Immune-related abnormalities in autism
A variety of organ systems exhibit inflammatory-like changes in autism. The evidence
comes from quantifying immune-related proteins and RNAs, as well as
immunohistochemistry. Findings from epidemiology are also relevant.
Brain and CSF
A groundbreaking paper by Carlos Pardo and colleagues (5) revealed an inflammatory-like
state in post-mortem autism brains as indicated by elevated cytokines and activated
microglia and astrocytes. Importantly, these changes were found in subjects ranging in age
from 5 to 44 years old, indicating that this immune-activated state is established early and
appears to be permanent. Moreover, cytokine elevation was also found in the cerebral spinal
fluid (CSF) of living autistic children ages 3 to 10 years old. Recent results from studies of
some of the same postmortem brains and new autism brain samples, as well as CSF, have
supported these conclusions (6, 7). Consistent with these findings are results from a variety
of microarray studies that show dysregulation of immune-related genes (e.g. cytokines and
chemokines) in autistic brains (8). It is also clear that there is considerable heterogeneity
among the autism samples, as might be expected from the extreme disparities in behavioral
symptoms among ASD subjects.
Peripheral immune system and GI tract
Possibly related to the inflammatory-like state in the central nervous system are
abnormalities in the peripheral immune system (9). Although there have been many papers
on this topic over the years, recent reports from Judy Van de Water and Paul Ashwood have
utilized blood samples from a well characterized, large cohort of ASD children. These
authors report that, compared to controls and non-ASD children with developmental
disabilities, several cytokines and chemokines, including interleukin-1β (IL-1β), IL-6, IL-8
and IL-12p40, are elevated in the ASD plasma of very young children (ages 2–5 years old),
and that these increases are associated with more impaired communication and aberrant
behaviors (8, 10, 11). In addition, peripheral blood mononuclear cells display altered
cytokine responses to stimulation in vitro (12, 13).
Although an early report from Wakefield and colleagues muddied the waters considerably,
there have been several subsequent papers providing evidence of inflammation in the
gastrointestinal (GI) tract of at least a subset of ASD children (14, 15). These findings
include immune cell infiltrates present in the colon, ileum and duodenum, as well as
increased T cell activation in the intestinal mucosa. These inflammatory changes are
associated with autoimmune responses that could contribute to the observations of decreased
mucosal integrity, or “leaky gut” (16). Disruption of the mucosal barrier can also occur in
the apparent absence of inflammation, however, as in irritable bowel syndrome. Thus, leaky
gut symptoms do not necessarily connote inflammation. This issue needs to be clarified in
ASD, as does the question of the frequency of GI symptoms in ASD compared to controls.
These are difficult questions to answer because of the problems in obtaining GI samples
from ASD and control children without overt GI symptoms. Perhaps related to GI symptoms
is the finding of an abnormal gut microbiota composition in ASD (17). It is thus of particular
interest that a small study of antibiotic treatment aimed at the gut found temporary
improvement in some behavioral symptoms (9). This is potentially important, as it
represents a possibly safe intervention and thus could be followed up with a large, blinded
study. In addition, dietary modification is reported to provide behavioral improvements for
some ASD children (14). There is considerable interest among parents of autistic children
regarding the possibility of adverse reactions to certain dietary components. This could then
lead to GI problems such as a leaky gut, which may or may not have an inflammatory basis.NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
The possibility of a connection between peripheral immune abnormalities and altered
behavior in ASD is fascinating, but unsubstantiated, at this point. On the one hand, it could
be that genetic susceptibility or an environmental insult biases the subject toward both brain
and immune dysregulation simultaneously and that these symptoms occur independently.
For example, several ASD candidate genes are known to regulate both brain and immune
system development and/or function (9). On the other hand, it is possible that immune
irregularities, such as in peripheral immune cells or the GI tract, interact with an abnormal
brain to exacerbate behavioral symptoms. For instance, it is well known from animal and
human studies that elevated peripheral cytokines can cause striking changes in behavior (4).
Autoimmune connections
Further support for immune system dysregulation comes from epidemiologic studies of
ASD. The largest of these found that some autoimmune diseases (rheumatoid arthritis, celiac
disease and type 1 diabetes) are more common in mothers of ASD children than in mothers
of typically developing children (18). These results and those from prior studies (9) could
mean that an abnormal immune system is genetically passed on to the offspring. It is also
possible that maternal autoimmune reactions could have deleterious effects on fetal brain
development. The latter hypothesis receives support from the finding that ~12% of mothers
with children with ASD offspring have anti-fetal brain antibodies in their serum, a figure
significantly higher than in mothers of typical children (9). Animal studies support the idea
that such antibodies could be relevant for pathophysiology; when IgG from human mothers
of children with ASD is injected into rhesus macaques or mice at midgestation, some of the
offspring display abnormal behaviors that are not seen in offspring of animals injected with
IgG from mothers of typically developing children (19, 20).Animal models of the maternal infection risk factor The maternal infection risk factor is currently being studied in mice, rats and monkeys. The
experiments involve infecting the mother or simply activating her immune system in the
absence of pathogens.
Rodent models
The epidemiologic evidence highlighting maternal infection as a risk factor for autism and
schizophrenia has stimulated the development of several rodent models. These involve
infection of pregnant mice or rats (nasal application of influenza virus) or mimicking such
infections by activating the maternal immune system in the absence of pathogen. The latter
approach has proven particularly popular, and involves maternal injection of the synthetic
double stranded RNA, poly(I:C), to evoke an anti-viral inflammatory response, or maternal
injection of lipopolysaccharide (LPS), to evoke an anti-bacterial inflammatory response.
Although these three approaches undoubtedly yield somewhat different cascades of gene
activation, analysis of the offspring has thus far revealed considerable overlap in behavioral
abnormalities and neuropathology (4,21). Moreover, similar results have been obtained in
both the mouse and rat models of maternal immune activation (MIA). Several cardinal
symptoms of autism are observed in the offspring of immune-activated dams, including
deficits in communication (assayed by ultrasonic vocalizations; 22) and social interaction
(assayed in the 3 chamber paradigm; 23). Other behaviors in the offspring that are consistent
with autism symptoms include elevated anxiety and a prepulse inhibition deficit (4, 21).
There is also a Theory of Mind deficit in autism, in which the subject has difficulty intuiting
the thoughts of another person, which can lead to social difficulties. Approaching this type
of deficit in rodents is just beginning, using assays for empathy (24), for instance. Regarding
neuropathology, the offspring of infected mothers, or mothers given poly(I:C), also exhibit
NIH-PA Author Manuscript NIH-PA Author Manuscript
NIH-PA Author Manuscript
several abnormalities commonly found in autism including a spatially-restricted deficit in Purkinje cells in the cerebellum (25).Because maternal infection is a risk factor for both autism and schizophrenia, it is not surprising that some of the features of the latter disorder have also been found in the offspring of immune-activated mothers. These include enlarged ventricles, changes in the serotonergic and dopaminergic pathways, as well as enhanced responses to a hallucinogen (4, 21, 27). At least some of these symptoms can be differentially expressed as a function of the timing of the maternal infection (28). It is also possible that the severity of MIA is a factor in which symptoms are expressed in the offspring. Genetic background also likely influences the outcome of maternal infection in terms of ASD versus schizophrenia. It should also be pointed out that, in addition to the obvious phenotypic differences, there are a number of striking similarities between schizophrenia and ASD phenotypes in humans.These include some shared behavioral abnormalities as well as neuropathological features (29). These overlaps in phenotypes make it difficult to firmly identify features that can be used to distinguish ASD and schizophrenia phenotypes in animal models. The response to hallucinogenic drugs, or even the presence of spontaneous hallucinogen-like activity in the brain, is a potentially fruitful area that can be explored in this context. Regarding features specific to autism, deficits in male neonate and adult communication are found in the MIA mouse model (22), and this can be further examined by analyzing the qualitative nature of these ultrasonic vocalizations (USVs), and as a function of the social settings in which they occur (24). That is, experiments can evaluate the types of syllables, their grouping and order,the consistency of usage in various social situations, how they change with development,and whether there is indeed “mouse song” that has the characteristics of bird song.How does activation of the maternal immune response alter fetal brain development? The manipulation of cytokines has revealed that the elevation of the pro-inflammatory cytokine IL-6 (which is induced by MIA) is essential for development of the abnormal behaviors and
changes in brain gene expression in the offspring (23). That is, injection of IL-6 alone is
sufficient to yield the abnormal behaviors in the offspring seen with MIA. Conversely,
blocking IL-6 during MIA prevents the development of these behaviors. Moreover,
elevation of the anti-inflammatory cytokine IL-10 also protects against MIA (30). These
results support the theory that the balance between pro-and anti-inflammatory influences is
important in fetal brain development.
