Melatonin reduces oxidative stress and improves vascular function in pulmonary hypertensive newborn sheep

Pulmonary hypertension of the newborn (PHN) constitutes a critical condition with severe cardiovascular and neurological consequences. One of its main causes is hypoxia during gestation, and thus, it is a public health concern in populations living above 2500 m. Although some mechanisms are recognized, the pathophysiological facts that lead to PHN are not fully understood, which explains the lack of an effective treatment. Oxidative stress is one of the proposed mechanisms inducing pulmonary vascular dysfunction and PHN. Therefore, we assessed whether melatonin, a potent antioxidant, improves pulmonary vascular function. Twelve newborn sheep were gestated, born, and raised at 3600 meters. At 3 days old, lambs were catheterized and daily cardiovascular measurements were recorded. Lambs were divided into two groups, one received daily vehicle as control and another received daily melatonin (1 mg/kg/d), for 8 days. At 11 days old, lung tissue and small pulmonary arteries (SPA) were collected. Melatonin decreased pulmonary pressure and resistance for the first 3 days of treatment. Further, melatonin significantly improved the vasodilator function of SPA, enhancing the endothelial‐ and muscular‐dependent pathways. This was associated with an enhanced nitric oxide‐dependent and nitric oxide independent vasodilator components and with increased nitric oxide bioavailability in lung tissue. Further, melatonin reduced the pulmonary oxidative stress markers and increased enzymatic and nonenzymatic antioxidant capacity. Finally, these effects were associated with an increase of lumen diameter and a mild decrease in the wall of the pulmonary arteries. These outcomes support the use of melatonin as an adjuvant in the treatment for PHN.     

藿香正气汤抑制新型冠状病毒复制过程的有效成分及机制初探＊

目的 收集藿香正气汤的主要活性成分，通过分子对接及网络药理学探讨其防控新型冠状病毒肺炎（COVID-19）的有效成分及治疗机制。方法 通过基于配体-蛋白质相互作用的计算方法，以瑞德西韦为对照，探索藿香正气汤潜在治疗COVID-19的成分，并选出对接较好成分进行药理学机制预测，初探其药理学机制。结果 本研究筛选出5种与新冠病毒3CLpro结合能力强于瑞德西韦的小分子成分。网络药理学初步预测抗病毒途径可能是通过PI3K-Akt 信号通路影响病毒复制。结论 成分C1-C5与3CLpro结合良好，推测其可能是潜在的3CLpro的抑制剂，为抗病毒天然药物的开发提供了理论依据。     

Successful Treatment of Severe Psoriasis in an Adolescent with Ustekinumab

Psoriasis is a chronic, inflammatory, immune‐mediated disease. Approximately 30% of patients have disease onset before age 18 years. Psoriasis in children and adolescents may be difficult to control, with subsequent poor quality of life and psychosocial consequences. We describe the case of a 12‐year‐old boy with severe, refractory, chronic plaque psoriasis for 6 years. Various therapeutic regimens including different topical corticosteroids, topical vitamin D analogs, phototherapy, photochemotherapy, systemic therapy with methotrexate, cyclosporin, and combination therapies showed only partial or transient responses with frequent relapses. Because anti‐interleukin‐12/23 agents have been successfully used in adults with psoriasis, ustekinumab was initiated and our patient showed a rapid, excellent, sustained response. No recurrence or flares have been observed after 33 months of follow‐up. This case illustrates that ustekinumab may be an effective and safe therapeutic option in adolescents with psoriasis.     

Ileocolic Intussusception Caused by a Giant Ulcerating Lipoma of Bauhin’s Valve: an Unusual Cause of Intestinal Obstruction in the Adult

We report a case of intestinal obstruction in a 73-year-old woman caused by ileocolic intussusception. The underlying cause was a giant submucosal ulcerating lipoma (6?×?3.3?×?3.8 cm) extending from the superior mucosal lip of Bauhin’s valve. Abdominal ultrasonography showed a pathognomonic target-like mass appearing as multiple concentric rings. CT scan confirmed the diagnosis. Because of apparent obstruction, a laparotomy with right hemicolectomy and ileocolic anastomosis was performed. Lipomas most frequently occur in the cecum and ascending colon where they represent the most common submucosal mesenchymal tumor. They typically occur in elderly women with an incidence that varies from 0.15 to 0.56 %. Pain, rectal bleeding, and obstruction are typical symptoms. When faced with an intussusception in children, reduction with air per rectum can be performed. In adults, however, malignant cell spreading and seeding is of big concern. Since approximately 20–50 % of all underlying causes are malignant, explorative surgery is favored in adults.