Flavonoids isolated from the flowers of Pulsatilla flavescens and their anti-piroplasm activity

Journal of Natural Medicines - Pulsatilla species are known as “Yargui”, and their flowers are traditionally used in Mongolia as a tonic and for the treatment of inflammatory diseases....     

Macrophages in trigeminal ganglion contribute to ectopic mechanical hypersensitivity following inferior alveolar nerve injury in rats

Background

Accidental mandibular nerve injury may occur during tooth extraction or implant procedures, causing ectopic orofacial pain. The exact mechanisms underlying ectopic orofacial pain following mandibular nerve injury is still unknown. Here, we investigated the role of macrophages and tumor necrosis factor alpha (TNFα) in the trigeminal ganglion (TG) in ectopic orofacial pain following inferior alveolar nerve transection (IANX).

Methods

IANX was performed and the mechanical head-withdrawal threshold (MHWT) in the whisker pad skin ipsilateral to IANX was measured for 15 days. Expression of Iba1 in the TG was examined on day 3 after IANX, and the MHWT in the whisker pad skin ipsilateral to IANX was measured following successive intra-ganglion administration of the macrophage depletion agent liposomal clodronate Clophosome-A (LCCA). TNFα expression in the TG and the MHWT in the whisker pad skin ipsilateral to IANX following successive intra-ganglion administration of the TNFα blocker etanercept were measured on day 3 after IANX, and tumor necrosis factor receptor-1 (TNFR1) immunoreactive (IR) cells in the TG were analyzed immunohistochemically on day 3.

Results

The MHWT in the whisker pad skin was significantly decreased for 15 days, and the number of Iba1-IR cells was significantly increased in the TG on day 3 after IANX. Successive intra-ganglion administration of the macrophage depletion agent LCCA significantly reduced the increased number of Iba1-IR cells in the TG and reversed the IANX-induced decrease in MHWT in the whisker pad skin. TNFα expression was increased in the TG on day 3 after IANX and was reduced following successive intra-ganglion administration of the TNFα inhibitor etanercept. The decreased MHWT was also recovered by etanercept administration, and TNFR1-IR cells in the TG were increased on day 3 following IANX.

Conclusions

These findings suggest that signaling cascades resulting from the production of TNFα by infiltrated macrophages in the TG contributes to the development of ectopic mechanical allodynia in whisker pad skin following IANX.

     

Review of the Captain America Graphic Novel ‘TRUTH: Red,White and Black’ Focusing on Parallels with the Infamous USPHS Syphilis Study at Tuskegee

This review presents the first detailed presentation of the parallelism between the Tuskegee Syphilis Study and the Captain America graphic novel ‘TRUTH: Red, White and Black’, published as a graphic novel by Marvel Comics in 2004 as a paperback, and then in 2009 as a hardcover. First written, published and distributed monthly in 2003 as pre-sequel seven comic book series to tell the story of the origins of the WWII superhero Captain America. In 2003, Marvel Comics chose to tell a ‘very dark story’ to explain the origins of Captain America, a half century after the initial introduction of Captain America as a WWII action hero in 1940. By detailing—for the first time—nine parallel aspects between these two storylines, this review demonstrates how Marvel Comics brought the tragic Tuskegee Syphilis Study story into the popular press, thus reaching an audience far beyond traditional bioethics academicians. This review is intended to stimulate and guide classroom discussions on the ethical issues at the core of the infamous Tuskegee Syphilis Study allowing bioethical issues to be made more accessible to the general public, via school curriculums, by the use of graphic novels.     

Recurrent subdural hematoma from a pseudoaneurysm at the cortical branch of the middle cerebral artery after mild head injury: case report

A 67-year-old man presented with a case of recurrent subdural hematomas (SDHs) from a pseudoaneurysm at the cortical artery after mild head trauma. He had undergone two episodes of burr hole trephination and evacuation of SDH in a 6-day interval. Review of previous imaging findings and additional cerebral angiography then identified a pseudoaneurysm arising from the precentral branch of the middle cerebral artery. Acute rebleeding suddenly occurred, and the leak point on the cortical artery was completely repaired with a single suture. SDH from pseudoaneurysm after mild head injury is very unusual. The high morbidity and mortality rates necessitate early detection, but the rarity of this type of injury makes detection difficult. If the clinical course is not easily explainable and is worse than the severity of trauma, repeated SDHs occur, or abnormal lesions and/or subarachnoid hemorrhage are identified, computed tomography or magnetic resonance imaging with contrast medium should be performed to identify the underlying cerebrovascular diseases and determine whether cerebral angiography is necessary.     

