Synthetic Studies of Azulenyl and Pseudoazulenyl Nitrones

Free radicals have been implicated in various pathological conditions such as, stroke, aging and ischemic heart disease (IHD), as well as neurodegenerative diseases like Alzheimer’s, Parkinson’s, and Huntington’s disease. The role of antioxidants in protection from the harmful effects of free radicals has long been recognized. Trapping extremely reactive free radicals and eliminating them from circulation has been shown to be effective in animal models. Nitrone-based free radical traps have been extensively explored in biological systems. Examples include nitrones such as PBN, NXY-059, MDL-101,002, DMPO and EMPO. However, these nitrones have extremely high oxidation potentials as compared to natural antioxidants such as Vitamin E (á-tocopherol), and glutathione. Becker et al. (1995) synthesized novel azulenyl nitrones, which were shown to have oxidation potentials much lower than that of any of the previously reported nitrone based spin traps. Another azulenyl nitrone derivative, stilbazulenyl nitrone (STAZN), was shown to have an even lower oxidation potential within the range of natural antioxidants. STAZN, a second generation free radical trap, was found to be markedly superior than the two most studied nitrones, PBN and NXY-059, in animal models of cerebral ischemia and in an in vitro assay of lipid peroxidation. In this study, a third generation azulenyl nitrone was synthesized with an electron donating group on the previously synthesized STAZN derivative with the aim to lower the oxidation potential even more. Pseudoazulenes, because of the presence of an annular heteroatom, have been reported to possess even lower oxidation potential than that of the azulenyl counterpart. Therefore, pseudoazulenyl nitrones were synthesized for the first time by extracting and elaborating valtrate from the roots of Centranthus ruber (Red valerian or Jupiter’s beard). Several pseudoazulenyl nitrones were synthesized by using a facile experimental protocol. The physical and biological properties of these pseudoazulenyl nitrones can be easily modified by simply changing the substituent on the heteroatom. Cyclic voltammetry experiments have shown that these pseudoazulenyl nitrones do indeed have low oxidation potentials. The oxidation potential of these nitrones was lowered even more by preparing derivatives bearing an electron donating group at the 3-position of the five membered ring of the pseudoazulenyl nitrone.

Making meaningful connections: Using insights from social pedagogy in statutory child and family social work practice

Reports into incidents of child death and serious injury have highlighted consistently concern about the capacity of social workers to communicate skilfully with children. Drawing on data collected as part of an Economic and Social Research Council funded UK-wide research project exploring social workers’ communicative practices with children, this paper explores how approaches informed by social pedagogy can assist social workers in connecting and communicating children. The qualitative research included data generated from 82 observations of social workers’ everyday encounters with children. Social pedagogical concepts of ‘haltung’ (attitude), ‘head, heart and hands’ and ‘the common third’ are outlined as potentially helpful approaches for facilitating the intimacies of inter-personal connections and enhancing social workers’ capacity to establish and sustain meaningful communication and relationships with children in the face of austere social, political and organisational contexts.

Ulnar artery aneurysm: case report and review of the literature

Aim. We report a case of ulnar and palmar arch artery aneurysm in a 77 years old man without history of any occupational or recreational trauma, vasculitis, infections or congenital anatomic abnormalities. We also performed a computed search of literature in PUBMED using the keywords “ulnar artery aneurysm” and “palmar arch aneurysm”. Case report. A 77 years old male patient was admitted to hospital with a pulsing mass at distal right ulnar artery and deep palmar arch; at ultrasound and CT examination a saccular aneurysm of 35 millimeters at right ulnar artery and a 15 millimeters dilatation at deep palmar arch were detected. He was asymptomatic for distal embolization and pain. In local anesthesia ulnar artery and deep palmar arch dilatations were resected. Reconstruction of vessels was performed through an end-to-end microvascular repair. Histological examination confirmed the absence of vasculitis and collagenopaties. In postoperative period there were no clinical signs of peripheral ischemia, Allen’s test and ultrasound examination were normal. At follow-up of six months, the patient was still asymptomatic with a normal Allen test, no signs of distal digital ischemia and patency of treated vessel with normal flow at duplex ultrasound. Conclusion. True spontaneous aneurysms of ulnar artery and palmar arch are rare and can be successfully treated with resection and microvascular reconstruction.

