Portosinusoidální vaskulární choroba (PSVD) je málo rozpoznávané onemocnění jater podmíněné postižením malých cév. Diagnóza je definována souborem klinických a/nebo histopatologických kritérií, absolutní podmínkou je vyloučení cirhózy jater biopsií. Klinicky se PSVD obvykle manifestuje komplikací portální hypertenze, ta ale nemusí byt vyjádřena u všech nemocných. V článku popisujeme případ 71letého pacienta se známou, hematologicky nevysvětlenou a dále neprošetřenou splenomegalií, který byl vyšetřen pro těžkou symptomatickou mikrocytární anemii, pravděpodobně sekundární k portální hypertenzi, byť bez deklarovaných krvácivých projevů. Za hospitalizace byla provedena ligace velkých rizikových varixů jícnu, jiný zdroj anemizace prokázán nebyl. U pacienta byla vyloučena pre- nebo posthepatální etiologie portální hypertenze, elastografie jater byla ve fyziologických hodnotách, jaterní testy byly vyjma marginální izolované elevace gama-glutamyltransferázy v normě, funkce jater byla intaktní. V jaterní biopsii byl nález kompatibilní s diagnózou PSVD. U pacienta nebylo rozpoznáno žádné z asociovaných onemocnění, rovněž neužíval rizikovou medikaci, léčba tudíž spočívala pouze v řešení komplikací portální hypertenze, ambulantně byla dokončena eradikace jícnových varixů. Při terapii perorálním preparátem železa došlo k normalizaci hemoglobinu, fyziologické hodnoty přetrvávají i měsíce po ukončení substituční léčby, jaterní funkce je nadále v normě.
Portosinusoidal vascular disease (PSVD) is a rarely recognized liver condition caused by the involvement of small hepatic vessels. The diagnosis is established based on a set of clinical and/or histopathological criteria, with the absolute requirement of excluding liver cirrhosis through biopsy. Clinically, PSVD often presents with complications related to portal hypertension, although not all patients exhibit these signs. This article discusses the case of a 71-year-old patient with known splenomegaly, which had not been fully investigated and lacked a hematological explanation. The patient was evaluated for severe symptomatic microcytic anemia, likely secondary to portal hypertension, despite the absence of overt bleeding symptoms. During hospitalization, ligation of large, high-risk esophageal varices was performed, and no other sources of anemia were identified. Pre- or post-hepatic causes of portal hypertension were ruled out. Liver elastography results were within normal ranges, and liver function tests were normal except for a marginal isolated elevation of gamma-glutamyltransferase. Liver function remained intact. Liver biopsy findings were consistent with a diagnosis of PSVD. The patient did not have any identifiable associated conditions and was not taking any medications known to pose a risk. Therefore, treatment was focused solely on managing the complications of portal hypertension. Outpatient follow-up included the eradication of esophageal varices. Treatment with oral iron supplements led to the normalization of hemoglobin levels, which remained stable for months after the discontinuation of therapy, and liver function tests continued to be normal.
- MeSH
- antihypertenziva terapeutické užití MeSH
- hypochromní anemie diagnóza farmakoterapie MeSH
- jaterní žilní okluze * diagnóza terapie MeSH
- karvedilol terapeutické užití MeSH
- lidé MeSH
- portální hypertenze * diagnóza farmakoterapie MeSH
- senioři MeSH
- splenomegalie MeSH
- železo terapeutické užití MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- kazuistiky MeSH
Investigating microorganisms in metal-enriched environments holds the potential to revolutionize the sustainable recovery of critical metals such as lanthanides (Ln3+). We observe Hyphomicrobium spp. as part of a Fe2+/Mn2+-oxidizing consortia native to the ferruginous bottom waters of a Ln3+-enriched lake in Czechia. Notably, one species shows similarities to recently discovered bacteria expressing proteins with picomolar Ln3+ affinity. This finding was substantiated by developing an in-silico ionic competition model and recombinant expression of a homolog protein (Hm-LanM) from Hyphomicrobium methylovorum. Biochemical assays validate Hm-LanM preference for lighter Ln3+ ions (from lanthanum to gadolinium). This is comparable to established prototypes. Bioinformatics analyses further uncover additional H. methylovorum metabolic biomolecules in genomic proximity to Hm-LanM analogously dependent on Ln3+, including an outer membrane receptor that binds Ln3+-chelating siderophores. These combined observations underscore the remarkable strategy of Hyphomicrobium spp. for thriving in relatively Ln3+ enriched zones of metal-polluted environments.