Emerging anti-HDV drugs and HBV cure strategies with anti-HDV activity

Hepatitis delta virus (HDV) is a satellite RNA virus that requires the presence of hepatitis B virus (HBV) for its replication. HDV/HBV co-infection is often associated with a faster disease progression of chronic hepatitis in comparison to HBV mono-infection. Therefore, the development of novel antiviral therapies targeting HDV represents a high priority and an urgent medical need. In this review, we summarize the ongoing efforts to evaluate promising HDV-specific drugs, such as lonafarnib (LNF), pegylated interferon lambda (PEG-IFN-λ) and their use as a combination therapy. Furthermore, we review the most recent developments in the area of anti-HBV drugs with potential effects against HDV, including therapeutic agents targeting hepatitis B surface antigen (HBsAg) expression, secretion and function. Finally, we consider the important insights that have emerged from the development of these potential antiviral strategies, as well as the intriguing questions that remain to be elucidated in this rapidly changing field.     

Hypertension knowledge,attitudes, and practices of nurses and physicians in primary care in Ulaanbaatar Mongolia

Increased blood pressure is a leading risk for death globally, and interventions to enhance hypertension control have become a high priority. An important aspect of clinical interventions is understanding the knowledge, attitudes, and practices (KAP) of differing primary healthcare practitioners. We examined KAP surveys from 803 primary care practitioners in Ulaanbaatar, Mongolia (response rate 80%), using a comprehensive KAP survey developed by the World Hypertension League (WHL). The WHL KAP survey uniquely includes an assessment of key World Health Organization recommended interventions to enhance hypertension control. There were few substantive differences between healthcare professional disciplines. Primary care practitioners mostly had a positive attitude toward hypertension management. However, confidence and practice in performing specific tasks to control hypertension were suboptimal. A low proportion indicated they systematically screened adults for hypertension and many were not aware of the need to or were confident in prescribing more than two antihypertensive medications. It was the practice of a high proportion of doctors to not pharmacologically treat most people with hypertension who were at high cardiovascular risk. There was a reluctance by physicians to task share hypertension diagnosis, drug prescribing and assessing cardiovascular risk to nurses. The minority of health care professions use a hypertension management algorithm, and few have patient registries with performance reporting functions. There were few substantive differences based on the age, gender, and years of clinical practice of the practitioners. The study findings support the need for standardized education and training of primary care practitioners in Ulaanbaatar to enhance hypertension control.     

Nerve Injury-Induced Protein 1 (Ninjurin-1) Is a Novel Therapeutic Target for Cavernous Nerve Injury-Induced Erectile Dysfunction in Mice

IntroductionRadical prostatectomy for prostate cancer can not only induce cavernous nerve injury (CNI) but also result in structural changes in the cavernous tissues. Nerve injuryinduced protein 1, Ninjurin1 (Ninj1), is known to be involved in neuroinflammatory processes and to be related to vascular regression during the embryonic period.AimThe study aims to determine whether and how Ninj1 neutralizing antibody (Ninj1Ab) restores erectile function in mice with CNI.MethodsTwelveweekold C57BL/6J mice were used and distributed into four groups: sham operation group and CNI groups receiving a single intracavernous injection of immunoglobulin G (IgG) control antibody, lowdose Ninj1Ab (1.0 μg/20 μL), or highdose Ninj1Ab (2.5 μg/20 μL).Main Outcome MeasuresOne week after bilateral cavernous nerve crush, erectile function was measured by electrical stimulation of the cavernous nerve. The penis was harvested for histologic examinations and Western blot analysis.ResultsThe cavernous expression of Ninj1 protein was upregulated up to 7 days after CNI and returned to baseline levels thereafter. Local delivery of Ninj1Ab significantly increased penile neuronal nitric oxide synthase and neurofilament contents, induced cavernous endothelial proliferation and phosphorylation of Akt and endothelial nitric oxide synthase, and decreased endothelial cell apoptosis in the CNI mice by upregulating angiopoietin1 and downregulating angiopoietin2. Highdose Ninj1Ab induced profound restoration of erectile function in the CNI mice (91% of sham control values), whereas lowdose Ninj1Ab elicited partial improvement.ConclusionThe dual neurotrophic and angiogenic effects of Ninj1 blockade may provide a good opportunity for treating erectile dysfunction resulting from radical prostatectomy.