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1.
We investigated whether commonly used injectable laboratory anesthetics alter the regulation of augmented breaths (ABs) in different respiratory backgrounds. Male rats were studied on three separate experimental days, receiving one of three injections in randomized order: ethyl carbamate (‘urethane’; 1.2 mg kg−1), ketamine/xylazine (ket/xyl; 80/10 mg kg−1), or normal saline. Following each of the three interventions, breathing was monitored during 15 min exposures to normoxia (room air), hypoxia (10% O2) and hypoxia + CO2 (10% O2, 5% CO2). Urethane anesthesia completely eliminated ABs from the breathing rhythm in room air conditions (p < 0.001), and decreased the hypocapnia-dependent component of this response (p < 0.001). ket/xyl left the normal incidence of ABs in room air breathing intact but significantly suppressed the hypoxia-induced facilitation of ABs (p = 0.0015). These results provide the first clear evidence that laboratory anesthesia can profoundly alter the regulation of ABs including the hypocapnia-dependent component of their facilitation.  相似文献   

2.
The diaphragm muscle (DIAm) is responsible for breathing and determines the ability to generate both ventilatory and non-ventilatory behaviors. Size limitations of the mouse make transdiaphragmatic pressure (Pdi) measurement using a dual balloon system untenable. Adult C57BL/6J mice (n = 8) and C57BL/6 × 129 (n = 9), underwent Pdi measurements using solid-state pressure catheters spanning the thoracic and abdominal surfaces of the DIAm. Measurements were conducted during eupnea, hypoxia (10% O2)–hypercapnia (5% CO2), chemical airway stimulation (i.e., sneezing), spontaneously occurring deep breaths, sustained tracheal occlusion, and bilateral phrenic nerve stimulation. There was a difference in the Pdi generated across the range of ventilatory and non-ventilatory behaviors (p = 0.001). No difference in Pdi across behaviors was evident between mouse strains (p = 0.161). This study establishes a novel method to determine Pdi across a range of DIAm behaviors in mice that may be useful in evaluating conditions associated with reduced ability to perform expulsive, non-ventilatory behaviors.  相似文献   

3.
To determine how central opioid receptor activation alters turtle breathing, respiratory-related hypoglossal (XII) motor bursts were recorded from isolated adult turtle brainstems during 60 min bath applications of agonists for delta- (DOR), kappa- (KOR), or nociceptin/orphanin (NOR) receptors. DADLE (DOR agonist) abolished XII burst frequency at 0.3–0.5 μM. DPDPE (DOR agonist) increased frequency by 40–44% at 0.01–0.1 μM and decreased frequency by 88 ± 8% at 1.0 μM. U-50488 and U-59693 (KOR agonists) decreased frequency by 65–68% at 100 and 50 μM, respectively. Orphanin (NOR agonist) decreased frequency by 31–51% at 1.0–2.0 μM during the first 30 min period. Orphanin (0.5 and 2.0 μM) increased bursts/episode. Although morphine (10 μM) abolished frequency in nearly all brainstems, subsequent co-application of phenylephrine (α1-adrenergic agonist, 20–100 μM) with morphine restored activity to 16–78% of baseline frequency. Thus, DOR, KOR, and NOR activation regulates frequency and NOR activation regulates episodicity, while α1-adrenergic receptor activation reverses opioid-induced respiratory depression in turtles.  相似文献   

4.
The periaqueductal gray (PAG) and nucleus cuneiformis (CnF), like the rostral ventromedial medulla, have functional roles in descending pain-inhibitory pathway related to morphine antinociception. There is not any evidence concerning the role of different regions of the PAG on antinociceptive effect of morphine administered into the CnF in pain modulatory system. In the present study, we investigate whether electrolytic lesion of dorsolateral periaqueductal gray (dl-PAG) influence the analgesic effect of morphine microinjected into the CnF. 71 adult male Wistar rats weighting 230–280 g cannulated bilaterally into the CnF, concurrently lesion of dl-PAG was done. The tail-flick and formalin tests were performed to measure pain and antinociceptive effect of morphine microinjected into the CnF (2.5 μg/0.3 μl saline per side). The tail-flick latency was measured at 15, 30, 45, 60 and 75 min following morphine microinjection. In formalin test, pain behavior was recorded for 60 min in early (0–5 min) and late (15–60 min) phases after formalin injection. Each rat was given a subcutaneous 50-μl injection of formalin 2.5% into plantar surface of hind paw following morphine administration. The results showed that dl-PAG lesion attenuated the effect of morphine microinjected into the CnF both in tail-flick and formalin tests while dl-PAG lesion solely did not alter basal pain behavior as compared to control group. In conclusion, our results suggest the existence of a direct or indirect projection from CnF to the dl-PAG at least at the level of the morphine antinociception in pain modulation.  相似文献   

