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Article ; Online: A Gut-Intrinsic Melanocortin Signaling Complex Augments L-Cell Secretion in Humans.

2021 Volume 161, Issue 2, Page(s) 536–547.e2

Abstract: ... activation. Mc4r transcript is enriched in mouse enteroendocrine L cells and peripheral administration ... to determine whether pathways linking MC4R and L-cell secretion exist in humans.: Design: GLP-1 and PYY ... of-function MC4R mutation. MC4R was localized to L cells and regulates GLP-1 and PYY secretion from ex vivo ...

Abstract	Objective: Hypothalamic melanocortin 4 receptors (MC4R) are a key regulator of energy homeostasis. Brain-penetrant MC4R agonists have failed, as concentrations required to suppress food intake also increase blood pressure. However, peripherally located MC4R may also mediate metabolic benefits of MC4R activation. Mc4r transcript is enriched in mouse enteroendocrine L cells and peripheral administration of the endogenous MC4R agonist, α-melanocyte stimulating hormone (α-MSH), triggers the release of the anorectic hormones Glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY) in mice. This study aimed to determine whether pathways linking MC4R and L-cell secretion exist in humans. Design: GLP-1 and PYY levels were assessed in body mass index-matched individuals with or without loss-of-function MC4R mutations following an oral glucose tolerance test. Immunohistochemistry was performed on human intestinal sections to characterize the mucosal MC4R system. Static incubations with MC4R agonists were carried out on human intestinal epithelia, GLP-1 and PYY contents of secretion supernatants were assayed. Results: Fasting PYY levels and oral glucose-induced GLP-1 secretion were reduced in humans carrying a total loss-of-function MC4R mutation. MC4R was localized to L cells and regulates GLP-1 and PYY secretion from ex vivo human intestine. α-MSH immunoreactivity in the human intestinal epithelia was predominantly localized to L cells. Glucose-sensitive mucosal pro-opiomelanocortin cells provide a local source of α-MSH that is essential for glucose-induced GLP-1 secretion in small intestine. Conclusion: Our findings describe a previously unidentified signaling nexus in the human gastrointestinal tract involving α-MSH release and MC4R activation on L cells in an autocrine and paracrine fashion. Outcomes from this study have direct implications for targeting mucosal MC4R to treat human metabolic disorders.
MeSH term(s)	Autocrine Communication ; Blood Glucose/metabolism ; Case-Control Studies ; Enteroendocrine Cells/drug effects ; Enteroendocrine Cells/metabolism ; Glucagon-Like Peptide 1/metabolism ; Glucose/administration & dosage ; Glucose Tolerance Test ; Humans ; Intestinal Mucosa/drug effects ; Intestinal Mucosa/metabolism ; Loss of Function Mutation ; Paracrine Communication ; Peptide YY/metabolism ; Pro-Opiomelanocortin/genetics ; Pro-Opiomelanocortin/metabolism ; Receptor, Melanocortin, Type 4/agonists ; Receptor, Melanocortin, Type 4/genetics ; Receptor, Melanocortin, Type 4/metabolism ; Secretory Pathway ; Signal Transduction ; Time Factors ; alpha-MSH/metabolism ; alpha-MSH/pharmacology
Chemical Substances	Blood Glucose ; MC4R protein, human ; Receptor, Melanocortin, Type 4 ; Peptide YY (106388-42-5) ; alpha-MSH (581-05-5) ; Pro-Opiomelanocortin (66796-54-1) ; Glucagon-Like Peptide 1 (89750-14-1) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2021-04-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80112-4
ISSN	1528-0012 ; 0016-5085
ISSN (online)	1528-0012
ISSN	0016-5085
DOI	10.1053/j.gastro.2021.04.014
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Article: Vitamin D and Covid-19: A Note of Caution.