Molecular Characterization and Localization of the NAD(P)H Oxidase Components gp91-phox and p22-phox in Endothelial Cells

The production of reactive oxygen species (ROS) within endothelial cells may have several effects, including alterations in the activity of paracrine factors, gene expression, apoptosis, and cellular injury. Recent studies indicate that a phagocyte-type NAD(P)H oxidase is a major source of endothelial ROS. In contrast to the high-output phagocytic oxidase, the endothelial enzyme has much lower biochemical activity and a different substrate specificity (NADH.NADPH). In the present study, we (1) cloned and characterized the cDNA and predicted amino acid structures of the 2 major subunits of rat coronary microvascular endothelial cell NAD(P)H oxidase, gp91-phox and p22-phox; (2) undertook a detailed comparison with phagocytic NADPH oxidase sequences; and (3) studied the subcellular location of these subunits in endothelial cells. Although these studies revealed an overall high degree of homology (.90%) between the endothelial and phagocytic oxidase subunits, the endothelial gp91-phox sequence has potentially important differences in a putative NADPH-binding domain and in putative glycosylation sites. In addition, the subcellular location of the endothelial gp91-phox and p22-phox subunits is significantly different from that reported for the neutrophil oxidase, in that they are predominantly intracellular and collocated in the vicinity of the endoplasmic reticulum. This first detailed characterization of gp91-phox and p22-phox structure and location in endothelial cells provides new data that may account, in part, for the differences in function between the phagocytic and endothelial NAD(P)H oxidases.

Acute phase proteins and biomarkers for health in chickens

Acute phase proteins (APPs) are proteins synthesised predominantly in the liver, whose plasma concentrations increase (positive APP) or decrease (negative APP) as a result of infection, inflammation, trauma and tissue injury. They also change as a result of the introduction of immunogens such as bacterial lipopolysaccharide (LPS), turpentine and vaccination. While publications on APPs in chickens are numerous, the limited availability of anti-sera and commercial ELISAs has resulted in a lot of information on only a few APPs. Disease is a threat to the poultry industry, as pathogens have the potential to evolve, spread and cause rapid onset of disease that is detrimental to the welfare of birds. Low level, sub-acute disease with non-specific, often undiagnosed causes can greatly affect bird health and growth and impact greatly on productivity and profitability. Developing and validating methods to measure and characterise APPs in chickens will allow these proteins to be used diagnostically for monitoring flock health. Using immune parameters such as APPs that correlate with disease resistance or improvements in production and welfare will allow the use of APPs as selection parameters for breeding to be evaluated. For APPs to be useful parameters on which to evaluate chicken health, information on normal APP concentrations is required. Ceruloplasmin (Cp) and PIT54 concentrations were found to be much lower in healthy birds form commercial production farms than the reported normal values obtained from the literature. These APPs were found to be significantly higher in culled birds from a commercial farm and Cp, PIT54 and ovotransferrin (Ovt) were significantly higher in birds classified as having obvious gait defects. Using quantitative shotgun proteomics to identify the differentially abundant proteins between three pools: highly acute phase (HAP), acute phase (AP) and non-acute phase (NAP), generated data from which a selection of proteins, based on the fold difference between the three pools was made. These proteins were targeted on a individual samples alongside proteins known to be APPs in chickens or other species: serum amyloid A (SAA), C-reactive protein (CRP), Ovt, apolipoprotein A-I (apo-AI), transthyretin (Ttn), haemopexin (Hpx) and PIT54. Together with immunoassay data for SAA, Ovt, alpha-1-acid glycoprotein (AGP) and Cp the results of this research reveal that SAA is the only major APP in chickens. Ovotransferrin and AGP behave as moderate APPs while PIT54 and Cp are minor APPs. Haemopexin was not significantly different between the three acute phase groups. Apolipoprotein AI and Ttn were significantly lower in the HAP and AP groups and as such can be classed as negative APPs. In an effort to identify CRP, multiple anti-sera cross reacting with CRP from other species were used and a phosphorylcholine column known to affinity purify CRP were used. Enriched fractions containing low molecular weight proteins, elutions from the affinity column together with HAP, AP and NAP pooled samples were applied to a Q-Exactive Hybrid Quadrupole–Orbitrap mass spectrometer (Thermo Scientific) for Shotgun analysis and CRP was not identified. It would appear that CRP is not present as a plasma protein constitutively or during an APR in chickens and as such is not an APP in this species. Of the proteins targeted as possible novel biomarkers of the APR in chickens mannan binding lectin associated serine protease-2, α-2-HS-glycoprotein (fetuin) and major facilitator superfamily domain-containing protein 10 were reduced in abundance in the HAP group, behaving as negative biomarkers. Myeloid protein and putative ISG(12)2 were positively associated with the acute phase being significantly higher in the HAP and AP groups. The protein cathepsin D was significantly higher in both HAP and AP compared to the NAP indicating that of all the proteins targeted, this appears to have the most potential as a biomarker of the acute phase, as it was significantly increased in the AP as well as the HAP group. To evaluate APPs and investigate biomarkers of intestinal health, a study using re-used poultry litter was undertaken. The introduction of litter at 12 days of age did not significantly increase any APPs measured using immunoassays and quantitative proteomics at 3, 6 and 10 days post introduction. While no APP was found to be significantly different between the challenged and control groups at anytime point, the APPs AGP, SAA and Hpx did increase over time in all birds. The protein apolipoprotein AIV (apo-AIV) was targeted as a possible APP and because of its reported role in controlling satiety. An ELISA was developed, successfully validated and used to measure apo-AIV in this study. While no significant differences in apo-AIV plasma concentrations between challenged and control groups were identified apo-AIV plasma concentrations did change significantly between certain time points in challenged and control groups. Apoliporotein AIV does not appear to behave as an APP in chickens, as it was not significantly different between acute phase groups. The actin associated proteins villin and gelsolin were investigated as possible biomarkers of intestinal health. Villin was found not to be present in the plasma of chickens and as such not a biomarker target. Gelsolin was found not to be differentially expressed during the acute phase or as a result of intestinal challenge. Finally a proteomic approach was undertaken to investigate gastrocnemius tendon (GT) rupture in broiler chickens with a view of elucidating to and identify proteins associated with risk of rupture. A number of proteins were found to be differentially expressed between tendon pools and further work would enable further detailing of these findings. In conclusion this work has made a number of novel findings and addressed a number of data poor areas. The area of chicken APPs research has stagnated over the last 15 years with publications becoming repetitive and reliant on a small number of immunoassays. This work has sought to characterise the classic APPs in chickens, and use a quantitative proteomic approach to measure and categorise them. This method was also used to take a fresh approach to biomarker identification for both the APR and intestinal health. The development and validation of assays for Ovt and apo-AIV and the shotgun data mean that these proteins can be further characterised in chickens with a view of applying their measurement to diagnostics and selective breeding programs.

