Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with multi-organ inflammation and defect, which is linked to many molecule mediators. Oxylipins as a class of lipid mediator have not been broadly investigated in SLE. Here, we applied targeted mass spectrometry analysis to screen the alteration of oxylipins in serum of 98 SLE patients and 106 healthy controls. The correlation of oxylipins to lupus nephritis (LN) and SLE disease activity, and the biomarkers for SLE classification, were analyzed. Among 128 oxylipins analyzed, 92 were absolutely quantified and 26 were significantly changed. They were mainly generated from the metabolism of several polyunsaturated fatty acids, including arachidonic acid (AA), linoleic acid (LA), docosahexanoic acid (DHA), eicosapentanoic acid (EPA) and dihomo-γ-linolenic acid (DGLA). Several oxylipins, especially those produced from AA, showed different abundance between patients with and without lupus nephritis (LN). The DGLA metabolic activity and DGLA generated PGE1, were significantly associated with SLE disease activity. Random forest-based machine learning identified a 5-oxylipin combination as potential biomarker for SLE classification with high accuracy. Seven individual oxylipin biomarkers were also identified with good performance in distinguishing SLE patients from healthy controls (individual AUC > 0.7). Interestingly, the biomarkers for differentiating SLE patients from healthy controls are distinct from the oxylipins differentially expressed in LN patients vs. non-LN patients. This study provides possibilities for the understanding of SLE characteristics and the development of new tools for SLE classification.

Lubiprostone, a derivative of prostaglandin E1, is the first chemical-type constipation treatment approved by FDA. Lubiprostone has low systemic exposure after oral administration. Therefore, it is recommended that 15-hydroxylubiprostone, which is a dominant active metabolite of lubiprostone, be used as the pharmacokinetic evaluation indicator. Due to the microdosage of the lubiprostone capsules, it is difficult to develop a highly sensitive bioanalytical method for 15-hydroxylubiprostone.In this study, a highly sensitive and selective liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method has been established and fully validated for the quantification of 15-hydroxylubiprostone in human plasma, and the validated bioanalytical method has been applied to a pharmacokinetic study of lubiprostone capsules successfully.The pharmacokinetics of 15-hydroxylubiprostone were observed after fed administration in healthy Chinese volunteers. The Cmax and AUC0-t were 75.8 ± 57.6 pg/mL and 222 ± 68.0 pg·h/mL for 15-hydroxylubiprostone.This study investigated the pharmacokinetic properties of 15-hydroxylubiprostone under fed conditions in healthy Chinese volunteers and would provide clinical guidance for the application and further development of lubiprostone capsules.

Type 1 interferons play a key role in the pathogenesis of systemic lupus erythematosus (SLE). An important clinical question is whether inhibiting the type 1 interferon pathway reduce the disease activity in SLE patients. This review evaluates the safety and efficacy of the monoclonal antibody against the type 1 interferon alpha receptor, anifrolumab, in patients with SLE.

Misoprostol, a synthetic PGE1, is becoming a common therapy for mares with suspected uterine tube obstruction. Recently, there have been concerns that uterine administration of misoprostol induces exacerbated uterine inflammation; however, this has not been critically evaluated. This study aimed to assess the inflammatory response and potential systemic reactions after uterine administration of misoprostol, either during prebreeding or immediately after postembryo flushing. Privately owned embryo donor mares (n = 11) were randomly assigned in a crossover design to receive misoprostol (3 mL +200 µg) or sham (3 mL of lactate Ringer's solution) infusions, bilaterally deposited via deep-horn, at least 72 hours prebreeding (experiment 1) or immediately after embryo flushing (experiment 2). Each mare had one cycle for misoprostol and sham in both experiments and a breeding cycle (no sham or misoprostol) between experiments. Uterine edema, fluid accumulation, and the number of uterine PMN were assessed before each infusion and then daily for 72 hours. Uterine lavage was performed the day after each infusion across groups and experiments. Ovulation was hastened with a GnRH agonist and confirmed at 24 hour-intervals. Mares were bred with semen from one of six stallions per owner's choice. Embryo flushing was performed 8 to 9 days postovulation. In either experiment, misoprostol did not affect uterine edema or fluid accumulation (P > .05). However, both the sham and misoprostol infusions increased the number of PMN up to 48 hours postinfusion in both experiments. Embryo recoveries were similar between sham (45%, 5/11) and misoprostol cycles in experiments 1 (45%, 5/11; P > .05) and 2 (sham, 68%, 7/11; misoprostol, 45%, 5/11; P > .05). In conclusion, misoprostol did not induce exacerbated uterine inflammation in mares or systemic adverse reactions when infused prebreeding or immediately after embryo flushing.

The recognition of the erectile dysfunction pathogenesis is essential to identify the appropriate erectile dysfunction management. As vascular erectile dysfunction could be a manifestation of a systemic arterial damage, the watershed in the erectile dysfunction diagnostic framework is the discrimination between psychological erectile dysfunction and vascular erectile dysfunction. However, reliable tools to directly diagnose psychological erectile dysfunction are currently lacking.

