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  • 1
    Online Resource
    Online Resource
    Oxytocin Treatment during Early Life Influences Reproductive Performance in ad libitum Fed and Food-Restricted Female Rats
    S. Karger AG ; 2002
    In:  Neonatology Vol. 81, No. 2 ( 2002), p. 132-138
    Details
    In: Neonatology, S. Karger AG, Vol. 81, No. 2 ( 2002), p. 132-138
    Abstract: Oxytocin treatment may permanently alter endocrine axes resulting in anti-stress and anabolic effects. However, the nutritional status influences the effects of oxytocin. The specific aims of this study were to investigate the effects of postnatal oxytocin treatment on reproductive performance in adult life, by studying maternal weight gain, adiposity, plasma levels of IGF-I as well as fetal and placental weights in the following groups of animals: (1) Ad libitum fed dams coming from ad libitum fed mothers. (2) Ad libitum fed dams coming from food-restricted mothers. (3) Food-restricted dams coming from ad libitum fed mothers. (4) Food-restricted dams coming from food-restricted mothers. Oxytocin treatment postnatally had long-term effects and increased adiposity in pregnant dams and stimulated placental and fetal growth relative to saline-treated dams. However, if the dams themselves had been exposed to food restriction during fetal life, the effect of postnatal oxytocin treatment changed. The oxytocin-treated mothers were still fatter but had smaller fetuses. In conclusion, postnatal oxytocin treatment influences reproductive performance in later life but is dependent on the mother’s previous and current nutritional experience.
    Type of Medium: Online Resource
    ISSN: 1661-7800 , 1661-7819
    URL: Article
    DOI: 10.1159/000047198
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2002
    detail.hit.zdb_id: 2403535-X
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  • 2
    Online Resource
    Online Resource
    Evaluation of Genetic Association and Expression Reduction of TRPC1 in the Development of Diabetic Nephropathy
    S. Karger AG ; 2009
    In:  American Journal of Nephrology Vol. 29, No. 3 ( 2009), p. 244-251
    Details
    In: American Journal of Nephrology, S. Karger AG, Vol. 29, No. 3 ( 2009), p. 244-251
    Abstract: 〈 i 〉 Background/Aims: 〈 /i 〉 The TRPC1 gene on chromosome 3q22–24 resides within the linkage region for diabetic nephropathy (DN) in type 1 (T1D) and type 2 diabetes mellitus (T2D). A recent study has demonstrated that TRPC1 expression is reduced in the kidney of diabetic ZDF- and STZ-treated rats. The present study aimed to evaluate the genetic and functional role of TRPC1 in the development of DN. 〈 i 〉 Methods: 〈 /i 〉 Genetic association study was performed with two independent cohorts, including 1,177 T1D European Americans with or without DN from GoKinD population and 850 African-American subjects with T2D-associated end-stage renal disease (ESRD), or with hypertensive (non-diabetic) ESRD, and nondiabetic controls. Seven tag SNP markers derived from HapMap data (phase II) were genotyped. TRPC1 gene expression was examined using real time RT-PCR. 〈 i 〉 Results: 〈 /i 〉 No significant association of TRPC1 DNA polymorphisms with DN or ERSD was found in GoKinD and African-American populations. TRPC1 gene mRNA expression in kidney was found to be trendily reduced in 12-week and significantly in 26-week-old db/db mice. 〈 i 〉 Conclusions: 〈 /i 〉 TRPC1 genetic polymorphism may not fundamentally contribute to the development of DN, while reduction of the gene expression in kidney may be a late phenomenon of DN as seen in diabetic animal models.
