ABSTRACT
INTRODUCTION: Although renal stenting is the standard revascularization method for atherosclerotic renal artery stenosis (RAS) (FMD-RAS), stenting in fibromuscular dysplasia (FMD) RAS is usually limited to periprocedural complications of angioplasty and primary arterial dissection. The main aim of the study was to retrospectively analyze the immediate and long-term results of renal stenting versus angioplasty in patients with FMD. METHODS: Of 343 patients in the ARCADIA-POL registry, 58 patients underwent percutaneous treatment due to FMD-RAS (in 70 arteries). Percutaneous transluminal renal angioplasty (PTRA) was performed as an initial treatment in 61 arteries (PTRA-group), whereas primary stenting was undertaken in nine arteries (stent-group). Stent-related complications were defined as: in-stent restenosis > 50% (ISR); stent fracture; under-expansion; or migration. RESULTS: In the PTRA-group, the initial restenosis rate was 50.8%. A second procedure was then performed in 22 arteries: re-PTRA (12 arteries) or stenting (10 arteries). The incidence of recurrent restenosis after re-PTRA was 41.7%. Complications occurred in seven of 10 (70%) arteries secondarily treated by stenting: two with under-expansion and five with ISR. In the stent-group, stent under-expansion occurred in one case (11.1%) and ISR in three of nine stents (33.3%). In combined analysis of stented arteries, either primarily or secondarily, stent-related complications occurred in 11/19 stenting procedures (57.9%): three due to under-expansion and eight due to ISRs. Finally, despite several revascularization attempts, four of 19 (21%) stented arteries were totally occluded and one was significantly stenosed at follow-up imaging. CONCLUSION: Our study indicates that renal stenting in FMD-RAS may carry a high risk of late complications, including stent occlusion. Further observational data from large-scale registries are required.
Subject(s)
Angioplasty, Balloon , Fibromuscular Dysplasia , Renal Artery Obstruction , Humans , Renal Artery/diagnostic imaging , Renal Artery/surgery , Fibromuscular Dysplasia/complications , Fibromuscular Dysplasia/diagnostic imaging , Fibromuscular Dysplasia/therapy , Angioplasty, Balloon/adverse effects , Retrospective Studies , Treatment Outcome , Renal Artery Obstruction/diagnostic imaging , Renal Artery Obstruction/etiology , Renal Artery Obstruction/therapy , Risk Assessment , Stents/adverse effectsABSTRACT
Chronic pancreatitis (CP) in young individuals may lead to disease-related secondary sarcopenia (SSARC), characterized by muscle loss and systemic inflammation. In this study, CP was induced in young pigs, and serum levels of key hormones, muscle fiber diameters in various muscles, and the mRNA expression of genes related to oxidative stress and programmed cell death were assessed. A decrease in muscle fiber diameters was observed in SSARC pigs, particularly in the longissimus and diaphragm muscles. Hormonal analysis revealed alterations in dehydroepiandrosterone, testosterone, oxytocin, myostatin, and cortisol levels, indicating a distinct hormonal response in SSARC pigs compared to controls. Oxytocin levels in SSARC pigs were significantly lower and myostatin levels higher. Additionally, changes in the expression of catalase (CAT), caspase 8 (CASP8), B-cell lymphoma 2 (BCL2), and BCL2-associated X protein (BAX) mRNA suggested a downregulation of oxidative stress response and apoptosis regulation. A reduced BAX/BCL2 ratio in SSARC pigs implied potential caspase-independent cell death pathways. The findings highlight the complex interplay between hormonal changes and muscle degradation in SSARC, underscoring the need for further research into the apoptotic and inflammatory pathways involved in muscle changes due to chronic organ inflammation in young individuals.
Subject(s)
Disease Models, Animal , Oxidative Stress , Pancreatitis, Chronic , Sarcopenia , Animals , Sarcopenia/metabolism , Sarcopenia/pathology , Swine , Pancreatitis, Chronic/metabolism , Pancreatitis, Chronic/pathology , Pancreatitis, Chronic/genetics , Apoptosis , Muscle, Skeletal/metabolism , Muscle, Skeletal/pathology , MaleABSTRACT
Chronic pancreatitis (CP), a progressive inflammatory disease, poses diagnostic challenges due to its initially asymptomatic nature. While CP's impact on exocrine and endocrine functions is well-recognized, its potential influence on other body systems, particularly in young individuals, remains underexplored. This study investigates the hypothesis that CP in growing pigs leads to alterations in articular cartilage and subchondral bone, potentially contributing to osteoarthritis (OA) development. Utilizing a pig model of cerulein-induced CP, we examined the structural and compositional changes in subchondral bone, articular cartilage, and synovial fluid. Histological analyses, including Picrosirius Red and Safranin-O staining, were employed alongside immuno-histochemistry and Western blotting techniques. Our findings reveal significant changes in the subchondral bone, including reduced bone volume and alterations in collagen fiber composition. Articular cartilage in CP pigs exhibited decreased proteoglycan content and alterations in key proteins such as MMP-13 and TGF-ß1, indicative of early cartilage degradation. These changes suggest a link between CP and musculoskeletal alterations, underscoring the need for further research into CP's systemic effects. Our study provides foundational insights into the relationship between CP and skeletal health, potentially guiding future pediatric healthcare strategies for early CP diagnosis and management.
