Exogenous hormones and hereditary angioedema

Gonadal hormones, estrogen and androgen are strongly involved in the control of the bradykinin production. Estrogen may worsen whereas androgen can be part of the long-term prophylactic treatment. In this review, we will describe the potential impact of estrogen in the pathophysiology of hereditary angioedema (HAE). Then we will review the different hormone treatments and their implication on the course of HAE in women and men: contraception, Assisted Reproductive Technology (ART), menopause, hormone dependent cancers in women and men, treatment of hyperandrogenism in women.     

Expression of TRIM22 mRNA in chronic hepatitis C patients treated with direct-acting antiviral drugs

Hepatitis C is a global public health problem, and Pakistan is the second largest country in the globe with highest prevalence rate of hepatitis C virus (HCV). Until 2014, pegylated interferon (PEG-IFN) plus ribavirin (RBV) has been the standard therapy for HCV, however, owing to its adverse side effects and very low sustained virologic response (SVR) rates therapeutics trend is shifted toward direct-acting antivirals. Tripartite motif containing 22 (TRIM22) is a dynamic antiviral protein that can inhibit multiple viruses in vivo. Expression of TRIM22 mRNA has been linked to outcome of PEG-IFN and ribavirin therapy, where its higher expression leads to rapid virus clearance. However, in terms of therapy with direct-acting antiviral (DAA) or double DAA, impact of TRIM22 expression is largely unknown. These new drugs show more than 90% of SVR rates and lesser side effects and have proven to be better than IFN therapy. Endogenous IFN system suppresses various pathogens through the induction of antiviral effectors termed as interferon-stimulating genes (ISGs). We have studied the expression levels of one of these antiviral effectors, TRIM22 in response to sofosbuvir (SOF) and daclatasvir (DAC) in combination with RBV, using quantitative PCR in the peripheral blood mononuclear cells (PBMCs) of HCV-infected patients. We have observed sustained virus clearance in more than 90% of patients treated with DAA and double DAA and have seen the expression of TRIM22 to be higher in patients who attained SVR as compared to the untreated patients. We have also observed downregulation of TRIM22 in patients who failed to attain rapid virus clearance, and upregulation in those who achieved rapid clearance of virus. Genetic factors that determine the lower TRIM22 expression in these patients are needed to be explored that may also play a role in lower response to anti-HCV therapy. Endogenous IFN system and effects of antiviral proteins in response to DAA therapy is needed to be studied in order to better understand the host response toward these drugs to make them more effective.     

Hepatitis C virus in MALT-lymphoma of the ocular adnexa

ObjectiveHepatitis C virus (HCV) has been proposed as a possible etiologic factor in ocular adnexal marginal zone lymphoma (OAML). We aimed to assess the prevalence of HCV infection in patients with OAML through a systematic review and meta-analysis.MethodsElectronic databases were searched from their inception to August 2019 for studies assessing HCV seroprevalence in patients with OAML. Pooled prevalence of HCV infection was calculated with 95 % confidence interval (CI). Statistical heterogeneity among studies was quantified via the inconsistency index (I²). Funnel plot symmetry was used to assess the risk of bias across studies.ResultsNine studies with 360 patients were included. Overall pooled prevalence of HCV in OAML was 12.7 %, with low statistical heterogeneity (I² = 17.4 %) and with asymmetrical funnel plot. The studies clustered into two groups: 5 studies (3 from Italy and 2 multicenter with a major Italian contribution) showed a higher HCV prevalence in OAML (15.6 %), while the other 4 (from countries other than Italy) showed a lower prevalence (4.7 %); in both subgroups, statistical heterogeneity was null (I² = 0%) and funnel plot was symmetrical.ConclusionHCV might be a significant etiologic factor of OAML in Italy.     

