Measurement of cytokines and chemokines and association with clinical severity of dermatomyositis and clinically amyopathic dermatomyositis.

BACKGROUND: Dermatomyositis (DM) is an autoimmune disease affecting primarily the skin, muscle and lung. Dysregulations of cytokines and chemokines are commonly found in inflammatory disorders. OBJECTIVES: To investigate the association between serum cytokines and chemokines and clinical severity, especially cutaneous lesions and interstitial lung disease (ILD) in patients with DM and clinically amyopathic DM (CADM). METHODS: Clinical features, laboratory findings and serum of 40 patients with DM or CADM were collected and analysed. Serum cytokines and chemokines were measured by enzyme-linked immunosorbent assay or cytometric bead array. A multiple unpaired t-test was performed to compare cytokines and chemokines in patients with DM and healthy controls. Correlations of serum cytokines and chemokines with disease severity were evaluated by Spearman's rank correlation test. RESULTS: Serum interferon (IFN)-ß [rs  = 0·37, 95% confidence interval (CI) 0·078-0·62; P = 0·019] and CXCL10 (rs  = 0·32, 95% CI to -0·004 to 0·57; P = 0·045) were significantly correlated with the Cutaneous Dermatomyositis Disease Area and Severity Index activity score in the subset of patients with DM or CADM. Serum levels of interleukin (IL)-6, IL-10, IL-18 and IFN-ß were significantly higher in the patients with acute/subacute interstitial pneumonia (A/SIP) than in the subset without A/SIP (P < 0·05). IL-6 (rs  = 0·54, 95% CI 0·27-0·72; P < 0·001) and IL-18 (rs  = 0·46, 95% CI 0·21-0·65; P = 0·003) were significantly correlated with the serum level of anti-melanoma differentiation-associated protein 5 antibody. CONCLUSIONS: Serum levels of IFN-ß and CXCL10 may be useful biomarkers for assessing cutaneous disease activity in patients with DM and CADM. In addition, serum IL-6, IL-10, IL-18 and IFN-ß were highly correlated with the occurrence of A/SIP. These cytokines may play a role in the pathogenesis of DM and CADM.

Association between the HER2 Ile655Val polymorphism and response to trastuzumab in women with operable primary breast cancer.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) Ile655Val polymorphism may affect the efficacy of trastuzumab treatment of breast cancer. PATIENTS AND METHODS: HER2 Ile655Val polymorphism was determined in 4167 patients with primary breast cancer using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. We investigated the associations between the HER2 Ile655Val polymorphism and clinical outcomes in women with HER2-negative breast cancer and with HER2-positive breast cancer who received trastuzumab or who did not. RESULTS: At a median follow-up of 44 months, HER2 Ile655Val polymorphism was not significantly associated with survival either in the entire study population of 4167 patients or in 2976 HER2-negative breast cancer patients. Among 816 HER2-positive patients who received adjuvant chemotherapy and/or endocrine therapy without trastuzumab treatment, patients with the Val/Ile or the Val/Val genotype had a significantly worse disease-free survival (DFS) and distant DFS (DDFS) than those with the Ile/Ile genotype (DFS, adjusted hazard ratio [HR] 1.5; 95% confidence interval [CI] 1.0-2.3; P = 0.037; DDFS, adjusted HR 1.9; 95% CI 1.2-2.9 P = 0.005). In contrast, among 212 HER2-positive patients who received chemotherapy in combination with trastuzumab treatment, patients with the Val/Ile or the Val/Val genotype had a significantly better DFS and DDFS than those with the Ile/Ile genotype (5-year DFS, 100% versus 83%; P = 0.008; 5-year DDFS, 100% versus 89%; P = 0.031). CONCLUSIONS: HER2 Ile655Val polymorphism affects the function of HER2 gene only restricted in HER2-positive breast cancers. HER2-positive breast cancer patients with the Val variant have an aggressive phenotype, but are sensitive to trastuzumab treatment.

