Living the categorical imperative: autistic perspectives on lying and truth telling–between Kant and care ethics

Lying is a common phenomenon amongst human beings. It seems to play a role in making social interactions run more smoothly. Too much honesty can be regarded as impolite or downright rude. Remarkably, lying is not a common phenomenon amongst normally intelligent human beings who are on the autism spectrum. They appear to be 'attractively morally innocent' and seem to have an above average moral conscientious objection against deception. In this paper, the behavior of persons with autism with regard to deception and truthfulness will be discussed in the light of two different ethical theories, illustrated by fragments from autobiographies of persons with autism. A systemizing 'Kantian' and an empathizing 'ethics of care' perspective reveal insights on high-functioning autism, truthfulness and moral behavior. Both perspectives are problematic from the point of view of a moral agent with autism. High-functioning persons with autism are, generally speaking, strong systemizes and weak empathizers. Particularly, they lack 'cognitive empathy' which would allow them to understand the position of the other person. Instead, some tend to invent a set of rules that makes their behavior compatible with the expectations of others. From a Kantian point of view, the autistic tendency to always tell the truth appears praiseworthy and should not be changed, though it creates problems in the social life of persons with autism. From a care ethics perspective, on the other hand, a way should be found to allow the high-functioning persons with autism to respect the feelings and needs of other persons as sometimes overruling the duty of truthfulness. We suggest this may even entail 'morally educating' children and adolescents with autism to become socially skilled empathic 'liars'.     

Influence of Topical Rectal Application of Drugs on Dextran Sulfate-Induced Colitis in Rats

A rat model of colitis [dextran sulfate (DSS)]was used to study the permeation of Evans blue (EB) fromthe lumen into the wall of proximal and distal colonicloops after exposure to the dye for 2 hr. Topical application of drugs used in human ulcerativecolitis (lidocaine, mesalazine, prednisolone, orsucralfate) was given daily during induction of colitisto protect the mucosa. The mucosal changes wereevaluated with special regard to peptidergic innervation[substance P (SP) and neuropeptide Y (NPY)], invasion ofantigen-presenting polydendritic cells, andmucin-containing goblet cells. DSS-treatment caused a significantly increased permeation of EB. Inthe proximal loops a significant inhibition was obtainedafter treatment with lidocaine, prednisolone, orsucralfate. In the distal loops only treatment with lidocaine had a preventive effect.Immunocytochemically there was a clear hyperplasia ofboth mucosal SP- and NPY-immunoreactive nerve fibers inregions with crypt abnormalities. In these regions alsomost of the goblet cells were devoid of mucus. Likethe changes in permeation, these morphological changeswere most prominent in the distal loops. With inductionof colitis, the mucosa and lamina propria were invaded by polydendritic cells; the visualscore was markedly decreased in the proximal loopstreated with lidocaine, prednisolone, or sucralfate. Inthe distal loops similar effects were obtained after treatment with lidocaine or prednisolone.Prevention of the influx of antigens in both loops afterlidocaine treatment with reduced recruitment ofpolydendritic cells into the lamina propria issuggested. The nerve hyperplasia may thus be secondary toluminal challenge with antigens during induction ofcolitis. The discrepancy between increased permeationand absence of polydendritic cell response in the distal loops after prednisolone may reflectseparate actions of steroids on the intestinalepithelium and the immune cells.     

EMLA cream and oral glucose for immunization pain in 3-month-old infants

The objective of this study is to determine whether use of lidocaine-prilocaine 5% cream (EMLA) and oral glucose decreases pain associated with diphteria-pertussis-tetanus (DPT) immunization in 3-month-old infants. DESIGN: randomized, double-blind, controlled trial in outpatient paediatric practice in northern Sweden. EMLA or placebo was applied to the infant's lateral region of the right thigh and covered with an occlusive dressing 1h before the immunization. In addition, 1 ml of glucose (300 mg/ml) or placebo (water) was instilled on the baby's tongue within 2 min before the DPT-injection. Forty-five infants received EMLA and glucose and 45 infants placebo cream and water. ECG was recorded and stored in a computer and the procedure was videotaped. The parents and the nurse assessed the infants' pain on a visual analogue scale (VAS) after the immunization. Heart rate and heart rate variability pre- and post-injection were calculated. From the videotapes, the modified behavioural pain scale (MBPS) was used to assess pain scores during baseline and after immunization. The latency of the first cry and total crying time were measured. The parents and the nurse scored the infants' pain on the VAS significantly lower in the treatment group than in the placebo group. The infants' responses to the immunization measured as the difference in MBPS scores pre- and post-injection were significantly lower in the EMLA-glucose group compared with the placebo group. More infants cried after the immunization in the placebo group compared with the EMLA-glucose group and the latency of the first cry after the injection was shorter in the placebo group. A biphasic transient heart rate response with a marked deceleration followed by a subsequent acceleration was seen more frequently in the placebo group compared to the EMLA-glucose group. EMLA and glucose alleviate immunization pain in 3-month-old infants.     

