Next Generation Metabolic Screening is a novel technique that can be applied to body fluids as urine, plasma or cerebrospinal fluid for the diagnosis of inborn errors of metabolism. The technique gives a holistic view on metabolism (metabolomics) and uses LC_Qtof mass spectrometry. The technique was developed in Nijmegen, The Netherlands in the group of Prof Ron Wevers (ron.wevers@radboudumc.nl)
alcohol relacionado con insuficiencia renalhectorvaldes08
1) An arginine challenge was given to 14 abstinent alcoholics and 15 healthy controls to examine urea cycle function and hormonal responses.
2) The alcoholics showed higher peak arginine levels and arginine/ornithine ratios compared to controls, suggesting disturbances in urea cycle metabolism.
3) The alcoholics also exhibited a blunted blood glucose response to arginine along with reduced insulin and glucagon surges, indicating impaired gluconeogenesis. Additionally, they showed an elevated growth hormone peak.
Hepatic and serum lipid signatures specific to NASH in mouse modelsFranck Chiappini
This study identified lipid signatures in the liver and serum that are specific to nonalcoholic steatohepatitis (NASH) using mouse models of NAFL and NASH. Mice were fed either a high-fat diet (HFD) to induce NAFL or a methionine choline deficient diet (MCDD) to induce NASH. Comprehensive lipidomic analysis of liver tissues and serum identified 21 lipids in the liver and 14 lipids in the serum that could discriminate mice with NASH from those with NAFL or normal controls. Machine learning techniques were able to characterize lipid signatures specific to NASH in both the liver and serum, opening possibilities for investigating early and non-invasive lipid markers for diagn
Bertin Pharma proposes an integrated bioanalysis platform for drug development from discovery through clinical trials. They have expertise in biomarker and drug assays including immunoassays, ligand binding assays, and LC-MS/MS. They have developed a ghrelin immunoassay to quantify acylated and unacylated ghrelin forms which is challenging due to peptide instability. They have validated the ghrelin assay for various species and clinical applications through overcoming issues like species differences and sensitivity requirements.
IOSR Journal of Pharmacy (IOSRPHR), www.iosrphr.org, call for paper, research...iosrphr_editor
1) The study examined serum gamma glutamyl transferase (GGT) levels in 30 patients with alcoholic hepatitis and 30 healthy controls.
2) GGT levels were significantly higher in patients with alcoholic hepatitis, averaging 107.73 U/L, compared to 20.43 U/L in controls.
3) GGT levels were increased by 527.31% in patients with alcoholic hepatitis, indicating that GGT measurement can be a sensitive marker for diagnosing alcoholic liver disease.
Oncodesign aacr 2018 development of a high throughput in vitro screening pl...Florence Fombertasse
Immunological cell death (ICD) is a form of cancer cell death induced by radiotherapy, photodynamic therapy and a few chemotherapeutic agents such as Doxorubicin, Mitoxantrone, and Oxaliplatin. Unlike apoptosis or necrosis, ICD can induce an effective immune response directed against the tumor whereby both dendritic cells and T lymphocytes are mediators of this response. Dying cancer cells recruit and activate immune cells by releasing damage-associated molecular patterns (DAMPS) that help and promote the immune response to antigenic tumor neo-epitopes. Three key DAMPS are associated with the ICD process: calreticulin exposition on the cell surface, ATP secretion and high-mobility group box 1 (HMGB1) release. In order to identify new therapeutic agents that promote ICD in malignant cells, we developed a screening strategy facilitated by an automated in vitro platform with four assays on three different tumor cell lines (human osteosarcoma U-2 OS, human breast MDA-MB-231 and murine liver Hepa 1-6). ICD inducers Doxorubicin and Mitoxantrone used as positive controls increased ATP secretion by 2 to 10-fold at a non-cytotoxic dose after 72 hours incubation on the three cell lines. Both compounds also increased calreticulin exposition by 2 to 4-fold (determined by immunofluorescence using the Operetta High-Content Imaging System) and HMGB1 release by two-fold on the three cell lines. Here we will present recent data from the screening of Oncodesign’s Nanocyclix® library using this platform to identify novel ICD inducers.
Results of DNA Horses before Columbus research by geneticist Alessandro AchilliRuben LLumihucci
The entire horse mtDNA was amplified in 11 overlapping PCR fragments, using a set of oligonucleotides with matching annealing temperatures (Table S10). Oligonucleotides were checked (through GenBank BLAST) in order to avoid amplification of nuclear insertions of mitochondrial sequences (numts) (1). After PCR, the fragments were purified using the ExoSAP-IT® enzymatic system (Exonuclease I and Shrimp Alkaline Phosphatase, GE Healthcare) and standard dideoxysequencing was performed by using a set of 33 nested primers (Table S11) specifically designed for this protocol. An ABI 3730 sequencer with 96 capillaries was employed for separation of the sequencing ladders. Complete sequences were aligned, assembled, and compared using the program Sequencher 4.9 (Gene Codes). Traces were generally of excellent quality and there was extensive overlap between reads with most observed mutations determined by at least two independent sequencing reactions. At least two independent operators read each sequence and any potentially ambiguous base call was tested by additional and independent PCR and sequencing reactions.
