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  • 1
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    Maternal Diet During Gestation and Lactation Modifies the Severity of Salt-Induced Hypertension and Renal Injury in Dahl Salt-Sensitive Rats
    Ovid Technologies (Wolters Kluwer Health) ; 2015
    In:  Hypertension Vol. 65, No. 2 ( 2015-02), p. 447-455
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 65, No. 2 ( 2015-02), p. 447-455
    Abstract: Environmental exposure of parents or early in life may affect disease development in adults. We found that hypertension and renal injury induced by a high-salt diet were substantially attenuated in Dahl SS/JrHsdMcwiCrl (SS/Crl) rats that had been maintained for many generations on the grain-based 5L2F diet compared with SS/JrHsdMcwi rats (SS/Mcw) maintained on the casein-based AIN-76A diet (mean arterial pressure, 116±9 versus 154±25 mm Hg; urinary albumin excretion, 23±12 versus 170±80 mg/d). RNAseq analysis of the renal outer medulla identified 129 and 82 genes responding to a high-salt diet uniquely in SS/Mcw and SS/Crl rats, respectively, along with minor genetic differences between the SS substrains. The 129 genes responding to salt in the SS/Mcw strain included numerous genes with homologs associated with hypertension, cardiovascular disease, or renal disease in human. To narrow the critical window of exposure, we performed embryo-transfer experiments in which single-cell embryos from 1 colony (SS/Mcw or SS/Crl) were transferred to surrogate mothers from the other colony, with parents and surrogate mothers maintained on their respective original diet. All offspring were fed the AIN-76A diet after weaning. Salt-induced hypertension and renal injury were substantially exacerbated in rats developed from SS/Crl embryos transferred to SS/Mcw surrogate mothers. Conversely, salt-induced hypertension and renal injury were significantly attenuated in rats developed from SS/Mcw embryos transferred to SS/Crl surrogate mothers. Together, the data suggest that maternal diet during the gestational–lactational period has substantial effects on the development of salt-induced hypertension and renal injury in adult SS rats.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/HYPERTENSIONAHA.114.04179
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2015
    detail.hit.zdb_id: 2094210-2
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  • 2
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    Abstract P136: Dietary Salt and Non-Salt Components Have Substantial Effects on Genome-Wide DNA Methylation Patterns in Dahl SS Rats
    Ovid Technologies (Wolters Kluwer Health) ; 2016
    In:  Hypertension Vol. 68, No. suppl_1 ( 2016-09)
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 68, No. suppl_1 ( 2016-09)
    Abstract: Epigenetic modifications of the genome play a key role in the regulation of gene expression. It has been reported that epigenetic modifications of several genes are associated with hypertension. To investigate the potential role of genome-wide changes in DNA methylation in salt-induced hypertension, experiments were performed on inbred Dahl SS rats obtained from two colonies maintained at the Medical College of Wisconsin (i.e. MCWSS) and Charles River Laboratory (CRLSS). The colonies are genetically identical, but CRLSS rats were maintained on a whole grain diet containing 1% NaCl (CRLSS_LS) while MCWSS rats were fed casein-based AIN-76A chow containing 0.4% NaCl (MCWSS_LS) until both colonies were switched to an AIN-76A chow containing 4% NaCl for 14 days starting at 6 weeks of age (CRLSS_HS and MCWSS_HS, respectively). Mean arterial pressure and albumin excretion rate in MCWSS_HS rats were significantly greater (142±14 mmHg and 100±16 mg/day, n=6) than in CRLSS_HS rats (118±2 mmHg and 20±2 mg/day, n=7). Reduced representation bisulfite genome sequencing (RRBS) measured 5-Methylcytosine levels at single-base resolution in the renal outer medulla in the above groups, each with four biological replicates. For genomic regions located within CpG islands (CGI’s) and exhibiting differential methylation between LS and HS in each colony, HS diet increased median methylation levels several-fold in both MCWSS (7.45% vs. 0.35% for MCWSS_HS vs. MCWSS_LS, respectively, p = 2.84E-31) and CRLSS rats (7.62% vs. 1.21% for CRLSS_HS vs. CRLSS_LS, respectively, p = 1.65E-32). For genomic regions exhibiting differential methylation between MCWSS and CRLSS, MCWSS_HS rats (which exhibited higher blood pressure) had higher median methylation levels than CRLSS_HS rats (7.56% vs. 2.75%, p = 2.12E-9). We observed 156 hypermethylated and 241 hypomethylated regions within CGI’s of MCWSS_LS compared to CRLSS_LS. Examples of differentially methylated genes include the serine protease Prss2 , the transcription factor E2f1 , and the matrix protein Spock2 . These results suggest that sodium-dependent and independent dietary components could induce changes in DNA methylation that may predispose and participate in the development of hypertension and renal damage.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/hyp.68.suppl_1.p136