Andjelkovic, Marija, Peter Paal, Susi Kriemler, Kaste Mateikaite-Pipiriene, Alison Rosier, Beth Beidleman, Mia Derstine, Jacqueline Pichler Hefti, David Hillebrandt, Lenka Horakova, Dominique Jean, and Linda E. Keyes. Nutrition in women at high altitude: a scoping review-UIAA Medical Commission recommendations. High Alt Med Biol. 25:9-15, 2024. Background: Nutritional concerns such as food composition, energy intake, and nutrient absorption are essential for performance at high altitude and may differ between men and women. We performed a scoping review to summarize what is currently known on nutrition for women during short-term, high-altitude, physically active sojourns. Methods: The UIAA Medical Commission convened an international team to review women's health issues at high altitude and to publish updated recommendations. Pertinent literature from PubMed and Cochrane was identified by keyword search combinations (including nutrition, metabolism, energy composition, micronutrients) with additional publications found by hand search. Results: We found 7,165 articles, of which 13 original articles assessed nutritional aspects in physically active women on short-term high-altitude sojourns, with other articles found by hand search. We summarize the main findings. Conclusions: Data on women's nutrition at altitude are very limited. Reduction in energy intake plus increased energy expenditure at high altitude can lead to unbalanced nutrition, negatively influencing high-altitude adaptation and physical performance. Therefore, adequate dietary and fluid intake is essential to maintaining energy balance and hydration at high altitude in women as in men. Iron supplementation should be considered for women with iron depletion before travel.
- MeSH
- dieta * MeSH
- lidé MeSH
- nadmořská výška * MeSH
- železo MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- MeSH
- anemie * etiologie klasifikace krev terapie MeSH
- hypochromní anemie dietoterapie etiologie farmakoterapie MeSH
- komplikace těhotenství * krev MeSH
- kyselina listová aplikace a dávkování MeSH
- lékové formy MeSH
- lidé MeSH
- těhotenství MeSH
- železo terapeutické užití MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- přehledy MeSH
Mitochondrial autophagy (mitophagy) is very important process for the maintenance of cellular homeostasis, functionality and survival. Its dysregulation is associated with high risk and progression numerous serious diseases (e.g., oncological, neurodegenerative and cardiovascular ones). Therefore, targeting mitophagy mechanisms is very hot topic in the biological and medicinal research. The interrelationships between the regulation of mitophagy and iron homeostasis are now becoming apparent. In short, mitochondria are central point for the regulation of iron homeostasis, but change in intracellular cheatable iron level can induce/repress mitophagy. In this review, relationships between iron homeostasis and mitophagy are thoroughly discussed and described. Also, therapeutic applicability of mitophagy chelators in the context of individual diseases is comprehensively and critically evaluated.
Bordetella pertussis infects the upper airways of humans and disarms host defense by the potent immuno-subversive activities of its pertussis (PT) and adenylate cyclase (CyaA) toxins. CyaA action near-instantly ablates the bactericidal activities of sentinel CR3-expressing myeloid phagocytes by hijacking cellular signaling pathways through the unregulated production of cAMP. Moreover, CyaA-elicited cAMP signaling also inhibits the macrophage colony-stimulating factor (M-CSF)-induced differentiation of incoming inflammatory monocytes into bactericidal macrophages. We show that CyaA/cAMP signaling via protein kinase A (PKA) downregulates the M-CSF-elicited expression of monocyte receptors for transferrin (CD71) and hemoglobin-haptoglobin (CD163), as well as the expression of heme oxygenase-1 (HO-1) involved in iron liberation from internalized heme. The impact of CyaA action on CD71 and CD163 levels in differentiating monocytes is largely alleviated by the histone deacetylase inhibitor trichostatin A (TSA), indicating that CyaA/cAMP signaling triggers epigenetic silencing of genes for micronutrient acquisition receptors. These results suggest a new mechanism by which B. pertussis evades host sentinel phagocytes to achieve proliferation on airway mucosa.IMPORTANCETo establish a productive infection of the nasopharyngeal mucosa and proliferate to sufficiently high numbers that trigger rhinitis and aerosol-mediated transmission, the pertussis agent Bordetella pertussis deploys several immunosuppressive protein toxins that compromise the sentinel functions of mucosa patrolling phagocytes. We show that cAMP signaling elicited by very low concentrations (22 pM) of Bordetella adenylate cyclase toxin downregulates the iron acquisition systems of CD14+ monocytes. The resulting iron deprivation of iron, a key micronutrient, then represents an additional aspect of CyaA toxin action involved in the inhibition of differentiation of monocytes into the enlarged bactericidal macrophage cells. This corroborates the newly discovered paradigm of host defense evasion mechanisms employed by bacterial pathogens, where manipulation of cellular cAMP levels blocks monocyte to macrophage transition and replenishment of exhausted phagocytes, thereby contributing to the formation of a safe niche for pathogen proliferation and dissemination.
