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Hyaluronan (HA) levels are dynamically regulated homeostatically through biosynthesis and degradation. HA homeostasis is often perturbed under disease conditions. HA degradation products are thought to contribute to disease pathology. The hyaluronidase CEMIP requires the presence of living cells for its HA depolymerizing activity. CEMIP is overexpressed in a variety of pathological conditions, and the inhibition of its hyaluronidase activity therefore has therapeutic potential. To identify novel inhibitors of the CEMIP hyaluronidase activity, we established here a cell-compatible, medium-throughput assay for CEMIP-dependent HA depolymerization. The assay employs ultrafiltration plates to separate low- from high-molecular-weight HA, followed by quantification of HA fragments using an HA ELISA-like assay. Using this assay, we tested a range of compounds that have been reported to inhibit other hyaluronidases. Thereby, we identified several sulfated hydrocarbon polymers that inhibit CEMIP more potently than other hyaluronidases. One of these is heparin, a sulfated glycosaminoglycan produced by mast cells that constitutes the first described physiological CEMIP inhibitor. The most potent inhibitor (IC50 of 1.8 nM) is dextran sulfate, a synthetic sulfated polysaccharide. Heparin and dextran sulfate are used in numerous established and experimental biomedical applications. Their ability to inhibit CEMIP needs to be taken into account in these contexts. [ABSTRACT FROM AUTHOR]

Introduction: Cancer diagnoses are constantly increasing in clinical practice. Therefore, more and more patients are interested in how they can actively participate in the process of treatment. Spirituality represents a hidden issue of the population, which counts as a branch of complementary and alternative treatment. Therefore, the aim of our study was to investigate whether there are associations between spirituality and demographic and psychosocial factors, as well as religious beliefs, in cancer patients. Methods: We conducted a survey with 451 participants in 10 oncology centers between March and July 2021. A composition of the following 9 different questionnaires was used to collect data on spirituality, demographics, resilience, self-efficiency, life satisfaction, and sense of coherence: Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp12), General Life Satisfaction Short Scale (L-1), Resilienzskala Kurzform (RS-13), Sense of Coherence Scale – Leipziger Kurzform (SOC-L9), Allgemeine Selbstwirksamkeit Kurzskala (AKSU), Adolescent Food Habits Checklist, Likert-Scale of daily activities, questionnaire of the Working group Prävention und Integrative Onkologie (PRiO), and personal opinion on the cause of the disease. Calculated data and analyzed group differences using ANOVA Bonferroni were used to test associations between spirituality and the variables studied. For more detailed examination of spirituality, we took a closer look at the different components of spirituality – peace, meaning, and faith – and their relation to each other (three-factor spirituality analyses). Results: Higher spirituality scores in total as well as meaning, peace, and faith were each associated with higher levels of resilience and life satisfaction. Higher religious belief was found to be associated with higher spiritual attitudes. High personal self-efficiency was found in people with higher spiritual beliefs in general as well as higher meaning and peace. Meaning and peace emerge as essential components of spiritual well-being and show a stronger association with expressions of general spirituality than faith. Conclusion: Spirituality takes a crucial role among the resources of life-threatening diseases. As such, further research is needed to expand and integrate patient options into a modernized concept of care. Our data indicate that higher spiritual well-being is associated with a more tolerant approach to illness. Thus, addressing spiritual needs in therapy is associated with better psychological adjustment to the individual situation and reduces negative distress. To promote spiritual needs in the future, cognitive as well as affective components of spirituality should be emphasized. [ABSTRACT FROM AUTHOR]

Background: Being diagnosed with cancer is challenging. Many patients wish to be actively involved in treatment and contribute to therapy, but the patients' coping abilities and desire for involvement differ. The individual level of resilience seems to play a major role. Our study aims to learn more about the associations of resilience and factors as demographics and psychological factors. Methods: This multicentric cross-sectional study was conducted in ten oncological centers in Germany in summer 2021. The questionnaire collected information on demographics, resilience, self-efficacy, general satisfaction with life, and sense of coherence. Considered lifestyle-aspects were diet and physical activity. 416 patients were included in the analyses. Results: A moderate mean resilience score was achieved (M = 69). Significant correlations in demographics were found for resilience and education (r = 0.146, p = 0.003), income (r = 0.205, p = 0.001), and time since receiving diagnosis (r = − 0.115, p = 0.021). Resilience and self-efficacy correlated on a high level (r = 0.595, p < 0.001), resilience and sense of coherence, and resilience and general satisfaction with life in a moderate way (r = 0.339, p < 0.001; r = 0.461, p = 0.001). Conclusions: Resilience portrays an important aspect in cancer treatment. Detecting patients at risk, stabilizing, or improving resilience are important to focus on and strengthen them accordingly. Possible negatively influencing factors (e.g., low self-efficacy) need to be considered. Factors affecting resilience but difficult to influence, as educational background, should be screened for. Also, the combination of low resilience and low income seems to describe a vulnerable patient group. [ABSTRACT FROM AUTHOR]

A metagenomic analysis of the virome of honey bees (Apis mellifera) from an apiary with high rates of unexplained colony losses identified a novel RNA virus. The virus, which was named Apis mellifera solinvivirus 1 (AmSV1), contains a 10.6 kb positive-strand genomic RNA with a single ORF coding for a polyprotein with the protease, helicase, and RNA-dependent RNA polymerase domains, as well as a single jelly-roll structural protein domain, showing highest similarity with viruses in the family Solinviviridae. The injection of honey bee pupae with AmSV1 preparation showed an increase in virus titer and the accumulation of the negative-strand of AmSV1 RNA 3 days after injection, indicating the replication of AmSV1. In the infected worker bees, AmSV1 was present in heads, thoraxes, and abdomens, indicating that this virus causes systemic infection. An analysis of the geographic and historic distribution of AmSV1, using over 900 apiary samples collected across the United States, showed AmSV1 presence since at least 2010. In the year 2021, AmSV1 was detected in 10.45% of apiaries (95%CI: 8.41–12.79%), mostly sampled in June and July in Northwestern and Northeastern United States. The diagnostic methods and information on the AmSV1 distribution will be used to investigate the connection of AmSV1 to honey bee colony losses. [ABSTRACT FROM AUTHOR]