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2016
    detail.hit.zdb_id: 2094210-2
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  • 3
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    Effects of long-term vasopressin receptor stimulation on medullary blood flow and arterial pressure
    American Physiological Society ; 1998
    In:  American Journal of Physiology-Regulatory, Integrative and Comparative Physiology Vol. 275, No. 5 ( 1998-11-01), p. R1420-R1424
    Details
    In: American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, American Physiological Society, Vol. 275, No. 5 ( 1998-11-01), p. R1420-R1424
    Abstract: Studies were carried out using instrumented unanesthetized rats to determine the long-term effects of arginine vasopressin (AVP) and a specific vasopressin V 1 receptor agonist (V 1 AG; [Phe 2 , Ile 3 , Orn 8 ]- vasopressin) on the renal medullary blood flow and arterial blood pressure. It was hypothesized that the hypertension observed with chronic medullary infusion of a V 1 receptor agonist may be associated with a sustained reduction of blood flow, whereas infusion of AVP may fail to produce a sustained reduction of blood flow and thereby be unable to produce hypertension. Uninephrectomized Sprague-Dawley rats were prepared with implanted renal cortical and medullary optical fibers for daily measurements of cortical and medullary blood flow using laser-Doppler flowmetry techniques. An implanted renal medullary interstitial infusion catheter delivered either AVP or a specific V 1 AG at a dose of 2 ng ⋅ kg −1 ⋅ min −1 over a period of 5 days. The V 1 AG produced no change of cortical blood flow but a chronic 35% reduction of medullary blood flow ( P 〈 0.05) and mild hypertension (11 ± 4 mmHg, P 〈 0.05). AVP produced only an initial, nonsignificant 1- to 2-day reduction of medullary blood flow (−13%) and failed to raise arterial pressure significantly. We conclude that a sustained V 1 AG response is necessary to achieve a chronic reduction of medullary blood flow and hypertension. The present data are consistent with the idea that chronic stimulation of V 2 receptors by AVP offsets the vasoconstrictor and hypertension actions of AVP-induced stimulation of medullary V 1 receptors.
    Type of Medium: Online Resource
    ISSN: 0363-6119 , 1522-1490
    URL: Article
    DOI: 10.1152/ajpregu.1998.275.5.R1420
    Language: English
    Publisher: American Physiological Society
    Publication Date: 1998
    detail.hit.zdb_id: 1477297-8
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  • 4
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    Effects of daily sodium intake and ANG II on cortical and medullary renal blood flow in conscious rats
    American Physiological Society ; 1998
    In:  American Journal of Physiology-Regulatory, Integrative and Comparative Physiology Vol. 274, No. 5 ( 1998-05-01), p. R1317-R1323
    Details
    In: American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, American Physiological Society, Vol. 274, No. 5 ( 1998-05-01), p. R1317-R1323
    Abstract: Implanted optical fibers and laser-Doppler flow measurement techniques were used for the sequential measurement of regional renal blood flow in conscious rats to determine the effects of an increase of daily NaCl intake on the renal cortical blood flow and blood flow to the outer and inner medulla. Cortical blood flow was increased significantly (32%) by the second day when NaCl intake was increased from 1 to 7 meq/day and was increased further (50%) on the second day after a further elevation of NaCl intake to 13 meq/day. Blood flow to the outer and inner medulla was not changed as NaCl intake was elevated. The increase in renal cortical flow was closely associated with significant reductions in circulating concentrations of ANG II from 31 to 16 pg/ml. Rats given a continuous infusion of nonpressor doses of ANG II (5.0 ng ⋅ kg −1 ⋅ min −1 ) to maintain constant plasma concentrations of ANG II as sodium intake was increased exhibited no increase of cortical flow. We conclude that reductions of plasma ANG II associated with incremental increases of daily sodium intake result in a rise of renal cortical flow. The elevated blood flow to the renal cortex may enhance sodium excretion and contribute to long-term sodium homeostasis.