A 4-hour-old infant with profound cyanosis on an alprostadil infusion was urgently transferred to Rady Children's Hospital with suspected CHD. Upon arrival, urgent echocardiography was performed but could not confirm the presence of discrete pulmonary veins or pulmonary venous drainage. Given the difficulty in delineating the anatomy, a cardiac CT scan was performed and demonstrated a nearly atretic common pulmonary vein with multiple small collaterals that drained to systemic veins. Due to the high risk of mortality associated with operative repair, the decision was made to proceed with compassionate withdrawal of care. The described anatomy of common pulmonary vein atresia remains rare, and to our knowledge, fewer than 40 cases have been reported in the literature. Albeit rare, common pulmonary vein atresia should be considered in the differential diagnosis of a severely cyanotic neonate.

Background: The extent of arterial disease in patients with erectile dysfunction (ED) non-responsive to intracavernosal injection of Alprostadil is of importance for therapeutic options. However, published evidence, in particular angiographically validated is scarce. Here we investigated arterial lesion patterns in this specific patient cohort by selective angiography. Patients and methods: A cohort of 239 patients received a clinical and duplex-sonographic workup for ED of suspected vascular origin. Duplex ultrasound of the cavernosal arteries was performed after intracavernosal injection of 10 μg Alprostadil. Consequently, standardized workup included grading of the erectile and determination of peak systolic velocity (PSV) and end-diastolic velocity (EDV) in both cavernosal arteries. PSV-values below 30 cm/sec indicated reduced arterial flow, whereas EDV-values above 15 cm/sec indicated a venous leak of the pudendal veins. All patients with suspected arterial ED based on duplex sonography underwent contrast-enhanced computed tomography. Endovascular therapy was carried out in ED patients not responsive or with significant side effects to PDE-5-inhibitors or Alprostadil by selective angiographic depiction of erection-related arteries. Results: 54 patients with a mean age of 61.2 (±9.8) years underwent angioplasty of erectionr elated arteries. Out of these 48/54 (89%) patients presented with an erection considered insufficient for penetration (E0-E3) subsequent to intracavernous application of 10 μg Alprostadil. 14/48 (29%) patients had bilateral arterial obstructions and 34/48 (71%) had unilateral disease. Commonly affected was the internal pudendal artery (n = 31, 65%), followed closely by the common penile artery (n = 30, 64%). The least affected arteries were the dorsal penile (n = 6, 13%), hypogastric (n = 4, 8%), common iliac (n = 4, 8%), cavernosal (n = 4, 8%), and inferior gluteal (n = 1, 2%) arteries. Conclusions: Arterial obstructions amenable to endovascular revascularization are frequent in patients non-responsive to intracavernosal prostaglandin administration. Therapeutic strategies in ED patients non-responsive to conservative measures should therefore consider endovascular treatment opportunities.

Objective: N-(2-methoxy) benzyl-phenethylamine (NBOMe) derivatives have a high affinity to the serotonin receptor 2A and emerged as new psychedelic agents. We report the case of a 30-year-old man admitted to the hospital because of acute ischemia of the left arm with clinical symptoms of pallor, pulselessness, paresthesia, and a motoric deficit. The patient had a history of schizophrenia and drug abuse and disclosed during the hospital stay the sublingual intake of a substance bought as 25I-NBOMe the night before the ischemic event. Methods: Routine clinical diagnostics including among others color-coded duplex sonography and computed tomography angiography (CTA) were performed. The remainder of the drugs was analyzed using high performance liquid chromatography. Results: Initial color-coded duplex sonography of the upper left limb showed pathological flow profiles of the axillary, brachial, ulnar, and radial artery with a reduced diameter of the ulnar (0.9 mm) and radial (1.1 mm) artery. In consequence, peripheral vasospasm, distal arterial thrombosis, or arterial embolization was anticipated. As therapeutic measures, the patient immediately received intravenous systemic vasodilators (alprostadil) and therapeutic anticoagulation with low molecular weight heparin. Instant symptom improvement was observed within the first day after therapy initiation. The subsequently performed CTA of the heart and left arm showed no signs of thrombotic material. Treatment was continued for five days and the patient was released thereafter having completely normalized perfusion in his left arm. Outpatient treatment was continued with calcium-channel blockers, as the patient had also displayed arterial hypertension. Drug analysis retrieved a composition of the isomers 25I-NBOMe, 25C-NBOMe, and 25H-NBOMe as well as traces of pentylon. Conclusion: NBOMe ingestion implicates the risk of peripheral vasospasms with severe, limb-threatening ischemia.

A Japanese female infant with trisomy 18 was diagnosed with hypoplastic left heart syndrome variant. She was administered oral prostaglandin E1 every 6 hours through a feeding tube as an alternative drug for lipo-prostaglandin E1. Oral prostaglandin E1 was effective for maintenance of the ductus arteriosus and may serve as a palliative treatment approach.

