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Background Standardized results for laboratory tests are particularly important when their interpretation depends on fixed medical practice guidelines or common reference intervals. The medical laboratory community has developed a roadmap for an infrastructure to achieve standardized test results described in the International Organization for Standardization standard 17511:2020 In vitro diagnostic medical devices – Requirements for establishing metrological traceability of values assigned to calibrators, trueness control materials and human samples. Among the challenges to implementing metrological traceability are the availability of fit-for-purpose matrix-based certified reference materials (CRMs) and requirements for regulatory review that differ among countries. A workshop in December 2021 focused on these two challenges and developed recommendations for improved practices. Discussion The participants agreed that prioritization of measurands for standardization should be based on their impact on medical decisions in a clinical pathway. Ensuring that matrix-based CRMs are globally available for more measurands will enable fit-for-purpose calibration hierarchies for more laboratory tests. Regulation of laboratory tests is important to ensure safety and effectiveness for the populations served. Because regulations are country or region specific, manufacturers must submit recalibration changes intended to standardize results for regulatory review to all areas in which a measuring system is marketed. Recommendations A standardization initiative requires collaboration and planning among all interested stakeholders. Global collaboration should be further developed for prioritization of measurands for standardization, and for coordinating the production and supply of CRMs worldwide. More uniform regulatory submission requirements are desirable when recalibration is implemented to achieve internationally standardized results.

Developments in "-omics" are creating a paradigm shift in laboratory medicine leading to personalized medicine. This allows the increase in diagnostics and therapeutics focused on individuals rather than populations. In order to investigate whether laboratory medicine is ready to play a key role in the integration of personalized medicine in routine health care and set the state-of-the-art knowledge about personalized medicine and laboratory medicine in Europe, a questionnaire was constructed under the auspices of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) and the European Society of Pharmacogenomics and Personalised Therapy (ESPT). The answers of the participating laboratory medicine professionals indicate that they are aware that personalized medicine can represent a new and promising health model, and that laboratory medicine should play a key role in supporting the implementation of personalized medicine in the clinical setting. Participants think that the current organization of laboratory medicine needs additional/relevant implementations such as (i) new technological facilities in -omics; (ii) additional training for the current personnel focused on the new methodologies; (iii) incorporation in the laboratory of new competencies in data interpretation and counseling; and (iv) cooperation and collaboration among professionals of different disciplines to integrate information according to a personalized medicine approach. ispartof: Drug Metab Pers Ther vol:30 issue:2 pages:121-128 ispartof: location:Germany status: published

Developments in "omics" are creating a paradigm shift in Laboratory Medicine leading to Personalised Medicine. This allows the increasing in diagnostics and therapeutics focused on individuals rather than populations. In order to investigate whether Laboratory Medicine is able to implement new diagnostic tools and expertise and commands proper state-of-the-art knowledge about Personalized Medicine and Laboratory Medicine in Europe, the joint Working Group "Personalized Laboratory Medicine" of the EFLM and ESPT societies compiled and conducted the Questionnaire "Is Laboratory Medicine ready for the era of Personalized Medicine?". 48 laboratories from 18 European countries participated at this survey. The answers of the participating Laboratory Medicine professionals indicate that they are aware that Personalized Medicine can represent a new and promising health model. Whereas they are aware that Laboratory Medicine should play a key role to support the implementation of Personalized Medicine in the clinical settings, the participants of this survey think that the current organization of the Laboratory Medicine needs additional/relevant implementations such as: 1. New technological Facilities in "omics"; 2. Additional training for the current personnel focused on the new methodologies; 3. Incorporation in the Laboratory of new competencies in data interpretation and counselling; 4. Improving cooperation and collaboration between professionals of different disciplines to integrate information suitable for a Personalized Medicine approach. This survey suggest a strategic plan that should be considered by both health care providers and scientific societies of Laboratory Medicine. The implementation of Personalized Medicine should be first tested in a limited number of centers (Academic / Hospitals) possessing a wide range of competencies and facilities in "-omics" and in bioinformatics. These centers should then be supported to gain the missing technological facilities and appropriately trained for this aim.