La concentración de calcio iónico se asocia a la presencia de fibrilación auricular post operatoria en pacientes llevados a revascularización miocardica

Objetivo. Determinar en un grupo de pacientes llevados a revascularización miocárdica si existió asociación entre la presencia de niveles de calcio iónico inferiores a 1,1 en las 24 horas del post operatorio y la ocurrencia de fibrilación auricular post operatoria. Metodología. Estudio observacional, analítico de casos y controles, en donde de manera consecutiva se incluyeron 110 sujetos (57 en el grupo de casos con presencia de fibrilación auricular post operatoria y 54 en el grupo de controles sin evidencia de fibrilación auricular) estos sujetos fueron llevados a revascularización miocárdica en la Fundación Cardioinfantil en los años 2010 a 2015. Resultados. Hubo 13 casos de fibrilación auricular post operatoria en pacientes con niveles de calcio iónico inferiores a 1,1 mmol/l en las primeras 24 horas del post operatorio OR: 0,5, IC (0,2-1,2) p: 0,1. Sin determinarse asociación por limitaciones del estudio, sin embargo un 29% de los pacientes con fibrilación auricular tuvieron niveles de calcio inferiores a 1,1 mmol/l en las primeras 24 horas del post operatorio, este valor aumenta a 31% cuando se analizan por separado los valores de calcio obtenidos a las 12 horas. Conclusiones. Aunque no se logró determinar asociación entre la fibrilación auricular post operatoria y las concentraciones de calcio iónico, de manera exploratoria se pudo establecer que un 29% de los pacientes con fibrilación auricular tuvieron concentraciones de calcio iónico inferiores a 1,1 mmol/l, este valor aumenta a 31% cuando se analizan los niveles de calcio iónico por separado.

