Hepatitis B Prophylaxis Using Lamivudine and Individualized Low-dose Hepatitis B Immunoglobulin in Living Donor Liver Transplantation

Background

Currently, most available experience concerning prophylaxis against hepatitis B virus (HBV) recurrence after living donor liver transplantation (LDLT) is limited to studies of small size and short follow-up. The objective of this study was to evaluate the efficacy of a prophylactic regimen using lamivudine and individualized low-dose intramuscular hepatitis B immunoglobulin (HBIG) in LDLT.

Methods

We used a database of adult-to-adult right-lobe LDLT procedures performed from June 2002 to April 2012 at our center for HBV-related end-stage liver diseases. Patients were divided into 3 groups: group A, HBV-related decompensated liver cirrhosis; group B, fulminant hepatitis B; and group C, hepatocellular carcinoma (HCC).

Results

During a mean follow-up of 38.3 ± 28.9 months, 8 of 165 (4.8%) recipients developed HBV recurrences. The mean time for HBV reinfection was 15.8 + 11.0 months after transplantation. The overall 1-, 3-, and 5-year HBV recurrence rates were 3%, 7%, and 8.2%, respectively. Both patients with fulminant hepatitis B or HCC seemed to have higher rates of HBV recurrence than those with decompensated liver cirrhosis, albeit not significantly. The independent predictor of HBV recurrence was high HBV DNA level (≥10⁵ copies/mL) at LDLT.

Conclusions

Lamivudine and individualized low-dose intramuscular HBIG provides effective prophylaxis against HBV recurrence after LDLT. Pre-LDLT HBV DNA of ≥ 10⁵ copies/mL was associated with HBV recurrence.     

MK2 plays an important role for the increased vascular permeability that follows thermal injury

We previously reported Rho kinase is involved in vessel hyper-permeability caused by burns. Here we further explore the Rho kinase downstream signaling, it is found that its specific inhibitor Y27632 significantly diminishes the activation of JNK and p38 MAPKs but not ERK that induced by serum from burned rats (burn-serum). JNK activation was found involved in the expression of HUVEC adhesion molecules following thermal injury, although not in the process of stress fiber formation. Inhibition of various MAPKs by specific inhibitors showed that SB203580 (inhibitor of p38), but neither SP600125 (inhibitor of JNK) nor PD98059 (inhibitor of ERK), abolish activation of the p38 downstream kinase MK2. Demonstration of stress fibers by fluorescent-labeled phalloidin showed that inhibition of MK2, either by its specific inhibitor or by dominant negative adeno-viral-carried constructs, significantly reduced burn-serum-induced HUVEC stress-fiber formation, while inhibition of another downstream p38 MAPK kinase, PRAK, had no such effects. Transfection of dominant negative adeno-viral MK2 (Ad-MK2(A)) significantly inhibited thermal injury-induced blood vessel hyper-permeability in rats and, moreover, prolonged the survival of burned rats beyond 72 h following thermal injury. One of the mechanisms behind these phenomena is that Ad-MK2(A) causes a significant depression of burn-serum-induced HSP27-phosphorylation, while the adeno-viral transported dominant negative PRAK (Ad-PRAK(A)) does not block. Although the effect of blockade of MK2 through its adeno-viral approach requires further study and investigation of alternatives to know for sure, we may have found a new pathway behind thermal-injury-induced blood vessel hyper-permeability, namely: Rho kinase > p38 > MK2 > HSP27.     

Comparison between the antero-posterior and posterior only approaches for treating thoracolumbar tuberculosis (T10-L2) with kyphosis in children: a minimum 3-year follow-up

Purpose

There are few papers in the literature comparing outcomes between antero-posterior and posterior-only approaches for treating thoracolumbar tuberculosis (T10–L2) in children

Methods

We performed a retrospective review of 47 children who were diagnosed and treated as thoracolumbar tuberculosis (T10–L2) in our department from January 2005 to June 2009. Forty-seven cases of thoracolumbar tuberculosis were treated by two different surgical approaches. All the cases were divided into two groups: 25 cases in group A underwent one-stage posterior debridement, transforaminal fusion, and instrumentation, and 22 cases in group B underwent anterior debridement, bone graft, and posterior instrumentation in a single- or two-stage procedure. Two approaches were compared in terms of average operative time, blood loss, hospitalizations, bony fusion, intraoperative and postoperative complications, the Oswestry disability index score, neurological status, and the angle of kyphosis.

