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| 23. |
- Patzak, Andreas, et al.
(författare)
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Angiotensin II response in afferent arterioles of mice lacking either the endothelial or neuronal isoform of nitric oxide synthase
- 2008
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Ingår i: American Journal of Physiology. Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 294:2, s. R429-R437
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study is to evaluate the impact of nitric oxide (NO) produced by endothelial NO synthase (eNOS) and neuronal NOS (nNOS) on the angiotensin II response in afferent arterioles (Af). Dose responses were assessed for angiotensin II in microperfused Af of mice homozygous for disruption of the eNOS gene [ eNOS(-/-)], or nNOS gene [ nNOS(-/-)], and their wild-type controls, eNOS(+/+) and nNOS(+/+). Angiotensin II at 10(-8) and 10(-6) mol/l reduced the lumen to 69% and 68% in eNOS(+/+), and to 59% and 50% in nNOS(+/+). N-G-nitro-L-arginine methyl ester (L-NAME) did not change basal arteriolar diameters, but augmented angiotensin II contraction, reducing diameters to 23% and 13% in eNOS(+/+), and 7% and 10% in nNOS(+/+) at 10(-8) and 10(-6) mol/l. The response to angiotensin II was enhanced in nNOS(-/-) mice (41% and 25% at 10(-8) and 10(-6) mol/l) and even more enhanced in eNOS(+/+) mice (12% and 9%) compared with nNOS(+/+) and eNOS(+/+). L-NAME led to complete constriction of Af in these groups. Mediato-lumen ratios of Af did not differ between controls and gene-deficient mice. mRNA expression of angiotensin II receptor types 1A and 1B and type 2 also did not differ. The results reveal that angiotensin II-induced release of NO from both eNOS and nNOS significantly contributes to the control of Af. Results also suggest that eNOS-derived NO is of greater importance than nNOS-derived NO in this isolated arteriolar preparation.
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| 26. |
- Schildroth, Janice, et al.
(författare)
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Endothelin type A and B receptors in the control of afferent and efferent arterioles in mice
- 2011
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Ingår i: Nephrology, Dialysis and Transplantation. - : Oxford University Press (OUP). - 0931-0509 .- 1460-2385. ; 26:3, s. 779-789
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Tidskriftsartikel (refereegranskat)abstract
- Background. Endothelin 1 contributes to renal blood flow control and pathogenesis of kidney diseases. The differential effects, however, of endothelin 1 (ET-1) on afferent (AA) and efferent arterioles (EA) remain to be established. Methods. We investigated endothelin type A and B receptor (ETA-R, ETB-R) functions in the control of AA and EA. Arterioles of ETB-R deficient, rescued mice [ETB (-/-)] and wild types [ETB(+/+)] were microperfused. Results. ET-1 constricted AA stronger than EA in ETB (-/-) and ETB(+/+) mice. Results in AA: ET-1 induced similar constrictions in ETB(-/-) and ETB(+/+) mice. BQ-123 (ETA-R antagonist) inhibited this response in both groups. ALA-ET-1 and IRL1620 (ETB-R agonists) had no effect on arteriolar diameter. L-NAME did neither affect basal diameters nor ET-1 responses. Results in EA: ET-1 constricted EA stronger in ETB(+/+) compared to ETB(-/-). BQ-123 inhibited the constriction completely only in ETB(-/-). ALA-ET-1 and IRL1620 constricted only arterioles of ETB(+/+) mice. L-NAME decreased basal diameter in ETB(+/+), but not in ETB(-/-) mice and increased the ET-1 response similarly in both groups. The L-NAME actions indicate a contribution of ETB-R in basal nitric oxide (NO) release in EA and suggest dilatory action of ETA-R in EA. Conclusions. ETA-R mediates vasoconstriction in AA and contributes to vasoconstriction in EA in this mouse model. ETB-R has no effect in AA but mediates basal NO release and constriction in EA. The stronger effect of ET-1 on AA supports observations of decreased glomerular filtration rate to ET-1 and indicates a potential contribution of ET-1 to the pathogenesis of kidney diseases.
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| 27. |
- Sendeski, Mauricio, et al.