Rabbitt, L / Slattery, E

Irish medical journal

2020 Volume 113, Issue 5, Page(s) 82

MeSH term(s)	Betacoronavirus ; COVID-19 ; Coronavirus Infections ; Humans ; Pandemics ; Pneumonia, Viral ; SARS-CoV-2 ; Vitamin D
Chemical Substances	Vitamin D (1406-16-2)
Keywords	covid19
Language	English
Publishing date	2020-05-07
Publishing country	Ireland
Document type	Letter ; Comment
ZDB-ID	193134-9
ISSN	0332-3102 ; 0021-129X
ISSN	0332-3102 ; 0021-129X
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Article ; Online: Focus on Metformin: Its Role and Safety in Pregnancy and Beyond.

Newman, Christine / Rabbitt, Louise / Ero, Adesuwa / Dunne, Fidelma P

Drugs

2023 Volume 83, Issue 11, Page(s) 985–999

Abstract: Metformin is used worldwide in the treatment of type 2 diabetes and has been used in the treatment of diabetes in pregnancy since the 1970s. It is highly acceptable to patients due to its ease of administration, cost and adverse effect profile. It is ... ...

Abstract	Metformin is used worldwide in the treatment of type 2 diabetes and has been used in the treatment of diabetes in pregnancy since the 1970s. It is highly acceptable to patients due to its ease of administration, cost and adverse effect profile. It is effective in reducing macrosomia, large-for-gestational-age infants and reduces maternal weight gain. Despite its many advantages, metformin has been associated with reductions in foetal size and has been associated with an increase in infants born small-for-gestational-age in certain cohorts. In this article, we review its efficacy, adverse effects and long-term follow-up before, during and after pregnancy for both mother and infant. We also evaluate the other forms of treatment for gestational diabetes, including oral therapies, insulin therapy and emerging treatments.
MeSH term(s)	Pregnancy ; Infant ; Female ; Humans ; Metformin/therapeutic use ; Metformin/adverse effects ; Hypoglycemic Agents/adverse effects ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/chemically induced ; Diabetes, Gestational/drug therapy ; Insulin
Chemical Substances	Metformin (9100L32L2N) ; Hypoglycemic Agents ; Insulin
Language	English
Publishing date	2023-06-24
Publishing country	New Zealand
Document type	Journal Article ; Review
ZDB-ID	120316-2
ISSN	1179-1950 ; 0012-6667
ISSN (online)	1179-1950
ISSN	0012-6667
DOI	10.1007/s40265-023-01899-0
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Article: Essential oil of Nepeta x faassenii Bergmans ex Stearn (N. mussinii Spreng. x N. nepetella L.): a comparison study.

Radulović, Niko / Blagojević, Polina D / Rabbitt, Kevin / Menezes, Fabio de Sousa

Natural product communications

2011 Volume 6, Issue 7, Page(s) 1015–1022

Abstract: ... Bergmans ex Steam, a hybrid species produced by crossbreeding N. mussinii Spreng. with N. nepetella L., led ... oils (3 different populations of N. nuda L. and N. cataria L. from Serbia) were included in this study ...

