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Article ; Online: Nitric oxide mediates anomalous tubuloglomerular feedback in rats fed high-NaCl diet after subtotal nephrectomy.

Thomson, Scott C

American journal of physiology. Renal physiology

2018 Volume 316, Issue 2, Page(s) F223–F230

Abstract: Tubuloglomerular feedback (TGF) responses become anomalous in rats fed high-NaCl diet after subtotal nephrectomy (STN), such that stimulating TGF causes single nephron GFR (SNGFR) to increase rather than decrease. Micropuncture experiments were performed ...

Abstract	Tubuloglomerular feedback (TGF) responses become anomalous in rats fed high-NaCl diet after subtotal nephrectomy (STN), such that stimulating TGF causes single nephron GFR (SNGFR) to increase rather than decrease. Micropuncture experiments were performed to determine whether this anomaly results from heightened nitric oxide response to distal delivery, which is a known mechanism for resetting TGF, or from connecting tubule TGF (cTGF), which is a novel amiloride-inhibitable system for offsetting TGF responses. Micropuncture was done in Wistar Froemter rats fed high-NaCl diet (HS) for 8-10 days after STN or sham nephrectomy. TGF was manipulated by orthograde microperfusion of Henle's loop with artificial tubular fluid with or without NOS inhibitor, LNMMA, or the cell-impermeant amiloride analog, benzamil. SNGFR was measured by inulin clearance in tubular fluid collections from the late proximal tubule. TGF responses were quantified as the increase in SNGFR that occurred when the perfusion rate was reduced from 50 to 8 nl/min in STN or 40 to 8 nl/min in sham animals. The baseline TGF response was anomalous in STN HS (-4 ± 3 vs 14 ± 3 nl/min, P < 0.001). TGF response was normalized by perfusing STN nephron with LNMMA (14 ± 3 nl/min, P < 0.005 for ANOVA cross term) but not with benzamil (-3 ± 4 nl/min, P = 0.4 for ANOVA cross term). Anomalous TGF occurs in STN HS due to heightened effect of tubular flow on nitric oxide signaling, which increases to the point of overriding the normal TGF response. There is no role for cTGF in this phenomenon.
MeSH term(s)	Animals ; Diuretics/pharmacology ; Enzyme Inhibitors/pharmacology ; Feedback, Physiological ; Glomerular Filtration Rate/drug effects ; Kidney Glomerulus/drug effects ; Kidney Glomerulus/metabolism ; Kidney Tubules, Proximal/drug effects ; Kidney Tubules, Proximal/metabolism ; Male ; Nephrectomy ; Nitric Oxide/metabolism ; Nitric Oxide Synthase/antagonists & inhibitors ; Nitric Oxide Synthase/metabolism ; Rats, Wistar ; Renal Reabsorption/drug effects ; Signal Transduction ; Sodium Chloride, Dietary/administration & dosage ; Sodium Chloride, Dietary/metabolism
Chemical Substances	Diuretics ; Enzyme Inhibitors ; Sodium Chloride, Dietary ; Nitric Oxide (31C4KY9ESH) ; Nitric Oxide Synthase (EC 1.14.13.39)
Language	English
Publishing date	2018-10-31
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	603837-2
ISSN	1522-1466 ; 0363-6127
ISSN (online)	1522-1466
ISSN	0363-6127
DOI	10.1152/ajprenal.00066.2018
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Article ; Online: Nontuberculous Mycobacteria in Cystic Fibrosis in the Era of Cystic Fibrosis Transmembrane Regulator Modulators.

Burke, Andrew / Thomson, Rachel M / Wainwright, Claire E / Bell, Scott C

Seminars in respiratory and critical care medicine

2023 Volume 44, Issue 2, Page(s) 287–296

Abstract: Nontuberculous mycobacteria (NTM) are a group of mycobacteria which represent opportunistic pathogens that are of increasing concern in people with cystic fibrosis (pwCF). The acquisition has been traditionally though to be from environmental sources, ... ...

