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groups in herbal medicine
TwHF and sulfasalazine
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clinical responses in Herbal
physical global score, pain score, tender joint count
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lab réponses in herbal
- serum levels of ESR (erthyrocyte sedimentation rate)
- CRP
- interleukin
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American College of Rheumatology Criteria (ACR20)
20% of population showed improvement in pain and physical scores
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further studies for herbal
- isolate effects from prednisone
- extraction of TwHF
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which are paranodal and nodal proteins
- paranode: contactin-1 and neurofascin 155
- node: neurofascin 186
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multifocal motor neuropathy
- affects peripheral motor nerves
- multifocal muscle weakness and conduction block
- auto-antibodies against neurofascin 186 and gilomedin
- responds to IVIg
- IgM auto-antibodies against gangliosides GM1 are present in 50% of the patients
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what was the question in contacting and NF study?
are contacting and NR targets of auto-antibodies in MMN?
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ELISA
measures concentration of antibody in solution using color change
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what was a control used in detecting contacting and NF autoantibodies?
- antibodies to contactin, NR 155/186 showed good binding to transfected cells
- no detection of binding in patient's or control's sera.
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what were the ways in which they measured the role of contactin and NF role in MMN?
- ELISA
- cell binding assay
- binding to murine teased fibers
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binding of murine teased fibers
- patient's sera did not bind to nodal or paranodel region of murine teased fibers or anti-NF 155-186
- clear detection in CIDP sera
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phase 2 how many people
100-300 people
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charcot marie tooth type 1A how many types total, what kind of disease is it, how many percentage of people have it
- rare inherited peripheral neuropathy
- caused by autosomal dominant duplication of gene on chromosome 17 (PMP22 protein)
- 5 types
- 70-80% of CMT diseases
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what does duplication of PMP22 mean?
- abnormal S.C. myelination
- affects structure and function, hence axonal loss and muscle wasting
- weakness in feet and lower legs (foot drop, high foot arch)
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what does PXT3003 consists of?
- baclofen
- naltrexone
- sorbitol
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baclofen
- skeletal muscle relaxant
- treat spasticity (muscles are always contracted)
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naltrexone
opiate receptor antagonist (interferes with and inhibits the action of another), treat opiate addiction
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sorbitol
metabolite in polyol pathway from glucose to fructose, treats intestinal disorders, reduces inflammation
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what are the four groups in CMT1A study?
placebo, low dose, intermediate dose, high dose
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measurements for improvement in CMT1A
- CMTNS (36 point scale based on 9 parameters)
- ONLS (quality of life)
- functional measures (walk test, finger dexterity)
- Electrophysiological parameters
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limitations of EMG
- can only examine distal nerves
- dependent on target innervation (if your target cannot elicit a response, the extent of distal regeneration cannot be evaluated
- variability in interpretation
- longitudinal biopsy not practical and serial
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DTI
diffusion of water in a tensor (direction vector) through an axon measured via imaging (MRI)
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what are the sizes of fiber in CNS vs. PNS?
- CNS (1-2 um)
- PNS (5-20 um)
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fraction anisotropy
- paths of many protons summed into a scalar value that describes the groups' elliptic diffusion path
- (lower more disease 0-1)
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what was the purpose of DTI experiment?
to see if DTI can distinguish between healthy and diseased individuals and how FA correlates with traditional evaluations of peripheral neuropathy
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conclusion for DTI
- mean FA provides a valid noninvasive assessment of axon integrity even in proximal regions
- -correlates with EMG and INCAT (correlates with axonal changes)
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for DTI what happens with damages to axonal structure?
decrease barriers imposing a diffusion tensor
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future studies for DTI
- increase power
- more sample size
- correlate longitudinal individual axonal changes with FA
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vinculin
- 117 kDa protein associated with integrin mediated cell matrix adhesion and cadherin-mediated cell cell junctions
- focal adhesion protein in S.C
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difference between active and inactive form of vinculin
- active localizes to focal adhesions at the membrane
- inactive form is cytoplasmic
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what mediates axon pathfinding through interactions with the extracellular matrix?
nerve growth cones
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what was found in previous studies to be responsible for chemorepulsion
MAG (myelin associated glycoprotein) stimulates Ca2+ signals in growth cone
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where was the proteins where patient antibodies could react with come from?
pig cauda equina (spinal nerves)
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how did they detect vinculin, potential auto-antigen?
- membrane with proteins from pig caudal equine
- membrane reacted with serum from CIDP patients and controls
- immunoreactive protein bands identified via mass spec
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how was it verified that vinculin was in fact in CIDP patient's serum?
human recombinant vinculin subjected to western blot and reacted with sera from patients
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recombinant DNA
inserting human vinculin gene into E.coli and producing the protein.
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igG
immunoglobulin G, the most common antibody found in human sera
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integrin protein
transmembrane receptors that are the bridges for cell-cell and cell-extracellular matrix (ECM) interactions
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what were the MAG studies done in?
Xenopus spinal neurons
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A focal MAG gradient induced
polarized endocytosis and concomitant asymmetric loss of beta(1)-integrin and vinculin-containing adhesions on the repellent side during repulsive turning
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where did Sarah sing in?
second soprano solo in Gregorio Allegri's Miserere
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