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1.
Violence Against Women ; : 10778012231220370, 2023 Dec 17.
Article in English | MEDLINE | ID: mdl-38105507

ABSTRACT

Research has long demonstrated that victim-survivors of intimate partner violence face barriers to being believed when they seek help via the legal system and are simultaneously at risk of their abuser weaponizing the legal system against them. This article draws on the experiences of 54 women victim-survivors of coercive control in Australia who had experienced legal systems abuse within criminal and civil protection order systems. Drawing on feminist legal theory, we highlight that the legal system continues to disbelieve women and validate abusers. These experiences hold implications for victim-survivor views on the merits and risks of criminalizing coercive control.

2.
J Interpers Violence ; 37(9-10): NP7958-NP7983, 2022 05.
Article in English | MEDLINE | ID: mdl-33231119

ABSTRACT

Domestic and family violence (DFV) disproportionately affects women and children in Australia and globally. On average, one in three women experiences DFV during adulthood and the majority of these women identify as mothers. The prevalence of DFV is higher for Indigenous women and their experiences disproportionately range at the more severe end of physical abuse. For women affected by DFV, mothering during and post this type of victimization is complicated by strategic entrapment, undermining of the mother-child relationship, and threats of harm directed at children and mothers. While a substantial body of literature has examined the experiences of mothers affected by DFV more broadly, research on the experiences of Indigenous mothers affected by DFV remains scarce. Research evidence is further limited when trying to understand the specific constraints experienced by mothers affected by DFV in regional settings. This article examines the experiences of Indigenous and non-Indigenous mothers affected by DFV in regional Queensland, Australia. Data derived from 17 qualitative face-to-face interviews are used to explore the lived experiences of these mothers. Findings identify the immediate and long-term effects of DFV on mothers and children, including similarities and differences in women's experiences of mothering in the context of DFV, experiences of entrapment in an abusive relationship, experiences of post-separation abuse, strategies used to mitigate its impact on children, and surviving as a female-headed single-parent household in regional settings. While mothers in this study shared a number of similar experiences, regionality, the risk of cultural disconnectedness, and socio-structural marginalization disproportionately affected Indigenous mothers in this study. Findings raise key implications for supporting mothers and children's safety and recovery, access to safe and sustainable housing in regional towns, and the empowerment of Indigenous women to overcome the lasting effects of colonization and disproportionate experiences of disadvantage.


Subject(s)
Crime Victims , Domestic Violence , Adult , Australia , Child , Female , Humans , Mother-Child Relations , Mothers
3.
J Interpers Violence ; 37(9-10): NP7369-NP7393, 2022 05.
Article in English | MEDLINE | ID: mdl-33118446

ABSTRACT

The connection between intimate partner violence (IPV) perpetration and problematic alcohol and/ or other drug (AOD) use has been well established in public health, social work and criminology research. Despite the overwhelming evidence of the correlation between these two problem behaviors, service systems addressing these issues have historically done so in siloed approaches to practice. AOD interventions have frequently been criticized for a lack of IPV focused assessment and practice. Similarly, specialist IPV interventions generally do not address clients' underlying risk factors, including problematic AOD use, through holistic intervention approaches. Suggestions to combine IPV and AOD focused interventions for men who use violence are often met with skepticism, raising questions around which sector could deliver a combined intervention approach and how different ideological standpoints in client work can and should be integrated into a combined framework. In this article, we examine the views of key stakeholders (n = 10) involved in the funding, development and/ or delivery of different service responses to men who use IPV in an Australian jurisdiction. Drawing on qualitative interview and focus group data, we explore their views around combined, group-based interventions, including the perceived need for such intervention models along with sector readiness and key considerations critical in informing the combining of IPV and AOD focused perpetrator interventions. Stakeholder findings identify the need for holistic responses to perpetrators of IPV with comorbid problematic AOD use. Further, findings provide guidance for funding bodies and community service providers considering combined, group-based interventions for perpetrators of IPV with comorbid problematic AOD use.