Subject(s)
Cartilage, Articular , Osteoarthritis , Humans , Animals , Child , Swine , Cartilage, Articular/metabolism , Bone and Bones/metabolism , Osteoarthritis/metabolism , Proteoglycans/metabolism , Synovial Fluid/metabolismABSTRACT
Osteoporosis stands out as a prevalent skeletal ailment, prompting exploration into potential treatments, including dietary strontium ion supplements. This study assessed the efficacy of supplementation of three strontium forms-strontium citrate (SrC), strontium ranelate (SrR), and strontium chloride (SrCl)-for enhancing bone structure in 50 female SWISS mice, aged seven weeks. In total, 40 mice underwent ovariectomy, while 10 underwent sham ovariectomy. Ovariectomized (OVX) mice were randomly assigned to the following groups: OVX (no supplementation), OVX + SrR, OVX + SrC, and OVX + SrCl, at concentrations equivalent to the molar amount of strontium. After 16 weeks, micro-CT examined trabeculae and cortical bones, and whole-bone strontium content was determined. Results confirm strontium administration increased bone tissue mineral density (TMD) and Sr content, with SrC exhibiting the weakest effect. Femur morphometry showed limited Sr impact, especially in the OVX + SrC group. This research highlights strontium's potential in bone health, emphasizing variations in efficacy among its forms.
Subject(s)
Citric Acid , Osteoporosis , Strontium , Thiophenes , Female , Animals , Mice , Bone Density , Chlorides , Citrates , Osteoporosis/drug therapy , Halogens , Disease Models, AnimalABSTRACT
The weaning phase in piglets causes significant physiological stress, disrupts intestinal integrity and reduces productivity, necessitating strategies to improve intestinal health and nutrient absorption. While current research highlights the role of diet in mitigating these adverse effects, identifying effective dietary supplements remains a challenge. This study evaluated the effects of Hermetia illucens (HI) larvae meal and astaxanthin (AST) on the intestinal histology of weaned piglets. In a controlled experiment, 48 weaned piglets were divided into six groups and received varying levels of HI larval meal (2.5% and 5%) and AST in their diets. The methodology involved comprehensive histological examinations of the small intestine, assessing absorption area, villi elongation, crypt depth, goblet cells, enterocytes and expression of ileal tight junction (TJ) proteins. The study found that HI larval meal significantly improved nutrient absorption in the jejunum and ileum (p < 0.001), thereby enhancing feed conversion. AST supplementation increased the number of enterocytes (p < 0.001). Both HI larval meal and AST positively affected intestinal morphology and function, increasing muscularis muscle mass and villi elongation (p < 0.001 and p < 0.05, respectively). The 2.5% HI meal improved the villi length to crypt depth ratio and slightly increased the goblet cell count (both p < 0.05). Ki-67 antibody analysis showed increased cell proliferation in the duodenal and jejunal crypts, particularly with the 2.5% HI meal (p < 0.001). Insect meal did not affect TJ protein expression, indicating that it had no effect on intestinal permeability. These findings suggest that HI larval meal and AST can enhance the intestinal wellness and productivity of weaned piglets.
ABSTRACT
PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic and the subsequent lockdown profoundly affected almost all aspects of daily life including health services worldwide. The established risk factors for increased blood pressure (BP) and hypertension may also demonstrate significant changes during the pandemic. This study aims to determine the impact of the COVID-19 pandemic on BP control and BP phenotypes as assessed with 24-hour ambulatory BP monitoring (ABPM). MATERIALS AND METHODS: This is a multi-centre, observational, retrospective and comparative study involving Excellence Centres of the European Society of Hypertension across Europe. Along with clinical data and office BP, ABPM recordings will be collected in adult patients with treated arterial hypertension. There will be two groups in the study: Group 1 will consist of participants who have undergone two ABPM recordings - the second one occurring during the COVID-19 pandemic, i.e. after March 2020, and the first one 9-15 months prior to the second. Participants in Group 2 will have two repeated ABPM recordings - both performed before the pandemic within a similar 9-15 month interval between the recordings. Within each group, we will analyse and compare BP variables and phenotypes (including averaged daytime and night-time BP, BP variability, dipper and non-dipper status, white-coat and masked hypertension) between the two respective ABPM recordings and compare these changes between the two groups. The target sample size will amount to least 590 participants in each of the study groups, which means a total of at least 2360 ABPM recordings overall. EXPECTED OUTCOMES: As a result, we expect to identify the impact of a COVID-19 pandemic on blood pressure control and the quality of medical care in order to develop the strategy to control cardiovascular risk factors during unpredictable global events.