Where do these cytokines act? Several groups have found that MIA induces pro-
inflammatory cytokines in the fetal brain itself. For example, IL-6 mRNA and protein are
elevated in the fetal brain following maternal poly(I:C) administration. This finding is
consistent with a feed-forward, self-reinforcing inflammatory cycle. This possibility needs
to be further tested with assays in postnatal offspring to determine if parallels to the findings
in autism brains can be found. It must also be determined if maternal IL-6 (or other signals)
is directly responsible for evoking the cytokine responses observed in the fetal brain.
Other work has highlighted the placental response to MIA as an indirect pathway towards
altering fetal brain development (31,32). Maternal injection of poly(I:C) increases IL-6
mRNA as well as maternally-derived IL-6 protein in the placenta. This activates the
endogenous immune cells in the decidua, and maternally-derived IL-6 activates the Janus
kinase (JAK)- signal transducer and activator of transcription 3 (STAT3) pathway
specifically in the spongiotrophoblast layer, which results in expression of acute phase
genes. Importantly, this parallels an IL-6-dependent disruption of the growth hormone-
insulin-like growth factor axis in the placenta. Together, these IL-6-mediated effects of MIA
represent an indirect mechanism by which MIA can alter fetal development (Fig. 1). There
is also severe placental inflammation when pregnant rats are given a high dose of LPS, and
NIH-PA Author Manuscript
NIH-PA Author Manuscript
NIH-PA Author Manuscript
this reaction can be blocked by administration of an IL-1 receptor antagonist (33).
Interestingly, a greater occurrence of placental trophoblast inclusions is found in placental
tissue from births of children who go on to develop ASD compared to non-ASD controls
(34). Relevant in this context are findings that chorioamnionitis and other obstetric
complications are significantly associated with socialization and communication deficits in
autistic infants (35).
As noted above, a number of abnormalities have been found in peripheral immune cells in
autism. Thus, it is of interest that T cells in mouse MIA offspring are in a hyper-responsive
state for at least a year after birth [36]. The prolonged nature of this pathology lends further
support to the hypothesis of a feed-forward, self-reinforcing cycle that begins in during
gestation and continues through adulthood. This is also consistent with the findings of
immune-related abnormalities in the brains of adult autism cases.
Non-human primate model
Thus far, there is a single report of a non-human primate model of maternal infection using
nasal application of influenza virus in the 3rd trimester of rhesus monkey pregnancy. The
choice of 3rd trimester does not, however, fit with what is known about the windows of
vulnerability for development of schizophrenia or autism. In the offspring of the infected
monkeys, widespread reduction in gray matter volume in the cortex, and reduced white
matter volume in the parietal cortex is observed (26). The infants born to infected mothers
appear to show signs of early autonomy from the mother, yet also exhibit increased distress.
Given the striking similarities between human and non-human primate behaviors during
normal early postnatal development (unlike rodents), much could be done with this type of
model using infection, LPS or poly(I:C).Gene-environment interactions A variety of mental disorders have been attributed in part to genes that increase the
susceptibility to environmental risk factors. To date, however, there is very little evidence
for such gene-environment interactions. Therefore, it is of interest that mice heterozygous
for the tuberous sclerosis 2 (Tsc2) gene display a social interaction deficit only when they
are born to mothers treated with poly(I:C) (37). That is, this behavioral deficit is most severe
when the MIA environmental risk factor is combined with a genetic defect that, in humans,
also carries a high risk for ASD. In addition, there is an excess of TSC-ASD individuals
born during the peak influenza season, an association that is not seen for TSC individuals
not displaying ASD symptoms (37). Similar experiments have been done looking at the
effects of poly(I:C) MIA in lines of DISC1 mice. DISC1 (disrupted in schizophrenia 1) is a
gene associated with schizophrenia, bipolar and major depressive disorders, as well as
autism (38). In an inducible transgenic mouse line expressing a human truncated DISC1
protein in the forebrain, the combination of MIA and prenatal transgene expression results in
increased anxiety and depression-like symptoms and decreased social interaction compared
to either insult alone (39). An unexpected finding is that the combined gene-environmental
risk factors cause a decrease in ventricular enlargement compared to either alone. This
combination of insults alters the levels of several cytokines; notably IL-1β and IL-6 are
increased. Much remains to be done in this important line of experiments that combine
environmental risk factors with ASD candidate genes, both in characterizing the phenotypes
and in exploring the cellular and molecular sites of action of each factor. Results from
combining these factors should illuminate the pathways for each of them.
NIH-PA Author Manuscript NIH-PA Author Manuscript
NIH-PA Author Manuscript
Therapeutic manipulations
The findings summarized in the prior sections demonstrate that the maternal infection and
MIA models display face (similar symptoms) as well as construct (similar cause) value for
both autism and schizophrenia. These models can have predictive value as well. For
example, the manipulation of cytokines during pregnancy can prevent the development of
abnormal behaviors in the offspring in the poly(I:C) and LPS models. In addition,
pretreatment of pregnant rats with N-acetyl-cysteine, which increases calcium influx when
binding to glutamate receptors in combination with the transmitter, and also suppresses fetal
inflammatory responses to LPS, prevents many of the effects of maternal LPS
administration (4). The ability of IL-10 to block the effects of MIA is an attractive
intervention because endogenous IL-10 is essential for resistance to LPS-induced preterm
labor and fetal loss. Thus, administration of this cytokine enhances a natural protective
mechanism. However, increased IL-10 in the absence of MIA in pregnant mice can lead to
behavioral abnormalities in the adult offspring (30), a finding consistent with the fact that
normal human pregnancy involves increased inflammation. Therefore, postnatal cytokine
perturbations would potentially be a safer therapeutic approach. It is also clear that postnatal
cytokine manipulations can induce behavioral changes in the absence of MIA (40). Such
manipulations in MIA models could be a fruitful area of research.
In fact, MIA models have proven valuable for testing other types of postnatal therapies.
Whereas acute antipsychotic drug administration in adult influenza and poly(I:C) MIA
offspring can ameliorate some of the behavioral deficits (4,21), administration of such
medications in immature MIA offspring, before the onset of behavioral abnormalities and
ventricular enlargement, is effective in preventing the onset of such symptoms (41,42).
Treatment for a week during adolescence, many weeks before beginning behavioral testing,
prevents the onset of abnormalities and the ventricular enlargement. Therefore, despite the
fact that MIA has induced many changes in the brain during fetal development, postnatal
behaviors can be subsequently altered. Although the classic action of these antipsychotic
medications involves blockade of the D2 dopamine receptor in the brain, it is also worth
noting in the present context that many of them have also been shown to influence cytokine
expression in peripheral immune cells (4).
It is also important to note, in the context of potential postnatal treatments, that in mouse
models of a number of rare genetic disorders with autistic symptoms such as fragile X, Rett
syndrome and TSC, behavioral abnormalities can be at least partially reversed in adulthood.
These findings have led to several clinical trials in these disorders (43).Concluding remarks
A variety of techniques have been used to demonstrate the presence of a sub-clinical,
inflammatory-like state in the brain, CSF and peripheral immune system in many ASD
samples. There is also evidence for abnormalities in the GI tract, although the prevalence
and the precise phenotype in that system remain to be determined. Mouse and rat models
that mimic the autism maternal infection risk factor display face, construct, and predictive
validity for ASD. Many of the symptoms in these rodent models are also similar to those
expected for a schizophrenia model, which is consistent with the fact that maternal infection
is a validated risk factor for the latter disorder as well. To aid in distinguishing ASD from
schizophrenia behavioral symptoms in this and many other animal models, it will be of great
interest to further develop assays for hallucination-like activity in the brain (27), and to
explore the qualitative features of USVs (24). The application of electrophysiological tools
to MIA models has only just begun (44, 45), and the same is true of combining MIA with
ASD candidate genes. Some of the genes near the top of the list for future testing include
NIH-PA Author Manuscript NIH-PA Author Manuscript
NIH-PA Author Manuscript
CNTNAP2 (contactin associated protein-like 2) and MET receptor kinase, the former
because of its connection with language (46), and the latter because of its roles in the
nervous, immune and GI systems (47). Another area of great promise is extending MIA to
non-human primates, where ASD-like behaviors can be assessed in much more human-like
context than in rodents. The first report on the young offspring of influenza-infected rhesus
mothers has recently appeared (26), and the development of non-human primate poly(I:C)
and LPS models should prove useful.Acknowledgments Work cited from the author’s laboratory was supported by the National Institute of Mental Health, the California Institute of Regenerative Medicine, and the Autism Speaks and Binational Science foundations. Due to space limitations, reviews are cited rather than primary research articles wherever possible.References 1. Brown AS, Derkits EJ. Prenatal infection and schizophrenia: A review of epidemiologic and translational studies. Am J Psychiat. 2010; 167:261–280. [PubMed: 20123911]2. Brown AS, Patterson PH. Maternal infection and schizophrenia: Implications for prevention. Schiz Bull. 2011 In press.3. Atladottir HO, et al. Maternal infection requiring hospitalization during pregnancy and autism spectrum disorders. J Autism Devel Dis. 2010; 40:1423–1430.4. Patterson PH. Immune involvement in schizophrenia and autism: Etiology, pathology and animal models. Behav Brain Res. 2009; 204:313–321. [PubMed: 19136031]5. Vargas DL, et al. Neuroglial activation and neuroinflammation in the brain of patients with autism.Ann Neurol. 2005; 57:67–81. [PubMed: 15546155]6. Chez MG, et al. Elevation of tumor necrosis factor-alpha in cerebrospinal fluid of autistic children.Pediat Neurol. 2007; 36:361–365. [PubMed: 17560496]7. Morgan JT, et al. Microglial activation and increased microglial density observed in the dorsolateral
prefrontal cortex in autism. Biol Psychiatry. 2010; 68:368376.
