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BMC Veterinary Research May 2024Myxomatous mitral valve disease (MMVD) is the most common acquired cardiovascular disease in small breed dogs. In contrast to human patients with heart failure (HF),...
BACKGROUND
Myxomatous mitral valve disease (MMVD) is the most common acquired cardiovascular disease in small breed dogs. In contrast to human patients with heart failure (HF), iron deficiency (ID) prevalence in dogs with MMVD is weakly known. The study aimed to assess the usability of ID markers in serum and reticulocyte parameters from whole blood of dogs with MMVD to evaluate early ID symptoms.
RESULTS
Sixty-eight dogs (43 male and 25 female) were included in the study. MMVD dogs were assigned according to the 2019 ACVIM guidelines for groups B1 (n = 9), B2 (n = 10), C (n = 27) and D (n = 10). Groups were also combined into B1 and B2 as non-symptomatic HF and C with D as symptomatic HF. Healthy controls were 12 dogs. Serum iron concentration below the reference range in dogs with MMVD was 12.5%. Other ID indices, such as %SAT, UIBC, and TIBC were similar in the MMVD groups and healthy controls (p > 0.05 for all parameters). Statistical comparison between control group and 4 groups of different stages of MMVD showed that significant differences occur only in serum transferrin. The assessment of ferritin and soluble transferrin receptors using Western Blotting did not show differences between control (n = 7) and MMVD (n = 33) dogs. Study has shown positive correlation between ID parameters and echocardiographic indices such as LA/Ao and LVIDdN, and some biochemical parameters. A significant increase in reticulocytes percentage, assessed manually, was observed in the HF group of animals (p = 0.027) compared to the control group.
CONCLUSIONS
Studies have shown that ID parameters in serum are not significantly different in dogs with MMVD compared to healthy dogs. However, there is a clear correlation between atrial size and normalised left ventricular size to body size and some biochemical parameters, including ID parameters and therefore the severity of MMVD.
Topics: Dogs; Animals; Dog Diseases; Female; Male; Iron; Biomarkers; Ferritins; Mitral Valve Insufficiency; Iron Deficiencies; Heart Valve Diseases; Mitral Valve; Anemia, Iron-Deficiency; Transferrin; Reticulocytes
PubMed: 38762716
DOI: 10.1186/s12917-024-04071-2 -
Environment International May 2024Liquid crystal monomers (LCMs) are the raw material for liquid crystal displays, and their use is steadily increasing in electronic products. Recently, LCMs have been...
Liquid crystal monomers (LCMs) are the raw material for liquid crystal displays, and their use is steadily increasing in electronic products. Recently, LCMs have been reported to be novel endocrine disrupting chemicals, however, the mechanisms underlying their potential for thyroid hormone disruption and visual toxicity are not well understood. In this study, six widely used fluorinated LCMs (FLCMs) were selected to determine putative mechanisms underlying FLCM-induced toxicity to the zebrafish thyroid and visual systems. Exposure to FLCMs caused damage to retinal structures and reduced cell density of ganglion cell layer, inner nuclear layer, and photoreceptor layer approximately 12.6-46.1%. Exposure to FLCMs also disrupted thyroid hormone levels and perturbed the hypothalamic-pituitary-thyroid axis by affecting key enzymes and protein in zebrafish larvae. A thyroid hormone-dependent GH3 cell viability assay supported the hypothesis that FLCMs act as thyroid hormone disrupting chemicals. It was also determined that FLCMs containing aliphatic ring structures may have a higher potential for T3 antagonism compared to FLCMs without an aliphatic ring. Molecular docking in silico suggested that FLCMs may affect biological functions of thyroxine binding globulin, membrane receptor integrin, and thyroid receptor beta. Lastly, the visual motor response of zebrafish in red- and green-light was significantly inhibited following exposure to FLCMs. Taken together, we demonstrate that FLCMs can act as thyroid hormone disruptors to induce visual dysfunction in zebrafish via several molecular mechanisms.
PubMed: 38761427
DOI: 10.1016/j.envint.2024.108747 -
Journal of Dairy Science May 2024A dysregulated inflammatory response contributes to the occurrence of disorders in cows during the transition period from pregnancy to lactation. However, a detailed...
