A critical role for Akt1 signaling in acute pancreatitis progression†

Acute pancreatitis (AP) is an inflammatory disease of the pancreas that causes significant morbidity and mortality worldwide. Unfortunately, there is no specific treatment available to date. Several studies have previously shown that inhibitors of the PI3K/Akt axis downregulate the degree of inflammation in animal models of AP. However, studies on in vivo side-effects of such inhibitors are still lacking. In a recent issue of The Journal of Pathology, Chen, Malagola et al investigated if inhibition of Akt signaling plays a negative role in the regenerative phase of AP. They showed that treating AP mice with an Akt inhibitor (MK2206) impaired acinar regeneration and increased the development of acinar-to-ductal metaplasia. This is the first study to highlight the negative impact of an Akt inhibitor on cellular regeneration while simultaneously inhibiting inflammation in AP. The authors also suggested combining Akt activators to recover pancreatic regeneration. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

Immunological relationship between a demyelinating RNA enveloped budding virus (Semliki Forest) and brain glycolipids

A monoclonal antibody (MAb) raised against central nervous system (CNS) myelin (212) and a MAb (308) raised against brain with Semliki Forest virus (SFV) were both found to react against the same CNS glycolipids. Both these MAbs were also found to react strongly with SFV and against certain brain glycolipid fractions in an immunosorbent assay (ELISA). This demonstrates the presence of common glycolipid antigens in the viral envelope and CNS myelin. MAb 212 had no SFV neutralising capacity and that of MAb 308 was not significant. However, MAb 212 inhibited the neutralisation of the virus by the MAbs (302, 307) specific to SFV proteins. The implications of these findings in relation to the viral induced CNS autoimmunity and persistence of virus in the CNS is discussed.     

Diagnosis and treatment of status epilepticus on a neurological intensive care unit

Status epilepticus refractory to first-line therapy is associated with a high morbidity and mortality. Correct diagnosis and adequate treatment of this condition require electrographic monitoring and anaesthetic facilities available in specialist intensive care units (ICUs). We carried out an audit of 26 patients admitted to a neurological ICU with a diagnosis of status epilepticus, to identify deficiencies in diagnosis and management prior to transfer to the ICU, and examine the effectiveness of ICU management. Or transfer, only 14 (54%) were in status epilepticus; six were in drug-induced coma or were encephalopathic, and six had pseudostatus epilepticus, of whom four had been intubated. The commonest treatments prior to transfer were benzodiazepines, chlormethiazole and phenytoin; the loading dose of phenytoin was adequate in at least 7/16 cases. All those in status epilepticus on transfer had their seizures successfully controlled, but ten required general anaesthesia with thiopentone, propofol, ketamine or midazolam. Two died--one had a severe encephalitis and the other had had a cardiac arrest prior to treatment. This study highlights deficiencies in the initial diagnosis and management of status epilepticus, the role of specialist neurological intensive care, and the importance of early referral.      

兔视网膜色素上皮细胞移植及长期形态学的研究

视网膜色素上皮（ＲＰＥ）功能失调或发生病理改变，可导致许多视网膜疾病，包括年龄相关性黄斑变性，青年性遗传性黄斑变性及视网膜色素变性等，严重危害人类视力。能否通过移植正常、健康的ＲＰＥ细胞治疗这类视网膜疾病，是当前眼科界关注的重要研究课题。我们采用了改良式玻璃体密闭式移植术，术中增加了玻璃体切割，应用带有色素标记的兔ＲＰＥ细胞移植于无色素性兔的视网膜下间隙。结果显示，移植长达１年后的ＲＰＥ细胞不但存活，结构形态正常，并且与邻近的ＲＰＥ细胞（包括移植的与自体的）建立了闭锁小带。移植的ＲＰＥ细胞与受体的感光细胞紧密结合，受体眼的神经外节盘正常脱落，被移植的ＲＰＥ细胞吞噬，且未发生排异反应。上述结果显示，本实验兔ＲＰＥ细胞移植的成功，为临床治疗某些视网膜疾病开辟了新的治疗途径，提供了可靠的实验室根据和应用前景。     

Electric compound action potentials (ECAPs) and impedances in an open and closed operative site during cochlear implantation

Introduction: In patients undergoing cochlear implantation, intraoperative measures of impedance and electrically evoked compound action potentials (ECAPs) are used to confirm device integrity and electrode array position. However, these electrophysiological parameters have been shown to decrease over time, with a small decrement observable as early as 24?h post implantation and becoming more apparent after 6 months. Whether the intraoperatively measured impedances and ECAPs recorded immediately after electrode insertion versus later in the operation or in an open versus closed operative site vary has not been documented. Such variation in measurement procedure may affect the ultimate operative outcome.

Patients and methods: Between February and October 2016, 38 patients received a cochlear implant (Cochlear^®), with half receiving a CI 522 device and the other half receiving a CI 512 device. These patients were distributed into three groups. In the first (group A; n?=?21), the impedance and threshold neural response telemetry (tNRT) measures were taken before (M1) and after cutaneous suture (M2), whereas in the second group (group B; n?=?11) they were taken twice in the open operative site, once at the time of electrode insertion (M1) and then again 10?min later (M2). The last group (group C; n?=?6) was measured only once after a 10?min waiting time before closing the operative site.

Results: tNRTs of both group A and B were significantly higher at M1 than measured at M2. The magnitude of change in tNRT did vary significantly by group (P?=?.027) with group A having a bigger decrease than group B. For impedances there was evidence for a significant difference in M2 between the three groups (P?=?.012), with group C having significantly higher values compared to group A and B.

Conclusion: Intraoperative tNRT measures change significantly over time, including within the first 10?min of implantation. One underlying etiology of this phenomenon for tNRTs seems to be the condition of the surgical site whereas changes of impedances can be best explained by the ‘electrochemical cleaning’ theory associated with the first stimulation of the electrode. However, for both impedances and tNRTs there also is an important impact of time as well as of acute perioperative changes in electrical conductivity.     

Effects of Korean ginseng berry extract (GB0710) on penile erection: evidence from in vitro and in vivo studies

Several reports have promoted the root-derived Korean red ginseng (KRG; Panax ginseng) as alternative treatment for erectile dysfunction (ED), and ginsenosides are known to be the principal active ingredients of ginseng. Recent studies showed that ginseng berries produce more ginsenosides than KRG; thus, we investigated the ability of the Korean ginseng berry extract GB0710 to relax the penile corpus cavernosum smooth muscle (CCSM) in this study. As a comparative control, the results were compared to those obtained using KRG. In addition, possible mechanisms of action for GB0710 were investigated. While KRG and GB0710 both displayed dose-dependent relaxation effects on precontracted rabbit CCSM in vitro, GB0710 was shown to be more potent than KRG. The GB0710-induced relaxation could be partially reduced by removing the endothelium. In addition, pre-treatment with several nitric oxide (NO) inhibitors significantly inhibited the relaxation of muscle strips. Furthermore, administration of GB0710 increased intracavernosal pressure (ICP) in a rat in vivo model in both a dose- and duration-dependent manner. Intracellular NO production in human microvascular endothelial cells could be induced by GB0710 and inhibited by N^G-monomethyl-L-arginine. In conclusion, GB0710 had a greater relaxation effect on rabbit CCSM than did KRG extract, and increased ICP in a rat model in both a dose- and a duration-dependent manner. This relaxing effect might be mediated by NO production.