8. Lintas C, et al. Genome-wide expression studies in Autism spectrum disorder, Rett syndrome, and
Down syndrome. Neurobiol Disease. 2011 in press. 10.1016/j.nbd2010.11.010
9. Careaga M, et al. Immune dysfunction in autism: a pathway to treatment. J Amer Soc Exper
NeuroTherap. 2010; 7:283–292.
10. Ashwood P, et al. Associations of impaired behaviors with elevated plasma chemokines in autism
spectrum disorders. J Neuroimmunol. 2010 Epub ahead of print.
11. Ashwood P, et al. Elevated plasma cytokines in autism spectrum disorders provide evidence of
immune dysfunction and are associated with impaired behavioral outcome. Brain Behav Immun.
2011; 25:40–45. [PubMed: 20705131]
12. Ashwood P, et al. Altered T cell responses in children with autism. Brain Behav Immun. 2010
epub ahead of print.
13. Enstrom AM, et al. Differential monocyte responses to TLR ligands in children with autism
spectrum disorders. Brain Behav Immun. 2010; 24:64–71. [PubMed: 19666104]
14. Buie T, et al. Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with
ASDs: a consensus report. Pediatrics. 2010; 125(Suppl 1):S1. [PubMed: 20048083]
15. Ashwood, P., et al. Autism, Gastrointestinal Disturbance, and Immune Dysfunction: What is the
Link?. In: Chauhan, A.; Chauhan, V.; BTW, editors. Autism: Oxidative Stress, Inflammation, and
Immune Abnormalities. CRC Press; Boca Raton: 2010. p. 278
16. deMagistris L, et al. Alterations of the intestinal barrier in patients with autism spectrum disorders
and in their fist-degree relatives. J Pediatr Gastroenterol Nutrition. 2010; 51:418–424. [PubMed:
20683204]
17. Feingold SM, et al. Pyrosequencing study of fecal microflora of autistic and control children.
Anaerobe. 2010; 16:444–453. [PubMed: 20603222]
NIH-PA Author Manuscript
NIH-PA Author Manuscript
NIH-PA Author Manuscript
18. Atladotiir HO, et al. Association of family history of autoimmune diseases and autism spectrum disorders. Pediatrics. 2010; 124:687–694.19. Martin LA, et al. Stereotypies and hyperactivity in rhesus monkeys exposed to IgG from mothers of children with autism. Brain Behav Immun. 2008; 22:806–816. [PubMed: 18262386]20. Singer HS, et al. Prenatal exposure of antibodies from mothers of children with autism produces neurobehavioral alterations: A pregnant dam mouse model. J Neuroimmunol. 2009; 211:39–48.[PubMed: 19362378]21. Meyer U, Feldon J. Epidemiology-driven neurodevelopmental animal models of schizophrenia.Progr Neurobiol. 2010; 90:285–326.22. Malkova N, et al. Maternal immune activation causes a deficit in social and communicative behavior in male mouse offspring. Program No. 561.29. Neurosci Mtg Planner, San Diego: Soc Neurosci. 2010 on line.23. Smith SEP, et al. Maternal immune activation alters fetal brain development through interleukin-6.J Neurosci. 2007; 27:10695–702. [PubMed: 17913903]24. Silverman JL, et al. Behavioral phenotyping assays for mouse models of autism. Nature Rev Neurosci. 2010; 11:490–502. [PubMed: 20559336]25. Shi L, et al. Activation of the maternal immune response alters cerebellar development in the offspring. Brain Behav Immun. 2009; 23:116–123. [PubMed: 18755264]26. Short SJ, et al. Maternal influenza infection during pregnancy impacts postnatal brain development in the rhesus monkey. Biol Psychiatry. 2010; 67:965–973. [PubMed: 20079486]27. Moreno JL, et al. Maternal influenza viral infection causes schizophrenia-like alterations of 5-HT2A and mGlu2 receptors in the adult offspring. J Neurosci. 2011; 31:1863–1872. [PubMed:21289196]28. Meyer U, et al. The time of prenatal immune challenge determines the specificity of inflammation-mediated brain and behavioral pathology. J Neurosci. 2006; 26:4752–62. [PubMed: 16672647]29. Meyer U, et al. Schizophrenia and autism: both shared and disorder-specific pathogenesis via perinatal inflammation? Pediatric Res. 2011 on line.30. Meyer U, et al. Adult behavioral and pharmacological dysfunctions following disruption of the
fetal brain balance between pro-inflammatory and IL-10mediated anti-inflammatory signaling.Molec Psychiat. 2008; 13:208–21.
31. Mandal M, et al. Maternal immune stimulation during pregnancy affects adaptive immunity in
offspring to promote development of TH17 cells. Brain Behav Immun. 2011 on line.
32. Hsiao E, Patterson PH. Activation of the maternal immune system induces endocrine changes in
the placenta via IL-6. Brain Behav Immun. 2011 on line.
33. Girard S, et al. IL-1 receptor antagonist protects against placental and neurodevelopmental defects
induced by maternal inflammation. J Immunol. 2010; 184:3997–4005. [PubMed: 20181892]
34. Anderson GM, et al. Placental trophoblast inclusions in autism spectrum disorder. Biol Psychiatry.
2007; 61:487–491. [PubMed: 16806106]
35. Limperopoulos C, et al. Positive screening for autism in ex-preterm infants: prevalence and risk
factors. Pediatrics. 2008; 121:758–765. [PubMed: 18381541]
36. Hsiao E, et al. Modeling an autism risk factor in mice leads to permanent changes in the immune
system. Internl Soc Autism Res. 2010; 130:124.
37. Ehninger D, et al. Gestational immune activation and TSC2 haploinsufficiency cooperate to disrupt
social behavior in mice. Molec Psychiatry. 2010 on line.
38. Kilpinen H, et al. Association of DISC1 with autism and Asperger syndrome. Molec Psychiatry.
2008; 13:187–196. [PubMed: 17579608]
39. Abazyan B, et al. Prenatal interaction of mutant DISC1 and immune activation produces adult
psychopathology. Biol Psychiatry. 2010; 68:1172–1181. [PubMed: 21130225]
40. Watanabe Y, et al. Cytokine hypothesis of schizophrenia pathogenesis: evidence from human
studies and animal models. Psychiatry Clin Neurosci. 2010; 64:217–230. [PubMed: 20602722]
41. Piontkewitz Y, et al. Clozapine administration in adolescence prevents postpubertal emergence of
brain structural pathology in an animal model of schizophrenia. Biol Psychiatry. 2009; 66:1038–1046. [PubMed: 19726031]
NIH-PA Author Manuscript
NIH-PA Author Manuscript
NIH-PA Author Manuscript
42. Li Q, et al. Prenatal immune challenge is an environmental risk factor for brain and behavior
change relevant to schizophrenia: evidence from MRI in a mouse model. PLoS One. 2009;
4:e6354. [PubMed: 19629183] NIH-PA Author Manuscript
43. Silva A, Ehninger D. Adult reversal of cognitive phenotypes in neurodevelopmental disorders. J
Neurodev Disorders. 2009; 1:150–157.
44. Ito HT, et al. Maternal immune activation alters nonspatial information processing in the
hippocampus of the offspring. Brain Behav Immun. 2010; 24:930–941. [PubMed: 20227486]
45. Dickerson DD, et al. Abnormal long-range neural synchrony in a maternal immune activation
animal model of schizophrenia. J Neurosci. 2010; 30:12424–12431. [PubMed: 20844137]
46. Alarcorn M, et al. Linkage, association, and gene-expression analyses identify CNTNAP2 as an
autism-susceptibility gene. Amer J Hum Gen. 2008; 82:150–159.