Background/Aim: People who are undergoing cancer treatment often ask themselves what they can do in addition to conventional medical therapy with regard to nutrition, activity, and complementary methods. However, we know little about the motivation why people opt for one or the other measure. The aim of this study was therefore to examine the extent of physical activity (PA), healthy nutrition, and the use of complementary methods in relation to both demographic and psychological data. Materials and Methods: A questionnaire was used to collect data on demographic data, resilience, coherence, self-efficacy, spirituality, satisfaction, and complementary and alternative medicine (CAM) behavior, PA, and diet. Between March and July 2021, data from 446 patients were collected. Regression models and correlation analyzes were used to examine the associations between CAM use, diet and PA with the other variables surveyed. Results: CAM usage could only be predicted based on the patient's spirituality. Women used CAM more often and ate more healthily. Healthy eating was also related to younger age, shorter medical history, resilience, satisfaction, and coherence. In addition, the results showed that daily PA was related to the level of resilience, spirituality, and self-efficacy. Conclusion: Which people or why patients use CAM remains a question to be further investigated. Our data suggest that CAM seeks to address similar needs that others find in spirituality. In order to promote a healthy diet and PA in cancer patients in the future, various psychological variables seem conceivable. Resilience stands out, which is related to an overall healthier lifestyle. [ABSTRACT FROM AUTHOR]

Current theories propose that anxiety adversely impacts working memory (WM) by restricting WM capacity and interfering with efficient filtering of task‐irrelevant information. The current study investigated the effect of shock‐induced state anxiety on WM capacity and the ability to filter task‐irrelevant neutral stimuli. We measured the contralateral delay activity (CDA), an event‐related potential that indexes the number of items maintained in WM, while participants completed a lateralized change detection task. The task included low and high WM loads, as well as a low load plus distracter condition. This design was used to assess WM capacity for low and high loads and investigate an individual's ability to filter neutral task‐irrelevant stimuli. Participants completed the task under two conditions, threat of shock and safe. We observed a reduced CDA in the threat compared to the safe condition that was specific for high memory load. However, we did not find any differences in CDA filtering cost between threat and safe conditions. In addition, we did not find any differences in behavioral performance between the threat and safe conditions. These findings suggest that being in an anxious state reduces the neural representation for large amounts of information in WM, but have little effect on the filtering of neutral distracters. Anxiety is believed to restrict working memory capacity and impact the ability to filter task‐irrelevant information, but little is known how an anxious state impacts these processes. Here, we provide electrophysiological evidence of reduced working memory capacity, but intact filtering abilities for neutral task‐irrelevant distracters in state anxious individuals. [ABSTRACT FROM AUTHOR]

In foundries with automatic moulding plants a complex system of different kinds of material flow exists. The multitude of technological constraints results in a dynamic and unstable production process. Therefore, small variances in process parameters may entail interruptions of a material flow and consequently cause downtime. Automatic moulding plants consist of rigidly chained units, so that to secure a high reliability corresponding expenditure is required. We present the results of an investigation of 21 automatic moulding plants in 15 German foundries. The analysis of the structure of downtime shows that the low efficiencies result not only from technical reasons, but also from missing materials and personnel, and technological disturbances due to planning and scheduling. [ABSTRACT FROM AUTHOR]

To support mechanistic inferences made for an iron-based dioxygenase model, a nickel analogue, i.e. a TpNi-malonate (1) was prepared. 1 proved to represent a rare case of a nickel complex reacting with O2 in a controlled manner – mechanistically different from the iron case – and leads to hydroxylation of the malonate. [ABSTRACT FROM AUTHOR]

Background: Eradication of HIV cannot be achieved with combination antiretroviral therapy (cART) because of the persistence of long-lived latently infected resting memory CD4+ T cells. We previously reported that HIV latency could be established in resting CD4+ T cells in the presence of the chemokine CCL19. To define how CCL19 facilitated the establishment of latent HIV infection, the role of chemokine receptor signalling was explored. Results: In resting CD4+ T cells, CCL19 induced phosphorylation of RAC-alpha serine/threonine-protein kinase (Akt), nuclear factor kappa B (NF-κB), extracellular-signal-regulated kinase (ERK) and p38. Inhibition of the phosphoinositol-3-kinase (PI3K) and Ras/Raf/Mitogen-activated protein kinase/ERK kinase (MEK)/ERK signalling pathways inhibited HIV integration, without significant reduction in HIV nuclear entry (measured by Alu-LTR and 2-LTR circle qPCR respectively). Inhibiting activation of MEK1/ERK1/2, c-Jun N-terminal kinase (JNK), activating protein-1 (AP-1) and NF-κB, but not p38, also inhibited HIV integration. We also show that HIV integrases interact with Pin1 in CCL19-treated CD4+ T cells and inhibition of JNK markedly reduced this interaction, suggesting that CCL19 treatment provided sufficient signals to protect HIV integrase from degradation via the proteasome pathway. Infection of CCL19-treated resting CD4+ T cells with mutant strains of HIV, lacking NF-κB binding sites in the HIV long terminal repeat (LTR) compared to infection with wild type virus, led to a significant reduction in integration by up to 40-fold (range 1-115.4, p = 0.03). This was in contrast to only a modest reduction of 5-fold (range 1.7-11, p > 0.05) in fully activated CD4+ T cells infected with the same mutants. Finally, we demonstrated significant differences in integration sites following HIV infection of unactivated, CCL19-treated, and fully activated CD4+ T cells. Conclusions: HIV integration in CCL19-treated resting CD4+ T cells depends on NF-κB signalling and increases the stability of HIV integrase, which allow subsequent integration and establishment of latency. These findings have implications for strategies needed to prevent the establishment, and potentially reverse, latent infection. [ABSTRACT FROM AUTHOR]