    Type of Medium: Online Resource
    ISSN: 0363-6119 , 1522-1490
    URL: Article
    DOI: 10.1152/ajpregu.1998.274.5.R1317
    Language: English
    Publisher: American Physiological Society
    Publication Date: 1998
    detail.hit.zdb_id: 1477297-8
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  • 5
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    Unstable TTTTA/TTTCA expansions in MARCH6 are associated with Familial Adult Myoclonic Epilepsy type 3
    Springer Science and Business Media LLC ; 2019
    In:  Nature Communications Vol. 10, No. 1 ( 2019-10-29)
    Details
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2019-10-29)
    Abstract: Familial Adult Myoclonic Epilepsy (FAME) is a genetically heterogeneous disorder characterized by cortical tremor and seizures. Intronic TTTTA/TTTCA repeat expansions in SAMD12 (FAME1) are the main cause of FAME in Asia. Using genome sequencing and repeat-primed PCR, we identify another site of this repeat expansion, in MARCH6 (FAME3) in four European families. Analysis of single DNA molecules with nanopore sequencing and molecular combing show that expansions range from 3.3 to 14 kb on average. However, we observe considerable variability in expansion length and structure, supporting the existence of multiple expansion configurations in blood cells and fibroblasts of the same individual. Moreover, the largest expansions are associated with micro-rearrangements occurring near the expansion in 20% of cells. This study provides further evidence that FAME is caused by intronic TTTTA/TTTCA expansions in distinct genes and reveals that expansions exhibit an unexpectedly high somatic instability that can ultimately result in genomic rearrangements.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    URL: Article
    DOI: 10.1038/s41467-019-12763-9
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
    detail.hit.zdb_id: 2553671-0
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  • 6
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    Balance between macrophage migration inhibitory factor and sCD74 predicts outcome in patients with acute decompensation of cirrhosis
    Elsevier BV ; 2021
    In:  JHEP Reports Vol. 3, No. 2 ( 2021-04), p. 100221-
    Details
    In: JHEP Reports, Elsevier BV, Vol. 3, No. 2 ( 2021-04), p. 100221-
    Type of Medium: Online Resource
    ISSN: 2589-5559
    URL: Article
    DOI: 10.1016/j.jhepr.2020.100221
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 2972660-8
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  • 7
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    Renal Perfusion Pressure Determines Infiltration of Leukocytes in the Kidney of Rats With Angiotensin II–Induced Hypertension
    Ovid Technologies (Wolters Kluwer Health) ; 2020
    In:  Hypertension Vol. 76, No. 3 ( 2020-09), p. 849-858
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 76, No. 3 ( 2020-09), p. 849-858
    Abstract: The present study examined the extent to which leukocyte infiltration into the kidneys in Ang II (angiotensin II)-induced hypertension is determined by elevation of renal perfusion pressure (RPP). Male Sprague-Dawley rats were instrumented with carotid and femoral arterial catheters for continuous monitoring of blood pressure and a femoral venous catheter for infusion. An inflatable aortic occluder cuff placed between the renal arteries with computer-driven servo-controller maintained RPP to the left kidney at control levels during 7 days of intravenous Ang II (50 ng/kg per minute) or vehicle (saline) infusion. Rats were fed a 0.4% NaCl diet throughout the study. Ang II–infused rats exhibited nearly a 50 mm Hg increase of RPP (carotid catheter) to the right kidney while RPP to the left kidney (femoral catheter) was controlled at baseline pressure throughout the study. As determined at the end of the studies by flow cytometry, right kidneys exhibited significantly greater numbers of T cells, B cells, and monocytes/macrophages compared with the servo-controlled left kidneys and compared with vehicle treated rats. No difference was found between Ang II servo-controlled left kidneys and vehicle treated kidneys. Immunostaining found that the density of glomeruli, cortical, and outer medullary capillaries were significantly reduced in the right kidney of Ang II–infused rats compared with servo-controlled left kidney. We conclude that in this model of hypertension the elevation of RPP, not Ang II nor dietary salt, leads to leukocyte infiltration in the kidney and to capillary rarefaction.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/HYPERTENSIONAHA.120.15295
