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Previous results have shown that the substance P (SP) N-terminal fragment SP1-7 may attenuate hyperalgesia and produce anti-allodynia in animals using various experimental models for neuropathic pain. The heptapeptide was found to induce its effects through binding to and activating specific sites apart from any known neurokinin or opioid receptor. Furthermore, we have applied a medicinal chemistry program to develop lead compounds mimicking the effect of SP1-7. The present study was designed to evaluate the pharmacological effect of these compounds using the mouse spared nerve injury (SNI) model of chronic neuropathic pain. Also, as no comprehensive screen with the aim to identify the SP1-7 target has yet been performed we screened our lead compound H-Phe-Phe-NH2 toward a panel of drug targets. The extensive target screen, including 111 targets, did not reveal any hit for the binding site among a number of known receptors or enzymes involved in pain modulation. Our animal studies confirmed that SP1-7, but also synthetic analogs thereof, possesses anti-allodynic effects in the mouse SNI model of neuropathic pain. One of the lead compounds, a constrained H-Phe-Phe-NH2 analog, was shown to exhibit a significant anti-allodynic effect.

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The use of road tunnels in urban areas creates water pollution problems, since the tunnels must be frequently cleaned for traffic safety reasons. The washing generates extensive volumes of highly polluted water, for example, more than fivefold higher concentrations of suspended solids compared to highway runoff. The pollutants in the wash water have an affinity for particulate material, so sedimentation should be a viable treatment option. In this study, 12 in situ sedimentation trials were carried out on tunnel wash water, with and without addition of chemical flocculent. Initial suspended solids concentration ranged from 804 to 9,690 mg/L. With sedimentation times of less than 24 hours and use of a chemical flocculent, it was possible to reach low concentrations of suspended solids (<15 mg/L), PAH (<0.1 µg/L), As (<1.0 µg/L), Cd (<0.05 µg/L), Hg (<0.02 µg/L), Fe (<200 µg/L), Ni (<8 µg/L), Pb (<0.5 µg/L), Zn (<60 µg/L) and Cr (<8 µg/L). Acute Microtox(®) toxicity, mainly attributed to detergents used for the tunnel wash, decreased significantly at low suspended solids concentrations after sedimentation using a flocculent. The tunnel wash water did not inhibit nitrification. The treated water should be suitable for discharge into recipient waters or a wastewater treatment plant.

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The abuse of anabolic androgenic steroids (AAS) is relatively widely spread and epidemiological studies in the western countries report a prevalence between 1-5 % among males. The impact of these steroids on the strength and muscle mass as well as many of the adverse physical effects that have been observed are well described. Several reports have also revealed severe psychological effects as results of the administration of AAS. Effects such as irritability, aggressiveness, anxiety and depression are reported to be associated with AAS abuse. The mechanistic rationales behind these effects are not well understood. Several systems are likely to be involved, including the monoamine and peptidergic systems. The aim of this review is to highlight the potential role of the neuropeptide systems in the brain with focus on how these systems are affected by repeated administration of AAS.

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The kappa opioid receptor ligand [(3)H]CI-977 was used to autoradiographically determine the density of kappa opioid receptors in the male rat brain following chronic treatment with the anabolic androgenic steroid nandrolone decanoate at two different doses. As compared to controls, significantly lower densities of the kappa opioid receptor were encountered after two weeks of high dose nandrolone decanoate (15 mg/kg) in the nucleus accumbens shell (16%), lateral hypothalamic area (36%), ventromedial hypothalamic nucleus (37%), dorsomedial hypothalamic nucleus (49%), central amygdaloid nucleus, capsular part (28%), lateral globus pallidus (35%) and in the stria terminalis (24%). Furthermore, an up-regulation of the receptor level was observed in the caudate putamen (18%) and in the dorsal endopiriform nucleus (23%). These alterations in the kappa opioid receptor expression are possibly attributed to a previously observed pronounced impact of nandrolone decanoate on the dynorphinergic system and could also include involvement of the dopaminergic reward system.

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OBJECTIVES: To identify the main knowledge gaps and to propose research lines that will be developed within the European Union-funded 'Healthy Lifestyle in Europe by Nutrition in Adolescence' (HELENA) project, concerning the nutritional status, physical fitness and physical activity of adolescents in Europe. DESIGN: Review of the currently existing literature. RESULTS: The main gaps identified were: lack of harmonised and comparable data on food intake; lack of understanding regarding the role of eating attitudes, food choices and food preferences; lack of harmonised and comparable data on levels and patterns of physical activity and physical fitness; lack of comparable data about obesity prevalence and body composition; lack of comparable data about micronutrient and immunological status; and lack of effective intervention methodologies for healthier lifestyles. CONCLUSIONS: The HELENA Study Group should develop, test and describe harmonised and state-of-the-art methods to assess the nutritional status and lifestyle of adolescents across Europe; develop and evaluate an intervention on eating habits and physical activity; and develop and test new healthy food products attractive for European adolescents.