Results

All 47 patients (24 M/23F), averaged 9.1?±?2.6 years old (range 5 to 14 years), who were followed up for mean of 49.3?±?8.6 months (range 36 to 65 months). Spinal tuberculosis (TB) was completely cured, and the grafted bones were fused in 9 months in all cases. It was obviously that the average operative time, blood loss, hospitalization, and complication rate of group A was less than those of group B. Good clinical outcomes were achieved in both groups.

Conclusions

Both the antero-posterior and posterior approaches can effectively heal T10–L2 vertebral tuberculosis, but the average surgical time, blood loss, complications, and hospital stay following the posterior approach are prominently less than those following the antero-posterior approach. It might be a better surgical treatment for thoracic spinal tuberculosis in children with poor health status, especially for cases in early phase of bone destruction and/or mild and moderate kyphosis.

     

Atorvastatin enhances kainate‐induced gamma oscillations in rat hippocampal slices

Atorvastatin has been shown to affect cognitive functions in rodents and humans. However, the underlying mechanism is not fully understood. Because hippocampal gamma oscillations (γ, 20–80 Hz) are associated with cognitive functions, we studied the effect of atorvastatin on persistent kainate‐induced γ oscillation in the CA3 area of rat hippocampal slices. The involvement of NMDA receptors and multiple kinases was tested before and after administration of atorvastatin. Whole‐cell current‐clamp and voltage‐clamp recordings were made from CA3 pyramidal neurons and interneurons before and after atorvastatin application. Atorvastatin increased γ power by ~ 50% in a concentration‐dependent manner, without affecting dominant frequency. Whereas atorvastatin did not affect intrinsic properties of both pyramidal neurons and interneurons, it increased the firing frequency of interneurons but not that of pyramidal neurons. Furthermore, whereas atorvastatin did not affect synaptic current amplitude, it increased the frequency of spontaneous inhibitory post‐synaptic currents, but did not affect the frequency of spontaneous excitatory post‐synaptic currents. The atorvastatin‐induced enhancement of γ oscillations was prevented by pretreatment with the PKA inhibitor H89, the ERK inhibitor U0126, or the PI3K inhibitor wortmanin, but not by the NMDA receptor antagonist D‐AP5. Taken together, these results demonstrate that atorvastatin enhanced the kainate‐induced γ oscillation by increasing interneuron excitability, with an involvement of multiple intracellular kinase pathways. Our study suggests that the classical cholesterol‐lowering agent atorvastatin may improve cognitive functions compromised in disease, via the enhancement of hippocampal γ oscillations.     

Differences in spatial and temporal frequency interactions between central and peripheral parts of the feline area 18

The visual system demonstrates significant differences in information processing abilities between the central and peripheral parts of the visual field. Optical imaging based on intrinsic signals was used to investigate the difference in stimulus spatial and temporal frequency interactions related to receptive field eccentricity in the cat area 18. Changing either the spatial or the temporal frequency of grating stimuli had a significant impact on responses in the cortical areas corresponding to the centre of the visual field and more peripheral parts at 10 degrees eccentricity. The cortical region corresponding to the centre of the gaze was tuned to 0.4 cycles per degree (c/deg) for spatial frequency and 2 Hz for temporal frequency. In contrast, the cortical region corresponding to the periphery of the visual field was tuned to a lower spatial frequency of 0.15 c/deg and a higher temporal frequency of 4 Hz. Interestingly, when we simultaneously changed both the spatial frequency and the temporal frequency of the grating stimuli, the responses were significantly different from those estimated with an assumption of independence between the spatial and temporal frequency in the cortical region corresponding to the periphery of the visual field. However, in the cortical area corresponding to the centre of the gaze, spatial frequency showed significant independence from temporal frequency. These properties support the notion of relative specialization of visual information processing for peripheral representations in cortical areas.     

Effect of rs1063843 in the CAMKK2 gene on the dorsolateral prefrontal cortex

Recently, a single nucleotide polymorphism (SNP) in the CAMKK2 gene (rs1063843) was found to be associated with lower expression of the gene in the dorsolateral prefrontal cortex (DLPFC) and with schizophrenia (SCZ) and deficits in working memory and executive function. However, the brain mechanism underlying this association is poorly understood. A functional magnetic resonance imaging (fMRI) study (N = 84 healthy volunteers) involving multiple cognitive tasks, including a Stroop task (to measure attentional executive control), an N‐back task (to measure working memory), and a delay discounting task (to measure decision making) to identify the brain regions affected by rs1063843 was performed. Across all three tasks, it was found that carriers of the risk allele consistently exhibited increased activation of the left DLPFC. In addition, the risk allele carriers also exhibited increased activation of the right DLPFC and the left cerebellum during the Stroop task and of the left caudate nucleus during the N‐back task. These findings helped to elucidate the role of CAMKK2 in cognitive functions and in the etiology of SCZ. Hum Brain Mapp 37:2398–2406, 2016. © 2016 Wiley Periodicals, Inc .     