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The hitherto most realistic low-molecular-weight analogue for the 1-aminocyclopropane-1-carboxylic acid oxidase (ACCO) is reported. The ACCOs 2-His-1-carboxylate iron(II) active site was mimicked by a TpFe moiety, to which the natural substrate ACC could be bound. The resulting complex [TpMe,PhFeACC] ( 1), according to X-ray diffraction analysis performed for the nickel analogue, represents an excellent structural model, featuring ACC coordinated in a bidentate fashion-as proposed for the enzymatic substrate complex-as well as a vacant coordination site that forms the basis for the first successful replication also of the ACCO function: 1 is the first known ACC complex that reacts with O2 to produce ethylene. As a FeOOH species had been suggested as intermediate in the catalytic cycle, H2O2 was tested as the oxidant, too, and indeed evolution of ethylene proceeded even more rapidly to give 65 % yield. [ABSTRACT FROM AUTHOR]

Cysteine dioxygenase is a unique nonheme iron enzyme that is involved in the metabolism of cysteine in the body. It contains an iron active site with an unusual 3-His ligation to the protein, which contrasts with the structural features of common nonheme iron dioxygenases. Recently, some of us reported a truly biomimetic model for this enzyme, namely a trispyrazolylborato iron(II) cysteinato complex, which not only has a structure very similar to the enzyme-substrate complex but also represents a functional model: Treatment of the model with dioxygen leads to cysteine dioxygenation, as shown by isolating the cysteine part of the product in the course of the work-up. However, little is known on the conversion mechanism and, so far, not even the structure of the actual product complex had been characterised, which is also unknown in case of the enzyme. In a multidisciplinary approach including density functional theory calculations and X-ray absorption spectroscopy, we have now determined the structure of the actual sulfinato complex for the first time. The Cys-SO2− functional group was found to be bound in an η2- O, O-coordination mode, which, based on the excellent resemblance between model and enzyme, also provides the first support for a corresponding binding mode within the enzymatic product complex. Indeed, this is again confirmed by theory, which had predicted a η2- O, O-binding mode for synthetic as well as the natural enzyme. [ABSTRACT FROM AUTHOR]

Interpretive phenomenology was used to analyze interviews with 14 women who were recruited from a Midwestern program that provides prostitution-specific services. The participants described day-to-day experiences living with labeling, violence, and discrimination that were directed at them because of their involvement in prostitution and substance use. They also discussed their perceptions of being altered permanently by their activities as well as the ways in which they resist internalizing the negative messages that were directed at them. In this article, the construct of stigma is used to characterize these experiences. This article details the women's experience of living with stigma and presents implications for direct practice and policy. [ABSTRACT FROM AUTHOR]

Little is known about the impact of prostitution involvement on women's substance use and recovery. Interpretive phenomenological data analysis was used to analyze transcribed, in-depth interviews conducted with 14 women recruited from a Midwestern program providing prostitution-specific services. Interviews focused on what it means to be a woman who has engaged in prostitution. Participants described patterns of using substances and exchanging sex as 'going hand-in-hand,' highlighting unique ways women understand the relationships between these phenomena and how they construct meaning. What emerges is a deeper understanding of the complexity and impact of these relationships, an issue not adequately addressed in existing literature. [ABSTRACT FROM AUTHOR]

Little is known about the impact of prostitution involvement on women's substance use and recovery. Interpretive phenomenological data analysis was used to analyze transcribed, in-depth interviews conducted with 14 women recruited from a Midwestern program providing prostitution-specific services. Interviews focused on what it means to be a woman who has engaged in prostitution. Participants described patterns of using substances and exchanging sex as “going hand-in-hand,” highlighting unique ways women understand the relationships between these phenomena and how they construct meaning. What emerges is a deeper understanding of the complexity and impact of these relationships, an issue not adequately addressed in existing literature. [ABSTRACT FROM AUTHOR]

The velocity at which blood lactate concentration ([LA]) of 4 mmol/L is reached (v4) is widely used to determine fitness, but there are few published data on using [LA] as a guide for the exercise speed for training in horses. In this study, the effect of 3 conditioning programs with [LA] guided exercise speeds on v4, v200 (speed at a heart rate of 200 beats/mm), blood [LA], plasma FFA ([FFA]), and alanine concentrations ([alaninel), before and after exercise, as well as heart rate during exercise, of horses was examined. Six 2-yr-old Haflinger stallions underwent an initial treadmill-based standard exercise test (SET). A regression analysis [LA]-speed relationship was used to calculate v15, v25, and v4. Horses were then randomly assigned to 1 of 3 conditioning programs according to a 3 x 6 Latin square design. During 6 wk, horses exercised on the treadmill every other day for 45 mm at their calculated v1.5 or v2.5 or 25 mill at their v4. Each conditioning period (CDP) was followed by 5 wk without conditioning. At 2 and 9 d, and 5 wk, after the end of the CDP, the horses performed another SET to evaluate again the v4 and v200. Blood [LA], plasma [FFA], and [alanine] were measured before and after heart rate during exercise sessions 1, 11, and 21 in each CDP. None of the exercise programs had an effect on v4 and v200 (P > 0.05). The increase of the mean [LA] after exercise decreased during CDP (P < 0.05), and the increase of mean heart rate during exercise tended to decrease as well (P = 0.07). There was no difference among the conditioning programs. Plasma [FFA] before exercise was not influenced by the CDP (F> 0.05). The plasma [FFA] was always greater after exercise (P < 0.05), but there was no difference among conditioning programs. Overall, the increase was greatest after the 21st exercise session compared with the 1st and 11th exercise sessions (P < 0.05). The mean plasma [alanine] before exercise remained similar during all CDP (P > 0.05). Mean plasma [alanine] of the horses was increased after all exercise sessions measured (P < 0.05). There was no difference among conditioning programs (P> 0.05). It is concluded that conditioning with the exercise types used had small effects. This could have been because the exercise stress was too small, but also because the workload was not increased during the CDP. [ABSTRACT FROM AUTHOR]