Expression profiling stratifies mesothelioma tumors and signifies deregulation of spindle checkpoint pathway and microtubule network with therapeutic implications.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a lethal neoplasm exhibiting resistance to most treatment regimens and requires effective therapeutic options. Though an effective strategy in many cancer, targeted therapy is relatively unexplored in MPM because the therapeutically important oncogenic pathways and networks in MPM are largely unknown. MATERIALS AND METHODS: We carried out gene expression microarray profiling of 53 surgically resected MPMs tumors along with paired normal tissue. We also carried out whole transcriptomic sequence (RNA-seq) analysis on eight tumor specimens. Taqman-based quantitative Reverse-transcription polymerase chain reaction (qRT-PCR), western analysis and immunohistochemistry (IHC) analysis of mitotic arrest deficient-like 1 (MAD2L1) was carried out on tissue specimens. Cell viability assays of MPM cell lines were carried out to assess sensitivity to specific small molecule inhibitors. RESULTS: Bioinformatics analysis of the microarray data followed by pathway analysis revealed that the mitotic spindle assembly checkpoint (MSAC) pathway was most significantly altered in MPM tumors with upregulation of 18 component genes, including MAD2L1 gene. We validated the microarray data for MAD2L1 expression using quantitative qRT-PCR and western blot analysis on tissue lysates. Additionally, we analyzed expression of the MAD2L1 protein by IHC using an independent tissue microarray set of 80 MPM tissue samples. Robust clustering of gene expression data revealed three novel subgroups of tumors, with unique expression profiles, and showed differential expression of MSAC pathway genes. Network analysis of the microarray data showed the cytoskeleton/spindle microtubules network was the second-most significantly affected network. We also demonstrate that a nontaxane small molecule inhibitor, epothilone B, targeting the microtubules have great efficacy in decreasing viability of 14 MPM cell lines. CONCLUSIONS: Overall, our findings show that MPM tumors have significant deregulation of the MSAC pathway and the microtubule network, it can be classified into three novel molecular subgroups of potential therapeutic importance and epothilone B is a promising therapeutic agent for MPM.

Promoter methylation of BRCA1 in triple-negative breast cancer predicts sensitivity to adjuvant chemotherapy.

BACKGROUND: BRCA1 function is inactivated through BRCA1 promoter methylation in a substantial number of triple-negative breast cancers. We investigated the impact of BRCA1-methylation status on the efficacy of adjuvant chemotherapy in patients with triple-negative breast cancer or with non-triple-negative breast cancer. METHODS: BRCA1 promoter methylation was assessed in 1163 unselected breast cancer patients. Methylation was evaluated using a methylation-specific PCR (MSP) assay. RESULTS: In the subgroup of 167 triple-negative breast cancer patients who received adjuvant chemotherapy, patients with BRCA1-methylated tumors had a superior 10-year disease-free survival (DFS)(78% versus 55%, P = 0.009) and 10-year disease-specific survival (DSS) (85% versus 69%, P = 0.024) than those with BRCA1-unmethylated tumors, and BRCA1 methylation was an independent favorable predictor of DFS and DSS in a multivariate analysis in this subgroup [DFS: hazard ratio (HR) = 0.45; 95% confidence interval (CI) 0.24-0.84; P = 0.019; DSS: HR = 0.43; 95% CI = 0.19-0.95; P = 0.044]. In contrast, in 675 non-triple-negative breast cancer patients who received adjuvant chemotherapy, BRCA1 methylation was an unfavorable predictor of DFS and DSS in univariate analysis (DFS: HR = 1.56; 95% CI 1.16-2.12; P = 0.003; DSS: HR = 1.53; 95% CI = 1.05-2.21; P = 0.026). CONCLUSIONS: Triple-negative breast cancer patients with BRCA1-methylated tumors are sensitive to adjuvant chemotherapy and have a favorable survival compared with patients with BRCA1-unmethylated triple-negative tumors.

Bronchial asthma and risk of 4 specific cardiovascular diseases and cardiovascular mortality: a meta-analysis of cohort studies.