47. Campbell DB, et al. Distinct genetic risk based on association of MET in families with co-
occurring autism and gastrointestinal conditions. Pediatrics. 2009; 123:1018–1024. [PubMed:
19255034]
NIH-PA Author Manuscript
NIH-PA Author Manuscript
Figure 1. Summary of MIA-induced effects on the placenta Maternal injection of poly(I:C) activates the maternal immune system, elevating IL-6, which enters the spiral arteries that descend through the decidua and spongiotrophoblast layers,filling the maternal bloodspaces of the labyrinth. Resident immune cells in the decidua are activated to express CD69 and further propagate the inflammatory response. IL-6 produced by decidual cells acts on target cells in the spongiotrophoblast layer. Ligation of the IL-6Ra with gp130 causes JAK/STAT3 activation and increases in acute phase proteins, such as SOCS3, and down-regulation of placental growth hormone (GH) production. This leads to reduced insulin-like growth factor binding protein 3 (IGFBP3) and IGFI. Global changes in STAT3 activation in the spongiotrophoblast layer alter the production of placenta-specific
pro-lactin protein (PLP) and other pro-lactin proteins. These various changes in endocrine factors very likely to lead to acute placental pathophysiology and subsequent effects on fetal development. (Reproduced from ref. 31, with permission.)
NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
脐带间充质干细胞的研究进展 间充质干细胞（mesenchymal stem cells,MSC S ）是来源于发育早期中胚层 的一类多能干细胞[1-5]，MSC S 由于它的自我更新和多项分化潜能，而具有巨大的 治疗价值 ,日益受到关注。MSC S 有以下特点：(1)多向分化潜能，在适当的诱导条件下可分化为肌细胞[2]、成骨细胞[3、4]、脂肪细胞、神经细胞[9]、肝细胞[6]、心肌细胞[10]和表皮细胞[11, 12]；(2)通过分泌可溶性因子和转分化促进创面愈合；(3) 免疫调控功能，骨髓源（bone marrow ）MSC S 表达MHC-I类分子，不表达MHC-II 类分子，不表达CD80、CD86、CD40等协同刺激分子，体外抑制混合淋巴细胞反应，体内诱导免疫耐受[11, 15]，在预防和治疗移植物抗宿主病、诱导器官移植免疫耐受等领域有较好的应用前景；(4)连续传代培养和冷冻保存后仍具有多向分化潜能，可作为理想的种子细胞用于组织工程和细胞替代治疗。1974年Friedenstein [16] 首先证明了骨髓中存在MSC S ，以后的研究证明MSC S 不仅存在于骨髓中，也存在 于其他一些组织与器官的间质中：如外周血[17]，脐血[5]，松质骨[1, 18]，脂肪组织[1]，滑膜[18]和脐带。在所有这些来源中，脐血(umbilical cord blood)和脐带(umbilical cord)是MSC S 最理想的来源，因为它们可以通过非侵入性手段容易获 得，并且病毒污染的风险低，还可冷冻保存后行自体移植。然而，脐血MSC的培养成功率不高[19, 23-24]，Shetty 的研究认为只有6%，而脐带MSC的培养成功率可 达100%[25]。另外从脐血中分离MSC S ，就浪费了其中的造血干/祖细胞(hematopoietic stem cells/hematopoietic progenitor cells,HSCs/HPCs) [26, 27]，因此，脐带MSC S (umbilical cord mesenchymal stem cells, UC-MSC S )就成 为重要来源。 一．概述 人脐带约40 g, 它的长度约60–65 cm, 足月脐带的平均直径约1.5 cm[28, 29]。脐带被覆着鳞状上皮，叫脐带上皮，是单层或复层结构，这层上皮由羊膜延续过来[30, 31]。脐带的内部是两根动脉和一根静脉，血管之间是粘液样的结缔组织，叫做沃顿胶质，充当血管外膜的功能。脐带中无毛细血管和淋巴系统。沃顿胶质的网状系统是糖蛋白微纤维和胶原纤维。沃顿胶质中最多的葡萄糖胺聚糖是透明质酸，它是包绕在成纤维样细胞和胶原纤维周围的并维持脐带形状的水合凝胶，使脐带免受挤压。沃顿胶质的基质细胞是成纤维样细胞[32]，这种中间丝蛋白表达于间充质来源的细胞如成纤维细胞的，而不表达于平滑肌细胞。共表达波形蛋白和索蛋白提示这些细胞本质上肌纤维母细胞。 脐带基质细胞也是一种具有多能干细胞特点的细胞，具有多项分化潜能，其 形态和生物学特点与骨髓源性MSC S 相似[5, 20, 21, 38, 46]，但脐带MSC S 更原始，是介 于成体干细胞和胚胎干细胞之间的一种干细胞，表达Oct-4, Sox-2和Nanog等多
脐带血造血干细胞库管理办法（试行） 第一章总则 第一条为合理利用我国脐带血造血干细胞资源，促进脐带血造血干细胞移植高新技术的发展，确保脐带血 造血干细胞应用的安全性和有效性，特制定本管理办法。 第二条脐带血造血干细胞库是指以人体造血干细胞移植为目的，具有采集、处理、保存和提供造血干细胞 的能力，并具有相当研究实力的特殊血站。 任何单位和个人不得以营利为目的进行脐带血采供活动。 第三条本办法所指脐带血为与孕妇和新生儿血容量和血循环无关的，由新生儿脐带扎断后的远端所采集的 胎盘血。 第四条对脐带血造血干细胞库实行全国统一规划，统一布局，统一标准，统一规范和统一管理制度。 第二章设置审批 第五条国务院卫生行政部门根据我国人口分布、卫生资源、临床造血干细胞移植需要等实际情况，制订我 国脐带血造血干细胞库设置的总体布局和发展规划。 第六条脐带血造血干细胞库的设置必须经国务院卫生行政部门批准。 第七条国务院卫生行政部门成立由有关方面专家组成的脐带血造血干细胞库专家委员会（以下简称专家委
员会），负责对脐带血造血干细胞库设置的申请、验收和考评提出论证意见。专家委员会负责制订脐带血 造血干细胞库建设、操作、运行等技术标准。 第八条脐带血造血干细胞库设置的申请者除符合国家规划和布局要求，具备设置一般血站基本条件之外， 还需具备下列条件： （一）具有基本的血液学研究基础和造血干细胞研究能力； （二）具有符合储存不低于1 万份脐带血的高清洁度的空间和冷冻设备的设计规划； （三）具有血细胞生物学、HLA 配型、相关病原体检测、遗传学和冷冻生物学、专供脐带血处理等符合GMP、 GLP 标准的实验室、资料保存室； （四）具有流式细胞仪、程控冷冻仪、PCR 仪和细胞冷冻及相关检测及计算机网络管理等仪器设备； （五）具有独立开展实验血液学、免疫学、造血细胞培养、检测、HLA 配型、病原体检测、冷冻生物学、 管理、质量控制和监测、仪器操作、资料保管和共享等方面的技术、管理和服务人员； （六）具有安全可靠的脐带血来源保证； （七）具备多渠道筹集建设资金运转经费的能力。 第九条设置脐带血造血干细胞库应向所在地省级卫生行政部门提交设置可行性研究报告，内容包括：
