A high throughput screen for 17 Dermorphin peptides in equine and human urine and equine plasma

The Dermorphins are a family of peptides that act as potent agonists of the opioid μ receptor. Originally identified as a seven amino acid peptide on the skin of the South American Phyllomedusa frog, peptide chemists have since developed a large number of Dermorphin variants, many with superior opioid activity to the original peptide. Dermorphins are unique among the peptide opioid agonists as they appear to have a limited ability to cross the blood brain barrier, producing effects on both the central and peripheral nervous systems. It is this ability of Dermorphins to provide central anaesthesia after intravenous or subcutaneous administration that allows their use as analogues of the opioid class of drugs. Recently, illicit use of the Dermorphin peptide in the racing industry has shown the need for an analytical method to control the use of these peptides. We present a high‐throughput liquid chromatography‐tandem mass spectrometry screen for 17 Dermorphin peptides in equine urine and plasma with limits of detection down to 5 pg/mL. The peptide extraction technique is also suitable for use in human urine. Copyright © 2013 John Wiley & Sons, Ltd.     

A high‐throughput LC‐MS/MS screen for GHRP in equine and human urine,featuring peptide derivatization for improved chromatography

The growth hormone releasing peptides (GHRPs) hexarelin, ipamorelin, alexamorelin, GHRP‐1, GHRP‐2, GHRP‐4, GHRP‐5, and GHRP‐6 are all synthetic met‐enkephalin analogues that include unnatural D‐amino acids. They were designed specifically for their ability to stimulate growth hormone release and may serve as performance enhancing drugs. To regulate the use of these peptides within the horse racing industry and by human athletes, a method is presented for the extraction, derivatization, and detection of GHRPs from equine and human urine. This method takes advantage of a highly specific solid‐phase extraction combined with a novel derivatization method to improve the chromatography of basic peptides. The method was validated with respect to linearity, repeatability, intermediate precision, specificity, limits of detection, limits of confirmation, ion suppression, and stability. As proof of principle, all eight GHRPs or their metabolites could be detected in urine collected from rats after intravenous administration. Copyright © 2014 John Wiley & Sons, Ltd.     

Relationship between use of proton pump inhibitors and IGF system in older subjects

Objectives

to investigate the effects of proton pump inhibitors (PPIs) on the insulin-like-growth factor 1(IGF-1) system in the elderly.

Design

cross-sectional.

Setting

InCHIANTI study.

Participants

938 older subjects (536 women, 402 men, mean age 75.7±7.4 years).

Measurements

complete data on age, sex, BMI, liver function, medications, dietary intake, IGF-1, IGF-binding protein-1 and -3 (IGFBP-1, IGFBP-3).

Results

Participants were categorized by PPI use, identifying 903 PPI non users and 35 users. After adjusting for age, male PPI users (107.0 ± 69.6 vs 127.1 ± 55.8, p<0.001) and female PPI users (87.6 ± 29.1 vs 107.6 ± 52.3, p=0.03) had lower IGF-1 levels than non-users. IGFBP-1 levels were similar in the two groups in both sexes. In whole population, after adjustment for age and sex, PPI users had lower IGF-1 levels 81.9 [61.1–113.8] than nonusers 110 [77.8–148.6], p=0.02. After further adjustment for BMI, albumin, liver function, C-reactive protein, Interleukin-6, number of medications, ACE-inhibitors use, caloric intake, protein intake, physical activity, glycemia, and IGFBP-1, the use of PPIs remained significantly and negatively associated with IGF-1 levels (β±SE=?19.60±9.83, p=0.045).

Conclusion

Use of PPIs was independently and negatively associated with IGF-1 levels.     