Switch from Enfuvirtide to Raltegravir Lowers Plasma Concentrations
of Darunavir and Tipranavir: a Pharmacokinetic Substudy of the
EASIER-ANRS 138 Tria
Differences in Antioxidant/Protective Efficacy of Hydrated C60 Fullerene Nan...Tamar Chachibaia
C60 fullerene nanoparticles were tested for their ability to reduce oxidative stress in a rat model of diabetes. Rats injected with streptozotocin to induce diabetes had higher levels of oxidative stress markers like lipid peroxidation and protein oxidation in the liver and brain compared to healthy rats. Treatment with hydrated C60 fullerene nanoparticles decreased these oxidative stress markers to normal levels in diabetic rats, indicating their antioxidant properties. However, the nanoparticles did not lower high blood glucose levels caused by diabetes. The results suggest hydrated C60 fullerene nanoparticles can protect against oxidative stress in diabetes but do not repair damage to insulin-producing cells from streptozotocin.
alcohol relacionado con insuficiencia renalhectorvaldes08
1) An arginine challenge was given to 14 abstinent alcoholics and 15 healthy controls to examine urea cycle function and hormonal responses.
2) The alcoholics showed higher peak arginine levels and arginine/ornithine ratios compared to controls, suggesting disturbances in urea cycle metabolism.
3) The alcoholics also exhibited a blunted blood glucose response to arginine along with reduced insulin and glucagon surges, indicating impaired gluconeogenesis. Additionally, they showed an elevated growth hormone peak.
Hepatic and serum lipid signatures specific to NASH in mouse modelsFranck Chiappini
This study identified lipid signatures in the liver and serum that are specific to nonalcoholic steatohepatitis (NASH) using mouse models of NAFL and NASH. Mice were fed either a high-fat diet (HFD) to induce NAFL or a methionine choline deficient diet (MCDD) to induce NASH. Comprehensive lipidomic analysis of liver tissues and serum identified 21 lipids in the liver and 14 lipids in the serum that could discriminate mice with NASH from those with NAFL or normal controls. Machine learning techniques were able to characterize lipid signatures specific to NASH in both the liver and serum, opening possibilities for investigating early and non-invasive lipid markers for diagn
Bertin Pharma proposes an integrated bioanalysis platform for drug development from discovery through clinical trials. They have expertise in biomarker and drug assays including immunoassays, ligand binding assays, and LC-MS/MS. They have developed a ghrelin immunoassay to quantify acylated and unacylated ghrelin forms which is challenging due to peptide instability. They have validated the ghrelin assay for various species and clinical applications through overcoming issues like species differences and sensitivity requirements.
IOSR Journal of Pharmacy (IOSRPHR), www.iosrphr.org, call for paper, research...iosrphr_editor
1) The study examined serum gamma glutamyl transferase (GGT) levels in 30 patients with alcoholic hepatitis and 30 healthy controls.
2) GGT levels were significantly higher in patients with alcoholic hepatitis, averaging 107.73 U/L, compared to 20.43 U/L in controls.
3) GGT levels were increased by 527.31% in patients with alcoholic hepatitis, indicating that GGT measurement can be a sensitive marker for diagnosing alcoholic liver disease.
Oncodesign aacr 2018 development of a high throughput in vitro screening pl...Florence Fombertasse
Immunological cell death (ICD) is a form of cancer cell death induced by radiotherapy, photodynamic therapy and a few chemotherapeutic agents such as Doxorubicin, Mitoxantrone, and Oxaliplatin. Unlike apoptosis or necrosis, ICD can induce an effective immune response directed against the tumor whereby both dendritic cells and T lymphocytes are mediators of this response. Dying cancer cells recruit and activate immune cells by releasing damage-associated molecular patterns (DAMPS) that help and promote the immune response to antigenic tumor neo-epitopes. Three key DAMPS are associated with the ICD process: calreticulin exposition on the cell surface, ATP secretion and high-mobility group box 1 (HMGB1) release. In order to identify new therapeutic agents that promote ICD in malignant cells, we developed a screening strategy facilitated by an automated in vitro platform with four assays on three different tumor cell lines (human osteosarcoma U-2 OS, human breast MDA-MB-231 and murine liver Hepa 1-6). ICD inducers Doxorubicin and Mitoxantrone used as positive controls increased ATP secretion by 2 to 10-fold at a non-cytotoxic dose after 72 hours incubation on the three cell lines. Both compounds also increased calreticulin exposition by 2 to 4-fold (determined by immunofluorescence using the Operetta High-Content Imaging System) and HMGB1 release by two-fold on the three cell lines. Here we will present recent data from the screening of Oncodesign’s Nanocyclix® library using this platform to identify novel ICD inducers.
