Prenatal immune activation potentiates endocannabinoid-related plasticity of inhibitory synapses in the hippocampus of adolescent rat offspring

There is strong evidence that immune activation from prenatal infection increases the risk for offspring to develop schizophrenia. The endocannabinoid (eCB) system has been implicated in the pathophysiology of schizophrenia while models of cortical dysfunction postulate an imbalance between neuronal excitation and inhibition in the disorder. The current study examined the impact of prenatal immune activation on eCB-mediated inhibitory mechanisms. We compared two forms of eCB-related plasticity of evoked inhibitory postsynaptic currents, namely depolarization-induced suppression of inhibition (DSI) and metabotropic glutamate receptor-induced long term depression (mGluR-iLTD), in both the dorsal and ventral hippocampus between adolescent offspring from rat dams that received either saline or bacterial lipopolysaccharide (LPS) during pregnancy. Compared to prenatal saline offspring, prenatal LPS offspring displayed prolonged DSI and stronger mGluR-iLTD in the dorsal and ventral hippocampus, respectively. The sensitivity of mGluR-iLTD to the CB1 receptor antagonist AM251 was also lower in the dorsal hippocampus of prenatal LPS compared to prenatal saline offspring. Testing whether changes in eCB receptor signaling or levels could contribute to these changes in inhibitory transmission, we found region specific increases in 2-arachidonoylglycerol-stimulated signaling and in basal and mGluR-induced levels of anandamide in prenatal LPS offspring when compared to prenatal saline offspring. Our findings indicate that prenatal immune activation can lead to long-term changes in eCB-related plasticity of hippocampal inhibitory synaptic transmission in adolescent rat offspring. Perturbation of the eCB system resulting from prenatal immune activation could represent a mechanism linking early life immune events to the development of psychopathology in adolescence.     

ProteinChip array profiling for identification of disease- and chemotherapy-associated biomarkers of nasopharyngeal carcinoma

BACKGROUND: We previously used ProteinChip array profiling analysis to discover a serum biomarker associated with nasopharyngeal carcinoma (NPC). In this study, we used the same method to examine other biomarkers associated with NPC and response to chemotherapy (CT) in NPC patients. METHODS: We performed ProteinChip array analysis in 209 serum samples from 66 relapsed patients before and after salvage CT with gemcitabine and cisplatin or etoposide and cisplatin combinations, 11 patients in remission, and 35 healthy individuals. Intensities of the biomarker peaks were correlated with CT response of the patients and other clinical parameters. RESULTS: We discovered 13 candidate biomarkers associated with different clinical parameters. Two biomarkers (2803 and 3953 Da) were significantly increased in patients compared with controls at all stages of disease. Analysis of pre- and post-CT paired serum samples revealed 7 biomarkers correlated with impact of CT. Of these 7 biomarkers, 2 (2509 and 2756 Da) were significantly increased and 5 (7588, 7659, 7765, 7843, and 8372 Da) were significantly decreased post-CT in either 1 or both CT cohorts. Four biomarkers from pre-CT sera were correlated with CT response, with 3 (2950, 13 510, and 14 855 Da) being significantly decreased and 1 (6701 Da) significantly increased in patients who did not respond to CT. Tandem mass spectrometric sequencing and/or immunoaffinity capture assay identified the 3953 Da biomarker as a fragment of interalpha-trypsin inhibitor precursor and 7765 Da biomarker as platelet factor-4. CONCLUSIONS: Treatment-associated serum biomarkers found might serve to triage NPC patients for appropriate CT treatment.     