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Previous and current research has revealed that most neuropeptides induce their actions on cellular systems through specific receptors located on the cell surface. These receptors are known as G-protein coupled receptors, which exert their effects through interaction with ion channels or enzymes located within the cell membrane. Following receptor stimulation and exerting their effects the peptides are inactivated by enzymatic degradation. However, in many cases the active neuropeptides are enzymatically converted to products with retained bioactivity. These bioactive fragments may mimic but also counteract the action of the parent peptide. Thus, the released fragment may serve as a modulator of the response of the original compound. This phenomenon has been found to occur in a number of peptide systems, including the opioid peptides, tachykinins, as well as peptides belonging to the renin-angiotensin system, such as angiotensin II. In some cases the conversion product interacts with the same receptor as the native compound but sometimes it appears that the released fragment interacts with receptors or binding sites distinct from those of the original peptide. This review is focused on peptide fragments released from opioid related peptides, substance P and angiotensin II, that have been shown to modulate the action of their parent compounds.

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It is understood that the major pollution from storm water is related to the content of particulate matter. One treatment practice is based on the first flush, i.e. detention of the initial part of the runoff that is considered to contain the highest concentrations of pollutants. This study has evaluated the concentration of total suspended solids in 30 consecutive runoff events during the winter season for an area of 6.7 hectares. A six-lane highway (E4) that has an annual average daily traffic load of 120,000 dominates the area and road de-icing salt (NaCl) and studded tires were in regular use during the studied period. The effluent standard for wastewater of 60 mg TSS per litre applied in EU was used to assess the treatment requirement of storm water. In only two of the events the event mean concentration was below 60 mg 1(-1). In four runoff events a partial event mean concentration below 60 mg 1(-1) was found, in 26 %, 12 %, 11 %, and 2 % respectively of the runoff volume. This would suggest that a capture of the initial part of the runoff for subsequent treatment is less applicable in this type of urban watershed.

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Biosynthetic pathways for the formation of neuroactive peptides and the processes for their inactivation include several enzymatic steps. In addition to enzymatic processing and degradation, several neuropeptides have been shown to undergo enzymatic conversion to fragments with retained or modified biological activity. This has most clearly been demonstrated for e.g. opioid peptides, tachykinins, calcitonin gene-related peptide (CGRP) as well as for peptides belonging to the renin-angiotensin system. Sometimes the released fragment shares the activity of the parent compound. However, in many cases the conversion reaction is linked to a change in the receptor activation profile, i.e. the generated fragment acts on and stimulates a receptor not recognized by the parent peptide. This review will describe the characteristics of certain neuropeptide fragments having the ability to modify the biological action of the peptide from which they are derived. Focus will be directed to the tachykinins, the opioid peptides, angiotensins as well as to CGRP, bradykinin and nociceptin. The kappa opioid receptor selective opioid peptide, dynorphin, recognized for its ability to produce dysphoria, is converted to the delta opioid receptor agonist Leu-enkephalin, with euphoric properties. The tachykinins, typified by substance P (SP), is converted to the bioactive fragment SP(1-7), a heptapeptide mimicking some but opposing other effects of the parent peptide. The bioactive angiotensin II, known to bind to and stimulate the AT-1 and AT-2 receptors, is converted to angiotensin IV (i.e. angiotensin 3-8) with preference for the AT-4 sites or to angiotensin (1-7), not recognized by any of these receptors. Both angiotensin IV and angiotensin (1-7) are biologically active. For example angiotensin (1-7) retains some of the actions ascribed for angiotensin II but is shown to counteract others. Thus, it is obvious that the activity of many neuroactive peptides is modulated by bioactive fragments, which are formed by the action of a variety of peptidases. This phenomenon appears to represent an important regulatory mechanism that modulates many neuropeptide systems but is generally not acknowledged.

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We report on the reversal of protein-losing enteropathy (PLE) after heart transplantation (HTx) in a 10-yr-old boy with Fontan circulation, previously treated unsuccessfully with heparin for several months. The protein loss continued immediately after the Tx. During the following month, however, a gradual decrease in protein loss was observed, which correlated with a decrease in the inferior vena cava (IVC) pressure. The patient is doing well with a normal serum albumin level and a normal IVC pressure, 2 yr after Tx.