A dysregulated inflammatory response contributes to the occurrence of disorders in cows during the transition period from pregnancy to lactation. However, a detailed characterization of clinically healthy cows that exhibit enhanced inflammatory response during this critical period remains incomplete. In this experiment, a total of 99 individual transition dairy cows and 109 observations (18 cows monitored in 2 consecutive lactations), submitted to similar transition management were involved to evaluate the relationship between elevated inflammatory response and metabolic, oxidative status as well as transition outcomes. Blood was taken at -7, 3, 6, 9 and 21 d in milk (DIM) and concentrations of metabolic parameters (glucose, β-hydroxybutyric acid (BHBA), nonesterified fatty acids (NEFA), insulin, insulin-like growth factor 1 (IGF-1) and fructosamine) were analyzed. Additionally, oxidative parameters (proportion of oxidized glutathione to total glutathione in red blood cells (GSSG (%)), the activity of glutathione peroxidase (GPx) and of superoxide dismutase (SOD), concentrations of malondialdehyde (MDA) and oxygen radical absorbance capacity (ORAC)) and acute phase proteins (APP) including haptoglobin (Hp), serum amyloid A (SAA) and albumin-to-globulin ratio (A:G) were determined in the blood of 21 DIM. The 3 APP parameters were used to group clinically healthy cows into 2 categories through k-medoids clustering, i.e., a group showing an acute phase response (APR, n = 39) and a group not showing such a response, i.e., non-APR (n = 50). Diseased cases (n = 20) were handled in a separate group. Lower SAA and Hp concentrations as well as higher A:G were observed in the non-APR group, although for Hp differences were observed from the APR group, not from the diseased group. Only one of the 5 oxidative parameters differed between the groups, with the non-APR group exhibiting lower GPx activity compared with the diseased group. The non-APR group showed the highest IGF-1 levels among the 3 groups, and lower NEFA concentrations compared with the diseased groups. The diseased group also showed reduced dry matter intake and milk yield compared with clinically healthy cows, regardless of their inflammatory status. Moreover, the APR group exhibited temporarily lower activity levels compared with the non-APR group. These findings highlight that cows with a lower inflammatory status after 21 DIM exhibited better metabolic health characteristics, productive performance as well as activity levels. Nevertheless, the detrimental effects of a higher inflammatory status in the absence of clinical symptoms are still relatively limited.
PubMed: 38754826
DOI: 10.3168/jds.2023-24156 -
JPMA. the Journal of the Pakistan... Apr 2024To assess the association of serum protein electrophoresis abnormalities with clinicopathological characteristics, and its impact on overall survival in chronic...
OBJECTIVE
To assess the association of serum protein electrophoresis abnormalities with clinicopathological characteristics, and its impact on overall survival in chronic lymphocytic leukaemia patients.
METHODS
The prospective study was conducted at Haematology and Immunology departments of the University of Health Sciences, Lahore, Pakistan, from 2019 to 2022, and comprised newly diagnosed chronic lymphocytic leukaemia patients. Lactate dehydrogenase and beta-2 microglobulin levels were measured by spectrophotometric principle, whereas serum protein electrophoresis was determined through commercially available capillary electrophoresis systems. Patients were followed up for 2 years post-diagnosis. Data was analysed using SPSS 21.
RESULTS
Of the 50 patients, 40(80%) were males and 10(20%) were females. The overall mean age was 60±11 years. Serum protein electrophoresis was available for 40(80%) patients, and, among them, 12(30%) patients had abnormal levels, while 29(72.5%) required treatment. Overall response rate was 25(86.2%), and median two-year overall survival was 16.5 months (95% confidence interval: 10-20 months). Abnormal serum protein electrophoresis was significantly associated with Binet stage C, lower mean haemoglobin levels and higher median levels of lactate dehydrogenase and beta-2 microglobulin (p<0.05)). Regarding overall survival, the survival curves of chronic lymphocytic leukaemia patients with normal and abnormal serum protein electrophoresis status differed significantly (p=0.04).
CONCLUSION
Abnormal serum protein electrophoresis could be considered a surrogate marker for advanced chronic lymphocytic leukaemia disease.
Topics: Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Female; Male; Middle Aged; Prognosis; Aged; Prospective Studies; beta 2-Microglobulin; Blood Protein Electrophoresis; L-Lactate Dehydrogenase; Pakistan; Hemoglobins; Survival Rate; Neoplasm Staging; Blood Proteins
PubMed: 38751267
DOI: 10.47391/JPMA.10116 -
BMJ Open May 2024To estimate the association between secondhand smoke (SHS) exposure and serum sex hormone concentrations in female adults (never smokers and former smokers).
