimicrobial and of different dosages were studied. Literature was searched in November 2012 from the electronic databases ISI Web of Science, PubMed, Scopus and a national literature database (DIMDI) as well as the database ProQuest LLC. The search was updated in March 2014. Original studies describing a treatment (A) and a control group of either non-treatment (C) or initial value (0) and determining AMR in E. coli at different sample points (SP) were included. The literature search resulted in 35 full text articles on the topic, seven (20%) of which contained sufficient information on the administered antimicrobial and the impact of treatment on AMR. Most papers described the use of more than one antimicrobial, several dosages, controls (non-treatment or pre-treatment) and measured AMR at different SPs leading to a total of 227 SPs on the impact of the use of antimicrobials on AMR in chickens. 74% of the SPs (168/227) described a higher AMR-rate in E. coli from treated animals than from controls. After the administration of a single antimicrobial, AMR increased at 72% of the SPs. Administration of more than one antimicrobial increased AMR at 82% of the SPs. Higher dosages were associated with similar or higher AMR rates. The limited number of studies for each antimicrobial agent and the high variability in the resistance effect call for more well designed studies on the impact of oral administration on AMR development and spread.

  13. Chemotherapy for Advanced Non-small Cell Lung Cancer.

    PubMed

    Dietrich, Martin F; Gerber, David E

    2016-01-01

    Non-small cell lung cancer has seen an unprecedented augmentation of therapeutic options over the last couple of years. Improved understanding of molecular drivers and the role of the immune system in cancer therapy have brought new drugs to the armamentarium. Despite these advances, cytotoxic chemotherapy remains a substantial part of therapy for most patients in locally advanced and metastatic stage. Initially thought to be a chemotherapy-resistant entity, meta-analyses in the mid-1990s demonstrated modest efficacy of platinum-based therapy. Further combination trials demonstrated enhanced efficacy for several regimen in first and second lines, including the introduction of antimetabolites, taxanes, and anti-angiogenic agents. Maintenance chemotherapy has been another novel, successful approach for management of metastatic disease. Herein, we summarize the current concepts of chemotherapy, its applicability to the different histologies, and novel concepts of therapy. PMID:27535392

  14. Combining Chemotherapy with Bevacizumab Improves Outcomes for Ovarian Cancer Patients

    Cancer.gov

    Results from two phase III randomized clinical trials suggest that, at least for some patients with ovarian cancer, adding the antiangiogenesis agent bevacizumab to chemotherapy increases the time to disease progression and may improve survival.

  15. A Review of Cancer Chemotherapy for Pet Animals

    PubMed Central

    Norris, A. M.; Withrow, S. J.

    1984-01-01

    A review of the principles of cancer chemotherapy for pet animals is presented. The various pharmacological classes of antineoplastic drugs are described with specific references to those drugs that have been widely used in veterinary medicine. PMID:17422381

  16. Chemotherapy Regimen Extends Survival in Advanced Pancreatic Cancer Patients

    Cancer.gov

    A four-drug chemotherapy regimen has produced the longest improvement in survival ever seen in a phase III clinical trial of patients with metastatic pancreatic cancer, one of the deadliest types of cancer.

  17. Cutaneous side effects of chemotherapy in pediatric oncology patients.

    PubMed

    Ceylan, Can; Kantar, Mehmet; Tuna, Arzu; Ertam, Ilgen; Aksoylar, Serap; Günaydın, Aslı; Çetingül, Nazan

    2015-01-01

    Pediatric oncology patients can present with various skin lesions related to both primary disease and immunosuppressive treatments. This study aimed to evaluate the cutaneous side effects of chemotherapy in pediatric oncology patients. Sixty-five pediatric oncology patients who were scheduled to undergo chemotherapy from May 2011 to May 2013 were included in the study. Three patients were excluded from the results, as 2 patients died during treatment and 1 patient withdrew from the study; therefore, a total of 62 patients were evaluated for mucocutaneous findings. Patients were grouped according to their oncological diagnoses and a statistical analysis was performed. There was no statistical significance in the incidence of cutaneous side effects of chemotherapy among the different diagnostic groups. Awareness among dermatologists of the possible cutaneous side effects of chemotherapy in pediatric patients and their causes can promote early diagnosis and treatment in this patient population.

