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groups in herbal medicine
TwHF and sulfasalazine
clinical responses in Herbal
physical global score, pain score, tender joint count
lab réponses in herbal
- serum levels of ESR (erthyrocyte sedimentation rate)
American College of Rheumatology Criteria (ACR20)
20% of population showed improvement in pain and physical scores
further studies for herbal
- isolate effects from prednisone
- extraction of TwHF
which are paranodal and nodal proteins
- paranode: contactin-1 and neurofascin 155
- node: neurofascin 186
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
what was the question in contacting and NF study?
are contacting and NR targets of auto-antibodies in MMN?
measures concentration of antibody in solution using color change
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.
what were the ways in which they measured the role of contactin and NF role in MMN?
- cell binding assay
- binding to murine teased fibers
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
phase 2 how many people
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
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)
what does PXT3003 consists of?
- skeletal muscle relaxant
- treat spasticity (muscles are always contracted)
opiate receptor antagonist (interferes with and inhibits the action of another), treat opiate addiction
metabolite in polyol pathway from glucose to fructose, treats intestinal disorders, reduces inflammation
what are the four groups in CMT1A study?
placebo, low dose, intermediate dose, high dose
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
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
diffusion of water in a tensor (direction vector) through an axon measured via imaging (MRI)
what are the sizes of fiber in CNS vs. PNS?
- CNS (1-2 um)
- PNS (5-20 um)
- paths of many protons summed into a scalar value that describes the groups' elliptic diffusion path
- (lower more disease 0-1)
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
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)
for DTI what happens with damages to axonal structure?
decrease barriers imposing a diffusion tensor
future studies for DTI
- increase power
- more sample size
- correlate longitudinal individual axonal changes with FA
- 117 kDa protein associated with integrin mediated cell matrix adhesion and cadherin-mediated cell cell junctions
- focal adhesion protein in S.C
difference between active and inactive form of vinculin
- active localizes to focal adhesions at the membrane
- inactive form is cytoplasmic
what mediates axon pathfinding through interactions with the extracellular matrix?
nerve growth cones
what was found in previous studies to be responsible for chemorepulsion
MAG (myelin associated glycoprotein) stimulates Ca2+ signals in growth cone
where was the proteins where patient antibodies could react with come from?
pig cauda equina (spinal nerves)
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
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
inserting human vinculin gene into E.coli and producing the protein.
immunoglobulin G, the most common antibody found in human sera
transmembrane receptors that are the bridges for cell-cell and cell-extracellular matrix (ECM) interactions
what were the MAG studies done in?
Xenopus spinal neurons
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
where did Sarah sing in?
second soprano solo in Gregorio Allegri's Miserere