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BMJ Case Reports Jun 2024In this paper, we report the case of a boy in early childhood who presented with iron-deficiency anaemia, initially thought to be nutritional, who had a subsequent...
In this paper, we report the case of a boy in early childhood who presented with iron-deficiency anaemia, initially thought to be nutritional, who had a subsequent diagnosis of idiopathic pulmonary haemosiderosis (IPH). This is a slowly progressive and life-threatening disorder and is of paramount importance that this is identified early and treated appropriately. His first chest CT was not typical for IPH, and this appearance should be highlighted (small cystic changes alone initially). He also had focal disease, which allowed us to make the diagnosis using CT-guided biopsy. During his treatment, he experienced an uncommon side effect to a commonly prescribed medication (bradycardia with methylprednisolone). Since starting azathioprine as a steroid-sparing agent, he has been doing well.
Topics: Humans; Hemosiderosis; Male; Hemosiderosis, Pulmonary; Lung Diseases; Tomography, X-Ray Computed; Anemia, Iron-Deficiency; Azathioprine; Diagnosis, Differential; Methylprednisolone
PubMed: 38937263
DOI: 10.1136/bcr-2024-261171 -
In Vivo (Athens, Greece) 2024Depression is associated with metabolic disorders, including non-alcoholic fatty liver disease (NAFLD). However, the mechanisms underlying the interaction between them...
BACKGROUND/AIM
Depression is associated with metabolic disorders, including non-alcoholic fatty liver disease (NAFLD). However, the mechanisms underlying the interaction between them are still poorly known.
MATERIALS AND METHODS
In this study, mice on a choline deficiency, L-amino acid-defined, high-fat diet (CDAHFD) developing steatosis were challenged with chronic restraint stress (CRS), a protocol widely used to induce depression. The development of depression and steatosis was evaluated using histopathology analysis, ELISA, q-PCR and Western Blot.
RESULTS
The contribution of the activated HPA axis to hepatic steatosis progress was fully established, which was validated using a hepatocyte model. Histopathological and biochemical analysis indicated that steatosis was exacerbated by CRS challenge, and behavioral tests indicated that the mice developed depression. Among the screened endocrinal pathways, the hypothalamic-pituitary-adrenal (HPA) axis was significantly activated and the synergistic effect of CDAHFD and CRS in activating the HPA axis was observed. In the hypothalamus, expression of corticotropin-releasing hormone (CRH) was increased by 86% and the protein levels of hypothalamic CRH were upregulated by 25% to 33% by CRS treatment. Plasma CRH levels were elevated by 45-56% and plasma adrenocorticotropic hormone (ACTH) levels were elevated by 29-58% by CRS treatment. In the liver, target genes of the HPA axis were activated, accompanied by disruption of the lipid metabolism and progression of steatohepatitis. The lipid metabolism in the Hepa1-6 cell line treated with endogenous corticosterone (CORT) was in accordance with the aforementioned in vivo responses.
CONCLUSION
Depression aggravated hepatic steatosis in CDAHFD-fed mice by activating the HPA axis. The risk of NAFLD development should be fully considered in depressive patients and improvement of psychotic disorders could be an etiological treatment strategy for them.
Topics: Animals; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Mice; Depression; Disease Models, Animal; Non-alcoholic Fatty Liver Disease; Male; Mice, Inbred C57BL; Corticotropin-Releasing Hormone; Diet, High-Fat; Adrenocorticotropic Hormone; Liver; Fatty Liver; Corticosterone
PubMed: 38936893
DOI: 10.21873/invivo.13618 -
Toxicon : Official Journal of the... Jun 2024The safety of bioactive compounds, especially those isolated from medicinal plants, is a major concern for health authorities, pharmaceutical industries, and the public....
Toxicity assessment of 3-O-[6-deoxy-3-O-methyl-β-D-allopyranosyl-(1→4)-β-D-oleandropyranosyl]-17β-marsdenin isolated from Gongronema latifolium leaf on selected brain and kidney function indices in mice.
