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Cerebral ischemia-reperfusion injury (CIRI) is the predominant cause of neurological disability after cardiac arrest/cardiopulmonary resuscitation (CA/CPR). The endoplasmic reticulum stress (ERs)-induced apoptosis plays an important role in neuronal survival/death in CIRI. Our previous studies reported that the extracellular signal-regulated kinase (ERK) inhibitor, PD98059, alleviates CIRI after CA/CPR. Whether ERs-induced apoptosis is involved in the neuroprotection of PD98059 remains unknown. This study aims to investigate the effects of ERK inhibition by PD98059 on ERs-induced apoptosis after CIRI in the CA/CPR rat model. The baseline characteristics of male adult Sprague-Dawley (SD) rats in all groups were evaluated before CA/CPR. The SD rats that survived from CA/CPR were randomly divided into 3 groups (n=12/group): normal saline group (1 ml/kg), dimethylsulfoxide (DMSO, the solvent of PD98059, 1 ml/kg) group, PD98059 group (0.3 mg/kg). Another 12 SD rats were randomly selected as the Sham group. Twenty-four hours after resuscitation, neural injury was assessed by survival rate, neurological deficit scores (NDS) and Nissl staining; apoptosis of brain cells was detected using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining; mRNA expression and protein levels of ERs-related protein BIP, PERK, ATF4 and CHOP were checked with RT-PCR and Western Blot. The results showed that there were no significant differences in baseline characteristics before CA/CPR among all groups. PD98059 significantly improved survival rate and NDS, increased the Nissl bodies in neurons, reduced apoptosis, downregulated the mRNA transcription and expression levels of BIP, PERK, ATF4 and CHOP at 24 h after CA/CPR. Our results demonstrate that inhibition of ERK by PD98059 alleviates ERs-induced apoptosis via BIP-PERK-ATF4-CHOP signaling pathway and mitigates CIRI in the CA/CPR rat model.

To explore roles of CDGSH iron-sulfur domain-containing protein 2 (CISD2) in the progression of prostate cancer (PCa) cells, and relationships between CISD2 expression and the prognosis and clinical pathological parameters in PCa patients.Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) analysis and Western blot analysis were used to detect the CISD2 expression in PCa tissues and cells. CISD2 siRNA was used to inhibit the CISD2 expression. Kaplan-Meier method and Log rank analysis were performed to determine survival analysis while Chi-square test was performed to analyze the association between CISD2 and clinicopathological parameters of PCa patients. Transwell assay and wound healing assay was conducted to examine the invasion and migration ability of PCa cells, respectively.CISD2 was up-regulated in PCa tissues and cells, and showed positive association with the poor prognosis, T stage, lymphatic invasion, prostate-specific antigen (PSA) level, and distant metastasis of PCa patients. Besides, we found that inhibition of CISD2 significantly impaired the migration and invasion ability of PCa cells.The paper demonstrated that CISD2 could act as a new target for the diagnosis and treatment of PCa patients.

Intracerebral hemorrhage (ICH) is a devastating cerebrovascular disease of the central nervous system. In this study, we aimed to investigate plasma ZCCHC14 expression and its correlation with the diagnosis, prognosis, and clinical features of ICH.The plasma levels of ZCCHC14, TNF-α, IL-6, and IL-10 were dynamically detected among 130 ICH patients and 60 corresponding healthy subjects. A receiver operating characteristic (ROC) curve was used for the statistical analysis of the diagnostic and prognostic efficacy of ICH.Hypertension (p = 0.005), ARB application (p = 0.014), ZCCHC14 level (p0.001), TNF-α (p0.001), IL-6 (p0.001), and IL-10 (p0.001) were found to be different between ICH patients and healthy controls. Multiple logistic regression analysis indicated that ZCCHC14 levels at admission were significantly different between the two groups (p = 0.002, OR = 0.440, 95% CI 0.290-0.718). Plasma ZCCHC14 levels dynamically changed, increasing at admission, and peaking on day 7. ZCCHC14 was a potential diagnostic marker for ICH (AUC = 0.953, p0.0001, 95% CI: 0.901-1.004) with a specificity and sensitivity of 84.6% and 95.5%, respectively. The plasma ZCCHC14 level was negatively correlated with IL-6 concentration (p = 0.024, r = -0.311) but was positively correlated with IL-10 concentration (p = 0.041, r = 0.298). Furthermore, the plasma ZCCHC14 level was correlated with hypertension (p = 0.005), GOS (p = 0.025), bleeding volume (p0.001), midline shift (p = 0.003), and poor outcome (p = 0.006). The low ZCCHC14 expression group had poorer outcomes (death or severe disability) than high ZCCHC14 expression group (Breslow, p0.001).We found that the plasma ZCCHC14 level might be a potential biomarker for both the early diagnosis of and prediction of outcomes in ICH.