Efficacy of 1400 W,a novel inhibitor of inducible nitric oxide synthase,in preventing interleukin-1beta-induced suppression of pancreatic islet function in vitro and multiple low-dose streptozotocin-induced diabetes in vivo

OBJECTIVE: Nitric oxide (NO), generated by inducible nitric oxide synthase (iNOS), has been implicated in beta-cell destruction in type 1 diabetes. In the present study, we tested a highly selective iNOS inhibitor, 1400 W, against interleukin-1beta (IL-1beta) induced suppression of rat pancreatic islets, and investigated whether 1400 W could prevent multiple low-dose streptozotocin (MLDS) induced diabetes in mice. Furthermore, we studied if 1400 W affected lipopolysaccharide (LPS) induced increase in plasma nitrite+nitrate (NO(x)) in mice. DESIGN AND METHODS: Precultured rat pancreatic islets were exposed for 48 h to 0, 1, 10 or 50 micromol/l 1400 W in the presence or absence of 25 U/ml IL-1beta, whereupon islet functions were analyzed. MLDS-treated mice were given 5.9 mg/kg body weight of 1400 W intraperitoneally daily or 14 mg/kg body weight twice a day. Blood glucose was monitored and degree of pancreatic mononuclear infiltration was determined. Mice previously injected intraperitoneally with LPS (500 microg) were given 1400 W (14 mg/kg body weight) intraperitoneally and plasma NO(x) was determined after 3, 6 and 10 h. RESULTS: The inhibitor alone did not affect islet functions. 1400 W (50 micromol/l) fully counteracted both the suppression of glucose oxidation rate, (pro)insulin biosynthesis and nitrite accumulation caused by IL-1beta. Cytokine-induced decrease in medium insulin accumulation and glucose-stimulated insulin release was partly counteracted by 1400 W, suggesting that inhibition of insulin release was partially NO independent. LPS-induced increase in plasma NO(x) was markedly inhibited for up to 10 h after 1400 W administration. Irrespective of 1400 W treatment, animals treated with MLDS developed hyperglycemia and pancreatic insulitis. CONCLUSIONS: 1400 W counteracted IL-1beta-induced suppression of rat islets in vitro and LPS induction of NO(x) in vivo, however, it failed to protect against MLDS diabetes in vivo. The latter might be due to a failure by 1400 W in vivo to inhibit NO formation at the level of the pancreatic islet.     

Adverse events during air and ground neonatal transport: 13 years’ experience from a neonatal transport team in Northern Sweden

Objective: To study the prevalence of adverse events (AEs) associated with neonatal transport, and to categorize, classify and assess the risk estimation of these events.

Methods: Written comments in 1082 transport records during the period 1999–2011 were reviewed. Comments related to events that infringed on patient and staff safety were included as AEs, and categorized and further classified as complaint, imminent risk of incident/negative event, actual incident or actual negative event. AEs were also grouped into emergency or planned transports, and risk estimation was calculated according to a risk assessment tool and defined as low, intermediate, high or extreme risk.

Results: AEs (N?=?883) were divided into five categories: logistics (n?=?337), organization (n?=?177), equipment (n?=?165), vehicle (n?=?129) and medical/nursing care (n?=?75). Eighty-five percent of AEs were classified as incidents or negative events. The majority of AEs were estimated to be of low or intermediate risk in both planned and emergency transports. AEs estimated to be of high or extreme risk were significantly more frequent in emergency transports (OR?=?10.1; 95%?CI: 5.0–20.9; p?<?0.001).

Conclusion: AEs are common in both planned and emergency neonatal transport, often related to imperfect transport logistics or equipment failure. AEs of high or extreme risk were more frequent in emergency transports.     

