To review the neuroprotective effects of minocycline in focal cerebral ischemia in animal models.By searching in the databases of PubMed,ScienceDirect,and Scopus,and considering the inclusion and exclusion criteria of...To review the neuroprotective effects of minocycline in focal cerebral ischemia in animal models.By searching in the databases of PubMed,ScienceDirect,and Scopus,and considering the inclusion and exclusion criteria of the study.Studies were included if focal cerebral ischemia model was performed in mammals and including a control group that has been compared with a minocycline group.Written in languages other than English;duplicate data;in vitro studies and combination of minocycline with other neuroprotective agents were excluded.Neurological function of patients was assessed by National Institute of Health Stroke Scale,modified Rankin Scale,and modified Barthel Index.Neuroprotective effects were assessed by detecting the expression of inflammatory cytokines.We examined 35 papers concerning the protective effects of minocycline in focal cerebral ischemia in animal models and 6 clinical trials which had evaluated the neuroprotective effects of minocycline in ischemic stroke.These studies revealed that minocycline increases the viability of neurons and decreases the infarct volume following cerebral ischemia.The mechanisms that were reported in these studies included anti-inflammatory,antioxidant,as well as anti-apoptotic effects.Minocycline also increases the neuronal regeneration following cerebral ischemia.Minocycline has considerable neuroprotective effects against cerebral ischemia-induced neuronal damages.However,larger clinical trials may be required before using minocycline as a neuroprotective drug in ischemic stroke.展开更多
Drug metabolism and pharmacokinetics(DMPK) is an important branch of pharmaceutical sciences.The nature of ADME(absorption,distribution,metabolism,excretion) and PK(pharmacokinetics) inquiries during drug discovery an...Drug metabolism and pharmacokinetics(DMPK) is an important branch of pharmaceutical sciences.The nature of ADME(absorption,distribution,metabolism,excretion) and PK(pharmacokinetics) inquiries during drug discovery and development has evolved in recent years from being largely descriptive to seeking a more quantitative and mechanistic understanding of the fate of drug candidates in biological systems.Tremendous progress has been made in the past decade,not only in the characterization of physiochemical properties of drugs that influence their ADME,target organ exposure,and toxicity,but also in the identification of design principles that can minimize drug-drug interaction(DDI) potentials and reduce the attritions.The importance of membrane transporters in drug disposition,efficacy,and safety,as well as the interplay with metabolic processes,has been increasingly recognized.Dramatic increases in investments on new modalities beyond traditional small and large molecule drugs,such as peptides,oligonucleotides,and antibody-drug conjugates,necessitated further innovations in bioanalytical and experimental tools for the characterization of their ADME properties.In this review,we highlight some of the most notable advances in the last decade,and provide future perspectives on potential major breakthroughs and innovations in the translation of DMPK science in various stages of drug discovery and development.展开更多
Compared to small molecule process analytical technology （PAT） applications, biotechnology product PAT applications have certain unique challenges and opportunities. Understanding process dynamics of bioreactor cell...Compared to small molecule process analytical technology （PAT） applications, biotechnology product PAT applications have certain unique challenges and opportunities. Understanding process dynamics of bioreactor cell culture process is essential to establish an appropriate process control strategy for biotechnology product PAT applications. Inline spectroscopic techniques for real time monitoring of bioreactor cell culture process have the distinct potential to develop PAT approaches in manufac- turing biotechnology drug products. However, the use of inline Fourier transform infrared （FTIR） spectroscopic techniques for bioreactor cell culture process monitoring has not been reported. In this work, real time inline FTIR Spectroscopy was applied to a lab scale bioreactor mAb IgG3 cell culture fluid biomolecular dynamic model. The technical feasibility of using FTIR Spectroscopy for real time tracking and monitoring four key cell culture metabolites （including glucose, glutamine, lactate, and ammonia） and protein yield at increasing levels of