Association between secondhand smoke exposure and serum sex hormone concentrations among US female adults: a cross-sectional analysis using data from the National Health and Nutrition Examination Survey, 2013-2016.
OBJECTIVE
To estimate the association between secondhand smoke (SHS) exposure and serum sex hormone concentrations in female adults (never smokers and former smokers).
DESIGN
Cross-sectional analysis.
SETTING
US National Health and Nutrition Examination Survey, 2013-2016.
OUTCOME MEASURES
Serum sex hormone measures included total testosterone (TT) and oestradiol (E2), sex hormone-binding globulin (SHBG), the ratio of TT and E2 and free androgen index (FAI). Isotope dilution-liquid chromatography tandem mass spectrometry was used to measure serum TT and E2. SHBG was measured using immunoassay. The ratio of TT and E2 and FAI were calculated. SHS exposure was defined as serum cotinine concentration of 0.05-10 ng/mL.
PARTICIPANTS
A total of 622 female participants aged ≥20 years were included in the analysis.
RESULTS
For never smokers, a doubling of serum cotinine concentration was associated with a 2.85% (95% CI 0.29% to 5.47%) increase in TT concentration and a 6.29% (95% CI 0.68% to 12.23%) increase in E2 in fully adjusted models. The never smokers in the highest quartile (Q4) of serum cotinine level exhibited a 10.30% (95% CI 0.78% to 20.72%) increase in TT concentration and a 27.75% (95% CI 5.17% to 55.17%) increase in E2 compared with those in the lowest quartile (Q1). For former smokers, SHBG was reduced by 4.36% (95% CI -8.47% to -0.07%, p for trend=0.049) when the serum cotinine level was doubled, and the SHBG of those in Q4 was reduced by 17.58% (95% CI -31.33% to -1.07%, p for trend=0.018) compared with those in Q1.
CONCLUSION
SHS was associated with serum sex hormone concentrations among female adults. In never smokers, SHS was associated with increased levels of TT and E2. In former smokers, SHS was associated with decreased SHBG levels.
Topics: Humans; Female; Tobacco Smoke Pollution; Cross-Sectional Studies; Nutrition Surveys; Adult; Cotinine; United States; Middle Aged; Sex Hormone-Binding Globulin; Estradiol; Testosterone; Young Adult; Gonadal Steroid Hormones; Tandem Mass Spectrometry
PubMed: 38749695
DOI: 10.1136/bmjopen-2023-073527 -
BMC Nephrology May 2024Atypical haemolytic uremic syndrome (aHUS) is an uncommon form of thrombotic microangiopathy (TMA). However, it remains difficult to diagnose the disease early, given...
BACKGROUND
Atypical haemolytic uremic syndrome (aHUS) is an uncommon form of thrombotic microangiopathy (TMA). However, it remains difficult to diagnose the disease early, given its non-specific and overlapping presentation to other conditions such as thrombotic thrombocytopenic purpura and typical HUS. It is also important to identify the underlying causes and to distinguish between primary (due to a genetic abnormality leading to a dysregulated alternative complement pathway) and secondary (often attributed by severe infection or inflammation) forms of the disease, as there is now effective treatment such as monoclonal antibodies against C5 for primary aHUS. However, primary aHUS with severe inflammation are often mistaken as a secondary HUS. We presented an unusual case of adult-onset Still's disease (AOSD) with macrophage activation syndrome (MAS), which is in fact associated with anti-complement factor H (anti-CFH) antibodies related aHUS. Although the aHUS may be triggered by the severe inflammation from the AOSD, the presence of anti-CFH antibodies suggests an underlying genetic defect in the alternative complement pathway, predisposing to primary aHUS. One should note that anti-CFH antibodies associated aHUS may not always associate with genetic predisposition to complement dysregulation and can be an autoimmune form of aHUS, highlighting the importance of genetic testing.