  18. Preoperative Chemotherapy, Radiation Improve Survival in Esophageal Cancer (Updated)

    Cancer.gov

    Patients with esophageal cancer who received chemotherapy and radiation before surgery survived, on average, nearly twice as long as patients treated with surgery alone, according to results of a randomized clinical trial published May 31, 2012, in NEJM.

  19. Managing Chemotherapy Side Effects: Sexual and Fertility Changes in Women

    MedlinePlus

    ... problems may last. u.s. Department of health anD human services national institutes of health Chemotherapy can harm an unborn baby (fetus). Ask what birth control methods you or your partner should use. Managing ...

  20. Influenza vaccination in children with cancer receiving chemotherapy.

    PubMed

    Esposito, Susanna; Cecinati, Valerio; Russo, Fabio Giovanni; Principi, Nicola

    2009-06-01

    Influenza has a significant clinical impact on pediatric cancer patients because it causes frequent febrile episodes and respiratory tract infections, possibly severe complications, delays in chemotherapy administration and even death, all of which supports the importance of prevention and the widespread use of influenza vaccination. Results from clinical studies show that influenza vaccination can be considered safe in children undergoing chemotherapy and, although weaker than in healthy children, the immune response seems to be sufficient in patients with leukemia or solid tumors even if it is less in children receiving chemotherapy than in those who are not. However, there is an urgent need for universally accepted guidelines concerning the type of vaccine that leads to the best immunological results, the number of administrations, and their timing in relation to the severity of immunosuppression and chemotherapy schedules. Such recommendations, together with a clear demonstration of vaccine efficacy, are also needed to increase influenza vaccination coverage in this high-risk category of patients.

  1. Tuberculosis chemotherapy: current drug delivery approaches

    PubMed Central

    du Toit, Lisa Claire; Pillay, Viness; Danckwerts, Michael Paul

    2006-01-01

    Tuberculosis is a leading killer of young adults worldwide and the global scourge of multi-drug resistant tuberculosis is reaching epidemic proportions. It is endemic in most developing countries and resurgent in developed and developing countries with high rates of human immunodeficiency virus infection. This article reviews the current situation in terms of drug delivery approaches for tuberculosis chemotherapy. A number of novel implant-, microparticulate-, and various other carrier-based drug delivery systems incorporating the principal anti-tuberculosis agents have been fabricated that either target the site of tuberculosis infection or reduce the dosing frequency with the aim of improving patient outcomes. These developments in drug delivery represent attractive options with significant merit, however, there is a requisite to manufacture an oral system, which directly addresses issues of unacceptable rifampicin bioavailability in fixed-dose combinations. This is fostered by the need to deliver medications to patients more efficiently and with fewer side effects, especially in developing countries. The fabrication of a polymeric once-daily oral multiparticulate fixed-dose combination of the principal anti-tuberculosis drugs, which attains segregated delivery of rifampicin and isoniazid for improved rifampicin bioavailability, could be a step in the right direction in addressing issues of treatment failure due to patient non-compliance. PMID:16984627

  2. Ovarian toxicity: from environmental exposure to chemotherapy.

    PubMed

    Iorio, Roberto; Castellucci, Annalisa; Ventriglia, Giovanni; Teoli, Flavia; Cellini, Valerio; Macchiarelli, Guido; Cecconi, Sandra

    2014-01-01

    Unlike men, who have continuous spermatogenesis throughout most of their lifetime, women are born with a fixed supply of follicles, and this number progressively declines with age until the menopause. Beside age, the speed of follicle depletion can be regulated by genetic, hormonal and environmental influences. In the course of their lives, women are exposed to multiple chemicals and radiation sources that can increase the chance of developing permanent infertility and premature ovarian failure (POF). A wealth of experimental data indicate that iatrogenic (chemotherapy, radiotherapy) and xenobiotic agents (e.g., chemicals, pharmaceuticals) are potent ovotoxicants capable of accelerating ovarian reserve depletion. In the present review we reported the negative effects exerted on mammalian ovary by some widely diffused environmental chemicals, as polycyclic aromatic hydrocarbons (PAHs) and dithiocarbamate mancozeb, and by 1-3 butadiene and 4-vinylcycloexene, two occupational chemicals known to be capable of inducing ovarian cancer and infertility. Furthermore, attention has been devoted to the consequences of chemo- and radiotherapy on the ovary, both known to affect reproductive lifespan. Our increasing understanding of metabolic alterations induced by these agents is fundamental to individuate new therapeutic strategies aimed to prevent ovarian dysfunction in fertile women. PMID:24502597