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The large number of signaling pathways and regulatory proteins that affect transcription highlights a need for funneling of information since transcription of all protein encoding genes is executed by the same set of general transcription factors and RNA polymerase II. This demand is met by large protein complexes such as Mediator that interact with the basic RNA polymerase II machinery and thus adds diversity simply by increasing the surface that is exposed to the incoming signals. The recent description of Mediator-like complexes in metazoans identifies it as a key player in transcriptional regulation.

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The effects of intramuscular (i.m.) injections of nandrolone decanoate (15 mg/kg/day), an anabolic-androgenic steroid, on the levels of substance P (SP) and on its N-terminal fragment SP(1-7) were examined in the male rat brain by radioimmunoassay. The results demonstrated that the SP immunoreactivity in amygdala, hypothalamus, striatum, and periaqueductal gray was significantly enhanced, whereas the concentration of the N-terminal fragment SP(1-7) was enhanced in the nucleus accumbens and in periaqueductal gray. In the striatum the steroid induced a decrease in the content of SP(1-7). The relevance of these peptides in connection with anabolic-androgenic steroid-induced aggression is discussed.

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In recent years, an increase in abuse of anabolic androgenic steroids (AAS) has been seen among individuals not directly connected to sports. Clinical evidence suggests that abuse of these steroids may result in profound changes in personality, expressed by depressive symptoms, irritability and increased aggression. It is still unknown whether these alterations are related to changes in any particular transmitter system or whether they are persistent or reversible. In this study we focused on AAS effect on the endogenous dynorphin and enkephalin system in the brain. Male rats were given intramuscular injections of the AAS nandrolone decanoate (15 mg/kg), once daily for 2 weeks. The levels of the opioid peptide immunoreactivities (ir) were assessed by radioimmunoassay in two groups immediately after the treatment and in two other groups after additional 3 weeks without any drug treatment (recovery period). The result indicates that chronic AAS treatment increased the activity in the dynorphin B- and Met-enkephalin-Arg(6)Phe(7)-ir in the hypothalamus, striatum and periaqueductal gray (PAG) compared to controls. In addition, the steroid induced an imbalance between the dynorphin and the enkephalin opioid system in the nucleus accumbens, hypothalamus and PAG. This imbalance remained after the recovery period. Since increased peptide activity was found in brain regions regulating emotions, dependence, defensive reactions and aggression, it was suggested that the actual endogenous opioid systems are involved in previously reported AAS-induced changes in these behaviours.

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The very evolutionarily conserved human carbonic anhydrase-related polypeptide (CA-RP VIII) lacks the carbon-dioxide hydration-activity, characteristic of the enzymatically active carbonic anhydrases. We have expressed HCA-RP VIII as a glutathione-S-transferase fusion protein (GST-HCA-RP VIII). The purified HCA-RP VIII showed a substantially higher apparent molecular weight by gel-filtration compared to the molecular weight calculated from the amino acid sequence, indicating a larger than expected Stoke's radius. Like other studied CA's, the protein unfolds through two transitions at increasing concentrations of guanidine hydrochloride. The far-UV CD spectra of HCA-RP VIII indicates a secondary structure similar to that of the catalytically active HCA II. The very high sequence identity between human and mouse CA-RP VIII (98%), might indicate that the function of the protein involves binding of another protein. However, an attempt to use the GST-HCA-RP VIII fusion protein to affinity purify a ligand was unsuccessful.

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The reduction of ferric cytochrome c by various thiols was studied. It was found that L-cysteine, L-cysteine methyl ester and D-penicillamine were very efficient reductants for cytochrome c, whereas N-acetylated amino acids (N-acetyl-L-cysteine and N-acetyl-D-cysteine) reacted considerably slower. A series of glutathione peroxidase mimetics and related compounds were studied as catalysts for the N-acetyl-L-cysteine reduction of ferric cytochrome c. Diphenyl diselenide, t-butylthio phenyl selenide, S-(phenylseleno)-glutathione, N-(phenylseleno)-phthalimide and alpha-(phenylselenenyl)-acetophenone were all efficient reduction catalysts. Diphenyl disulfide, Ebselen and several derivatives thereof were less potent catalysts whereas diaryl selenides and diphenyltelluride did not affect the rate of reduction when present in catalytic amounts. The catalysis of diphenyl diselenide, selenosulfides, alpha-(phenylselenenyl)acetophenone, N-(phenylseleno)-phthalimide and Ebselen and derived compounds was suggested to involve the formation of areneselenolate ions as redox-active species capable of transferring one electron to the ferric cytochrome c. The resulting selenium centered arylseleno radicals would then dimerize to regenerate the catalyst in the diselenide form. In the presence of diaryl ditellurides and N-acetyl-L-cysteine, ferric cytochrome c was also rapidly reduced. This reaction was stoichiometric with respect to the ditelluride reagent.

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