5.
The problem of morphine tolerance and dependence is a universal phenomenon threatening social health everywhere the world. The major objective of this paper was to investigate the effects of fruit essential oil (FEO) of Cuminum cyminum on acquisition and expression of morphine tolerance and dependence in mice. Animals were rendered dependent on morphine using the well-established method in which was morphine (50, 50, 75 mg/kg; s.c.) injected three times daily for 3 days. In experimental groups, administration of FEO (0.001, 0.01, 0.1, 0.5, 1 and 2%; 5 ml/kg; i.p.) or Tween-80 (5 ml/kg; i.p.) was performed 60 min prior to each morphine injection (for acquisition) or the last injection of morphine on test day (for expression). Morphine tolerance was measured by tail-flick before and after administration of a single dose of morphine (50 mg/kg; s.c.) in test day (4th day). Morphine dependence was also evaluated by counting the number of jumps after injection of naloxone (5 mg/kg; i.p.) on the test day. The results showed that Cumin FEO, only at the dose of 2%, significantly attenuated the development of morphine tolerance (P < 0.01) and dependence (P < 0.05) while it could be significantly effective on expression of morphine tolerance (1 and 2%) and dependence (0.5, 1 and 2%) in a dose-dependent manner. Solely Cumin FEO injection (0.001–2%) did not show any analgesic effect. In conclusion, the essential oil of Cuminum cyminum seems to ameliorate the morphine tolerance and dependence in mice.  相似文献   

6.
This paper presents the results of a meta-analysis of the treatment outcome studies of different types of psychotherapeutic approaches for adults sexually abused as children. There were 44 studies included comprising 59 treatment conditions, and most of the studies aimed to treat the psychological effects of childhood sexual abuse. Separate meta-analyses were conducted according to study design and outcome domain, in keeping with meta-analytic conventions. For most outcome domains, there was remarkable consistency in overall effect sizes across study design. Effect sizes were predominantly of moderate magnitude for post-traumatic stress disorder or trauma symptoms (g = 0.72–0.77), internalizing symptoms (g = 0.68–0.72), externalizing symptoms (g = 0.41–0.53), self-esteem (g = 0.56–0.58), and global functioning or symptoms (g = 0.57–0.60). Studies measuring interpersonal functioning outcomes had inconsistent effect sizes across study design. Effects were largely maintained at follow-up, although relatively few studies provided follow-up data. A number of moderating variables were examined given the inherent heterogeneity of the studies. Moderator analysis revealed a variety of variables, particularly treatment characteristics, that were associated with better outcomes. However, different variables were identified for the diverse outcomes that were measured, emphasizing the importance of moderator analysis in looking beyond overall treatment effects to ascertain specific elements that confer additional benefit in therapy for the diverse psychological effects of child sexual abuse.  相似文献   

7.
8.

Introduction

The purpose of this study was to identify differentially expressed (DE) genes and biological processes associated with changes in gene expression in primary Sjogren’s syndrome (pSS).

Methods

We performed a meta-analysis using the INMEX program (integrative meta-analysis of expression data) of publicly available microarray GEO datasets of pSS. We performed Gene Ontology (GO) enrichment analyses and pathway analysis using Kyoto Encyclopedia of Genes and Genomes (KEGG).

Results

Three GEO datasets including 37 cases and 33 controls were available for the meta-analysis. We identified 179 genes across the studies which were consistently DE in pSS (146 up-regulated and 33 down-regulated). The up-regulated gene with the largest effect size (ES) (ES = −2.4228) was SELL (selectin L), whose product is required for the binding and subsequent rolling of leucocytes on endothelial cells to facilitate their migration into secondary lymphoid organs and inflammation sites. The most significant enrichment was in the immune response GO category (P = 2.52 × 10−25). The most significant pathway in our KEGG analysis was Epstein–Barr virus infection (P = 9.91 × 10−06).