  3. Molecular mechanisms for tumour resistance to chemotherapy.

    PubMed

    Pan, Shu-Ting; Li, Zhi-Ling; He, Zhi-Xu; Qiu, Jia-Xuan; Zhou, Shu-Feng

    2016-08-01

    Chemotherapy is one of the prevailing methods used to treat malignant tumours, but the outcome and prognosis of tumour patients are not optimistic. Cancer cells gradually generate resistance to almost all chemotherapeutic drugs via a variety of distinct mechanisms and pathways. Chemotherapeutic resistance, either intrinsic or acquired, is caused and sustained by reduced drug accumulation and increased drug export, alterations in drug targets and signalling transduction molecules, increased repair of drug-induced DNA damage, and evasion of apoptosis. In order to better understand the mechanisms of chemoresistance, this review highlights our current knowledge of the role of altered drug metabolism and transport and deregulation of apoptosis and autophagy in the development of tumour chemoresistance. Reduced intracellular activation of prodrugs (e.g. thiotepa and tegafur) or enhanced drug inactivation by Phase I and II enzymes contributes to the development of chemoresistance. Both primary and acquired resistance can be caused by alterations in the transport of anticancer drugs which is mediated by a variety of drug transporters such as P-glycoprotein (P-gp), multidrug resistance associated proteins, and breast cancer resistance protein. Presently there is a line of evidence indicating that deregulation of programmed cell death including apoptosis and autophagy is also an important mechanism for tumour resistance to anticancer drugs. Reversal of chemoresistance is likely via pharmacological and biological approaches. Further studies are warranted to grasp the full picture of how each type of cancer cells develop resistance to anticancer drugs and to identify novel strategies to overcome it.

  4. Magnetically responsive siliceous frustules for efficient chemotherapy.

    PubMed

    Javalkote, Vivek S; Pandey, Abhijeet P; Puranik, Pravin R; Deshmukh, Prashant K

    2015-05-01

    In the present investigation, curcumin loaded magnetically active frustules have been reported. The diatoms were cultured and frustules were obtained by chemical and thermal processes. The frustules were rendered magnetically active by incorporation of iron oxide nanoparticle using two different methods involving ferrofluid (CMDM-F) and in situ synthesis (CMDM-I) of iron oxide nanoparticle. These CMDM prepared by two techniques were characterized using FT-IR and vibrating sample magnetometer (VSM) analyses. Particle size and potential were measured using the Malvern Zetasizer. Scanning electron microscopy (SEM) was utilized for studying the surface morphology of CMDM, and in addition to this elemental analysis was also performed for confirming the presence of iron. The cell viability assay was carried out using the HeLa cell line. SEM images showed a change in surface morphology of diatoms before and after rendering magnetic activity. Cell viability assay revealed that CMDM-F had reasonably high cytotoxicity (60.2%) compared to Curcumin (42.1%), DM (1.9%), CDM (44.8%), and CMDM-I (59.9). Both, CMDM-F and CMDM-I showed improved cytotoxicity when compared with pure curcumin. The overall study suggests that the developed CMDM could be utilized as a potential carrier to deliver cargo for efficient chemotherapy. PMID:25746251

  5. Glutamine facilitates chemotherapy while reducing toxicity.

    PubMed

    Klimberg, V S; Nwokedi, E; Hutchins, L F; Pappas, A A; Lang, N P; Broadwater, J R; Read, R C; Westbrook, K C