Sex differences in coronary artery disease severity and mortality: the impact of conventional cardiovascular risk factors

It is still unknown whether traditional risk factors may have a sex specific impact on the severity of coronary artery disease (CAD) and subsequent mortality in acute coronary syndromes (ACS). We identified 14 793 patients who underwent coronary angiography for acute coronary syndromes in the ISACS-TC (NCT01218776) registry from 2010 to 2019. The main outcome measure was the association between conventional risk factors and severity of CAD and its relationship with 30-day mortality. Risk ratios (RRs) and 95% CIs were calculated from the ratio of the absolute risks of women versus men using inverse probability of weighting. Severity of disease was categorized as obstructive (≥50% stenosis) versus nonobstructive CAD, specifically Ischemia and No Obstructive Coronary Artery disease (INOCA) and Myocardial Infarction with Non obstructive Coronary Arteries (MINOCA). The RR ratio for obstructive CAD in women versus men among people without diabetes mellitus was 0.49(95%CI,0.41–0.60) and among those with diabetes mellitus was 0.89(95% CI,0.62–1.29), with an interaction by diabetes mellitus status of P =0.002. Exposure to smoking shifted the RR ratios from 0.50 (95% CI, 0.41–0.61) in nonsmokers to 0.75 (95%CI, 0.54–1.03) in current smokers, with an interaction by smoking status of P=0.018. There were no significant sex-related interactions with hypercholesterolemia and hypertension. Women with obstructive CAD had higher 30-day mortality rates than men (RR, 1.75; 95% CI, 1.48–2.07). No sex differences in mortality were observed in patients with INOCA/MINOCA. In conclusion, obstructive CAD in women signifies a higher risk for mortality compared with men. Current smoking and diabetes mellitus disproportionally increase the risk of obstructive CAD in women. Achieving the goal of improving cardiovascular health in women still requires intensive efforts toward further implementation of lifestyle and treatment interventions.

Hepatic Involvement In Paediatric Patients With Paracoccidioidomycosis: A Histological Study.

Paracoccidioidomycosis is a systemic mycosis that is endemic to certain countries in Latin America. This study aimed to describe the histological features of liver involvement in patients with paracoccidioidomycosis aged <16 years of age who were treated between 1980 and 2010, with a diagnosis that was confirmed by detection of the fungus by pathological examination. Liver tissue was obtained from one necropsy and 12 biopsies. Throughout 2007, biopsies were taken from patients with persistent jaundice or portal hypertension, after which biopsies became indicated due to elevated aminotransferase and low albumin levels. Using haematoxylin and eosin (H&E), Masson's trichrome and immunohistochemical (CK7 and CK19) staining, we noted degenerative alterations in bile duct cells and inflammatory injury to the bile ducts in 10 biopsies. Using immunohistochemistry for CK7 and CK19, we observed ductal proliferation in all 12 samples. Bile duct injuries by inflammatory cells might explain the predominant increase in canalicular enzymes; immunohistochemistry is more sensitive in demonstrating ductular reactions and might show changes that are not apparent on H&E staining.

Deregulation Of Adipokines Related To Target Organ Damage On Resistant Hypertension.

Resistant hypertension (RHTN) includes patients with controlled blood pressure (BP) (CRHTN) and uncontrolled BP (UCRHTN). In fact, RHTN patients are more likely to have target organ damage (TOD), and resistin, leptin and adiponectin may affect BP control in these subjects. We assessed the relationship between adipokines levels and arterial stiffness, left ventricular hypertrophy (LVH) and microalbuminuria (MA). This cross-sectional study included CRHTN (n=51) and UCRHTN (n=38) patients for evaluating body mass index, ambulatory blood pressure monitoring, plasma adiponectin, leptin and resistin concentrations, pulse wave velocity (PWV), MA and echocardiography. Leptin and resistin levels were higher in UCRHTN, whereas adiponectin levels were lower in this same subgroup. Similarly, arterial stiffness, LVH and MA were higher in UCRHTN subgroup. Adiponectin levels negatively correlated with PWV (r=-0.42, P<0.01), and MA (r=-0.48, P<0.01) only in UCRHTN. Leptin was positively correlated with PWV (r=0.37, P=0.02) in UCRHTN subgroup, whereas resistin was not correlated with TOD in both subgroups. Adiponectin is associated with arterial stiffness and renal injury in UCRHTN patients, whereas leptin is associated with arterial stiffness in the same subgroup. Taken together, our results showed that those adipokines may contribute to vascular and renal damage in UCRHTN patients.

