Patents review in siRNA delivery for pulmonary disorders

siRNA inhibits protein expression by degrading complementary mRNA sequence and hence, it is widely applicable for the treatment of various diseases where single or multiple gene knock down is necessary. Due to the severity and lethality of pulmonary diseases, siRNA has been focused for improved health in these diseases. Pulmonary accumulation of siRNA can be achieved by different means like intranasal or inhalation administration or intratracheal route which is mainly utilized for in vivo animal studies. However, various pulmonary obstacles and intracellular barriers for siRNA transport challenge this novel therapeutic moiety. Researchers have utilized different viral and non-viral delivery vectors for intracellular delivery of siRNA to knock down target mRNA. The promise of RNA interference, mediated by siRNAs, has revolutionized the prospects for modulating gene expression as a way to achieve therapeutic aims in disease treatment. This review focuses on patents describing the siRNA delivery either in naked form or along with a single/multiple delivery vectors. Many inventors have shown promising results for pulmonary utilization of siRNA and more concentration on delivery system may make this genomic approach available to the clinics soon.     

红姜叶提取物所含化学成分的抗肿瘤及抗茵作用

目的：研究红姜叶提取物中的化学成分的抗肿瘤及抗菌活性。方法：用自来水充分洗净红姜叶,晾干后制成粉剂,用连续溶剂系统提取其化学成分。对植物化学成分进行评估,运用纸片扩散法检测植物提取物的抗菌活性,利用四甲基偶氮唑盐比色法检测植物叶子的乙酸乙酯提取物的抗肿瘤作用。结果：红姜叶经乙酸乙酯提取后,能最大限度得到有效的植物化学成分。不同浓度的红姜叶植物提取物抑制细菌的区域为5～14mm;并且在48h内、植物提取物半数抑制浓度为110．25μg／mL时表现出抗PA1卵巢癌细胞株活性,且细胞数量呈剂量依赖性递减。结论：红姜叶的乙酸乙酯提取物中的化学成分可有效抑制细菌活性,并具有抗肿瘤的作用。     

Iatrogenic Intradural Lumbosacral Cyst Following Epiduroscopy

We report a rare complication of iatrogenic spinal intradural following minimally invasive extradural endoscopic procedues in the lumbo-sacral spines. To our knowledge, intradural cyst following epiduroscopy has not been reported in the literature. A 65-year-old woman with back pain related with previous lumbar disc surgery underwent endoscopic epidural neuroplasty and nerve block, but her back pain much aggravated after this procedure. Postoperative magnetic resonance imaging revealed a large intradural cyst from S1-2 to L2-3 displacing the nerve roots anteriorly. On T1 and T2-weighted image, the signal within the cyst had the same intensity as cerebrospinal fluid. The patient underwent partial laminectomy of L5 and intradural exploration, and fenestration of the cystic wall was accomplished. During operation, the communication between the cyst and subarachnoid space was not identified, and the content of the cyst was the same as that of cerebrospinal fluid. Postoperatively, the pain attenuated immediately. Incidental durotomy which occurred during advancing the endoscope through epidural space may be the cause of formation of the intradural cyst. Intrdural cyst should be considered, if a patient complains of new symptoms such as aggravation of back pain after epiduroscopy. Surgical treatment, simple fenestration of the cyst may lead to improved outcome. All the procedures using epiduroscopy should be performed with caution.     

Efficacy and safety of pan-genotypic sofosbuvir and velpatasvir in patients with hepatitis C and HIV coinfection on dolutegravir-based antiretroviral therapy

Hepatitis C virus (HCV) infection is more prevalent in people living with HIV-AIDS (PLHA) and portends a poorer prognosis. Pharmacokinetic studies suggest the absence of significant interaction between velpatasvir and dolutegravir which has been recently recommended as part of preferred first-line antiretroviral therapy (ART) regimens by WHO. However, clinical data on the use of velpatasvir-based regimen in PLHA taking dolutegavir is lacking. Hence, we aimed to assess the efficacy and safety of sofosbuvir and velpatasvir (SOF + VEL) in HCV and HIV coinfected patients on dolutegravir-based ART. Forty-five consecutive PLHA with HCV coinfection on dolutegravir-based ART were prospectively enrolled. All patients were treated SOF + VEL for 12 weeks. Complete haemogram, liver and renal function tests were assessed at baseline, 4 weeks and at end of treatment. Sustained virological response (SVR) was assessed at 12 weeks after end of treatment. The majority were males (95.5%) with a mean age of 32.8 ± 12.3 years. Cirrhosis was present in 6 (13.3%) patients. All patients completed 12 weeks of therapy with SOF + VEL, but SVR could not be assessed in two patients. Forty-two (97.7%) of the remaining 43 patients attained SVR-12. SVR-12 rate was 97.7% and 93.3% by per protocol and intention to treat analysis, respectively. No grade III/IV adverse events were reported, and there was no worsening of blood counts, liver or renal function test parameters. The pan-genotypic regimen of SOF + VEL is safe and effective in PLHA with HCV coinfection who are on dolutegravir-based ART.