    1992-01-01

    Dose intensification of chemotherapy is thought to increase survival. With recent advances in hemopoietic cell modulators such as granulocyte colony stimulating factor, the limiting toxicity of intensifying chemotherapeutic regimens has become the severity of the associated enterocolitis. In animal models, glutamine protects the host from methotrexate-induced enterocolitis. This study evaluates the effects of a glutamine-supplemented diet on the tumoricidal effectiveness of methotrexate. Sarcoma-bearing Fisher 344 rats (n = 30) were pair-fed an isocaloric elemental diet containing 1% glutamine or an isonitrogenous amount of glycine beginning on day 25 of the study. Rats from each group received two intraperitoneal injections of methotrexate (5 mg/kg) or saline on days 26 and 33 of the study. On day 40, rats were killed, tumor volume and weight were recorded, and tumor glutaminase activity and tumor morphometrics were measured. Blood was taken for arterial glutamine content, complete blood count, and blood culture. The gut was processed for glutaminase activity and synthesis phase of the deoxyribonucleic acid. In rats receiving methotrexate, the tumor volume loss was nearly doubled when glutamine was added to the diet. Significant differences in tumor glutaminase activity and morphometrics were not detected. The toxicity to the host was ameliorated. Significantly increased synthesis phase of deoxyribonucleic acid of the whole jejunum, decreased bacteremia, "sepsis," and mortality were demonstrated. Glutamine supplementation enhances the tumoricidal effectiveness of methotrexate while reducing its morbidity and mortality in this sarcoma rat model.

  6. CHK1 Inhibitors in Combination Chemotherapy

    PubMed Central

    Dent, Paul; Tang, Yong; Yacoub, Adly; Dai, Yun; Fisher, Paul B.; Grant, Steven

    2011-01-01

    Cellular sensing of DNA damage, along with concomitant cell cycle arrest, is mediated by a great many proteins and enzymes. One focus of pharmaceutical development has been the inhibition of DNA damage signaling, and checkpoint kinases (Chks) in particular, as a means to sensitize proliferating tumor cells to chemotherapies that damage DNA. 7-Hydroxystaurosporine, or UCN-01, is a clinically relevant and well-studied kinase activity inhibitor that exerts chemosensitizing effects by inhibition of Chk1, and a multitude of Chk1 inhibitors have entered development. Clinical development of UCN-01 has overcome many initial obstacles, but the drug has nevertheless failed to show a high level of clinical activity when combined with chemotherapeutic agents. One very likely reason for the lack of clinical efficacy of Chk1 inhibitors may be that the inhibition of Chk1 causes the compensatory activation of ATM and ERK1/2 pathways. Indeed, inhibition of many enzyme activities, not necessarily components of cell cycle regulation, may block Chk1 inhibitor–induced ERK1/2 activation and enhance the toxicity of Chk1 inhibitors. This review examines the rationally hypothesized actions of Chk1 inhibitors as cell cycle modulatory drugs as well as the impact of Chk1 inhibition upon other cell survival signaling pathways. An understanding of Chk1 inhibition in multiple signaling contexts will be essential to the therapeutic development of Chk1 inhibitors. PMID:21540473

  7. Symptoms: Chemotherapy-Induced Peripheral Neuropathy.

    PubMed

    Schneider, Bryan P; Hershman, Dawn L; Loprinzi, Charles

    2015-01-01

    Chemotherapy-induced peripheral neuropathy (CIPN) is a problematic, treatment-induced toxicity that has the potential to impact quality of life and limit the doses of curative intent therapy. This therapy-induced side effect is one of the most troublesome in oncology clinical practices, considering the morbidity, the frequency, and the potential irreversibility of this problem. Patients with breast cancer are particularly impacted by this side effect as multiple agents commonly used for this disease can cause neuropathy. In this chapter, we provide an overview of CIPN, including: clinical predictors, frequency, and its impact on quality of life. Further, we highlight the pathophysiology and review the literature to date for agents designed to prevent or treat CIPN. We also highlight the most important ongoing clinical and translational research questions that hope to help better predict and prevent this toxicity. This includes optimizing the methods of assessment, using host specific factors (Race and genetics) to predict those more likely to experience CIPN, and determining how CIPN might impact clinical decisions toward therapy.

