Epilepsy surgery for patients with genetic refractory epilepsy: a systematic review

Aims. In recent years, many different DNA mutations underlying the development of refractory epilepsy have been discovered. However, genetic diagnostics are still not routinely performed during presurgical evaluation and reports on epilepsy surgery outcome for patients with genetic refractory epilepsy are limited. We aimed to create an overview of the literature on seizure outcome following epilepsy surgery in patients with different genetic causes of refractory epilepsy. Methods. We systematically searched PubMed and Embase prior to January 2017 and included studies describing treatment outcome following epilepsy surgery in patients with genetic causes of epilepsy. We excluded studies in which patients were described with epilepsy due to Tuberous Sclerosis Complex or Sturge‐Weber syndrome (since this extensive body of research has recently been described elsewhere) and articles in which surgery was aimed to be palliative. Results. We identified 24 eligible articles, comprising a total of 82 patients who had undergone surgery for (mainly childhood‐onset) refractory epilepsy due to 15 different underlying genetic causes. The success rate of surgery varied widely across these different genetic causes. Surgery was almost never effective in patients with epilepsy due to mutations in genes involved in channel function and synaptic transmission, whereas surgery was significantly more successful regarding seizure control in patients with epilepsy due to mutations in the mTOR pathway. Patients with a lesion on MRI tended to have higher seizure freedom rates than those who were MRI‐negative. Conclusion. Although the evidence is still scarce, this systematic review suggests that studying genetic variations in patients with refractory epilepsy could help guide the selection of surgical candidates.     

EXPRESSION OF FLIP IN HUMAN COLON CARCINOMAS： A NEW MECHANISM OF IMMUNE EVASION

Objective： It has been proposed that Fas ligand （FasL） may play an important role in immune escape of tumors and FLIP is an important mediator of Fas/FasL pathway. In this study, the expression of FLIP was determined in human colon carcinoma cell lines and tissue to investigate the new mechanism of immune evasion of human colon carcinomas. Methods： RT-PCR and immunohistochemistry （IHC） were performed to investigate the expression of FLIP in human colon carcinoma cell lines SW480, LS174 and twenty human primary colon carcinoma specimens. Results： It was shown that SW480 cells, LS174 cells and primary colon carcinoma specimen constitutively expressed FLIP at the mRNA and protein level. The expression of FLIP was not found in the epithelial cells of normal colon mucosa. Conclusion： FLIP was expressed in human primary colon carcinoma specimens but not in the normal counterpart. It suggested that the expression of FLIP may occur during the malignant transformation from normal colon epithelial cells to colon carcinoma cells. Tumor cells might obtain the ability to resist the Fas-mediated apoptosis by expressing FLIP. The expression of FLIP might contribute to the formation of colon carcinomas.     

三环氟喹诺酮类化合物的合成及抗菌活性

芦氟沙星(Rufloxacin)是氟喹诺酮类抗菌药物,由于它在体内有高效、广谱、长效和口服吸收良好等特点,我们在保留芦氟沙星母核基本骨架的基础上进行结构修饰,合成了12个新化合物。体外抑菌试验发现随着10位边链的极性增大,对革兰氏阴性(G^-)菌的抗菌活性增强,而对革兰氏阳性(G⁺)菌活性则变化不大。     

Effectiveness of neurosurgical clip application in patients with aneurysmal subarachnoid hemorrhage

OBJECT: Neurosurgical clip application is the standard method used to prevent rebleeding in patients with aneurysmal subarachnoid hemorrhage (SAH). The authors assessed the magnitude of the reduction in poor outcomes that accompanies a strategy aimed at surgery. METHODS: Three hundred forty-six consecutive patients with aneurysmal SAH were studied. The authors estimated the number of surgically treated patients with good outcomes who would have had poor outcomes as a consequence of rebleeding if clip application had not been performed (A). They also assessed the number of patients whose poor outcomes were exclusively caused by operative complications (B). Without an operation some of these patients would have had poor outcomes because of rebleeding (C). The authors represented the number of patients in whom poor outcome was prevented by surgery with the following formula: A - B + C. They assessed the relationships between baseline characteristics of patients and aneurysms and the likelihood that a patient underwent surgery, the risk of operative complications, and the risk of rebleeding. The absolute reduction in the risk of poor outcome found in patients who undergo surgery was 9.7%. This implies that to prevent a poor outcome in one patient, surgery had to be performed in 10. The relative risk of poor outcome following surgery compared with that after conservative treatment was estimated to be 0.81. Logistic regression analysis showed a statistically significant relationship between patient age older than 65 years and the occurrence of operative complications (odds ratio [OR] 2.49; 95% confidence interval [CI] 1.03-6.03), between age older than 65 years and the likelihood of undergoing surgery (OR 0.12; 95% CI 0.07-0.2), and between a poor clinical condition at admission and the likelihood of undergoing surgery (OR 0.26; 95% CI 0.14-0.47). The authors did not identify any predictive factors for rebleeding when the Cox proportional hazard model was used. CONCLUSIONS: The beneficial effect of a treatment strategy in which the goal is surgery is substantial. If new treatment modalities such as embolization with coils are explored, these should carefully be compared with surgery before they are generally introduced.     