Results of DNA Horses before Columbus research by geneticist Alessandro AchilliRuben LLumihucci
The entire horse mtDNA was amplified in 11 overlapping PCR fragments, using a set of oligonucleotides with matching annealing temperatures (Table S10). Oligonucleotides were checked (through GenBank BLAST) in order to avoid amplification of nuclear insertions of mitochondrial sequences (numts) (1). After PCR, the fragments were purified using the ExoSAP-IT® enzymatic system (Exonuclease I and Shrimp Alkaline Phosphatase, GE Healthcare) and standard dideoxysequencing was performed by using a set of 33 nested primers (Table S11) specifically designed for this protocol. An ABI 3730 sequencer with 96 capillaries was employed for separation of the sequencing ladders. Complete sequences were aligned, assembled, and compared using the program Sequencher 4.9 (Gene Codes). Traces were generally of excellent quality and there was extensive overlap between reads with most observed mutations determined by at least two independent sequencing reactions. At least two independent operators read each sequence and any potentially ambiguous base call was tested by additional and independent PCR and sequencing reactions.
Switch from Enfuvirtide to Raltegravir Lowers Plasma Concentrations
of Darunavir and Tipranavir: a Pharmacokinetic Substudy of the
EASIER-ANRS 138 Tria
Differences in Antioxidant/Protective Efficacy of Hydrated C60 Fullerene Nan...Tamar Chachibaia
C60 fullerene nanoparticles were tested for their ability to reduce oxidative stress in a rat model of diabetes. Rats injected with streptozotocin to induce diabetes had higher levels of oxidative stress markers like lipid peroxidation and protein oxidation in the liver and brain compared to healthy rats. Treatment with hydrated C60 fullerene nanoparticles decreased these oxidative stress markers to normal levels in diabetic rats, indicating their antioxidant properties. However, the nanoparticles did not lower high blood glucose levels caused by diabetes. The results suggest hydrated C60 fullerene nanoparticles can protect against oxidative stress in diabetes but do not repair damage to insulin-producing cells from streptozotocin.
Using Targeted Resequencing Microarrays for Simultaneous Definitive Detection...Agnieszka Caruso
The document describes how targeted resequencing microarray technology can be used to simultaneously detect and identify multiple respiratory pathogens from a single sample in 3 sentences or less:
Targeted resequencing microarray (RPM) technology uses thousands of DNA probes to interrogate sequences from respiratory pathogens and can detect genetic variants to identify known pathogens and potentially novel pathogens from a single sample, representing an improvement over traditional techniques that can only detect one pathogen at a time.
This document describes a study using ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC/QTOF) for multi-residue screening of veterinary drugs. Researchers developed a method to separate 70 veterinary drug standards using UPLC and detected the drugs using QTOF MS. The method was then tested on pork muscle tissue extracts spiked with veterinary drugs. The study aimed to develop a single extraction and detection method for screening banned and regulated veterinary drugs in various animal tissues and fluids.
Grant Moore
Section Head Toxicology
Canterbury Health Labs,
PO Box 151, Christchurch 8014
grant.moore@cdhb.govt.nz
(P27, Thursday 27, Ilott Theatre, 2.00)
Este documento resume la fenilcetonuria (PKU), un trastorno genético del metabolismo causado por la deficiencia de la enzima fenilalanina hidroxilasa. Describe la bioquímica, genética y manifestaciones clínicas de la PKU, así como los métodos de detección y diagnóstico como el método de Guthrie y técnicas moleculares como la secuenciación del gen PAH y análisis de MLPA.
For the IB DP Biology course, core unit: Genetics. To get the file, please make a donation to one of my preferred charities via Biology4Good. Find out more here: http://sciencevideos.wordpress.com/about/biology4good/
The EMIT technique is an immunoassay method used to screen blood and urine samples for therapeutic drugs and abused substances. It works by using antibodies linked to enzymes that react with the target substance in a sample. This reaction is then measured spectrophotometrically. EMIT assays are homogeneous, requiring no separation steps, and provide reliable quantitative results. While less sensitive than other immunoassays like ELISA, EMIT is widely used in clinical settings due to its low cost, simplicity, and long shelf life of reagents.
Using LC-MS/MS and Advanced Software Tools to Screen for unknown and Non-targ...AB SCIEX India
LC-MS/MS is a powerful tool for the analysis of Pharmaceuticals and Personal Care Products in environmental samples. The combination of high resolution LC separation and high sensitivity MS/MS is the most powerful tool to screen and quantify targeted compounds.