Chronic infantile neurological cutaneous and articular (CINCA) syndrome is an autoinflammatory disease, defined by the triad of urticarial rash, neurological manifestations, and arthropathy, accompanied by recurrent fevers and systemic inflammation. Increasing neurological deficits result from aseptic meningitis. Sensorineural hearing loss and progressive loss of vision caused by keratoconjunctivitis or papilloedema may emerge. An autosomal-dominant inheritance is suspected although sporadic cases are reported frequently. Sixty per cent of CINCA patients carry mutations in the cold-induced autoinflammatory syndrome (CIAS1) gene. We report the favourable response of a 23-year-old CINCA patient without CIAS1 mutations to treatment with the recombinant interleukin-1 (IL-1) receptor antagonist anakinra. [ABSTRACT FROM AUTHOR]

Chilblain lupus erythematosus (CHLE) is a rare, chronic form of cutaneous lupus erythematosus. Sporadic cases and two families with autosomal dominant-inherited CHLE have been reported. In familial CHLE, two missense mutations in TREX1 encoding the 3′–5′ repair exonuclease 1 were described in affected individuals. The pathogenesis of sporadic CHLE remains unknown. Up to 20% of patients develop systemic lupus erythematosus (SLE). An association with anorexia is discussed. In many cases, there is good response to symptomatic therapy. SLE therapeutics have good effects on SLE-typical symptoms but not on chilblains themselves. This article reviews the clinical presentation, pathogenesis, diagnosis and treatment of CHLE. As an index patient with unique features, we report a 13-year-old boy developing CHLE after anorexia nervosa. Sequencing of TREX1 was normal. With psychotherapeutic support for anorexia and after antibiotic therapy, topical steroids, physical warming and calcium channel blockers, the patient experienced significant relief. Improvement of phalangeal perfusion was demonstrated by angio-MRI. [ABSTRACT FROM AUTHOR]

In ruminants, the uptake of inorganic phosphate (Pi) across the intestinal mucosa epithelium by Na-dependent and Na-independent mechanisms is a main regulatory factor in P homeostasis. The aim of the study was to elucidate to which extent Na-independent mechanisms, including pH effects or composition of mucosal brush-border membranes, could be involved in positive stimulation of Pi absorptive processes seen under the P deficient condition. Therefore, luminal, surface and intracellular pH of the jejunal epithelial cells in control and P depleted goats were compared and biochemical analyses of membrane phospholipids in the apical membrane of the jejunal epithelium were performed. Dietary P depletion resulted in decreased plasma Pi levels. While pH in jejunal ingesta was not significantly changed, P depletion resulted in a significantly lower surface pH in the crypt region compared to control animals (7.62 ± 0.02 vs. 7.77 ± 0.04, n = 4, P < 0.01). Inhibition of apical Na+/H+-exchange resulted in an increase of the jejunal surface pH in P depleted animals by 0.07 ± 0.01 ( n = 6, P < 0.01) and 0.05 ± 0.01 ( n = 6, P < 0.01) for the villus and the crypt region, respectively. This increase were inversely correlated with the initial surface pH prior to inhibition. In contrast to surface pH, intracellular pH of the jejunal epithelium and the phospholipid composition of the apical jejunal membrane were not affected by P depletion. Although the data suggest the existence of a Na+/H+-exchange mechanism at the luminal surface of goat jejunum they do not support the hypothesis that adaptational processes of active Pi absorption from goat jejunum in response to low dietary P could be based on “non Pi transporter events”. [ABSTRACT FROM AUTHOR]

Background: Nystagmus is common to all types of albinism. Some subjects with nystagmus lack convincing signs of albinism, have no other visual pathway disease, and are classified as possessing congenital idiopathic nystagmus (CN). It has been postulated that CN may be a form of ocular albinism. Methods: The presence of nystagmus, iris transillumination, and visual acuity were recorded in 39 CN and albino patients and their families. Physical characteristics were also noted. DNA from buccal swabs was obtained for use in denaturing high performance liquid chromatography (DHPLC) and chemical cleavage of mismatch (CCM) to scan several hotspots for X-linked ocular albinism (OA1) mutations. Results: Two previously reported polymorphisms were confirmed: neither was found to be a causative mutation. Conclusion: No correlation was identified between nystagmus and OA1. [ABSTRACT FROM AUTHOR]

Euglycemic, hyperinsulinemic clamp tests have shown that adult ruminants are less insulin-sensitive than monogastric omnivores. The present study was carried out to elucidate possible cellular mechanisms contributing to this impaired insulin sensitivity of ruminants. Western blotting was used to measure glucose transporters 1 and 4 (GLUT1, GLUT4) in oxidative (musculus masseter and diaphragm) and glycolytic (musculus longissimus dorsi and semitendinosus) skeletal muscle in the crude membranes of pigs and cows. Muscles were characterized biochemically. To determine insulin-stimulated 3-O-D-[³H]-methylglucose (3-O-MG) uptake and GLUT4 translocation, porcine and bovine musculus semitendinosus strips were removed by open muscle biopsy and incubated without and with 0.1 or 20 mIU insulin/ml. GLUT4 translocation was analyzed using subcellular fractionation techniques to isolate partially purified plasma membranes and cytoplasmic vesicles and using Western blotting. GLUT4 protein contents were significantly higher in oxidative than in glycolytic muscles in pigs and cows. GLUT1 protein contents were significantly higher in glycolytic than in oxidative muscles in bovines but not in porcines. The 3-O-MG uptake into musculus semitendinosus was similar in both species. Maximum insulin-induced GLUT4 translocation into musculus semitendinosus plasma membrane was significantly lower in bovines than in porcines. These results indicate that GLUT1 is the predominant glucose transporter in bovine glycolytic muscles and that a reinforced insulin-independent glucose uptake via GLUT1 may compensate for the impaired insulin-stimulated GLUT4 translocation, resulting in a similar 3-O-MG uptake in bovine and porcine musculus semitendinosus. These findings may explain at least in part the impaired in vivo insulin sensitivity of adult ruminants compared with that of omnivorous monogastric animals. [ABSTRACT FROM AUTHOR]