CASE PRESENTATION
A 42 years old man was admitted with suspected adult-onset Still's disease. Intravenous methylprednisolone was started but patient was complicated with acute encephalopathy and low platelet. ADAMTS13 test returned to be normal and concurrent aHUS was eventually suspected, 26 days after the initial thrombocytopenia was presented. Plasma exchange was started and patient eventually had 2 doses of eculizumab after funding was approved. Concurrent tocilizumab was also used to treat the adult-onset Still's disease with MAS. The patient was eventually stabilised and long-term tocilizumab maintenance treatment was planned instead of eculizumab following haematology review. Although the aHUS may be a secondary event to MAS according to haematology opinion and the genetic test came back negative for the five major aHUS gene, high titre of anti-CFH antibodies was detected (1242 AU/ml).
CONCLUSION
Our case highlighted the importance of prompt anti-CFH antibodies test and genetic testing for aHUS in patients with severe AOSD and features of TMA. Our case also emphasized testing for structural variants within the CFH and CFH-related proteins gene region, as part of the routine genetic analysis in patients with anti-CFH antibodies associated aHUS to improve diagnostic approaches.
Topics: Humans; Still's Disease, Adult-Onset; Atypical Hemolytic Uremic Syndrome; Complement Factor H; Adult; Male; Autoantibodies; Macrophage Activation Syndrome
PubMed: 38745129
DOI: 10.1186/s12882-024-03548-4 -
Nature Communications May 2024Vesicular transport is essential for delivering cargo to intracellular destinations. Evi5 is a Rab11-GTPase-activating protein involved in endosome recycling. In humans,...
Vesicular transport is essential for delivering cargo to intracellular destinations. Evi5 is a Rab11-GTPase-activating protein involved in endosome recycling. In humans, Evi5 is a high-risk locus for multiple sclerosis, a debilitating disease that also presents with excess iron in the CNS. In insects, the prothoracic gland (PG) requires entry of extracellular iron to synthesize steroidogenic enzyme cofactors. The mechanism of peripheral iron uptake in insect cells remains controversial. We show that Evi5-depletion in the Drosophila PG affected vesicle morphology and density, blocked endosome recycling and impaired trafficking of transferrin-1, thus disrupting heme synthesis due to reduced cellular iron concentrations. We show that ferritin delivers iron to the PG as well, and interacts physically with Evi5. Further, ferritin-injection rescued developmental delays associated with Evi5-depletion. To summarize, our findings show that Evi5 is critical for intracellular iron trafficking via transferrin-1 and ferritin, and implicate altered iron homeostasis in the etiology of multiple sclerosis.
Topics: Animals; Iron; Drosophila Proteins; Ferritins; Transferrin; Drosophila melanogaster; Endosomes; Humans; Protein Transport
PubMed: 38744835
DOI: 10.1038/s41467-024-48165-9 -
Cellular and Molecular Neurobiology May 2024Central nervous system (CNS) disorders represent the leading cause of disability and the second leading cause of death worldwide, and impose a substantial economic... (Review)
Review
Central nervous system (CNS) disorders represent the leading cause of disability and the second leading cause of death worldwide, and impose a substantial economic burden on society. In recent years, emerging evidence has found that beta2 -microglobulin (B2M), a subunit of major histocompatibility complex class I (MHC-I) molecules, plays a crucial role in the development and progression in certain CNS diseases. On the one hand, intracellular B2M was abnormally upregulated in brain tumors and regulated tumor microenvironments and progression. On the other hand, soluble B2M was also elevated and involved in pathological stages in CNS diseases. Targeted B2M therapy has shown promising outcomes in specific CNS diseases. In this review, we provide a comprehensive summary and discussion of recent advances in understanding the pathological processes involving B2M in CNS diseases (e.g., Alzheimer's disease, aging, stroke, HIV-related dementia, glioma, and primary central nervous system lymphoma).
Topics: Humans; beta 2-Microglobulin; Central Nervous System Diseases; Animals
PubMed: 38743119
DOI: 10.1007/s10571-024-01481-6 -
Frontiers in Public Health 2024Inflammation and liver function are associated with cognitive decline and dementia. Little is known about the serum albumin-to-globulin ratio on cognitive function.
Non-linear relationship of serum albumin-to-globulin ratio and cognitive function in American older people: a cross-sectional national health and nutrition examination survey 2011-2014 (NHANES) study.
BACKGROUND
Inflammation and liver function are associated with cognitive decline and dementia. Little is known about the serum albumin-to-globulin ratio on cognitive function.
OBJECTIVE
The objective of this study was to investigate the association between albumin-to-globulin ratio and cognitive function among the American older people.