Use and tolerability of newer antipsychotics and antidepressants: a chart review in a paediatric setting

Objective To analyse the prescribing pattern and the safety profile of different atypical antipsychotics and selective serotonin reuptake inhibitors (SSRIs) during the years 2002–2003 in paediatric setting. Setting Two Child Neurology and Psychiatry Divisions of Southern Italy (University of Messina and “Oasi Institute for Research on Mental Retardation and Brain Aging” of Troina). Methods A retrospective chart review of all children and adolescents starting an incident treatment with atypical antipsychotics or SSRIs was performed. Within the first 3 months of therapy, any potential adverse drug reaction (ADR) was identified and the clinical outcome of psychotropic drug treatment was assessed. Main Outcome Measure Rate of ADR in the first 3 months of therapy with atypical antipsychotics and SSRIs in children and adolescents. Results On a total of 97 patients’ charts being reviewed, 73 (75%) concerned atypical antipsychotics and 24 (25%) SSRIs. Risperidone (N = 45, 62%) was the most frequently prescribed antipsychotic drug, followed by olanzapine (24, 32%). Overall, 50 (68%) antipsychotic users reported a total of 108 ADRs during the first 3 months of therapy, leading to drug discontinuation in 23 patients (31%). Among 24 users of SSRI, 12 (50%) received paroxetine, 6 (25%) sertraline, 5 (21%) citalopram and 1 (4%) fluoxetine. Only paroxetine users (21%) reported at least one ADR, however, none of SSRI users withdrew drug treatment within first 3 months. Conclusions ADRs occurred frequently during first 3 months of treatment with atypical antipsychotics and, to a lesser extent, with SSRIs in children and adolescents. Further investigations are urgently needed to better define the benefit/risk ratio of psychotropic medications in paediatric setting.     

Contraceptive Implant Discontinuation in Huambo and Luanda,Angola: A Qualitative Exploration of Motives

Introduction The Government of Angola is engaged in ongoing efforts to increase access to contraceptives, in particular contraceptive implants (CIs). Discontinuation of CIs, however, has been identified as being a challenge to this work, hindering the improvement of contraceptive prevalence, and in turn, maternal and child health. The objective of this study was to understand motives for contraceptive implant discontinuation in Luanda and Huambo, Angola. Methods We conducted 45 in-depth interviews and six focus groups amongst former and current contraceptive implant clients and family planning nurses in eight clinics across the provinces of Huambo and Luanda. Data collectors transcribed and translated key information from Portuguese into English. We used a combined deductive/inductive approach to code and analyze data. Results Participants described adverse side effects, desire for pregnancy, partner dissatisfaction, quality of care, alternative or lack of information, and religion as motives for discontinuation. Adverse side effects, including prolonged bleeding, amenorrhea, and headaches were most commonly cited by both clients and providers. Discussion Motives for discontinuation reflect existing findings from other studies in similar settings, in particular the influence of adverse side effects and desire for pregnancy as motivating factors. We contextualize these findings in the Angolan setting to tease out the relationship between cultural norms of ideal family size and the perceived role of women in regards to fertility and child-bearing. We suggest that programs enter into dialog with communities to address these concerns, rather than working exclusively on improving service delivery and quality.     

Integrative ecotoxicological assessment of sediment in Portmán Bay (southeast Spain)

Portmán Bay, southeast Spain, contains the most seriously metal-contaminated sediments of the Mediterranean Sea. From 1958 to 1991, approximately 50 million tons of mine tailings were dumped into the bay, completely filling up the bay and dispersing over an extensive area of the continental platform and continental slope. The objective of our study was to characterize the nature and extent of metal contamination and the responses of natural communities to it and to assess the toxicity of the sediment deposits 10 years after mining had ceased. We studied the physical and chemical characteristics of the sediments and toxicity (of the porewater and sediment–water interface) using two sea urchin species (Arbacia lixula and Paracentrotus lividus). Metal bioavailability and patterns of macroinvertebrate community composition along the contamination gradient were also studied. Univariate and multivariate analyses showed positive correlation between the sediment metal concentrations associated to the all biological effects (sea urchins toxicity tests and benthic indices). The effects of sediment contamination on the benthic community structure are visible among sampling stations.     