To investigate the efficacy, tolerability, and patient's preference of alprostadil cream for topical use administered within the urethral meatus versus the standard administration route, in erectile dysfunction (ED) treatment. Seventy-one patients (mean age 59.7 ± 9.0 years) affected by ED were analyzed in this multicenter, randomized, two-administration routes, cross-over trial. All patients received a single dose of alprostadil cream applying the dispenser to the tip of the penis (without contacting the urethral meatus) (Standard administration route or ST.AR) alternating with a single dose of alprostadil cream applying the dispenser within the urethral meatus (New administration route or NEW.AR) separated by a one-week washout period, according to randomization. The primary objective of the study was to evaluate the change in International Index of Erectile Function (IIEF-5) total score from baseline to the control visit by comparing the ST.AR and NEW.AR. Secondary objectives of the study were to compare the different methods of administration by evaluating the change in the Sexual Encounter Profile (SEP-2 and SEP-3) questionnaire score and the Patient Reported Outcomes (PROs) by scoring the Patient Self-Assessment of Erection (PSAE) questionnaire. The treatment safety profile was assessed by analysis of adverse events (AEs). Based on the study findings it is evident that the NEW.AR is more efficacious than the ST.AR in improving IIEF-5 and SEP scores from baseline to control visit (IIEF-5: +3.8 vs +6.3; p < 0.001; positive response to SEP-2: 10 vs 27; p = 0.002) and in terms of PSAE (a significant improvement from the baseline in 31% of patients; p < 0.001). As regards the safety profile, no difference in terms of local and systemic side effects was found.

Circumcision is one of the most frequent procedures performed by pediatric surgeons. A dorsal penile nerve block (DPNB) is commonly used for perioperative analgesia. We report the case of a 16-year-old boy with ischemia of the glans who presented on the first postoperative day after circumcision under DPNB (0.25% bupivacaine) at an outside hospital. The patient underwent immediate angiography under sedation. An intra-arterial spasmolysis was performed with alprostadil and nitroglycerine and a sufficient perfusion of the glans penis was confirmed. Subsequently, systemic sildenafil, arginine, and heparin were given. Following this 3-day medical treatment, ischemia resolved completely. Our case emphasizes the role of invasive angiography in the diagnostic workup and the therapeutic possibilities of local spasmolysis, systemic vasodilatation, and anticoagulation.

Background/aim: Alprostadil and iloprost are successful agents used for both pulmonary hypertension and extremity ischemia treatment. Different systemic effects of these agents may change the preferences of clinical usage. Superiority of preventing ischemia/ reperfusion (IR) injury is a criterion for clinical preference of these agents. The present study was designed to compare the protective effects of alprostadil and iloprost in a rat model of IR injury. Materials and methods: Twenty-three male Sprague Dawley rats were used (aged 8-12 weeks, mean weight 230 ± 30 g). They were randomized into 4 groups: Group 1 (iloprost + IR), Group 2 (alprostadil + IR), Group 3 (saline + IR), and Group 4 (control). Under general anesthesia, in all groups except Group 4, the abdominal region was explored and the abdominal aorta was temporarily clamped for 60 min. After the clamp was removed, 120 min of reperfusion was applied. In Group 4, the rats were placed under general anesthesia and abdominal exploration was performed without the IR procedure. For all rats, body temperature was kept at 36 °C with a heater pad through the whole procedure. The rats were euthanized under general anesthesia to remove the kidneys and lungs for study. Histopathological and biochemical analyses were conducted with kidney and lung tissues. Histopathological scoring was done by analyzing cellular damage at tissue level. Malondialdehyde (MDA), superoxide dismutase, and glutathione levels were studied for biochemical analysis. Results: Histopathologic analysis showed that, as compared with alprostadil, iloprost provided a significantly higher level of renal protection against IR injury (P < 0.01). Renal tissue levels of MDA were significantly lower in the alprostadil group as compared to Group 3 (P < 0.05). Conclusion: Alprostadil and iloprost seem to provide protection against IR injury, with iloprost being more protective in renal tissue. Alprostadil is more effective than iloprost in protecting lung tissue against IR injury.

Malignant atrophic papulosis (MAP) is a rare type of obliterating vasculopathy that can present as pure cutaneous lesions or a systemic entity affecting multiple organs. Systemic disease, such as gastrointestinal or central nervous system involvement, may predispose the patients to poorer or even fatal outcomes. We present a 30-year-old female patient with systemic manifestation of MAP 10 days after delivery of a full-term pregnancy who subsequently developed motor aphasia and intestinal perforation. The patient was administrated empirical treatment with an antiplatelet, anticoagulant, methylprednisolone sodium succinate and alprostadil. Antibiotics were administrated due to intestinal perforation and secondary sepsis. Despite all treatment, the patient died a week later. We summarized all the previous reports of MAP based on thorough review of previous published work. Overall, this is the first patient with MAP combined with motor aphasia and intestinal perforation and may provide insights for future studies on the treatment of this disease.