- MeSH
- adenylátcyklasový toxin * metabolismus genetika MeSH
- AMP cyklický * metabolismus MeSH
- antigeny CD14 * metabolismus MeSH
- antigeny diferenciační myelomonocytární MeSH
- Bordetella pertussis * MeSH
- buněčná diferenciace * MeSH
- CD antigeny metabolismus genetika MeSH
- lidé MeSH
- monocyty * metabolismus imunologie mikrobiologie MeSH
- proteinkinasy závislé na cyklickém AMP metabolismus MeSH
- receptory buněčného povrchu metabolismus genetika MeSH
- signální transdukce * MeSH
- upregulace MeSH
- železo metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Exercise-induced inflammation can influence iron metabolism. Conversely, the effects of vitamin D3, which possesses anti-inflammatory properties, on ultramarathon-induced heart damage and changes in iron metabolism have not been investigated. Thirty-five healthy long-distance semi-amateur runners were divided into two groups: one group received 150,000 IU of vitamin D3 24 h prior to a race (n = 16), while the other group received a placebo (n = 19). Serum iron, hepcidin (HPC), ferritin (FER), erythroferrone (ERFE), erythropoietin (EPO), neopterin (NPT), and cardiac troponin T (cTnT) levels were assessed. A considerable effect of ultramarathon running on all examined biochemical markers was observed, with a significant rise in serum levels of ERFE, EPO, HPC, NPT, and cTnT detected immediately post-race, irrespective of the group factor. Vitamin D3 supplementation showed a notable interaction with the UM, specifically in EPO and cTnT, with no other additional changes in the other analysed markers. In addition to the correlation between baseline FER and post-run ERFE, HPC was modified by vitamin D. The ultramarathon significantly influenced the EPO/ERFE/HPC axis; however, a single substantial dose of vitamin D3 had an effect only on EPO, which was associated with the lower heart damage marker cTnT after the run.
- MeSH
- běh fyziologie MeSH
- biologické markery * krev MeSH
- cholekalciferol * aplikace a dávkování MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- erythropoetin krev aplikace a dávkování MeSH
- hepcidiny krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- maratonský běh * MeSH
- nemoci srdce prevence a kontrola etiologie MeSH
- potravní doplňky * MeSH
- troponin T krev MeSH
- železo * krev aplikace a dávkování MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
Isolated REM sleep behavior disorder (iRBD) is an early stage of synucleinopathy with most patients progressing to Parkinson's disease (PD) or related conditions. Quantitative susceptibility mapping (QSM) in PD has identified pathological iron accumulation in the substantia nigra (SN) and variably also in basal ganglia and cortex. Analyzing whole-brain QSM across iRBD, PD, and healthy controls (HC) may help to ascertain the extent of neurodegeneration in prodromal synucleinopathy. 70 de novo PD patients, 70 iRBD patients, and 60 HCs underwent 3 T MRI. T1 and susceptibility-weighted images were acquired and processed to space standardized QSM. Voxel-based analyses of grey matter magnetic susceptibility differences comparing all groups were performed on the whole brain and upper brainstem levels with the statistical threshold set at family-wise error-corrected p-values <.05. Whole-brain analysis showed increased susceptibility in the bilateral fronto-parietal cortex of iRBD patients compared to both PD and HC. This was not associated with cortical thinning according to the cortical thickness analysis. Compared to iRBD, PD patients had increased susceptibility in the left amygdala and hippocampal region. Upper brainstem analysis revealed increased susceptibility within the bilateral SN for both PD and iRBD compared to HC; changes were located predominantly in nigrosome 1 in the former and nigrosome 2 in the latter group. In the iRBD group, abnormal dopamine transporter SPECT was associated with increased susceptibility in nigrosome 1. iRBD patients display greater fronto-parietal cortex involvement than incidental early-stage PD cohort indicating more widespread subclinical neuropathology. Dopaminergic degeneration in the substantia nigra is paralleled by susceptibility increase, mainly in nigrosome 1.
- MeSH
- lidé MeSH
- mozek diagnostické zobrazování patologie MeSH
- Parkinsonova nemoc * komplikace MeSH
- porucha chování v REM spánku * diagnostické zobrazování MeSH
- substantia nigra diagnostické zobrazování patologie MeSH
- synukleinopatie * komplikace patologie MeSH
- železo MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