complexity （simple binary system, fully formulated media, actual bioreactor cell culture process） was evaluated via a stepwise approach. The FTIR fingerprints of the key metabolites were identified. The multivariate partial least squares （PLS） calibration models were established to correlate the process FTIR spectra with the concentrations of key metabolites and protein yield of in-process samples, either individually for each metabolite and protein or globally for all four metabolites simultaneously. Applying the 2＇ld derivative pre-processing algorithm to the FTIR spectra helps to reduce the number of PLS latent variables needed significantly and thus simplify the interpretation of the PLS models. The validated PLS models show promise in predicting the concentration profiles of glucose, glutamine, lactate, and ammonia and protein yield over the course of the bioreactor cell culture process. Therefore, this work demonstrated the technical feasibility of re展开更多
There is an urgent need for developing a procedure for biomarker standardization and relative quantificationin clinical laboratories. Measuring the expression levels of cell antigens is critical for the diagnosis of m...There is an urgent need for developing a procedure for biomarker standardization and relative quantificationin clinical laboratories. Measuring the expression levels of cell antigens is critical for the diagnosis of many diseases, e.g. leukemia, lymphoma and immunodeficiency diseases. One of the most significant challenges in flow cytometry is obtaining inter-laboratory and intra-laboratory consistent and reproducible results across multiple cytometer platforms and locations longitudinally over time. To obtain measurement consistency, the target flow cytometer voltages should be optimized to segregate the negative population from the electronic noise, and to keep the brightest positive population within the dynamic range of each detector. Then target values should be determined and transferred to selected cytometers. In this study, we optimized a procedure for instrument standardization across three different flow cytometer platforms from the same vendor and in two different locations. The biomarker quantification was implemented on standardized instruments using CD4 expression on T lymphocytes with a known amount of antibody bound per cell as a quantification standard. Our results on blood cell subset typing and CD19 quantification demonstrated that consistent and reliable results could be accomplished between instruments using the developed procedure. Quantitating the expression levels of certain cell biomarkers relative to a known reference marker before, during, and after therapy would provide important information for monitoring antibody-based therapy and could be potentially used to adjust dosing. Presently, we are implementing this protocol to quantify critical disease biomarkers, and making necessary modifications to the procedure to include instruments from different instrument manufacturers.展开更多
Objective:Intrahepatic cholangiocarcinoma(ICC)and hepatocellular carcinoma(HCC)are clinically disparate primary liver cancers with etiological and biological heterogeneity.In Thailand,both cancer types represent the p...Objective:Intrahepatic cholangiocarcinoma(ICC)and hepatocellular carcinoma(HCC)are clinically disparate primary liver cancers with etiological and biological heterogeneity.In Thailand,both cancer types represent the primary cause of cancer-related deaths and are a major public health concern.展开更多
This past year was another successful year for the new drugs program in FDA＇s Center for Drug Evaluation and Research （CDER）. CDER reviewed and approved 22 novel drugs, most of which have the potential to add signi...This past year was another successful year for the new drugs program in FDA＇s Center for Drug Evaluation and Research （CDER）. CDER reviewed and approved 22 novel drugs, most of which have the potential to add significant clinical value to the care of thousands of patients with serious and life-threatening diseases.展开更多