（医院感染护理学）医院感染与护理管理考纲： 常见医院感染的预防与护理 一、下呼吸道医院感染的预防 （一）下呼吸道医院感染临床诊断标准符合下述两条之一即可诊断。 1.患者出现咳嗽、痰黏稠，肺部出现湿啰音，并有下列情况之一： ①发热。 ②白细胞总数和（或）嗜中性粒细胞比例增高。 ③X线显示肺部有炎性浸润性病变。 2.慢性气道疾病患者稳定期（慢性支气管炎伴或不伴阻塞性肺气肿、哮喘、支气管扩张症）继发急性感染，并有病原学改变或X线胸片显示与入院时比较有明显改变或新病变。 （二）病原学诊断临床诊断基础上，符合下述六条之一即可诊断。 1.经筛选的痰液，连续两次分离到相同病原体。 2.痰细菌定量培养分离病原菌数≥106CFU/ml。 3.血培养或并发胸腔积液者的胸液分离到病原体。 4.经纤维支气管镜或人工气道吸引采集的下呼吸道分泌物病原菌数≥105CFU/ml；经支气管肺泡灌洗（BAL）分离到病原菌数≥104CFU/ml；或经防污染标本刷（PSB）、防污染支气管肺泡灌洗（PBAL）采集的下呼吸道分泌物分离到病原菌，而原有慢性阻塞性肺病包括支气管扩张者病原菌数必须≥103CFU/ml。 5.痰或下呼吸道采样标本中分离到通常非呼吸道定植的细菌或其他特殊病原体。 6.免疫血清学、组织病理学的病原学诊断证据。 （三）说明 1.痰液筛选的标准为痰液涂片镜检鳞状上皮细胞＜10个/低倍视野和白细胞＞25个/低倍视野或鳞状上皮细胞:白细胞≤1: 2.5；免疫抑制和粒细胞缺乏患者见到柱状上皮细胞或锥状上皮细胞与白细胞同时存在，白细胞数量可以不严格限定。 2.应排除非感性原因如肺栓塞、心力衰竭、肺水肿、肺癌等所致的下呼吸道的胸片的改变。 3.病变局限于气道者为医院感染气管-支气管炎；出现肺实质炎症（X线显示）者为医院感染肺炎（包括肺脓肿），报告时需分别标明。 （四）预防 1.预防下呼吸道感染特别是作好呼吸机相关性肺炎（VAP发生率为18%～60%，治疗困难，病死率高达30%～60%）的预防与护理最重要。使用声门下分泌物引流（SSD）方法可能是预防VAP有效的且简单的方法。 VAP危险因素较多，采取综合措施以减少VAP的发病率可能更重要。如呼吸机的湿化器使用无菌水，每
卫生部办公厅关于印发《脐带血造血干细胞治疗技术管理规 范(试行)》的通知 【法规类别】采供血机构和血液管理 【发文字号】卫办医政发[2009]189号 【失效依据】国家卫生计生委办公厅关于印发造血干细胞移植技术管理规范(2017年版)等15个“限制临床应用”医疗技术管理规范和质量控制指标的通知 【发布部门】卫生部(已撤销) 【发布日期】2009.11.13 【实施日期】2009.11.13 【时效性】失效 【效力级别】部门规范性文件 卫生部办公厅关于印发《脐带血造血干细胞治疗技术管理规范（试行）》的通知 （卫办医政发〔2009〕189号） 各省、自治区、直辖市卫生厅局，新疆生产建设兵团卫生局： 为贯彻落实《医疗技术临床应用管理办法》，做好脐带血造血干细胞治疗技术审核和临床应用管理，保障医疗质量和医疗安全，我部组织制定了《脐带血造血干细胞治疗技术管理规范（试行）》。现印发给你们，请遵照执行。 二〇〇九年十一月十三日
脐带血造血干细胞 治疗技术管理规范（试行） 为规范脐带血造血干细胞治疗技术的临床应用，保证医疗质量和医疗安全，制定本规范。本规范为技术审核机构对医疗机构申请临床应用脐带血造血干细胞治疗技术进行技术审核的依据，是医疗机构及其医师开展脐带血造血干细胞治疗技术的最低要求。 本治疗技术管理规范适用于脐带血造血干细胞移植技术。 一、医疗机构基本要求 （一）开展脐带血造血干细胞治疗技术的医疗机构应当与其功能、任务相适应，有合法脐带血造血干细胞来源。 （二）三级综合医院、血液病医院或儿童医院，具有卫生行政部门核准登记的血液内科或儿科专业诊疗科目。 1.三级综合医院血液内科开展成人脐带血造血干细胞治疗技术的，还应当具备以下条件： （1）近3年内独立开展脐带血造血干细胞和（或）同种异基因造血干细胞移植15例以上。 （2）有4张床位以上的百级层流病房，配备病人呼叫系统、心电监护仪、电动吸引器、供氧设施。 （3）开展儿童脐带血造血干细胞治疗技术的，还应至少有1名具有副主任医师以上专业技术职务任职资格的儿科医师。 2.三级综合医院儿科开展儿童脐带血造血干细胞治疗技术的，还应当具备以下条件：
---------------------------------------------------------------范文最新推荐------------------------------------------------------ 护理管理在医院感染控制的运用 摘要：医院是一个特殊的场所，由于患者众多，医院就成了人员密集的场所，患者患有的疾病种类有很多，携带的病菌种类也不同，因此，医院是最容易发生感染的场所，一旦出现感染情况就会给患者的治疗带来不利影响，严重危害医院内患者与医护人员的身体健康。目前抗菌药物在临床广泛地应用，应用频率也越来越高，细菌耐药情况变得十分严重，在发生感染之后导致死亡率很高，这是当前医院要面对的一个十分重要的问题，怎样预防、控制医院感染的发生，需要加强护理管理措施，本文就来谈一谈这个方面的问题。 关键词：护理管理；医院感染；控制；效果 医院感染当前已经成为一个严重的公共卫生问题，需要医院管理者与医护人员广泛重视。导致医院感染发生的原因是很复杂的，因此需要加强护理管理工作，在源头上控制医院感染的发生[1]。医院感染控制要注重护理的各个环节，医院中除了治疗环节之外，比较重要的环节就是护理，可以说护士是医院最基层的工作人员，要承担的工作是繁重的，包括清洁、消毒、灭菌、无菌技术等等都要护士去完成， 1 / 8
从这个方面来看，医院中护理质量高低，与医院内发生感染的几率是密切相关的。 1建立健全有关制度并切实将其落实 要建立健全感染控制标准相关规章制度，平时要加强对护士的培训，让护士充分认识监控医院感染的重要意义，让护士明白医院感染是与医院建立与逐渐发展而同时存在的，并且在造成医院感染的原因中，护理质量是主要原因，因此，要想较好地控制感染出现，就要从提升护理质量抓起。护理管理和医院感染控制存在交叉管理，是具有协同效果的。在控制医院感染的工作中每个环节都涉及到护理工作[2]，例如：无菌技术操作、消毒隔离技术、物品消毒与供应等等，只有不断地提升护理质量，才能提升医院感染控制工作的效果，不但要使护士明白个中规范制度的重要意义，还要让其在实际工作中真正的践行好。 2成立控制医院感染的管理系统 护理部要主动与医院感染管理委员会进行沟通，并采纳委员会的指导意见，建立分级管理制度，成立控制医院感染的管理体系，主要由护理部中的相关人员担任职务，该机构的主要任务就是制定预防医院感染的具体计划（包括近期计划与远期计划），要有步骤、有顺序
卫生部关于印发《脐带血造血干细胞库设置管理规范(试行)》的通知 发文机关：卫生部(已撤销) 发布日期： 2001.01.09 生效日期： 2001.02.01 时效性：现行有效 文号：卫医发(2001)10号 各省、自治区、直辖市卫生厅局： 为贯彻实施《脐带血造血干细胞库管理办法（试行）》，保证脐带血临床使用的安全、有效，我部制定了《脐带血造血干细胞库设计管理规范（试行）》。现印发给你们，请遵照执行。 附件：《脐带血造血干细胞库设置管理规范（试行）》 二○○一年一月九日 附件： 脐带血造血干细胞库设置管理规范（试行） 脐带血造血干细胞库的设置管理必须符合本规范的规定。 一、机构设置 （一）脐带血造血干细胞库（以下简称脐带血库）实行主任负责制。 （二）部门设置 脐带血库设置业务科室至少应涵盖以下功能：脐带血采运、处理、细胞培养、组织配型、微生物、深低温冻存及融化、脐带血档案资料及独立的质量管理部分。 二、人员要求
（一）脐带血库主任应具有医学高级职称。脐带血库可设副主任，应具有临床医学或生物学中、高级职称。 （二）各部门负责人员要求 1．负责脐带血采运的人员应具有医学中专以上学历，2年以上医护工作经验，经专业培训并考核合格者。 2．负责细胞培养、组织配型、微生物、深低温冻存及融化、质量保证的人员应具有医学或相关学科本科以上学历，4年以上专业工作经历，并具有丰富的相关专业技术经验和较高的业务指导水平。 3．负责档案资料的人员应具相关专业中专以上学历，具有计算机基础知识和一定的医学知识，熟悉脐带血库的生产全过程。 4．负责其它业务工作的人员应具有相关专业大学以上学历，熟悉相关业务，具有2年以上相关专业工作经验。 （三）各部门工作人员任职条件 1．脐带血采集人员为经过严格专业培训的护士或助产士职称以上卫生专业技术人员并经考核合格者。 2．脐带血处理技术人员为医学、生物学专业大专以上学历，经培训并考核合格者。 3．脐带血冻存技术人员为大专以上学历、经培训并考核合格者。 4．脐带血库实验室技术人员为相关专业大专以上学历，经培训并考核合格者。 三、建筑和设施 （一）脐带血库建筑选址应保证周围无污染源。 （二）脐带血库建筑设施应符合国家有关规定，总体结构与装修要符合抗震、消防、安全、合理、坚固的要求。 （三）脐带血库要布局合理，建筑面积应达到至少能够储存一万份脐带血的空间；并具有脐带血处理洁净室、深低温冻存室、组织配型室、细菌检测室、病毒检测室、造血干/祖细胞检测室、流式细胞仪室、档案资料室、收/发血室、消毒室等专业房。 （四）业务工作区域应与行政区域分开。
医院感染与护理管理 报道基层医院在院内感染控制护理管理中存在的一些问题和针对问题制定并执行的护理管理措施。存在的主要问题是：护理人员对自身在控制医院感染工作中所起作用认识不足、对医院感染的危害性重视不够，护理人员手卫生意识不强，对院内感染监控管理相关知识仍显缺乏，部分护士长对院内感染监控管理的力度不够，医院消毒、隔离所需的基础设施不健全，护士数量达不到卫生部规定的配备标准。近10年来，针对上述问题加强护理管理，预防院内感染，取得了较好效果。 （一）存在的问题 1.护理人员对自身在控制医院感染工作中所起作用认识不足：护理器具的污染是造成医院内交叉感染的途径之一，也是危害患者健康的重要因素。护理器具时刻伴随在护理操作过程中，因此，预防由护理器具污染造成的院内感染，是护理工作中不可忽视的重要工作，特别是在基层医院工作的护理人员，更应重视这一问题。 2.护理人员对医院感染及其危害性认识不足，工作责任心不强，消毒隔离知识掌握不全面，操作中落实不到位，不严格执行无菌技术和消毒隔离制度等。 3.护理人员手卫生意识欠缺，据美国2002年调查，医务人员手卫生依从性也只能达到5%～8%，两成多医生护士洗手后在白大褂上擦干。 4.护理人员对院内感染监控管理的相关知识仍显缺乏：院内感染监控管理是近十年来兴起并迅速发展的新兴学科。因为我国现行的护理在校教育对院内感染监控相关知识的学习涉及较少，而毕业后继续教育又没有将其作为护理学科的重点科目，所以目前部分护理人员还缺乏与之相应的知识和技能，造成相关理论不扎实、基本概念不清晰、常用物品消毒技术不熟练以及常规物品监测方法不准确等现象发生。 5.部分护士长对院内感染监控管理的力度不够：主要是对感染监控管理中“隐性”，和“内涵”质量的管理认识肤浅，对工作“缺陷”带来的危害认识不足，因此在管理上还缺乏力度。所以，近年来院内感染监控的质量虽然有了明显提高，但质量控制达标率高低起伏不稳定，科室间发展不够平衡。 6.医院消毒隔离所需的设施不健全：如住院病人没有卫生处置设施、重点病房没有气体消毒设施、洗手池太少等，致使感染源传播。 7.护士配备不足：县级以下基层卫生院护士缺编更为严重，护士缺编使护士只注重完成打针、输液、发药等治疗性工作，而对消毒、隔离等医院感染控制制度的落实存在不到位现象。 （二）管理措施 1.建立完善的院内感染管理组织：适应院内感染管理发展的需求，有效地控制医院内感染发生率，要在转变管理行为上下功夫，首先将医院感染管理
