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Cells May 2023Research on Alzheimer's disease (AD) has classically focused on alterations that occur in the brain and their intra- and extracellular neuropathological hallmarks....
Research on Alzheimer's disease (AD) has classically focused on alterations that occur in the brain and their intra- and extracellular neuropathological hallmarks. However, the oxi-inflammation hypothesis of aging may also play a role in neuroimmunoendocrine dysregulation and the disease's pathophysiology, where the liver emerges as a target organ due to its implication in regulating metabolism and supporting the immune system. In the present work, we demonstrate organ (hepatomegaly), tissue (histopathological amyloidosis), and cellular oxidative stress (decreased glutathione peroxidase and increased glutathione reductase enzymatic activities) and inflammation (increased IL-6 and TNF𝛼) as hallmarks of hepatic dysfunction in 16-month-old male and female 3xTg-AD mice at advanced stages of the disease, and as compared to age- and sex-matched non-transgenic (NTg) counterparts. Moreover, liver-brain axis alterations were found through behavioral (increased neophobia) and HPA axis correlations that were enhanced under forced isolation. In all cases, sex (male) and isolation (naturalistic and forced) were determinants of worse hepatomegaly, oxidative stress, and inflammation progression. In addition, obesity in old male NTg mice was translated into a worse steatosis grade. Further research is underway determine whether these alterations could correlate with a worse disease prognosis and to establish potential integrative system targets for AD research.
Topics: Mice; Male; Female; Animals; Alzheimer Disease; Hypothalamo-Hypophyseal System; Hepatomegaly; Pituitary-Adrenal System; Brain; Aging; Mice, Transgenic; Inflammation; Obesity
PubMed: 37296638
DOI: 10.3390/cells12111517 -
Academic Radiology May 2012The aims of this study were to define volumetric nomograms for identifying hepatomegaly and to retrospectively evaluate the performance of radiologists in assessing...
RATIONALE AND OBJECTIVES
The aims of this study were to define volumetric nomograms for identifying hepatomegaly and to retrospectively evaluate the performance of radiologists in assessing hepatomegaly.
MATERIALS AND METHODS
Livers were automatically segmented from 148 abdominal contrast-enhanced computed tomographic scans: 77 normal livers and 71 cases of hepatomegaly (diagnosed by visual inspection and/or linear liver height by radiologists). Quantified liver volumes were compared to manual measurements using volume overlap and error. Liver volumes were normalized to body surface area, from which hepatomegaly nomograms were defined (H scores) by analyzing the distribution of liver sizes in the healthy population. H scores were validated against consensus reports. The performance of radiologists in diagnosing hepatomegaly was retrospectively evaluated.
RESULTS
The automated segmentation of livers was robust, with volume overlap and error of 96.2% and 2.2%, respectively. There were no significant differences (P > .10) between manual and automated segmentation for either the normal or the hepatomegaly subgroup. The average volumes of normal and enlarged livers were 1.51 ± 0.25 and 2.32 ± 0.75 L, respectively. One-way analysis of variance found that body surface area (P = .004) and gender (P = .02), but not age, significantly affected normal liver volume. No significant effects were observed for two-way and three-way interactions among the three variables (P > .18). H-score cutoffs of 0.92 and 1.08 L/m2 were used to define mild and massive hepatomegaly (95% confidence interval, ± 0.02 L/m2). Using the H score as the reference standard, the sensitivity of radiologists in detecting all, mild, and massive hepatomegaly was 84.4%, 56.7%, and 100.0% at 90.1% specificity, respectively. Radiologists disagreed on 20.9% of the diagnosed cases (n = 31). The area under the receiver-operating characteristic curve of the H-score criterion for hepatomegaly detection was 0.98.
CONCLUSIONS
Nomograms for the identification and grading of hepatomegaly from automatic volumetric liver assessment normalized to body surface area (H scores) are introduced. H scores match well with clinical interpretations for hepatomegaly and may improve hepatomegaly detection compared with height measurements or visual inspection, commonly used in current clinical practice.
Topics: Adolescent; Adult; Aged; Algorithms; Female; Hepatomegaly; Humans; Imaging, Three-Dimensional; Male; Middle Aged; Observer Variation; Pattern Recognition, Automated; Radiographic Image Interpretation, Computer-Assisted; Reproducibility of Results; Sensitivity and Specificity; Tomography, X-Ray Computed; Young Adult
PubMed: 22361033
DOI: 10.1016/j.acra.2012.01.015 -
JPMA. the Journal of the Pakistan... May 2022Berardinelli Seip Congenital Lipodystrophy (BSCL) or Congenital Generalized Lipodystrophy (CGL) is one of the four subgroups of lipodystrophy syndrome which is...