BACKGROUND Liver fibrosis is a common pathway of liver injury and is a feature of most chronic liver diseases.Fibrosis progression varies markedly in patients with hepatitis C virus(HCV).Liver stiffness has been recom...BACKGROUND Liver fibrosis is a common pathway of liver injury and is a feature of most chronic liver diseases.Fibrosis progression varies markedly in patients with hepatitis C virus(HCV).Liver stiffness has been recommended as a parameter of fibrosis progression/regression in patients with HCV.AIM To investigate changes in liver stiffness measured by transient elastography(TE)in a large,racially diverse cohort of United States patients with chronic hepatitis C(CHC).METHODS We evaluated the differences in liver stiffness between patients treated with direct-acting antiviral(DAA)therapy and untreated patients.Patients had≥2 TE measurements and no prior DAA exposure.We used linear regression to measure the change in liver stiffness between first and last TE in response to treatment,controlling for age,sex,race,diabetes,smoking status,human immunodeficiency virus status,baseline alanine aminotransferase,and baseline liver stiffness.Separate regression models analyzed the change in liver stiffness as measured by kPa,stratified by cirrhosis status.RESULTS Of 813 patients,419(52%)initiated DAA treatment.Baseline liver stiffness was 12 kPa in 127(16%).Median time between first and last TE was 11.7 and 12.7 mo among treated and untreated patients,respectively.There was no significant change in liver stiffness observed over time in either the group initiating DAA treatment(0.016 kPa/month;CI:-0.051,0.084)or in the untreated group(0.001 kPa/mo;CI:-0.090,0.092),controlling for covariates.A higher baseline kPa score was independently associated with decreased liver stiffness.CONCLUSION DAA treatment was not associated with a differential change in liver stiffness over time in patients with CHC compared to untreated patients.展开更多
A biofilm contains a consortium of cohesive bacterial cells forming a complex structure that is a sedentary, but dynamic, community. Biofilms adhere on biotic and abiotic surfaces, including the surfaces of practicall...A biofilm contains a consortium of cohesive bacterial cells forming a complex structure that is a sedentary, but dynamic, community. Biofilms adhere on biotic and abiotic surfaces, including the surfaces of practically all medical devices. Biofilms are reported to be responsible for approximately 60% of nosocomial infections due to implanted medical devices, such as intravenous catheters, and they also cause other foreign-body infections and chronic infections. The presence of biofilm on a medical device may result in the infection of surrounding tissues and failure of the device, necessitating the removal and replacement ofthe device. Bacteria from biofilms formed on medical devices may be released and disperse, with the potential for the formation of new biofilms in other locations and the development of a systemic infection. Regardless of their location, bacteria in biofilms are tolerant of the activities of the immune system, antimicrobial agents, and antiseptics. Concentrations of antimicrobial agents sufficient to eradicate planktonic cells have no effect on the same microorganism in a biofilm. Depending on the microbial consortium or component of the biofilm that is involved, various combinations of factors have been suggested to explain the recalcitrant nature of biofilms toward killing by antibiotics. In this mini-review, some of the factors contributing to antimicrobial resistance in biofilms are discussed.展开更多
Posted on September 15,2015 by FDA VoiceIf you personally know 100 people living in the U.S.,chances are that almost 10 will suffer from some form of a rare disease.If that makes it sound like rare diseases are not ac...Posted on September 15,2015 by FDA VoiceIf you personally know 100 people living in the U.S.,chances are that almost 10 will suffer from some form of a rare disease.If that makes it sound like rare diseases are not actually very rare in this country,that’s because there are 7,000 different rare diseases,80%of which are caused by faulty genes.A rare disease is defined展开更多
Objective Genistein, a major soy isoflavone metabolite （SIF）, inactivates oxidation activity of bovine lactoperoxidase （LPO）. Modification of the heme moiety of LPO by nitrogen-containing compounds has been shown ...Objective Genistein, a major soy isoflavone metabolite （SIF）, inactivates oxidation activity of bovine lactoperoxidase （LPO）. Modification of the heme moiety of LPO by nitrogen-containing compounds has been shown to inactivate LPO. In contrast, SIF mediated inactivation of LPO does not involve a heme modification and the mechanism of SIF inhibition is poorly understood. Methods After inactivation of LPO by genistein in the presence of H202, trypsin-digested LPO peptide fragments were collected and analyzed by MALDI-TOF-MS to characterize the chemical binding of genistein（s） to LPO. Results The heme moiety of LPO was not modified by genistein. A covalent binding study showed that 3H-genistein bound to LPO with a ratio of ~12 to 1. After HPLC analysis and peak collection, trypsin-digested peptide fragments were analyzed by MALDI-TOF-MS. The 3H-genistein co-eluted