Post-ischemic administration of nimodipine following focal cerebral ischemic-reperfusion injury in rats alleviated excitotoxicity, neurobehavioural alterations and partially the bioenergetics

The present study focuses on the temporal calcium significance in middle cerebral artery occluded (2 h ischemia)-reperfused (70 h reperfusion) rats treated with nimodipine (NM) through concurrent measurements of excitotoxicity, bioenergetics and neurobehavioural paradigms. Further, the suitable therapeutic time window of calcium channel antagonism in stroke was also ascertained. NM (5 mg/kg, i.p.) was administered at pre (30 min before the induction of ischemia), during (1 h following occlusion of MCA) and post-ischemic (3 h after begin of reperfusion) states. The magnitude of neuroprotection in terms of excitotoxicity (glutamate, glutamine synthetase, Na⁺K⁺ATPase), bioenergetics (ATP, NAD⁺) and neurobehavioural paradigms (neurological score and open field exploratory behaviour) were measured and compared to ensure the therapeutic time-window of NM in stroke. Middle cerebral artery occlusion-reperfusion (MCAO/R) was found to elevate glutamate, glutamine synthetase levels and deplete Na⁺K⁺ATPase activity in the vehicle treated group (IR group). Significant decrease in bioenergetics such as ATP and NAD⁺ levels was also observed. Further, IR group demonstrated grievous oxidative stress (increase in lipid peroxidation, protein carbonyl content, nitrite/nitrate levels and decrease in superoxide dismutase and glutathione levels) along with anxiogenic behaviour, neurological deficits and neuronal damage and decreased nuclear to cytoplasm ratio in CA1 hippocampal region. Post-ischemic NM administration reversed the excitotoxicity, neurobehavioural and histopathological alterations significantly, but it restored bioenergetics level in MCAO/R rats only partially.These findings were further confirmed with the combination treatment (CT) of post-ischemic NM and pre-ischemic memantine (MN) administration, since MN showed protective effect in the pre-ischemic administration (Babu and Ramanathan, 2009). The failure of NM to forefend the neurodegeneration on pre- and during-ischemic administration suggests that the initial phase damages in ischemic-reperfusion (IR) might be mediated through other mechanism(s) such as glutamergic overstimulation or reverse operation of glutamate transporters. From the present study, it is concluded that calcium plays a crucial role in post-ischemic status and the suitable therapeutic time window of calcium antagonism is the post-ischemic state.     

Short and long-term effects of pandemic unadjuvanted influenza A(H1N1)pdm09 vaccine on clinical manifestations and autoantibody profile in primary Sjögren's syndrome

Despite WHO recommendations about the A/California/7/2009/H1N1-like virus vaccination, studies evaluating its possible influence on clinical manifestations and autoantibody profile in primary Sjögren's syndrome (SS) are scarce. The aim of this study was to evaluate the possible influence of the unadjuvanted A/California/7/2009/H1N1-like virus vaccination on clinical manifestations and autoantibody profile in SS in the short/long-term. Thirty-six SS patients (The American-European Consensus Group Criteria, 2002) and 36 healthy controls with comparable mean age and gender were evaluated before and 21-days after this vaccination regarding seroprotection/seroconversion, factor increase in geometric mean titer (FI-GMT) and side effects. New onset of disease flares and autoantibody profile [antinuclear antibodies, anti-dsDNA, anti-Ro(SSA)/La(SSB), anti-RNP/anti-Sm, rheumatoid factor, anti-alpha-fodrin, anticardiolipin and anti-beta2-glycoprotein-I] were assessed before, 21-days and 1-year after vaccination. Patients and controls had similar rates of seroconversion (77.8 vs. 69.4%, p = 0.42), seroprotection (83.3 vs. 72.2%, p = 0.26) and FI-GMT (p = 0.85). Disease duration, prednisone (2.1 ± 4.9 mg/day), methotrexate and azathioprine did not affect seroconversion (p > 0.05). Regarding short-term, no change in the frequency or levels of autoantibodies was observed (p > 0.05) and only mild side effects were reported in comparable rates to controls (p > 0.05). During 1-year follow-up, the frequency of new disease flares was similar to the previous year (11 vs. 19%, p = 0.51), and four patients developed positivity to one of the following specificities: anti-Ro(SSA)/anti-La/(SSB), anti-alpha-fodrin, or IgM anticardiolipin. None developed specific lupus autoantibodies. Of note, a significant increase in the mean levels of anti-Ro/SSA (p = 0.0001) and anti-La/SSB (p = 0.002) was detected after 1-year with no change in the other autoantibodies. This is the first study indicating that influenza A(H1N1)pdm09 vaccine induces long-term changes in autoantibody profile restricted to SS spectrum without a deleterious effect in disease course.     

抗SSA、抗SSB、抗α-胞衬蛋白抗体及类风湿因子联合检测在原发性干燥综合征的诊断价值

目的 研究抗干燥综合征A抗体（抗SSA）、抗干燥综合征B抗体（抗SSB）、抗α-胞衬蛋白抗体（抗α-fodrin）及类风湿因子（RF）联合检测对原发性干燥综合征的诊断价值.方法 检测75例干燥综合征（SS）[原发性SS 35例（pSS组）、继发性SS 40例（sSS组）]、80例其他结缔组织病（非SS的CTD组）及80例健康对照者（健康对照组）血清中抗核抗体（ANA）、RF、抗SSA、抗SSB、抗α- fodrin,比较各抗体诊断的敏感性和特异性.结果 抗SSA、抗SSB、抗α-fodrin、ANA、RF在pSS组敏感性分别为77.1%、62.9%、25.7%、80%、51.4%;3种特异性抗体联合RF检测的敏感性高于单一抗体,而四者联合检测时敏感性达91.4%;在抗SSA或抗SSB均阴性时,抗α-fodrin联合RF的敏感性为75%.结论 抗α-fodrin与抗SSA、抗SSB、RF的联合检测可提高pSS的诊断率;抗SSA、抗SSB阴性时联合检测抗α-fodrin和RF可避免漏诊.     