The safety of bioactive compounds, especially those isolated from medicinal plants, is a major concern for health authorities, pharmaceutical industries, and the public. Of recent, anti-tumor pregnane glycosides were isolated from Gongronema latifolium leaf, of which the toxicity of one, 3-O-[6-deoxy-3-O-methyl-β-D-allopyranosyl-(1→4)-β-D-oleandropyranosyl]-17β-marsdenin (3DMAOM), has not been evaluated. This study, therefore, evaluated the effects of 3DMAOM on selected brain and kidney function indices in mice. Female Swiss albino mice were randomly administered 5% dimethyl sulphoxide and different doses of 3DMAOM (0.5, 1, 2, and 4 mg/kg body weight) for fourteen (14) days, and their blood, brains, and kidneys were collected for biochemical analysis. There was no significant alteration in the activities of alkaline phosphatase (ALP), acetylcholinesterase, creatine kinase, Na/K-ATPase, Ca/Mg-ATPase, and Mg-ATPase in the brain of the treated groups compared to control. Also, no significant changes in the activities of ALP, gamma-glutamyltransferase, Na/K-ATPase, Ca/Mg-ATPase, and Mg-ATPase in the kidney of the treated groups compared to control. The plasma concentrations of Na, K, Cl, PO, creatinine, and urea of mice were not significantly altered at all doses of the 3DMAOM compared to controls. However, the plasma concentration of Ca was significantly reduced (p<0.05) at all doses of the 3DMAOM, and the plasma concentration of uric acid was significantly reduced (p<0.05) at 2 mg/kg body weight of the 3DMAOM compared to controls. These findings suggest that 3DMAOM isolated from Gongronema latifolium leaf may not adversely affect brain function but may affect calcium ion homeostasis in subjects.
PubMed: 38936671
DOI: 10.1016/j.toxicon.2024.107830 -
Medicina (Kaunas, Lithuania) Jun 2024: Cervical radiculopathy (CR) manifests as pain and sensorimotor disturbances in the upper extremities, often resulting from nerve root compression due to intervertebral...
: Cervical radiculopathy (CR) manifests as pain and sensorimotor disturbances in the upper extremities, often resulting from nerve root compression due to intervertebral disc herniation, degenerative changes, or trauma. While conservative treatments are initially preferred, persistent or severe cases may require surgical intervention. Ultrasound-guided selective nerve root block (SNRB) has emerged as a promising intervention for alleviating symptoms and potentially obviating the need for surgery. This study evaluates the therapeutic efficacy of ultrasound-guided SNRB in managing chronic CR, aiming to determine its potential in symptom relief and delaying or avoiding surgical procedures. : A retrospective analysis was conducted on 720 outpatients treated for CR between October 2019 and March 2022. After excluding patients with traumatic CR, previous surgeries, malignancies, progressive neurological symptoms requiring immediate surgery, or inadequate conservative treatment, 92 patients who had experienced cervical radicular pain for more than three months and had failed to improve after more than six weeks of conservative treatment with VAS scores ≥ 5 were included. The patients underwent single or multiple ultrasound-guided SNRB procedures, involving the injection of dexamethasone and lidocaine under real-time ultrasound guidance. Symptom severity was assessed at the baseline, and at 4, 8, and 12 weeks post-procedure using the Visual Analog Scale (VAS). The data collected included age, sex, presence of neck and/or radicular pain, physical examination findings, recurrence of symptoms, improvement in symptoms, and whether surgical intervention was ultimately required. Statistical analyses were performed to identify the factors associated with symptom improvement or recurrence. : Significant symptom improvement was observed in 69 (75.0%) participants post-SNRB, with 55 (79.7%) showing improvement at 4 weeks, 11 (15.9%) at 8 weeks, and 3 (4.4%) at 12 weeks. Symptom recurrence, defined by an increase in VAS score accompanied by a pain flare lasting at least 24 h after a pain-free interval of at least one month, was noted in 48 (52.2%) patients. The presence of combined neck and radicular pain was a significant predictor of recurrence ( = 0.008). No significant associations were found between symptom relief and factors such as age, gender, initial pain severity, or MRI findings. : Ultrasound-guided SNRB effectively manages chronic CR, providing substantial symptom relief and potentially reducing the need for surgical intervention. This technique offers a promising conservative treatment option, especially given its real-time visualization advantages and minimal radiation exposure.