Berardinelli Seip Congenital Lipodystrophy (BSCL) or Congenital Generalized Lipodystrophy (CGL) is one of the four subgroups of lipodystrophy syndrome which is characterized by varying degrees of loss of adipose mass in the body. It is an extremely rare autosomal recessive disorder and commonly reported clinical presentations include muscular hypertrophy, gigantism, hepatomegaly, impaired glucose tolerance, acanthosis nigricans, hypertriglyceridaemia, cardiomyopathy, intellectual impairment, bone cysts and phlebomegaly. We present a case of a 4.5 years old male child born to consanguineous parents, presented with pneumonia. There was history of recurrent diarrhea and chest infection in the past. He had acromegaly like features, hirsutism, firm hepatomegaly, a well defined bone cyst in proximal right femur, pancytopenias with normal bone marrow biopsy report, hypertriglyceridemia and selective IgA deficiency. This is the first case of BSCL, reported in Pakistan with a bone cyst and IgA deficiency. Such patients need to be identified and monitored for complications like diabetes mellitus and hypertrophic cardiomyopathy.
Topics: Bone Cysts; Child, Preschool; Hepatomegaly; Humans; IgA Deficiency; Lipodystrophy; Lipodystrophy, Congenital Generalized; Male
PubMed: 35713067
DOI: 10.47391/JPMA.3182 -
Rheumatology International Feb 2022The association between COVID-19 infection and the development of autoimmune diseases is currently unknown, but there are already reports presenting induction of... (Review)
Review
BACKGROUND
The association between COVID-19 infection and the development of autoimmune diseases is currently unknown, but there are already reports presenting induction of different autoantibodies by SARS-CoV-2 infection. Kikuchi-Fuimoto disease (KFD) as a form of histiocytic necrotizing lymphadenitis of unknown origin.
OBJECTIVE
Here we present a rare case of KFD with heart involvement after COVID-19 infection. To our best knowledge only a few cases of COVID-19-associated KFD were published so far. Based on presented case, we summarize the clinical course of KFD and its association with autoimmune diseases, as well we discuss the potential causes of perimyocarditis in this case.
METHODS
We reviewed the literature regarding cases of "Kikuchi-Fujimoto disease (KFD)" and "COVID-19" and then "KFD" and "heart" or "myocarditis" by searching medical journal databases written in English in PubMed and Google Scholar.
RESULTS
Only two cases of KFD after COVID infection have been described so far.
CONCLUSION
SARS-CoV-2 infection can also be a new, potential causative agent of developing KFD.
Topics: Adult; COVID-19; COVID-19 Nucleic Acid Testing; COVID-19 Serological Testing; Echocardiography; Hepatomegaly; Histiocytic Necrotizing Lymphadenitis; Humans; Male; Myocarditis; SARS-CoV-2; Splenomegaly; Stroke Volume; Ventricular Dysfunction, Left
PubMed: 35024942
DOI: 10.1007/s00296-021-05088-8 -
Critical Care (London, England) Nov 2015Propofol infusion syndrome (PRIS) is a rare, but potentially lethal adverse effect of a commonly used drug. We aimed to review and correlate experimental and clinical... (Review)
Review
INTRODUCTION
Propofol infusion syndrome (PRIS) is a rare, but potentially lethal adverse effect of a commonly used drug. We aimed to review and correlate experimental and clinical data about this syndrome.
METHODS
We searched for all case reports published between 1990 and 2014 and for all experimental studies on PRIS pathophysiology. We analysed the relationship between signs of PRIS and the rate and duration of propofol infusion causing PRIS. By multivariate logistic regression we looked at the risk factors for mortality.
RESULTS
Knowledge about PRIS keeps evolving. Compared to earlier case reports in the literature, recently published cases describe older patients developing PRIS at lower doses of propofol, in whom arrhythmia, hypertriglyceridaemia and fever are less frequently seen, with survival more likely. We found that propofol infusion rate and duration, the presence of traumatic brain injury and fever are factors independently associated with mortality in reported cases of PRIS (area under receiver operator curve = 0.85). Similar patterns of exposure to propofol (in terms of time and concentration) are reported in clinical cases and experimental models of PRIS. Cardiac failure and metabolic acidosis occur early in a dose-dependent manner, while arrhythmia, other electrocardiographic changes and rhabdomyolysis appear more frequently after prolonged propofol infusions, irrespective of dose.
