Potential health risks to adults and children in the UK from exposure to dietary lead in gamebirds shot with lead ammunition

We estimate potential risks to human health in the UK from dietary exposure to lead from wild gamebirds killed by shooting. The main source of exposure to lead in Europe is now dietary. We used data on lead concentrations in UK gamebirds, from which gunshot had been removed following cooking to simulate human exposure to lead. We used UK food consumption and lead concentration data to evaluate the number of gamebird meals consumed weekly that would be expected, based upon published studies, to result in changes, over and above those resulting from exposure to lead in the base diet, in intelligence quotient (IQ), Systolic Blood Pressure and chronic kidney disease (CKD) considered in a recent opinion of the European Food Safety Authority (EFSA) to be significant at a population level and also in SAT test scores and in rates of spontaneous abortion. We found the consumption of <1 meal of game a week may be associated with a one point reduction in IQ in children and 1.2–6.5 gamebird meals per week may be associated with the other effects. These results should help to inform the development of appropriate responses to the risks from ingesting lead from ammunition in game in the UK and European Union (EU).     

Postmarketing safety evaluation: depside salt injection made from Danshen (Radix Salviae Miltiorrhizae)

ObjectiveTo systematically examine the postmarketing safety of depside salt injection made from Danshen (Radix Salviae Miltiorrhizae), identify the potential risk factors, and ensure its clinical safety.MethodsWe examined a comprehensive series of studies on the production process, quality standards, pharmacology, population pharmacokinetics, and safety evaluation of depside salt injection made from Danshen (Radix Salviae Miltiorrhizae). Data from I-IV clinical drug trials, hospital information systems (HIS), and spontaneous reporting systems (SRS) were also analyzed.ResultsThe effective components of salvianolic acid salt content reached almost 100%, and the magnesium lithospermate B content reached more than 80%. The median lethal dose (LD50) calculated by the Bliss method was 1.49 g/kg, with 95% confidence intervals of 1.29–1.72 g/kg. Long-term tests on Beagle dogs indicated that doses of less than 80 mg/kg were safe and doses of 320 mg/kg were toxic. Adverse drug reactions (ADRs) included digestive disorders; drug-induced erythrocyte deformation in lung, liver, spleen, kidney, bone marrow, intestinal mucosa, lymph nodes, and other tissues; megakaryocytes in lung, liver, and spleen resulting from mild hemolysis; and mild hyperplasia in bone marrow hematopoietic tissue. Other studies indicated no irritative effect of the injection on local tissues and blood vessels, and no allergic reactions, erythrocyte coagulation, or hemolysis. SRS data showed that the most common ADRs were headache, head distention, dizziness, facial flushing, skin itching, thrombocytopenia, and the reversibility of elevated Aspartate transaminase. HIS data indicated no damage to renal function from using depside salt injection made from Danshen (Radix Salviae Miltiorrhizae) at a dosage higher than the recommended dose.ConclusionThis study analyzes the clinical characteristics of ADRs from depside salt injection made from Danshen (Radix Salviae Miltiorrhizae), and discusses the factors influencing such reactions. It provides scientific reference and recommendations for clinically safe medication of the Danshen injection.     

PEGylated Carboxyhemoglobin Bovine (SANGUINATE): Results of a Phase I Clinical Trial

PEGylated carboxyhemoglobin bovine (SANGUINATE) is a dual action carbon monoxide releasing (CO)/oxygen (O₂) transfer agent for the treatment of hypoxia. Its components inhibit vasoconstriction, decrease extravasation, limit reactive oxygen species production, enhance blood rheology, and deliver oxygen to the tissues. Animal models of cerebral ischemia, peripheral ischemia, and myocardial ischemia demonstrated SANGUINATE's efficacy in reducing myocardial infarct size, limiting necrosis from cerebral ischemia, and promoting more rapid recovery from hind limb ischemia. In a Phase I trial, three cohorts of eight healthy volunteers received single ascending doses of 80, 120, or 160 mg/kg of SANGUINATE. Two volunteers within each cohort served as a saline control. There were no serious adverse events. Serum haptoglobin decreased, but did not appear to be dose related. The T_1/2 was dose dependent and ranged from 7.9 to 13.8 h. In addition to the Phase I trial, SANGUINATE was used under an expanded access emergency Investigational New Drug. SANGUINATE was found to be safe and well tolerated in a Phase I clinical trial, and therefore it will advance into further clinical trials in patients.     

Rituximabe para o tratamento da artrite reumatoide: Revisão sistemática

IntroductionRheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic joint inflammation that often leads to significant disability. Several effective anti–TNF agents have been used, but some patients have shown an inadequate response. Rituximab is a therapeutic monoclonal antibody indicated in such cases.MethodsWe conducted a systematic review to access efficacy and safety of rituximab in patients with active RA which have or have not been treated with anti–TNF agents before, and to relate outcome with RF and anti–CCP serology. We searched major electronics databases, grey literature and searched for references manually. We used Review Manager®5.1 for meta–analysis.ResultsWe included six RCTs comparing rituximab 1000 mg with placebo. Methotrexate was used by both groups. Treatment with rituximab was more effective in naïve and in anti–TNF treatment failure patients ACR20/50/70 and EULAR response. We observed lower changes in Total Genant–modified Sharp score, erosion score and joint narrowing scores in the rituximab group, and SF–36, FACIT–T and HAQ–DI scores were also better in this group. There were no differences between groups regarding safety outcomes, with exception of acute injection reactions, which were more common on rituximab group. More RF/anti–CCP seropositive patients achieved ACR20 than RF/anti–CP negative patients in rituximab group.ConclusionAvailable data support the use of rituximab for the treatment of RA, as it is an effective and safe option for naïve and anti–TNF treatment failure patients. RF and anti–CCP seam to influence treatment results, but this inference needs further research.     

开腹与后腹腔镜术式治疗肾上腺良性肿瘤的比较

目的 探讨开腹与后腹腔镜术式对肾上腺良性肿瘤患者围手术期临床指标、ICU转送率及并发症的影响。方法 选取120例肾上腺良性肿瘤患者为研究对象，以随机数字表法分为对照组和观察组，每组各60例；其中对照组患者采用开腹术式治疗，观察组患者则采用后腹腔镜术式治疗；比较两组患者的手术时间、术中失血量、肛门排气时间、术后引流量、术后拔管时间、住院时间、ICU转送率及并发症发生率。结果 观察组患者手术时间、肛门排气时间、术后拔管时间及住院时间均显著短于对照组（P＜0.05）；观察组患者术中失血量和术后引流量均显著少于对照组（P＜0.05）；两组患者ICU转送率比较差异无统计学意义（P＞0.05）；同时观察组患者术中和术后并发症发生率均显著低于对照组（P＜0.05）。结论 后腹腔镜术式治疗肾上腺良性肿瘤可有效减轻医源性损伤程度，促进术后早期康复，且有助于避免术中及术后出现并发症，其临床应用价值优于开腹术式。