Subject(s)
Intimate Partner Violence , Substance-Related Disorders , Australia , Humans , Male , Risk Factors , Substance-Related Disorders/epidemiology , Substance-Related Disorders/therapy , Violence
4.
J Res Nurs ; 26(5): 427-438, 2021 Aug.
Article in English | MEDLINE | ID: mdl-35251272

ABSTRACT

BACKGROUND: Integrative reviews within healthcare promote a holistic understanding of the research topic. Structure and a comprehensive approach within reviews are important to ensure the reliability in their findings. AIM: This paper aims to provide a framework for novice nursing researchers undertaking integrative reviews. DISCUSSION: Established methods to form a research question, search literature, extract data, critically appraise extracted data and analyse review findings are discussed and exemplified using the authors' own review as a comprehensive and reliable approach for the novice nursing researcher undertaking an integrative literature review. CONCLUSION: Providing a comprehensive audit trail that details how an integrative literature review has been conducted increases and ensures the results are reproducible. The use of established tools to structure the various components of an integrative review increases robustness and readers' confidence in the review findings. IMPLICATIONS FOR PRACTICE: Novice nursing researchers may increase the reliability of their results by employing a framework to guide them through the process of conducting an integrative review.

5.
Emerg Nurse ; 28(4): 18-23, 2020 Jul 13.
Article in English | MEDLINE | ID: mdl-32452172

ABSTRACT

The first article in this two-part series evaluated healthcare professionals' approaches to the care of women who present to the emergency department (ED) with injuries related to intimate partner violence (IPV). It identified barriers to appropriate care provision, which included a lack of knowledge on the part of healthcare professionals and negative professional attitudes. This second article details the findings of a literature review of three databases that aimed to evaluate strategies to address the lack of knowledge of healthcare professionals and negative attitudes concerning IPV. A total of 11 articles were included in the review. Two main strategies to address ED healthcare professionals' knowledge deficits and negative attitudes about IPV were identified. These were developed into the themes of IPV/domestic violence specialists, and education and training.


Subject(s)
Attitude of Health Personnel , Emergency Service, Hospital , Health Knowledge, Attitudes, Practice , Intimate Partner Violence , Adult , Female , Humans
6.
Emerg Nurse ; 27(6): 19-25, 2019 Nov 05.
Article in English | MEDLINE | ID: mdl-31549493

ABSTRACT

This integrative review is the first of a two-part series about intimate partner violence (IPV). Part 2 will explore strategies to address barriers to the care of women who experience IPV in the emergency department (ED). IPV has become a major concern globally and specifically in Australia. Healthcare professionals in the ED are often the first point of contact for women experiencing IPV and therefore the provision of a comprehensive healthcare response to these vulnerable patients remains a priority. The review evaluated healthcare professionals' approaches to the care of women who present to the ED with injuries related to IPV. A systematic search of studies was undertaken using four databases. After the selection process, a total of 24 articles was identified. Six themes emerged: IPV care protocols, physical care provision, psychosocial care provision, provision of safety, role of referrals and barriers to appropriate care provision. There is a lack of evidence supporting healthcare approaches in the ED to address IPV. ED healthcare professionals experience numerous barriers that hinder their ability to provide patient-centred care, which suggests that patients presenting with IPV-related concerns may not be receiving adequate or appropriate healthcare in ED settings.

7.
Emerg Nurse ; 27(6): 19-25, 2019 Nov 05.
Article in English | MEDLINE | ID: mdl-32339451

ABSTRACT

This integrative review is the first of a two-part series about intimate partner violence (IPV). Part 2 will explore strategies to address barriers to the care of women who experience IPV in the emergency department (ED). IPV has become a major concern globally and specifically in Australia. Healthcare professionals in the ED are often the first point of contact for women experiencing IPV and therefore the provision of a comprehensive healthcare response to these vulnerable patients remains a priority. The review evaluated healthcare professionals' approaches to the care of women who present to the ED with injuries related to IPV. A systematic search of studies was undertaken using four databases. After the selection process, a total of 24 articles was identified. Six themes emerged: IPV care protocols, physical care provision, psychosocial care provision, provision of safety, role of referrals and barriers to appropriate care provision. There is a lack of evidence supporting healthcare approaches in the ED to address IPV. ED healthcare professionals experience numerous barriers that hinder their ability to provide patient-centred care, which suggests that patients presenting with IPV-related concerns may not be receiving adequate or appropriate healthcare in ED settings.