El documento presenta una introducción al tema de la administración de la cultura y el cambio organizacional. Explica que existen dos fuerzas que gobiernan una organización: la gestión operativa (rutina) y la gestión estratégica (cambio). También describe las siete etapas del cambio organizacional, que incluyen el cambio personal, la asociación, el diseño del cambio, la gestión del apoyo político, la implementación, el afianzamiento y el monitoreo. Finalmente, presenta algunas referencias bibliográficas clave
1. The document describes a study analyzing serum protein profiles from 15 individual samples using online two-dimensional low-flow liquid chromatography-tandem mass spectrometry (LC-MS/MS).
2. Over 400 proteins were quantified across the samples, with 237 proteins showing at least a two-fold change in abundance between samples.
3. Principal component analysis separated the samples obtained from one source, indicating the impact sample preparation can have on protein profiles. Deeper profiling of individual samples is needed for precision medicine applications like biomarker discovery.
Translational Genomics and Prostate Cancer: Meet the NGS Experts Series Part 2QIAGEN
Advanced prostate cancer is highly heterogeneous but this inter-patient heterogeneity has until recently not been understood. We have through an international research effort dissected the molecular landscape of advanced castration resistant prostate, elucidating key molecular targets in this group of diseases. We have also shown that PARP inhibitors have antitumor activity against a significant proportion of these cancers, mainly in men whose cancers harbor DNA repair defects.
Perioperative n acetylcysteine for patients undergoing living donor orthotopichanaa
This study evaluated the efficacy of perioperative intravenous N-acetylcysteine (NAC) in reducing acute kidney injury (AKI) and improving liver graft function in patients undergoing living donor orthotopic liver transplantation. 100 patients undergoing transplantation were randomly assigned to receive either intravenous NAC or saline as control. The results showed NAC decreased the incidence of postoperative AKI, primary graft non-function, and reduced hospital and ICU stay compared to the control group. However, NAC had no effect on the number of ventilator days or mortality.
SCORING AND RISK STRATIFICATION OF ACUTE PANCREATITISArkaprovo Roy
The document discusses various classification systems and severity scoring methods for acute pancreatitis (AP), including the revised Atlanta classification. It recommends early severity stratification within 48 hours using methods like Glasgow score and CRP. The APACHE II score can be used for initial assessment and monitoring of severe cases in order to predict outcomes and guide management, which may include referral to specialist units for organ failure or local complications. Accurate classification and scoring is important for individualizing treatment protocols based on severity.
A short history of glucose control in critical illnessSteve Mathieu
- The document discusses the history of glucose control in critical care, from early studies identifying the role of the pancreas and islets of Langerhans in diabetes, to the discovery and development of insulin as a treatment.
- Two landmark studies, the Leuven 1 and Leuven 2 trials, found that intensive insulin therapy to tightly control blood glucose levels reduced mortality in critically ill patients compared to conventional treatment. However, subsequent larger trials failed to replicate these benefits and found an increased risk of hypoglycemia.
- The validity and generalizability of the Leuven trials have been questioned due to aspects of their methodology and patient populations. Overall, the topic of optimal glucose management in critical illness remains controversial
This document summarizes the laboratory testing and work done by the Department of Laboratory Medicine at J.P.N.A.T.C., A.I.I.M.S., New Delhi from January 2011 to December 2011. It provides statistics on the number of tests and samples processed in areas such as haematology, coagulation, biochemistry, microbiology, hospital infection control and histopathology. It also discusses antimicrobial resistance patterns, compliance to infection prevention practices, environmental surveillance, teaching and research activities undertaken, and awards received by the department.
Non Invasive Biomarkers in NASH (non-alcoholic steatohepatitis) Webinar SlidesCovance
This document discusses non-invasive biomarkers for non-alcoholic steatohepatitis (NASH). It provides an agenda for a meeting on this topic, including discussions of the need for non-invasive biomarkers in NASH, current and future methods for non-invasive diagnosis of NASH and liver fibrosis, leveraging genomics in biomarker development, and the strategic use of non-invasive testing in NASH drug development and clinical practice. Specific non-invasive tests are discussed, such as blood-based biomarkers, imaging techniques, and genomic and proteomic profiling methods for assessing liver fat, inflammation, fibrosis and other aspects of NASH.
Target Validation Academy Of Medical Sciences 1 Dec 2006Mike Romanos
An overview of the issues and approaches in selecting the best targets for drug discovery and validating them. Given at the Drug Discovery Forum held at the Royal Society, London and organised by the Academy of Medical Sciences
Non biopsy diagnosis of acute rejection of Renal allograftBakshish Singh
This document discusses non-invasive methods for diagnosing acute rejection in renal transplant patients. Currently, graft biopsy is the gold standard but it is invasive and detects rejection at a late stage. The presentation evaluates various potential biomarkers being studied through genomics, proteomics, and metabolomics approaches. Several individual studies are highlighted that found biomarkers like urinary MCP-1, VEGF, cytokines, and certain metabolites that showed potential for detecting early acute rejection non-invasively. Magnetic resonance imaging is also discussed as a non-invasive imaging technique being researched. In summary, the ideal non-invasive biomarker has yet to be identified but a combination of markers may provide a more realistic approach for different clinical scenarios.