(författare)
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Iodixanol, Constriction of Medullary Descending Vasa Recta, and Risk for Contrast Medium-induced Nephropathy
- 2009
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Ingår i: Radiology. - : Radiological Society of North America (RSNA). - 0033-8419 .- 1527-1315. ; 251:3, s. 697-704
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To determine whether a type of contrast medium (CM), iodixanol, modifies outer medullary descending vasa recta (DVR) vasoreactivity and nitric oxide (NO) production in isolated microperfused DVR. Materials and Methods: Animal handling conformed to the Animal Care Committee Guidelines of all participating institutions. Single specimens of DVR were isolated from rats and perfused with a buffered solution containing iodixanol. A concentration of 23 mg of iodine per milliliter was chosen to mimic that expected to be used in usual examinations in humans. Luminal diameter was determined by using video microscopy, and NO was measured by using fluorescent techniques. Results: Iodixanol led to 52% reduction of DVR luminal diameter, a narrowing that might interfere with passage of erythrocytes in vivo. Vasoconstriction induced by angiotensin II was enhanced by iodixanol. Moreover, iodixanol decreased NO bioavailability by more than 82%. Use of 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (a superoxide dismutase mimetic) prevented both vasoconstriction with iodixanol alone and increased constriction with angiotensin II caused by CM. Conclusion: Iodixanol in doses typically used for coronary interventions constricts DVR, intensifies angiotensin II-induced constriction, and reduces bioavailability of NO. CM-induced nephropathy may be related to these events and scavenging of reactive oxygen species might exert a therapeutic benefit by preventing the adverse effects that a CM has on medullary perfusion.
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| 28. |
- Wallenius, Joel, et al.
(författare)
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Exonic trinucleotide repeat expansions in ZFHX3 cause spinocerebellar ataxia type 4 : A poly-glycine disease.
- 2024
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Ingår i: American Journal of Human Genetics. - 0002-9297 .- 1537-6605. ; 111:1, s. 82-95
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Tidskriftsartikel (refereegranskat)abstract
- Autosomal-dominant ataxia with sensory and autonomic neuropathy is a highly specific combined phenotype that we described in two Swedish kindreds in 2014; its genetic cause had remained unknown. Here, we report the discovery of exonic GGC trinucleotide repeat expansions, encoding poly-glycine, in zinc finger homeobox 3 (ZFHX3) in these families. The expansions were identified in whole-genome datasets within genomic segments that all affected family members shared. Non-expanded alleles carried one or more interruptions within the repeat. We also found ZFHX3 repeat expansions in three additional families, all from the region of Skåne in southern Sweden. Individuals with expanded repeats developed balance and gait disturbances at 15 to 60 years of age and had sensory neuropathy and slow saccades. Anticipation was observed in all families and correlated with different repeat lengths determined through long-read sequencing in two family members. The most severely affected individuals had marked autonomic dysfunction, with severe orthostatism as the most disabling clinical feature. Neuropathology revealed p62-positive intracytoplasmic and intranuclear inclusions in neurons of the central and enteric nervous system, as well as alpha-synuclein positivity. ZFHX3 is located within the 16q22 locus, to which spinocerebellar ataxia type 4 (SCA4) repeatedly had been mapped; the clinical phenotype in our families corresponded well with the unique phenotype described in SCA4, and the original SCA4 kindred originated from Sweden. ZFHX3 has known functions in neuronal development and differentiation n both the central and peripheral nervous system. Our findings demonstrate that SCA4 is caused by repeat expansions in ZFHX3.
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| 29. |
- Xu, Nan, et al.
(författare)
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Reactive oxygen species in renal vascular function
- 2020
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Ingår i: Acta Physiologica. - : WILEY. - 1748-1708 .- 1748-1716. ; 229:4
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Forskningsöversikt (refereegranskat)abstract
- Reactive oxygen species (ROS) are produced by the aerobic metabolism. The imbalance between production of ROS and antioxidant defence in any cell compartment is associated with cell damage and may play an important role in the pathogenesis of renal disease. NADPH oxidase (NOX) family is the major ROS source in the vasculature and modulates renal perfusion. Upregulation of Ang II and adenosine activates NOX via AT1R and A1R in renal microvessels, leading to superoxide production. Oxidative stress in the kidney prompts renal vascular remodelling and increases preglomerular resistance. These are key elements in hypertension, acute and chronic kidney injury, as well as diabetic nephropathy. Renal afferent arterioles (Af), the primary resistance vessel in the kidney, fine tune renal hemodynamics and impact on blood pressure. Vice versa, ROS increase hypertension and diabetes, resulting in upregulation of Af vasoconstriction, enhancement of myogenic responses and change of tubuloglomerular feedback (TGF), which further promotes hypertension and diabetic nephropathy. In the following, we highlight oxidative stress in the function and dysfunction of renal hemodynamics. The renal microcirculatory alterations brought about by ROS importantly contribute to the pathophysiology of kidney injury, hypertension and diabetes.