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 2094210-2
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  • 8
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    Abstract 78: Protective Effect of Nox4 in Salt-induced Hypertension in Dahl Salt-induced Rats
    Ovid Technologies (Wolters Kluwer Health) ; 2013
    In:  Hypertension Vol. 62, No. suppl_1 ( 2013-09)
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 62, No. suppl_1 ( 2013-09)
    Abstract: It is recognized that oxidative stress plays a critical role in the development of salt-sensitive hypertension, especially in the kidney. The most abundant renal isoform is Nox4, but there is controversy regarding its distribution and function. There have been no studies of the role of Nox4 in a naturally occurring form of hypertension (Dahl salt-sensitive (SS) rat). We have therefore knocked out the Nox4 gene in the SS genetic background (SS Nox4-/- ) to determine the effect upon the development of salt-sensitive hypertension and renal kidney injury in the SS rat. The SS Nox4-/- rat, developed using zinc finger nuclease (ZFN) techniques, exhibits an 8 base-pair frame-shift deletion within exon 7 resulting in a truncation of the Nox4 peptide by 195 amino acids with a molecular weight of 22 kD predicted (compared to the full length Nox4 peptide of 594 amino acids with a molecular weight of 68 kD). Western blot analysis confirmed the loss of the Nox4 band at ~65 kD in renal medullary tissue of SS Nox4-/- rats vs. SS. The functional consequence of this deletion was substantial over a 21 day period following an increase in salt intake from 0.4 (LS) to 4.0% NaCl (HS). SS Nox4-/- rats exhibited a change in MAP from 105±3 on LS to 130±2 mmHg (a change of 25 mmHg; n=10) on d21 of HS compared to a change from 107±2 mmHg in SS rats to 171±7 on d21 of HS (a change of 64 mmHg; n=10) as determined by telemetry. Albuminuria was virtually eliminated in SS Nox4-/- rats who also exhibited a large reduction of tubular cast (2.4±0.3% positive strained region vs 12.6±1.3 in SS). Glomerular injury in both the cortex and medulla was significantly less in the SS Nox4-/- than the SS. The % of glomeruli with an injury score of 〉 2 (0-4 scale) was 43±1.5% (258 of 600 glomeruli) in the SS Nox4-/- but 65±3.9% (390 of 600) in the SS. We conclude that Nox4 plays an important role in the development of this form of salt-sensitive hypertension and renal injury in SS rats.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/hyp.62.suppl_1.A78
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2013
    detail.hit.zdb_id: 2094210-2
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  • 9
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    Null Mutation of the Nicotinamide Adenine Dinucleotide Phosphate–Oxidase Subunit p67 phox Protects the Dahl-S Rat From Salt-Induced Reductions in Medullary Blood Flow and Glomerular Filtration Rate
    Ovid Technologies (Wolters Kluwer Health) ; 2015
    In:  Hypertension Vol. 65, No. 3 ( 2015-03), p. 561-568
    Details
    In: Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 65, No. 3 ( 2015-03), p. 561-568
    Abstract: Null mutations in the p67 phox subunit of nicotinamide adenine dinucleotide phosphate–oxidase confer protection from salt sensitivity on Dahl salt-sensitive rats. Here, we track the sequential changes in medullary blood flow (MBF), glomerular filtration rate (GFR), urinary protein, and mean arterial pressure in SS p67 phox null rats and wild-type littermates during 21 days of 4.0% NaCl high-salt (HS) diet. Optical fibers were implanted in the renal medulla and MBF was measured in conscious rats by laser Doppler flowmetry. Separate groups of rats were prepared with femoral venous catheters and GFR was measured by the transcutaneous assessment of fluorescein isothiocyanate-sinistrin disappearance curves. Mean arterial blood pressure was measured by telemetry. In wild-type rats, HS caused a rapid reduction in MBF, which was significantly lower than control values by HS day-6. Reduced MBF was associated with a progressive increase in mean arterial pressure, averaging 170±5 mm Hg by HS salt day-21. A significant reduction in GFR was evident on day-14 HS, after the onset of hypertension and reduced MBF. In contrast, HS had no significant effect on MBF in SS p67 phox null rats and the pressor response to sodium was blunted, averaging 150±3 mm Hg on day-21 HS. GFR was maintained throughout the study and proteinuria was reduced. In summary, when p67 phox is not functional in the salt-sensitive rats, HS does not cause reduced MBF and salt-sensitive hypertension is attenuated, and consequently renal injury is reduced and GFR is maintained.