    Type of Medium: Online Resource
    ISSN: 0250-8095 , 1421-9670
    URL: Article
    DOI: 10.1159/000157627
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2009
    detail.hit.zdb_id: 1468523-1
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  • 3
    Online Resource
    Online Resource
    Genetic and Functional Effects of Membrane Metalloendopeptidase on Diabetic Nephropathy Development
    S. Karger AG ; 2011
    In:  American Journal of Nephrology Vol. 34, No. 5 ( 2011), p. 483-490
    Details
    In: American Journal of Nephrology, S. Karger AG, Vol. 34, No. 5 ( 2011), p. 483-490
    Abstract: 〈 i 〉 Background/Aims: 〈 /i 〉 Vasopeptidase as an agent inhibits membrane metalloendopeptidase (MME, also known as neutral endopeptidase). MME is widely distributed in the body and particularly abundant in the kidney. The 〈 i 〉 MME 〈 /i 〉 gene is located on chromosome 3q25.1 within a linkage region for diabetic nephropathy (DN). The present study aims to evaluate the genetic and functional effects of MME in the development of DN. 〈 i 〉 Methods: 〈 /i 〉 A case-control genetic study of the 〈 i 〉 MME 〈 /i 〉 gene in type 1 diabetes (T1D) patients with and without DN (n = 578/599) was performed. All subjects were selected from the Genetics of Kidneys in Diabetes study. Genotyping was performed with TagMan allelic discrimination. 〈 i 〉 Mme 〈 /i 〉 mRNA and protein expression levels in kidney tissues of db/db mice at the ages of 5, 12 and 26 weeks were analyzed with TaqMan real-time RT-PCR and Western blot. 〈 i 〉 Results: 〈 /i 〉 The haplotype A-C constructed with single nucleotide polymorphisms (SNPs) rs3796268A/G and rs3773885C/T in the 〈 i 〉 MME 〈 /i 〉 gene was found to be associated with DN (p = 0.015, OR = 1.33, 95% CI 1.05–1.68) in female T1D patients. Further analyses of renal traits in T1D patients with DN and end-stage renal disease according to the genotypes of SNP rs3773885 indicated that the C allele carriers had higher serum creatinine levels compared to the subjects carrying T allele in both females and males. 〈 i 〉 Mme 〈 /i 〉 expression at mRNA and protein levels was upregulated in kidneys of db/db mice at the ages of 12 and 26 weeks (p = 0.017 and 〈 0.001) but not at the age of 5 weeks compared to the controls. 〈 i 〉 Conclusions: 〈 /i 〉 The present study provides the first evidence that 〈 i 〉 MME 〈 /i 〉 has genetic and biological effects on the development of DN, and suggests that the inhibition of 〈 i 〉 MME 〈 /i 〉 expression in the kidney with the agent of vasopeptidase may be a useful therapeutic approach for this disease.
    Type of Medium: Online Resource
    ISSN: 0250-8095 , 1421-9670
    URL: Article
    DOI: 10.1159/000333006
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2011
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  • 4
    Online Resource
    Online Resource
    Genetic and Biological Effects of Sodium-Chloride Cotransporter (〈b〉〈i〉SLC12A3〈/i〉〈/b〉) in Diabetic Nephropathy
    S. Karger AG ; 2014
    In:  American Journal of Nephrology Vol. 40, No. 5 ( 2014), p. 408-416
    Details
    In: American Journal of Nephrology, S. Karger AG, Vol. 40, No. 5 ( 2014), p. 408-416
    Abstract: 〈 b 〉 〈 i 〉 Background/Aims: 〈 /i 〉 〈 /b 〉 Solute carrier family 12 member 3 ( 〈 i 〉 SLC12A3 〈 /i 〉 ) encodes a sodium/chloride transporter in kidneys. Previous reports suggest that Arg913Gln polymorphism in this gene is associated with diabetic nephropathy (DN), but the data appear to be inconsistent. Up to now, there is no biological evidence concerning the effects of 〈 i 〉 SLC12A3 〈 /i 〉 in DN. In this study, we aim to evaluate the genetic effects of the 〈 i 〉 SLC12A3 〈 /i 〉 gene and its Arg913Gln polymorphism with genetic and functional analyses. