Integrating attachment theory with other approaches to developmental psychopathology

Abstract

Recent studies have shown how children develop an understanding of emotion: pre-school children identify and talk accurately about the basic emotions and increasingly appreciate the way that desires and beliefs give rise to those emotions. However, children also display stable individual differences in their understanding. Two different interpretations of such individual differences are discussed. Caregivers show more or less sensitivity to their children's emotions. One interpretation, therefore, is that early variation in caregiver sensitivity is responsible for individual differences in children's attachment status; in turn, children's attachment status leads to enduring differences in their understanding of emotion. A second interpretation focuses on the fact that children grow up in families that vary in the manner and extent to which feelings are put into words. Accordingly, early differences in family discourse about emotion, especially on the part of the primary caregiver, may lead to variation among children in their understanding of emotion. Evidence supporting or undermining these two different interpretations is reviewed.     

Changes in Class I and IIb HDACs by δ-Opioid in Chronic Rat Glaucoma Model

PurposeThis study determines if δ-opioid receptor agonist (i.e. SNC-121)-induced epigenetic changes via regulation of histone deacetylases (HDACs) for retinal ganglion cell (RGC) neuroprotection in glaucoma model.MethodsIntraocular pressure was raised in rat eyes by injecting 2M hypertonic saline into the limbal veins. SNC-121 (1 mg/kg; i.p.) was administered to the animals for 7 days. Retinas were collected at days 7 and 42, post-injury followed by measurement of HDAC activities, mRNA, and protein expression by enzyme assay, quantitative real-time PCR (qRT-PCR), Western blotting, and immunohistochemistry.ResultsThe visual acuity, contrast sensitivity, and pattern electroretinograms (ERGs) were declined in ocular hypertensive animals, which were significantly improved by SNC-121 treatment. Class I and IIb HDACs activities were significantly increased at days 7 and 42 in ocular hypertensive animals. The mRNA and protein expression of HDAC 1 was increased by 1.33 ± 0.07-fold and 20.2 ± 2.7%, HDAC 2 by 1.4 ± 0.05-fold and 17.0 ± 2.4%, HDAC 3 by 1.4 ± 0.06-fold and 17.4 ± 3.4%, and HDAC 6 by 1.5 ± 0.09-fold and 15.1 ± 3.3% at day 7, post-injury. Both the mRNA and protein expression of HDACs were potentiated further at day 42 in ocular hypertensive animals. HDAC activities, mRNA, and protein expression were blocked by SNC-121 treatment at days 7 and 42 in ocular hypertensive animals.ConclusionsData suggests that class I and IIb HDACs are activated and upregulated during early stages of glaucoma. Early intervention with δ-opioid receptor activation resulted in the prolonged suppression of class I and IIb HDACs activities and expression, which may, in part, play a crucial role in RGC neuroprotection.     

Investigation of the μ- and κ-opioid receptor activation by eight new synthetic opioids using the [35S]-GTPγS assay: U-47700, isopropyl U-47700, U-49900, U-47931E,N-methyl U-47931E,U-51754, U-48520, and U-48800

In 2009, new synthetic opioids appeared on the new psychoactive substances market. This class of new psychoactive substances generally poses a health risk due to the high affinity and potency of most of these compounds for the opioid receptors. It is known that overdoses can lead to respiratory depression and result in death. However, for many new synthetic opioids, data on toxicological and toxicokinetic properties are scarce. In the present study, eight U-opioids were investigated for their structure activity relationships at the μ- and κ-opioid receptors using a [³⁵S]-GTPγS assay. The potencies of the investigated U-opioids were lower than those of the reference compounds (μ-opioid receptor: hydromorphone, fentanyl; κ-opioid receptor: U-69593, U-50488). At the μ-opioid receptor, U-47700 showed the highest potency with an EC₅₀ value of 111 nM, and at the κ-opioid receptor, U-51754 was found to be the most potent compound with an EC₅₀ value of 120 nM. The following structural features were advantageous for activating the μ-opioid receptor: two chlorine substituents in 3,4-position at the aromatic ring, the absence of the methylene group between the amide group and the aromatic ring, a methyl group at the amide nitrogen, and/or a dimethylamine residue at the amine nitrogen of the cyclohexane ring. Further, the following structural features were beneficial for κ-opioid receptor activation: a methylene group between the amide group and the aromatic ring, a pyrrolidine residue at the amine nitrogen of the cyclohexane ring, a methyl group at the amide nitrogen, and/or a chlorine substitution at the 3,4-position of the aromatic ring.     

The future of the international drug control system and national drug prohibitions

A major impediment to any nation abandoning the policy of drug prohibition has been the fact that international drug treaties to which the majority of United Nations (UN) member states are signatory prohibit the non‐medical use of amphetamines, cannabis, cocaine and heroin. The future of these treaties is now uncertain because of decisions by Uruguay, eight US states and Canada to legalize cannabis use. This paper: (1) provides a brief account of the international drug control treaties; (2) outlines the major criticisms of the treaties; (3) analyses critically proposals for treaty reform; and (4) provides a personal view on policies that nation states could adopt to minimize the harms from the use of cannabis, party drugs and hallucinogens, opioids, stimulants and new psychoactive substances. It is argued that: a major risk of cannabis legalization in the United States is promotion of heavy use and increased harm by a weakly regulated industry; some cautious national experiments with the regulation of party drugs and hallucinogens would be informative; a strong case remains for prohibiting the nonmedical use of opioids while mitigating the adverse effects that this policy has on opioid‐dependent people; stimulant legalization will probably increase problem use but prohibition is difficult to enforce, highlighting the urgency of finding better ways to reduce demand for these drugs and respond to problem users; and that it is unclear what the best approach is to reducing possible harms that may arise from the use of new psychoactive substances.     

Fentanyl is less toxic on adult human mesenchymal stem cells compared to ropivacaine when used intraarticularly. A controlled in vitro study

Abstract

The purpose of this study was to evaluate the toxicity of ropivacaine and fentanyl on adult human mesenchymal stem cells (hMSC). hMSC’s were seeded in monolayer triple-flasks and then plated into 96-well plates at a density of 5000 cells per well. After fully aspirating the culture medium, ropivacaine or fentanyl in its corresponding concentration (0.5%, 0.25%, 0.125% for ropivacaine and 0.05%, 0.025%, 0.0125% for fentanyl) or culture medium only was added to each well. After 30?min, the anaesthetic was removed and fresh culture medium was added. hMSCs mitochondrial activity as a marker of cell proliferation and apoptosis marker was evaluated after 1, 24?h and 7 days. Proliferation was significantly decreased after a 30?min exposure to 0.5% and 0.125% ropivacaine, respectively compared to the control group after 24?h (p?<?0.001). Simultaneously, apoptosis was significantly induced. Proliferation of hMSC’s was decreased after 24?h when exposed to 0.05%, 0.025% and 0.0125% fentanyl (p?<?0.001). Apoptosis was only induced 24?h after an exposure to 0.05% fentanyl. Our data suggest that both drugs have a concentration-dependent effect on proliferation in adult hMSC’s in vitro. This effect was more distinct with ropivacaine compared to fentanyl. Translating these results into clinical practice, this in vitro study suggests fentanyl as a potentially less toxic analgetic drug for intraarticular application after arthroscopic bone marrow stimulation or rotator cuff repair with comparable to prolonged pain reduction.