OBJECTIVE: It has been shown that asthma is significantly associated with the risk of cardiovascular disease (CVD). Under this background, this study aimed to systematically classify and summarize the epidemiological evidence of asthma and the risk of 4 specific cardiovascular diseases (CVDs) and cardiovascular mortality (CVM). MATERIALS AND METHODS: PubMed and Embase databases were searched from inception to December 1st, 2021 in order to identify relevant studies. The random-model was used to assess the pooled results. All pooled results were expressed as risk ratios (RRs) and corresponding 95% confidence intervals (CIs). RESULTS: Finally, a total of 18 studies were included in the present meta-analysis. Compared with non-asthmatic group, patients with asthma had significantly increased risks of subsequent cardiovascular heart disease (CHD, RR 1.33; 1.19-1.50, I2=80.3%; p<0.001), and CVM (RR 1.35; 1.15-1.59, I2=0%; p<0.001). Similarly, the risks of heart failure (HF, RR 2.10; 1.98-2.22, I2=17.4%; p<0.001) and myocardial infraction (MI, RR 1.39; 1.16-1.66, I2=59.3%; p<0.001) were higher in the asthmatic population. However, the higher risk of atrial fibrillation (RR 1.70; 1.45-2.00, I2=0%; p<0.001) was observed only in the active asthmatic population. CONCLUSIONS: In general, asthma is associated with subsequent increased risks of CHD, MI, AF, HF, and CVM. In addition, among patients with asthma, females have a higher risk of CHD than males, while active asthmatic patients have a higher risk of CVM than non-active asthmatic patients.

Experimental research on wild-type p53 plasmid transfected into retinoblastoma cells and tissues using an ultrasound microbubble intensifier.

The transfection efficiency of wild-type p53 (wtp53) was investigated in retinoblastoma (RB) Y79 cells using an ultrasound microbubble technique. A human RB nude mouse xenograft tumour model was also used to investigate whether this technique could deliver wtp53 into solid tumours. Reverse transcription-polymerase chain reaction (RT-PCR) demonstrated that wtp53 was successfully transfected into Y79 cells in the plasmid with microbubbles and ultrasound group and in the plasmid with liposomes group, but not in the plasmid with ultrasound group or in the untreated control group. Flow cytometry showed that apoptosis was highest in the microbubbles and ultrasound group (25.58%) compared with the plasmid with liposomes group (19.50%), and the other two groups (< 10%). RT-PCR also showed that the wtp53 gene was successfully transfected into solid tumours in the plasmid with microbubbles and ultrasound group. This study provides preliminary evidence in support of a potential new approach to RB gene therapy.

Correlation between serum microRNA-136 levels and RAAS biochemical markers in patients with essential hypertension.

OBJECTIVE: The aim of this study was to investigate the correlation between microRNA-136 levels and biochemical markers of renin-angiotensin-aldosterone system (RAAS) in patients with essential hypertension (EH). PATIENTS AND METHODS: The subjects were divided into EH group (n=110) and healthy control group (n=110). MicroRNA-136 expression, angiotensin-converting enzyme (ACE) activity, and expression of renin (RA) and angiotensin II (Ang II), and aldosterone (ALD) in peripheral blood serum were examined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), equine glycylglycine glycine method, magnetic particle chemistry, and radioimmunoassay, respectively. In addition, the correlation between microRNA-136 and RAAS biochemical markers was estimated by Pearson linear regression. Meanwhile, ROC curve analysis was carried out to evaluate the potential of microRNA-136 for the diagnosis of EH. Follow-up data were recorded for assessing the influence of microRNA-136 on the prognosis in patients with EH. RESULTS: It was found that microRNA-136 expression was remarkably elevated in peripheral blood serum of patients with EH, and the expression levels of biochemical markers of RASS, such as ACE, RA, Ang II, and ALD were also found higher than those in healthy controls. Meanwhile, a significant positive correlation was confirmed between microRNA-136 level and ACE activity, RA, Ang II, as well as ALD levels in patients with EH. In addition, the area under the ROC curve (AUC) was calculated as 0.8662, with a sensitivity of 82.73% and a specificity of 80.91%. After two-months medication intervention, patients with EH expressing a high level of microRNA-136 had better therapeutic efficacy than those with a low level. CONCLUSIONS: In peripheral blood serum, microRNA-136 expression was dramatically negatively correlated with biochemical markers of RASS. High level of microRNA-136 predicts a good prognosis in patients with EH following medication. Therefore, microRNA-136 can be used as a potential biomarker for the diagnosis of EH.

Use of quantum dots to detect human papillomavirus in oral squamous cell carcinoma.

