Inflammation and wound healing

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Inflammation and wound healing
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Inflammatory response
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Macrophage-monocyte system

• Formerly reticuloendothelial system (RES)

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Diapedesis
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Chemotaxis
Note not OUR definition of diapedesis!
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Opsonization
Once attached to the phagocyte by way of IgG
and/or C3b, the microbe can be engulfed more
efficiently and placed in a phagosome
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Leukocyte emigration
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Microcirculatory changes in inflammation
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Rouleaux formation
The RBC's here have stacked together in long
chains. This is known as "rouleaux formation" and
it happens with increased serum proteins,
particularly fibrinogen and globulins. Such long
chains of RBC's sediment more readily. This is
the mechanism for the sedimentation rate, which
increases non-specifically with inflammation and
increased "acute phase" serum proteins.
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Triple response and dual probe thermography
Neurocalometer (above), nervoscope (below)
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Is Nervoscope reliable?
C4-T2 Kappa.03
as instrument was used in repeat sequence,
findings became more stable
T4-T8 Kappa..57 (1st observation) Kappa.65
(2nd observation)
L2-L5 Kappa could not be computed, too many
positives for each examiner
It must be noted that this type of concordance
is regional and not segmentally specific. (!)
Plaugher G, Lopes MA, Melch PE, Cremata EE. The
inter- and intraexaminer reliability of a
paraspinal skin temperature differential
instrument. Journal of Manipulative and
Physiological Therapeutics 199114(6)361-367.
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Field study in mis-citation

• One study of the Gonstead system by Plaugher et
  al showed fair to good interexaminer reliability
  for the Nervoscope . . . as it is used to
  determine segmental side-to-side temperature
  differences (breaks)

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TyTron C-3000
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Mediators of inflammation
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Inflammatory systems
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Arachadonic acid pathways
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Selective Cox-II PRO
Pronai, L., I. Hritz, et al. (2003).
COX-2-selective inhibitors (COXIBs)
gastrointestinal safety. International journal
of immunopathology and pharmacology 16(2 Suppl)
23-30. COX-2 selective inhibitors (coxibs) have
been developed with the primary aim to
reduce/avoid gastrointestinal (GI) toxicity
observed during conventional (non-selective)
non-steroidal anti-inflammatory (NSAID) therapy.
Coxibs have clearly and convincingly been shown
to be superior to conventional NSAIDs with
significantly less GI side effects. When hard
endpoints such as perforation, obstruction, and
serious bleeding considered, coxibs reduce the
risk by approximately 50 percent. Although
selective COX-2 inhibition seems not to be enough
for complete elimination of GI toxicity, coxibs
posses no more GI toxicity than placebo in
prospective clinical studies and further increase
in COX-2 selectivity does not reduce GI toxicity.
For the initial aim developed, thus coxibs
fulfilled their promise and will soon replace
conventional NSAIDs.
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Selective Cox-II inhibitors ANTI
Gomez-Cerezo, J., R. Lubomirov-Hristov, et al.
(2003). Outcome trials of COX-2 selective
inhibitors global safety evaluation does not
promise benefits. European journal of clinical
pharmacology 59(2) 169-75. BACKGROUND
Gastrointestinal toxicity is the most frequent
adverse effect associated with nonsteroidal
anti-inflammatory drug use. The most clinically
relevant side effects of this toxicity are ulcer
complications, including perforation,
obstruction, or bleeding. Selective
cyclooxygenase (COX-2) inhibitors (coxibs) have
been proposed as a safer alternative to
traditional, nonsteroidal anti-inflammatory drugs
and they are currently widely used in clinical
practice. The aim of this review was to analyze
the available evidence and then critically
evaluate the outcome trials supporting the use of
coxibs in terms of their clinical
gastrointestinal benefits and global safety.
METHODS All published clinical trials on
selective COX-2 inhibitors were identified by
searching Medline, the World Wide Web (WWW), and
abstracts in Congress proceedings. From these, we
selected randomized trials that clinically
evaluated relevant safety outcome measures.
Papers only describing endoscopic evaluation were
excluded. RESULTS Our search yielded three
outcome trials and two pooled safety analyses.
The outcome studies supporting the
gastrointestinal and global safety of coxibs were
found to be biased in their design, analysis, and
dissemination, and interpretation of a clinical
benefit. Cost considerations would make the use
of coxibs acceptable only in patients at high
gastrointestinal risk. CONCLUSIONS The
association of the reduced gastroerosive
potential of coxibs with improved meaningful
outcomes is debatable. Bias in the design of the
trials, selection of outcome measures, post-hoc
changes in analysis and the variables used, as
well as flaws in the publication and reporting of
trial results cast serious doubts on the
gastrointestinal and global safety profile of
coxibs. In addition, their high cost and the lack
of clear identification of patients that would
benefit most from treatment means the
effectiveness of these drugs is uncertain at the
moment.
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Vioxx withdrawn
Study Says Drug's Dangers Were Apparent Years
Ago Merck and federal officials should have
withdrawn the painkiller Vioxx from the market as
early as 2000 because studies of the drug had
clearly shown that it doubled the risk of heart
attacks among users, according to a study
released yesterday by The Lancet, a British
medical journal. Authors of the study pooled data
from 25,273 patients who participated in 18
clinical trials conducted before 2001. They found
that patients given Vioxx had 2.3 times the risk
of heart attacks as those given placebos or other
pain medications. Merck withdrew Vioxx on Sept.
30 of this year after a company-sponsored trial
found a doubling of the risks for heart attack or
stroke among those who took the medicine for 18
months or more.
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Chronic vs. acute inflammation
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Epithelioid granulomas
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Granuloma typesand examples
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Types of granulomatous chronic inflammation