What is the context?A wide range of daily activities, including health care worldwide, were deeply affected by the Coronavirus disease 2019 pandemic and the subsequent lockdown.What is new?Our multicenter study will examine the impact of the COVID-19 pandemic on blood pressure control in hypertensive patients across Europe by analysing results of 24-hour ambulatory blood pressure monitoring.What is the impact?Optimising strategies for dealing with future unpredictable global situations will depend on understanding how the pandemic affected blood pressure control.
Subject(s)
COVID-19 , Hypertension , Humans , Blood Pressure Monitoring, Ambulatory , Pandemics , Retrospective Studies , COVID-19/epidemiology , Communicable Disease Control , Hypertension/drug therapy , Hypertension/epidemiology , Blood Pressure/physiologyABSTRACT
The goal of the current study was to examine the effects of prenatal exposure to fumonisins (FBs) on bone properties and metabolism in weaned rat offspring divided into groups intoxicated with FBs at either 0 (the 0 FB group), 60 (the 60 FB group), or 90 mg/kg b.w. 0 (the 90 FB group). Female and male offspring exposed to FBs at a dose of 60 mg/kg b.w. had heavier femora. Mechanical bone parameters changed in a sex and FBs dose-dependent manner. Growth hormone and osteoprotegerin decreased in both sexes, regardless of FBs dose. In males osteocalcin decreased, while receptor activator for nuclear factor kappa-Β ligand increased regardless of FBs dose; while in females changes were dose dependent. Leptin decreased in both male FBs-intoxicated groups, bone alkaline phosphatase decreased only in the 60 FB group. Matrix metalloproteinase-8 protein expression increased in both female FBs-intoxicated groups and decreased in male 90 FB group. Osteoprotegerin and tissue inhibitor of metalloproteinases 2 protein expression decreased in males, regardless of FBs dose, while nuclear factor kappa-Β ligand expression increased only in the 90 FB group. The disturbances in bone metabolic processes seemed to result from imbalances in the RANKL/RANK/OPG and the OC/leptin systems.
Subject(s)
Fumonisins , Osteoprotegerin , Rats , Male , Female , Animals , Osteoprotegerin/genetics , Osteoprotegerin/metabolism , Receptor Activator of Nuclear Factor-kappa B/metabolism , Fumonisins/toxicity , Leptin , Ligands , NF-kappa B/metabolism , Bone Development , RANK Ligand/genetics , RANK Ligand/metabolismABSTRACT
Chronic pancreatitis (CP) is an irreversible and progressive inflammatory disease. Knowledge on the development and progression of CP is limited. The goal of the study was to define the serum profile of pro-inflammatory cytokines and the cell antioxidant defense system (superoxidase dismutase-SOD, and reduced glutathione-GSH) over time in a cerulein-induced CP model and explore the impact of these changes on selected cytokines in the intestinal mucosa and pancreatic tissue, as well as on selected serum biochemical parameters. The mRNA expression of CLDN1 and CDH1 genes, and levels of Claudin-1 and E-cadherin, proteins of gut barrier, in the intestinal mucosa were determined via western blot analysis. The study showed moderate pathomorphological changes in the pigs' pancreas 43 days after the last cerulein injection. Blood serum levels of interleukin (IL)-1-beta, IL-6, tumor necrosis factor alpha (TNF-alpha), C-reactive protein (CRP), lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (GGTP), SOD and GSH were increased following cerulein injections. IL-1-beta, IL-6, TNF-alpha and GSH were also increased in jejunal mucosa and pancreatic tissue. In duodenum, decreased mRNA expression of CDH1 and level of E-cadherin and increased D-lactate, an indicator of leaky gut, indicating an inflammatory state, were observed. Based on the current results, we can conclude that repetitive cerulein injections in growing pigs not only led to CP over time, but also induced inflammation in the intestine. As a result of the inflammation, the intestinal barrier was impaired.