Bioanalytical method development and validation .Shubham Bora
1) A bioanalytical method was developed and validated for the quantification of levodopa and carbidopa in rat plasma using LC-MS/MS. Derivatization and ion-pairing chromatography were used to improve the chromatographic retention of the polar analytes.
2) The method was fully validated as per FDA guidelines and demonstrated selectivity, linearity, accuracy, precision, recovery, matrix effects and stability in accordance with acceptance criteria.
3) The validated method was successfully applied to support toxicokinetic studies of levodopa and carbidopa in rats.
Poster demonstrating the results from the development/verification project for the quantitation of all- trans retinol and alpha tocopherol in human serum.
This document discusses biomarkers for assessing immune function throughout the drug development process. It describes how various techniques can be used to identify, validate, and qualify biomarkers. These include flow cytometry to analyze cell populations and activation markers, Luminex to measure cytokine levels, and gene expression profiling using NanoString. Whole blood stimulation assays are discussed as a way to assess target engagement and immune responses ex vivo. The importance of assay validation and understanding sources of variation are also covered. Biomarkers can provide insights into mechanisms of action, safety, and efficacy to support clinical development.
DEVELOPMENT AND VALIDATION OF SPECTROSCOPIC AND CHROMATOGRAPHIC METHOD FOR D...Dipak Reddy
A simple, precise & accurate UV spectroscopy & HPLC method was developed & validated as per ICH guideline.
In UV spectroscopy 0.1HCL used as diluent & in HPLC Methanol :ortho phosphoric acid (40:60%v/v) used.
Thus based on validation data it is concluded that present method is economical, less time consuming, precise , accurate for estimation of Pioglitazone in bulk drug & formulations.
This method can be used to determine the purity of the drug available from various sources by detecting the related impurities.
Using Targeted Resequencing Microarrays for Simultaneous Definitive Detection...Agnieszka Caruso
The document describes how targeted resequencing microarray technology can be used to simultaneously detect and identify multiple respiratory pathogens from a single sample in 3 sentences or less:
Targeted resequencing microarray (RPM) technology uses thousands of DNA probes to interrogate sequences from respiratory pathogens and can detect genetic variants to identify known pathogens and potentially novel pathogens from a single sample, representing an improvement over traditional techniques that can only detect one pathogen at a time.
This document describes a study using ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC/QTOF) for multi-residue screening of veterinary drugs. Researchers developed a method to separate 70 veterinary drug standards using UPLC and detected the drugs using QTOF MS. The method was then tested on pork muscle tissue extracts spiked with veterinary drugs. The study aimed to develop a single extraction and detection method for screening banned and regulated veterinary drugs in various animal tissues and fluids.
Grant Moore
Section Head Toxicology
Canterbury Health Labs,
PO Box 151, Christchurch 8014
grant.moore@cdhb.govt.nz
(P27, Thursday 27, Ilott Theatre, 2.00)
Este documento resume la fenilcetonuria (PKU), un trastorno genético del metabolismo causado por la deficiencia de la enzima fenilalanina hidroxilasa. Describe la bioquímica, genética y manifestaciones clínicas de la PKU, así como los métodos de detección y diagnóstico como el método de Guthrie y técnicas moleculares como la secuenciación del gen PAH y análisis de MLPA.
For the IB DP Biology course, core unit: Genetics. To get the file, please make a donation to one of my preferred charities via Biology4Good. Find out more here: http://sciencevideos.wordpress.com/about/biology4good/
The EMIT technique is an immunoassay method used to screen blood and urine samples for therapeutic drugs and abused substances. It works by using antibodies linked to enzymes that react with the target substance in a sample. This reaction is then measured spectrophotometrically. EMIT assays are homogeneous, requiring no separation steps, and provide reliable quantitative results. While less sensitive than other immunoassays like ELISA, EMIT is widely used in clinical settings due to its low cost, simplicity, and long shelf life of reagents.
Using LC-MS/MS and Advanced Software Tools to Screen for unknown and Non-targ...AB SCIEX India
LC-MS/MS is a powerful tool for the analysis of Pharmaceuticals and Personal Care Products in environmental samples. The combination of high resolution LC separation and high sensitivity MS/MS is the most powerful tool to screen and quantify targeted compounds.
El documento presenta una introducción al tema de la administración de la cultura y el cambio organizacional. Explica que existen dos fuerzas que gobiernan una organización: la gestión operativa (rutina) y la gestión estratégica (cambio). También describe las siete etapas del cambio organizacional, que incluyen el cambio personal, la asociación, el diseño del cambio, la gestión del apoyo político, la implementación, el afianzamiento y el monitoreo. Finalmente, presenta algunas referencias bibliográficas clave
1. The document describes a study analyzing serum protein profiles from 15 individual samples using online two-dimensional low-flow liquid chromatography-tandem mass spectrometry (LC-MS/MS).