大剂量细胞色素C在抢救儿童急性磷化氢中毒的临床作用

目的 探讨儿童急性磷化氢中毒的临床特点,及大剂量细胞色素C的临床作用。方法 收集2013年11月—2018年6月本中心救治的急性磷化氢中毒儿童22例临床资料,并回顾性分析。结果 男13例,女9例;年龄29 d~13岁;轻中度磷化氢中毒10例,重度磷化氢中毒12例;轻中度中毒患儿出现症状至就诊时间明显短于重度中毒患儿(P=0.029)。轻中度磷化氢中毒主要表现为头晕、恶心、呕吐、腹痛;重度中毒主要表现为昏迷、口唇紫绀、低血压,甚至心源性休克。实验室检查:脑钠肽异常升高12例;心肌酶异常12例;血乳酸升高10例;心电图异常16例,均表现为快速心律失常,其中1例为尖端扭转型心律失常。除常规治疗外,均给予大剂量细胞色素C治疗,轻中度中毒患儿均治愈,重度中毒患儿治愈6例,死亡6例,22例儿童磷化氢中毒总死亡率为27.3%,重度磷化氢中毒死亡率50%。结论 儿童急性磷化氢中毒死亡率高,在常规治疗的基础上,给予静脉应用大剂量细胞色素C可明显降低儿童急性磷化氢中毒的死亡率。     

Higher mass meningococcal group C-tetanus toxoid vaccines conjugated with carbodiimide correlate with greater immunogenicity

To examine the link between meningococcal C (MenC) vaccine size and immunogenic response, a panel of MenC glycoconjugate vaccines were prepared differing in chain length, molar mass and hydrodynamic volume. The preparations consisted of different lengths of MenC polysaccharide (PS) covalently linked to monomeric purified tetanus toxoid (TT) carrier protein using the coupling reagent ethylcarbodiimide hydrochloride (EDC). Size exclusion chromatography with multi-angle light scattering (SEC-MALS) and viscometry analysis confirmed that the panel of MenC-TT conjugates spanned masses of 191,500 to 2,348,000 g/mol, and hydrodynamic radii ranging from 12.1 to 47.9 nm. The two largest conjugates were elliptical in shape, whereas the two smallest conjugates were more spherical. The larger conjugates appeared to fit a model described by multiple TTs with cross-linked PS, typical of lattice-like networks described previously for TT conjugates, while the smaller conjugates were found to fit a monomeric or dimeric TT configuration. The effect of vaccine conjugate size on immune responses was determined using a two-dose murine immunization. The two larger panel vaccine conjugates produced higher anti-MenC IgG1 and IgG2b titres after the second dose. Larger vaccine conjugate size also stimulated greater T-cell proliferative responses in an in vitro recall assay, although cytokines indicative of a T-helper response were not measurable. In conclusion, larger MenC-TT conjugates up to 2,348,000 g/mol produced by EDC chemistry correlate with greater humoral and cellular murine immune responses. These observations suggest that conjugate size can be an important modulator of immune response.     

The activity prediction of indole inhibitors against HCV NS5B polymerase

Non‐structural viral protein 5B (NS5B) is a viral protein in hepatitis C virus. Although various inhibitors against NS5B have been found, the activity prediction of similar untested inhibitors is still highly desirable. In this respect, the Tchebichef moments (TMs) calculated from the images of molecular structures were regarded as the independent variables while the inhibitory activity (pIC₅₀) was the dependent variable, and the predictive model was established by means of stepwise regression. The R‐squared of leave‐one‐out cross‐validation (Q²) for the training set and the R‐squared of prediction () for external independent test set were 0.919 and 0.927, respectively. The obtained model was also evaluated strictly. Compared with the multivariate curve resolution with alternating least squares (MCR‐ALS) and the QSAR approaches derived from the literature, the proposed method is more accurate and reliable. This study not only provides an effective approach to predict the biological activity of RNA replication's inhibitors, but also extends the QSAR modeling technique.     