脐带血间充质干细胞的分离培养和鉴定 【摘要】目的分离培养脐带血间充质干细胞并检测其生物学特性。方法在无菌条件下用密度梯度离心的方法获得脐血单个核细胞，接种含10%胎牛血清的DMEM培养基中。单个核细胞行贴壁培养后，进行细胞形态学观察，绘制细胞生长曲线，分析细胞周期，检测细胞表面抗原。结果采用Percoll(1.073 g/mL)分离的脐血间充质干细胞大小较为均匀，梭形或星形的成纤维细胞样细胞。细胞生长曲线测定表明接后第5天细胞进入指数增生期，至第9天后数量减少;流式细胞检测表明50%～70%细胞为CD29和CD45阳性。结论体外分离培养脐血间充质干细胞生长稳定，可作为组织工程的种子细胞。 【关键词】脐血;间充质干细胞;细胞周期;免疫细胞化学 Abstract: Objective Isolation and cultivation of mesenchymal stem cells (MSCs) in human umbilical cord in vitro, and determine their biological properties. Methods The mononuclear cells were isolated by density gradient centrifugation from human umbilical cord blood in sterile condition, and cultured in DMEM medium containing 10% fetal bovine serum. After the adherent mononuclear cells were obtained, the shape of cells were observed by microscope, then the cell growth curve, the cell cycle and the cell surface antigens were obtained by immunocytochemistry and flow cytometry methods. Results MSCs obtained by Percoll (1.073 g/mL) were similar in size, spindle-shaped or star-shaped fibroblasts-liked cells. Cell growth curve analysis indicated that MSCs were in the exponential stage after 5d and in the stationary stages after 9d. Flow cytometry analysis showed that the CD29 and CD44 positive cells were about 50%～70%. Conclusions The human umbilical cord derived mesenchymal stem cells were grown stably in vitro and can be used as the seed-cells in tissue engineering. Key words:human umbilical cord blood; mesenchymal stem cells; cell cycle; immunocytochemistry 间充质干细胞(mesenchymal stem cells，MSCs)在一定条件下具有多向分化的潜能，是组织工程研究中重要的种子细胞来源。寻找来源丰富并不受伦理学制约的间充质干细胞成为近年来的研究热点[1]。脐血(umbilical cord blood, UCB)在胚胎娩出后，与胎盘一起存在的医疗废物。与骨髓相比，UCB来源更丰富，取材方便，具有肿瘤和微生物污染机会少等优点。有人认为脐血中也存在间充质干细胞(Umbilical cord blood-derived mesenchymal stem cells，UCB-MSCs)。如果从脐血中培养出MSCs，与胚胎干细胞相比，应用和研究则不受伦理的制约，蕴藏着巨大的临床应用价值[2,3]。本研究将探讨人UCB-MSCs体外培养的方法、细胞的生长曲线、增殖周期和细胞表面标志等方面，分析UCB-MSCs 作为间充质干细胞来源的可行性。
护理管理与医院感染的预防控制【摘要】目的：探讨医院感染发生的原因及护理管理工作在预防控制医院感染发生中的重要性。方法：健全的制度与措施，抓好重点科室管理，预防控制院内感染的发生率。结果：通过培训工作及护理管理工作的进一步加强，重点科室的管理，院内感染的发生率明显降低。结论：加强医院护理工作的管理，能降低医院感染率，有效预防和控制院内感染的发生。 【关键词】医院感染；预防控制；护理管理 医院感染也称医院获得性感染，是指住院患者在医院获得的感染，包括住院期间发生的感染或在医院内获得出院不久发生的感染，但不包括病人在入院前已经开始的或入院时已处于潜伏其中的感染，医院感染的主要对象是住院病人和医院工作人员，医院感染的预防控制是当前医院管理中的一个重要内容，是医疗护理质量的综合体现。 1医院感染的原因 1.1滥用抗生素：大量抗菌药的不合理应用是造成院内感染的重要因素，滥用抗生素我国在全球占首位，这与我国的一些管理机制有关。一些鲜为人知的因素，导致滥用抗生素，造成病人菌群失调而发生感染。 1.2大量使用侵袭性手段：侵袭性操作导尿、妇科阴道检查、人工流产、气管切开、气管插管、内镜检查、静脉给药、深浅静脉置管等所用的器械、物体表面、工作人员的手、空气等污染或消毒
不彻底或无菌操作不严格，均可导致院内交叉感染。 1.3无菌操作不严格 医护人员每天为患者进行各种操作，要求的都很严格，如：戴口罩、帽子、洗手、穿相应的工作服等，这些如果执行的不严，都可能引起感染。医护人员、患者的手污染是造成院内感染的重要传播途径。由于医护人员接触患者污染的物品机会多，易将病原体通过手传递给其他患者或用品，造成间接污染，因此医护人员接触患者后不认真洗手消毒，就可成为输送病原体的工具。此外操作用具混合使用，可造成患者间病原体的直接传染。 1.4易感人群 是指容易发生感染的人群，其发生感染的威险比一般人大得多，如年老体弱、慢性病人、放化疗病人。 2护理管理工作在控制医院感染中的重要作用 医院感染的预防控制离不开护理管理，完善的护理制度和正确的操作程序，是控制医院管理的关键。护士是医院感染的预防者和控制者，护理工作在医院感染中发挥着重要的作用，在预防和控制医院感染的全过程中，护理管理者及护理人员是预防和控制医院感染的主力。世界卫生组织提出有效控制医院感染的关键措施为：消毒、灭菌、无菌技术、隔离、合理使用抗生素，以及检测效果评价。这些无一不与护理工作密切相关，实际上这些预防、控制医院感染的手段，就是护理工作的基础。 3医院感染的预防控制措施
脐带血干细胞检测 对每份脐血干细胞进行下列检测： ①母体血样做梅毒、HIV和CMV等病原体检测，这一检测使脐血干细胞适合于其它家庭成员应用。如任何一种病原体测试阳性，需重复测定。 ②每份脐血干细胞样本同时检测确定没有微生物污染。 ③细胞活性检测、有核细胞数、CD34+细胞数、集落形成试验等。CD34是分子量115KD 的糖蛋白分子，使用特定单克隆抗体（抗-CD34）确定，脐血祖细胞的大部分，包括体外培养产生造血集落的细胞都包含在表达CD34抗原的细胞群中。 ④HLA组织配型、ABO血型。 一、采血方式及其优点 再生缘生物科技公司采用最严谨的封闭式血袋收集法，避免在收集脐带血液时可能遭受微生物污染的发生，且以最少之操作步骤，收集最大量之脐带血液方式，在产房内即可完成。 二、脐带血处理与保存 脐带血收集于血袋，经专人运送至再生缘生物科技公司之无菌细胞分离实验室后，由专业的技术人员于完全无菌的环境下，依标准操作程序将血液进行分离，收集具有细胞核的细胞，其中含有丰富的血液干细胞，经加入冷冻保护剂和适当品管检测后，并进行以最适合
