Anyone have immature red blood cells indicating a bone marrow issue? I have the right number of red blood cells but they are immature.
On the CBC my MPV is 11.4 H
This is abnormal (out of range) Is this a morgie thingy?
ABSTRACT
Few studies have investigated the ability of dental
resins to induce cellular stress at sublethal
concentrations. Cellular stress, especially in
immune cells such as monocytes, may modulate
the biological response to materials or the host’s
ability to respond to bacterially mediated inflammation.
The current study examined the ability of
sublethal concentrations of 2-hydroxylethylmethacrylate
(HEMA) and triethyleneglycol dimethacrylate
(TEGDMA) to induce heat shock
protein 72 (HSP72) in human monocytes. HEMA
and TEGDMA significantly suppressed heatinduced
HSP72 expression, even at sublethal
levels, but did not induce HSP72 by themselves.
The results of the current study suggest that
components released from dental resin could
modulate the HSP stress response without altering
cellular metabolic activity.
DISCUSSION
The highest concentrations of monomers tested in the present
study approached cytotoxic concentrations when SDH activity
was used as a measure of cellular activity and at 24-hour exposure
times (Yoshii, 1997). With an exposure time of not more than 7
hrs, the resin components were not highly cytotoxic, as measured
by SDH activity (Fig. 1). Although a synergism between the
stress of the material and heat might have been expected to
decrease SDH activity more than with the components alone, this
result was not observed. In most cases, the combination of heat
and resin was similar to heat or resin alone. The exceptions to this
trend were HEMA and TEGDMA at their highest concentrations
(Fig. 1). The lack of effect of heat on SDH activity indicates that
these stress conditions do not alter the energy-producing
capability of these cells. Based on the assumption that
mitochondrial activity is central to the survival of the cell, the
conditions of heat and chemicals applied in the current study
appeared to be below lethal levels.
Exposure to chemicals and heat tends to cause errors in
protein production or production of immature proteins in cells
(Fink, 1999; Yenari et al., 1999). HSP72 has an essential role
in assisting protein folding and refolding and is thought to aid
in preventing or repairing protein errors under conditions of
cellular stress (Polla et al., 1995). HSPs are induced by activation
of heat shock factor in the cytoplasm, which is then transferred
to the nucleus, where it binds heat shock elements, leading
to transcription and synthesis of HSP72 and other HSPs
(Yenari et al., 1999). In the current THP-1 model, heat stress of 43°C for 1 hr induced HSP72 fully at 4 and 6 hrs, with minimal
expression at 2 hrs (Figs. 2, 3). These results agree with those
previously published (Samali and Cotter, 1996; Bachelet et al.,
1998), indicating that the THP-1 monocytes successfully
modeled the heat shock response.
HEMA and TEGDMA significantly suppressed HSP72 even
at apparently sublethal concentrations (Fig. 3). Both resins
affected the monocytes similarly. The sublethal suppression of
other cellular functions, such as cytokine secretion, has been
observed previously with these resins in both the THP-1 and
peripheral blood monocyte model (Rakich et al., 1999; Heil et al.,
2002). The ability of these resins to potently inhibit transcription
at levels that leave cellular metabolism intact may compromise
the ability of the monocytes to respond adequately to heat or other
biological stress in the pulpal tissues. This possibility is supported
by reports that have shown that HEMA and TEGDMA rapidly
traverse dentin (Gerzina and Hume, 1996; Bouillaguet et al.,
1998) and the use of dentin bonding agents directly on exposed
pulp (Costa et al., 2000). These results also support the
importance of measuring more than cellular metabolism to assess
cellular response to restorative material components.
The current study does not address the mechanism by which
HEMA and TEGDMA modulate HSP72 expression. Recent
results show that HEMA and TEGDMA damage the nucleus
(Schweikl et al., 2001) and therefore may alter the activity of
the heat shock element and the levels of HSP. Alternatively,
HEMA and TEGDMA could inhibit phosphorylation of the heat
shock factor, thereby limiting levels of HSP. The role of these
or other mechanisms for HSP72 inhibition cannot be determined
from the current data. Furthermore, it is currently not known if
HEMA and TEGDMA modulate the expression of other HSPs.
HEMA and TEGDMA modulated heat-induced HSP72 at
concentrations from 2.5 to 10 mmol/L for HEMA and 0.25 to 1
mmol/L for TEGDMA. Although these concentrations appear
higher than would be observed clinically, closer analysis
supports their relevance to the clinical situation. Dentinal
adhesive primers are mostly HEMA, and pure HEMA is
approximately 8 mol/L. If used in a direct pulp-capping
procedure, then this concentration is clearly higher than those
used in the current study. However, the primer is more often
used on intact dentin. HEMA has been shown to have a dilution
factor of 1000-5000 times across 0.5 mm of dentin with a 10-
cm H2O back-pressure (Bouillaguet et al., 1996). Thus, the
concentration of HEMA diffusing across the dentin would be
on the order of 1.5-8 mmol/L. These concentrations are similar
to those used in the current study. TEGDMA is a component of
many dentinal bonding resins in approximately 50% concentration.
Since pure TEGDMA has a 3.8 mol/L concentration,
many bonding resins would have approximately a 2 mol/L concentration
of TEGDMA. The dilution of TEGDMA across 0.5
mm of dentin has been shown to be approximately 500 times
(Hanks et al., 1994). Thus, the concentration of TEGDMA
reaching the pulp would be on the order of 4 mmol/L, again
within the range used in the current study. Although there are
many factors to consider when converting the in vitro results of
the current study to an in vivo situation, the concentrations of
monomers used in the current study are plausible.
In summary, the current study has shown that several
components released from dentinal adhesives can
significantly modulate the expression of HSP72 at sublethal
concentrations in monocytes. The response can be enhanced or suppressed, depending on the component, its concentration,
and time after heat stress.
jdr.sagepub.com/content/81/4/265.full.pdfJust a thought...