It has been reported that more than 50% of lupus patients show various forms of neurological deficits including impaired cognitive functions and psychiatric disorders. Using an animal model of lupus we investigated the production of neuropeptides in the brain of NZB/W F1 female hybrid mice and its parental strain NZB and NZW. Our results indicate that the alteration in learning and memory described in lupus mice are paralleled by a decrease in calcitonin gene-related peptide, substance P and neuropeptide Y (NPY) levels in the hippocampus and a significant decrease of NPY in the cortex. These findings are interesting in the light of previously reported results suggesting that these neuropeptides can play an important role in cognitive functions. We also observed a decrease of NPY and vasoactive intestinal polypeptide levels in the hypothalamus of lupus prone mice and these changes may be related to the disregulation of the hypothalamus-pituitary-adrenal axis observed in lupus prone mice.

The worldwide financial crisis during recent years has raised concerns of negative public health effects. This is notably evident in southern Europe. In Greece, where the financial austerity has been especially pronounced, the prevalence of mental health problems including depression and suicide has increased, and outbreaks of infectious diseases have risen. The main objective in this study was to investigate whether different indicators of health and stress levels measured by a new biomarker based on cortisol in human hair were different amongst comparable Greek and Swedish young adults, considering that Sweden has been much less affected by the recent economic crises. In this cross-sectional comparative study, young adults from the city of Athens in Greece (n = 124) and from the city of Linkoping in Sweden (n = 112) participated. The data collection comprised answering a questionnaire with different health indicators and hair samples being analyzed for the stress hormone cortisol, a biomarker with the ability to retrospectively measure long-term cortisol exposure. The Greek young adults reported significantly higher perceived stress (p

The effects of MSG treatment on NGF and NPY levels were analysed in the hypothalamus, pituitary, adrenal, thyroid and testis of adult rats. Daily i.v. injections of MSG (1 g kg-1 for 1 week) induced an increase of NGF in the hypothalamus (control (C) = 378 +/- 54; saline (S) = 369 +/- 36; MSG = 479 +/- 35 pg g-1 tissue; p < 0.001) and pituitary (C = 310 +/- 34; S = 376 +/- 114; MSG = 576 +/- 98 pg g-1 tissue; p < 0.01). Hypothalamic and pituitary NPY concentrations were also altered in the MSG-treated rats. Compared with saline-treated rats, the NPY concentration increased by 43% in the hypothalamus and 37.5% in the pituitary of MSG-treated rats. No significant changes in NGF and NPY content were found in the adrenal or thyroid of treated animals. These results suggest that hypothalamic and pituitary NGF and NPY levels may be involved in the control of neuroendocrine functions that are affected by MSG treatment.

In the present study we used a well-characterised model of murine lupus, the female NZB/W hybrid, to study the possible involvement of neuropeptides in the pathogenesis of systemic lupus erythematosus (SLE). Analysis of neuropeptides with a possible role in inflammation showed that substance P (SP) calcitonin gene-related peptide (CGRP) and neuropeptide Y (NPY) are present in increased quantities in the inflamed kidneys of SLE mice, confirming their involvement in local inflammation, while there is a general reduction in the peptide concentrations in the lymphoid organs of lupus mice, except for NPY. Our results suggest that the altered neuropeptide concentrations observed in the SLE lymphoid organs may be partly responsible for the altered immune response and contribute to the development of autoimmune diseases.

In the present work we investigated the production of nerve growth factor (NGF) in the brain and peripheral tissues of female NZB/W F1 mice, a well characterized model of murine lupus. Our results indicate that while no significant difference in the NGF content was observed in the sera and tissues of NZB/W mice and its parental strains during the first months of life, the levels of circulating NGF and the NGF content in the kidneys significantly increase in the autoimmune mice during the development of the disease. The NGF-producing brain regions showed a decrease in NGF concentration in 8 month-old NZB/W mice. Moreover, we found a modification of the NGF concentration in the spleens of autoimmune mice at 5 and 8 months. Our data support the hypothesis of a correlation between NGF and the inflammatory state of systemic lupus erythematosus (SLE) and indicate that NGF could have a role in the pathogenesis of this disease.