peptide fragments （RT=24 min） were putatively identified as 1991VGYLDEEGVLDQNR214 with two bound genistein molecules or a genistein dimer （2 259 Da）, 486TPDNIDIWlGGNAEPMVER504 with two bound genistein molecules or a genistein dimer （2 663 Da）, and 161ARWLPAEYEDGLALPFGWTQR182 with three bound genistein molecules or a genistein trimer （3 060 Da）. The fragment with a mass of 2 792 Da （RT=36 min） was identified as 132CDENSPYR139 with three genistein molecules or a genistein trimer. Conclusions The results suggest that LPO was inactivated by irreversible covalent binding of genistein or genistein polymers to particular peptide fragments constituting regions of the outward domain. No genistein interaction with the prosthetic heme moiety of LPO was observed.展开更多
CBER is providing interested persons with information concerning the storage and use of temperature-sensitive biological products that have been involved in a temporary electrical power failure or flood conditions.Whi...CBER is providing interested persons with information concerning the storage and use of temperature-sensitive biological products that have been involved in a temporary electrical power failure or flood conditions.While people should not be put at risk by using a product that may be unsafe due to the conditions under which it was stored,shortages should not展开更多
Here at FDA, we work diligently to be part of our nation＇s solution to the opioid abuse epidemic. While there is no single solution to this complex problem, we continue to encourage efforts to develop new opioid form...Here at FDA, we work diligently to be part of our nation＇s solution to the opioid abuse epidemic. While there is no single solution to this complex problem, we continue to encourage efforts to develop new opioid formulations with abuse-deterrent properties that make it harder to abuse these powerful medications展开更多
We present results of real-time and sensitive MR Thermometry (MRT) using a paramagnetic lanthanide complex thulium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethyl-1,4,7,10-tetraa-cetate (Tm-DOTMA) to study radio f...We present results of real-time and sensitive MR Thermometry (MRT) using a paramagnetic lanthanide complex thulium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethyl-1,4,7,10-tetraa-cetate (Tm-DOTMA) to study radio frequency (RF) heating induced by a copper wire and a titanium bone screw in an agarose gel phantom. The temperature dependent chemical shift coefficient (TDCSC) of the methyl resonance was found to be 0.7 ± 0.03 ppm/°;C in agarose gel. The methyl protons of Tm-DOTMA were imaged using 2D chemical shift imaging (CSI) and 3D phase mapping methods (PMM), approximately 7 sec long, and compared with conventional water proton resonance frequency (PRF) method. Two RF-induced heating approaches were tested: 1) using a prescan before the MRT;or 2) using the heating caused by the imaging pulse during continuous imaging. Both approaches allowed detection of temperature changes which are less than 1°;C and continuously mapping temperature changes around the copper wire. Using a heating pre-scan, the Tm-DOTMA 2D-CSI allowed better qualitative visualization of the temperature changes around the titanium screw compared with water phase shift thermometry. Numerical electromagnetic field simulations were also conducted for the evaluation of orientation dependency using the copper wire in 4.7 T (200 MHz). Thermometry approach using Tm-DOTMA can detect smaller temperature changes with decreased scanning time resulting in real-time and sensitive temperature mapping.展开更多
We experimentally and theoretically investigated the performance of a fiber-optic based Fourier-domain common-path optical coherence tomography （OCT）. The fiber-optic common-path OCT operated at the 840-nm center wa...We experimentally and theoretically investigated the performance of a fiber-optic based Fourier-domain common-path optical coherence tomography （OCT）. The fiber-optic common-path OCT operated at the 840-nm center wavelength. The resolution of the system was 8.8 μm （in air） and the working depth using a bare fiber probe was approximately 1.5 mm. The signal-to-noise ratio （SNR） of the system was analyzed. OCT images obtained by the system were also presented.展开更多