Subject(s)
Pancreatitis, Chronic , Tumor Necrosis Factor-alpha , Animals , Swine , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism , Ceruletide/pharmacology , Pilot Projects , Interleukin-6/metabolism , Pancreatitis, Chronic/pathology , Pancreas/metabolism , Cytokines/metabolism , Inflammation/metabolism , Superoxide Dismutase/metabolism , RNA, Messenger/metabolism , Disease Models, AnimalABSTRACT
Overactive bladder syndrome (OAB) is a prevalent condition that affects the elderly population in particular and significantly impairs quality of life. Imperatorin, a naturally occurring furocoumarin, possesses diverse pharmacological properties that warrant consideration for drug development. The aim of this study was to investigate the potential of imperatorin (IMP) to attenuate the cystometric and biochemical changes typically associated with retinyl acetate-induced overactive bladder (OAB) and to assess its viability as a pharmacological intervention for OAB patients. A total of 60 rats were divided into four groups: I-control, II-rats with rapamycin (RA)-induced OAB, III-rats administered IMP at a dose of 10 mg/kg/day, and IV-rats with RA-induced OAB treated with IMP. IMP or vehicle were injected intraperitoneally for 14 days. The cystometry and assessment of bladder blood flow were performed two days after the last dose of IMP. The rats were then placed in metabolic cages for 24 h. Urothelial thickness measurements and biochemical analyses were performed. Intravesical infusion of RA induced OAB. Notably, intraperitoneal administration of imperatorin had no discernible effect on urinary bladder function and micturition cycles in normal rats. IMP attenuated the severity of RA-induced OAB. RA induced increases in urothelial ATP, calcitonin gene-related peptide (CGRP), organic cation transporter 3 (OCT3), and vesicular acetylcholine transporter (VAChT), as well as significant c-Fos expression in all micturition areas analyzed, which were attenuated by IMP. Furthermore, elevated levels of Rho kinase (ROCK1) and VAChT were observed in the detrusor, which were reversed by IMP in the context of RA-induced OAB in the urothelium, detrusor muscle, and urine. Imperatorin has a mitigating effect on detrusor overactivity. The mechanisms of action of IMP in the bladder appear to be diverse and complex. These findings suggest that IMP may provide protection against RA-induced OAB and could potentially develop into an innovative therapeutic strategy for the treatment of OAB.
Subject(s)
Furocoumarins , Urinary Bladder, Overactive , Humans , Aged , Rats , Animals , Urinary Bladder, Overactive/drug therapy , Urinary Bladder, Overactive/etiology , Urinary Bladder, Overactive/metabolism , Quality of Life , Urinary Bladder , Furocoumarins/pharmacology , Furocoumarins/therapeutic use , rho-Associated KinasesABSTRACT
OBJECTIVE: The aim of the study was to investigate a new possible background of increased risk of cardiovascular events in two forms of endocrine hypertension: in primary aldosteronism (PA) and pheochromocytoma/paraganglioma (PPGL) in comparison to essential hypertension (EHT). CONTEXT: Prothrombotic properties of the fibrin clot structure, impaired fibrinolysis and enhanced thrombin generation have been reported to be associated with increased cardiovascular risk. DESIGN: Patients with PA and PPGL were evaluated at baseline and re-evaluated 3 months after causative treatment. At baseline PA and PPGL patients were compared to matched EHT patients and to healthy controls. PATIENTS: The study included 35 patients with PA, 16 patients with PPGL and two reference groups of patients with EHT (32 and 22 patients) and healthy controls (35 and 23 subjects). MEASUREMENTS: All subjects underwent evaluation according to the study protocol that included plasma fibrin clot permeability (Ks), clot lysis time, endogenous thrombin potential. RESULTS: There were no differences in clot structure and fibrinolytic activity in PA and PPGL patients as compared to matched patients with EHT, whereas all hypertensive groups were characterized by more compact fibrin clot structure, faster clot formation and enhanced thrombin generation in comparison to healthy controls. Both in PA and PPGL patients, fibrin clot properties and fibrinolytic parameters remained stable after the causative treatment. CONCLUSIONS: Patients with PA and PPGL are at a prothrombic state comparable to patients with EHT. The results suggest the higher risk of cardiovascular events observed in hypertensive PA and PPGL as compared to EHT is not mediated through investigated prothrombic mechanisms.