超敏C反应蛋白与自发性脑出血患者血肿量及预后的相关性分析

目的探讨超敏C反应蛋白(hs-CRP)与自发性脑出血患者(SICH)血肿量和预后的相关性。方法选取2016-01-2018-10萍乡市人民医院收治的SICH患者162例。将其分为大量血肿组、小量血肿组,选择同时期江西萍乡市人民医院80例门诊体检者为对照组。检测和比较3组入院时hs-CRP水平,比较预后良好和不良患者的hs-CRP水平,评价血清hs-CRP水平与血肿体积、预后的相关性。结果大量及小量血肿组hs-CRP水平显著高于对照组(P<0.01),且大量血肿组hs-CRP水平显著高于小量血肿组(P<0.05)。预后良好组hs-CRP水平显著低于预后不良组(P<0.05)。SICH患者hs-CRP水平与血肿量大小和GOS评分呈正相关(r=0.452,0.433,P<0.05)。结论SICH患者血清hs-CRP水平显著升高,与血肿量大小和预后明显相关。     

C57BL/6小鼠放射性心肺功能不全动物模型建立

目的 建立C57BL/6小鼠放射性心肺功能不全动物模型。方法 24只雄性C57BL/6小鼠随机分为对照组、照射组。照射组接受胸部局部单次20 Gy电子线照射,照后饲养6个月。超声心动检查心功能,血气分析检测血氧分压(PaO₂),Tunel染色法检测细胞凋亡,Masson染色法检测心肺纤维化。结果 照射组LVEF (68.60±10.92)%与对照组(81.75±8.79)%降低(P<0.01);照射组心脏凋亡指数(23.90±6.60)%比对照组(3.25±3.38)%增高(P<0.01);照射组心脏CVF (15.42±5.72)%比对照组(1.45±0.64)%增高(P<0.01)。照射组PaO₂(86.10±7.60) mmHg比对照组PaO₂(107.16±9.01) mmHg下降(P<0.01);照射组肺脏凋亡指数(27.90±8.94)%比对照组(2.50±3.55)%增高(P<0.01);照射组肺脏CVF (17.76±5.77)%比对照组(2.50±3.55)%增高(P<0.01)。结论 辐射使心肺凋亡纤维化重塑,进而导致心肺功能的下降,成功构建C57BL/6小鼠放射性心肺功能不全动物模型。     

Directly observed hepatitis C treatment with opioid substitution therapy in community pharmacies: A qualitative study

BackgroundThe hepatitis C virus (HCV) will only be eliminated through successful engagement with people who inject drugs (PWID), however some of this population experience socioeconomic and individual issues that can lead to poor HCV treatment adherence. A key sub-group of (PWID) are those who receive opioid substitution therapy (OST). In Australia, OST is most often delivered under direct supervision by a community pharmacist every day or multiple times a week. This regular interaction could be an ideal opportunity to enhance direct-acting antiviral (DAA) treatment adherence under directly observed therapy (DOT) by the pharmacist.AimThe aim of this study was to explore the perspectives of OST patients with a lived experience of HCV to understand whether or not dispensing DAAs in the same way as, or simultaneously with OST would benefit HCV treatment.MethodsData collection occurred from June to August 2017. Semi-structured interviews were conducted with a sample of PWID living with HCV and on OST programs (n = 12) in Melbourne, Australia. Interviews were voice recorded and transcribed in verbatim. Interpretive phenomenology guided analysis of the data.ResultsThemes reported by participants that provide insight into the suitability of DOT of DAAs include: Adherence and non-adherence to DAA treatment; Mixed views towards DOT of DAAs; Experiences and perceptions of OST providers; and Perceived stigma in the pharmacy.ConclusionsCommunity pharmacies offering OST may be an effective place for DOT of HCV treatment, but is likely only to benefit people who face significant challenges to adherence. We suggest that a positive pharmacist-patient relationship, high OST adherence, and commitment to reducing stigma in the pharmacy would be necessary for the intervention to be effective. Further research is needed to evaluate the expanded-role of community pharmacies in improving DAA adherence and eliminating HCV.