OBJECTIVE: To examine the association of oral squamous cell carcinoma with human papillomavirus (HPV) using quantum dots (QD) in situ hybridization (ISH). METHODS: Expression of HPV16/18 was analyzed in a representative collection of 21 oral squamous cell carcinomas by tissue microarrays. The presence of HPV16/18 high risk was detected by applying QDISH which is compared with conventional ISH. RESULTS: Seven cases out of 21 (33.3%) were positive for QDISH while 1 out of 21 (4.8%) was positive for ISH, although all of HPV DNA were localized in the nuclei in the spinous and basal cell layer of the epithelium. The difference between these two methods was significant (P < 0.05). CONCLUSIONS: These results demonstrate that the QD might be an efficient method for determination of HPV infection and HPV-associated oral squamous cell carcinoma.

[Prevalence of hyperuricemia in the elderly in 7 areas of China].

Objective: To investigate the prevalence of hyperuricemia (HUA) in the elderly in China. Methods: A randomized stratified cluster sampling survey was conducted. And 5 376 residents aged ≥60 year in 7 Beijing, Xi'an and Harbin in northern China and Chengdu, Chongqing, Changsha and Shanghai in southern China were surveyed. A unified questionnaire was used to collect their basic information, and blood samples were taken from them to detect the level of plasma uric acid (UA). The differences in hyperuricemia prevalence among different groups were compared with χ(2) test. Results: The mean concentration of plasma UA was 302.8 µmol/L in the elderly surveyed, 329.5 µmol/L in males and 282.7 µmol/L in females, 272.4 µmol/L in rural residents and 315.5 µmol/L in urban residents. Our study showed the prevalence of hyperuricemia was 13.1% in the elderly surveyed. The prevalence of hyperuricemia in women (14.1%) was higher than that in men (12.0%) (P<0.05); and the prevalence of hyperuricemia was higher in urban residents (15.8%) than in rural residents (6.9%) (P<0.01); in southern area (16.0%) than in northern area (11.6%) (P<0.01). Both the plasma UA level and the prevalence of hyperuricemia increased with age in those aged ≥60 years. The average prevalence of hyperuricemia were 9.5%, 11.9%, 14.5%, 16.4% and 21.9% and the plasma UA levels were 287.7, 295.9, 308.1, 311.6 and 323.3 µmol/L respectively in age group ≥60, 65, 70, 75 and 80 years (P<0.01). Conclusion: The result showed that mean concentration of plasma UA was 302.8 µmol/L and the overall prevalence of hyperuricemia was 13.1% in the elderly surveyed in China. The prevalence of hyperuricemia in females was higher than in males, in urban residents than in rural residents and in southern area than in northern area. Both the UA level and prevalence of hyperuricemia increased with age.

Association of HLA-DQ alleles with the presence of an anti-ß2-glycoprotein I antibody in patients with recurrent miscarriage.

Immunogenetic studies have suggested that autoantibody production is commonly associated with particular human leukocyte antigens (HLA) class II genotypes in certain autoimmune diseases. The objective of this study was to investigate whether the production of anti-ß2-glycoprotein I antibody (aß2GPI) was associated with particular HLA-DQ alleles in patients with recurrent miscarriage (RM). The HLA-DQ genotypes in 126 patients with RM were determined using the polymerase chain reaction-sequence-specific primer method. Both the IgG and IgM isotypes of aß2GPI were measured via enzyme-linked immunosorbent assay. Positive results for either IgG or IgM on two occasions within an interval of 12 weeks were defined as antiphospholipid antibody-positive. The frequencies of the HLA-DQA1*01:02 [odds ratio (OR) 3.4, 95% confidence interval (CI) 1.6-7.0, Pc = 0.018] and HLA-DQB1*02:01 alleles (OR 4.6, 95% CI 2.1-10.2, Pc = 9.18 × 10(-4)) were significantly increased in aß2GPI-positive RM patients compared with aß2GPI-negative RM patients. These results suggest that the HLA-DQA1*0102 and HLA-DQB1*0201 alleles may be involved in the production of aß2GPI in RM patients.

The miR-200 family and the miR-183~96~182 cluster target Foxf2 to inhibit invasion and metastasis in lung cancers.