Subject(s)
Adrenal Gland Neoplasms , Hypertension , Aldosterone , Catecholamines , Fibrin , Fibrin Clot Lysis Time , Fibrinolysis , HumansABSTRACT
BACKGROUND: Data on the relationship between longitudinal changes in maternal volume-dependent echocardiographic parameters and placentation in uncomplicated pregnancy are limited. OBJECTIVE: This study aimed to evaluate changes in volume-dependent echocardiographic parameters in uncomplicated pregnancy to test the hypothesis of the existence of an association between volume-dependent echocardiographic parameters and Doppler ultrasound parameters of fetal circulation and the uterine artery in uncomplicated pregnancy and to establish which of the volume-dependent echocardiographic parameters best depicts volume changes and correlates best with Doppler ultrasound of fetal circulation and the uterine artery in healthy pregnancy. STUDY DESIGN: Data from 60 healthy pregnant women were analyzed. A complete echocardiographic study was performed at 11 to 13, 20 to 22, and 30 to 32 weeks' gestation: left ventricular end-diastolic volume, early diastolic peak flow velocity, late diastolic peak flow velocity, left atrial area, and left atrial volume index were assessed. Obstetrical assessment was performed including fetal growth and uterine artery pulsatility index. Fetal well-being was assessed by umbilical and middle cerebral artery blood flow. Serum pregnancy-associated plasma protein A and free ß-human chorionic gonadotropin were assessed during the routine first-trimester scan (11-13 weeks' gestation). RESULTS: Left ventricular end-diastolic volume and left atrial area increased significantly between 11 to 13 and 20 to 22 weeks' gestation but not between 20 to 22 and 30 to 32 weeks' gestation. Left atrial volume index measured at 30 to 32 weeks' gestation correlated with uterine artery pulsatility indices in 3 trimesters. Changes in the left atrial volume index between the third and first trimesters correlated significantly with the uterine artery pulsatility index measured at 20 to 22 weeks' gestation (r=-0.345; P=.020) and at 30 to 32 weeks' gestation (r=-0.452; P=.002). Changes in the left atrial volume index between the second and first trimesters significantly correlated with the uterine artery pulsatility index measured in the first trimester (r=-0.316; P=.025). CONCLUSION: Our study showed that in an uncomplicated pregnancy, among volume-dependent echocardiographic parameters, left atrial volume index increased between both the first and second trimesters and the second and third trimesters and correlated with parameters of Doppler ultrasound of the fetal circulation and the uterine artery. Our results expand on the previous observation on the relationship between maternal cardiovascular adaptation and placentation in women with heart diseases to the population of healthy women with uncomplicated pregnancy.
Subject(s)
Heart Atria/diagnostic imaging , Middle Cerebral Artery/diagnostic imaging , Pregnancy/physiology , Pulsatile Flow , Umbilical Arteries/diagnostic imaging , Uterine Artery/diagnostic imaging , Adult , Blood Flow Velocity/physiology , Chorionic Gonadotropin, beta Subunit, Human/metabolism , Echocardiography , Female , Heart Atria/anatomy & histology , Humans , Organ Size , Pregnancy/metabolism , Pregnancy Trimester, First , Pregnancy Trimester, Second , Pregnancy Trimester, Third , Pregnancy-Associated Plasma Protein-A/metabolism , Stroke Volume/physiology , Ultrasonography, Doppler , Ultrasonography, PrenatalABSTRACT
PURPOSE: Current evidence regarding renal involvement in pheochromocytoma and paraganglioma (PPGL) is scant. More accurate diagnostic methods, such as renal Doppler ultrasound for intrarenal hemodynamic studies, may provide more detailed information on renal function. It might be postulated that renal function in PPGL patients might be altered by high blood pressure and excess secretion of catecholamines. The aim of this prospective study was to assess intrarenal blood flow parameters in PPGL patients included in the prospective monoamine-producing tumour (PMT) study and to evaluate the effects of normalisation of catecholamine production after surgical treatment on long-term renal function. MATERIALS AND METHODS: Seventy consecutive patients (aged 46.5 ± 14.0 years) with PPGL were included. Forty-eight patients from the PMT study cohort, matched for age, gender, blood pressure level and presence of hypertension, served as a control group. Renal artery doppler ultrasound spectral analysis included mean resistance index (RRI) and pulsatility index (PI). Forty-seven patients completed 12 months follow-up. RESULTS: There were no differences in renal parameters such as RRI, PI and kidney function between PPGL and non-PPGL patients as assessed by renal ultrasound, serum creatinine, eGFR and albumin excretion rate. No correlations between kidney function parameters, intrarenal doppler flow parameters and plasma catecholamines were observed in PPGL patients. At 12 months after surgery, no differences in creatinine level, eGFR, albumin excretion rate, RI and PI were found as compared to baseline results. CONCLUSIONS: In contrast to patients with other forms of secondary hypertension, our study did not show differences in intrarenal blood flow parameters and renal function between PPGL and non-PPGL subjects. Intrarenal hemodynamics and renal function did not change after normalisation of catecholamine levels by surgical treatment.