椎弓根螺钉内固定术有关角度测量及其临床意义

目的 :为椎弓根螺钉内固定术提供椎弓根相关角度的解剖学资料。方法 :在 10 0例脊柱骨标本 (C2 ～L5)上 ,测量椎弓根长轴与椎体矢状面及上平面之间的夹角。结果 :绝对值 :E角C4 ～C5最大 ,L5次之 ,而T12 最小 ,总体出现两个高峰一个低谷值 ;F角胸段均较大 ,其中T4 最大 ,颈段及腰段较小 ,呈典型的“山峰”形趋势 ;C2～L5的E角和F角侧别间差异均无显著性 (P <0 0 5 ) ,而性别间差异E角均为男大于女 ,C2 ～T6有显著性差异(P <0 .0 5 ) ,而T7～L5无显著性差异 (P >0 .0 5 ) ;F角除C3 、C4 女大于男且差异有显著性 (P <0 0 5 )外 ,其余均为男大于女 ,C2 、C5～T12 差异有极显著性 (P <0 0 1) ,而L1～L5则无显著性差异 (P >0 0 5 )。结论 :E角和F角值均有明显的规律性 ,参照E角F角及椎弓根的骨质结构确定相应的TSA角及SSA角。     

人自身抗原SSA/Ro60的基因克隆和原核表达

目的:克隆并表达人自身抗原SSA/Ro60。方法:应用RT-PCR技术,从HL-60细胞株中克隆人自身抗原SSA/Ro60全长基因,将PCR产物直接TA克隆、鉴定及测序,再定向克隆至pGEX-5T载体中,转入大肠杆菌BL-21,阳性克隆鉴定后在IPTG诱导下表达,产物行SDS-PAGE和Western blot。结果:PCR产物约为1.6 kb,与预期1614 bp接近,测序结果与Genebank报道的完全一致。pGEX-5T-SSA/Ro60重组阳性克隆酶切鉴定正确,SDS-PAGE和Western blot结果显示融合蛋白分子量为86 KD,具有天然人自身抗原SSA/Ro60的免疫原性。结论:成功克隆表达人自身抗原SSA/Ro60,为下一步工作奠定了基础。     

Peptide receptor radionuclide therapy for patients with advanced pancreatic neuroendocrine tumors

¹⁷⁷Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) is now approved for patients with advanced gastroenteropancreatic neuroendocrine tumors (NET), and it is therefore important to understand the efficacy and safety of PRRT in this patient population. PRRT efficacy and safety outcomes have frequently been summarized for patient populations with gastroenteropancreatic NET, but not specifically in patients with pancreatic NET (panNET). The pivotal phase 3 trial of ¹⁷⁷Lu-DOTATATE PRRT in NET was restricted to patients with a midgut primary site. No phase 3 trial data on PRRT treatment outcomes are currently available for the panNET patient population. This review presents the available evidence for panNET treatment outcomes with PRRT and demonstrates that the available data favor PRRT as a modality for this NET primary site. However, several other therapies for advanced panNET are currently available, and the sequencing and combination of PRRT with these other therapies is set to become the big challenge for the future of panNET management. Patient, tumor, and logistical factors (tumor burden, expression of somatostatin receptors, availability of PRRT, patient preferences, and concerns over long-term toxicity) need to be taken into consideration when selecting therapy.     

Anti-Ro/SSA and La/SSB antibodies

The Ro/La system is considered as an heterogeneous antigenic complex, constituted by three different proteins (52?kDa Ro, 60?kDa Ro and La) and four small RNAs particles. Anti-Ro/SSA are the most prevalent specificity among many autoimmune diseases, such as systemic lupus erythematosus (SLE), SS/SLE overlap syndrome, subacute cutaneous LE (SCLE), neonatal lupus and primary biliary cirrhosis. In contrast, anti-La/SSB is more associated with Sjögren's syndrome (SS). The differences between 52?kDa, 60?kDa Ro and La could explain why different assays did not show equivalent performance in anti-Ro and anti-La autoantibodies detection. The RNA precipitation assay had the highest sensitivity and specificity, usually considered as the reference methods. CIE is considered the most reliable to detect anti-Ro/SSA antibodies in routine practice, performing better than immunoblotting (IB) and some ELISAs. It shows a high sensitivity (89%) and specificity (100%). ELISA is generally considered a safe, rapid, sensitive and specific tecnique. Therefore, its high sensitivity often corresponds to a very low clinical specificity and the assay can give false positive results. Therefore, it is very important to search anti-Ro and anti-La only in selected patients, using the assay with high specificity and good predictive value, in order to have clinically significant and true positive results.     

Acceptability of a Pilot Intervention of Voluntary Medical Male Circumcision and HIV Education for Street-Connected Youth in Western Kenya

Purpose

Street-connected youth (SCY) in Kenya and elsewhere in sub–Saharan Africa are at high risk of HIV. Voluntary Male Medical Circumcision (VMMC) reduces the risk of female-to-male HIV transmission. Circumcision is also a traditional coming-of-age process in many Kenyan ethnic groups. This paper describes the acceptability of VMMC delivered as part of a ten-day healing, educational, and ‘coming-of-age’ retreat implemented as a pilot with SCY.