Metastatic lung cancer is one of the most lethal forms of cancer and molecular pathways driving metastasis are still not clearly elucidated. Metastatic cancer cells undergo an epithelial-mesenchymal transition (EMT) where they lose their epithelial properties and acquire a migratory and invasive phenotype. Here we identify that the expression of microRNAs from the miR-200 family and the miR-183~96~182 cluster are significantly co-repressed in non-small cell lung cancer cell lines and primary tumors from multiple TCGA dataset with high EMT scores. Ectopic expression of the miR-183~96~182 cluster inhibited cancer cell migration and invasion, whereas its expression was tightly modulated by miR-200. We identified Foxf2 as a common, novel and direct target of both these microRNA families. Foxf2 expression tightly correlates with the transcription factor Zeb1 and is elevated in mesenchymal-like metastatic lung cancer cells. Foxf2 expression induced robust EMT, migration, invasion and metastasis in lung cancer cells, whereas Foxf2 inhibition significantly repressed these phenotypes. We also demonstrated that Foxf2 transcriptionally represses E-cadherin and miR-200, independent of Zeb1, to form a double-negative feedback loop. We, therefore, identified a novel mechanism whereby the miR-200 family and the miR-183~96~182 cluster inhibit lung cancer invasion and metastasis by targeting Foxf2.

The role of cyclic AMP as a precursor of extracellular adenosine in the rat hippocampus.

Extracellular adenosine 3':5'-cyclic monophosphate (cAMP) is a potential source of the inhibitory neuromodulator adenosine in the brain. Previous work has demonstrated that cAMP, which is formed intracellularly, can be transported into the extracellular space and subsequently catabolized to adenosine. However, the physiological conditions under which cAMP release might lead to adenosine formation and activation of adenosine receptors are not well understood. In this study we demonstrate that superfusion of hippocampal slices with cAMP or forskolin led to the formation of extracellular adenosine which activated adenosine receptors in a manner comparable to that seen with adenosine superfusion. In contrast, application of brief pulses of cAMP onto the cell bodies of CA1 pyramidal neurons failed to produce an adenosine receptor-mediated response, while application of brief pulses of adenosine or AMP elicited significant responses. These data suggest that large, prolonged increases in extracellular cAMP levels can result in the formation of extracellular adenosine and the activation of adenosine receptors, but brief increases in cAMP levels in the vicinity of individual neurons cannot. These findings imply that increases in cAMP levels may lead to relatively slow increases in extracellular adenosine, as opposed to the fast, spatially restricted increases that would occur following the release of other adenine nucleotides.

Regulation of extracellular adenosine in rat hippocampal slices is temperature dependent: role of adenosine transporters.

While a great deal is known about stimuli that can induce the release of adenosine from brain tissue, relatively little is known about the regulation of the basal extracellular concentration of adenosine that is present in the absence of stimulation. Under normal conditions, enough adenosine is present to tonically activate a significant portion of the high-affinity adenosine A1 receptors. The present experiments demonstrated that the estimated basal concentration of extracellular adenosine in rat hippocampal slices maintained at 21 degrees C (430 nM) is approximately twice that at 32 degrees C (220 nM). The sensitivity of presynaptic modulatory adenosine A1 receptors was not significantly different at 21 degrees C or at 32 degrees C. Slices maintained at 21 degrees C also showed a reduced ability to inactivate extracellular adenosine, which reflects a reduction in adenosine transport across cell membranes. This effect appears to be primarily due to a reduction in the function of the equilibrative, dipyridamole-sensitive (ei) adenosine transporter; the nitrobenzylthioinosine-sensitive equilibrative transporter (es transporter) appears to be relatively less affected by temperature than is the ei transporter. These experiments demonstrate that extracellular concentrations of adenosine in the brain are sensitive to temperature, and suggest that some of the neurological effects of hypothermia might be mediated via increased concentrations of adenosine in the extracellular space.

Excitatory amino acid neurotransmission in the primary gustatory nucleus of the goldfish Carassius auratus.

