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The acute inflammatory response in trauma / hemorrhage and traumatic brain injury: current state and emerging prospects.

Namas R, Ghuma A, Hermus L, Zamora R, Okonkwo DO, Billiar TR, Vodovotz Y - Libyan J Med (2009)

Bottom Line: DAMPs perpetuate inflammation through the release of pro-inflammatory cytokines, but may also inhibit anti-inflammatory cytokines.Various animal models of T/HS in mice, rats, pigs, dogs, and non-human primates have been utilized in an attempt to move from bench to bedside.Novel approaches, including those from the field of systems biology, may yield therapeutic breakthroughs in T/HS and TBI in the near future.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery.

ABSTRACT
Traumatic injury/hemorrhagic shock (T/HS) elicits an acute inflammatory response that may result in death. Inflammation describes a coordinated series of molecular, cellular, tissue, organ, and systemic responses that drive the pathology of various diseases including T/HS and traumatic brain injury (TBI). Inflammation is a finely tuned, dynamic, highly-regulated process that is not inherently detrimental, but rather required for immune surveillance, optimal post-injury tissue repair, and regeneration. The inflammatory response is driven by cytokines and chemokines and is partially propagated by damaged tissue-derived products (Damage-associated Molecular Patterns; DAMP's). DAMPs perpetuate inflammation through the release of pro-inflammatory cytokines, but may also inhibit anti-inflammatory cytokines. Various animal models of T/HS in mice, rats, pigs, dogs, and non-human primates have been utilized in an attempt to move from bench to bedside. Novel approaches, including those from the field of systems biology, may yield therapeutic breakthroughs in T/HS and TBI in the near future.

No MeSH data available.


Related in: MedlinePlus

A vision for the future of drug design for T/HS and TBI. The future of rational drug design for T/HS and TBI may involve the use of in silico (computer simulated) that would be based on a mechanistic understanding of the inflammatory response as well as pharmacokinetic and pharmacodynamic principles and used to determine the optimal properties, dosage, timing, and inclusion/exclusion criteria for a given drug candidate's clinical trial. Key aspects of these simulations would be tested iteratively in cell culture experiments and pre-clinical animal models, streamlining the process (and reducing the time and cost) of clinical trial design and implementation.
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Figure 0004: A vision for the future of drug design for T/HS and TBI. The future of rational drug design for T/HS and TBI may involve the use of in silico (computer simulated) that would be based on a mechanistic understanding of the inflammatory response as well as pharmacokinetic and pharmacodynamic principles and used to determine the optimal properties, dosage, timing, and inclusion/exclusion criteria for a given drug candidate's clinical trial. Key aspects of these simulations would be tested iteratively in cell culture experiments and pre-clinical animal models, streamlining the process (and reducing the time and cost) of clinical trial design and implementation.

Mentions: New knowledge derived from a rich set of studies in cells, animals, and humans, combined with computational methods that are rapidly coming into use, promises to revolutionize the way in which clinical studies and clinical practice in T/HS and TBI are being conducted. We are rapidly gaining a new understanding of the complex interactions between injury and the inflammatory response and vice versa, and these new insights will hopefully serve as the foundation for improving patient care worldwide. We may envision a point at which an integrated, rational, and iterative program of simulated clinical trials, in vitro screening for new drug compounds, pre-clinical studies, and human clinical trials will lead to a raft of new therapeutic options for T/HS and TBI (Fig. 4). This new frontier increasingly requires training not only in clinical medicine, but also in quantitative sciences, bioinformatics, and translational science. Moreover, this new approach highlights the need for inter- and multi-disciplinary teams. Finally, emphasis should be placed on applying this new methodology to the difficult, complex clinical scenarios of combined T/HS and TBI, and especially integrating additional factors such as age, gender, genetics, and co-morbidities. Despite the many challenges that remain, we are optimistic that a bright future lies ahead for the care of traumatic injury and critical illness.