  8. Molecular mechanisms for tumour resistance to chemotherapy.

    PubMed

    Pan, Shu-Ting; Li, Zhi-Ling; He, Zhi-Xu; Qiu, Jia-Xuan; Zhou, Shu-Feng

    2016-08-01

    Chemotherapy is one of the prevailing methods used to treat malignant tumours, but the outcome and prognosis of tumour patients are not optimistic. Cancer cells gradually generate resistance to almost all chemotherapeutic drugs via a variety of distinct mechanisms and pathways. Chemotherapeutic resistance, either intrinsic or acquired, is caused and sustained by reduced drug accumulation and increased drug export, alterations in drug targets and signalling transduction molecules, increased repair of drug-induced DNA damage, and evasion of apoptosis. In order to better understand the mechanisms of chemoresistance, this review highlights our current knowledge of the role of altered drug metabolism and transport and deregulation of apoptosis and autophagy in the development of tumour chemoresistance. Reduced intracellular activation of prodrugs (e.g. thiotepa and tegafur) or enhanced drug inactivation by Phase I and II enzymes contributes to the development of chemoresistance. Both primary and acquired resistance can be caused by alterations in the transport of anticancer drugs which is mediated by a variety of drug transporters such as P-glycoprotein (P-gp), multidrug resistance associated proteins, and breast cancer resistance protein. Presently there is a line of evidence indicating that deregulation of programmed cell death including apoptosis and autophagy is also an important mechanism for tumour resistance to anticancer drugs. Reversal of chemoresistance is likely via pharmacological and biological approaches. Further studies are warranted to grasp the full picture of how each type of cancer cells develop resistance to anticancer drugs and to identify novel strategies to overcome it. PMID:27097837

  9. [Systemic chemotherapy for transitional cell carcinoma of the urothelium].

    PubMed

    Lehmann, J; Retz, M; Hack, M; Siemer, S; Stöckle, M

    2003-10-01

    Moderate activity of systemic chemotherapy for advanced urothelial cancer has been reported for more than 30 years. Only with the advent of potent combination therapy in the mid eighties of the past century clinically significant response rates as well as prolonged survival has been documented. This review summarizes seven Phase-III trials of systemic chemotherapy for advanced urothelial carcinoma as well as results from adjuvant and neoadjuvant Phase-III trials for muscle-invasive bladder cancer including the most recent reports.

  10. Perivascular M2 Macrophages Stimulate Tumor Relapse after Chemotherapy

    PubMed Central

    Hughes, Russell; Qian, Bin-Zhi; Rowan, Charlotte; Muthana, Munitta; Keklikoglou, Ioanna; Olson, Oakley C.; Tazzyman, Simon; Danson, Sarah; Addison, Christina; Clemons, Mark; Gonzalez-Angulo, Ana Maria; Joyce, Johanna A.; De Palma, Michele; Pollard, Jeffrey W.; Lewis, Claire E.

    2016-01-01

    Tumor relapse after chemotherapy-induced regression is a major clinical problem, because it often involves inoperable metastatic disease. Tumor-associated macrophages (TAM) are known to limit the cytotoxic effects of chemotherapy in preclinical models of cancer. Here, we report that an alternatively activated (M2) subpopulation of TAMs (MRC1+TIE2HiCXCR4Hi) accumulate around blood vessels in tumors after chemotherapy, where they promote tumor revascularization and relapse, in part, via VEGF-A release. A similar perivascular, M2-related TAM subset was present in human breast carcinomas and bone metastases after chemotherapy. Although a small proportion of M2 TAMs were also present in hypoxic tumor areas, when we genetically ablated their ability to respond to hypoxia via hypoxia-inducible factors 1 and 2, tumor relapse was unaffected. TAMs were the predominant cells expressing immunoreactive CXCR4 in chemotherapy-treated mouse tumors, with the highest levels expressed by MRC1+ TAMs clustering around the tumor vasculature. Furthermore, the primary CXCR4 ligand, CXCL12, was upregulated in these perivascular sites after chemotherapy, where it was selectively chemotactic for MRC1+ TAMs. Interestingly, HMOX-1, a marker of oxidative stress, was also upregulated in perivascular areas after chemotherapy. This enzyme generates carbon monoxide from the breakdown of heme, a gas known to upregulate CXCL12. Finally, pharmacologic blockade of CXCR4 selectively reduced M2-related TAMs after chemotherapy, especially those in direct contact with blood vessels, thereby reducing tumor revascularization and regrowth. Our studies rationalize a strategy to leverage chemotherapeutic efficacy by selectively targeting this perivascular, relapse-promoting M2-related TAM cell population. PMID:26269531

