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Developmental Medicine and Child... Apr 2024Bachmann-Bupp syndrome (BABS) is a neurodevelopmental disorder characterized by developmental delay, hypotonia, and varying forms of non-congenital alopecia. The... (Review)
Review
Bachmann-Bupp syndrome (BABS) is a neurodevelopmental disorder characterized by developmental delay, hypotonia, and varying forms of non-congenital alopecia. The condition is caused by 3'-end mutations of the ornithine decarboxylase 1 (ODC1) gene, which produce carboxy (C)-terminally truncated variants of ODC, a pyridoxal 5'-phosphate-dependent enzyme. C-terminal truncation of ODC prevents its ubiquitin-independent proteasomal degradation and leads to cellular accumulation of ODC enzyme that remains catalytically active. ODC is the first rate-limiting enzyme that converts ornithine to putrescine in the polyamine pathway. Polyamines (putrescine, spermidine, spermine) are aliphatic molecules found in all forms of life and are important during embryogenesis, organogenesis, and tumorigenesis. BABS is an ultra-rare condition with few reported cases, but it serves as a convincing example for drug repurposing therapy. α-Difluoromethylornithine (DFMO, also known as eflornithine) is an ODC inhibitor with a strong safety profile in pediatric use for neuroblastoma and other cancers as well as West African sleeping sickness (trypanosomiasis). Patients with BABS have been treated with DFMO and have shown improvement in hair growth, muscle tone, and development.
Topics: Humans; Child; Putrescine; Spermidine; Polyamines; Spermine; Eflornithine
PubMed: 37469105
DOI: 10.1111/dmcn.15687 -
Nutrients Apr 2024Histamine intolerance is a condition characterized by the accumulation of histamine to a point that exceeds the body's capacity to eliminate it. Researchers have... (Review)
Review
Histamine intolerance is a condition characterized by the accumulation of histamine to a point that exceeds the body's capacity to eliminate it. Researchers have attributed several reasons to this condition, such as genetic factors, alcohol, and dietary deficiencies, among other elements. Symptoms of histamine intolerance have been found to extend beyond the gastrointestinal tract and to the whole body, with these symptoms being sporadic and non-specific. This review will explore various aspects related to histamine intolerance, such as its causes, symptoms, diagnosis, and information related to management.
Topics: Humans; Histamine; Food Intolerance; Food Hypersensitivity
PubMed: 38674909
DOI: 10.3390/nu16081219 -
IUCrData Dec 2023The reaction of ethane-1,2-di-amine (en, CHN), the sodium salt of naphthalene-1,5-di-sulfonic acid (HNDS, CHOS), and nickel sulfate in an aqueous solution resulted in...
The reaction of ethane-1,2-di-amine (en, CHN), the sodium salt of naphthalene-1,5-di-sulfonic acid (HNDS, CHOS), and nickel sulfate in an aqueous solution resulted in the formation of the title salt, [Ni(CHN)(HO)](CHOS)·2HO or [Ni(en)(HO)](NDS)·2HO. In the asymmetric unit, one half of an [Ni(en)(HO)] cation and one half of an NDS anion, and one water mol-ecule of crystallization are present. The Ni cation in the complex is positioned on a twofold rotation axis and exhibits a slight tetra-gonal distortion of the -NiON octa-hedron, with an Ni-N bond length of 2.0782 (16) Å, and Ni-O bond lengths of 2.1170 (13) Å and 2.0648 (14) Å. The anion is completed by inversion symmetry. In the extended structure, the cations, anions, and non-coordinating water mol-ecules are connected by inter-molecular N-H⋯O and O-H⋯O hydrogen bonding, as well as C-H⋯π inter-actions, forming a three-dimensional network.
PubMed: 38313205
DOI: 10.1107/S2414314623010325 -
Biomedical Papers of the Medical... Sep 2023A case report of a 40-year-old patient with tuberculosis treated with ethambutol is described. Within six months of starting treatment, there was a painless sudden...
PURPOSE
A case report of a 40-year-old patient with tuberculosis treated with ethambutol is described. Within six months of starting treatment, there was a painless sudden decline in visual function. Despite the known complications of ethambutol treatment, it was discontinued after another three months.
METHODS
In the case report, we highlight the damage to the dominantly peripheral visual pathways. Using electrophysiological examinations, we showed a significant alteration in the optic nerves. Optical Coherence Tomography (OCT) showed progressive loss of vessel density and nerve fibre layer of retinal ganglion cells. Perimetric examination showed both a central decrease in sensitivity and mainly scotomas in the temporal parts of the visual fields. Although there was improvement in visual fields over time, OCT findings indicated progression of ethambutol-induced optic neuropathy (EON). Magnetic Resonance Imaging confirmed the alteration in the peripheral part of the visual pathway (intraorbital, intracranial parts of optic nerves, chiasma, and optic tracts).
CONCLUSION
Even though EON is not an unknown complication, new cases still occur and, unfortunately, with an irreversible course. Therefore, it is important to draw attention constantly to this complication and to consider it not only in ophthalmologists' surgeries.