Subject(s)
Adrenal Gland Neoplasms/surgery , Hemodynamics , Kidney , Paraganglioma/surgery , Pheochromocytoma/surgery , Ultrasonography, Doppler , Adrenal Gland Neoplasms/blood , Adrenal Gland Neoplasms/diagnostic imaging , Adult , Cross-Sectional Studies , Female , Humans , Kidney/blood supply , Kidney/diagnostic imaging , Kidney/metabolism , Kidney/physiopathology , Kidney Function Tests , Male , Middle Aged , Paraganglioma/blood , Paraganglioma/diagnostic imaging , Pheochromocytoma/blood , Pheochromocytoma/diagnostic imaging , Retrospective StudiesABSTRACT
The current study examined the effects of exposure of pregnant dams to fumonisins (FBs; FB1 and FB2), from the seventh day of pregnancy to parturition, on offspring bone metabolism and properties. The rats were randomly divided into three groups intoxicated with FBs at either 0, 60, or 90 mg/kg b.w. Body weight and bone length were affected by fumonisin exposure, irrespective of sex or dose, while the negative and harmful effects of maternal FBs' exposure on bone mechanical resistance were sex and dose dependent. The immunolocalization of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa-Β ligand (RANKL), in bone and articular cartilage, indicated that the observed bone effects resulted from the FB-induced alterations in bone metabolism, which were confirmed by the changes observed in the Western blot expression of OPG and RANKL. It was concluded that the negative effects of prenatal FB exposure on the general growth and morphometry of the offspring bones, as a result of the altered expression of proteins responsible for bone metabolism, were dose and sex dependent.
Subject(s)
Cancellous Bone/metabolism , Fumonisins/toxicity , Osteoprotegerin/metabolism , Prenatal Exposure Delayed Effects/metabolism , RANK Ligand/metabolism , Animals , Body Weight/drug effects , Cancellous Bone/drug effects , Cartilage, Articular/metabolism , Dose-Response Relationship, Drug , Female , Male , Pregnancy , Prenatal Exposure Delayed Effects/chemically induced , Rats , Sex CharacteristicsABSTRACT
Fumonisins are protein serine/threonine phosphatase inhibitors and potent inhibitors of sphingosine N-acyltransferase (ceramide synthase) disrupting de novo sphingolipid biosynthesis. The experiment was conducted to evaluate the effects of fumonisins (FB) exposure from the 7th day of pregnancy to parturition on offspring bone development. The rats were randomly allocated to either a control group (n = 6), not treated with FBs, or to one of the two groups intoxicated with FBs (either at 60 mg FB/kg b.w. or at 90 mg FB/kg b.w. Numerous negative, offspring sex-dependent effects of maternal FB exposure were observed with regards to the histomorphometry of trabecular bone. These effects were due to FB-inducted alterations in bone metabolism, as indicated by changes in the expression of selected proteins involved in bone development: tissue inhibitor of metalloproteinases 2 (TIMP-2), matrix metalloproteinase 8 (MMP-8), matrix metalloproteinase 13 (MMP-13), and vascular endothelial growth factor (VEGF). The immunolocalization of MMPs and TIMP-2 was performed in trabecular and compact bone, as well as articular and growth plate cartilages. Based on the results, it can be concluded that the exposure of pregnant dams to FB negatively affected the expression of certain proteins responsible for bone matrix degradation in newborns prenatally exposed to FB in a dose- and sex-dependent manner.
Subject(s)
Fumonisins/pharmacology , Matrix Metalloproteinase 13/genetics , Matrix Metalloproteinase 8/genetics , Tissue Inhibitor of Metalloproteinase-2/genetics , Vascular Endothelial Growth Factor A/genetics , Animals , Animals, Newborn , Bone Development/genetics , Cancellous Bone/drug effects , Cancellous Bone/growth & development , Cartilage/growth & development , Cartilage/metabolism , Female , Gene Expression Regulation, Developmental/drug effects , Growth Plate/drug effects , Oxidoreductases/antagonists & inhibitors , Oxidoreductases/genetics , Pregnancy , Rats , Sphingolipids/biosynthesisABSTRACT
The aim of this study was to determine the effects of ß-hydroxy-ß-methylbutyrate (HMB) supplementation during pregnancy on postpartum bone tissue quality by assessing changes in trabecular and compact bone as well as in hyaline and epiphyseal cartilage. The experiment was carried out on adult 6-month-old female spiny mice (Acomys cahirinus) divided into three groups: pregnant control (PregCont), pregnant HMB-treated (supplemented with 0.02 g/kg b.w of HMB during the second trimester of pregnancy, PregHMB), and non-pregnant females (NonPreg). Cross-sectional area and cortical index of the femoral mid-shaft, stiffness, and Young modulus were significantly greater in the PregHMB group. Whole-bone mineral density was similar in all groups, and HMB supplementation increased trabecular number. Growth plate cartilage was the thinnest, while the articular cartilage was the thickest in the PregHMB group. HMB supplementation increased the content of proteoglycans in the articular cartilage and the percentage of immature collagen content in metaphyseal trabeculae and compact bone. In summary, dietary HMB supplementation during the second trimester of pregnancy intensifies bone metabolic processes and prevents bone loss during pregnancy.
