Involvement of the 12-lipoxygenase pathway of arachidonic acid metabolism in homosynaptic long-term depression of the rat hippocampus

Low-frequency stimulation is associated with long-term depression (LTD) of synaptic efficacy in various brain structures. Like long-term potentiation (LTP), homosynaptic LTD in area CA1 of the hippocampus appears to require NMDA receptor activation, changes in postsynaptic calcium concentration and phospholipase A₂ (PLA₂) activation. Arachidonic acid (AA) is released after the activation of calcium-dependent phospholipases and free AA is rapidly metabolized to a family of bioactive products (the eicosanoids) which are thought to be both intracellular and extracellular messengers. In the present study, we investigated the involvement of the cyclooxygenase and lipoxygenase pathways of AA metabolism in the formation of homosynaptic LTD in the rat hippocampus. Stimulation at 1 Hz for 15 min was used to produce homosynaptic depression in area CA1 of hippocampal slices. LTD induction was partially blocked by bromophenacyl bromide (50–100 μM), a selective PLA₂ inhibitor, and by the a nonselective lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA; 100 μM). In contrast, the specific cyclooxygenase blocker indomethacin (100 μM) did not significantly reduce hippocampal LTD. Since NDGA interferes with LTD formation, we examined whether specific inhibitors of 5- and 12-lipoxygenases were capable of blocking LTD expression. The 12-lipoxygenase inhibitor baicalein at a concentration of 50 μM reduced LTP formation when given in the bath, an effect that was less pronounced with the 5-lipoxygenase inhibitor AA-861. These data suggest that the activation of endogenous PLA₂ and the formation of 12-lipoxygenase metabolites of AA may be important factors controlling the expression of hippocampal LTD.     

COVID-19 and its effects upon orthopaedic surgery: The Trinidad and Tobago experience

The World Health Organisation(WHO) declared coronavirus disease 2019(COVID-19) a pandemic on March 11, 2020. COVID-19 is not the first infectious disease to affect Trinidad and Tobago. The country has faced outbreaks of both Chikungunya and Zika virus in 2014 and 2016 respectively. The viral pandemic is predicted to have a significant impact upon all countries, but the healthcare services in a developing country are especially vulnerable. The Government of Trinidad and Tobago swiftly established a parallel healthcare system to isolate and treat suspected and confirmed cases of COVID-19. Strick ‘lockdown' orders, office closures, social distancing and face mask usage recommendation were implemented following advice from the WHO. This approach has seen Trinidad and Tobago emerge from the second wave of infections, with the most recent Oxford COVID-19 Government Response Tracker report indicating a favourable risk of openness index for the country. The effects of the pandemic on the orthopaedic services in the public and private healthcare systems show significant differences. Constrained by shortages in personal protective equipment and inadequate testing facilities, the public system moved into emergency mode prioritizing the care of urgent and critical cases. Private healthcare driven more by economic considerations, quickly instituted widespread safety measures to ensure that the clinics remained open and elective surgery was not interrupted. Orthopaedic teaching at The University of the West Indies was quickly migrated to an online platform to facilitate both medical students and residents. The Caribbean Association of Orthopedic Surgeons through its frequent virtual meetings provided a forum for continuing education and social interaction amongst colleagues. The pandemic has disrupted our daily routines leading to unparalleled changes to our lives and livelihoods. Many of these changes will remain long after the pandemic is over, permanently transforming the practice of orthopaedics.     

Medical education about the care of addicted incarcerated persons: A national survey of residency programs

In June 1998, there were 1.8 million inmates in correctional facilities for adults; 1.2 million in state and federal prisons and 600,000 in municipal/county jails (668 persons per 100,000 U.S. population). Rates of TB, AIDS, mental illness, and substance abuse are 2–13 times higher in persons living in jails and prisons. This study was designed to assess the level of training offered to residents in seven medical specialties in the care of addicted incarcerated persons. The study design involved two stages. The first entailed a mailed survey to 1,831 residency directors in family medicine, internal medicine, osteopathic medicine, pediatrics, obstetrics and gynecology, psychiatry, and emergency medicine. The second stage was a telephone interview, about substance use disorders, of faculty listed by the residency directors as teaching residents. The mailed survey was completed by 1,205 residency directors (66%). The 769 faculty from those identified programs, who participated in the telephone interview, reported that only 14% of their residency programs offered lectures or conferences on the care of incarcerated persons, yet 44% of the programs had residents caring for incarcerated persons with substance abuse problems, in a clinical setting. Only 22% offered clinical experiences for residents in a correctional facility.

We recognize that our survey of correctional health and substance abuse training is limited, but as such, a greater number of respondents to our survey do not teach residents addiction medicine topics pertaining to prevention, evaluation, intervention, and management of the addicted criminal offender/patient in a correctional setting or give adequate clinical exposure to this special population. The data suggests a need to develop and implement educational programs on medical care for this high‐risk and expanding population.     