Soybeans have been shown to contain larger concentrations of isoflavones than other plant foods. The colonic micro-floras of some individuals metabolize isoflavones, including the soy phytoestrogen daidzein, to compou...Soybeans have been shown to contain larger concentrations of isoflavones than other plant foods. The colonic micro-floras of some individuals metabolize isoflavones, including the soy phytoestrogen daidzein, to compounds with altered estrogenic activity that may affect health. Monkeys have been used as models to predict the effect of colonic microorganisms on the metabolism of phytoestrogens. We studied the effect of consumption of a diet rich in soy protein on the metabolism of added daidzein by the intestinal microfloras of monkeys. The metabolism of daidzein by cultures of the colonic microfloras from eight males and eight females of Macaca fascicularis, 6 - 12 years old, consuming diets containing either soy or casein, and two males and three females of Macaca nemestrina, 3 - 5 months old, consuming infant formula, was investigated using high-performance liquid chromatographic analyses. Cultures from ten of the 16 adult monkeys and all five infant monkeys metabolized the added daidzein within 24 h. Daidzein was metabolized within 48 h by cultures from five other monkeys, but it remained even after 72 h in a culture from one female monkey on a casein diet. Equol and dihydrodaidzein were the only metabolites found. Individual variation among monkeys in the efficiency of daidzein metabolism was observed, but there appeared to be no correlation between diet and daidzein metabolism by the intestinal microflora. The intestinal microfloras of most monkeys tested were efficient in the biotransformation of daidzein to equol, regardless of the animals’ consumption of soy protein. Differences in the metabolism of isoflavones by the colonic microfloras of humans and experimental animals should be considered when extrapolating results from animals to humans.展开更多
文摘To review the neuroprotective effects of minocycline in focal cerebral ischemia in animal models.By searching in the databases of PubMed,ScienceDirect,and Scopus,and considering the inclusion and exclusion criteria of the study.Studies were included if focal cerebral ischemia model was performed in mammals and including a control group that has been compared with a minocycline group.Written in languages other than English;duplicate data;in vitro studies and combination of minocycline with other neuroprotective agents were excluded.Neurological function of patients was assessed by National Institute of Health Stroke Scale,modified Rankin Scale,and modified Barthel Index.Neuroprotective effects were assessed by detecting the expression of inflammatory cytokines.We examined 35 papers concerning the protective effects of minocycline in focal cerebral ischemia in animal models and 6 clinical trials which had evaluated the neuroprotective effects of minocycline in ischemic stroke.These studies revealed that minocycline increases the viability of neurons and decreases the infarct volume following cerebral ischemia.The mechanisms that were reported in these studies included anti-inflammatory,antioxidant,as well as anti-apoptotic effects.Minocycline also increases the neuronal regeneration following cerebral ischemia.Minocycline has considerable neuroprotective effects against cerebral ischemia-induced neuronal damages.However,larger clinical trials may be required before using minocycline as a neuroprotective drug in ischemic stroke.
基金supported in part by grants from the National Institutes of Health (CA023074,CA092596,ES004940,ES006694,and ES020867,USA)。
文摘Drug metabolism and pharmacokinetics(DMPK) is an important branch of pharmaceutical sciences.The nature of ADME(absorption,distribution,metabolism,excretion) and PK(pharmacokinetics) inquiries during drug discovery and development has evolved in recent years from being largely descriptive to seeking a more quantitative and mechanistic understanding of the fate of drug candidates in biological systems.Tremendous progress has been made in the past decade,not only in the characterization of physiochemical properties of drugs that influence their ADME,target organ exposure,and toxicity,but also in the identification of design principles that can minimize drug-drug interaction(DDI) potentials and reduce the attritions.The importance of membrane transporters in drug disposition,efficacy,and safety,as well as the interplay with metabolic processes,has been increasingly recognized.Dramatic increases in investments on new modalities beyond traditional small and large molecule drugs,such as peptides,oligonucleotides,and antibody-drug conjugates,necessitated further innovations in bioanalytical and experimental tools for the characterization of their ADME properties.In this review,we highlight some of the most notable advances in the last decade,and provide future perspectives on potential major breakthroughs and innovations in the translation of DMPK science in various stages of drug discovery and development.