Avaliação física do tomate de mesa 'Romana' durante manuseio na pós-colheita

Tomato postharvest losses are very high in Brazil and the goal of this research was to evaluate the effect of handling and the transport of tomato fruits, cultivar Romana on the steps of harvesting, weight and transportation to the packinghouse, pointing some critical points. Tomatoes were harvested at plastic boxes, weighted and shipped to a packinghouse. Fruits taken directly from the plant were determined as reference. The parameters evaluated were weight loss and mechanical injury and tomato physical quality after storage during 21 days. It was observed an increasing on the weight loss, external damage, and postharvest losses, after storage. Handling and transportation were the cause of an increase in 6.6% in external damage and 1.93% of weight loss after storage, when comparing harvested fruits and fruits evaluated on the packing-house. The main reason for postharvest losses was due to mechanical injury caused during transportation mainly due to the compressure force among fruits and against the plastic boxes.

Protocolo de lesão esportiva no esporte paralímpico (PLEEP) : proposta para a coleta de dados

Universidade Estadual de Campinas . Faculdade de Educação Física

Influência do estreitamento do canal vertebral e do tempo para a descompressão na recuperação locomotora de ratos

OBJETIVO: o objetivo deste trabalho foi estudar as consequências da lesão por contusão da medula espinhal, associada ao estreitamento do canal vertebral, no comportamento motor de ratos, avaliando-se o efeito do tempo para descompressão na recuperação neurológica dos animais. MÉTODOS: foram utilizados ratos Wistar machos (n=6 por grupo), subdivididos nos seguintes grupos experimentais: laminectomia (T9-T10, Grupo Controle), contusão por queda de peso (10 g de peso, 15 cm de altura), estreitamento do canal vertebral em 35% (hastes de policarbonato; espessura de 0,78 mm) e contusão associada ao estreitamento do canal vertebral. O grupo de lesão associada foi ainda subdividido em sem ou com descompressão 24 ou 72 horas após a cirurgia. Os animais foram sacrificados sete dias após os procedimentos cirúrgicos. A função locomotora dos animais foi avaliada por meio do teste do campo aberto, do teste do plano inclinado e pela aplicação da escala BBB, antes da cirurgia, 24 e 72 horas depois da cirurgia e após 7 dias do procedimento cirúrgico. RESULTADOS: a lesão por queda de peso e compressão da medula espinhal, bem como a lesão mista, prejudicaram o comportamento motor dos animais, sendo que a descompressão cirúrgica após 24 e 72 horas da cirurgia não melhorou a recuperação motora dos animais, como mostram os resultados da avaliação de campo aberto, no plano inclinado e pela escala BBB. Por outro lado, os animais que sofreram lesão medular por queda de peso apresentaram melhores escores na escala BBB e ângulos maiores no plano inclinado do que aqueles que sofreram lesão por estreitamento do canal vertebral ou lesão mista. CONCLUSÕES: a lesão por queda de peso ou estreitamento do canal vertebral provocou alterações no comportamento motor dos animais, sendo que a descompressão não trouxe melhora funcional significativa.