The production of neuropeptide Y (NPY) in lymphocytes obtained from human tonsils was investigated using radioimmunoassay. While unstimulated lymphocytes did not produce detectable amounts of NPY, NPY synthesis was induced after cell activation. Our results show that the addition of nerve growth factor (NGF) to unstimulated lymphocytes has an effect similar to that of mitogens, both leading to production of NPY. The study of purified B and T cells confirmed that only activated cells are able to synthesize NPY. The stimulatory effect of NGF on NPY production is not a common characteristic of all lymphocytes: only unstimulated T cells respond to NGF by synthesizing NPY. No such effects is seen in purified B cells.

Both intrinsic and extrinsic neurons of the gut respond to mechanical and chemical stimuli by the release of neurotransmitters. We summarize here some of our recent work on the role of vasoactive intestinal polypeptide (VIP), substance P (SP) and neurokinin A (NKA) in the secretory, motor and vascular effects of hydrochloric acid stimulation in the isolated rat duodenal loop and electrical nerve stimulation and mechanical stimulation of the cat colon. Isolated duodenal loops of conscious rats were perfused with isotonic saline, and challenged at hourly intervals with brief exposures to increasing concentrations of HCL. The concentrations of bicarbonate and prostaglandin E2 (PGE2) released from the duodenal mucosa were significantly augmented already by pH 5.0 whereas VIP was significantly augmented at pH 3.0 and the tachykinins SP and NKA at pH 2.0. Continuous electric stimulation of the pelvic nerve in cats at 4 Hz during 1 s with 10 s rest produced a marked release of NKA-LI and SP-LI from the colon to blood. Reflex activation of the pelvic nervae by mechanical stimulation of the anus or rectal distension produced a less pronounced release of NKA-LI and SP-LI from the colon to blood. There was a simultaneous colonic contraction and vasodilation during each nerve stimulation. Close intraarterial infusions of NKA, neurokinin B, SP, neuropeptide K (NPK), eledoisin and physalemin at doses of 0.1-100 pmol/min induced dose-dependent proximal and distal colonic contractions and vasodilation, NKA being the most potent. The effects of the tachykinins were reduced after tetrodotoxin and atropine, but unchanged after treatment with hexamethonium.(ABSTRACT TRUNCATED AT 250 WORDS)

The distribution of galanin mRNA-expressing cells and galanin-immunoreactive (IR) cell bodies and processes was studied in the brain of mice overexpressing galanin under the PDGF-B promoter (GalOE mice) and of wild type (WT) mice, both in colchicine-treated and non-treated animals. In this abstract, we only describe the results in GalOE mouse. A widespread ectopic expression of galanin (both mRNA and peptide) was found, that is a situation when neither transcript nor peptide could be seen in WT mice, not even after colchicine treatment. However, in some regions, such as claustrum, basolateral amygdala, thalamus, CA1 pyramidal cells, and Purkinje cells only galanin mRNA could be detected. In the forebrain galanin was seen in the mitral cells of the olfactory bulb, throughout the cortex, in the basolateral amygdaloid nucleus, claustrum, granular and pyramidal cell layers of the hippocampus, subiculum and presubiculum. In the thalamus, the anterodorsal, mediodorsal, intermediodorsal and mediodorsal lateral nuclei, the reuniens and reticular nuclei showed ectopic expression of galanin. Within the hypothalamus, neurons of the suprachiasmatic nucleus contained galanin. In the mesencephalon, the geniculate nucleus, nucleus ruber, the mesencephalic trigeminal and reticulotegmental nuclei ectopically expressed galanin. In the cerebellum, galanin was observed in the Purkinje cells and in the lateral and interposed cerebellar nuclei. In the pons, sensory and motor nuclei of the trigeminal nerve, the laterodorsal and dorsal tegmental nuclei, the pontine, reticulotegmental and gigantocellular reticular nuclei expressed galanin. Within the medulla oblongata, labeled cells were detected in the facial, ambiguus, prepositus, lateral paragigantocellular and lateral reticular nuclei, and spinal trigeminal nucleus. High densities of galanin-IR fibers were found in the axonal terminals of the lateral olfactory tract, the hippocampal and presumably the cerebellar mossy fibers system, in several thalamic and hypothalamic regions and the lower brain stem. Possible functional consequences of galanin overexpression are discussed.