Subject(s)
Bone Resorption/drug therapy , Bone Resorption/prevention & control , Valerates/therapeutic use , Animals , Body Weight/drug effects , Bone Resorption/diagnostic imaging , Cancellous Bone/diagnostic imaging , Cancellous Bone/drug effects , Cancellous Bone/pathology , Cartilage, Articular/diagnostic imaging , Cartilage, Articular/drug effects , Cartilage, Articular/pathology , Collagen/metabolism , Epiphyses/drug effects , Epiphyses/pathology , Female , Femur/diagnostic imaging , Femur/drug effects , Femur/pathology , Murinae , Pregnancy , Proteoglycans/metabolism , Valerates/pharmacology , X-Ray MicrotomographyABSTRACT
The potential of Fourier Transform infrared microspectroscopy (FTIR microspectroscopy) and multivariate analyses were applied for the classification of the frequency ranges responsible for the distribution changes of the main components of articular cartilage (AC) that occur during dietary ß-hydroxy-ß-methyl butyrate (HMB) supplementation. The FTIR imaging analysis of histological AC sections originating from 35-day old male piglets showed the change in the collagen and proteoglycan contents of the HMB-supplemented group compared to the control. The relative amount of collagen content in the superficial zone increased by more than 23% and in the middle zone by about 17%, while no changes in the deep zone were observed compared to the control group. Considering proteoglycans content, a significant increase was registered in the middle and deep zones, respectively; 62% and 52% compared to the control. AFM nanoindentation measurements collected from animals administered with HMB displayed an increase in AC tissue stiffness by detecting a higher value of Young's modulus in all investigated AC zones. We demonstrated that principal component analysis and artificial neural networks could be trained with spectral information to distinguish AC histological sections and the group under study accurately. This work may support the use and effectiveness of FTIR imaging combined with multivariate analyses as a quantitative alternative to traditional collagenous tissue-related histology.
Subject(s)
Cartilage, Articular/drug effects , Valerates/pharmacology , Animals , Cartilage, Articular/chemistry , Cartilage, Articular/metabolism , Collagen/metabolism , Dietary Supplements , Elastic Modulus , Male , Neural Networks, Computer , Principal Component Analysis , Proteoglycans/metabolism , Spectroscopy, Fourier Transform Infrared , Swine , Valerates/administration & dosageABSTRACT
The association between fibromuscular dysplasia (FMD) and spontaneous cervical artery dissection (SCeAD) has been recognized, but the available evidence on this relationship is scant. Therefore, the main goal of our study was to systematically evaluate FMD frequency, clinical characteristics and vascular bed involvement in patients with SCeAD. Among 230 patients referred to the ARCADIA-POL study, 43 patients (mean age 44.1 ± 8.9 years; 15 men and 28 women) with SCeAD were referred. Also, 135 patients with FMD were compared to patients with and without SCeAD. Patients underwent: ambulatory blood pressure measurements, biochemical evaluation, echocardiographic examination, and whole body computed tomographic angiography. FMD changes were found in 39.5% of patients with SCeAD. There were no differences in clinical characteristics between patients with SCeAD and FMD and those without FMD, except for a tendency towards a higher female ratio in SCeAD patients with FMD. There were no differences in other parameters describing target organ and SCeAD characteristics. Patients with SCeAD and FMD compared to those without SCeAD were characterized by a lower frequency of hypertension and a higher frequency of hyperlipidemia and history of contraceptive hormone use. Our study indicates a high incidence (39.5%) of FMD in subjects with SCeAD. Since there are no distinctive discriminating factors between patients with SCeAD and FMD and those without FMD, FMD should be suspected in all patients with SCeAD.
Subject(s)
Cervical Vertebrae/blood supply , Fibromuscular Dysplasia/epidemiology , Vertebral Artery Dissection/epidemiology , Adult , Blood Pressure Monitoring, Ambulatory , Comorbidity , Computed Tomography Angiography , Echocardiography , Female , Fibromuscular Dysplasia/diagnosis , Fibromuscular Dysplasia/physiopathology , Humans , Hypertension/diagnosis , Hypertension/epidemiology , Hypertension/physiopathology , Incidence , Male , Middle Aged , Poland/epidemiology , Prospective Studies , Risk Factors , Sex Factors , Vertebral Artery Dissection/diagnosis , Vertebral Artery Dissection/physiopathology , Whole Body ImagingABSTRACT
PURPOSE: Smoking was identified as a potential factor contributing to fibromuscular dysplasia (FMD). To evaluate the prevalence of smoking and clinical characteristics in FMD subjects. MATERIAL AND METHODS: We analysed 190 patients with confirmed FMD in at least one vascular bed. The rate of smokers in FMD patients was compared to that in two control groups selected from a nationwide survey. RESULTS: The rate of smokers in FMD patients was 42.6%. There were no differences in frequency of smokers between FMD patients and: a group of 994 matched control subjects from general population and a group of matched hypertensive subjects. There were no differences in the characteristics of FMD (including rates of multisite FMD and significant renal artery stenosis) and its complications (including rates of dissections and aneurysms) between smokers and non-smokers. Smokers as compared with non-smokers were characterized by higher left ventricle mass index. CONCLUSIONS: There is no difference in the rate of smokers between FMD patients and subjects from the general population. Moreover, we did not find any association between smoking and clinical characteristics of FMD patients nor its extent and vascular complications. Our results do not support the hypothesis that smoking is involved in the pathophysiology of FMD.