Abstract	Nontuberculous mycobacteria (NTM) are a group of mycobacteria which represent opportunistic pathogens that are of increasing concern in people with cystic fibrosis (pwCF). The acquisition has been traditionally though to be from environmental sources, though recent work has suggested clustered clonal infections do occur and transmission potential demonstrated among pwCF attending CF specialist centers. Guidelines for the screening, diagnosis, and identification of NTM and management of pwCF have been published. The emergence of CF-specific therapies, in particular cystic fibrosis transmembrane regulator (CFTR) modulator drugs, have led to significant improvement in the health and well-being of pwCF and may lead to challenges in sampling the lower respiratory tract including to screen for NTM. This review highlights the epidemiology, modes of acquisition, screening and diagnosis, therapeutic approaches in the context of improved clinical status for pwCF, and the clinical application of CFTR modulator therapies.
MeSH term(s)	Humans ; Cystic Fibrosis/drug therapy ; Nontuberculous Mycobacteria ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics ; Mycobacterium Infections, Nontuberculous/diagnosis ; Mycobacterium Infections, Nontuberculous/drug therapy ; Mycobacterium Infections, Nontuberculous/epidemiology
Chemical Substances	Cystic Fibrosis Transmembrane Conductance Regulator (126880-72-6)
Language	English
Publishing date	2023-01-17
Publishing country	United States
Document type	Review ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1183617-9
ISSN	1098-9048 ; 1069-3424
ISSN (online)	1098-9048
ISSN	1069-3424
DOI	10.1055/s-0042-1759883
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Article ; Online: The tubular hypothesis of nephron filtration and diabetic kidney disease.

Vallon, Volker / Thomson, Scott C

Nature reviews. Nephrology

2020 Volume 16, Issue 6, Page(s) 317–336

Abstract: Kidney size and glomerular filtration rate (GFR) often increase with the onset of diabetes, and elevated GFR is a risk factor for the development of diabetic kidney disease. Hyperfiltration mainly occurs in response to signals passed from the tubule to ... ...

Abstract	Kidney size and glomerular filtration rate (GFR) often increase with the onset of diabetes, and elevated GFR is a risk factor for the development of diabetic kidney disease. Hyperfiltration mainly occurs in response to signals passed from the tubule to the glomerulus: high levels of glucose in the glomerular filtrate drive increased reabsorption of glucose and sodium by the sodium-glucose cotransporters SGLT2 and SGLT1 in the proximal tubule. Passive reabsorption of chloride and water also increases. The overall capacity for proximal reabsorption is augmented by growth of the proximal tubule, which (alongside sodium-glucose cotransport) further limits urinary glucose loss. Hyperreabsorption of sodium and chloride induces tubuloglomerular feedback from the macula densa to increase GFR. In addition, sodium-glucose cotransport by SGLT1 on macula densa cells triggers the production of nitric oxide, which also contributes to glomerular hyperfiltration. Although hyperfiltration restores sodium and chloride excretion it imposes added physical stress on the filtration barrier and increases the oxygen demand to drive reabsorption. Tubular growth is associated with the development of a senescence-like molecular signature that sets the stage for inflammation and fibrosis. SGLT2 inhibitors attenuate the proximal reabsorption of sodium and glucose, normalize tubuloglomerular feedback signals and mitigate hyperfiltration. This tubule-centred model of diabetic kidney physiology predicts the salutary effect of SGLT2 inhibitors on hard renal outcomes, as shown in large-scale clinical trials.
MeSH term(s)	Cellular Senescence ; Chlorides/metabolism ; Diabetes Mellitus/metabolism ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/metabolism ; Diabetic Nephropathies/metabolism ; Fibrosis ; Glomerular Filtration Barrier ; Glomerular Filtration Rate ; Glucose/metabolism ; Humans ; Hypertrophy ; Inflammation ; Kidney Glomerulus/metabolism ; Kidney Glomerulus/pathology ; Kidney Tubules/metabolism ; Kidney Tubules/pathology ; Nephrons/metabolism ; Nephrons/pathology ; Nitric Oxide/metabolism ; Renal Reabsorption ; Sodium/metabolism ; Sodium-Glucose Transporter 1/metabolism ; Sodium-Glucose Transporter 2/metabolism ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use
Chemical Substances	Chlorides ; Sodium-Glucose Transporter 1 ; Sodium-Glucose Transporter 2 ; Sodium-Glucose Transporter 2 Inhibitors ; Nitric Oxide (31C4KY9ESH) ; Sodium (9NEZ333N27) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2020-03-09
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	2490366-8
ISSN	1759-507X ; 1759-5061
ISSN (online)	1759-507X
ISSN	1759-5061
DOI	10.1038/s41581-020-0256-y
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Article ; Online: Renal Effects of Sodium-Glucose Co-Transporter Inhibitors.

Thomson, Scott C / Vallon, Volker

The American journal of cardiology

2019 Volume 124 Suppl 1, Page(s) S28–S35

Abstract: Sodium-glucose co-transporter 2 (SGLT2) inhibitors immediately reduce the glomerular filtration rate (GFR) in patients with type 2 diabetes mellitus. When given chronically, they confer benefit by markedly slowing the rate at which chronic kidney disease ...