Topics: Humans; Female; Male; Middle Aged; Radiculopathy; Retrospective Studies; Nerve Block; Ultrasonography, Interventional; Adult; Treatment Outcome; Pain Measurement; Aged; Lidocaine; Chronic Disease; Dexamethasone
PubMed: 38929619
DOI: 10.3390/medicina60061002 -
Medicina (Kaunas, Lithuania) Jun 2024: Temporomandibular disorders or dysfunction (TMDs) encompass a range of complex conditions that impact the temporomandibular joint (TMJ), chewing muscles, teeth, and/or... (Observational Study)
Observational Study
: Temporomandibular disorders or dysfunction (TMDs) encompass a range of complex conditions that impact the temporomandibular joint (TMJ), chewing muscles, teeth, and/or their supporting tissues. Stress is one of the most associated factors studied as a TMD predictor. The aim is to figure out the influence of stress on TMJ status and salivary cortisol in university students during and before exams. : The study was non-experimental, employing a longitudinal, analytical, observational cohort design. The study population consisted of students enrolled in the physiotherapy degree program at the Alfonso X El Sabio University (Madrid, Spain). Data were collected during two distinct academic periods: the first period was characterized by low academic stress and no exams, and the second period coincided with the high academic stress of final course exams. The collected results included sociodemographic data, assessment of TMJ status (Fonseca Index), evaluation of muscle evaluation (masseter, upper trapezius, and sternocleidomastoid) using a MOXY Monitor (muscle oxygenation) and Neurotrac (surface EMG, sEMG), assessment of perceived stress (PSS-14), and measurement of salivary cortisol (enzyme immunoassay with Elisa). The statistical analysis was conducted with a confidence level of 95% ( ≤ 0.05) and asymptotic or bilateral significance. : 70 students were analyzed during two different measurement periods. According to the Fonseca Index, initially, 37.14% of the analyzed students showed mild TMDs, 17.14% moderate TMDs, and 45.72% showed no TMDs. In general terms, stress increased with age and is related to female sex, maximum mouth opening decreased with age, oxygen saturation decreased with age and academic stress, and myoglobin concentration was related to age. Furthermore, muscle contraction decreased during higher academic stress and increased with age. For women, age was a risk factor for suffering from TMDs, and stress worsened the transition from having TMDs to having no TMDs in both sexes. : Academic stress influences TMJ status and muscle outcomes such as oxygen saturation, myoglobin concentration, and muscle contraction, although more research is needed.
Topics: Humans; Female; Male; Pilot Projects; Stress, Psychological; Temporomandibular Joint Disorders; Temporomandibular Joint; Spain; Adult; Hydrocortisone; Saliva; Young Adult; Longitudinal Studies; Students; Cohort Studies
PubMed: 38929569
DOI: 10.3390/medicina60060952 -
International Journal of Molecular... Jun 2024The decline in the function and mass of skeletal muscle during aging or other pathological conditions increases the incidence of aging-related secondary diseases,...
The decline in the function and mass of skeletal muscle during aging or other pathological conditions increases the incidence of aging-related secondary diseases, ultimately contributing to a decreased lifespan and quality of life. Much effort has been made to surmise the molecular mechanisms underlying muscle atrophy and develop tools for improving muscle function. Enhancing mitochondrial function is considered critical for increasing muscle function and health. This study is aimed at evaluating the effect of an aqueous extract of (GTAE) on myogenesis and muscle atrophy caused by dexamethasone (DEX). The GTAE promoted myogenic differentiation, accompanied by an increase in peroxisome proliferator-activated receptor γ coactivator α (PGC-1α) expression and mitochondrial content in myoblast cell culture. In addition, the GTAE alleviated the DEX-mediated myotube atrophy that is attributable to the Akt-mediated inhibition of the Atrogin/MuRF1 pathway. Furthermore, an in vivo study using a DEX-induced muscle atrophy mouse model demonstrated the efficacy of GTAE in protecting muscles from atrophy and enhancing mitochondrial biogenesis and function, even under conditions of atrophy. Taken together, this study suggests that the GTAE shows propitious potential as a nutraceutical for enhancing muscle function and preventing muscle wasting.
Topics: Animals; Muscular Atrophy; Dexamethasone; Muscle Development; Mice; Plant Extracts; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Cell Differentiation; Myoblasts; Cell Line; Muscle Proteins; Male; Muscle, Skeletal; Muscle Fibers, Skeletal; Mice, Inbred C57BL; Tripartite Motif Proteins; Rhodophyta
PubMed: 38928510
DOI: 10.3390/ijms25126806 -
International Journal of Molecular... Jun 2024Genetic variation among inhaled corticosteroid (ICS)-metabolizing enzymes may affect asthma control, but evidence is limited. This study tested the hypothesis that...