A practical guide for the study of human and murine sebaceous glands in situ

The skin of most mammals is characterised by the presence of sebaceous glands (SGs), whose predominant constituent cell population is sebocytes, that is, lipid‐producing epithelial cells, which develop from the hair follicle. Besides holocrine sebum production (which contributes 90% of skin surface lipids), multiple additional SG functions have emerged. These range from antimicrobial peptide production and immunomodulation, via lipid and hormone synthesis/metabolism, to the provision of an epithelial progenitor cell reservoir. Therefore, in addition to its involvement in common skin diseases (e.g. acne vulgaris), the unfolding diversity of SG functions, both in skin health and disease, has raised interest in this integral component of the pilosebaceous unit. This practical guide provides an introduction to SG biology and to relevant SG histochemical and immunohistochemical techniques, with emphasis placed on in situ evaluation methods that can be easily employed. We propose a range of simple, established markers, which are particularly instructive when addressing specific SG research questions in the two most commonly investigated species in SG research, humans and mice. To facilitate the development of reproducible analysis techniques for the in situ evaluation of SGs, this methods review concludes by suggesting quantitative (immuno‐)histomorphometric methods for standardised SG evaluation.     

Cells of origin and tumor-initiating cells for nonmelanoma skin cancers

The epidermis of the skin is a multilayered stratified epithelium whose primary function is to provide a barrier against our external environment. As a result, cells in the epidermis are subject to constant assault from environmental pathogens, many of which can cause deleterious mutations. However, most of these mutations do not lead to skin cancer. One explanation is that most genetic hits are sustained by mature or transit cells with limited proliferative capacity and only stem cells that acquire genetic alterations have the potential to propagate a frank tumor. In this mini-review we will discuss recent studies that provide some of the first genetic evidence to support a stem cell origin for a number of skin cancer types.     

Gestational high-fat programming impairs insulin release and reduces Pdx-1 and glucokinase immunoreactivity in neonatal Wistar rats

Hyperglycemia and compromised β-cell development were demonstrated in neonatal rats programmed with a gestational high-fat diet. The aim of this study was to determine whether these changes were attributed to impaired insulin release and altered immunoreactivity of Pdx-1, glucokinase (GK), and glucose transporter (GLUT)–2 in high-fat–programmed neonates. Fetuses were maintained, via maternal nutrition, on either a standard laboratory diet (control) or a high-fat diet throughout gestation (HFG). Pancreata from 1-day–old neonates were excised for islet isolation and the subsequent measurement of insulin release at 2.8, 6.5, 13, and 22 mmol/L glucose. Other pancreata were either snap frozen for quantitative polymerase chain reaction or formalin fixed for immunohistochemistry followed by image analysis. The HFG neonates had reduced insulin release at 13- and 22-mmol/L glucose concentrations. No significant differences were found in Pdx-1, GK, or GLUT-2 messenger RNA expression. In HFG neonates, immunoreactivity of both Pdx-1 and GK was significantly reduced, with a nonsignificant reduction in GLUT-2. Gestational high-fat programming impairs insulin release and reduces Pdx-1 and GK immunoreactivity.     

Subepicardial Aneurysm: Echocardiographic Evaluation and Evolution

Subepicardial aneurysms (SEA) are an infrequent and serious form of subacute cardiac rupture complicating myocardial infarction. An early diagnosis and surgical repair may be life saving. SEA comprise an abrupt interruption of the myocardium, with a narrow neck and thin wall containing only the epicardium. It may progress to fatal cardiorrhexis. We describe the echocardiographic evolution of this type of cardiac rupture and the contribution of contrast-enhanced echocardiography. A possible pathophysiological mechanism is proposed.     

Ratio of hepatic arterial flow to recipient body weight predicts biliary complications after deceased donor liver transplantation

ObjectivesAdequate hepatic arterial (HA) flow to the bile duct is essential in liver transplantation. This study was conducted to determine if the ratio of directly measured HA flow to weight is related to the occurrence of biliary complications after deceased donor liver transplantation.MethodsA retrospective review of 2684 liver transplants carried out over a 25-year period was performed using data sourced from a prospectively maintained database. Rates of biliary complications (biliary leaks, anastomotic and non-anastomotic strictures) were compared between two groups of patients with HA flow by body weight of, respectively, <5 ml/min/kg (n = 884) and ≥5 ml/min/kg (n = 1800).ResultsPatients with a lower ratio of HA flow to weight had higher body weight (92 kg versus 76 kg; P < 0.001) and lower HA flow (350 ml/min versus 550 ml/min; P < 0.001). A lower ratio of HA flow to weight was associated with higher rates of biliary complications at 2 months, 6 months and 12 months (19.8%, 28.2% and 31.9% versus 14.8%, 22.4% and 25.8%, respectively; P < 0.001).ConclusionsA ratio of HA flow to weight of < 5 ml/min/kg is associated with higher rates of biliary complications. This ratio may be a useful parameter for application in the prevention and early detection of biliary complications.