Environmental Risk Factors for Parkinson's Disease

Parkinson’s disease (PD) is a progressive, degenerative, neurological disease. The progressive disability associated with PD results in substantial burdens for those with the condition, their families and society in terms of increased health resource use, earnings loss of affected individuals and family caregivers, poorer quality of life, caregiver burden, disrupted family relationships, decreased social and leisure activities, and deteriorating emotional well-being. Currently, no cure is available and the efficacy of available treatments, such as medication and surgical interventions, decreases with longer duration of the disease. Whilst the cause of PD is unknown, genetic and environmental factors are believed to contribute to its aetiology. Descriptive and analytical epidemiological studies have been conducted in a number of countries in an effort to elucidate the cause, or causes, of PD. Rural residency, farming, well water consumption, pesticide exposure, metals and solvents have been implicated as potential risk factors for PD in some previous epidemiological studies. However, there is substantial disagreement between the results of existing studies. Therefore, the role of environmental exposures in the aetiology of PD remains unclear. The main component of this thesis consists of a case-control study that assessed the contribution of environmental exposures to the risk of developing PD. An existing, previously unanalysed, dataset from a local case-control study was analysed to inform the design of the new case-control study. The analysis results suggested that regular exposure to pesticides and head injury were important risk factors for PD. However, due to the substantial limitations of this existing study, further confirmation of these results was desirable with a more robustly designed epidemiological study. A new exposure measurement instrument (a structured interviewer-delivered questionnaire) was developed for the new case-control study to obtain data on demographic, lifestyle, environmental and medical factors. Prior to its use in the case-control study, the questionnaire was assessed for test-retest repeatability in a series of 32 PD cases and 29 healthy sex-, age- and residential suburb-matched electoral roll controls. High repeatability was demonstrated for lifestyle exposures, such as smoking and coffee/tea consumption (kappas 0.70-1.00). The majority of environmental exposures, including use of pesticides, solvents and exposure to metal dusts and fumes, also showed high repeatability (kappas >0.78). A consecutive series of 163 PD case participants was recruited from a neurology clinic in Brisbane. One hundred and fifty-one (151) control participants were randomly selected from the Australian Commonwealth Electoral Roll and individually matched to the PD cases on age (± 2 years), sex and current residential suburb. Participants ranged in age from 40-89 years (mean age 67 years). Exposure data were collected in face-to-face interviews. Odds ratios and 95% confidence intervals were calculated using conditional logistic regression for matched sets in SAS version 9.1. Consistent with previous studies, ever having been a regular smoker or coffee drinker was inversely associated with PD with dose-response relationships evident for packyears smoked and number of cups of coffee drunk per day. Passive smoking from ever having lived with a smoker or worked in a smoky workplace was also inversely related to PD. Ever having been a regular tea drinker was associated with decreased odds of PD. Hobby gardening was inversely associated with PD. However, use of fungicides in the home garden or occupationally was associated with increased odds of PD. Exposure to welding fumes, cleaning solvents, or thinners occupationally was associated with increased odds of PD. Ever having resided in a rural or remote area was inversely associated with PD. Ever having resided on a farm was only associated with moderately increased odds of PD. Whilst the current study’s results suggest that environmental exposures on their own are only modest contributors to overall PD risk, the possibility that interaction with genetic factors may additively or synergistically increase risk should be considered. The results of this research support the theory that PD has a multifactorial aetiology and that environmental exposures are some of a number of factors to contribute to PD risk. There was also evidence of interaction between some factors (eg smoking and welding) to moderate PD risk.

Early Brief Treatment with Losartan plus Mycophenolate Mofetil Provides Lasting Renoprotection in a Renal Ablation Model

Background: Inflammatory events antecede established renal injury in rats with 5/6 renal ablation (Nx), as indicated by the beneficial effects of early, uninterrupted treatment with mycophenolate mofetil (MMF). Angiotensin II also exerts a major pathogenic role at this initial phase. We investigated whether losartan (L) or L+MMF treatment, started early, and L+MMF treatment, started late, would exert lasting renoprotection in Nx even after being discontinued. Methods: Adult male Munich-Wistar rats underwent Nx and were divided into three groups: Nx (untreated), Nx(L) (given L), and Nx(LMMF) (given L and MMF). Protocol 1: treatments began on day 1, and ceased on day 30, after Nx. Protocol 2: L+MMF treatment began on day 30 and ceased on day 60. Results: Protocol 1: on day 30, hypertension, albuminuria and renal injury were strongly attenuated in Groups Nx(L) and Nx(LMMF). On day 120, these abnormalities were still attenuated in group Nx(LMMF). Protocol 2: on day 120, all parameters were similar between this late Nx(LMMF) group and untreated Nx. Conclusion: In Nx, temporary suppression of early, transitory hemodynamic/inflammatory phenomena affords relatively durable renoprotection even after treatment discontinuation. This effect is not obtained with similar temporary treatment initiated later in the course of renal disease. Copyright (C) 2010 S. Karger AG, Basel

Egr transcription factors in the nervous system

The Egr proteins, Egr-1, Egr-2, Egr-3 and Egr-4, are closely related members of a subclass of immediate early gene-encoded, inducible transcription factors. They share a highly homologous DNA-binding domain which recognises an identical DNA response element. In addition, they have several less-well conserved structural features in common. As immediate early proteins, the Egr transcription factors are rapidly induced by diverse extracellular stimuli within the nervous system in a discretely controlled manner. The basal expression of the Egr proteins in the developing and adult rat brain and the induction of Egr proteins by neurotransmitter analogue stimulation, physiological mimetic and brain injury paradigms is reviewed. We review evidence indicating that Egr proteins are subject to tight differential control through diverse mechanisms at several levels of regulation. These include transcriptional, translational and posttranslational (including glycosylation, phosphorylation and redox) mechanisms and protein-protein interaction. Ultimately the differentially co-ordinated Egr response may lead to discrete effects on target gene expression. Some of the known target genes of Egr proteins and functions of the Egr proteins in different cell types are also highlighted. Future directions for research into the control and function of the different Egr proteins are also explored. (C) 1997 Elsevier Science Ltd.