Abstract	Sodium-glucose co-transporter 2 (SGLT2) inhibitors immediately reduce the glomerular filtration rate (GFR) in patients with type 2 diabetes mellitus. When given chronically, they confer benefit by markedly slowing the rate at which chronic kidney disease progresses and are the first agents to do so since the advent of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). Salutary effects on the kidney were first demonstrated in cardiovascular outcomes trials and have now emerged from trials enriched in subjects with type 2 diabetes mellitus and chronic kidney disease. A simple model that unifies the immediate and long-term effects of SGLT2 inhibitors on kidney function is based on the assumption that diabetic hyperfiltration puts the kidney at long-term risk and evidence that hyperfiltration is an immediate response to a reduced signal for tubuloglomerular feedback, which occurs to the extent that SGLT2 activity mediates a primary increase in sodium and fluid reabsorption by the proximal tubule. This model will likely continue to serve as a useful description accounting for the beneficial effect of SGLT2 inhibitors on the diabetic kidney, similar to the hemodynamic explanation for the benefit of ACEIs and ARBs. A more complex model will be required to incorporate positive interactions between SGLT2 and sodium-hydrogen exchanger 3 in the proximal tubule and between sodium-glucose co-transporter 1 (SGLT1) and nitric oxide synthase in the macula densa. The implication of these latter nuances for day-to-day clinical medicine remains to be determined.
MeSH term(s)	Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/metabolism ; Disease Progression ; Glomerular Filtration Rate/drug effects ; Glomerular Filtration Rate/physiology ; Humans ; Kidney/drug effects ; Kidney Tubules/drug effects ; Kidney Tubules/metabolism ; Kidney Tubules, Distal/drug effects ; Kidney Tubules, Distal/metabolism ; Kidney Tubules, Proximal/drug effects ; Kidney Tubules, Proximal/metabolism ; Nitric Oxide Synthase/metabolism ; Renal Circulation/drug effects ; Renal Circulation/physiology ; Renal Insufficiency, Chronic/complications ; Renal Insufficiency, Chronic/metabolism ; Sodium-Glucose Transporter 1/metabolism ; Sodium-Glucose Transporter 2/metabolism ; Sodium-Glucose Transporter 2 Inhibitors/pharmacology ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use ; Sodium-Hydrogen Exchanger 3/metabolism
Chemical Substances	Sodium-Glucose Transporter 1 ; Sodium-Glucose Transporter 2 ; Sodium-Glucose Transporter 2 Inhibitors ; Sodium-Hydrogen Exchanger 3 ; Nitric Oxide Synthase (EC 1.14.13.39)
Language	English
Publishing date	2019-11-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	80014-4
ISSN	1879-1913 ; 0002-9149
ISSN (online)	1879-1913
ISSN	0002-9149
DOI	10.1016/j.amjcard.2019.10.027
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Article: Nontuberculous Mycobacteria in Cystic Fibrosis in the Era of Cystic Fibrosis Transmembrane Regulator Modulators

Burke, Andrew / Thomson, Rachel M. / Wainwright, Claire E. / Bell, Scott C.

Seminars in Respiratory and Critical Care Medicine

(Cystic Fibrosis)

2023 Volume 44, Issue 02, Page(s) 287–296

Series title	Cystic Fibrosis
Abstract	Nontuberculous mycobacteria (NTM) are a group of mycobacteria which represent opportunistic pathogens that are of increasing concern in people with cystic fibrosis (pwCF). The acquisition has been traditionally though to be from environmental sources, though recent work has suggested clustered clonal infections do occur and transmission potential demonstrated among pwCF attending CF specialist centers. Guidelines for the screening, diagnosis, and identification of NTM and management of pwCF have been published. The emergence of CF-specific therapies, in particular cystic fibrosis transmembrane regulator (CFTR) modulator drugs, have led to significant improvement in the health and well-being of pwCF and may lead to challenges in sampling the lower respiratory tract including to screen for NTM. This review highlights the epidemiology, modes of acquisition, screening and diagnosis, therapeutic approaches in the context of improved clinical status for pwCF, and the clinical application of CFTR modulator therapies.
Keywords	cystic fibrosis ; nontuberculous mycobacteria ; complex ; CFTR modulator ; epidemiology ; environmental exposure
Language	English
Publishing date	2023-01-17
Publisher	Thieme Medical Publishers, Inc.
Publishing place	Stuttgart ; New York
Document type	Article
ZDB-ID	1183617-9
ISSN	1098-9048 ; 1069-3424
ISSN (online)	1098-9048
ISSN	1069-3424
DOI	10.1055/s-0042-1759883
Database	Thieme publisher's database

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Article ; Online: Responses in Blood Pressure and Kidney Function to Soluble Guanylyl Cyclase Stimulation or Activation in Normal and Diabetic Rats.