光动力疗法与Nd：YAG激光对胃胶原纤维损伤机制的比较

光动力疗法对于胃肠道肿瘤治疗效果令人鼓舞。但有关ＰＤＴ对胃肠道正常组织损伤的研究甚少。探讨了ＰＤＴ与Ｎｄ：ＹＡＧ激光对胃组织损伤的差异。结构发现：Ｎｄ：ＹＡＧ激光治疗过程中光纤周围组织温度明显高于ＰＤＴ组。光镜下二者均可造成明显组织损伤，但二周后修复方式不同，Ｎｄ：ＹＡＧ激光以纤维疤痕组织修复，而ＰＤＴ以正常组织再生修复，电镜发现Ｎｄ：ＹＡＧ激光致胃粘膜下胶原纤维明显损伤。     

Interleukin-6 enhances growth factor-dependent proliferation of the blast cells of acute myeloblastic leukemia

The effects of recombinant interleukin-6 (IL-6) on the proliferation of blast precursors present in the peripheral blood of patients with acute myeloblastic leukemia (AML) was investigated. IL-6 had little effect by itself; however, it synergized with granulocyte macrophage colony- stimulating factor (GM-CSF) and interleukin-3 (IL-3) in the stimulation of AML blast colony formation. Responsiveness of blast progenitors to IL-6 was heterogeneous. On normal bone marrow cells the same synergy was observed on granulocyte and monocyte precursors (GM-CFC), while there was no significant effect on erythroid and multipotential precursors.     

6q deletions define distinct clinico-pathologic subsets of non- Hodgkin's lymphoma

Commonly observed in lymphoid neoplasms, deletions of 6q have been correlated with histologic and clinical subsets of non-Hodgkin's lymphoma (NHL). Our recent analysis of loss of heterozygosity of 6q loci in NHL showed two regions of minimal molecular deletion (RMD), an RMD1 at 6q25-27 and an RMD2 at 6q21-23. To establish correlations between these RMDs and regions of minimal cytogenetic deletions (RCDs) on 6q, and to define associations between RCDs and clinico-pathologic features, we have analyzed chromosome 6 abnormalities in 459 consecutively ascertained, karyotypically abnormal cases of NHL. Among these, 126 (27.5%) cases had structural abnormalities of chromosome 6, of which 94 were deletions. Analysis of these deletions identified three RCDs. An RCD1 encompassing 6q25-27 was seen in 45 intermediate- grade NHL. An RCD2 at 6q21 was observed in 11 high-grade NHL, 9 of which were of the immunoblastic subtype. An RCD3 at 6q23 was noted in 18 low-grade NHL lacking a t(14;18) translocation. Of these 18 cases, 12 were small lymphocytic NHL and, in 2 of these, del(6q) was the sole karyotypic abnormality. In 20 cases of low-grade NHL with t(14;18), the deletions spanned both RCD1 and RCD3. These data suggested the presence of at least 3 tumor suppressor genes on 6q within RCD1, RCD2, and RCD3; they also showed associations between RCDs in 6q and subsets of NHL, including a specific association between a group of well-differentiated lymphoid neoplasms and RCD3. The apparent heterogeneity of breakpoints when all NHLs are considered together explains the inability of previous studies to reliably establish correlations between recurring 6q deletions and histologic and clinical features of NHL.     

Guided bone regeneration to reduce root migration after coronectomy of lower third molar: a randomized clinical trial

Purpose

Root migration occurs after most third molar coronectomy and a portion may be exposed in the oral cavity. This study compared the root migration rate, surgical morbidities after third molar coronectomy with or without adjunctive guided bone regeneration (GBR).

Methods

A split-mouth randomized clinical trial was conducted on patients with bilateral lower third molars close to the inferior alveolar nerve. One side of the lower third molars was randomized to receive coronectomy with adjunctive GBR (study group) and the other side received coronectomy alone (control group). The cases were followed up for 2 years. Root migration, root exposure rate, surgical morbidities, and adjacent second molar periodontal regeneration were analyzed.

Results

Forty-eight subjects (19 males, 29 females) with a mean age of 2.6 years (SD 5.8 years) were recruited. There was no root exposure in the review period. There were no statistical differences in pain and infection rate between the two groups at all time-points. The root migration was significantly less in the study group than the control group from 3 months onwards, and migrated only 1 mm (SD 1.3 mm) in 2 years (versus 3.5 mm (S.D.1.9 mm) in the control group). There were no differences in the periodontal attachment regeneration between the two groups.

Conclusions

Root migration in coronectomy with adjunctive GBR was less when compared with coronectomy alone, and with similar surgical morbidities and periodontal regeneration of adjacent second molars.