Association between angiotensin-converting enzyme insertion/deletion polymorphism and migraine: a meta-analysis

Background: Many studies investigated the association between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and migraine, with controversial results. Thus, we performed a meta-analysis to better evaluate the correlation of this polymorphism and migraine. Methods: We retrieved studies published up to September 2014 about the ACE gene polymorphism and migraine from electronic database. Pooled odds ratios (ORs) with 95% confidence interval (CI) were calculated to examine the strength of association between the ACE I/D polymorphism and migraine, using random-effects models. Results: We identified 14 separate studies, in which 7334 migraineurs and 22 990 healthy controls were eligible for the meta-analysis. The results showed no relationship between the ACE I/D polymorphism and any migraine. Stratification revealed a protective effect in the Turkish population against migraine with aura for the II genotype model (II vs. DD: pooled OR = 0.366, 95% CI = 0.137–0.980; II vs. DI + DD: pooled OR = 0.370, 95% CI = 0.145–0.945). Similar results were obtained for Turkish people with migraine without aura (II vs. DD: pooled OR = 0.386; 95% CI = 0.166–0.900; II vs. DI + DD: pooled OR = 0.347; 95% CI = 0.156–0.773). Conclusions: The data suggest that the ACE II genotype could exert a protective effect against migraine with aura and without aura at least in the Turkish population.     

Wnt/β‐catenin signaling mediates the seizure‐facilitating effect of postischemic reactive astrocytes after pentylenetetrazole‐kindling

Ischemia not only leads to tissue damage, but also induces seizures, which in turn worsens the outcome of ischemia. Recent studies have revealed the impaired homeostatic functions of reactive astrocytes, which were thought to facilitate the development of seizures. However, how this phenotype of reactive astrocytes is regulated remains unclear. Here, using pentylenetetrazole (PTZ)‐kindling model, we investigated the roles of reactive astrocytes and their intracellular Wnt/β‐catenin signaling in the ischemia‐increased seizure susceptibility. Our data showed that somatosensory cortical ischemia significantly increased the susceptibility to PTZ‐induced seizure. Genetic ablation of Nestin‐positive reactive astrocytes significantly decreased the incidence and severity of seizures. By using a Wnt signaling reporter mice line Topgal mice, we found that Wnt/β‐catenin signaling was upregulated in reactive astrocytes after ischemia. Depletion of β‐catenin in reactive astrocytes significantly decreased the susceptibility of seizures and the expression of c‐Fos induced by PTZ in the ischemic cortex. Overexpression of β‐catenin in reactive astrocytes, in contrast, significantly increased seizure susceptibility and the expression of c‐Fos. Furthermore, the expression of aquaporin‐4 (AQP‐4) and inwardly rectifying K⁺ channel 4.1 (Kir4.1), two molecules reportedly associated with seizure development, was oppositely affected in reactive astrocytes with β‐catenin depletion or overexpression. Taken together, these data indicated that astrocytic Wnt/β‐catenin signaling accounts, at least partially, for the ischemia‐increased seizure susceptibility. Inhibiting Wnt/β‐catenin signaling may be utilized in the future for preventing postischemic seizures. GLIA 2016;64:1083–1091     

颈动脉支架成形术治疗颅外段颈动脉夹层的疗效观察

目的 评价颈动脉支架成形术治疗颅外段颈动脉夹层的有效性及安全性。方法 选择颅外段颈动脉夹层患者9例,均行颈动脉支架成形术,观察术后血管狭窄及夹层动脉瘤改善情况,围术期并发症的发生情况,对患者随访3个月到1年。结果 手术技术成功率为100%,术后平均残余狭窄率均≤30%,患者颈动脉平均狭窄程度从(75.0±17.6)%降低至(15.8±9.2)%,夹层动脉瘤均消失,支架置入手术前后比较,差异有统计学意义(P<0.05)。患者术后缺血相关症状均有明显改善,围术期所有患者均未出现症状性脑卒中,无手术相关死亡事件发生,随访无缺血性脑血管事件发生,1例患者可见支架内再狭窄。结论 颈动脉支架成形术治疗颅外段颈动脉夹层安全、有效。