METHODS
The public data available on the US National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014 was used for this cross-sectional study. Participants aged ≥60 years completed the cognitive function assessments, including word learning and recall modules from the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), the animal fluency (AF) test, and the digit symbol substitution test (DSST). A composite cognition score was calculated to evaluate global cognition. The univariate and multivariate linear regression analysis, curve fitting, a threshold effect, along with a subgroup analysis and interaction tests were conducted.
RESULTS
Serum albumin-to-globulin ratio (per 0.1 unit) was positively associated DSST score (β = 0.36, 95% CI: 0.21, 0.51), AF score (β = 0.1, 95% CI: 0.04, 0.16) and global cognition score (β = 0.05, 95% CI: 0.02, 0.07), after being fully adjusted, while albumin-to-globulin ratio was not related to CERAD score (β = 0.05, 95% CI: -0.02, 0.12). A non-linear was observed in the dose-response relationship between albumin-to-globulin ratio and global cognition ( for non-linearity < 0.001). The subgroup analysis was overall stable, yet the interaction test was significant for age on global cognition ( for interaction = 0.036).
CONCLUSION
The findings of this cross-sectional study suggested a positive and non-linear association between albumin-to-globulin ratio and cognitive function in the American older people. Maintaining albumin-to-globulin ratio with an appropriate range may be one of the therapeutic strategies to limit the progression of cognitive decline for the older people.
Topics: Humans; Cross-Sectional Studies; Male; Female; Nutrition Surveys; Aged; Cognition; United States; Middle Aged; Serum Albumin; Cognitive Dysfunction; Aged, 80 and over; Serum Globulins; Globulins
PubMed: 38737864
DOI: 10.3389/fpubh.2024.1375379 -
Frontiers in Endocrinology 2024Low testosterone levels in men have been linked to decreased physical and mental function, as well as a reduced quality of life. Previous prospective observational...
Low testosterone levels in men have been linked to decreased physical and mental function, as well as a reduced quality of life. Previous prospective observational studies have suggested an association between testosterone and sleep traits, but the causality of this relationship remains unclear. We aimed to explore the potential causal link between genetically determined sleep traits and testosterone levels in men using Mendelian randomization (MR) analysis from the UK Biobank dataset. Our exposures were genetic variants associated with sleep traits (chronotype and sleep duration), whereas our outcomes were traits of sex steroid hormones (total testosterone, TT; bioavailable testosterone, BAT; and sex hormone-binding globulin, SHBG). We employed inverse variance weighted (IVW) and weighted median (WM) methods to assess the causal associations. The IVW method offers a robust estimate of causality, whereas the WM method provides reliable results even when some genetic variants are invalid instruments. Our main analysis involving sex steroid hormones and chronotype identified 155 chronotype-related variants. The primary findings from the analysis, which used chronotype as the exposure and sex steroid hormones as the outcomes, showed that a genetically predicted chronotype score was significantly associated with an increased levels of TT (association coefficient β, 0.08; 95% confidence interval [CI], 0.02-0.14; = 0.008) and BAT (β, 0.08; 95% CI, 0.02-0.14; = 0.007), whereas there was no significant association with SHBG (β, 0.01; 95% CI, -0.02-0.03; = 0.64). Meanwhile, MR analysis of sex steroid hormones and sleep duration was performed, and 69 variants associated with sleep duration were extracted. There were no significant association between sleep duration and sex steroid hormones (TT, = 0.91; BAT, = 0.82; and SHBG, = 0.95). Our data support a causal association between chronotype and circulating testosterone levels in men. These findings underscore a potential causal relationship between chronotype and testosterone levels in men, suggesting that lifestyle adjustments are crucial for men's health. Recognizing factors that influence testosterone is essential. One limitation of this study is the use of one-sample MR, which can introduce potential bias due to non-independence of genetic associations for exposure and outcome. In conclusion, our findings indicate that a morning preference is correlated with circulating testosterone levels, emphasizing the potential impact of lifestyle habits on testosterone levels in men.
Topics: Humans; Mendelian Randomization Analysis; Male; Testosterone; Sleep; Sex Hormone-Binding Globulin; Middle Aged; Circadian Rhythm; Polymorphism, Single Nucleotide; Aged; Chronotype
PubMed: 38737549
DOI: 10.3389/fendo.2024.1264410