CONCLUSION
PRIS can develop with propofol infusion <4 mg/kg per hour and its diagnosis may be challenging as some of its typical features (hypertriglyceridaemia, fever, hepatomegaly, heart failure) are often (>95 %) missing and others (arrhythmia, electrocardiographic changes) occur late.
Topics: Anesthetics, Intravenous; Arrhythmias, Cardiac; Fever; Heart Failure; Hepatomegaly; Humans; Hypertriglyceridemia; Mortality; Propofol; Risk Factors; Syndrome
PubMed: 26558513
DOI: 10.1186/s13054-015-1112-5 -
Lipids in Health and Disease Jan 2017It has been demonstrated that acute oral administration of schisandrin B (Sch B), an active dibenzocyclooctadiene isolated from Schisandrae Fructus (a commonly used...
BACKGROUND
It has been demonstrated that acute oral administration of schisandrin B (Sch B), an active dibenzocyclooctadiene isolated from Schisandrae Fructus (a commonly used traditional Chinese herb), increased serum and hepatic triglyceride (TG) levels and hepatic mass in mice. The present study aimed to investigate the biochemical mechanism underlying the Sch B-induced hypertriglyceridemia, hepatic steatosis and hepatomegaly.
METHODS
Male ICR mice were given a single oral dose of Sch B (0.25-2 g/kg). Sch B-induced changes in serum levels of biomarkers, such as TG, total cholesterol (TC), apolipoprotein B48 (ApoB 48), very-low-density lipoprotein (VLDL), non-esterified fatty acid (NEFA) and hepatic growth factor (HGF), as well as hepatic lipids and mass, epididymal adipose tissue (EAT) and adipocyte size, and histological changes of the liver and EAT were examined over a period of 12-120 h after Sch B treatment.
RESULTS
Serum and hepatic TG levels were increased by 1.0-4.3 fold and 40-158% at 12-72 h and 12-96 h, respectively, after Sch B administration. Sch B treatment elevated serum ApoB 48 level (up to 12%), a marker of exogenous TG, but not VLDL, as compared with the vehicle treatment. Treatment with Sch B caused a time-/dose-dependent reduction in EAT index (up to 39%) and adipocyte size (up to 67%) and elevation in serum NEFA level (up to 55%). Sch B treatment induced hepatic steatosis in a time-/dose-dependent manner, as indicated by increases in total vacuole area (up to 3.2 fold vs. the vehicle control) and lipid positive staining area (up to 17.5 × 10 μm) in liver tissue. Hepatic index and serum HGF levels were increased by 18-60% and 42-71% at 12-120 h and 24-72 h post-Sch B dosing, respectively. In addition, ultrastructural changes, such as increase in size and disruption of cristae, in hepatic mitochondria were observed in Sch B-treated mice.
CONCLUSION
Our findings suggest that exogenous sources of TG and the breakdown of fat storage in the body contribute to Sch B-induced hypertriglyceridemia and hepatic steatosis in mice. Hepatomegaly (a probable hepatotoxic action) caused by Sch B may result from the fat accumulation and mitochondrial damage in liver tissue.
Topics: Adipocytes; Adipose Tissue; Animals; Antineoplastic Agents, Phytogenic; Apolipoprotein B-48; Cell Size; Cholesterol; Cholesterol, VLDL; Cyclooctanes; Fatty Acids, Nonesterified; Fatty Liver; Hepatocyte Growth Factor; Hepatomegaly; Hypertriglyceridemia; Lignans; Liver; Male; Mice; Mice, Inbred ICR; Mitochondria; Polycyclic Compounds; Schisandra; Triglycerides
PubMed: 28086886
DOI: 10.1186/s12944-017-0406-9 -
American Journal of Physiology.... Jun 2014Hepatosteatosis, the ectopic accumulation of lipid in the liver, is one of the earliest clinical signs of alcoholic liver disease (ALD). Alcohol-dependent deregulation...