• Epithelioid type, with Langhans type giant cells
• Foreign-body type, with foreign-body type giant
  cells

Crohn's Disease granuloma
Foreign-body giant cell
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Crohns disease
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Syphilis, congenital
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Cat-scratch fever Stellate granuloma
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Cause of epithelioid granulomas
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Healing responses
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Skeletal muscle hyperplasia

• Journal of Applied Physiology, Vol. 81, No. 4,
  pp. 1584-1588, October 1996
• Mechanical overload and skeletal muscle fiber
  hyperplasia a meta-analysis George Kelley
• With use of the meta-analytic approach, the
  purpose of this study was to examine the effects
  of mechanical overload on skeletal muscle fiber
  number in animals. A total of 17 studies yielding
  37 data points and 360 subjects met the initial
  inclusion criteria 1) "basic" research studies
  published in journals, 2) animals (no humans) as
  subjects, 3) control group included, 4) some type
  of mechanical overload (stretch, exercise, or
  compensatory hypertrophy) used to induce changes
  in muscle fiber number, and 5) sufficient data to
  accurately calculate percent changes in muscle
  fiber number. Across all designs and categories,
  statistically significant increases were found
  for muscle fiber number 15.00 19.60 (SD), 95
  confidence interval 8.65-21.53, muscle fiber
  area (31.60 44.30, 95 confidence interval
  16.83-46.37), and muscle mass (90.50 86.50,
  95 confidence interval 61.59-119.34). When
  partitioned according to the fiber-counting
  technique, larger increases in muscle fiber
  number were found by using the histological vs.
  nitric acid digestion method (histological
  20.70, nitric acid digestion 11.10 P
  0.14). Increases in fiber number partitioned
  according to species were greatest among those
  groups that used an avian vs. mammalian model
  (avian 20.95, mammalian 7.97 P 0.07).
  Stretch overload yielded larger increases in
  muscle fiber number than did exercise and
  compensatory hypertrophy (stretch 20.95,
  exercise 11.59, compensatory hypertrophy
  5.44 P 0.06). No significant differences
  between changes in fiber number were found when
  data were partitioned according to type of
  control (intra-animal 15.20, between animal
  13.90 P 0.82) or fiber arrangement of muscle
  (parallel 15.80, pennate 11.60 P 0.61).
  The results of this study suggest that in several
  animal species certain forms of mechanical
  overload increase muscle fiber number.

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Cardiac muscle hyperplasia

• Are adult cardiocytes still able to proliferate?
  (Swynghedauw B.)
• In all mammals including humans, adult
  cardiocytes become post mitotic cells, while
  cardiac non muscle cells still have the capacity
  to proliferate, and cardiac hypertrophy in adults
  is known to be due to cardiocyte hypertrophy and
  non muscle cell hyperplasia. Such a dogma was
  supported by several, rather ancient,
  observations, and has been recently challenged by
  two different groups. Several new paradigms in
  cell biology have modified these views the
  entire determinants of the cell cycle are now
  entirely known apoptosis, and cardiac apoptosis,
  is central in the process of cell division, and
  has a rather complicated significance telomeres
  are specialized DNA-protein structures that
  prevent end-to-end chromosome fusion, and are
  rather characteristic of germ and stem cells,
  these structures are maintained by telomerase.
  Using several markers, including telomerase
  activity, endogenous self-renewing, clonogenic
  and multipotent stem cells were identified in the
  adult myocardium in human, mice and rat. These
  cells are activated during cardiac overload or
  ischemia to produce new cardiocytes. New
  endothelial cells also appeared, and are likely
  to have a circulatory origin. The physiological
  importance of these new cells is debatable at the
  moment. Nevertheless, these findings provide an
  important new basis for cell cardiomyoplasty. It
  is also possible to envisage stimulation of the
  production and activity of these new cells to
  compensate for the lack of substance after
  myocardial infarction.

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Skin healing inflammatory phase
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Skin healingmigratory phase
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Contact inhibition
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Skin healing proliferative phase
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Skin healing maturation phase
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Healing by 1st and 2nd intention
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Wallerian Degeneration
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Neuronal regeneration

• For almost one hundred years, it has been a
  mantra of biology - brain cells do not
  regenerate. In a startling discovery that could
  have profound implications for treating brain
  disorders and injuries, researchers at Princeton
  University have discovered that new neurons are
  continually being added to the brains of adult
  monkeys. The neurons are added to the cerebral
  cortex of the brain.
• The researchers found the formation of new nerve
  cells, a process called neurogenesis, in three
  areas of the cerebral cortex
• Prefrontal region which controls decision making.
  
• Inferior temporal region which plays a role in
  visual recognition.
• Posterior parietal region which plays a role in
  3D representation.

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Rehabilitation considerations