Cocaine Modulation of Frontostriatal Expression of Zif268, D2, and 5-HT2c Receptors in High and Low Impulsive Rats

Impulsivity shares high comorbidity with substance abuse in humans, and high impulsivity (HI) in rats has been identified as a predictive factor for cocaine addiction-like behavior. Despite the evidence that high impulsivity is associated with altered function of corticostriatal networks, the specific neural substrates underlying the increased vulnerability of impulsive individuals to develop cocaine addiction remain unknown. We therefore investigated specific neural correlates of HI within the corticostriatal circuitry and determined how they interact with a protracted history of cocaine self-administration. We used in situ hybridization to map brain expression of two major genes implicated in impulsivity, encoding the dopamine D2 receptor (DA D2R) and the 5-HT2c receptor (5-HT2cR), and an immediate early gene associated with neuronal plasticity, zif268, in groups of rats selected for HI and low impulsivity (LI) on a 5-choice serial reaction time task (5-CSRTT) immediately after 5-CSRTT training, and following 10 or 50 days of cocaine self-administration. HI rats exhibited decreased DA D2R mRNA in the mesolimbic pathway, and increased 5-HT2cR mRNA in the orbitofrontal cortex compared with LI rats. HI rats also showed decreased zif268 mRNA in the ventral and dorsomedial striatum. Cocaine exposure decreased striatal D2R mRNA in both HI and LI rats, decreased 5-HT2cR mRNA differentially in striatal and prefrontal areas between HI and LI rats, and selectively decreased zif268 mRNA in the orbitofrontal and infralimbic cortices of HI animals. These findings implicate novel markers underlying the vulnerability of impulsive rats to cocaine addiction that localize to the OFC, infralimbic cortex, and striatum.     

The effect of experimental streptococcus infection in myocarditis on some biochemical and inflammatory markers in albino rats

Background

Myocarditis is an uncommon disease that presents with a wide range of symptoms in children and adults. It is histologically characterized by varying degrees of myocardialnecrosis, edema and cellular infiltration myocardial inflammation is a nonspecificresponse to many triggers such as bacterial infection, cardio toxic agents, ormechanical injury.

Objective

This study was carried out to investigate the experimental Streptococcus faecalis induction of myocarditis and its effect on some blood parameters, inflammatory markers and histopathological changes in male albino rats.

Methods

Rats were infected by intraperitoneal injection of 10 8 CFU/ml of Streptococcus faecalis and sacrificed after one, two and seven days post infection. Biochemical analyses of blood were carried out to investigate the serum biomarkers of inflammation, liver function tests, cardiac enzymes & kidney function tests.

Results

All biochemical analyses showed statistically significant increase in the measured parameters due to bacterial infections except for blood urea which appear to be normal. A significant positive correlation was observed between lactate dehydrogenase enzyme (LDH) with creatinine (r =0.778, P<0.01). In the 7 days group, there were significant positive correlations between aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (r=0.675, P<0.05), erythrocyte sedimentation rate (ESR) with Urea (r=0.659, P<0.05) and alkaline phosphatase (ALP) with C-reactive protein (CRP) (r=0.765, p<0.01).

Conclusion

Many of these biomarkers will provide important new insights into pathophysiology and aid in the diagnosis and management of cardiovascular patients.     

Autoimmunity as an aetiological factor in vitiligo

Vitiligo is a common dermatological disorder characterized by the presence on the skin of depigmented macules resulting from the destruction of cutaneous melanocytes. Autoimmunity is an important hypothesis with regard to vitiligo aetiology and the evidence for autoimmune responses being involved in the pathogenesis of this disorder will be discussed in the present review. All immune system compartments, including innate and adaptive immunity have been implicated in vitiligo development. Particularly relevant are autoantibodies and autoreactive T cells in vitiligo patients that have cytotoxic effects upon pigment cells. Furthermore, predisposition to vitiligo appears to be associated with certain alleles of the major histocompatibility complex class II antigens as well as with other autoimmune-susceptibility genes. Moreover, the association of vitiligo with autoimmune disorders, the animal models of the disease, and the positive response to immunosuppressive therapeutic agents emphasize the role of autoimmunity in the development of this disorder.