Subject(s)
Intimate Partner Violence , Nursing Assessment , Women's Health Services , Wounds and Injuries/therapy , Emergency Nursing , Emergency Service, Hospital , Female , Humans , Surveys and Questionnaires , Wounds and Injuries/nursing
8.
BMJ Case Rep ; 20182018 Sep 23.
Article in English | MEDLINE | ID: mdl-30249732

ABSTRACT

A 25-year-old man presented to the trauma department following a penetrating stab wound to his left infraorbital margin with retained knife blade causing superoposterior displacement of the globe. Plain skull X-ray revealed an extensive retained blade with subsequent CT imaging revealing the tip of the blade had reached the right styloid process with no neurovascular compromise. Initial concern was primarily for the left eye leading to ophthalmology being the first specialty requested to review the patient. However, once the extent of the injury was established, ophthalmology requested further review from maxillofacial, ENT and neurosurgery. This resulted in an 84 hours wait between the initial injury and the removal of the knife blade. Incredibly, the patient had no initial sequelae from such an extensive injury and had an unremarkable recovery with no further complications aside from a laceration to the left inferior rectus muscle that was conservatively managed.


Subject(s)
Foreign Bodies/diagnosis , Head Injuries, Penetrating/diagnosis , Wounds, Stab/diagnosis , Adult , Foreign Bodies/therapy , Head Injuries, Penetrating/therapy , Humans , Male , Uncertainty , Wounds, Stab/therapy
9.
Glob Public Health ; 11(1-2): 198-210, 2016.
Article in English | MEDLINE | ID: mdl-26110781

ABSTRACT

Intimate partner violence (IPV) has a detrimental impact on women and children's emotional, physical and social well-being and has been identified as one of the most common contributors to women's experiences of housing instabilities and homelessness. Women affected by IPV often experience a great level of uncertainty around housing solutions when trying to leave an abusive partner. This study explores women's responses to IPV and the related risk of homelessness through women's narratives (n = 22) in Queensland, Australia. Of particular interest are women's decisions and actions to minimise the impact of IPV as well as homelessness on their and their children's safety and well-being. Findings reveal that women's agency in relation to harm minimisation can take various forms, including the decision to stay with, leave or return to an abusive partner. The data offer insights into women's strategic attempts to manage IPV and the related risk of homeless while trying to minimise the harm associated with one and the other. Implications for understanding women's agency in managing IPV and the related risk of homelessness and providing adequate support mechanisms to improve women and children's social, emotional and physical well-being are discussed.


Subject(s)
Child Welfare/economics , Housing/economics , Ill-Housed Persons , Intimate Partner Violence/economics , Safety/economics , Women's Rights/economics , Adolescent , Adult , Child , Female , Harm Reduction , Housing/classification , Humans , Interviews as Topic , Intimate Partner Violence/prevention & control , Intimate Partner Violence/psychology , Mother-Child Relations , Queensland , Time Factors , Women's Rights/standards , Young Adult
10.
Mech Dev ; 133: 105-16, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24859129

ABSTRACT

Organs are characterized by a specific shape that is often remodeled during development. The dynamics of organ shape is in particular evident during the formation of the Drosophila nervous system. During embryonic stages the central nervous system compacts, whereas selective growth occurs during larval stages. The nervous system is covered by a layer of surface glial cells that form the blood brain barrier and a thick extracellular matrix called neural lamella. The size of the neural lamella is dynamically adjusted to the growing nervous system and we show here that perineurial glial cells secrete proteases to remodel this matrix. Moreover, an imbalance in proteolytic activity results in an abnormal shape of the nervous system. To identify further components controlling nervous system shape we performed an RNAi based screen and identified the gene nolo, which encodes an ADAMTS-like protein. We generated loss of function alleles and demonstrate a requirement in glial cells. Mutant nolo larvae, however, do not show an abnormal nervous system shape. The only predicted off-target of the nolo(dsRNA) is Oatp30B, which encodes an organic anion transporting protein characterized by an extracellular protease inhibitor domain. Loss of function mutants were generated and double mutant analyses demonstrate a genetic interaction between nolo and Oatp30B which prevented the generation of maternal zygotic mutant larvae.