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| 30. |
- Aghazadeh, Ahmad
(författare)
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Peri-implantitis : risk factors and outcome of reconstructive therapy
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis is focused on (I) the outcome of reconstructive treatment of peri-implant defects and (II) risk factors for the development of peri-implantitis.BackgroundAn increasing number of individuals have dental implant-supported reconstructions. The long-time survival rate of dental implants is good, but complications do occur. Accumulation of bacteria on oral implants and the development of a pathogenic biofilm at the mucosal margin will result in inflammatory responses diagnosed as peri-implant mucositis(PiM). Furthermore, PiM may progress to peri-implantitis (Pi) involving the implant-supporting bone and potentially result in a severe inflammatory process resulting in alveolar bone destruction and consequently implantloss. Currently, Pi is a common clinical complication following implant therapy.The prevalence of peri-implantitis has been reported to be around 20 %. Susceptibility to infections and a history of periodontitis are considered as important risk indicators for peri-implantitis. It seems logical that a past history of periodontitis is linked to an increased risk of peri-implantitis. It is possible that other patient-associated factors such as a smoking habit, and presence of general diseases may also be linked to a higher risk for developing peri-implantitis.Treatment of peri-implantitis is difficult. Non-surgical treatment modalities may not be sufficient to resolve the inflammatory process to obtain healthy conditions.Surgical treatment of peri-implantitis has commonly been employed in clinical practice to obtain access to the implant surface thereby increasing the possibility to effectively decontaminate the implant surfaces.The effectiveness and long-term outcomes of reconstructive surgical treatments of peri-implantitis has been debated. The scientific evidence suggests that regular supportive care is an essential component in order to maintain and secure long-term results following treatment of peri-implantitis.Aims1. To assess the short-term efficacy of reconstructive surgical treatmentof peri-implantitis (Study I).2. To analyse risk factors related to the occurrence of peri-implantitis(Study II).3. To assess the importance of defect configuration on the healing response after reconstructive surgical therapy of peri-implantitis (Study III).4. To assess the long-term efficacy of reconstructive surgical treatmentof peri-implantitis (Study IV).MethodsFour studies were designed to fulfil the aims:- A single-blinded prospective randomised controlled longitudinal human clinical trial evaluating the clinical and radiographic results of reconstructive surgical treatment of peri-implantitis defects usingeither AB or BDX.- A retrospective analysis of individuals with either peri-implantitis, or presenting with either peri-implant health, or peri-implant mucositis assessing the likelihood that peri-implantitis was associated with a history of systemic disease, a history of periodontitis, and smoking.- A prospective study evaluating if the alveolar bone defect configuration at dental implants diagnosed with peri-implantitisis related to clinical parameters at the time of surgical intervention and if the short- and long-term outcome of surgical intervention of peri-implantitis is dependent on defect configuration at the time of treatment.- A prospective 5-year follow-up of patients treated either with AB or BDX.Results- The success for both surgical reconstructive procedures was limited. Nevertheless, bovine xenograft provided evidence of more radiographic bone fill than AB. Improvements in PD, BOP, and SUP were observed for both treatment modalities-In relation to a diagnosis of peri-implantitis, a high likelihood of comorbidity was expressed in the presence of a history of periodontitis and a medical history of cardiovascular disease- The buccal-lingual width of the alveolar bone crest was explanatory to defect configuration- 4-wall defects and deeper defects demonstrated more radiographic evidence of defect fill- Reconstructive surgical treatment of peri-implant defects may result in successful clinical outcomes, that can be maintained over at least five years- The use of BDX is more predictable than use of harvested bone from the patient (AB)ConclusionsThe study results suggest that a bovine xenograft provides better radiographic evidence of defect fill than the use of autogenous bone harvested from cortical autologous bone grafts.Treatment with bone grafts to obtain radiographic evidence of defect fill is more predictable at 3- and 4-wall defects than at peri-implantitis bone defects with fewer bone walls.In relation to a diagnosis of peri-implantitis, a high likelihood of comorbidity was found for a history of periodontitis and a history of cardiovascular disease.
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