Most researchers have studied physical and/or sexual abuse, substance use, and mental health problems separately or as a dual diagnosis, and from a theory-driven, empirical perspective. In this study, the authors examined these three phenomena together and from a phenomenological perspective. Thirty women each participated in an individual interview about living with a history of physical and/or sexual abuse, substance use, and mental health problems. Using a hermeneutic approach, a team of researchers analyzed the transcribed interview texts. They identified three themes: (a) being thrown: the cycle of abuse; (b) living life fearfully: a restricted world; and (c) helping: hearing my story. The results are significant, in that they challenge current assumptions underlying health care for women with histories of physical and/or sexual abuse, substance use, and mental health problems. [ABSTRACT FROM AUTHOR]

Most researchers have studied physical and/or sexual abuse, substance use, and mental health problems separately or as a dual diagnosis, and from a theory-driven, empirical perspective. In this study, the authors examined these three phenomena together and from a phenomenological perspective. Thirty women each participated in an individual interview about living with a history of physical and/or sexual abuse, substance use, and mental health problems. Using a hermeneutic approach, a team of researchers analyzed the transcribed interview texts. They identified three themes: (a) being thrown: the cycle of abuse; (b) living life fearfully: a restricted world; and (c) helping: hearing my story. The results are significant, in that they challenge current assumptions underlying health care for women with histories of physical and/or sexual abuse, substance use, and mental health problems. [ABSTRACT FROM AUTHOR]

Findings are presented from one site in a federal study of services for women who have co-occurring mental health and substance use problems and histories of physical or sexual abuse. Among sampled women with two or more publicly funded substance abuse or mental health treatment episodes in 1998, one-third reported co-occurring mental health and substance use problems. Compared to other sample members, these women reported greater numbers of abuse experiences and other adverse life circumstances and had more complex diagnostic and treatment histories. They also show a greater tendency to suicidal ideation and are more likely to use prescription medications. [ABSTRACT FROM AUTHOR]

Pörksen G, Lohse P, Rösen-Wolff A, Heyden S, Förster T, Wendisch J, Heubner G, von Bernuth H, Sallmann S, Gahr M, Roesler J. Periodic fever, mild arthralgias, and reversible moderate and severe organ inflammation associated with the V198M mutation in the CIAS1 gene in three German patients – expanding phenotype of CIAS1 related autoinflammatory syndrome. Eur J Haematol 2004: 73: 123–127. © Blackwell Munksgaard 2004. Dominant mutations in the CIAS1 gene cause a spectrum of autoinflammatory diseases such as familial cold autoinflammatory syndrome, FCAS, which is characterized by episodes of urticaria, arthralgia, fever and conjunctivitis after generalized exposure to cold. We here describe patients of two German families with the 592G→A, V198M mutation, which has been described to induce FCAS before. However, in our patients the clinical phenotype was very different from this disease. They never had urticaria, cold induced fever or conjunctivitis; instead the following symptoms occurred: Very regular periodic fever, irregular severe febrile episodes, relatively mild arthralgia, dry cough, cardiomyopathy, nephropathy and euthyroid thyroiditis all being reversible. We conclude that the clinical phenotype associated with mutations in the CIAS1 gene is much broader than assumed before. [ABSTRACT FROM AUTHOR]

Summary This study was an attempt to find whether the reproductive performance of cocks would be influenced by oral administration of different amounts of dietary vitamin E over a long period of time. For that purpose 60 cocks were divided into five dietary groups of 12 animals each, and supplemented with 0 (control group), 100, 1000, 10 000 or 20 000 IU α-tocopherol/kg diet, respectively, over a period of 12 months. The effect on semen parameters and biochemical parameters measured in pooled semen samples and the weight of the testes were determined. The weight of testes decreased with increasing amounts of supplemented vitamin E. Volume, pH, colour, consistency and motility were not influenced by the diets, but density of ejaculate (sperm/μ l), total amount of spermatozoa and morphology of sperm were significantly lowered by increasing amounts of supplemented vitamin E. The α-tocopherol concentration in ejaculates increased significantly in relation to the diet whereas phospholipid content and thiobarbituric acid-reactive substances (TBARS) of the semen samples decreased significantly with increasing vitamin E supplementation. The reproductive performance of cocks was negatively influenced by high doses of vitamin E although decreased TBARS indicated rising oxidative defence. [ABSTRACT FROM AUTHOR]