Hepatosteatosis, the ectopic accumulation of lipid in the liver, is one of the earliest clinical signs of alcoholic liver disease (ALD). Alcohol-dependent deregulation of liver ceramide levels as well as inhibition of AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor α (PPAR-α) activity are thought to contribute to hepatosteatosis development. Adiponectin can regulate lipid handling in the liver and has been shown to reduce ceramide levels and activate AMPK and PPAR-α. However, the mechanisms by which adiponectin prevents alcoholic hepatosteatosis remain incompletely characterized. To address this question, we assessed ALD progression in wild-type (WT) and adiponectin knockout (KO) mice fed an ethanol-containing liquid diet or isocaloric control diet. Adiponectin KO mice relative to WT had increased alcohol-induced hepatosteatosis and hepatomegaly, similar modest increases in serum alanine aminotransferase, and reduced liver TNF. Restoring circulating adiponectin levels using recombinant adiponectin ameliorated alcohol-induced hepatosteatosis and hepatomegaly in adiponectin KO mice. Alcohol-fed WT and adiponectin KO animals had equivalent reductions in AMPK protein and PPAR-α DNA binding activity compared with control-fed animals. No difference in P-AMPK/AMPK ratio was detected, suggesting that alcohol-dependent deregulation of AMPK and PPAR-α in the absence of adiponectin are not primary causes of the observed increase in hepatosteatosis in these animals. By contrast, alcohol treatment increased liver ceramide levels in adiponectin KO but not WT mice. Importantly, pharmacological inhibition of de novo ceramide synthesis in adiponectin KO mice abrogated alcohol-mediated increases in liver ceramides, steatosis, and hepatomegaly. These data suggest that adiponectin reduces alcohol-induced steatosis and hepatomegaly through regulation of liver ceramides, but its absence does not exacerbate alcohol-induced liver damage.
Topics: Adenylate Kinase; Adiponectin; Animals; Biomarkers; Energy Intake; Ethanol; Fatty Acids, Monounsaturated; Fatty Liver; Hepatomegaly; Mice; Mice, Knockout; PPAR alpha
PubMed: 24742988
DOI: 10.1152/ajpgi.00395.2013 -
International Journal of Infectious... Jun 2010Brucellosis is the most prevalent bacterial zoonosis worldwide. In this study, we aimed to compare our 1028 brucellosis cases with other big series in the literature in... (Review)
Review
INTRODUCTION
Brucellosis is the most prevalent bacterial zoonosis worldwide. In this study, we aimed to compare our 1028 brucellosis cases with other big series in the literature in view of epidemiological, clinical, and laboratory findings and therapeutic features.
METHODS
A total of 1028 brucellosis cases admitted to the Department of Infectious Diseases and Clinical Microbiology over a 10-year period were included in the study. A retrospective analysis was undertaken and patient files were reviewed for history, clinical and laboratory findings, and therapeutic features, as well as complications.
RESULTS
Of the 1028 patients, 539 (52.4%) were female and 489 (47.6%) were male. The mean age of patients was 33.7+/-16.34 years and 69.6% of cases were aged 13-44 years. Four hundred and thirty-five cases (42.3%) had a history of raising livestock and 55.2% of the cases were found to have no occupational risk for brucellosis. Six hundred and fifty-four of the cases (63.6%) had a history of raw milk and dairy products consumption. The most frequently seen symptoms were arthralgia (73.7%) and fever (72.2%), while the most common clinical findings were fever (28.8%) and hepatomegaly (20.6%). The most frequent laboratory finding was a high C-reactive protein level (58.4%). The standard tube agglutination (STA) test+Coombs STA test was positive in 1016 cases (98.8%). Focal involvement was present in 371 (36.1%) cases. The most frequent involvement was osteoarticular involvement with 260 cases (25.3%). The overall relapse rate for patients with brucellosis was 4.7%. The highest relapse rate, 8.5%, was observed in the group of patients with osteoarticular involvement. Regimens including doxycycline and streptomycin with or without rifampin appeared more effective than other regimens in osteoarticular involvement.
CONCLUSIONS
In humans, brucellosis may lead to serious morbidity, and it continues to be a major health problem in Turkey. There is no recommended treatment protocol for complicated brucellosis. Large multicenter studies are needed to determine the most appropriate treatment choices and durations in complicated brucellosis.
Topics: Adolescent; Adult; Aged; Arthralgia; Arthritis; Bone Diseases; Brucellosis; Child; Child, Preschool; Dairy Products; Female; Fever; Hepatomegaly; Humans; Male; Middle Aged; Nervous System Diseases; Occupational Diseases; Retrospective Studies; Risk Factors; Turkey
PubMed: 19910232
DOI: 10.1016/j.ijid.2009.06.031 -
Hepatology (Baltimore, Md.) Aug 2011Glypican 3 (GPC3) is a family of glycosylphosphatidylinositol-anchored, cell-surface heparan sulfate proteoglycans. Loss-of-function mutations of GPC3 cause...