A simple, rapid, selective and sensitive HPLC-UV method was developed and validated for the determination of swainsonine (SWSN) in rat plasma. The analyte was extracted from rat plasma with methanol as the extraction solvent. The LC separation was performed on a Diamonsil® C18 (250×4.6 mm, 5 µm) analytical column with a mobile phase consisting of acetonitrile-potassium dihydrogen phosphate (25 mmol/l, pH=7.5) at a flow rate of 1.0 ml/min. There was a good linearity over the range of 10-500 ng/ml (r=0.9995) with a weighted (1/C2) least square method. The lower limit of quantification was proved to be 10 ng/ml. The accuracy was within 4.8% in terms of relative error and the intra- and inter-day precisions were less than 9.0% in terms of relative standard deviation. After validation, the method was successfully applied to characterize the pharmacokinetics of SWSN in rats.

To explore the effects of progesterone (PROG) on brain edema in rats.Forty eight rats were randomly divided into 6 groups that were ischemia/reperfusion (I/R), dimethylsulfoxide (DMSO), and pretreatment, pre + posttreatment, posttreatment with PROG, and dexamethasone (DEXA) groups. The model of focal cerebral ischemia was established in rats by reversible inserting a nylon thread into the anterior cerebral artery. All rats were decapitated at 24 hours after the left middle cerebral artery occlusion (MCAO) respectively, and then brain H2O, Na+, K+, Ca2+ contents were determined.Compared with the result in DMSO group, the content of water (P0.01), Na+ (P0.01), Ca2+ (P0.01) was significantly reduced, but K+ (P0.01) was obviously elevated in ischemia cortex in pretreatment group or pre + posttreatment group with PROG. There was also significant reduction in water (P0.05) and Na+ (P0.01), but was not significantly changed in Ca2+ (P0.05) and K+ (P0.05) in posttreatment group with PROG. The changes occurring in DEXA group were similar to those found in pretreatment group or pre + posttreatment group with PROG.Pretreatment or pretreatment plus posttreatment with progesterone can significantly reduce brain edema in I/R.

An incidental finding of focal thyroid uptake (thyroid incidentaloma) from an 18F-fluorodeoxyglucose positron emission tomography (PET) positron presents a diagnostic challenge. We evaluated the incidence of thyroid incidentaloma identified by PET scans and the likelihood of malignancy associated with this finding. Records from all patients from January 1, 2000 to November 30, 2003 who had focal thyroid uptake without any history of thyroid disease were culled. Of the 6241 PET scans performed, focal thyroid uptake was observed in 76 patients (1.2%). Only 14 patients (18%) underwent biopsy. Four of 14 patients (28.6%) had papillary thyroid carcinoma, 7 (50%) had hyperplasia, and 1 each had thyroiditis, nodular goiter, and follicular neoplasm. The incidence of PET thyroid incidentalomas was 1.2 per cent and the incidence of malignancy was 28.6 per cent. Given the high likelihood of malignancy, a further diagnostic workup for surgically fit patients is warranted.

Sestamibi scan is generally recognized in the literature to play a role in the imaging of parathyroid adenoma. Most institutions quote sensitivities ranging from 80 to 100 per cent. There is still a question as to whether patients need preoperative localization studies. Preoperative localization can potentially result in less invasive surgery, shorter operative times, decreased hospital stays, and decreased need for re-exploration. Our hypothesis is that the sestamibi scan is a sensitive predictor of parathyroid adenomas. The objectives of this study are to determine the sensitivity of sestamibi scan in detecting parathyroid adenoma, and to determine whether either parathyroid hormone (PTH) level or calcium level is an independent predictor of a positive scan. One hundred patients were retrospectively reviewed at Louisiana State University Health Sciences Center-Shreveport and Louisiana State University Health Sciences Center-Monroe from March 1993 through December 2000. All patients had a preoperative sestamibi scan. This scan was performed using the dual-phase technique in which the parathyroid glands are visualized after washout of tracer from the thyroid. The scan was followed by either a unilateral or bilateral neck dissection. There were 82 female patients and 18 male patients who ranged in age from 23 to 78 years. The median weight of glands with a positive scan was 795 mg. The median weight of glands with a negative scan was 480 mg. This difference was statistically significant (P0.04). Overall there were 107 adenomas. Of these 93 had positive scans and 14 had negative scans. This results in a sensitivity of 87 per cent. There were 67 glands that weighed at least 500 mg. Of these 67 glands 61 had positive scans and six had negative scans. This resulted in a sensitivity of 91 per cent. There were 40 glands that weighed less than 500 mg. Of these 40 glands 32 had positive scans and eight had negative scans. This resulted in a sensitivity of 80 per cent. Using multiple linear regression analysis calcium level correlated with the weight of the gland (P0.01). Calcium level also correlated with the PTH level (P0.01). However, neither the PTH level nor the calcium level correlated with a positive sestamibi scan. Sestamibi scan is a sensitive predictor for parathyroid adenoma greater than 500 mg (91% sensitivity). Even in smaller glands (500 mg) 80 per cent sensitivity was demonstrated. Although the calcium level correlates with the PTH level neither PTH level nor calcium level is predictive of a positive sestamibi scan.