  11. Ginger Helps Reduce Nausea from Chemotherapy | Division of Cancer Prevention

    Cancer.gov

    Ginger helped prevent or reduce chemotherapy-induced nausea when taken with traditional anti-nausea drugs by patients with cancer, researchers have found. The results are from a randomized, double-blind, placebo-controlled clinical trial, the largest study to examine the potential effects of ginger on chemotherapy-related nausea. The study will be presented May 30 at the ASCO annual meeting in Orlando, FL. |

  12. First experiences with intraperitoneal chemotherapy in ovarian cancer.

    PubMed

    Gitsch, E; Sevelda, P; Schmidl, S; Salzer, H

    1990-01-01

    The Authors report their experience with intraperitoneal chemotherapy in post surgical management of ovarian cancer. 24 patients were evaluable for the study and the results indicate that in patients with bulky disease the complication rate was high and the therapeutical outcome very poor. Only in patients with microscopic disease and residual tumor smaller than 2 cm seemed to benefit from intraperitoneal chemotherapy. Despite pharmacological advantages, Mitoxantrone causes local discomfort up to peritonitis. PMID:2347331

  13. Imaging enhancement of malignancy by cyclophosphamide: surprising chemotherapy opposite effects

    NASA Astrophysics Data System (ADS)

    Yamauchi, Kensuke; Yang, Meng; Hayashi, Katsuhiro; Jiang, Ping; Xu, Mingxu; Yamamoto, Norio; Tsuchiya, Hiroyuki; Tomita, Katsuro; Moossa, A. R.; Bouvet, Michael; Hoffman, Robert M.

    2008-02-01

    Although side effects of cancer chemotherapy are well known, "opposite effects" of chemotherapy which enhance the malignancy of the treated cancer are not well understood. We have observed a number of steps of malignancy that are enhanced by chemotherapy pre-treatment of mice before transplantation of human tumor cells. The induction of intravascular proliferation, extravasation, and colony formation by cancer cells, critical steps of metastasis was enhanced by pretreatment of host mice with the commonly-used chemotherapy drug cyclophosphamide. Cyclophosphamide appears to interfere with a host process that inhibits intravascular proliferation, extravasation, and extravascular colony formation by at least some tumor cells. Cyclophosphamide does not directly affect the cancer cells since cyclophosphamide has been cleared by the time the cancer cells were injected. Without cyclophosphamide pretreatment, human colon cancer cells died quickly after injection in the portal vein of nude mice. Extensive clasmocytosis (destruction of the cytoplasm) of the cancer cells occurred within 6 hours. The number of apoptotic cells rapidly increased within the portal vein within 12 hours of injection. However, when the host mice were pretreated with cyclophosphamide, the cancer cells survived and formed colonies in the liver after portal vein injection. These results suggest that a cyclophosphamide-sensitive host cellular system attacked the cancer cells. This review describes an important unexpected "opposite effects" of chemotherapy that enhances critical steps in malignancy rather than inhibiting them, suggesting that certain current approaches to cancer chemotherapy should be modified.