强化面粉专用复配营养素物理性质形态观察

对强化面粉专用复配营养素的物理性质和混合均匀度进行观察。试验观察了面粉专用营养素单体和复配营养素的形态、粒度、比重、流动性以及不同混合时间的混合均匀度。结果表明 ,各营养素单体形态具有明显差异 ,粒度分布、比重和流动性差异显著 ,混合时间对混合均匀度有明显影响。观察所得到的数据不仅对复配的面粉专用营养素的质量保障提供了基础 ,同时为复配营养素与面粉生产工艺的结合和保障强化面粉质量提供了基础。     

Peroxidase-like activity of ferruginous bodies isolated by exploiting their magnetic property

Ferruginous bodies (FB) are polymorphic structures whose formation is macrophage dependent, and are composed of a core, which may consist of an asbestos fiber coated with proteins, among which ferritin is the main component. Within ferritin, the ferric and ferrous ions are coordinated as ferrihydrite, which is the main iron (Fe) storage compound. However, when ferritin accumulates in some tissues following Fe overload it also contains magnetite along with ferrihydrite, which endows it with magnetic properties. Recently studies showed that magnetite exerts peroxidase-like activity, and since ferruginous bodies display magnetic properties, it was postulated that these particular structures may also contain magnetite within the ferritin coating, and thus may also exert peroxidase-like activity. Histochemical analysis for peroxidase of isolated FB smears demonstrated positive staining. Samples isolated from 4 different autopsy lung fragments were also able to oxidize 3,3',5,5'-tetramethyl-benzidine to a blue colored compound that absorbs at 655 nm. This activity was (1) azide and heat insensitive with optimal pH from 5 to 6, and (2) highly variable, changing more than 25-fold from one sample to another. These findings, together with evidence that the peroxidase-like activity of ferruginous bodies has a hydrogen peroxide and substrate requirement different from that of human myeloperoxidase, can exclude that this enzyme gives a significant contribution to the formation of FB. Standard Fe-rich asbestos fibers also express a peroxidase-like activity, but this appears negligible compared to that of ferruginous bodies. Strong acidification of standard Fe-containing asbestos fibers or magnetically isolated ferruginous bodies liberates a high amount of peroxidase-like activity, which is probably accounted for by the release of Fe ions. Further, FB also damage mesothelial cells in vitro. Data suggest that FB exert peroxidase-like activity and cytotoxic activity against mesothelial cells, and hence may be an important factor in pathogenesis of asbestos-related diseases.     

Tea consumption and cardiovascular disease: effects on endothelial function

Epidemiological studies suggest that tea consumption is associated with reduced cardiovascular disease risk, but the mechanisms for these observations have remained uncertain. In recent years, it has become apparent that the endothelium plays a central role in the regulation of vascular homeostasis and that endothelial dysfunction contributes to the pathogenesis and clinical expression of cardiovascular disease. This article reviews the evidence that human tea consumption has a beneficial effect on the vascular endothelium and the clinical implications of these findings.     

Distinct roles of group I mGlu receptors in striatal function

In the recent past, evidence accumulated in favour of a central role of group I metabotropic glutamate (mGlu) receptors, mGlu1 and mGlu5, in the modulation of cell excitability both of striatal medium spiny projection neurons (MSNs) and interneuronal population. Electrophysiological and pharmacological studies have clearly shown that activation of mGlu1 and mGlu5 receptors exerts distinct actions, depending on the neuronal subtype involved. MGlu5 receptor activation mediates the potentiation of NMDA responses in MSNs, and underlies the retrograde inhibitory signaling by endocannabinoids at corticostriatal synapses. Conversely, both group I mGlu receptors are involved in long-term synaptic plasticity of MSNs. Likewise, either mGlu1 or mGlu5 receptors are engaged in shaping the excitability of large cholinergic interneurons, playing different roles in the membrane responses. Differently, although GABAergic parvalbumin-positive, fast-spiking interneurons have been shown to express both group I receptors, only mGlu1 receptor seems to mediate membrane and synaptic responses. This review provides a brief survey of the cellular and synaptic actions of group I mGlu receptors, and discusses the potential relevance of these findings in neostriatal function and motor control.