Subject(s)
Fibromuscular Dysplasia/etiology , Smoking/adverse effects , Aneurysm , Case-Control Studies , Dissection/statistics & numerical data , Female , Fibromuscular Dysplasia/complications , Fibromuscular Dysplasia/epidemiology , Humans , Hypertension , Male , Middle Aged , Prevalence , Registries , Renal Artery Obstruction/complications , Smoking/epidemiologyABSTRACT
It has been demonstrated in animal studies that prenatal administration of ß-hydroxy-ß-methylbutyrate (HMB, metabolite of leucine) influences general growth and mechanical endurance of long bones in newborn offspring in sex-dependent manner. The present experiment was conducted to evaluate the effect of HMB treatment of pregnant sows on bone development in offspring at weaning. From 70th day until the 90th day of gestation, sows received either a basal diet (n = 12) or the same diet supplemented with HMB (n = 12) at the dose of 0.2 g/kg of body weight/day. Femora obtained from six males and females in each group weaned at the age of 35 days were examined. Maternal HMB treatment significantly enhanced body weight and changed bone morphology increasing femur mechanical strength in both sexes. Maternal HMB supplementation also elevated bone micro- and macroelement concentrations and enhanced content of proteoglycans in articular cartilage. Based on the obtained results, it can be concluded that maternal HMB supplementation in the mid-gestation period significantly accelerated bone development in both sexes by upregulation of a multifactorial system including leptin and osteoprotegerin. However, the sex (irrespective of the HMB treatment) was the factor which influenced the collagen structure in cartilages and trabecular bone, as demonstrated both by the Picrosirius red staining and performed analysis of thermal stability of collagenous tissues. The structural differences in collagen between males and females were presumably related to a different collagen maturity. No studies conducted so far provided a detailed morphological analysis of bone, articular cartilage, growth plate and the activities of the somatotropic and pituitary-gonadal axes, as well as leptin/osteoprotegerin system in weaned offspring prenatally treated with HMB. This study showed also the relationship between the maternal HMB treatment and bone osteometric and mechanical traits, hormones, and growth and bone turnover markers such as leptin, osteoprotegerin and insulin-like growth factor-1.
Subject(s)
Diet/veterinary , Dietary Supplements , Hyaline Cartilage/drug effects , Leptin/metabolism , Swine , Valerates/pharmacology , Animal Feed/analysis , Animal Nutritional Physiological Phenomena , Animals , Biomechanical Phenomena , Bone Development/drug effects , Female , Gene Expression Regulation/drug effects , Hyaline Cartilage/growth & development , Pregnancy , Prenatal Nutritional Physiological Phenomena , Random Allocation , Valerates/administration & dosageABSTRACT
Cadmium (Cd) and lead (Pb) are toxic elements that accumulate to the largest extent in bones. Rats were used to investigate whether tannic acid (TA; 0.5%, 1.0%, 1.5%. 2.0%, or 2.5%) would have a protective effect on the structure and properties of bones in the case of exposure to Cd and Pb (diet: 7 mg Cd/kg and 50 mg Pb/kg) for 6 weeks. The effects of administration of TA in Cd- and Pb-poisoned rats on bone characteristics and the morphology of articular and growth cartilages were determined. All the rats administered Cd and Pb had an enhanced Cd and Pb concentration in blood plasma and bone and reduced bone Ca content irrespective of the TA administration. Cd and Pb alone reduced the mechanical endurance and histomorphometric parameters of trabecular bone and the thickness of the growth plate and articular cartilage. Tannic acid improved cancellous bone parameters in the rat exposed to Cd and Pb. A diet rich in TA improved articular cartilage constituents in heavy metal-poisoned rats. These results suggest that alimentary TA supplementation can counteract in a dose-dependent manner some of the destructive changes evoked by Cd and Pb possibly by reducing the exposure.