文摘Compared to small molecule process analytical technology （PAT） applications, biotechnology product PAT applications have certain unique challenges and opportunities. Understanding process dynamics of bioreactor cell culture process is essential to establish an appropriate process control strategy for biotechnology product PAT applications. Inline spectroscopic techniques for real time monitoring of bioreactor cell culture process have the distinct potential to develop PAT approaches in manufac- turing biotechnology drug products. However, the use of inline Fourier transform infrared （FTIR） spectroscopic techniques for bioreactor cell culture process monitoring has not been reported. In this work, real time inline FTIR Spectroscopy was applied to a lab scale bioreactor mAb IgG3 cell culture fluid biomolecular dynamic model. The technical feasibility of using FTIR Spectroscopy for real time tracking and monitoring four key cell culture metabolites （including glucose, glutamine, lactate, and ammonia） and protein yield at increasing levels of complexity （simple binary system, fully formulated media, actual bioreactor cell culture process） was evaluated via a stepwise approach. The FTIR fingerprints of the key metabolites were identified. The multivariate partial least squares （PLS） calibration models were established to correlate the process FTIR spectra with the concentrations of key metabolites and protein yield of in-process samples, either individually for each metabolite and protein or globally for all four metabolites simultaneously. Applying the 2＇ld derivative pre-processing algorithm to the FTIR spectra helps to reduce the number of PLS latent variables needed significantly and thus simplify the interpretation of the PLS models. The validated PLS models show promise in predicting the concentration profiles of glucose, glutamine, lactate, and ammonia and protein yield over the course of the bioreactor cell culture process. Therefore, this work demonstrated the technical feasibility of re
文摘There is an urgent need for developing a procedure for biomarker standardization and relative quantificationin clinical laboratories. Measuring the expression levels of cell antigens is critical for the diagnosis of many diseases, e.g. leukemia, lymphoma and immunodeficiency diseases. One of the most significant challenges in flow cytometry is obtaining inter-laboratory and intra-laboratory consistent and reproducible results across multiple cytometer platforms and locations longitudinally over time. To obtain measurement consistency, the target flow cytometer voltages should be optimized to segregate the negative population from the electronic noise, and to keep the brightest positive population within the dynamic range of each detector. Then target values should be determined and transferred to selected cytometers. In this study, we optimized a procedure for instrument standardization across three different flow cytometer platforms from the same vendor and in two different locations. The biomarker quantification was implemented on standardized instruments using CD4 expression on T lymphocytes with a known amount of antibody bound per cell as a quantification standard. Our results on blood cell subset typing and CD19 quantification demonstrated that consistent and reliable results could be accomplished between instruments using the developed procedure. Quantitating the expression levels of certain cell biomarkers relative to a known reference marker before, during, and after therapy would provide important information for monitoring antibody-based therapy and could be potentially used to adjust dosing. Presently, we are implementing this protocol to quantify critical disease biomarkers, and making necessary modifications to the procedure to include instruments from different instrument manufacturers.
文摘Objective:Intrahepatic cholangiocarcinoma(ICC)and hepatocellular carcinoma(HCC)are clinically disparate primary liver cancers with etiological and biological heterogeneity.In Thailand,both cancer types represent the primary cause of cancer-related deaths and are a major public health concern.
文摘This past year was another successful year for the new drugs program in FDA＇s Center for Drug Evaluation and Research （CDER）. CDER reviewed and approved 22 novel drugs, most of which have the potential to add significant clinical value to the care of thousands of patients with serious and life-threatening diseases.
基金Supported by the National Center for Advancing Translational Sciences,No.5KL2TR001077-05(to Po-Hung Chen).