Abstract	Analysis (GC and GC/MS) of an essential oil sample obtained from dry leaves of Nepeta x faassenii Bergmans ex Steam, a hybrid species produced by crossbreeding N. mussinii Spreng. with N. nepetella L., led to the identification of 109 constituents that represented 95.9% of the oil. The major constituents were 4aalpha,7alpha,7aalpha-nepetalactone (67.8%), 1,8-cineole (6.6%), germacrene D (4.8%), beta-pinene (2.7%), (E)-beta-ocimene (2.6%), 4aalpha,7beta,7aalpha-nepetalactone (2.3%) and (E)-beta-farnesene (1.0%). Chemical composition of the oil was compared, using multivariate statistical analyses (MVA) with those of the oils of other Nepeta taxa, in particular N. mussinii and N. nepetella. This was done in order to explore the mode of inheritance of the monoterpene biosynthetic apparatus of N. faassenii. Chemical composition of the volatiles of a Nepeta taxon (different populations) can be subject to variation due to environmental and geographical factors. To accommodate this fact in the MVAs, along side with N. faassenii essential oil, additional 6 oils (3 different populations of N. nuda L. and N. cataria L. from Serbia) were included in this study (isolated and analyzed (chemically and statistically)). The MVA analyses recognized N. faassenii as being closely related to both N. mussinii and N. nepetella. If the relative content of oil constituents per plant and not per chromatogram were used as variables in the MVA (this was done by simple multiplication of the yields and relative percentages of components) a higher degree of mutual similarity (in respect to the monoterpene biosynthesis) of N. faassenii to N. mussinii, than to the other parent species, was observed.
MeSH term(s)	Crosses, Genetic ; Gas Chromatography-Mass Spectrometry ; Monoterpenes/isolation & purification ; Nepeta/chemistry ; Plant Components, Aerial/chemistry ; Plant Oils/chemistry ; Principal Component Analysis
Chemical Substances	Monoterpenes ; Plant Oils
Language	English
Publishing date	2011-07
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1934-578X
ISSN	1934-578X
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Article: Vitamin d and covid-19: A note of caution

Rabbitt, L. / Slattery, E.

Irish Medical Journal

Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #525628
Database	COVID19

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Article ; Online: Caregiver Reports of Infant Distress and Injury in Abused Infants.

Rabbitt, Angela L / Olson, Nora L / Liegl, Melodee Nugent / Simpson, Pippa / Sheets, Lynn K

The Journal of pediatrics

2022 Volume 245, Page(s) 190–195.e2

Abstract: Objectives: To determine whether in infants evaluated for physical abuse, medical encounters for infant distress are correlated with physical abuse or a history of sentinel injuries.: Study design: This retrospective, case-control analysis of infants ...

Abstract	Objectives: To determine whether in infants evaluated for physical abuse, medical encounters for infant distress are correlated with physical abuse or a history of sentinel injuries. Study design: This retrospective, case-control analysis of infants aged <12 months evaluated for physical abuse identified demographic characteristics, prior injuries, and medical encounters for infant distress. Variables were compared between abused infants and nonabused infants with and without sentinel injuries. A nonparametric recursive classification tree analysis assessed interactions between variables. Results: Infant distress was associated with abuse (67.9% vs 44.7%; P = .008; OR, 2.6; 95% CI, 1.3-5.2). Infants with sentinel injuries had higher rates of infant distress (74.1% vs 42.4%; P ≤ .001) and crying (81.5% vs 62.7%; P = .012). Previous falls (32.6% vs 18.1%; P = .03) and nonsentinel injuries (18.2% vs 5.4%; P = .002) also were associated with abuse, although sentinel injuries were the most important predictor of abuse, followed by infant distress. Conclusions: Infants with medical encounters for distress and injury may be at higher risk for abuse and may benefit from intensive educational and support services for their caregivers. Additional research evaluating the most effective interventions for caregivers of fussy infants is needed.
MeSH term(s)	Caregivers ; Case-Control Studies ; Child ; Child Abuse ; Crying ; Humans ; Infant ; Retrospective Studies
Language	English
Publishing date	2022-03-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3102-1
ISSN	1097-6833 ; 0022-3476
ISSN (online)	1097-6833
ISSN	0022-3476
DOI	10.1016/j.jpeds.2022.02.056
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Article ; Online: A cost-analysis of managing secondary and apparent treatment-resistant hypertension in a specialist multidisciplinary hypertension clinic.

Rabbitt, Louise / Curneen, James / Hobbins, Anna / Browne, Darragh / Joyce, Mary / Lappin, David / McEvoy, John William / Gillespie, Paddy / Dennedy, Michael Conall

Journal of hypertension

2023 Volume 42, Issue 1, Page(s) 58–69

Abstract: Objectives: A knowledge gap exists around the costs and budget impact of specialist hypertension clinics. This study reports on the cost of providing care in a multidisciplinary hypertension clinic staffed by nephrologist, endocrinologist and ... ...