2. Over 400 proteins were quantified across the samples, with 237 proteins showing at least a two-fold change in abundance between samples.
3. Principal component analysis separated the samples obtained from one source, indicating the impact sample preparation can have on protein profiles. Deeper profiling of individual samples is needed for precision medicine applications like biomarker discovery.
Translational Genomics and Prostate Cancer: Meet the NGS Experts Series Part 2QIAGEN
Advanced prostate cancer is highly heterogeneous but this inter-patient heterogeneity has until recently not been understood. We have through an international research effort dissected the molecular landscape of advanced castration resistant prostate, elucidating key molecular targets in this group of diseases. We have also shown that PARP inhibitors have antitumor activity against a significant proportion of these cancers, mainly in men whose cancers harbor DNA repair defects.
Perioperative n acetylcysteine for patients undergoing living donor orthotopichanaa
This study evaluated the efficacy of perioperative intravenous N-acetylcysteine (NAC) in reducing acute kidney injury (AKI) and improving liver graft function in patients undergoing living donor orthotopic liver transplantation. 100 patients undergoing transplantation were randomly assigned to receive either intravenous NAC or saline as control. The results showed NAC decreased the incidence of postoperative AKI, primary graft non-function, and reduced hospital and ICU stay compared to the control group. However, NAC had no effect on the number of ventilator days or mortality.
SCORING AND RISK STRATIFICATION OF ACUTE PANCREATITISArkaprovo Roy
The document discusses various classification systems and severity scoring methods for acute pancreatitis (AP), including the revised Atlanta classification. It recommends early severity stratification within 48 hours using methods like Glasgow score and CRP. The APACHE II score can be used for initial assessment and monitoring of severe cases in order to predict outcomes and guide management, which may include referral to specialist units for organ failure or local complications. Accurate classification and scoring is important for individualizing treatment protocols based on severity.
A short history of glucose control in critical illnessSteve Mathieu
- The document discusses the history of glucose control in critical care, from early studies identifying the role of the pancreas and islets of Langerhans in diabetes, to the discovery and development of insulin as a treatment.
- Two landmark studies, the Leuven 1 and Leuven 2 trials, found that intensive insulin therapy to tightly control blood glucose levels reduced mortality in critically ill patients compared to conventional treatment. However, subsequent larger trials failed to replicate these benefits and found an increased risk of hypoglycemia.
- The validity and generalizability of the Leuven trials have been questioned due to aspects of their methodology and patient populations. Overall, the topic of optimal glucose management in critical illness remains controversial
This document summarizes the laboratory testing and work done by the Department of Laboratory Medicine at J.P.N.A.T.C., A.I.I.M.S., New Delhi from January 2011 to December 2011. It provides statistics on the number of tests and samples processed in areas such as haematology, coagulation, biochemistry, microbiology, hospital infection control and histopathology. It also discusses antimicrobial resistance patterns, compliance to infection prevention practices, environmental surveillance, teaching and research activities undertaken, and awards received by the department.
Non Invasive Biomarkers in NASH (non-alcoholic steatohepatitis) Webinar SlidesCovance
This document discusses non-invasive biomarkers for non-alcoholic steatohepatitis (NASH). It provides an agenda for a meeting on this topic, including discussions of the need for non-invasive biomarkers in NASH, current and future methods for non-invasive diagnosis of NASH and liver fibrosis, leveraging genomics in biomarker development, and the strategic use of non-invasive testing in NASH drug development and clinical practice. Specific non-invasive tests are discussed, such as blood-based biomarkers, imaging techniques, and genomic and proteomic profiling methods for assessing liver fat, inflammation, fibrosis and other aspects of NASH.
Target Validation Academy Of Medical Sciences 1 Dec 2006Mike Romanos
An overview of the issues and approaches in selecting the best targets for drug discovery and validating them. Given at the Drug Discovery Forum held at the Royal Society, London and organised by the Academy of Medical Sciences
Non biopsy diagnosis of acute rejection of Renal allograftBakshish Singh
This document discusses non-invasive methods for diagnosing acute rejection in renal transplant patients. Currently, graft biopsy is the gold standard but it is invasive and detects rejection at a late stage. The presentation evaluates various potential biomarkers being studied through genomics, proteomics, and metabolomics approaches. Several individual studies are highlighted that found biomarkers like urinary MCP-1, VEGF, cytokines, and certain metabolites that showed potential for detecting early acute rejection non-invasively. Magnetic resonance imaging is also discussed as a non-invasive imaging technique being researched. In summary, the ideal non-invasive biomarker has yet to be identified but a combination of markers may provide a more realistic approach for different clinical scenarios.
Bioanalytical method development and validation .Shubham Bora
1) A bioanalytical method was developed and validated for the quantification of levodopa and carbidopa in rat plasma using LC-MS/MS. Derivatization and ion-pairing chromatography were used to improve the chromatographic retention of the polar analytes.