文摘BACKGROUND Liver fibrosis is a common pathway of liver injury and is a feature of most chronic liver diseases.Fibrosis progression varies markedly in patients with hepatitis C virus(HCV).Liver stiffness has been recommended as a parameter of fibrosis progression/regression in patients with HCV.AIM To investigate changes in liver stiffness measured by transient elastography(TE)in a large,racially diverse cohort of United States patients with chronic hepatitis C(CHC).METHODS We evaluated the differences in liver stiffness between patients treated with direct-acting antiviral(DAA)therapy and untreated patients.Patients had≥2 TE measurements and no prior DAA exposure.We used linear regression to measure the change in liver stiffness between first and last TE in response to treatment,controlling for age,sex,race,diabetes,smoking status,human immunodeficiency virus status,baseline alanine aminotransferase,and baseline liver stiffness.Separate regression models analyzed the change in liver stiffness as measured by kPa,stratified by cirrhosis status.RESULTS Of 813 patients,419(52%)initiated DAA treatment.Baseline liver stiffness was 12 kPa in 127(16%).Median time between first and last TE was 11.7 and 12.7 mo among treated and untreated patients,respectively.There was no significant change in liver stiffness observed over time in either the group initiating DAA treatment(0.016 kPa/month;CI:-0.051,0.084)or in the untreated group(0.001 kPa/mo;CI:-0.090,0.092),controlling for covariates.A higher baseline kPa score was independently associated with decreased liver stiffness.CONCLUSION DAA treatment was not associated with a differential change in liver stiffness over time in patients with CHC compared to untreated patients.
文摘A biofilm contains a consortium of cohesive bacterial cells forming a complex structure that is a sedentary, but dynamic, community. Biofilms adhere on biotic and abiotic surfaces, including the surfaces of practically all medical devices. Biofilms are reported to be responsible for approximately 60% of nosocomial infections due to implanted medical devices, such as intravenous catheters, and they also cause other foreign-body infections and chronic infections. The presence of biofilm on a medical device may result in the infection of surrounding tissues and failure of the device, necessitating the removal and replacement ofthe device. Bacteria from biofilms formed on medical devices may be released and disperse, with the potential for the formation of new biofilms in other locations and the development of a systemic infection. Regardless of their location, bacteria in biofilms are tolerant of the activities of the immune system, antimicrobial agents, and antiseptics. Concentrations of antimicrobial agents sufficient to eradicate planktonic cells have no effect on the same microorganism in a biofilm. Depending on the microbial consortium or component of the biofilm that is involved, various combinations of factors have been suggested to explain the recalcitrant nature of biofilms toward killing by antibiotics. In this mini-review, some of the factors contributing to antimicrobial resistance in biofilms are discussed.
文摘Posted on September 15,2015 by FDA VoiceIf you personally know 100 people living in the U.S.,chances are that almost 10 will suffer from some form of a rare disease.If that makes it sound like rare diseases are not actually very rare in this country,that’s because there are 7,000 different rare diseases,80%of which are caused by faulty genes.A rare disease is defined
基金supported by the National Science Council, Taiwan #NSC 95‐2320‐B‐408001the Interagency Agreement between NCTR/FDA and the National Institute for Environmental Health Sciences/National Toxicology Program, USA
文摘Objective Genistein, a major soy isoflavone metabolite （SIF）, inactivates oxidation activity of bovine lactoperoxidase （LPO）. Modification of the heme moiety of LPO by nitrogen-containing compounds has been shown to inactivate LPO. In contrast, SIF mediated inactivation of LPO does not involve a heme modification and the mechanism of SIF inhibition is poorly understood. Methods After inactivation of LPO by genistein in the presence of H202, trypsin-digested LPO peptide fragments were collected and analyzed by MALDI-TOF-MS to characterize the chemical binding of genistein（s） to LPO. Results The heme moiety of LPO was not modified by genistein. A covalent binding study showed that 3H-genistein bound to LPO with a ratio of ~12 to 1. After HPLC analysis and peak collection, trypsin-digested peptide fragments were analyzed by MALDI-TOF-MS. The 3H-genistein co-eluted peptide fragments （RT=24 min） were putatively identified as 1991VGYLDEEGVLDQNR214 with two bound genistein molecules or a genistein dimer （2 259 Da）, 486TPDNIDIWlGGNAEPMVER504 with two bound genistein molecules or a genistein dimer （2 663 Da）, and 161ARWLPAEYEDGLALPFGWTQR182 with three bound genistein molecules or a genistein trimer （3 060 Da）. The fragment with a mass of 2 792 Da （RT=36 min） was identified as 132CDENSPYR139 with three genistein molecules or a genistein trimer. Conclusions The results suggest that LPO was inactivated by irreversible covalent binding of genistein or genistein polymers to particular peptide fragments constituting regions of the outward domain. No genistein interaction with the prosthetic heme moiety of LPO was observed.