Subject(s)
Drosophila melanogaster/growth & development , Drosophila melanogaster/genetics , Nervous System/growth & development , Neuroglia/cytology , ADAM Proteins/genetics , ADAM Proteins/metabolism , Animals , Animals, Genetically Modified , Drosophila Proteins/genetics , Drosophila Proteins/metabolism , Drosophila melanogaster/metabolism , Extracellular Matrix/metabolism , Genes, Insect , Integrins/genetics , Integrins/metabolism , Larva/cytology , Larva/growth & development , Larva/metabolism , Mutation , Nervous System/cytology , Nervous System/metabolism , Neuroglia/metabolism , Organic Anion Transporters/genetics , Organic Anion Transporters/metabolism , RNA Interference
11.
J Interpers Violence ; 28(3): 577-601, 2013 Feb.
Article in English | MEDLINE | ID: mdl-22946106

ABSTRACT

Given the far-reaching social, personal, and economic costs of crime and violence, as well as the lasting health effects, understanding how women respond to domestic violence and the types of help sought are critical in addressing intimate partner violence. We use a nationally representative dataset (Canadian General Social Survey, Personal Risk, 1999) to examine the help-seeking behaviors of female intimate partner violence victims (N = 250). Although victims of violent crime often do not call the police, many victims, particularly women who have been battered by their partner rely on family, friends, social service, and mental health interventions in dealing with the consequences of violent crime. We examine the role of income, education, and employment status in shaping women's decisions to seek help, and we treat these economic variables as symbolic and relative statuses as compared to male partners. Although family violence researchers have conceptualized the association between economic variables and the dynamics of intimate partner violence with respect to the structural dimensions of sociodemographic factors, feminist researchers connect economic power to family dynamics. Drawing on these literatures, we tap the power in marital and cohabiting relationships, rather than treating these variables as simply socioeconomic resources. Controlling for other relevant variables we estimate a series of multivariate models to examine the relationship between status compatibilities and help-seeking from both formal and informal sources. We find that status incompatibilities between partners that favor women increase the likelihood of seeking support in dealing with the impact of violence.


Subject(s)
Battered Women/statistics & numerical data , Crime Victims/statistics & numerical data , Patient Acceptance of Health Care/statistics & numerical data , Spouse Abuse/statistics & numerical data , Women's Health , Adult , Attitude to Health , Battered Women/psychology , Canada/epidemiology , Crime Victims/psychology , Female , Humans , Male , Middle Aged , Patient Acceptance of Health Care/psychology , Self Disclosure , Social Environment , Socioeconomic Factors , Spouse Abuse/prevention & control , Spouse Abuse/psychology , Young Adult
12.
Respir Res ; 12: 31, 2011 Mar 18.
Article in English | MEDLINE | ID: mdl-21418564

ABSTRACT

The role of vitamin D (VitD) in calcium and bone homeostasis is well described. In the last years, it has been recognized that in addition to this classical function, VitD modulates a variety of processes and regulatory systems including host defense, inflammation, immunity, and repair. VitD deficiency appears to be frequent in industrialized countries. Especially patients with lung diseases have often low VitD serum levels. Epidemiological data indicate that low levels of serum VitD is associated with impaired pulmonary function, increased incidence of inflammatory, infectious or neoplastic diseases. Several lung diseases, all inflammatory in nature, may be related to activities of VitD including asthma, COPD and cancer. The exact mechanisms underlying these data are unknown, however, VitD appears to impact on the function of inflammatory and structural cells, including dendritic cells, lymphocytes, monocytes, and epithelial cells. This review summarizes the knowledge on the classical and newly discovered functions of VitD, the molecular and cellular mechanism of action and the available data on the relationship between lung disease and VitD status.