Genetic variation among inhaled corticosteroid (ICS)-metabolizing enzymes may affect asthma control, but evidence is limited. This study tested the hypothesis that single-nucleotide polymorphisms (SNPs) in Cytochrome P450 3A5 (CYP3A5) would affect asthma outcomes. Patients aged 2-18 years with persistent asthma were recruited to use the electronic AsthmaTracker (e-AT), a self-monitoring tool that records weekly asthma control, medication use, and asthma outcomes. A subset of patients provided saliva samples for SNP analysis and participated in a pharmacokinetic study. Multivariable regression analysis adjusted for age, sex, race, and ethnicity was used to evaluate the impact of CYP3A5 SNPs on asthma outcomes, including asthma control (measured using the asthma symptom tracker, a modified version of the asthma control test or ACT), exacerbations, and hospital admissions. Plasma corticosteroid and cortisol concentrations post-ICS dosing were also assayed using liquid chromatography-tandem mass spectrometry. Of the 751 patients using the e-AT, 166 (22.1%) provided saliva samples and 16 completed the PK study. The e-AT cohort was 65.1% male, and 89.6% White, 6.0% Native Hawaiian, 1.2% Black, 1.2% Native American, 1.8% of unknown race, and 15.7% Hispanic/Latino; the median age was 8.35 (IQR: 5.51-11.3) years. frequency was 75.8% in White subjects, 50% in Native Hawaiians and 76.9% in Hispanic/Latino subjects. Compared with , the genotype was associated with reduced weekly asthma control (OR: 0.98; 95% CI: 0.97-0.98; < 0.001), increased exacerbations (OR: 6.43; 95% CI: 4.56-9.07; < 0.001), and increased asthma hospitalizations (OR: 1.66; 95% CI: 1.43-1.93; < 0.001); analysis of , and separately showed an allelic copy effect. Finally, PK analysis post-ICS dosing suggested muted changes in cortisol concentrations for patients with the genotype, as opposed to an effect on ICS PK. Detection of , , and could impact inhaled steroid treatment strategies for asthma in the future.
Topics: Humans; Asthma; Child; Male; Female; Polymorphism, Single Nucleotide; Cytochrome P-450 CYP3A; Adolescent; Child, Preschool; Adrenal Cortex Hormones; Genotype; Hydrocortisone; Saliva; Treatment Outcome
PubMed: 38928254
DOI: 10.3390/ijms25126548 -
International Journal of Molecular... Jun 2024The objective of the study was to evaluate the profile and diagnostic significance of serum autoantibodies in infertile patients with premature ovarian insufficiency...
The objective of the study was to evaluate the profile and diagnostic significance of serum autoantibodies in infertile patients with premature ovarian insufficiency (POI). The pilot study included 26 patients of reproductive age with POI and diminished ovarian reserve who received complex treatment using new surgical technologies (Group 1) and 18 patients without POI (Group 2). The profile of serum autoantibodies, including anti-ovarian antibodies, antibodies against thyroid peroxidase (TPO), steroidogenic enzymes, and steroid and gonadotropic hormones, was studied using modified ELISAs and human recombinant steroidogenic enzymes (CYP11A1, CYP19A1, CYP21A2). Patients in Group 1 had higher levels of IgG autoantibodies against steroidogenic enzymes, estradiol, progesterone, and TPO than those in Group 2. Tests for IgG antibodies against CYP11A1, CYP19A1, and CYP21A2 exhibited high sensitivity (65.4-76.9%), specificity (83.3-89.9%), and AUC values (0.842-0.910) for POI, the highest in the first test. Three-antibodies panel screening showed higher diagnostic accuracy (84.1% versus 75-79.6%). The levels of these antibodies correlated with menstrual irregularities and a decrease in the antral follicle count. Thus, antibodies against CYP11A1, CYP19A1, and CYP21A2 have a high diagnostic value for POI. Three-antibody panel screening may improve the accuracy of POI diagnosis and be useful for identifying high-risk groups, early stages of the disease, and predicting POI progression.
Topics: Humans; Female; Autoantibodies; Primary Ovarian Insufficiency; Adult; Infertility, Female; Cholesterol Side-Chain Cleavage Enzyme; Aromatase; Steroid 21-Hydroxylase; Iodide Peroxidase; Pilot Projects; Immunoglobulin G; Biomarkers; Progesterone; Estradiol
PubMed: 38928251
DOI: 10.3390/ijms25126545 -
International Journal of Molecular... Jun 2024Based on the lack of differences in progression-free and overall survival after a median follow-up of 93 months in our HOVON-65/GMMG-HD4 trial (German part; = 395)... (Randomized Controlled Trial)
Randomized Controlled Trial
Molecular Long-Term Analysis of the GMMG-HD4 Trial in Multiple Myeloma-Patterns of Association of Chromosomal Aberrations with Response and Proliferation Determining Survival in Selecting Treatments in View of Limited Resources in Low- and Middle-Income Countries.