It had been suggested that marked species differences in glucose tolerance tests were due to differences in insulin resistance. To compare insulin responsiveness, euglycemic hyperinsulinemic clamps were carried out in sheep, ponies, miniature pigs and camels. Porcine insulin was infused as primed-continuous infusions for 2 h (6 mU·kg–1·min–1). The steady state glucose infusion rates in the pigs, sheep, ponies and camels were 96.0, 18.6, 7.1 and 6.1 µmol·kg–1·min–1, respectively. The maximal plasma insulin concentrations during the insulin infusions were 2,700 µU·ml–1 in the camels, 1,400 µU·ml–1 in the sheep and ponies and 600 µU·ml–1 in the pigs. The rate of insulin removal from plasma was lowest in the camels as compared to the sheep, ponies and pigs (0.019, 0.038, 0.035 and 0.070 min–1, respectively). In all species the concentrations of plasma non-esterified fatty acids dropped significantly 10–30 min after the start of the insulin infusion. However, the rates of non-esterified fatty acid reduction were higher in the pigs and sheep than in the camels and ponies. Results confirm a considerably higher insulin responsiveness in the pigs as compared to the sheep. The ponies and camels were found to be even more insulin-resistant than the sheep. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the influence of a fat-supplemented diet compared with a carbohydrate diet on the lipid metabolism and the enteroinsular axis of Shetland ponies. The ‘crossover’ experiment was divided into two parts: in the first 10 weeks the diets comprised the correct number of calories according to requirements and in the following 10 weeks they were hypercaloric, in order to check the effect of a different energy content of the diets. Feeding the fat-enriched diet, independently of its energy content, led to a significant decrease in plasma triglycerides, associated with a mean 50% increase of plasma lipoprotein lipase activity. After oral glucose load the ponies on fat-enriched diets showed higher plasma glucose concentrations. Oral glucose administration after feeding the hypercaloric fat-enriched diet led to a 25-fold increase of plasma insulin levels. Glucose-dependent insulinotropic polypeptide plasma levels were increased in the animals on the fat-enriched diets. The results of this study suggest that fat feeding improves triglyceride clearance. However, the fat supplementation of the diet also led to impaired glucose tolerance. These results are important for a better understanding of the function of the enteroinsular axis. To investigate the influences of fat on lipid metabolism in relation to the aetiopathogenesis of equine hyperlipaemia further studies involving diseased animals are needed. [ABSTRACT FROM AUTHOR]

Summary The effects of feeding 75 versus 750 IU vitamin A/kg body mass (BM) per day to eight healthy pony geldings were studied in a cross-over design experiment for 20 weeks. The vitamin E intake was 2 mg/kg BM per day. α-tocopherol and retinoid distribution was examined in serum and lipoproteins. No effect was seen on retinol, α-tocopherol, cholesterol, triglycerides, phospholipids and protein. The α-tocopherol was distributed between high-density lipoprotein (69%), low-density lipoprotein (LDL; 22%) and very-low-density lipoprotein (VLDL; 9%). A retinol dose response (RDR)-test was carried out in both experimental groups to analyse the vitamin A status. The RDR-test indicated in some cases a false insufficient supply in spite of increased dietary vitamin A. However increased retinyl ester concentrations were found in serum and lipoproteins. Therefore concentrations of retinyl esters seems to be an excellent indicator for the vitamin A status of ponies. In lipoproteins, retinyl ester were measurable in VLDL and LDL. The main ester was retinyl stearate followed by retinyl palmitate. Data suggest that feeding increased concentration of vitamin A did not influence the serum vitamin E status and lipid parameters in ponies, but increased the retinyl esters in serum, VLDL and LDL. [ABSTRACT FROM AUTHOR]

SummaryVitamin E deficiency and linoleic acid-feeding lead to nutritional encephalomalacia (NE) in chicks, affecting the cerebellum exclusively. The relevance of lipid peroxidation (LPO) products to the pathogenesis of the disease was studied. Laying hens received a diet low in vitamin E. Resulting chicks were assigned to four groups fed either with linoleic (C18: 2n-6) or linolenic (C18: 3n-3) acid together with 1 or 50 p.p.m. vitamin E. Nine days post-hatching NE occurred in the vitamin E-deficient group fed linoleic acid. With each chick showing NE, a healthy one from all four groups was killed. Unsaturated aldehydes were determined in plasma, liver, cerebrum and cerebellum. Results underlined that the type of dietary fat is decisive for the aldehyde pattern. In the liver of linoleic acid-fed animals total aldehydes were increased. Diseased animals had increased aldehydes stemming from n-3 fatty acids. In plasma, vitamin E deficiency led to higher malondialdehyde and OH-nonenal concentrations. In brain, neither vitamin E deficiency nor NE were accompanied by increased aldehyde concentrations. In consequence a direct role of unsaturated aldehydes for the development of NE in the cerebellum is not probable. [ABSTRACT FROM AUTHOR]

A novel complex TpMe,PhFe(SCH2CH2NH2) has been synthesized as a speculative model for ADO. Indeed its reaction with O2 led to the dioxygenation of the S atom and thus to hypotaurine. This finding may allow us to draw conclusions on the constitution of the ADO active site, whose structure is still unknown. [ABSTRACT FROM AUTHOR]

Abstract: Bradykinin, a mediator of inflammation, is produced in the brain during trauma and stroke. It is thought to open the blood-brain barrier, although the mechanism is unclear. We have investigated, therefore, the effect of bradykinin on the expression of interleukin-6 (IL-6), a putative modulator of the blood-brain barrier, in astrocytes. IL-6 gene transcription was evaluated by transient transfection of the human IL-6 promoter linked to the luciferase gene. In murine astrocytes, bradykinin stimulated IL-6 secretion and gene transcription. The effect of bradykinin was blocked by KN-93, an inhibitor of Ca2+/calmodulin-dependent protein kinases, and by bisindolyl-maleimide I, an inhibitor of protein kinase C, suggesting the involvement of these protein kinases. Mutations in the multiple response element and the binding site for nuclear factor-κB (NF-κB), but not in other known elements of the IL-6 promoter, interfered with induction of IL-6 transcription. The involvement of NF-κB was supported further by the binding that overexpression of nmIκBα, a stable inhibitor of NF-κB, inhibited the induction of IL-6 by bradykinin. Bradykinin activated NF-κB in primary astrocytes as shown by increased DNA binding of NF-κB. These data demonstrate that bradykinin stimulates IL-6 expression through activation of NF-κB, which may explain several inflammatory effects of bradykinin. [ABSTRACT FROM AUTHOR]