Tripeptide interference with human immunodeficiency virus type 1 morphogenesis

Capsid assembly during virus replication is a potential target for antiviral therapy. The Gag polyprotein is the main structural component of retroviral particles, and in human immunodeficiency virus type 1 (HIV-1), it contains the sequences for the matrix, capsid, nucleocapsid, and several small polypeptides. Here, we report that at a concentration of 100 micro M, 7 of 83 tripeptide amides from the carboxyl-terminal sequence of the HIV-1 capsid protein p24 suppressed HIV-1 replication (>80%). The three most potent tripeptides, glycyl-prolyl-glycine-amide (GPG-NH(2)), alanyl-leucyl-glycine-amide (ALG-NH(2)), and arginyl-glutaminyl-glycine-amide (RQG-NH(2)), were found to interact with p24. With electron microscopy, disarranged core structures of HIV-1 progeny were extensively observed when the cells were treated with GPG-NH(2) and ALG-NH(2). Furthermore, nodular structures of approximately the same size as the broad end of HIV-1 conical capsids were observed at the plasma membranes of treated cells only, possibly indicating an arrest of the budding process. Corresponding tripeptides with nonamidated carboxyl termini were not biologically active and did not interact with p24.     

Profitable Exchanges for Scientists: The Case of Swedish Human Embryonic Stem Cell Research

In this article two inter-related issues concerning the ongoing commercialisation of biomedical research are analyzed. One aim is to explain how scientists and clinicians at Swedish public institutions can make profits, both commercially and scientifically, by controlling rare human biological material, like embryos and embryonic stem cell lines. This control in no way presupposes legal ownership or other property rights as an initial condition. We show how ethically sensitive material (embryos and stem cell lines) have been used in Sweden as a foundation for a commercial stem cell enterprise--despite all official Swedish strictures against commercialisation in this area. We also show how political decisions may amplify the value of controlling this kind of biological material. Another aim of the article is to analyze and discuss the meaning of this kind of academic commercial enterprise in a wider context of research funding strategies. A conclusion that is drawn is that the academic turn to commercial funding sources is dependent on the decline of public funding.     

Reactive intermediates and the dynamics of glutathione transferases.

Reactive intermediates are a continuous burden in biology and several defense mechanisms have evolved. Here we focus on the functions of glutathione transferases (GSTs) with the aim to discuss the quantitative aspects of defense against reactive intermediates. Humans excrete approximately 0.1 mmol of thioether conjugates per day. As the amount of GST active sites in liver is approximately 0.5 mmol, it appears that glutathione transferase catalysts are present in tremendous excess. In fact, the known catalytic properties of GSTs reveal that the enzymes can empty the liver glutathione (GSH) pool in a matter of seconds when provided with a suitable substrate. However, based on the urinary output of conjugates (or derivatives thereof), individual GSTs turn over (i.e., catalyze a single reaction) only once every few days. Glutathione transferase overcapacity reflects the fact that there is a linear relation between GST enzyme amount and protection level (provided that GSH is not depleted). Put in a different perspective, a few reactive molecules will always escape conjugation and reach cellular targets. It is therefore not surprising that signaling systems sensing reactive intermediates have evolved resulting in the increase of GSH and GST levels. Precisely for this reason, more moderately reactive electrophiles (Michael acceptors) are receiving growing interest due to their anticarcinogenic properties. Another putative regulatory mechanism involves direct activation of microsomal GST1 by thiol-reactive electrophiles through cysteine 49. The toxicological significance of low levels of reactive intermediates are of interest also in drug development, and here we discuss the use of microsomal GST1 activation as a surrogate detection marker.     

Mammalian histidine decarboxylase; Changes in molecular properties induced by oxidation and reduction

Histidine decarboxylase from a murine mastocytoma has been submitted to different separation methods. In these experiments the activity peaks were often very broad. This heterogeneity of the enzyme is traced back to the formation of aggregates, differing in apparent molecular weight by a multiple of about 55,000, as a result of oxidation.Under non-oxidative conditions the histidine decarboxylase activity is confined to one peak in both molecular sieve chromatography, hydrophobic interaction chromatography, chromatography on hydroxy apatite, pore gradient electrophoresis and electrofocusing.The molecular weight of the enzyme is estimated to be 110,000 by pore gradient electrophoresis (alkylated enzyme). The isoelectric point is pH 4.9–5.0, determined by electrofocusing under reducing conditions.