Conclusions

Our meta-analysis demonstrated genes that were consistently DE and biological pathways associated with gene expression changes with pSS.  相似文献   

9.
Folate has long been implicated in both the metabolism of neurotransmitter molecules, and as an agonist with a direct effect upon neuronal tissue. Folates mediate transfer of one-carbon units into major biosynthetic pathways. From a developmental perspective, the most important reactions are de novo methionine and thymine synthesis, critical for DNA expression and elaboration, respectively. Dihydrofolate reductase (DHFR) is the sole enzyme responsible for maintaining the reduced state of the vitamin needed for these two pathways. Here, we report that the 19 bp-deletion polymorphism of DHFR acts independently (OR 2.69, 95% CI; 1.00–7.28, p < 0.05) and in concert with related folate polymorphisms as a significant risk factor for autism. Possible consequences of this are discussed in the context of the interaction between folate and the glutamatergic nervous system, an area of promising candidate genes for contributing to autism.  相似文献   

10.
Surveys and drug surveillance have demonstrated that the abuse liability of tramadol is considerably low in the general population but appears to be higher in opiate addicts, and this difference could attribute to the poly-drug abuse of opioid addicts, although this hypothesis has not been tested in the laboratory. The present study examined the interactions between tramadol and a full μ opioid receptor agonist morphine or a partial μ opioid receptor agonist buprenorphine in a conditioned place preference (CPP) paradigm in rats. Rats were conditioned with tramadol (2–54 mg/kg, i.p.), morphine (0.125–8 mg/kg, s.c.), buprenorphine (0.01–0.316 mg/kg, s.c.) or a combination of a subeffective dose of tramadol (2 mg/kg) with a subeffective dose of morphine or buprenorphine and the CPP effect was measured. The retention of CPP effect was also examined. Tramadol, morphine and buprenorphine all produced a dose-dependent and significant CPP. A smaller dose of tramadol (2 mg/kg) enhanced morphine- and buprenorphine-induced CPP and shifted the dose-effect curves of both drugs leftward. In addition, the combination of tramadol with morphine or buprenorphine prolonged the retention of CPP. These findings indicate that tramadol potentiates the rewarding effects of morphine or buprenorphine largely in an additive manner and support the general contention that tramadol has relatively low abuse liability.  相似文献   

11.
Programmed cell death 6 (PDCD6), a calcium binding protein of the penta EF-hand protein family, and its receptors are involved in regulation of apoptosis pathways. To evaluate the relationship between genetic polymorphisms of PDCD6 gene and endometriosis (ED) risk, we investigated the association of two single nucleotide polymorphisms (SNPs) of PDCD6 gene (rs4957014 and rs3756712) in 220 endometriosis patients and 386 unrelated healthy controls. The genotypes of these two SNPs were determined by using polymerase chain reaction (PCR)–restriction fragment length polymorphism (RFLP) and DNA sequencing methods. Significantly increased endometriosis risk was observed to be associated with G allele of rs4957014 locus (OR = 1.31, 95% CI = 1.03–1.69). We have also observed increased ED risk was statistically associated with rs4957014 polymorphism in a dominant model (OR = 1.52, 95% CI = 1.09–2.13). Although no association has been found between ED risk and the allele frequencies of rs3756712 locus (a marginal P = 0.066, OR = 1.27, 95% CI = 0.98–1.65), but in a dominant model, increased endometriosis risk was significantly associated with rs3756712 polymorphism (OR = 1.54, 95% CI = 1.11–2.17). In conclusion, the current study indicates that PDCD6 gene may be a new susceptibility gene to endometriosis.  相似文献   