Subject(s)
Asthma/metabolism , Lung Neoplasms/metabolism , Lung/metabolism , Pulmonary Disease, Chronic Obstructive/metabolism , Respiratory Tract Infections/metabolism , Vitamin D Deficiency/metabolism , Vitamin D/metabolism , Asthma/drug therapy , Asthma/epidemiology , Asthma/immunology , Bone Remodeling , Dietary Supplements , Humans , Lung/drug effects , Lung/immunology , Lung Neoplasms/drug therapy , Lung Neoplasms/epidemiology , Lung Neoplasms/immunology , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/immunology , Receptors, Calcitriol/metabolism , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/immunology , Signal Transduction , Vitamin D/therapeutic use , Vitamin D Deficiency/drug therapy , Vitamin D Deficiency/epidemiology , Vitamin D Deficiency/immunology
13.
Pharmacogenomics ; 10(10): 1599-608, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19842933

ABSTRACT

AIMS: Contradictory reports exist regarding the influence of the exon 3 deleted (d3)/full-length (fl) growth hormone receptor (GHR) polymorphism on responsiveness to recombinant human growth-hormone therapy in idiopathic short stature, small for gestational age and GH-deficient children, Turner syndrome patients and GH-deficient adults. In some of these studies, the d3 allele was associated with increased responsiveness to GH. The aim of this study was to test this association in a group of GH-deficient adult patients receiving recombinant GH treatment. MATERIALS & METHODS: Patients were derived from the prospective German Pfizer International Metabolic Study (KIMS) Pharmacogenetics Study. The GHRd3/fl polymorphism was determined in 133 German adult patients (66 men and 67 women; mean age: 45.4 years +/- 13.1 standard deviation; majority Caucasian) with a GH-deficiency of different origin. Patients received GH treatment for 12 months with a finished dose-titration of GH and standardized insulin-like growth factor (IGF)-1 measurements in one central laboratory. GH dose after 1 year of treatment, IGF-1 serum concentrations, IGF-1 standard deviation score (SDS) values and anthropometric data were analyzed by GHRd3/fl genotypes. RESULTS: After 1 year of GH treatment, the individually required GH dose was significantly lower in GH-deficient patients carrying one or two d3 alleles, compared with patients with the full-length receptor (p = 0.04). Genotype groups (d3-allele carriers vs noncarriers) showed no significant differences in IGF-1 serum concentrations (p = 0.51), IGF-1 SDS (p = 0.36) nor in gender (p = 0.53), age (p = 0.28), weight (p = 0.13), height (p = 0.53) or BMI (p = 0.15). CONCLUSION: The d3-allele carriers required approximately 25% less exogenous GH compared with the homozygous fl-allele carriers, which may express an increased responsiveness to exogenous GH. Variability of the individually required GH dose in adult GH-deficient patients may therefore be partly due to the GHRd3/fl polymorphism. Further studies are required to confirm these results.


Subject(s)
Exons/genetics , Human Growth Hormone/genetics , Human Growth Hormone/therapeutic use , Polymorphism, Genetic/genetics , Receptors, Somatotropin/genetics , Adult , Alleles , Female , Gene Frequency , Genotype , Heterozygote , Homozygote , Human Growth Hormone/deficiency , Humans , Insulin-Like Growth Factor I/metabolism , Male , Pharmacogenetics/methods , Prospective Studies , Recombinant Proteins/therapeutic use , Sequence Deletion , Time Factors
14.
Pharmacogenomics ; 10(2): 293-302, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19207031