Abstract	Objectives: A knowledge gap exists around the costs and budget impact of specialist hypertension clinics. This study reports on the cost of providing care in a multidisciplinary hypertension clinic staffed by nephrologist, endocrinologist and cardiologist, which manages patients with suspected secondary hypertension and/or apparent treatment-resistant hypertension. The aim of this study is to provide the evidence required to inform policy and planning care pathways for this patient group. Methods: A cost analysis from a healthcare provider perspective using micro-costing techniques was conducted to estimate the direct implementation costs of existing standard practice for the care pathway of patients attending the multidisciplinary hypertension clinic. Sixty-five patients originally recruited for a study of medication adherence in hypertension were included in the sample. Results: The total care-pathway cost per patient, taking into account clinic visits, clinical reviews, investigations and MDT discussion, was estimated to be €3277, on average. For the patient subgroups, the average cost was €5644 for patients diagnosed with primary aldosteronism and €1446 for patients diagnosed with essential hypertension. Conclusion: There is significant cost associated with providing specialized hypertension care for patients with apparent treatment-resistant hypertension. Given the high rates of nonadherence in this population, it is likely that some of this cost could be avoided with better detection and management of medication adherence in this challenging population. Future studies should consider the cost-effectiveness of this or similar models of care by exploring the benefit to patients and the wider healthcare context of providing care of this type.
MeSH term(s)	Humans ; Costs and Cost Analysis ; Hypertension/drug therapy ; Ambulatory Care ; Medication Adherence
Language	English
Publishing date	2023-11-16
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	605532-1
ISSN	1473-5598 ; 0263-6352 ; 0952-1178
ISSN (online)	1473-5598
ISSN	0263-6352 ; 0952-1178
DOI	10.1097/HJH.0000000000003535
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Article ; Online: Peptidoglycan-Targeted [

Sorlin, Alexandre M / López-Álvarez, Marina / Biboy, Jacob / Gray, Joe / Rabbitt, Sarah J / Rahim, Junaid Ur / Lee, Sang Hee / Bobba, Kondapa Naidu / Blecha, Joseph / Parker, Mathew F L / Flavell, Robert R / Engel, Joanne / Ohliger, Michael / Vollmer, Waldemar / Wilson, David M

JACS Au

2024 Volume 4, Issue 3, Page(s) 1039–1047

Abstract: Imaging is increasingly used to detect and monitor bacterial infection. Both anatomic (X-rays, computed tomography, ultrasound, and MRI) and nuclear medicine ([ ...

Abstract	Imaging is increasingly used to detect and monitor bacterial infection. Both anatomic (X-rays, computed tomography, ultrasound, and MRI) and nuclear medicine ([
Language	English
Publishing date	2024-02-26
Publishing country	United States
Document type	Journal Article
ISSN	2691-3704
ISSN (online)	2691-3704
DOI	10.1021/jacsau.3c00776
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Article ; Online: Alterations in GLP-1 and PYY release with aging and body mass in the human gut.

Jones, Lauren A / Sun, Emily W / Lumsden, Amanda L / Thorpe, Daniel W / Peterson, Rochelle A / De Fontgalland, Dayan / Sposato, Luigi / Rabbitt, Philippa / Hollington, Paul / Wattchow, David A / Keating, Damien J

Molecular and cellular endocrinology

2023 Volume 578, Page(s) 112072

Abstract: ... YY (PYY) which are co-secreted from L cells. While much is known about the effects of these hormones ... occur in human gut, as do site-specific relationships of L cell secretion with aging and body mass. ...