Various nutritional peculiarities including important features of protein and carbohydrate as well as fat metabolism are well known in cats (Rogers and Morris 1991). In this study, we investigated whether dietary changes have the same effect on plasma parameters of lipid metabolism in cats as in other species. For this purpose, triglycerides (TGL)3, cholesterol (CHOL), β-hydroxybutyrate (βHB) and free fatty acids (FFA) were determined after feeding different test meals. Materials and methods. Nine adult healthy European short-haired cats were available for this investigation. They were fed either a commercial canned cat food (COM) or one of three tuna-based test diets with goose fat, glucose or without addition (FAT, GLUC, PROT, Table 1) for 3 wk before the trial. After this period, blood samples were taken preprandially (12 h after the last meal) and 3 h after the test meal (postprandially) for determination of metabolites. For determination of β-hydroxybutyrate in blood (denatured with 0.33 mol/L perchloric acid), the method of Williamson and Mellanby (1974) was used. The FFA were measured by the method of Itaya (1977), a modification of the method of Duncombe. TGL and CHOL were determined with commercial test kits (Test-combination Triglycerides GPOPAP, Boehringer, Mannheim, Germany and CHOD-PAP method, Diagnostica Merck, Darmstadt, Germany). The fatty acid patterns of the test meals were determined by gas chromatography (Klaus et al. 1995). Data are expressed as means ± SD. The influence of diet composition and sampling time were analyzed by two-way ANOVA. Means were compared by Student’s t test to determine significant differences between sampling times or by one-way ANOVA and Tukey’s test to determine significant differences between the diets. The study was approved by the Regierung of Oberbayern, which is the proper authority according to German laws on animal welfare (Tierschutzgesetz). Results. The two-way ANOVA revealed a significant influence of sampling time and diet composition for all determined plasma parameters of lipid metabolism in cats except for the effect of time on plasma CHOL. The level of TGL was influenced mainly by the time after feeding but also by diet composition (Fig. 1). As expected, the highest concentrations of TGL in plasma were found 3 h postprandially in the diets rich in fat (FAT, COM). The values of FFA ranged between 0.4 and 0.71 mmol/L (Fig. 2). Significant differences between the sampling times were seen only in group GLUC. This diet led to a decrease in plasma FFA concentration especially after feeding. The plasma CHOL (Fig. 3) was influenced only by diet composition, i.e., fat and cholesterol content in the diet as well as fatty acid pattern. The highest values were found after the high fat diets (FAT and COM, Table 2) were fed. Diets nearly free of carbohydrates led to high plasma concentrations of β-HB (FAT and PROT, Fig. 4). In conclusion the fat metabolism parameters studied are influenced in a similar way in cats as described for other species (Barth et al. 1990, Freudenthal 1990). [ABSTRACT FROM AUTHOR]

The enzymatic fundamentals of lipid metabolism of equine have not been thoroughly investigated at this point in time. It is still unclear why ponies in contrast to horses may become hyperlipaemic when coming negative energy balance. In this study, the activities of the triglyceride-cleaving key enzymes of ponies are large bred horses were investigated in order to obtain insight into the aetiology of the syndrome. The objective of the study was to measure the activities of hormone-sensitive lipase (HSL), lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) in ponies and horses in ex vivo in vitro assays. Norepinephrine (NE) stimulated pony adipocytes to release FFA in a linear fashion (4.57 ± 2.09 nmol FFA · 105 cells-1 · min-1). This was not observed in horses. Lipolysis was significantly higher in fat cells of ponies than in horses when adenosine deaminase (ADA) and NE were added (12.71 ± 3.12 vs. 1.96 ± 1.22 nmol FFA · 105 cells-1 · min-1). Relative inhibition of lipolysis by the action of insulin was comparable in adipocytes of horses and ponies. However, absolute FFA release in pony fat cells was as high as the maximal NE and ADA stimulated lipolysis in horse adipocytes. Postheparin plasma lipase activities in ponies and horses did not differ between the sub-species. This finding was supported by the results obtained from measurement of LPL activity in adipose and muscle tissue showing only a tendency of increased activities in pony explants when compared to horse tissue incubations. This study further supports the hypothesis that differences in regulation of TG release from fat stores rather than clearance of TG from plasma is causative for the development of hyperlipaemia in ponies. Abbreviations used: ADA, adenosine deaminase; BW, body weight; FFA, free fatty acid; HSL, hormone-sensitive lipase; HTGL, hepatic triglyceride lipase; LPL, lipoprotein lipase; NE,... [ABSTRACT FROM AUTHOR]

Describes a fluorometric method for the measurement of lipolytic activity in isolated adipocytes of rats and horses. Direct and continuous monitoring of free fatty acid release; Change in fluorescence intensity; Detection of decreasing hydrogen-ion concentration.

Examines the pregnancy toxaemia (Ketosis) in ewes. Clinical findings during the onset and course of the disease; Comparison of the clinical findings of the ewes with toxaemia which survives and those which died; Role of insulin in the disease.