Patel, Rohit / Fu, Yiling / Khang, Ser / Benardeau, Agnes M / Thomson, Scott C / Vallon, Volker

Nephron

2022 Volume 147, Issue 5, Page(s) 281–300

MeSH term(s)	Rats ; Animals ; Soluble Guanylyl Cyclase ; Blood Pressure ; Diabetes Mellitus, Experimental ; Kidney ; Nitric Oxide/physiology ; Guanylate Cyclase
Chemical Substances	Soluble Guanylyl Cyclase (EC 4.6.1.2) ; Nitric Oxide (31C4KY9ESH) ; Guanylate Cyclase (EC 4.6.1.2)
Language	English
Publishing date	2022-10-20
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	207121-6
ISSN	2235-3186 ; 1423-0186 ; 1660-8151 ; 0028-2766
ISSN (online)	2235-3186 ; 1423-0186
ISSN	1660-8151 ; 0028-2766
DOI	10.1159/000526934
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Article ; Online: Omicron BA.2.86 cross-neutralising activity in community sera from the UK.

Willett, Brian J / Logan, Nicola / Scott, Sam / Davis, Chris / McSorley, Therese / Asamaphan, Patawee / Hosie, Margaret J / Olmo, Paula / Grove, Joe / Orton, Richard / Ho, Antonia / Haughney, John / Robertson, David L / Thomson, Emma C

Lancet (London, England)

2023 Volume 402, Issue 10417, Page(s) 2075–2076

MeSH term(s)	Humans ; United Kingdom ; Antibodies, Viral ; Antibodies, Neutralizing
Chemical Substances	Antibodies, Viral ; Antibodies, Neutralizing
Language	English
Publishing date	2023-11-09
Publishing country	England
Document type	Letter
ZDB-ID	3306-6
ISSN	1474-547X ; 0023-7507 ; 0140-6736
ISSN (online)	1474-547X
ISSN	0023-7507 ; 0140-6736
DOI	10.1016/S0140-6736(23)02397-8
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Article ; Online: In vitro susceptibility testing of imipenem-relebactam and tedizolid against 102 Mycobacterium abscessus isolates.

Burke, Andrew / Carter, Robyn / Tolson, Carla / Congdon, Jacob / Duplancic, Christine / Bursle, Evan / Bell, Scott C / Roberts, Jason A / Thomson, Rachel

International journal of antimicrobial agents

2023 Volume 62, Issue 4, Page(s) 106938

Abstract: Objectives: Mycobacterium abscessus is an emerging infection in people living with lung diseases, including cystic fibrosis (CF) and bronchiectasis, and it has limited treatment options and low cure rates. The off-label use of novel antibiotics ... ...

Abstract	Objectives: Mycobacterium abscessus is an emerging infection in people living with lung diseases, including cystic fibrosis (CF) and bronchiectasis, and it has limited treatment options and low cure rates. The off-label use of novel antibiotics developed for other bacterial pathogens offers potential new therapeutic options. We aimed to describe the in vitro activity of imipenem, imipenem-relebactam and tedizolid against comparator antibiotics in M. abscessus isolates from Australian patients with and without CF. Methods: We performed susceptibility testing for imipenem-relebactam, tedizolid and comparator antibiotics by Clinical and Laboratory Standards Institute (CLSI) criteria against 102 clinical M. abscessus isolates, including 46 from people with CF. Results: In this study, the minimum inhibitory concentration (MICs) of imipenem-relebactam was one-fold dilution less than of imipenem alone. The MIC Conclusions: This study shows lower MICs for imipenem-relebactam and tedizolid compared to other more commonly used antibiotics and supports their consideration in clinical trials for M. abscessus treatment.
MeSH term(s)	Humans ; Mycobacterium abscessus ; Australia ; Anti-Bacterial Agents/pharmacology ; Imipenem/pharmacology ; Microbial Sensitivity Tests
Chemical Substances	relebactam (Y1MYA2UHFL) ; tedizolid (97HLQ82NGL) ; Anti-Bacterial Agents ; Imipenem (71OTZ9ZE0A)
Language	English
Publishing date	2023-07-28
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1093977-5
ISSN	1872-7913 ; 0924-8579
ISSN (online)	1872-7913
ISSN	0924-8579
DOI	10.1016/j.ijantimicag.2023.106938
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Article ; Online: Renal Effects of Incretin-Based Diabetes Therapies: Pre-clinical Predictions and Clinical Trial Outcomes.