文摘CBER is providing interested persons with information concerning the storage and use of temperature-sensitive biological products that have been involved in a temporary electrical power failure or flood conditions.While people should not be put at risk by using a product that may be unsafe due to the conditions under which it was stored,shortages should not
文摘Here at FDA, we work diligently to be part of our nation＇s solution to the opioid abuse epidemic. While there is no single solution to this complex problem, we continue to encourage efforts to develop new opioid formulations with abuse-deterrent properties that make it harder to abuse these powerful medications
文摘We present results of real-time and sensitive MR Thermometry (MRT) using a paramagnetic lanthanide complex thulium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethyl-1,4,7,10-tetraa-cetate (Tm-DOTMA) to study radio frequency (RF) heating induced by a copper wire and a titanium bone screw in an agarose gel phantom. The temperature dependent chemical shift coefficient (TDCSC) of the methyl resonance was found to be 0.7 ± 0.03 ppm/°;C in agarose gel. The methyl protons of Tm-DOTMA were imaged using 2D chemical shift imaging (CSI) and 3D phase mapping methods (PMM), approximately 7 sec long, and compared with conventional water proton resonance frequency (PRF) method. Two RF-induced heating approaches were tested: 1) using a prescan before the MRT;or 2) using the heating caused by the imaging pulse during continuous imaging. Both approaches allowed detection of temperature changes which are less than 1°;C and continuously mapping temperature changes around the copper wire. Using a heating pre-scan, the Tm-DOTMA 2D-CSI allowed better qualitative visualization of the temperature changes around the titanium screw compared with water phase shift thermometry. Numerical electromagnetic field simulations were also conducted for the evaluation of orientation dependency using the copper wire in 4.7 T (200 MHz). Thermometry approach using Tm-DOTMA can detect smaller temperature changes with decreased scanning time resulting in real-time and sensitive temperature mapping.
文摘We experimentally and theoretically investigated the performance of a fiber-optic based Fourier-domain common-path optical coherence tomography （OCT）. The fiber-optic common-path OCT operated at the 840-nm center wavelength. The resolution of the system was 8.8 μm （in air） and the working depth using a bare fiber probe was approximately 1.5 mm. The signal-to-noise ratio （SNR） of the system was analyzed. OCT images obtained by the system were also presented.
文摘Soybeans have been shown to contain larger concentrations of isoflavones than other plant foods. The colonic micro-floras of some individuals metabolize isoflavones, including the soy phytoestrogen daidzein, to compounds with altered estrogenic activity that may affect health. Monkeys have been used as models to predict the effect of colonic microorganisms on the metabolism of phytoestrogens. We studied the effect of consumption of a diet rich in soy protein on the metabolism of added daidzein by the intestinal microfloras of monkeys. The metabolism of daidzein by cultures of the colonic microfloras from eight males and eight females of Macaca fascicularis, 6 - 12 years old, consuming diets containing either soy or casein, and two males and three females of Macaca nemestrina, 3 - 5 months old, consuming infant formula, was investigated using high-performance liquid chromatographic analyses. Cultures from ten of the 16 adult monkeys and all five infant monkeys metabolized the added daidzein within 24 h. Daidzein was metabolized within 48 h by cultures from five other monkeys, but it remained even after 72 h in a culture from one female monkey on a casein diet. Equol and dihydrodaidzein were the only metabolites found. Individual variation among monkeys in the efficiency of daidzein metabolism was observed, but there appeared to be no correlation between diet and daidzein metabolism by the intestinal microflora. The intestinal microfloras of most monkeys tested were efficient in the biotransformation of daidzein to equol, regardless of the animals’ consumption of soy protein. Differences in the metabolism of isoflavones by the colonic microfloras of humans and experimental animals should be considered when extrapolating results from animals to humans.