2) The method was fully validated as per FDA guidelines and demonstrated selectivity, linearity, accuracy, precision, recovery, matrix effects and stability in accordance with acceptance criteria.
3) The validated method was successfully applied to support toxicokinetic studies of levodopa and carbidopa in rats.
Poster demonstrating the results from the development/verification project for the quantitation of all- trans retinol and alpha tocopherol in human serum.
This document discusses biomarkers for assessing immune function throughout the drug development process. It describes how various techniques can be used to identify, validate, and qualify biomarkers. These include flow cytometry to analyze cell populations and activation markers, Luminex to measure cytokine levels, and gene expression profiling using NanoString. Whole blood stimulation assays are discussed as a way to assess target engagement and immune responses ex vivo. The importance of assay validation and understanding sources of variation are also covered. Biomarkers can provide insights into mechanisms of action, safety, and efficacy to support clinical development.
DEVELOPMENT AND VALIDATION OF SPECTROSCOPIC AND CHROMATOGRAPHIC METHOD FOR D...Dipak Reddy
A simple, precise & accurate UV spectroscopy & HPLC method was developed & validated as per ICH guideline.
In UV spectroscopy 0.1HCL used as diluent & in HPLC Methanol :ortho phosphoric acid (40:60%v/v) used.
Thus based on validation data it is concluded that present method is economical, less time consuming, precise , accurate for estimation of Pioglitazone in bulk drug & formulations.
This method can be used to determine the purity of the drug available from various sources by detecting the related impurities.
The document discusses hepatitis C virus (HCV) resistance to different antiviral treatments. It finds that HCV resistance to interferon-alpha therapy exists but accounts for only a small portion of treatment failures. Resistance to ribavirin is unclear as its mechanism of action is not fully understood. Direct acting antivirals in development target various stages of the HCV life cycle and resistance can emerge through amino acid substitutions, but combination therapy aims to prevent resistance.
Biomarkers – in Toxicology and Clinical Researchsuruchi71088
This document presents information about biomarkers presented by Ms. Suruchi Ramkumar Sharma at the M.E.T Institute of Pharmacy under the guidance of Dr. Vaishali Dixit. It defines biomarkers as characteristics that can objectively measure normal biological, pathogenic, or pharmacological responses. Examples provided include serum LDL for cholesterol and blood pressure for stroke. The document discusses disease-related biomarkers, drug-related biomarkers, and how biomarkers can be classified based on their characteristics. It explores the discovery of molecular biomarkers and various assay techniques used in toxicology and clinical trials. Various biomarkers are mentioned that can help with early diagnosis, drug development, and determining toxic effects.
Dr. Robert Langer - Simposio Internacional 'Terapias oncológicas avanzadas'Fundación Ramón Areces
Los días 15 y 16 de octubre de 2014, la Fundación Ramón Areces y la Real Academia Nacional de Farmacia, en colaboración con la Fundación de la Innovación Bankinter, reunieron en Madrid a algunos de los mayores expertos mundiales en nuevas terapias contra el cáncer. El Simposio Internacional, coordinado por la profesora y académica María José Alonso, analizó el momento actual de la lucha contra esta enfermedad. También fue un punto de encuentro para científicos de los más innovadores institutos de investigación en oncología, quienes debatieron sobre tres grandes temas: la Medicina Personalizada contra el cáncer, los nanomedicamentos en la terapia del cáncer y las terapias basadas en la inmunomodulación.
This document describes the development and validation of a quantitative method for determining penbutolol and its metabolite 4-hydroxy penbutolol in human plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The method involves solid phase extraction of the analytes from plasma followed by separation using liquid chromatography with mass spectrometric detection in multiple reaction monitoring mode. The method was validated according to FDA guidelines and showed good linearity, accuracy, precision, recovery, selectivity and stability. The developed and validated LC-MS/MS method was found to be suitable for pharmacokinetic studies of penbutolol in human volunteers.
Gastrocon 2016 - Dr S.K Sinha's observation on Acute PancreatitisApolloGleaneagls
The patient is a 40-year old male alcohol abuser presenting with abdominal pain, vomiting, and distension. Investigations show elevated lipase and CT scan shows bulky pancreas and gallbladder sludge. The patient meets criteria for acute pancreatitis and CT severity index of 8/10 suggests severe disease. While antibiotics are not routinely recommended, they may be considered for infected necrosis seen on imaging or clinical deterioration. Aggressive fluid resuscitation and pain management with tramadol are the primary treatments, with nutritional support and monitoring for organ dysfunction.