The vagal lobe in goldfish is a laminated structure in the midmedulla responsible for processing vagal gustatory input from the oropharynx. The anatomical arrangement of the vagal lobe is conducive to an in vitro slice preparation for investigating the physiology and pharmacology of primary gustatory fibers. Postsynaptic population responses (N2 and N3) were evoked from sensory layers of the vagal lobe following stimulation of the incoming vagal fibers. Application of 100 microM kynurenic acid, a broad spectrum glutamate receptor antagonist, abolished or significantly decreased the evoked responses. These results indicate that excitatory amino acids are the neurotransmitter at the first relay in the taste pathway in the central nervous system.

Caloric restriction enhances evoked DA overflow in striatum and nucleus accumbens of aged Fischer 344 rats.

Previous studies have shown deficits in DA neuronal systems in senescence. Other studies indicate that prolonged dietary restriction can attenuate many of the detrimental effects of age. We have shown previously using in vivo electrochemistry that K+-evoked striatal DA overflow decreases as a function of age. This was a regional effect that appeared to be due to functional changes in DA neurons, rather than a decrease in the storage and synthesis of DA. In the present studies, we used in vivo electrochemistry to investigate the effects of caloric restriction on age related decreases in K+-evoked DA overflow along a dorsal to ventral axis in the striatum of aged female Fischer 344 rats. Aged (26-28-month-old) diet restricted animals (DRF) showed evoked DA overflow that was significantly greater in amplitude and duration compared to aged (26-28-month-old) ad lib fed animals (ALF). These results provide additional evidence that decreased DA neuronal function resulting from age is improved by caloric restriction.

Heparin-free hemodialysis in the treatment of hypernatremia in severely burned patients.

BACKGROUND: Hypernatremia in severely burned patients is associated with high morbidity and mortality rates. As the causes of hypernatremia in major burn patients are still not clear, hemodialysis is the method of choice for the treatment. While hemodialysis is effective for the control of hypernatremia, it can cause bleeding complications that may be fatal for burn patients with extensive wounds and potential gastro-intestinal mucosal damage. CLINICAL DATA: In the present study heparin-free hemodialysis in which the heparin is firmly absorbed to the haemofiltration membrane, hemophan, dispensed with systemic use of heparin. In two extensively burned patients with burn area of 100% TBSA and 98% TBSA respectively and hypernatremia with serum sodium concentration as high as 169 and 158 mmol/l respectively, heparin-free hemodialysis was performed five times and three times each. RESULTS: Hypernatremia was satisfactorily corrected with no interference to the coagulation system in the two patients as indicated by clinical observation and biochemical analysis. The patient with burn area of 98% TBSA survived and the patient with burn area of 100% TBSA died of wound coverage failure 6 weeks after injury because of non-availability of autograft. CONCLUSION: Heparin-free hemodialysis is an effective and safe method in the treatment of hypernatremia in extensively burned patients.

Extensive wound excision in the acute shock stage in patients with major burns.

In order to reduce excessive plasma loss, to alleviate the effects of devitalized tissues on the body, and to shorten the time in hospital, we attempted to perform extensive escharectomy during the shock period in extensively burned patients. Group A consisted of 21 patients, aged 9-45 years, with a mean total burn area of 63.2 +/- 18.1 per cent TBSA, and full-thickness injury involving 35.9 +/- 19.6 per cent TBSA. The first escharectomy was performed at 24.1 +/- 13.9 h postburn. The excision area averaged 32.3 +/- 6.7 per cent TBSA (range 24-96 per cent). In 15 patients a Swan-Ganz catheter was introduced to monitor haemodynamic changes. It was found that RAP, PAP, PAWP, ABP, HR, CO and CI were all stable during and after the operation. Group B consisted of 29 patients, and escharectomy was begun 4-5 days postburn. The mean healing time of the patients in group A was 33.1 days, which was shorter than that in group B (40.1 days). The period of haemoconcentration was shorter in group A and the amount of blood required during the first 2 weeks was almost 700 ml less in group A. There were fewer visceral complications in group A and smaller amounts of antibiotics were required in this group. The authors believe that escharectomy during the shock stage is feasible.

Successful treatment of invasive burn wound infection with sepsis in patients with major burns.