12.
The baroreflex is mainly involved in short-term blood pressure regulation and strongly influenced by activations of medullary circulation centres in the brain stem and higher brain centres. One important feature of the baroreflex is its strong preference for oscillations around 0.1 Hz, which can be seen as resonance or “eigenfrequency” (EF) of the control loop (so-called Mayer waves). In the present study we investigated beat-to-beat heart rate intervals (RRI) and arterial blood pressure (BP) changes after brisk finger movement and their relationship to the “eigenfrequency” determined by cross spectral analysis between RRI and arterial blood pressure time series of 17 healthy subjects. The analyses revealed significant correlations between BP response magnitude (r = 0.63, p < 0.01) respectively RRI response magnitude (r = 0.59, p < 0.05) and EF. This can be interpreted in such a way that subjects with a “high” EF (>0.10 Hz) elicit larger BP responses as well as larger RRI responses when compared to subjects with a “low” EF (<0.10 Hz).  相似文献   

13.

Objective

Aim was to investigate the psychometric properties of a Dutch version of the “Wake Forest Physician Trust Scale”, which intends to measure patients’ trust in their physician.

Methods

A random sample of internal medicine patients visiting the outpatient clinic completed the questionnaire (N = 201). Dimensionality, reliability and validity of the instrument were examined.

Results

The structure of the questionnaire was best explained by a unidimensional construct. Reliability was confirmed: internal consistency was high (α = .88), and mean item-total correlations were all above .40. Construct validity was indicated by patients’ trust in their physician correlating significantly and as hypothesized with (1) satisfaction with their physician (r = .64), (2) with the length of the patient–physician relationship (r = .28), (3) with their willingness to recommend their physician (r = .71) and (4) their unwillingness to switch their physician (r = .61).

Conclusion

The results suggest the Dutch version of the Wake Forest Physician Trust Scale to be a psychometrically sound instrument to assess patients’ interpersonal trust.

Practice implications

Trust is a key feature of the patient–physician relationship, yet has been scarcely researched in other than Anglophone cultures. An adequate Dutch trust questionnaire forms the first step to gaining more knowledge about patient–physician trust in another culture and health care setting.  相似文献   

14.
This study determined whether the membrane-permeable ventilatory stimulant, l-cysteine ethylester (l-CYSee), reversed the deleterious actions of morphine on arterial blood–gas chemistry in isoflurane-anesthetized rats. Morphine (2 mg/kg, i.v.) elicited sustained decreases in arterial blood pH, pO2 and sO2, and increases in pCO2 (all responses indicative of hypoventilation) and alveolar–arterial gradient (indicative of ventilation–perfusion mismatch). Injections of l-CYSee (100 μmol/kg, i.v.) reversed the effects of morphine in tracheotomized rats but were minimally active in non-tracheotomized rats. l-cysteine or l-serine ethylester (100 μmol/kg, i.v.) were without effect. It is evident that l-CYSee can reverse the negative effects of morphine on arterial blood–gas chemistry and alveolar–arterial gradient but that this positive activity is negated by increases in upper-airway resistance. Since l-cysteine and l-serine ethylester were ineffective, it is evident that cell penetrability and the sulfur moiety of l-CYSee are essential for activity. Due to its ready penetrability into the lungs, chest wall muscle and brain, the effects of l-CYSee on morphine-induced changes in arterial blood–gas chemistry are likely to involve both central and peripheral sites of action.  相似文献   

15.
The number of studies on psychological treatments of depression in older adults has increased considerably in the past years. Therefore, we conducted an updated meta-analysis of these studies. A total of 44 studies comparing psychotherapies to control groups, other therapies or pharmacotherapy could be included. The overall effect size indicating the difference between psychotherapy and control groups was g = 0.64 (95% CI: 0.47–0.80), which corresponds with a NNT of 3. These effects were maintained at 6 months or longer post randomization (g = 0.27; 95%CI: 0.16–0.37). Specific types of psychotherapies that were found to be effective included cognitive behavior therapy (g = 0.45; 95% CI: 0.29–0.60), life review therapy (g = 0.59; 95% CI: 0.36–0.82) and problem-solving therapy (g = 0.46; 95% CI: 0.18–0.74). Treatment compared to waiting list control groups resulted in larger effect sizes than treatments compared to care-as-usual and other control groups (p < 0.05). Studies with lower quality resulted in higher effect sizes than high-quality studies (p < 0.05). Direct comparisons between different types of psychotherapy suggested that cognitive behavior therapy and problem-solving therapy may be more effective than non-directive counseling and other psychotherapies may be less effective than other therapies. This should be considered with caution, however, because of the small number of studies. There were not enough studies to examine the long-term effects of psychotherapies and to compare psychotherapy with pharmacotherapy or combined treatments. We conclude that it is safe to assume that psychological therapies in general are effective in late-life depression, and this is especially well-established for cognitive behavior therapy and problem-solving therapy.  相似文献   