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2014 lecture next generation metabolic screening - Marrakech
1. Next Generation Metabolic Screening
11th Middle East Metabolic
Group meeting - MEMG
22-25 October 2014,
Marrakech, Morocco
Prof. dr. Ron Wevers,
Department of Laboratory Medicine,
Radboudumc, Nijmegen, The Netherlands
2. 1997
There is no single analytical platform that can
measure all metabolites
The metabolome
3. NMR based metabolomics
BODY FLUID NMR SPECTROSCOPY IN INBORN ERRORS OF METABOLISM
Body fluid NMR
• Diagnosis of 106 IEM (1D
and 2D COSY)
• 1H resonances from 158
metabolites involved IEM
• Seven novel inborn errors
could be defined
Limitation
Sensitivity: low micromolar
range
4. Molecular complexity in Life Science
Number of Dynamic
molecular entities range__
Genomics 104 103
Proteomics 106 1010+
Metabolomics 104 106+
Typical eukaryotic organisms contain between 4000 and 50000
metabolites (Kegg: 16896; HMDB 2012: 7900; HMDB 3.6: 41808)
6. Metabolomics – analysis of “all” metabolites
Human plasma, CSF
(urine)
Controls vs. patient
Agilent QTOF MS-data
- Reverse phase liquid chromatography
- Positive and negative mode
- Features
• Accurate mass (165.07898)
• Retention time
• Intensity
(New) biomarkers for diseases
XCMS
Alignment
Peak comparison
> 10,000 Features
8. Accuracy of Q-tof analysis
Deviation from actual mass for 19 metabolites
(Mass range 90.0552 – 428.3737 Dalton)
mass number of
metabolites
0.0000 2
0.0001 10
0.0002 4
0.0003 2
0.0004 1
19
9. Q-tof sensitivity
Sensitivity
Q-TOF
low nanomolar range
NMR
low micromolar range
Factor 1000 more
sensitive than
NMR!
Pipecolic acid
S/N=20
500 nmol/L
50 nmol/L
5 nmol/L
no addition
Pipecolic acid added to urine (diluted 50x)
10. Validation Next Generation Metabolic Screening (NGMS)
• Comparison signal intensity with
concentratios classical assays
• Mass accuracy on QTOF:
95%: ΔM < 0,0003 Da
(range: 90-425 Da; n=19)
• Sensitivity of UHPLC-QTOF MS assay in low nM range!
(~1000 fold more sensitive than NMR)
• Intra: CV in RT: <0.5%; CV in signal intensity: <15%
Inter: CV in RT: <1%; CV in signal intensity: <25-30%
• Clinical validation: diagnosis established in
16 individual patients with different IEMs
Standard operation procedure for plasma and CSF samples introduced in patient care in 2014
11. Where is/are the biomarker(s)?
10,480
features
10,480 Features (incl. adducts etc)
Mass, Retention time, Intensity
12. INPUT
Endogenous metabolites
Diet derived
Intestinal flora input
Medication
ANALYTICAL
Original small molecules
Adduct information (Na+, K+, NH4
+)
In source fragments
13C variants
How to explain 10.000 features in plasma?
13. Which features are the IEM biomarkers
10,480 features
Experiment
Alignment
Peak Comparison
Raw data
Corrected t-test
Intensity/P Ranking
Dataanalyses
Identification T20
Verification
DataPreprocessing
&Pretreatment
Data
interpretation
19. Targeted analysis of markers specific for xanthinuria type II
CONCLUSION:
Xanthinuria type II (diagnosed in urine sample without allopurinol loading)
Hydantoin 5-propionate Pyridoxal
20. The clinical validation
Amino acid
disorders
Fatty acid
oxidation
Organic acidurias Miscellaneous
PKU MCAD MSUD Xanthinuria II
Hyperprolinemia II VLCAD HMG-CoA lyase Amino acylase I
Hyperlysinemia MCC Antiquitin (ATQ) def.
MAT I/III IVA Beta-ketothiolase
Alcaptonuria Dimethylglycinuria
Ureidopropionase
Diagnosis on plasma samples
Current status: 23 inborn errors
23. Nijmegen four day march
The bridge between the exome and the metabolome
The Nijmegen approach
24. Conclusions
• Next Generation Metabolic Screening (NGMS) introduced
in diagnostics of the individual patient
• NGMS will change the metabolic laboratory
• NGMS bridges whole exome sequencing and metabolic
diagnostics: integrative biology in a functional genomics
setting
• The technique we have developed is also of interest outside
the field of inborn errors
25. METABOLIC SCREENING
The individual patient suspected for an IEM
WES and NMGS in parallel together with dept. Genetics Radboudumc
26. C.D.G Huigen
E. van der Heeft
U.F.H. Engelke
R.A. Wevers
L.A.J. Kluijtmans
Nijmegen metabolomics
C. van Karnebeek,
Vancouver
J. Engel
S. Wortmann-Hagemann
30. Challenge - 3
The big data
• Pathway analysis
• How to integrate Whole Exome Sequencing data with the
metabolomics data?
METABOLIC SCREENING
IN THE INDIVIDUAL PATIENT
DNA SEQUENCING
IN THE INDIVIDUAL PATIENT
Integrating
software
The next step
The coding data of the human
genes
10,480