ABSTRACT

AIMS: Several SNPs and a microsatellite cytosine-adenine repeat promoter polymorphism of the IGF-1 gene have been reported to be associated with circulating IGF-1 serum concentrations. Variance in IGF-1 concentrations due to genetic variations may affect different response to growth hormone (GH) treatment, resulting in different individually required GH-doses in GH-deficient patients. The aim of this study was to test if the IGF-1 gene polymorphisms are associated with the GH-dose of GH-deficient adults. MATERIALS & METHODS: A total of nine tagging SNPs, five additionally selected SNPs and a cytosine-adenine repeat polymorphism were determined in 133 German adult patients (66 men, 67 women; mean age 45.4 years +/- 13.1 standard deviation; majority Caucasian) with GH-deficiency (GHD) of different origin, derived from the prospective Pfizer International Metabolic Study (KIMS) Pharmacogenetics Study. Patients received GH-treatment for 12 months with finished dose-titration of GH and centralized IGF-1 measurements. GH-dose after 1 year of treatment, IGF-1 concentrations, IGF-1-standard deviation score (SDS), the IGF-1:GH ratio and anthropometric data were analyzed by genotype. RESULTS: Except for rs1019731, which showed a significant difference of IGF-1-SDS by genotypes (p = 0.02), all polymorphisms showed no associations with the GH-doses, IGF-1 concentrations, IGF-1-SDS and IGF-1:GH ratio after adjusting for the confounding variables gender, age and BMI. CONCLUSION: IGF-1 gene polymorphisms were not associated with the responsiveness to exogenous GH in GHD. Therefore, genetic variations of the IGF-1 gene seem not to be major influencing factors of the GH-IGF-axis causing variable response to exogenous GH-treatment.


Subject(s)
Human Growth Hormone/deficiency , Human Growth Hormone/therapeutic use , Insulin-Like Growth Factor I/genetics , Polymorphism, Genetic , Polymorphism, Single Nucleotide , Adult , Female , Gene Frequency , Genetic Variation , Humans , Insulin-Like Growth Factor I/metabolism , Introns , Male , Microsatellite Repeats , Middle Aged , Polymerase Chain Reaction , Promoter Regions, Genetic , Transcription, Genetic
15.
Pharmacogenomics ; 9(8): 1017-26, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18681778

ABSTRACT

OBJECTIVE: Collagen type I is a common structural protein in bone and skin. Similar to its association with the mechanical properties of the skeleton and, thus, bone-fracture risk, the collagen type I alpha (COLIA)-1 specific protein (Sp)-1 polymorphism may be related to variations in the collagen type I-containing subcutaneous tissue and its biological properties. In this study, we analyzed a possible influence of the COLIA1 Sp1 polymorphism on the effect of subcutaneously injected recombinant human growth hormone (hGH) in GH-deficient adults. MATERIALS & METHODS: We determined the COLIA1 Sp1 polymorphism in 122 adults with GH deficiency of different origin, who were derived from the prospective Pfizer International Growth Database (KIMS) Pharmacogenetics Study. Inclusion criteria were subcutaneous applied treatment with hGH for over 12 months, finished dose titration of hGH by following serum IGF-1 concentrations until desired levels were achieved, and centralized, standardized IGF-1 measurements. The genotypes (GG/GT/TT) were statistically related to clinical data from the KIMS database. RESULTS: The dose of injected hGH was significantly related to the COLIA1 Sp1 genotypes (p = 0.049), whereby the GG homozygotes were treated with a significantly higher dose of hGH than TT homozygotes (p = 0.03). Accordingly, the IGF-1:GH ratios were significantly lower in GG compared with TT homozygotes (p = 0.04). Both groups showed no significant differences in their IGF-1 serum concentrations (p = 0.98) and IGF-1 SDS (p = 0.79). CONCLUSION: The COLIA1 Sp1 polymorphism is related to the dose of individually required, subcutaneous injected hGH in GH-deficient adults, probably because of an alteration of the subcutaneous collagen type I structure, content and/or biological/biomechanical properties. GG homozygotism, which is related to a more stable bone structure and decreased fracture risk, may impact skin resistance to subcutaneous injected protein-based drugs, as shown for hGH in this study.


Subject(s)
Collagen Type I/genetics , Dwarfism, Pituitary/drug therapy , Dwarfism, Pituitary/genetics , Human Growth Hormone/physiology , Polymorphism, Genetic/genetics , Recombinant Proteins/pharmacology , Adult , Dwarfism, Pituitary/pathology , Female , Genotype , Guanine/metabolism , Homozygote , Human Growth Hormone/therapeutic use , Humans , Injections, Subcutaneous , Male , Middle Aged , Prospective Studies , Recombinant Proteins/therapeutic use
16.
J Endocrinol ; 182(1): 173-82, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15225142