16.
Migraine is a common neurological disorder with a complex inheritance pattern. Mutations in genes encoding proteins that are involved in ion transport across the neuronal membrane have been linked to rare monogenic variants of migraine. These or other related genes and proteins are also candidates to be involved in the inherited predisposition to the more common forms of migraine without aura (MO) or migraine with aura (MA). One of these proteins, syntaxin 1A, encoded by the STX1A gene, is a key molecule in ion channel regulation and synaptic exocytosis. We assessed the contribution of STX1A to migraine by analyzing three SNPs that cover the entire gene (rs6951030–rs941298–rs4363087), in a case–control association study in 210 migraine patients (102 MO, 86 MA, 22 hemiplegic migraine) and 210 sex-matched unrelated controls. The single-marker analysis revealed significant differences in both allele frequencies (P = 0.0087, OR = 1.48) and genotype distributions (P = 0.0133) of the rs941298 SNP between migraineurs and controls, with an overrepresentation of T-allele carriers in the migraine sample (OR = 1.78). We subsequently performed a haplotype-based analysis and observed evidence of an overrepresentation of the A–T–G (rs6951030–rs941298–rs4363087) allelic combination in migraine patients and an increased frequency of carriers of this risk haplotype (P = 0.008, OR = 1.71). These differences remained significant when patients were subdivided into MO and MA. When the control series was enlarged for rs941298, we confirmed the association only with the whole migraine group.  相似文献   

17.

Aim of study

Monitor evolution of antibiotic resistance of Pseudomonas aeruginosa from 2002 to 2006 in our hospital to optimize antibiotherapy.

Patients and method

The infections/colonizations with P. aeruginosa have been identified by the hospital's informatic database. Bacteriological samples realized 48 hours after patient's admission was considered as nosocomial. A Cochran-Armitage test was conducted to assess the evolution of resistance.

Results

During this period, 2098 infections/colonizations with P. aeruginosa have been identified. Bacteriological samples (68.5%) were nosocomial. Among the β-lactam antibiotics, ceftazidime and imipenem were the most active (R = 16.8% and 15.2%, respectively), followed by piperacillin and piperacillin–tazobactam (R = 24.8%, 18.4%, respectively). Amikacin and tobramycin were more active than gentamicin (R = 19.9%; 22.2% and 40.6%, respectively). 28.9% of strains were resistant to ciprofloxacin. Nosocomial strains were significantly more resistant than non-hospital strains: ceftazidime: 17.9% versus 14.2%, p = 0.0346; ticarcillin–clavulanic acid: 47.5% versus 39.6%, p = 0.0009; piperacillin–tazobactam: 20.0% versus 14.8%, p = 0.0046; ciprofloxacin: 30.7% versus 25.2%, p = 0.0112. A significant increase in the resistance of nosocomial strains to ceftazidime, ticarcillin–clavulanic acid and piperacillin–tazobactam was noted. Resistance from non-hospital strains to fluoroquinolones, aminoglycosides, ceftazidime, piperacillin and ticarcillin–clavulanic acid decreased significantly.

Conclusion

P. aeruginosa is a predominantly nosocomial microorganism. There is a decrease of resistance for non-hospital strains. But the resistance of nosocomial strains to antibiotics widely prescribed in hospital is worrying.  相似文献   