The acute inflammatory response in trauma / hemorrhage and traumatic brain injury: current state and emerging prospects.

Namas R, Ghuma A, Hermus L, Zamora R, Okonkwo DO, Billiar TR, Vodovotz Y - Libyan J Med (2009)

A vision for the future of drug design for T/HS and TBI. The future of rational drug design for T/HS and TBI may involve the use of in silico (computer simulated) that would be based on a mechanistic understanding of the inflammatory response as well as pharmacokinetic and pharmacodynamic principles and used to determine the optimal properties, dosage, timing, and inclusion/exclusion criteria for a given drug candidate's clinical trial. Key aspects of these simulations would be tested iteratively in cell culture experiments and pre-clinical animal models, streamlining the process (and reducing the time and cost) of clinical trial design and implementation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3066737&req=5

Figure 0004: A vision for the future of drug design for T/HS and TBI. The future of rational drug design for T/HS and TBI may involve the use of in silico (computer simulated) that would be based on a mechanistic understanding of the inflammatory response as well as pharmacokinetic and pharmacodynamic principles and used to determine the optimal properties, dosage, timing, and inclusion/exclusion criteria for a given drug candidate's clinical trial. Key aspects of these simulations would be tested iteratively in cell culture experiments and pre-clinical animal models, streamlining the process (and reducing the time and cost) of clinical trial design and implementation.
Mentions: New knowledge derived from a rich set of studies in cells, animals, and humans, combined with computational methods that are rapidly coming into use, promises to revolutionize the way in which clinical studies and clinical practice in T/HS and TBI are being conducted. We are rapidly gaining a new understanding of the complex interactions between injury and the inflammatory response and vice versa, and these new insights will hopefully serve as the foundation for improving patient care worldwide. We may envision a point at which an integrated, rational, and iterative program of simulated clinical trials, in vitro screening for new drug compounds, pre-clinical studies, and human clinical trials will lead to a raft of new therapeutic options for T/HS and TBI (Fig. 4). This new frontier increasingly requires training not only in clinical medicine, but also in quantitative sciences, bioinformatics, and translational science. Moreover, this new approach highlights the need for inter- and multi-disciplinary teams. Finally, emphasis should be placed on applying this new methodology to the difficult, complex clinical scenarios of combined T/HS and TBI, and especially integrating additional factors such as age, gender, genetics, and co-morbidities. Despite the many challenges that remain, we are optimistic that a bright future lies ahead for the care of traumatic injury and critical illness.

Bottom Line: DAMPs perpetuate inflammation through the release of pro-inflammatory cytokines, but may also inhibit anti-inflammatory cytokines.Various animal models of T/HS in mice, rats, pigs, dogs, and non-human primates have been utilized in an attempt to move from bench to bedside.Novel approaches, including those from the field of systems biology, may yield therapeutic breakthroughs in T/HS and TBI in the near future.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery.

ABSTRACT
Traumatic injury/hemorrhagic shock (T/HS) elicits an acute inflammatory response that may result in death. Inflammation describes a coordinated series of molecular, cellular, tissue, organ, and systemic responses that drive the pathology of various diseases including T/HS and traumatic brain injury (TBI). Inflammation is a finely tuned, dynamic, highly-regulated process that is not inherently detrimental, but rather required for immune surveillance, optimal post-injury tissue repair, and regeneration. The inflammatory response is driven by cytokines and chemokines and is partially propagated by damaged tissue-derived products (Damage-associated Molecular Patterns; DAMP's). DAMPs perpetuate inflammation through the release of pro-inflammatory cytokines, but may also inhibit anti-inflammatory cytokines. Various animal models of T/HS in mice, rats, pigs, dogs, and non-human primates have been utilized in an attempt to move from bench to bedside. Novel approaches, including those from the field of systems biology, may yield therapeutic breakthroughs in T/HS and TBI in the near future.

No MeSH data available.


Related in: MedlinePlus