Abstract	The lining of our intestinal surface contains an array of hormone-producing cells that are collectively our bodies' largest endocrine cell reservoir. These "enteroendocrine" (EE) cells reside amongst the billions of absorptive epithelial and other cell types that line our gastrointestinal tract and can sense and respond to the ever-changing internal environment in our gut. EE cells release an array of important signalling molecules that can act as hormones, including glucagon-like peptide (GLP-1) and peptide YY (PYY) which are co-secreted from L cells. While much is known about the effects of these hormones on metabolism, insulin secretion and food intake, less is understood about their secretion from human intestinal tissue. In this study we assess whether GLP-1 and PYY release differs across human small and large intestinal tissue locations within the gastrointestinal tract, and/or by sex, body weight and the age of an individual. We identify that the release of both hormones is greater in more distal regions of the human colon, but is not different between sexes. We observe a negative correlation of GLP-1 and BMI in the small, but not large, intestine. Increased aging correlates with declining secretion of both GLP-1 and PYY in human large, but not small, intestine. When the data for large intestine is isolated by region, this relationship with age remains significant for GLP-1 in the ascending and descending colon and in the descending colon for PYY. This is the first demonstration that site-specific differences in GLP-1 and PYY release occur in human gut, as do site-specific relationships of L cell secretion with aging and body mass.
Language	English
Publishing date	2023-09-20
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	187438-x
ISSN	1872-8057 ; 0303-7207
ISSN (online)	1872-8057
ISSN	0303-7207
DOI	10.1016/j.mce.2023.112072
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Article ; Online: Characteristics associated with spine injury on magnetic resonance imaging in children evaluated for abusive head trauma.

Rabbitt, Angela L / Kelly, Teresa G / Yan, Ke / Zhang, Jian / Bretl, Deborah A / Quijano, Carla V

Pediatric radiology

2020 Volume 50, Issue 1, Page(s) 83–97

Abstract: Background: Spine injuries are increasingly common in the evaluation for abusive head trauma (AHT), but additional information is needed to explore the utility of spine MRI in AHT evaluations and to ensure an accurate understanding of injury mechanism.!# ...

Abstract	Background: Spine injuries are increasingly common in the evaluation for abusive head trauma (AHT), but additional information is needed to explore the utility of spine MRI in AHT evaluations and to ensure an accurate understanding of injury mechanism. Objective: To assess the incidence of spine injury on MRI in children evaluated for AHT, and to correlate spine MRI findings with clinical characteristics. Materials and methods: We identified children younger than 5 years who were evaluated for AHT with spine MRI. Abuse likelihood was determined a priori by expert consensus. We blindly reviewed spine MRIs and compared spinal injury, abuse likelihood, patient demographics, severity of brain injury, presence of retinal hemorrhages, and pattern of head injury between children with and without spine injury. Results: Forty-five of 76 (59.2%) children had spine injury. Spine injury was associated with more severe injury (longer intensive care stays [P<0.001], lower initial mental status [P=0.01] and longer ventilation times [P=0.001]). Overall abuse likelihood and spine injury were not associated. Spinal subdural hemorrhage was the only finding associated with a combination of retinal hemorrhages (P=0.01), noncontact head injuries (P=0.008) and a diagnosis of AHT (P<0.05). Spinal subdural hemorrhage was associated with other spine injury (P=0.004) but not with intracranial hemorrhage (P=0.28). Conclusion: Spinal injury is seen in most children evaluated for AHT and might be clinically and forensically valuable. Spinal subdural hemorrhage might support a mechanism of severe acceleration/deceleration head injury and a diagnosis of AHT.
MeSH term(s)	Child Abuse/diagnosis ; Craniocerebral Trauma/complications ; Craniocerebral Trauma/diagnostic imaging ; Diagnosis, Differential ; Female ; Humans ; Infant ; Magnetic Resonance Imaging/methods ; Male ; Retrospective Studies ; Spinal Injuries/complications ; Spinal Injuries/diagnostic imaging ; Spine/diagnostic imaging
Keywords	covid19
Language	English
Publishing date	2020-01-04
Publishing country	Germany
Document type	Journal Article
ZDB-ID	124459-0
ISSN	1432-1998 ; 0301-0449
ISSN (online)	1432-1998
ISSN	0301-0449
DOI	10.1007/s00247-019-04517-y
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