Clinical relevance

Minimal root migration occurred in coronectomy with adjunctive GBR. The chance of long-term (3 years or more) root exposure and the need of subsequent second operation to remove the exposed root would be reduced.

     

Zotarolimus-eluting stent utilization in small-vessel coronary artery disease (ZEUS)

The role of the second-generation zotarolimus-eluting stent RESOLUTE in small-vessel coronary artery disease is unclear. The aim of this study was examine the angiographic results of RESOLUTE in de novo coronary lesions of ≥50 % diameter stenosis in target vessels ≤2.5 mm. From August 2008 to April 2010, 142 symptomatic patients with 159 lesions who fitted the inclusion criteria were treated with RESOLUTE. The mean age of patients was 66 ± 10 years, with male predominance (66 %). Diabetes mellitus was found in 62 (43.7 %) patients, whereas multivessel disease was observed in 105 (73.9 %). The mean stent size and length used were 2.33 ± 0.13 and 22 ± 8 mm, respectively. Follow-up angiography was performed on 143 (89.9 %) lesions in 127 (89.4 %) patients at a mean of 10.3 ± 3.6 months. Angiographic restenosis was found in 9 (6.3 %) lesions; the late loss was 0.26 ± 0.34 mm. At 1-year follow-up there were four cardiovascular deaths, two nonfatal myocardial infarctions, and six repeated revascularizations. The resultant major adverse cardiac event rate was 8.5 %. The use of RESOLUTE to treat small-vessel disease is associated with good clinical and angiographic outcomes at 1 year.     

The CHADS2 and CHA2DS2-VASc scores predict adverse vascular function,ischemic stroke and cardiovascular death in high-risk patients without atrial fibrillation: Role of incorporating PR prolongation

Objectives

To investigate whether the CHADS₂ and CHA₂DS₂-VASc scores have clinical utility for prediction of adverse vascular function and vascular dysfunction-mediated incident cardiovascular (CV) events among high-risk patients without atrial fibrillation (AF), and the additional value of incorporating PR prolongation to the scores.

Methods

We analyzed 579 high-risk CV outpatients without clinical AF in a prospective cohort for new-onset ischemic stroke, myocardial infarction (MI), congestive heart failure (CHF), and CV death. Brachial flow-mediated dilation (FMD) and nitroglycerin-mediated dilatation (NMD), carotid intima-media thickness (IMT) and pulse wave velocity (PWV) were determined.

Results

Baseline CHADS₂ score was associated with lower FMD (Pearson r = −0.16, P < 0.001) and NMD (r = −0.17, P < 0.001), higher carotid IMT (r = 0.30, P < 0.001) and PWV (r = 0.35, P < 0.001; similar for CHA₂DS₂-VASc score: All P < 0.05). After follow-up of 63 ± 11 months, 82 patients (14.2%) developed combined CV endpoint. ROC curve analysis showed that both CHADS₂ and CHA₂DS₂-VASc scores were predictors for ischemic stroke (C-Statistic: CHADS₂ 0.70, P = 0.004; CHA₂DS₂-VASc 0.68, P = 0.010), MI (CHADS₂ 0.63, P = 0.030; CHA₂DS₂-VASc 0.70, P = 0.001), and CV death (CHADS₂ 0.63, P = 0.022; CHA₂DS₂-VASc 0.65, P = 0.011). Higher CHADS₂ score was associated with reduced event-free survival from combined CV endpoints (log-rank = 16.7, P < 0.001) with differences potentiated if stratified by CHA₂DS₂-VASc score (log-rank = 29.2, P < 0.001). Incorporating PR prolongation, the CHA₂DS₂-VASc-PR score achieved the highest C-Statistic for CV death prediction (0.70, P < 0.001) superior to the CHADS₂ score (chi-square: 12.1, P = 0.0005).

Conclusions

The CHADS₂ and CHA₂DS₂-VASc predict vascular dysfunction and cardiovascular events in high-risk CV patients without clinical AF, with further improved performance incorporating PR prolongation.