血液干细胞的冷冻降温程序方式，进行细胞冷冻程序，达到避免细胞受到冷冻过程之伤害。完成后，冷冻细胞立刻保存于摄氏零下196度的液态氮槽中。所有操作程序记录和细胞保存相关数据，均由计算机条形码系统追踪确认，完全符合国际脐带血库之标准操作程序和品管要求。 母亲血液之检测 为确保所操作和保存的脐带血液细胞，符合国际血液操作规范，并提供客户最大的保障，对于产妇血液必须同时进行一些病毒传染病的检测，以确保没有下列病毒，如艾滋病毒(HIV)、C型肝炎病毒(HCV)、人类T细胞淋巴病毒(HTLV)和梅毒(syphilis)，同时对于B型肝炎病毒(HBV)和巨细胞病毒(CMV)加以侦测和纪录，作为将来可能应用脐带血细胞时之必要参考数据并符合卫生医疗之要求。 脐带血细胞之品管 对于所保存之脐带血细胞均进行多项操作流程监控和品管检测，如微生物污染检测、血液细胞浓度、细胞存活率、细胞活性测定等，每一步骤均有详细之纪录，在操作方法和使用仪器方面均定期进行验证和校验，以符合国际医疗标准。 三、实验室、贮存处所介绍 再生缘生物科技公司拥有符合美国联邦标准(FED-STD-209E)和中华民国优良药品制造标准（一区、二区、三区）的生物安全实验室和无菌操作设备，在专业的技术人员依标准操作程序下进行血液分离和保存步骤，保障客户珍贵样品和权益。 分离后之细胞将依浓度分装入4-6个冷冻管，计算机降温冷冻完成后，即由食品工业发展研究所国家细胞库专业液态氮库房人员，将冷冻细胞分别存放于二个不同的脐带血细胞专属液态氮槽中保存，在安全机制上更有保障。液态氮库房拥有五吨的液态氮供应系统，每一液氮槽均有自动充填装置和异常警报系统，和每日值勤人员监控，确保冷冻细胞处于最佳的冷冻状态。 四、安全管制措施 脐带血液经快递送达无菌细胞分离实验室后，每一步骤均有专业技术人员操作和监督，并将所有分析数值详细填于具有条形码管制之分析表格和计算机数据表中，利用条形码和读码系统确认样品之专一性，避免人为失误，且便于追溯和数据品管。 在冷冻细胞保存上
胎盘干细胞与脐带血干细胞的区别 干细胞是一类具有自我复制和多向分化能力的原始的未分化的细胞，它可以向多种类型细胞分化，并具有相应的功能，可以用来修复和替代受到损伤，病变的组织和器官。目前主要的成体干细胞来源有胎盘来源、脐带来源、脐带血来源和骨髓来源的干细胞，本文主要介绍一下胎盘来源的干细胞和脐带血来源的干细胞的区别： 1、分离部位不同：胎盘干细胞是从胎盘组织中分离提取的干细胞，脐带血干细胞是从脐带里面血液中分离提取的干细胞。 2、种类不同：胎盘中的干细胞主要指的是间充质干细胞，而脐带血干细胞主要指的是造血干细胞。 3、分化能力不同：1）胎盘干细胞分化能力强，在特定的诱导条件下可以分化成血管干细胞、神经干细胞、肝干细胞等多种类型的干细胞，从而修复受损和病变的组织和器官2）脐带血干细胞可以在体内向红细胞、血小板等各种血液细胞分化。 4、数量不同：1）胎盘体积大，从中提取的干细胞数量丰富，并可以在体外培养扩增，扩增培养的子细胞数量达十亿个，可以供成人多次使用2）脐带血干细胞的数量要根据抽取的脐带血多少而定，不可以在体外培养扩增，一份脐带血干细胞可以供40kg以下患者一次使用。 5、治疗使用：1）胎盘干细胞目前在治疗脑瘫、糖尿病、肝硬化、心血管疾病等诸多疾病都显示了良好的效果2）脐带血干细胞可以治疗白血病，再生障碍性贫血等血液系统疾病。不过对于儿童白血病多以先天性为主，所以对于这种情况，自己的脐带血干细胞是不能使用的，需要配型使用捐献的脐血干细胞。 6、配型方面：二者自体使用都不需要配型，如果异体使用，胎盘干细胞由于免疫源性低的特点，所以配型成功率非常高，有血缘关系的亲属都可以使用；脐带血干细胞与父母配型有1/2的几率，与兄弟姐妹有1/4的几率。
脐带血造血干细胞库技术规范(试行) I 脐带血造血干细胞库(简称脐带血库)的质量控制 1 规章制度和操作规程 脐带血库必须制定脐带血采集、制备、检测、库存、选择和发放的规章制度、操作规程。 1.1 脐带血供者筛选标准和咨询。 1.2 脐带血采集和运送。 1.3 脐带血制备、冷冻、库存。 1.4 标签。 1.5 传染性疾病、人类组织相容性抗原（HLA）分型、造血干细胞和其他检测。 1.6 库存脐带血和脐带血检测标本的确认。 1.7 脐带血的发放。 1.8 脐带血库与移植机构之间的运输。 1.9 数据管理、申请查询、供者与受者配型、脐带血的选择。 1.10 移植随访资料的收集和分析。 1.11 人员培训和继续教育。 1.12 材料、试剂和设备。 1.13 不合格产品、操作错误和事故的报告。 1.14 卫生清洁。 1.15 保密制度。 2 规章制度和操作规程的执行 2.1有脐带血库主任的签字及开始实施的日期。 2.2各项规章制度和操作规程修改，须由脐带血库主任或文件起草人进行审查、签字并标明日期。 2.3 规章制度和操作规程应置于方便工作人员随时取用的位置。 2.4 存档的各种规程和标准记录应长期保留。 2.5 如认为本技术规范不适应当前发展，允许各脐带血库根据情况适当调整，但应报脐带血造血干细胞库专家委员会备案，备案期为30天。专家委员会如不同意备案的规章制度和操作规程，应在备案期间内通知备案单位停止执行。 3 质量控制 3.1 应有专门的质量控制规程，以便对脐带血库工作人员在常规操作中所使用的规程、试剂、设备和材料进行质量控制。 3.2 脐带血库内部的质量控制 3.2.1应由脐带血库主任或指定专人进行质量控制。 3.2.2脐带血库内部的质量控制包括质量评估，改进和修正的措施，错误和事故的处理。 3.2.2.1 脐带血库必须有不合格产品的记录和报告。 3.2.2.2 脐带血库主任应定期召开质量评价会议，对错误和事故进行评价；对重大事故应及时处理。 3.2.2.3 脐带血库主任必须签发对规程的修正。
医院感染预防和控制的护理管理 护理管理是预防和控制医院感染的关键。医院应按照要求建立健全医院感染管理制度，加强感染管理运行机制保障责任落实，强化护理分级管理落实责任；加强医院感染知识培训提高控制医院感染意识，发挥护士长的主观能动性落实医院感染管理措施，认真执行消毒和无菌管理，合理使用抗菌药物，做好医院感染的健康教育和应急管理；加强医院内环境管理，清除污染源；做好医院感染监测，以有效降低医院感染的发生，保护医患双方的身心健康。 标签：护理管理；医院感染；预防和控制；医院管理 [Abstract] The nursing management is the key to prevent and control the hospital infection，the hospital should establish and improve the hospital infection management system，enhance the hand hygiene management，enhance the infection management operation mechanism，ensure the implementation of duties，enhance the implementation responsibility of nursing grading management，enhance the hospital infection knowledge training，improve and control the hospital infection awareness，develop the subjectivity of head nurses，implement the hospital infection management measures，carefully carry out the disinfection and aseptic management，rationally use the antibacterials，do a good job in the health education and emergency management of hospitals，enhance the environment management in the hospital，clear the pollution source and do a good job in the hospital infection monitoring，which can effectively reduce the occurrence of hospital infection and protect the mental and physical health of doctors and patients. [Key words] Nursing management；Hospital infection；Prevention and control；Hospital management 抗菌藥物的不合理应用和各种微创技术的发展，医院感染的发生机率不断提高，已经引起人们的高度重视[1]。医院感染与医院管理关系密切，研究表明30%～50%医院感染与护理管理和护理操作有关[2]。预防与控制医院感染应贯穿护理工作的每一环节，其中任何一环出现问题，都可能导致医院感染的发生，甚至造成医院感染的局部爆发。可见，护理管理与医院感染之间是相互依赖相互促进的，护理质量决定了医院感染的发生和控制水平[3]。为此，笔者总结分析医院感染预防和控制的护理管理措施如下。 1 建立健全管理制度和执行 1.1 建立健全医院感染管理制度 建章立制是保证工作开展的基础。医院必须依据《医院感染管理规范》及《消毒技术规范》[4]以及相关法律法规，成立医院感染管理委员会组织机构，下设相关科室小组，具体负责整个医院和对应科室的医院感染管理工作。要根据相关