  14. Oral toxicity produced by chemotherapy: A systematic review

    PubMed Central

    2014-01-01

    Introduction: Antineoplastic chemotherapy remains one of the most widely used management strategies in cancer, either alone or in combination with other types of treatment. The main inconvenience of chemotherapy is its lack of selectivity, since it acts upon both tumor cells and rapidly multiplying normal cells such as bone marrow cells, hair follicle cells and oral and gastrointestinal mucosal cells. Material and method: An exhaustive search was made of the main oral toxic effects of chemotherapy in the PubMed-Medline, Cochrane Library and Scopus databases. A total of 1293 articles were identified, of which 333 met the study inclusion criteria. Results: The toxic effects of chemotherapy at oral mucosal level comprise mucositis, osteonecrosis of the jaws secondary to bisphosphonate use, susceptibility to infections, dental alterations, salivary and neurological disorders, dysgeusia and bleeding tendency. These complications have a negative impact upon patient quality of life, and in some cases can prove life-threatening. Conclusions: Evaluation of patient oral and dental health is essential before administering chemotherapy, in order to minimize the risk of oral and systemic complications of such treatment. Key words:Chemotherapy, oral complications, dental, saliva and osteonecrosis jaw. PMID:24596641

  15. New Horizon in Life: Experiences of Patients Receiving Chemotherapy

    PubMed Central

    Nasrabadi, Alireza Nikbakht; Mohammadpour, Ali; Fathi, Mohammad

    2016-01-01

    Introduction: The treatment quality of diseases can affect the patient's experience. Due to its different complications among cancer patients, the experience of chemotherapy is unique. The present study was conducted to explore the lived experience among cancer patients who had received chemotherapy. Methods: The study was conducted by a qualitative approach and a phenomenological method. In so doing, 12 cancer patients who had received chemotherapy were purposefully selected were interviewed using an in-depth method. After the required data were collected, they were analyzed by Tanner, Allen, Diekelmann method. Results: Analysis of the collected data indicated that the experience of chemotherapy appeared as “a new horizon in life” for the patients. Secondary themes of the new horizon in life included rebirth, understanding of life values, dependence, and need. Conclusion: According to the results of the study, it was concluded that in addition to taking into providing mental-spiritual support and reducing the complications of the treatment, nurses in chemotherapy wards should pay attention to the experiences of the patients receiving chemotherapy and enhance hope and positive attitude among them. PMID:26573050

  16. Clinical overview of metronomic chemotherapy in breast cancer.

    PubMed

    Munzone, Elisabetta; Colleoni, Marco

    2015-11-01

    Over 15 years ago, low-dose metronomic chemotherapy was shown to induce disease control in patients with advanced-stage breast cancer with a lower incidence of adverse events compared with conventional maximum tolerated dose chemotherapy. Good response rates have been seen in heavily pre-treated patients for whom limited treatment options are available. Most patients prefer oral therapy and metronomic chemotherapy is a convenient alternative in patients with advanced-stage disease in which minimal toxicity and good tumour control are the overall aims of treatment. The addition of metronomic protocols to standard neoadjuvant chemotherapy regimens has produced promising pathological complete response rates. Ongoing trials including the SYSUCC-001 trial in patients with triple-negative breast cancer and the IBCSG 22-00 trial that is assessing a cyclophosphamide-methotrexate maintenance regimen after standard adjuvant therapy in hormone receptor-negative disease, will clarify the value of adding this approach to conventional therapies. The low cost associated with metronomic chemotherapy represents an opportunity for the utilization of this treatment option, especially in developing countries, and poses a challenge for the launch of large trials sponsored by industry. Using breast cancer as the principal example, we discuss the key clinical advances in this area, including new trial design, appropriate patient and end point selection, as well as the evolving rationale for metronomic chemotherapy combinations.

  17. Chemotherapy for gliomas in mainland China: An overview

    PubMed Central

    SAI, KE; YANG, QUN-YING; SHEN, DONG; CHEN, ZHONG-PING

    2013-01-01

    Chemotherapy is currently the standard treatment modality for malignant gliomas. Many patients with gliomas are treated in mainland China every year. The history and development of chemotherapy for glioma, however, are not well documented. In this study, an extensive literature search of Pubmed and major Chinese electronic databases was performed to identify clinical studies. A total of 210 publications were identified, with a total of 10,105 patients. Among these studies, 76.2% were retrospective and 23.8% were prospective. Chemotherapy was found to have been administered by the Department of Neurosurgery in 143 studies (68.1%). Oral or intravenous administration was found in 55.7% of studies, followed by intra-arterial (26.7%) and interstitial (15.7%) chemotherapy. Nitrosoureas were the most frequently used chemotherapeutic agents, as found in 133 studies (63.3%). Since 2003, 56 studies on temozolomide (TMZ) have been published. Studies on chemotherapy for gliomas began in the 1970s in mainland China but well-designed randomized controlled trials (RCTs) are rare. Much effort and collaboration should be made to carry out high-quality multicenter RCTs on chemotherapy for gliomas. PMID:23761809