ABSTRACT

G-protein-coupled receptor kinases (GRKs) are implicated in the pathophysiology of human diseases such as arterial hypertension, heart failure and rheumatoid arthritis. While G-protein-coupled receptor kinases 2 and 5 have been shown to be involved in the desensitization of the rat thyrotropin receptor (TSHR), their role in the pathophysiology of hyperfunctioning thyroid nodules (HTNs) is unknown. Therefore, we analyzed the expression pattern of the known GRKs in human thyroid tissue and investigated their function in the pathology of HTNs. The expression of different GRKs in human thyroid and HTNs was measured by Western blotting. The influence of GRK expression on TSHR function was analyzed by coexpression experiments in HEK 293 cells. We demonstrate that in addition to GRKs 2, 5 and 6, GRKs 3 and 4 are also expressed in the human thyroid. GRKs 2, 3, 5 and 6 are able to desensitize the TSHR in vitro. This GRK-induced desensitization is amplified by the additional over-expression of beta-arrestin 1 or 2. We did not find any mutations in the GRKs 2, 3 and 5 from 14 HTNs without TSHR mutations and Gsalpha mutations. The expression of GRKs 3 and 4 was increased in HTNs independently from the existence of TSHR mutations or Gsalpha mutations. In conclusion, the increased expression of GRK 3 in HTNs and the ability of GRK 3 to desensitize the TSHR in vitro, suggest a potential role for GRK 3 as a negative feedback regulator for the constitutively activated cAMP pathway in HTNs.


Subject(s)
Hyperthyroidism/metabolism , Protein Serine-Threonine Kinases/metabolism , Thyroid Nodule/metabolism , Animals , Blotting, Western/methods , Cell Line , Cyclic AMP/metabolism , G-Protein-Coupled Receptor Kinase 3 , G-Protein-Coupled Receptor Kinase 4 , Humans , Mutation , Protein Serine-Threonine Kinases/analysis , Protein Serine-Threonine Kinases/genetics , Rats , Receptors, Thyrotropin/genetics , Reverse Transcriptase Polymerase Chain Reaction , Sequence Analysis, DNA , Thyroid Gland/chemistry
17.
J Nutr ; 132(2): 197-203, 2002 Feb.
Article in English | MEDLINE | ID: mdl-11823578

ABSTRACT

Vitamin A is a well-established teratogen in all animal species. A number of case reports also suggest a teratogenic potential of vitamin A in humans. A possible teratogenic risk of dietary liver vitamin A intake, the kinetics of vitamin A and its metabolites in humans after intake of either a vitamin A supplement or a liver meal have been studied. Major differences were described for the kinetics of all-trans-retinoic acid (all-trans-RA), which occurred at much higher concentrations after supplementation than after liver consumption. Therefore, we investigated whether the intestine may be responsible for the differences in vitamin A metabolism after supplementation or liver feeding. We found that cytosolic fractions of porcine enterocytes oxidized retinol to all-trans-RA in vitro with a K(m) of 94-96 micromol/L and a V(max) of 7.9-8.6 pmol/(min x mg protein). In an in vivo approach, the portal vein and the central vein (external jugular vein) of a pig were cannulated. In two subsequent experiments, the pig was given a vitamin A supplement or liver. Plasma samples were taken from portal and central veins. Comparison of retinoid levels in these veins indicated that all-trans-RA was already formed from supplemental vitamin A in the intestine and released into the systemic circulation. Two major metabolic pathways were additionally present in the pig, leading to the formation of glucuronides of all-trans-RA and retinol itself. Our results indicate that intestinal metabolism contributes to the elevated levels of all-trans-RA in the systemic circulation after supplementation with vitamin A, but not after consumption of liver.


Subject(s)
Enterocytes/metabolism , Liver/chemistry , Retinoids/blood , Tretinoin/pharmacokinetics , Vitamin A/metabolism , Animals , Area Under Curve , Chromatography, High Pressure Liquid , Cytosol/metabolism , Dietary Supplements , Enterocytes/ultrastructure , Intestinal Absorption , Jugular Veins , Microsomes/metabolism , Models, Animal , Oxidation-Reduction , Portal Vein , Swine , Tretinoin/blood , Vitamin A/administration & dosage
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