生命科学 Chinese Bulletin of Life Sciences 第18卷 第4期2006年8月 Vol. 18, No. 4Aug., 2006 脐带血干细胞的基础与应用研究 顾东生, 刘 斌, 韩忠朝* （中国医学科学院中国协和医科大学血液学研究所实验血液学国家重点实验室，天津 300020） 摘 要：作为造血干/祖细胞(hematopoietic stem cells/hematopoietic progenitor cells, HSCs/HPCs)的另一 来源，脐带血已经应用于临床治疗多种恶性和非恶性疾病。脐带血中HSCs/HPCs 的质与量是决定其临床应用效果的最重要因素。同时，脐带血中还存在多种非造血的干细胞和前体细胞，如间充质干细胞(mesenchymal stem cells, MSCs)、内皮前体细胞(endothelial progenitor cells, EPCs)和非限制性体干细胞(unrestricted somatic stem cells, USSCs)等，这些细胞可能会在未来的细胞治疗和再生医学中发挥重要作用。本综述还讨论了脐带血的临床应用及HSCs/HPCs 的体外扩增、增加HSCs 归巢和再植能力等提高其临床应用能力的相关研究。关键词：脐带血；造血干细胞；移植 中图分类号：R322.2; R323.3; Q813 文献标识码：A The research and application of cord blood stem cells GU Dong-Sheng, LIU Bin, HAN Zhong-Chao* (State Key Laboratory of Experimental Hematology, Institute of Hematology, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China) Abstract: Umbilical cord blood (UCB), as an alternative source of hematopoietic/progenitor stem cells (HSCs/HPCs), has been used clinically for a large number of malignant and non-malignant disorders. The quality and quantity of HSC and HPC may be the most important factors on which the capacity of UCB to perform clinical function depends. Other non-HSCs/HPCs, such as mesenchymal stem cells (MSCs), endothelial progenitor cells (EPCs) and unrestricted somatic stem cells (USSCs), also present in cord blood, which may play a future role in cell therapy and regenerative medicine. This review also covers the efforts to expand HSCs and HPCs ex vivo and recent studies on attempts to enhance the homing and engrafting capability of HSCs as means to enhance the clinical utility of UCB. Key words: umbilical cord blood; hematopoietic stem cells; transplantation 收稿日期：2006-04-25 基金项目：“863”计划(2003AA205060)；“973”项目子项(2001C B5101) 作者简介：顾东生(1981—)，男，硕士研究生；刘 斌(1973—)，男，硕士，助理研究员；韩忠朝(1953—)，男，博士，教授，博士生导师，*通讯作者。 文章编号 ：1004-0374(2006)04-0323-05 1988年，Broxmeyer 首先以实验证明脐带血(umbilical cord blood, UCB)中富含造血干细胞(hematopoietic stem cells, HSCs)。法国Gluckman 等[1]在巴黎圣路易斯医院为一位患有先天性再生不良性贫血的儿童实施了世界上首例脐带血移植术，并取得成功。从此，人们对于一直被当成废弃物丢掉 的胎盘和脐带血有了全新的评价和认识，至今，各国学者对脐带血的基础研究和临床应用进行了大量工作并取得很大成绩。本文对脐带血中存在的多种干/祖细胞的生物学特性及临床应用研究进行综述。1 脐带血干细胞 在现阶段，脐带血之所以能够应用于临床治疗
重视护理管理控制医院感染 发表时间：2013-08-05T10:30:10.310Z 来源：《中外健康文摘》2013年第25期供稿作者：马秀丽 [导读] 建立健全的护理感染管理体系是做好控制医院感染工作的前提。因此，护理部成立了护理感染管理三级监控网络。马秀丽(吉林省松原市中心医院吉林松原 138000) 【中图分类号】R47 【文献标识码】B【文章编号】1672-5085(2013)25-0357-02 【摘要】目的探讨加强护理管理在控制医院感染的作用。方法在护理管理中健全控制医院感染监督组织，完善控制医院感染规章制度，加强培训，落实管理措施。结果增强了护理人员的医院感染控制意识，提高了环境卫生学合格率，减少护理人员职业暴露的发生，降低了医院感染发生率。结论加强护理管理对控制医院感染、提高医疗护理质量是十分重要的。 【关键词】护理管理医院感染控制质量 护理管理是医院管理的重要组成部分，其质量评价是医院整体医疗质量的重要标准之一。护理工作贯穿于预防医院感染的各个环节，任何环节的疏忽，都有可能造成医院感染的发生，影响医疗护理质量，也给患者带来不必要的损害和经济损失。自2009年开始，我院在护理管理工作中，健全医院感染护理的组织管理、加强培训和落实院感控制的各项措施，有效地降低医院感染的发生，现报道如下。 1 具体做法 1.1 建立护理感染管理体系建立健全的护理感染管理体系是做好控制医院感染工作的前提。因此，护理部成立了护理感染管理三级监控网络。三级组织明确职责，分工负责，层层把关，相互制约。 1.2 建立和完善护理管理制度是规范医院感染管理的重要保证护理部在严格执行国家规范和贯彻落实有关法律法规的基础上，及时修订和完善各项管理制度和措施，并规范操作规程，量化考核细则。 1.3 加强培训，提高护理人员、卫生员预防医院感染意识 1.3.1 通过培训，使护理人员在医疗活动中强化法规意识及安全意识，规范自己的医疗行为，提高其参与医院感染控制的责任感，有效地控制医院感染的发生。 1.3.2 医院的保洁人员文化程度低，未受过专业培训，缺乏科学的清洁卫生理念。因此，对保洁人员采取针对性的培训，使他们认识到预防医院感染对个人、家庭、医院及社会的重要性，提高对清洁、消毒制度执行的依从。 1.3.3 我们重视对刚毕业的护士、进修人员、实习生的培训和管理，在上岗前进行院感相关知识培训并考核，增强他们对医院感染的预防和控制意识。 1.4 强化预防与控制措施 1.4.1 加强清洁和消毒工作:(1)每天按时打开空气消毒机、紫外线进行空气消毒。湿式清扫地面，病室通风3次／d。每周清洗空调机过滤网1次。(2)重视操作台、婴儿磅秤、培养箱、光疗箱、治疗车、床头桌、门把手的清洁和消毒，每日用500mg／L氯消毒液擦拭2次。(3)对医务人员和患者频繁接触的物体表面(如心电监护仪、微量输液泵、呼吸机等医疗器械的面板或旋钮表面、听诊器等)进行擦拭消毒。(4)感染病人专室放置，所用的物品专室使用。(5)新生儿用品一人一用一消毒，奶瓶奶嘴采用高压蒸汽灭菌。 1.4.2 加强医务人员手卫生我院严格执行《医务人员手卫生规范》(WS／T313-2009)。在每个护理单元的洗手池上安装感应水龙头和洗手液感应器，张贴了洗手流程标识图；在全院护理治疗室的每辆治疗车上配备了速干手消毒剂，要求护士在给每一个患者做治疗后，必须洗手或使用速干手消毒剂进行手消毒。 1.4.3 遵守无菌技术操作规程，尽量减少各种侵袭性操作。若病情需要，医务人员应当严格遵守无菌技术操作规程，特别是在实施各种侵入性操作时，应当严格执行无菌技术操作和标准操作规程，避免污染。 1.5 认真做好环境卫生、消毒灭菌效果检测工作。 1.6 严格抓好供应室的消毒灭菌工作：(1)供应室流程布局合理，明确划分清洁区、无菌区、污染区。(2)强化人员的质量管理意识，规范操作流程，对各种医疗器械从清洗、包装、灭菌到无菌物品的保管发放的每个环节都严格把关。(3)按规范要求做好灭菌炉的物理监测、化学监测和生物监测，以确保供应室的灭菌质量。 1.7 开展普遍预防知识教育，要求护理人员在护理活动中坚持做到标准预防，正确掌握针刺伤的预防和处理方法，建立职业暴露应急预案和血液追踪的有关规定，为医务人员的职业防护工作提供指导，配备防护用品，争取最大限度地降低职业暴露的风险和伤害，保障医务人员的安全。 2 效果 2009年开始加强护理管理后，护理人员的医院感染控制意识明显提高，消毒灭菌效果检测合格率逐年上升、职业暴露发生例数和医院感染发生情况逐年下降。 3 讨论 环境卫生学常规监测往往是在有充分准备的情况下，即消毒后、医疗操作前采样，一般都能够达到标准要求，并不一定能真实反映医院环境的污染程度，不能作为判断医院感染风险的指标。在医院环境卫生学合格率提高的同时，医院感染率也呈下降趋势，因此，我们认为加强护理管理、提高环境卫生学合格率是控制医院感染的有效途径之一。 实践证明，通过加强护理管理和培训，可提高护士医院感染控制意识和防护意识，正确使用防护用品，减少职业暴露的发生，也可以有效地促进《医院感染管理办法》和《消毒技术规范》的落实。同时，加强护理管理、完善工作制度、规范操作规程、健全监督管理机制是促进护理质量的有力保证，又是控制院内感染的有效手段之一，在医院感染管理中占有极其重要的位置。