18.
Japanese encephalitis (JE) is the commonest encephalitis in South East Asia associated with high morbidity and mortality. Neuronal injury is attributed to a number of proinflammatory cytokines. This study evaluates cerebrospinal fluid (CSF) cytokines and chemokines in encephalitis and correlates these with clinical and magnetic resonance imaging (MRI) findings. We examined 14 patients with encephalitis (8 JE, 1 dengue, 5 nonspecific encephalitis) and 10 healthy controls. CSF cytokines (IL-1β, IL-6, IL-10, IL-12p70, TNF-α, IL-8) and chemokines (IP-10, MCP-1, MIG, IL-8 and RANTES) were estimated using Cytometric Bead Array, compared with controls and were correlated with severity of encephalitis, radiological findings and presence of movement disorders. Median age of the patients was 25.5 (range 6–55 years); 6 had seizures, 10 movement disorders and 6 out of 11 had MRI abnormalities. The MRI abnormalities included thalamic involvement in 5, basal ganglia and mid brain in 3 each and cortical involvement in 2 patients. Both the patients with cortical involvement had seizures and 5 of the 10 patients with movement disorders had thalamic, basal ganglia and/or mid brain involvement. There was significant increase in IL-6 (p = 0.01), RANTES (p = 0.02) and IL-8 (p = 0.02) in encephalitis compared to controls but there was no difference in IL12p70, TNF-α, IL-10, IL-1β and MCP-1. Cytokines and chemokines did not correlate with severity of encephalitis, radiological changes and presence of movement disorders. CSF IL-6, IL-8 and RANTES were significantly higher in encephalitis patients compared to controls.  相似文献   

19.

Introduction

NK cell function is regulated by cell surface inhibitory and activating receptors including the C-type lectin receptors and Killer Immunoglobulin-like receptors (KIR). The effect of immune modulating cytokines produced by NK cells in the pathogenesis of end stage renal disease (ESRD) remained intriguing. In this regard the present study assesses the combinatorial association of KIR gene content and KIR receptor–HLA ligand in the North Indian ESRD patients.

Material and methods

KIR gene polymorphism as a susceptible marker in ESRD among 512 patients and 512 ethnically matched controls was analyzed. PCR-SSP based genotyping for KIR gene content and HLA-A, B, C typing was carried out.

Results

Significant difference in frequencies of KIR2DS1–HLA-C2 (p ? 0.0001, OR = 1.98, CI = 1.50–2.61), KIR2DS2–HLAC1 (p ? 0.0001, OR = 1.87, CI = 1.42–2.46), KIR3DS1–HLA-Bw4 (p = 0.0038, OR = 1.46, CI = 1.13–1.88) combinations for ESRD was found. In the combinatorial analysis Bw4+/3DL1/3DS1+ (p ? 0.0001, OR = 4.90, CI = 2.75–8.71) and C1+/2DL2/2DL3/2DS2+/2DS3+ (p = 0.0037, OR = 2.50, CI = 1.35–4.63) showed risk association. KIR3DS1 was observed to be susceptible for all four primary kidney disease groups.

Conclusion

NK cell de-regulation due to HLA ligand binding KIR receptors may be involved in the patho-physiology of ESRD. Upon analyzing the data in this context it was found that C2/C2 donor might improve the clinical outcome of patients having C2 ligands.  相似文献   

20.
Our present study aimed to investigate the effect of four SNPs (G1793A, C1859A, A1980G, G1934A) in toll-like receptor 6 (TLR6) on bovine tuberculosis (bTB) resistance in a case–control study. A total of 603 Chinese Holstein cattle (264 from a dairy farm of Henan province, 339 from Hubei province) were selected to analyze the genotype of TLR6 gene by PCR-RFLP. Genotype frequencies of C1859A and A1980G site differed significantly between bTB-infected and non-infected cows (χ2 = 6.062, P = 0.048 and χ2 = 6.749, P = 0.034, respectively). Relative risk of tuberculosis incidence result showed that genotypes of AA or CA had greater relative risk (OR = 2.730, 95%CI = 0.869–8.573; OR = 1.547, 95CI% = 0.803–2.982, respectively) than those with genotype CC at C1859A site between bTB-infected and non-infected animals. Genotypes of GG or GA had greater relative risk (OR = 2.986, 95%CI = 1.245–7.165; OR = 1.582, 95%CI = 0.734–3.409, respectively) than those with genotype AA at A1980G site. No significant association can be inferred from G1793A and G1934A polymorphism site. The present study suggests that variants in the TLR6 gene are associated with susceptibility to bTB and the TLR6 gene may be considered as a candidate gene for bTB resistance.  相似文献   

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