Recent studies suggest that the basic molecular control mechanisms of early heart development are remarkably conserved in Drosophila, vertebrate and human being. Drosophila can be used as a prototype to explore the genetic basis of cardiogenesis in human being. Here, mutations of genes affecting heart development of Drosophila are produced by chemical mutagen methanesulfonicaeid ethyl. With staining of antibody expressed in heart precussor cells of Drosophila, 112 lethal lines were observed to show mutant phenotypes in pericardial cells. Of them, 32 lines differ in their mutant phenotypes from those of known genes. Analysis of cytogenetic mapping shows that they are located in 13 chromosomal regions without known heart-related genes, which implies that these loci contain genes probably involved in the heart development.

The stimulation of food consumption after i.c.v. administration of various neuropeptide Y (NPY) receptor agonists was examined in CD-1 mice. These agonists, including endogenous peptides NPY, peptide YY (PYY), and pancreatic polypeptide, as well as several N-terminal truncated and synthetic peptides that are prototypic receptor agonists at Y1-Y6 NPY receptors ([Leu31Pro34]NPY, NPY2-36, NPY3-36, NPY13-36, PYY3-36, Pro34PYY, and D-Trp32NPY), showed varying abilities to elicit food consumption such that PYYNPY2-36 = NPY = PYY3-36Pro34PYYNPY3-36[Leu31Pro34]NPYNPY13-36 = D-Trp32NPY = pancreatic polypeptide. Published reports have suggested that NPY-induced feeding is mediated via the Y1 or the Y5 receptor subtypes. However, the relative ability of the various peptide analogs to elicit feeding differed from the relative ability of these peptides to bind to cloned Y1-Y6 receptors. The effects of prototypic Y1 receptor antagonists on NPY-induced feeding were also evaluated after i.c.v. administration. GR231118 (1229U91), a peptide Y1 antagonist, did not block NPY-induced feeding at the doses tested. BIBP3226, a nonpeptide Y1 receptor antagonist, as well as its opposite enantiomer, BIBP3435, which is inactive at Y1 receptors, blocked feeding elicited by NPY, [Leu31Pro34], or PYY at doses that did not cause overt behavioral dysfunction. The lack of effects with GR231118 and the nonstereoselective effects of BIBP3226 suggested that NPY-induced feeding in mice was not mediated via the Y1 receptor. Thus, by using currently available prototypic peptide NPY receptor agonists for Y1-Y6 receptors and peptide and nonpeptide Y1 receptor antagonists GR231118 and BIBP3226, the mediation of NPY-induced feeding cannot be unequivocally attributed to any one of the known NPY receptors. It is possible that NPY-induced feeding is mediated either by a combination of more than one NPY receptor subtype or by a unique NPY receptor subtype. Additional subtype-selective receptor antagonists, when available, will help to clarify this issue further.

The selective neurokinin (NK)-1 antagonist LY303870 has high affinity and specificity for human and guinea pig brain NK-1 receptors labeled with 125I-substance P. It has approximately 15- to 30-fold lower affinity for rat and mouse brain NK-1 receptors, consistent with previously reported species differences in the affinities of nonpeptide antagonists for NK-1 receptors. In vivo, LY303870 blocked the characteristic, caudally directed, biting and scratching response elicited by intrathecal administration of the selective NK-1 agonist Ac-[Arg6,Sar9,Met(O2)11]substance P6-11 in conscious mice. The potentiation of the tail-flick response elicited by intrathecal administration of the NK-1 agonist [Sar9,Met(O2)11]substance P in rats was also selectively blocked by LY303870. When tested in a model of persistent nociceptive activation induced by tissue injury (the formalin test), LY303870 blocked licking behavior in the late phase of the formalin test, in a dose-dependent manner. After oral administration of 10 mg/kg, the blockade of the late-phase licking behavior was evident for at least 24 hr. Ex vivo binding studies in guinea pigs showed that orally administered LY303870 potently inhibited binding to central and peripheral NK-1 receptors labeled with 125I-substance P. This inhibition was long-lasting, consistent with other in vivo activities. LY306155, the opposite enantiomer of LY303870, was less active in all of the functional assays. In rodents, LY303870 did not exhibit any neurological, motor, cardiovascular, gastrointestinal or autonomic side effects at doses ofor = 50 mg/kg p.o. Thus, LY303870 is a potent, centrally active, NK-1 antagonist in vivo, with long-lasting oral activity.

Secretion was taken from lower respiratory tract for bacterial culture using Japanese made single-sheath catheter brush (SSC) via fiberoptic bronchoscopy in 53 cases with community acquired pneumonia and 16 control cases without pulmonary infection. The results showed that bacteria were isolated in 42 out of the 53 patients, the organisms being pathogenic in 39 out of the 53 (73.5%). Among the bacteria isolated from the 42 cases, gram-negative bacilli accounted for the highest rate of 36% and pneumococcus the next of 31%. There were only 3 cases yielding contamination. It is shown that SSC technique has less chance of contamination and is convenient and practical.