  18. A Simple Assay to Screen Antimicrobial Compounds Potentiating the Activity of Current Antibiotics

    PubMed Central

    Iqbal, Junaid; Kazmi, Shahana Urooj; Khan, Naveed Ahmed

    2013-01-01

    Antibiotic resistance continues to pose a significant problem in the management of bacterial infections, despite advances in antimicrobial chemotherapy and supportive care. Here, we suggest a simple, inexpensive, and easy-to-perform assay to screen antimicrobial compounds from natural products or synthetic chemical libraries for their potential to work in tandem with the available antibiotics against multiple drug-resistant bacteria. The aqueous extract of Juglans regia tree bark was tested against representative multiple drug-resistant bacteria in the aforementioned assay to determine whether it potentiates the activity of selected antibiotics. The aqueous extract of J. regia bark was added to Mueller-Hinton agar, followed by a lawn of multiple drug-resistant bacteria, Salmonella typhi or enteropathogenic E. coli. Next, filter paper discs impregnated with different classes of antibiotics were placed on the agar surface. Bacteria incubated with extract or antibiotics alone were used as controls. The results showed a significant increase (>30%) in the zone of inhibition around the aztreonam, cefuroxime, and ampicillin discs compared with bacteria incubated with the antibiotics/extract alone. In conclusion, our assay is able to detect either synergistic or additive action of J. regia extract against multiple drug-resistant bacteria when tested with a range of antibiotics. PMID:23865073

  19. Antimicrobial cyclic peptides for plant disease control.

    PubMed

    Lee, Dong Wan; Kim, Beom Seok

    2015-03-01

    Antimicrobial cyclic peptides derived from microbes bind stably with target sites, have a tolerance to hydrolysis by proteases, and a favorable degradability under field conditions, which make them an attractive proposition for use as agricultural fungicides. Antimicrobial cyclic peptides are classified according to the types of bonds within the ring structure; homodetic, heterodetic, and complex cyclic peptides, which in turn reflect diverse physicochemical features. Most antimicrobial cyclic peptides affect the integrity of the cell envelope. This is achieved through direct interaction with the cell membrane or disturbance of the cell wall and membrane component biosynthesis such as chitin, glucan, and sphingolipid. These are specific and selective targets providing reliable activity and safety for non-target organisms. Synthetic cyclic peptides produced through combinatorial chemistry offer an alternative approach to develop antimicrobials for agricultural uses. Those synthesized so far have been studied for antibacterial activity, however, the recent advancements in powerful technologies now promise to provide novel antimicrobial cyclic peptides that are yet to be discovered from natural resources.

  20. Antimicrobial Cyclic Peptides for Plant Disease Control

    PubMed Central

    Lee, Dong Wan; Kim, Beom Seok

    2015-01-01

    Antimicrobial cyclic peptides derived from microbes bind stably with target sites, have a tolerance to hydrolysis by proteases, and a favorable degradability under field conditions, which make them an attractive proposition for use as agricultural fungicides. Antimicrobial cyclic peptides are classified according to the types of bonds within the ring structure; homodetic, heterodetic, and complex cyclic peptides, which in turn reflect diverse physicochemical features. Most antimicrobial cyclic peptides affect the integrity of the cell envelope. This is achieved through direct interaction with the cell membrane or disturbance of the cell wall and membrane component biosynthesis such as chitin, glucan, and sphingolipid. These are specific and selective targets providing reliable activity and safety for non-target organisms. Synthetic cyclic peptides produced through combinatorial chemistry offer an alternative approach to develop antimicrobials for agricultural uses. Those synthesized so far have been studied for antibacterial activity, however, the recent advancements in powerful technologies now promise to provide novel antimicrobial cyclic peptides that are yet to be discovered from natural resources. PMID:25774105