Based on the lack of differences in progression-free and overall survival after a median follow-up of 93 months in our HOVON-65/GMMG-HD4 trial (German part; = 395) randomizing VAD induction (vincristin/adriamycin/dexamthasone)/tandem-transplantation/thalidomide-maintenance vs. PAD induction (bortezomib/adriamycin/dexamethasone)/tandem transplantation/bortezomib maintenance, we discern how chromosomal aberrations determine long-term prognosis by different patterns of association with proliferation and treatment-dependent response, whether responses achieved by different regimens are equal regarding prognosis, and whether subpopulations of patients could be defined as treatable without upfront "novel agents" in cases of limited resources, e.g., in low- or middle-income countries. Serum parameters and risk factors were assessed in 395 patients. CD138-purified plasma cells were subjected to fluorescence in situ hybridization ( = 354) and gene expression profiling ( = 204). We found chromosomal aberrations to be associated in four patterns with survival, proliferation, and response: deletion (del) del17p13, del8p21, del13q14, (gain) 1q21+, and translocation t(4;14) (all adverse) associate with higher proliferation. Of these, del17p is associated with an response (pattern 1), and 1q21+, t(4;14), and del13q14 with a treatment-dependent response (pattern 2). Hyperdiploidy associates with lower proliferation without impacting response or survival (pattern 3). Translocation t(11;14) has no association with survival but a treatment-dependent adverse response (pattern 4). Significantly fewer patients reach a near-complete response or better with "conventional" (VAD) vs. bortezomib-based treatment after induction or high-dose melphalan. These patients, however, show significantly median progression-free and overall survival. Molecularly, patients responding to the two regimens differ in gene expression, indicating distinct biological properties of the responding myeloma cells. Patients with normal renal function (89.4%), low cytogenetic risk (72.5%), or low proliferation rate (37.9%) neither benefit in progression-free nor overall survival from bortezomib-based upfront treatment. We conclude that response level, the treatment by which it is achieved, and molecular background determine long-term prognosis. Chromosomal aberrations are associated in four patterns with proliferation and treatment-dependent responses. Associations with faster and deeper responses can be deceptive in the case of prognostically adverse aberrations 1q21+ and t(4;14). Far from advocating a return to "outdated" treatments, if resources do not permit state-of-the-art-treatment, normal renal function and/or molecular profiling identifies patient subpopulations doing well without upfront "novel agents".
Topics: Humans; Multiple Myeloma; Chromosome Aberrations; Female; Male; Middle Aged; Aged; Antineoplastic Combined Chemotherapy Protocols; Cell Proliferation; Prognosis; Adult; Developing Countries; Dexamethasone; Bortezomib; Thalidomide
PubMed: 38928138
DOI: 10.3390/ijms25126431 -
International Journal of Molecular... Jun 2024Wnt/β-catenin signaling dysregulation is associated with the pathogenesis of many human diseases, including hypertension and heart disease. The aim of this study was to...
Wnt/β-catenin signaling dysregulation is associated with the pathogenesis of many human diseases, including hypertension and heart disease. The aim of this study was to immunohistochemically evaluate and compare the expression of the Fzd8, WNT1, GSK-3β, and β-catenin genes in the hearts of rats with spontaneous hypertension (SHRs) and deoxycorticosterone acetate (DOCA)-salt-induced hypertension. The myocardial expression of Fzd8, WNT1, GSK-3β, and β-catenin was detected by immunohistochemistry, and the gene expression was assessed with a real-time PCR method. In SHRs, the immunoreactivity of Fzd8, WNT1, GSK-3β, and β-catenin was attenuated in comparison to that in normotensive animals. In DOCA-salt-induced hypertension, the immunoreactivity of Fzd8, WNT1, GSK-3β, and β-catenin was enhanced. In SHRs, decreases in the expression of the genes encoding Fzd8, WNT1, GSK-3β, and β-catenin were observed compared to the control group. Increased expression of the genes encoding Fzd8, WNT1, GSK-3β, and β-catenin was demonstrated in the hearts of rats with DOCA-salt-induced hypertension. Wnt signaling may play an essential role in the pathogenesis of arterial hypertension and the accompanying heart damage. The obtained results may constitute the basis for further research aimed at better understanding the role of the Wnt/β-catenin pathway in the functioning of the heart.
Topics: Animals; Wnt Signaling Pathway; Hypertension; Rats; Glycogen Synthase Kinase 3 beta; Male; Myocardium; beta Catenin; Wnt1 Protein; Rats, Inbred SHR; Frizzled Receptors; Desoxycorticosterone Acetate
PubMed: 38928134
DOI: 10.3390/ijms25126428