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 We genotyped 〈 i 〉 SLC12A3 〈 /i 〉 genetic polymorphisms including Arg913Gln in 784 non-diabetes controls and 633 type 2 diabetes (T2D) subjects with or without DN in a Malaysian population and performed a meta-analysis of the present and previous studies. We further analyzed the role of 〈 i 〉 slc12a3 〈 /i 〉 in kidney development and progress of DN in zebrafish and db/db mice. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 We found that 〈 i 〉 SLC12A3 〈 /i 〉 Arg913Gln polymorphism was associated with T2D (p = 0.028, OR = 0.772, 95% CI = 0.612-0.973) and DN (p = 0.038, OR = 0.547, 95% CI = 0.308-0.973) in the Malaysian cohort. The meta-analysis confirmed the protective effects of 〈 i 〉 SLC12A3 〈 /i 〉 913Gln allele in DN (Z-value = -1.992, p = 0.046, OR = 0.792). Furthermore, with knockdown of zebrafish ortholog, 〈 i 〉 slc12a3 〈 /i 〉 led to structural abnormality of kidney pronephric distal duct at 1-cell stage. 〈 i 〉 Slc12a3 〈 /i 〉 mRNA and protein expression levels were upregulated in kidneys of db/db mice from 6, 12, and 26 weeks at the age. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 The present study provided the first biological and further genetic evidence that 〈 i 〉 SLC12A3 〈 /i 〉 has genetic susceptibility in the development of DN, while the minor 913Gln allele in this gene confers a protective effect in the disease. i 2014 S. Karger AG, Basel
    Type of Medium: Online Resource
    ISSN: 0250-8095 , 1421-9670
    URL: Article
    DOI: 10.1159/000368916
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2014
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  • 5
    Online Resource
    Online Resource
    Endothelin-A Receptor Blockade Increases Nutritive Skin Capillary Circulation in Patients with Type 2 Diabetes and Microangiopathy
    S. Karger AG ; 2008
    In:  Journal of Vascular Research Vol. 45, No. 4 ( 2008), p. 295-302
    Details
    In: Journal of Vascular Research, S. Karger AG, Vol. 45, No. 4 ( 2008), p. 295-302
    Abstract: 〈 i 〉 Aims: 〈 /i 〉 Endothelin-1 levels are elevated in patients with type 2 diabetes mellitus and may contribute to impaired microvascular function. We investigated the effect of selective endothelin-A (ET 〈 sub 〉 A 〈 /sub 〉 ) receptor blockade (BQ123) on skin microcirculation in patients with type 2 diabetes and albuminuria. 〈 i 〉 Methods: 〈 /i 〉 Ten type 2 diabetes patients and 8 non-diabetic controls were investigated. Nutritive skin capillary circulation, investigated by videophotometric capillaroscopy, and total skin microcirculation, assessed by laser Doppler fluxmetry (LDF), were studied during intra-arterial infusion of saline for 15 min, followed by BQ123 infusion for 60 min. 〈 i 〉 Results: 〈 /i 〉 Following BQ123 infusion there was a significant increase in resting capillary blood cell velocity (CBV) in patients with type 2 diabetes from 0.24 (0.20–0.34) mm/s at baseline to 0.61 (0.46–0.88) mm/s at 60 min, but no significant change in the control subjects [0.55 (0.10–0.68) vs. 0.38 (0.13–0.88) mm/s; p 〈 0.005 for difference between groups]. Peak CBV following arterial occlusion and skin temperature increased significantly in the type 2 diabetes group but not in the control group during BQ123 infusion. There were no significant changes in LDF parameters during infusion of BQ123 in either group. 〈 i 〉 Conclusion: 〈 /i 〉 ET 〈 sub 〉 A 〈 /sub 〉 receptor blockade improves nutritive skin capillary circulation in patients with type 2 diabetes and microangiopathy.
    Type of Medium: Online Resource
    ISSN: 1018-1172 , 1423-0135
    URL: Article
    DOI: 10.1159/000113601
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2008
    detail.hit.zdb_id: 1482726-8
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