Topics: Humans; Adult; Ethambutol; Antitubercular Agents; Optic Nerve Diseases; Optic Nerve; Tuberculosis; Tomography, Optical Coherence
PubMed: 35582729
DOI: 10.5507/bp.2022.022 -
Heart (British Cardiac Society) Jul 2023Hypertrophic cardiomyopathy (HCM) is characterised by left ventricular hypertrophy (LVH), myocardial fibrosis, enhanced oxidative stress and energy depletion.... (Randomized Controlled Trial)
Randomized Controlled Trial
AIMS
Hypertrophic cardiomyopathy (HCM) is characterised by left ventricular hypertrophy (LVH), myocardial fibrosis, enhanced oxidative stress and energy depletion. Unbound/loosely bound tissue copper II ions are powerful catalysts of oxidative stress and inhibitors of antioxidants. Trientine is a highly selective copper II chelator. In preclinical and clinical studies in diabetes, trientine is associated with reduced LVH and fibrosis, and improved mitochondrial function and energy metabolism. Trientine was associated with improvements in cardiac structure and function in an open-label study in patients with HCM.
METHODS
The Efficacy and Mechanism of Trientine in Patients with Hypertrophic Cardiomyopathy (TEMPEST) trial is a multicentre, double-blind, parallel group, 1:1 randomised, placebo-controlled phase II trial designed to evaluate the efficacy and mechanism of action of trientine in patients with HCM. Patients with a diagnosis of HCM according to the European Society of Cardiology Guidelines and in New York Heart Association classes I-III are randomised to trientine or matching placebo for 52 weeks. Primary outcome is change in left ventricular (LV) mass indexed to body surface area, measured using cardiovascular magnetic resonance. Secondary efficacy objectives will determine whether trientine improves exercise capacity, reduces arrhythmia burden, reduces cardiomyocyte injury, improves LV and atrial function, and reduces LV outflow tract gradient. Mechanistic objectives will determine whether the effects are mediated by cellular or extracellular mass regression and improved myocardial energetics.
CONCLUSION
TEMPEST will determine the efficacy and mechanism of action of trientine in patients with HCM.
TRIAL REGISTRATION NUMBERS
NCT04706429 and ISRCTN57145331.
Topics: Humans; Trientine; Copper; Cardiomyopathy, Hypertrophic; Heart; Hypertrophy, Left Ventricular; Fibrosis
PubMed: 37137675
DOI: 10.1136/heartjnl-2022-322271 -
Cell Reports. Medicine Nov 2023In preclinical models, α-difluoromethylornithine (DFMO), an ornithine decarboxylase (ODC) inhibitor, delays the onset of type 1 diabetes (T1D) by reducing β cell... (Randomized Controlled Trial)
Randomized Controlled Trial
In preclinical models, α-difluoromethylornithine (DFMO), an ornithine decarboxylase (ODC) inhibitor, delays the onset of type 1 diabetes (T1D) by reducing β cell stress. However, the mechanism of DFMO action and its human tolerability remain unclear. In this study, we show that mice with β cell ODC deletion are protected against toxin-induced diabetes, suggesting a cell-autonomous role of ODC during β cell stress. In a randomized controlled trial (ClinicalTrials.gov: NCT02384889) involving 41 recent-onset T1D subjects (3:1 drug:placebo) over a 3-month treatment period with a 3-month follow-up, DFMO (125-1,000 mg/m) is shown to meet its primary outcome of safety and tolerability. DFMO dose-dependently reduces urinary putrescine levels and, at higher doses, preserves C-peptide area under the curve without apparent immunomodulation. Transcriptomics and proteomics of DFMO-treated human islets exposed to cytokine stress reveal alterations in mRNA translation, nascent protein transport, and protein secretion. These findings suggest that DFMO may preserve β cell function in T1D through islet cell-autonomous effects.
Topics: Humans; Mice; Animals; Diabetes Mellitus, Type 1; Ornithine Decarboxylase; Ornithine Decarboxylase Inhibitors; Eflornithine; Putrescine
PubMed: 37918404
DOI: 10.1016/j.xcrm.2023.101261 -
Journal of Clinical Medicine Dec 2023Histamine intolerance arises when there is a disparity between the production of histamine and the body's ability to break it down. In the gastrointestinal tract, the...
Histamine intolerance arises when there is a disparity between the production of histamine and the body's ability to break it down. In the gastrointestinal tract, the primary enzyme responsible for metabolizing ingested histamine is diamine oxidase (DAO), and a shortage of this enzyme has been associated with some diseases related to the respiratory, cardiovascular, nervous, muscular, and digestive systems, in addition to migraines. The treatment of migraines typically revolves around the utilization of both anti-migraine and anti-inflammatory drugs, but their interaction with DAO is not thoroughly understood. In this study, we examined the impact of nonsteroidal anti-inflammatory drugs (NSAIDs) and anti-migraine medications on DAO activity through in vitro experiments. We also investigated their effects on the human intestinal cell line Caco-2, assessing changes in DAO expression (both at the mRNA and protein levels) as well as DAO activity. The tested drugs, including ibuprofen, acetylsalicylic acid, paracetamol, a combination of acetylsalicylic acid with paracetamol and caffeine, zolmitriptan, and sumatriptan, did not inhibit DAO activity or reduce their levels. However, naproxen reduced DAO protein levels in human enterocyte cultures while not affecting DAO activity. These results suggest that combining anti-inflammatory and anti-migraine drugs with DAO enzyme supplementation for migraine patients with DAO deficiency could be beneficial for healthcare professionals in their daily practice.
PubMed: 38068554
DOI: 10.3390/jcm12237502