    Type of Medium: Online Resource
    ISSN: 0194-911X , 1524-4563
    URL: Article
    DOI: 10.1161/HYPERTENSIONAHA.114.04468
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2015
    detail.hit.zdb_id: 2094210-2
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  • 10
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    Monitoring for COVID-19 by universal testing in a homeless shelter in Germany: a prospective feasibility cohort study
    Springer Science and Business Media LLC ; 2021
    In:  BMC Infectious Diseases Vol. 21, No. 1 ( 2021-12)
    Details
    In: BMC Infectious Diseases, Springer Science and Business Media LLC, Vol. 21, No. 1 ( 2021-12)
    Abstract: Living conditions in homeless shelters facilitate the transmission of COVID-19. Social determinants and pre-existing health conditions place homeless people at increased risk of severe disease. Described outbreaks in homeless shelters resulted in high proportions of infected residents and staff members. In addition to other infection prevention strategies, regular shelter-wide (universal) testing for COVID-19 may be valuable, depending on the level of community transmission and when resources permit. Methods This was a prospective feasibility cohort study to evaluate universal testing for COVID-19 at a homeless shelter with 106 beds in Berlin, Germany. Co-researchers were recruited from the shelter staff. A PCR analysis of saliva or self-collected nasal/oral swab was performed weekly over a period of 3 weeks in July 2020. Acceptability and implementation barriers were analyzed by process evaluation using mixed methods including evaluation sheets, focus group discussion and a structured questionnaire. Results Ninety-three out of 124 (75%) residents were approached to participate in the study. Fifty-one out of the 93 residents (54.8%) gave written informed consent; thus 41.1% (51 out of 124) of all residents were included in the study. Among these, high retention rates (88.9–93.6%) of a weekly respiratory specimen were reached, but repeated collection attempts, as well as assistance were required. Around 48 person-hours were necessary for the sample collection including the preparation of materials. A self-collected nasal/oral swab was considered easier and more hygienic to collect than a saliva specimen. No resident was tested positive by RT-PCR. Language barriers were the main reason for non-participation. Flexibility of sample collection schedules, the use of video and audio materials, and concise written information were the main recommendations of the co-researchers for future implementation. Conclusions Voluntary universal testing for COVID-19 is feasible in homeless shelters. Universal testing of high-risk facilities will require flexible approaches, considering the level of the community transmission, the available resources, and the local recommendations. Lack of human resources and laboratory capacity may be a major barrier for implementation of universal testing, requiring adapted approaches compared to standard individual testing. Assisted self-collection of specimens and barrier free communication may facilitate implementation in homeless shelters. Program planning must consider homeless people’s needs and life situation, and guarantee confidentiality and autonomy.
    Type of Medium: Online Resource
    ISSN: 1471-2334
    URL: Article
    DOI: 10.1186/s12879-021-06945-4
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2041550-3
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