OBJECTIVE: To investigate the clinical characteristics of invasive burn wound infection with sepsis in patients with major burns and to summarize the successful experiences in the treatment of such patients. METHODS: Eight patients with major burns, complicated by invasive burn would infection and sepsis were consecutively admitted to our hospital from September 1997 to October 1998. Among them, 6 patients developed multiple organ dysfunction syndrome (MODS) and 2 developed septic shock. The plasma concentrations of IL-6, IL-8, TNF alpha and lypopolysaccharide (LPS) were assayed before and after surgical intervention, as well as when the patient's vital signs became stable. RESULTS: The patients' conditions usually deteriorated abruptly when extensive invasive burn wound infection emerged. While multi-microbial infection was usually found, Pseudomonas aeruginosa was the predominant bacteria isolated from the subeschar tissue. The plasma concentrations of IL-6, IL-8, TNF alpha and LPS before surgical intervention were significantly higher than those after surgical intervention (P < 0.05). The lowest levels of the inflammatory mediators were observed when the patients' conditions became stable, and the values were significantly lower than those before surgical intervention (P < 0.001). CONCLUSION: Since the main cause of burn wound sepsis is the presence of a large area of infected burn wound, they should be excised and covered as early as possible. LPS and pro-inflammatory mediators play an important role in the pathogenesis of burn sepsis. Although favorable results should be attributed to comprehensive treatment, we believe that early, aggressive and thorough surgical excision of infected burn wounds, followed by sound and complete coverage of the area, play a crucial role.

Extensive wound excision in shock stage in patients with major burns.

To stop excessive plasma loss, alleviate noxious effects of devitalized tissues on the body and shorten the hospitalization time, we performed extensive escharectomy during the shock period in extensively burned patients. Group A consisted of 21 patients aged 9-45 years (26.1 +/- 7.9 years), with a mean total burn area of 63.2% +/- 18.1% TBSA, and full-thickness injury involving 35.9% +/- 19.6% TBSA. The first escharectomy was done at 24.1 +/- 13.9 hours postburn, and excision area averaged 32.3% +/- 6.7% TBSA (24%-46%). In 15 of them, Swan-Ganz catheter was introduced to monitor the hemodynamic changes. It was found that RAP, PAP, PAWP, ABP, HR, CO and CI were all stable during and after the operation. Group B consisted of 29 patients aged 11-50 years (30.4 +/- 11.7 years), in whom escharectomy was begun 4-5 days postburn. The mean healing time of the patients in group A was 33.1 days, shorter than that of group B patients (40.1 days). The duration of hemoconcentration was shorter in group A. The amount of blood transfusion was almost 700 ml less in group A during the first two weeks. Less antibiotics were used with fewer visceral complications in group A. We believe that escharectomy during the burn shock stage is feasible.

Purinoceptors in the Central Nervous System.

New exciting developments on the occurrence and functional role of purinoceptors in mammalian brain were presented at the session "Purinoceptors in the central nervous system" chaired by Flaminio Cattabeni and Tom Dunwiddie at the Purines '96 international conference. The focus of the session were topics of recent interest, including the sources and mechanisms involved in ATP and adenosine release during physiological neurotransmission in hippocampus, the brain expression of the recently cloned P2 receptors, and the role of the various adenosine receptor subtypes in brain protection from neurodegeneration associated with trauma-, ischemia-and excessive excitatory amino acid neurotransmission. New important insights into the mechanisms responsible for the formation and release of adenosine into the extracellular space were provided by data obtained by Dunwiddie and coworkers in hippocampal pyramidal neurons. These data may have functional implications for the role of purines in modulation of synaptic plasticity and long-term potentiation in this brain area, and hence in cognitive functions. Buell provided an updated overview on the cloning, molecular characteristics and brain expression of various ligand-gated P2X purinoceptors; although the functional role of these receptors in mammalian brain still awaits elucidation, their widespread distribution in the nervous system strongly suggests that ATP-mediated events are more prevalent and important in brain than expected. Pedata presented data on the functional interrelationships between adenosine and glutamate in the brain, and also provided evidence for alterations of the reciprocal regulation between these two systems in aged brain, which may have important implications for both ischemia-and trauma-associated neurodegenerative events and senescence-associated cognitive impairment. Finally, von Lubitz provided novel data on the molecular mechanisms likely to be at the basis of the brain protective effects associated with the chronic stimulation of the adenosine A3 receptor, further confirming that this receptor represents a crucial target for the development of new antiischemic and antineurodegenerative therapeutic agents.