Hepatocyte proliferation and hepatomegaly induced by phenobarbital and 1,4-bis [2-(3,5-dichloropyridyloxy)] benzene is suppressed in hepatocyte-targeted glypican 3 transgenic mice.
UNLABELLED
Glypican 3 (GPC3) is a family of glycosylphosphatidylinositol-anchored, cell-surface heparan sulfate proteoglycans. Loss-of-function mutations of GPC3 cause Simpson-Golabi-Behmel syndrome characterized by overgrowth of multiple organs, including liver. Our previous study showed that in GPC3 transgenic (TG) mice, hepatocyte-targeted overexpression of GPC3 suppresses hepatocyte proliferation and liver regeneration after partial hepatectomy and alters gene expression profiles and potential cell cycle-related proteins. This study investigates the role of GPC3 in hepatocyte proliferation and hepatomegaly induced by the xenobiotic mitogens phenobarbital (PB) and TCPOBOP (1, 4-bis [2-(3, 5-dichloropyridyloxy)] benzene). Wildtype (WT) and GPC3 TG mice were given 0.1% PB in drinking water for 10 days or a single dose of TCPOBOP (3 mg/kg) by oral gavage. At day 5 the WT mice showed a 2.2- and 3.0-fold increase in liver weight, whereas the GPC3 TG mice showed a 1.3- and 1.6-fold increase in liver weight after PB and TCPOBOP administration, respectively. There was a significant suppression of proliferative response in the GPC3 TG mice, as assessed by percent of Ki67-positive hepatocyte nuclei. Moreover, gene array analysis showed a panel of changes in the gene expression profile of TG mice, both before and after administration of the xenobiotic mitogens. Expression of cell cycle-related genes in the TG mice was also decreased compared to the WT mice.
CONCLUSION
Our results indicate that in GPC3 TG mice, hepatocyte-targeted overexpression of GPC3 plays an important role for regulation of liver size and termination of hepatocyte proliferation induced by the xenobiotic mitogens PB and TCPOBOP, comparable to the effects seen in the GPC3 TG mice during liver regeneration after partial hepatectomy.
Topics: Animals; Cell Proliferation; Gene Expression Regulation; Genes, cdc; Glypicans; Hepatocytes; Hepatomegaly; Mice; Mice, Transgenic; Phenobarbital; Pyridines
PubMed: 21574168
DOI: 10.1002/hep.24417 -
Italian Journal of Pediatrics Jan 2019Hepatic glycogenosis is characterized by excessive glycogen accumulation in hepatocytes and represents a complication of poor controlled type 1 diabetes. It can be...
BACKGROUND
Hepatic glycogenosis is characterized by excessive glycogen accumulation in hepatocytes and represents a complication of poor controlled type 1 diabetes. It can be caused by excessive insulin doses or recurrent ketoacidosis episodes. Mauriac's syndrome is a rare disease, which includes short stature, growth maturation delay, dyslipidemia, moon facies, protuberant abdomen, hepatomegaly with transaminase elevation. It has become even less common after the emergence of advances on diabetes treatment, but still exists. Recent reports described glycogenosis without the full spectrum of Mauriac's syndrome in both adults and children with brittle diabetes. Clinical, laboratory and histological abnormalities are reversible with appropriate glycemic control.
CASE PRESENTATION
We hereby report a case of 11-year-old male who presented with hepatic glycogenosis mimicking Mauriac's syndrome. The patient was admitted at our Pediatric Diabetes Clinic for marked hepatomegaly, short stature and for the poor metabolic control. Blood investigations and liver tests excluded most of major causes of hepatopathy. A liver biopsy allowed us to make diagnosis of hepatic glycogenosis. To control hyperglycaemia, initially we titrated daily insulin dosage, and then intravenous insulin treatment was practiced with the consequent normalization of liver enzymes.
CONCLUSION
Mauriac's syndrome should be considered in subjects with brittle type 1 diabetes and hepatomegaly.
Topics: Child; Diabetes Mellitus, Type 1; Dwarfism; Glycogen Storage Disease; Hepatomegaly; Humans; Liver Glycogen; Male; Syndrome
PubMed: 30616577
DOI: 10.1186/s13052-018-0598-2