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PDLA a potential new potent topical analgesic: a case report.

Goldberg JS - Local Reg Anesth (2014)

Bottom Line: Lactate has been shown to have many functions within the nervous system including its use as a secondary fuel to sustain neural activity and as a neuromodulator.In the central nervous system, lactate is produced in glial cells and shuttled to neurons to be used mostly as a fuel.Lactate dehydrogenase (LDH)1 is the predominant LDH isoform within neurons and unlike LDH5, it preferentially converts lactate to pyruvate which can be used to produce adenosine triphosphate (ATP).

View Article: PubMed Central - PubMed

Affiliation: Durham Veterans Affairs Medical Center ; Duke University School of Medicine, Durham, NC, USA.

ABSTRACT
Polymer D-lactic acid (PDLA) is a hydrogel that has been shown to sequester L-lactate (lactate). This reaction is rapid, spontaneous, and non-enzymatic. Lactate has been shown to have many functions within the nervous system including its use as a secondary fuel to sustain neural activity and as a neuromodulator. In the central nervous system, lactate is produced in glial cells and shuttled to neurons to be used mostly as a fuel. Lactate dehydrogenase (LDH)1 is the predominant LDH isoform within neurons and unlike LDH5, it preferentially converts lactate to pyruvate which can be used to produce adenosine triphosphate (ATP). Considering that lactate is intimately involved in the sustenance of neural activity, PDLA was applied to an open wound and its effects were examined. The results showed that the application of PDLA induced topical analgesia. This may be the first report to demonstrate that sequestering lactate, a source of energy required to sustain the firing of action potentials in neurons, may produce analgesia.

No MeSH data available.


Related in: MedlinePlus

Enzymatic testing for lactic acid using Accuvin test strips.Notes: Accuvin test strips from Accuvin LLC, St Napa, CA, USA. 180 mg/L lactic acid tested positive for lactic acid. 180mg/L lactic acid and PDLA dimer (N=2) tested negative for lactic acid. 180mg/L lactic acid and PDLA tetramer (N=4) tested positive for lactic acid. 180mg/L lactic acid and PDLA oligomer mixture tested negative for lactic acid.Abbreviation: PDLA, polymer D-lactic acid.
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f1-lra-7-059: Enzymatic testing for lactic acid using Accuvin test strips.Notes: Accuvin test strips from Accuvin LLC, St Napa, CA, USA. 180 mg/L lactic acid tested positive for lactic acid. 180mg/L lactic acid and PDLA dimer (N=2) tested negative for lactic acid. 180mg/L lactic acid and PDLA tetramer (N=4) tested positive for lactic acid. 180mg/L lactic acid and PDLA oligomer mixture tested negative for lactic acid.Abbreviation: PDLA, polymer D-lactic acid.

Mentions: Pandey and Aswath first described the synthesis of poly-L-lactic acid (PLLA) from L-lactic acid in a home microwave.7 The method to produce PDLA from D-lactic acid follows the same procedures as those used to produce PLLA from L-lactic acid. Beginning with low power and short time intervals, D-lactic acid was dehydrated and polymerized to form PDLA. D-lactic acid was then microwaved until there was approximately 50% loss of weight secondary to dehydration and esterification. In addition, the PDLA dimer (n=2) and tetramer (n=4) were synthesized at the Duke University Small Molecule Synthesis Facility by Dr David M Gooden and tested for enzymatic activity using Accuvin test strips (Accuvin LLC, St Napa, CA, USA). Fifty microliter aliquots of 180 mg/L lactic acid were incubated with 10 mg of PDLA, PDLA dimer (n=2), and PDLA tetramer (n=4) in three separate vials for 5 minutes at 37°C, and then a 20 μL aliquot from each vial was applied to each test strip (Figure 1).


PDLA a potential new potent topical analgesic: a case report.

Goldberg JS - Local Reg Anesth (2014)

Enzymatic testing for lactic acid using Accuvin test strips.Notes: Accuvin test strips from Accuvin LLC, St Napa, CA, USA. 180 mg/L lactic acid tested positive for lactic acid. 180mg/L lactic acid and PDLA dimer (N=2) tested negative for lactic acid. 180mg/L lactic acid and PDLA tetramer (N=4) tested positive for lactic acid. 180mg/L lactic acid and PDLA oligomer mixture tested negative for lactic acid.Abbreviation: PDLA, polymer D-lactic acid.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4216030&req=5

f1-lra-7-059: Enzymatic testing for lactic acid using Accuvin test strips.Notes: Accuvin test strips from Accuvin LLC, St Napa, CA, USA. 180 mg/L lactic acid tested positive for lactic acid. 180mg/L lactic acid and PDLA dimer (N=2) tested negative for lactic acid. 180mg/L lactic acid and PDLA tetramer (N=4) tested positive for lactic acid. 180mg/L lactic acid and PDLA oligomer mixture tested negative for lactic acid.Abbreviation: PDLA, polymer D-lactic acid.
Mentions: Pandey and Aswath first described the synthesis of poly-L-lactic acid (PLLA) from L-lactic acid in a home microwave.7 The method to produce PDLA from D-lactic acid follows the same procedures as those used to produce PLLA from L-lactic acid. Beginning with low power and short time intervals, D-lactic acid was dehydrated and polymerized to form PDLA. D-lactic acid was then microwaved until there was approximately 50% loss of weight secondary to dehydration and esterification. In addition, the PDLA dimer (n=2) and tetramer (n=4) were synthesized at the Duke University Small Molecule Synthesis Facility by Dr David M Gooden and tested for enzymatic activity using Accuvin test strips (Accuvin LLC, St Napa, CA, USA). Fifty microliter aliquots of 180 mg/L lactic acid were incubated with 10 mg of PDLA, PDLA dimer (n=2), and PDLA tetramer (n=4) in three separate vials for 5 minutes at 37°C, and then a 20 μL aliquot from each vial was applied to each test strip (Figure 1).

Bottom Line: Lactate has been shown to have many functions within the nervous system including its use as a secondary fuel to sustain neural activity and as a neuromodulator.In the central nervous system, lactate is produced in glial cells and shuttled to neurons to be used mostly as a fuel.Lactate dehydrogenase (LDH)1 is the predominant LDH isoform within neurons and unlike LDH5, it preferentially converts lactate to pyruvate which can be used to produce adenosine triphosphate (ATP).

View Article: PubMed Central - PubMed

Affiliation: Durham Veterans Affairs Medical Center ; Duke University School of Medicine, Durham, NC, USA.

ABSTRACT
Polymer D-lactic acid (PDLA) is a hydrogel that has been shown to sequester L-lactate (lactate). This reaction is rapid, spontaneous, and non-enzymatic. Lactate has been shown to have many functions within the nervous system including its use as a secondary fuel to sustain neural activity and as a neuromodulator. In the central nervous system, lactate is produced in glial cells and shuttled to neurons to be used mostly as a fuel. Lactate dehydrogenase (LDH)1 is the predominant LDH isoform within neurons and unlike LDH5, it preferentially converts lactate to pyruvate which can be used to produce adenosine triphosphate (ATP). Considering that lactate is intimately involved in the sustenance of neural activity, PDLA was applied to an open wound and its effects were examined. The results showed that the application of PDLA induced topical analgesia. This may be the first report to demonstrate that sequestering lactate, a source of energy required to sustain the firing of action potentials in neurons, may produce analgesia.

No MeSH data available.


Related in: MedlinePlus