Thirty dairy cows with left abomasal displacement (LAD) and 14 healthy control cows were studied to assess the status of the natural antioxidant vitamin E, lipid peroxidation in the liver (malondialdehyde-formation) and its relationship to hepatic lipidosis. Blood concentrations of α-tocopherol, aminotransferase, glutamin dehydrogenase, free fatty acids, β-hydroxybutyrate and glucose were determined, α-tocopherol, tryglyceride, glycogen and malondialdehyde (MDA) in wet liver tissue samples were examined. The dietary α-tocopherol intake and its plasma changes in LDA cows were also investigated. Cows were divided into four groups according to their liver triglyceride contents (< 20; 20-80; > 80 mg/g of fresh tissue; and control groups). The lowest plasma vitamin E and the highest liver vitamin E levels were found in cows with highest hepatic triglyceride content. The highest increase in plasma α-tocopherol within 5 days was seen in cows with the lowest liver triglyceride (P < 0.01). The liver triglyceride was positively correlated with liver MDA (r = 0.38; P < 0.05) and negatively with plasma α-tocopherol (r = −0.41; P < 0.01). [ABSTRACT FROM AUTHOR]

Tissue Lipid Peroxidation in Nutritional Encephalomalacia of Broiler Chickens The consequences of different dietary fats in combination with two vitamin E levels on peroxidative tissue damage of chicken brain and liver and its meaning for development of nutritional encephalomalacia (NE) were investigated. A feeding experiment was performed with 1-day-old chickens from hens on a vitamin-E-poor diet. The animals received a vitamin-E-deficient basic diet containing 10% fat, rich in either C18:3n3-, C18:2n6- or C18:1n9-fatty acids. The fat was given either fresh or oxidized (peroxidation number: 250) and 0 or 50 ppm α-tocopherylacetate was added. Typical symptoms of NE occurred mainly in those groups fed with n6-fatty acids beginning on day 7. In order to evaluate oxidative tissue damage, conjugated dienes, fluorescent pigments and TBA-reactive substances were determined in liver, cerebrum and cerebellum. Brain was examined histologically. In liver and cerebrum, the feeding of oxidized fats led to a 20% increase in conjugated dienes. Fluorescent pigments could be determined only in the brain tissues. However, feeding conditions had no effect, although autofluorescence was observed histologically in the affected animals. TBA-reactive substances were heightened in cerebrum (30%) and liver (130%) as a result of feeding linolenic acid. Vitamin E deficiency doubled TBA-reactive substances only in the liver. The parameters measured did not show intensified lipid peroxidation in the cerebellum of the animals fed the NE producing diet. Rather, the liver seems to be affected by the oxidative stress. Zusammenfassung Gegenstand dieser Studie war die Wirkung verschiedener Fettdiäten und einer abgestuften Vitamin E-Versorgung auf die peroxidative Schädigung von Gehirn- und Lebergewebe im Hinblick auf die Nutritive Enzephalomalazie (NE) des Broilers. Dazu wurde ein Fütterungsversuch mit Eintagsküken aus Vitamin E-arm ernährten Elterntieren durchgeführt. Die Küken erhielten nach dem Schlupf verschiedene Fettdiäten mit überwiegendem Anteil von n3-, n6- oder n9-Fettsäuren in 10%iger Zumischung zu einem fettfreien und Vitamin E-armen Grundfutter. Eine Hälfte der Tiere erhielt die Fette in frischer, die andere in oxidierter Form (Peroxidzahl 250). Die Vitamin E-Zulagen betrugen 0 bzw. 50 ppm α-Tocopherylacetat. Die typischen Symptome der NE traten vornehmlich in den Gruppen mit hohem Linolsäureanteil bereits ab dem 7. Lebenstag auf. Zur Abschätzung der oxidativen Schädigung wurden in Leber, Groß- und Kleinhirn konjugierte Diene, fluoreszierende Pigmente und Thiobarbitursäurereaktive Substanzen (TBArS) bei Auftreten der ersten klinischen Symptome einer NE bestimmt und die Gehirngewebe histologisch untersucht. In Leber und Großhirn führte die Gabe oxidierter Fette zu einem Anstieg der konjugierten Diene um ca. 20%. Fluoreszierende Pigmente konnten nur in den Gehirngeweben bestimmt werden. Es ergaben sich hierbei keine fütterungsbedingten Veränderungen, obwohl bei den erkrankten Tieren histologisch Autofluoreszens zu beobachten war. Eine Erhöhung der TBArS wurde in Großhirn (um 30%) und Leber (um 130%) bei Linolensäure-reicher im Vergleich zu Linolsäure-reicher Fütterung registriert. Nur in der Leber nahmen bei Vitamin E-Zulage die TBArS um die Hälfte ab. In der vorliegenden Studie konnte im Kleinhirn zwischen den gewählten Parametern und dem Auftreten der Enzephalomalazie kein Zusammenhang hergestellt werden. Vielmehr scheint vor allem die Leber von der oxidativen Belastung betroffen zu sein. [ABSTRACT FROM AUTHOR]

Responses to twice daily milk feeding, total parenteral nutrition (TPN) and fasting (saline infusion) were studied for 24 h in 1-week-old calves. Following milk intake glucose (G) and insulin (I) concentrations increased, whereas free fatty acid (FFA) and triglyceride (TG) levels and glutamate oxalacetatate transaminase (GOT) and gamma-glutamyl transferase (GGT) activities decreased, while heart rate, respiration rate, rectal temperature, white blood cell number (WBC), serum iron (SFe), total protein (TP), albumin, aminoacids, urea, cholesterol, sodium (Na), potassium (K), calcium (Ca), inorganic phosphorus (Pin), insulin-like growth factor I (IGF-I), growth hormone (GH), cortisol and 3, 5, 3′-triiodothyronine (T3) concentrations and alkaline phosphatase (AP) activity did not change significantly. During saline infusion, Ca, G, TG, PL, I, IGF-I and T3 concentrations and AP and GGT activities decreased, while Na, FFA and urea concentrations increased. In response to TPN, G, urea, Na, tryptophane and I concentrations increased, while SFe, Ca, Pin, TG, FFA, serine, phospholipids (PL), cholesterol and T3 concentrations and AP, GOT and GGT activities decreased. Typical metabolic and endocrine changes were thus seen in response to milk intake and fasting. Changes during TPN remained within physiological limits. [ABSTRACT FROM AUTHOR]