Thomson, Scott C / Vallon, Volker

Current diabetes reports

2018 Volume 18, Issue 5, Page(s) 28

Abstract: Purpose of review: The purpose of this review is to correlate predictions based on pre-clinical data with outcomes from clinical trials that examine the effects of incretin-based diabetes treatments on the kidney. The incretin-based treatments include ... ...

Abstract	Purpose of review: The purpose of this review is to correlate predictions based on pre-clinical data with outcomes from clinical trials that examine the effects of incretin-based diabetes treatments on the kidney. The incretin-based treatments include agonists of the glucagon-like peptide 1 receptor (GLP-1R) and inhibitors of the enzyme, dipeptidyl peptidase-4 (DPP-4). In addition, what is known about the incretin-based therapies will be compared to what is known about the renal effects of SGLT2 inhibitors. Recent findings: Large-scale clinical trials have shown that SGLT2 inhibitors reduce albuminuria and preserve estimated glomerular filtration rate (eGFR) in patients with diabetic nephropathy. A concise and plausible hemodynamic mechanism is supported by pre-clinical research on the physiology and pharmacology of SGLT2. Large-scale clinical trials have shown that incretin-based therapies mitigate albuminuria but have not shown beneficial effects on eGFR. Research on the incretin-based therapies has yielded a diverse array of direct effects throughout the body, which fuels speculation as to how these drugs might benefit the diabetic kidney and affect its function(s). But in vivo experiments have yet to confirm that the proposed mechanisms underlying emergent phenomena, such as proximal tubular fluid reabsorption, are the ones predicted by cell and molecular experiments. There may be salutary effects of incretin-based treatments on the diabetic kidney, but the system is complex and not amenable to simple explanation or prior prediction. This contrasts with the renal effects of SGLT2 inhibitors, which can be explained concisely.
MeSH term(s)	Clinical Trials as Topic ; Diabetes Mellitus/drug therapy ; Hemodynamics/drug effects ; Humans ; Incretins/pharmacology ; Incretins/therapeutic use ; Kidney/pathology ; Kidney/physiopathology ; Treatment Outcome
Chemical Substances	Incretins
Language	English
Publishing date	2018-04-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	2065167-3
ISSN	1539-0829 ; 1534-4827
ISSN (online)	1539-0829
ISSN	1534-4827
DOI	10.1007/s11892-018-0991-7
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Article ; Online: Item-specific proportion congruency (ISPC) modulates, but does not generate, the backward crosstalk effect.

Thomson, Sandra J / Simone, Ariana C / Watter, Scott

Psychological research

2020 Volume 85, Issue 3, Page(s) 1093–1107

Abstract: When both tasks in a psychological refractory period (PRP) paradigm have compatible manual responses, a compatibility benefit in RT can often be observed on Task1 performance, in apparent violation of a strict traditional response selection bottleneck ... ...

Abstract	When both tasks in a psychological refractory period (PRP) paradigm have compatible manual responses, a compatibility benefit in RT can often be observed on Task1 performance, in apparent violation of a strict traditional response selection bottleneck model. This compatibility-based backward crosstalk effect (BCE) has been generally attributed to automatic activation of Task2 response information, in parallel with attended Task1 performance. This paper tests a potential alternative mechanism of the BCE. Item-specific proportion congruency (ISPC) effects are previously well demonstrated, where learning of associations between stimuli and task conflict (e.g., that particular Stroop items are typically incongruent) allows rapidly and automatically elicited control adjustments in performance. Similar proportion manipulations have recently been shown to modulate the BCE in dual-task performance. If participants could similarly learn associations between particular pairs of stimuli and resulting response conflict in a PRP task, this kind of mechanism could produce relative speeding versus slowing of Task1 RT on response compatible versus incompatible trials. This pattern of data directly describes the BCE, and represents a potential alternative mechanism that does not require any response crosstalk, and would reinforce a stricter view of the response selection bottleneck model, if true. Over two experiments, we demonstrate that while the BCE is sensitive to ISPC-like effects based on Task1 conflict contingencies, the BCE is insensitive to relationships between particular pairs of stimuli and associated conflict. While ISPC effects can modulate the BCE, they do not generate the BCE. These findings reinforce the current Task2 parallel response activation account of the BCE.
MeSH term(s)	Female ; Humans ; Learning ; Male ; Psychomotor Performance/physiology ; Reaction Time ; Refractory Period, Psychological ; Reinforcement, Psychology ; Task Performance and Analysis ; Young Adult
Language	English
Publishing date	2020-03-28
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1463034-5
ISSN	1430-2772 ; 0340-0727
ISSN (online)	1430-2772
ISSN	0340-0727
DOI	10.1007/s00426-020-01318-z
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